Sample records for areas mediating motion-induced

  1. The effects of area postrema lesions and selective vagotomy on motion-induced conditioned taste aversion

    NASA Technical Reports Server (NTRS)

    Fox, Robert A.; Sutton, R. L.; Mckenna, Susan

    1991-01-01

    Conditioned taste aversion (CTA) is one of several behaviors which was suggested as a putative measure of motion sickness in rats. A review is made of studies which used surgical disruption of area postrema or the vagus nerve to investigate whether CTA and vomiting induced by motion may depend on common neural pathways or structures. When the chemoreceptive function of the area postrema (AP) is destroyed by complete ablation, rats develop CTA and cats and monkeys develop CTA and vomit. Thus the AP is not crucially involved in either CTA or vomiting induced by motion. However, after complete denervation of the stomach or after labyrinthectomy rats do not develop CTA when motion is used as the unconditioned stimulus. Studies of brainstem projections of the vagus nerve, the area postrema, the periaqueductal grey, and the vestibular system are used as the basis for speculation about regions which could mediate both motion-induced vomiting and behavioral food aversion.

  2. Induced rotational motion with nonabutting inducing and induced stimuli: implications regarding two forms of induced motion.

    PubMed

    Reinhardt-Rutland, A H

    2003-07-01

    Induced motion is the illusory motion of a static stimulus in the opposite direction to a moving stimulus. Two types of induced motion have been distinguished: (a) when the moving stimulus is distant from the static stimulus and undergoes overall displacement, and (b) when the moving stimulus is pattern viewed within fixed boundaries that abut the static stimulus. Explanations of the 1st type of induced motion refer to mediating phenomena, such as vection, whereas the 2nd type is attributed to local processing by motion-sensitive neurons. The present research was directed to a display that elicited induced rotational motion with the characteristics of both types of induced motion: the moving stimulus lay within fixed boundaries, but the inducing and induced stimuli were distant from each other. The author investigated the properties that distinguished the two types of induced motion. In 3 experiments, induced motion persisted indefinitely, interocular transfer of the aftereffect of induced motion was limited to about 20%, and the time-course of the aftereffect of induced motion could not be attributed to vection. Those results were consistent with fixed-boundary induced motion. However, they could not be explained by local processing. Instead, the results might reflect the detection of object motion within a complex flow-field that resulted from the observer's motion.

  3. Using Simulated Ground Motions to Constrain Near-Source Ground Motion Prediction Equations in Areas Experiencing Induced Seismicity

    NASA Astrophysics Data System (ADS)

    Bydlon, S. A.; Dunham, E. M.

    2016-12-01

    Recent increases in seismic activity in historically quiescent areas such as Oklahoma, Texas, and Arkansas, including large, potentially induced events such as the 2011 Mw 5.6 Prague, OK, earthquake, have spurred the need for investigation into expected ground motions associated with these seismic sources. The neoteric nature of this seismicity increase corresponds to a scarcity of ground motion recordings within 50 km of earthquakes Mw 3.0 and greater, with increasing scarcity at larger magnitudes. Gathering additional near-source ground motion data will help better constraints on regional ground motion prediction equations (GMPEs) and will happen over time, but this leaves open the possibility of damaging earthquakes occurring before potential ground shaking and seismic hazard in these areas are properly understood. To aid the effort of constraining near-source GMPEs associated with induced seismicity, we integrate synthetic ground motion data from simulated earthquakes into the process. Using the dynamic rupture and seismic wave propagation code waveqlab3d, we perform verification and validation exercises intended to establish confidence in simulated ground motions for use in constraining GMPEs. We verify the accuracy of our ground motion simulator by performing the PEER/SCEC layer-over-halfspace comparison problem LOH.1 Validation exercises to ensure that we are synthesizing realistic ground motion data include comparisons to recorded ground motions for specific earthquakes in target areas of Oklahoma between Mw 3.0 and 4.0. Using a 3D velocity structure that includes a 1D structure with additional small-scale heterogeneity, the properties of which are based on well-log data from Oklahoma, we perform ground motion simulations of small (Mw 3.0 - 4.0) earthquakes using point moment tensor sources. We use the resulting synthetic ground motion data to develop GMPEs for small earthquakes in Oklahoma. Preliminary results indicate that ground motions can be amplified

  4. Area postrema ablations in cats: Evidence for separate neural routes for motion- and xylazine-induced CTA and emesis

    NASA Technical Reports Server (NTRS)

    Corcoran, Meryl Lee; Fox, Robert A.; Brizzee, Kenneth R.; Crampton, G.; Daunton, Nancy G.

    1991-01-01

    Previous studies on the role of the area postrema (AP) in vomiting induced in the cat by motion and drugs have shown that the AP is not essential for motion-induced vomiting, but is necessary for vomiting to apomorphine and xylazine. To confirm these findings and to determine the role of the AP in the formation of Conditioned Taste Aversion (CTA), the AP was ablated bilaterally in 10 adult female cats. With one exception, the ablated cats continued to vomit to the same motion that elicited emesis before the ablation. Doses of xylazine and apomorphine that elicit emesis in intact cats, failed to induce emesis in the ablated cats. Histological examination indicated that 8 cats had complete lesions and 2 had partial lesions. Investigations of effects of AP ablations on CTA revealed that cats with complete lesions did not form CTA to flavored milk paired with xylazine-induced CTA. Seven of the eigth completely lesioned cats developed motion-induced CTA, even though emesis was not consistently elicited by motion. These results suggest that there are multiple routes for inducing CTA and the emetic reflex, that CTA can form without eliciting emesis, and that CTA may be a sensitive measure of sub-emetic motion sickness.

  5. Neural mechanisms underlying sound-induced visual motion perception: An fMRI study.

    PubMed

    Hidaka, Souta; Higuchi, Satomi; Teramoto, Wataru; Sugita, Yoichi

    2017-07-01

    Studies of crossmodal interactions in motion perception have reported activation in several brain areas, including those related to motion processing and/or sensory association, in response to multimodal (e.g., visual and auditory) stimuli that were both in motion. Recent studies have demonstrated that sounds can trigger illusory visual apparent motion to static visual stimuli (sound-induced visual motion: SIVM): A visual stimulus blinking at a fixed location is perceived to be moving laterally when an alternating left-right sound is also present. Here, we investigated brain activity related to the perception of SIVM using a 7T functional magnetic resonance imaging technique. Specifically, we focused on the patterns of neural activities in SIVM and visually induced visual apparent motion (VIVM). We observed shared activations in the middle occipital area (V5/hMT), which is thought to be involved in visual motion processing, for SIVM and VIVM. Moreover, as compared to VIVM, SIVM resulted in greater activation in the superior temporal area and dominant functional connectivity between the V5/hMT area and the areas related to auditory and crossmodal motion processing. These findings indicate that similar but partially different neural mechanisms could be involved in auditory-induced and visually-induced motion perception, and neural signals in auditory, visual, and, crossmodal motion processing areas closely and directly interact in the perception of SIVM. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Measuring attention using induced motion.

    PubMed

    Gogel, W C; Sharkey, T J

    1989-01-01

    Attention was measured by means of its effect upon induced motion. Perceived horizontal motion was induced in a vertically moving test spot by the physical horizontal motion of inducing objects. All stimuli were in a frontoparallel plane. The induced motion vectored with the physical motion to produce a clockwise or counterclockwise tilt in the apparent path of motion of the test spot. Either a single inducing object or two inducing objects moving in opposite directions were used. Twelve observers were instructed to attend to or to ignore the single inducing object while fixating the test object and, when the two opposing inducing objects were present, to attend to one inducing object while ignoring the other. Tracking of the test spot was visually monitored. The tilt of the path of apparent motion of the test spot was measured by tactile adjustment of a comparison rod. It was found that the measured tilt was substantially larger when the single inducing object was attended rather than ignored. For the two inducing objects, attending to one while ignoring the other clearly increased the effectiveness of the attended inducing object. The results are analyzed in terms of the distinction between voluntary and involuntary attention. The advantages of measuring attention by its effect on induced motion as compared with the use of a precueing procedure, and a hypothesis regarding the role of attention in modifying perceived spatial characteristics are discussed.

  7. Gamma-aminobutyric acid (GABA) and neuropeptides in neural areas mediating motion-induced emesis

    NASA Technical Reports Server (NTRS)

    Damelio, F.; Daunton, Nancy G.; Fox, Robert A.

    1991-01-01

    Immunocytochemical methods were employed to localize the neurotransmitter amino acid gamma-aminobutyric acid and the neuropeptides substance P and Met-enkephalin in the area postrema (AP), area subpostrema (ASP), nucleus of the tractus solitarius (NTS), dorsal motor nucleus of the vagus nerve (DMNV), and lateral vestibular nucleus (LVN). Glutamic acid decarboxylase immunoreactive (GAD-IR) terminals and fibers were observed in the AP and particularly in the ASP. A gradual decrease in the density of terminals was seen towards the solitary complex. The DMNV revealed irregularly scattered GAD-IR terminals within the neuropil or closely surrounding neuronal cell bodies. The LVN, particularly the dorsal division, showed numerous axon terminals which were mostly localize around large neurons and their proximal dendrites. Substance P immunoreactive (SP-IR) terminals and fibers showed high density in the solitary complex, in particular within the lateral division. The ASP showed medium to low density of SP-IR fibers and terminals. The AP exhibited a small number of fibers and terminals irregularly distributed. The DMNV revealed a high density of SP-IR terminals and fibers that were mainly concentrated in the periphery. Very few terminals were detected in the LVN. Met-enkephalin immunoreactive (Met-Enk-IR) fibers and terminals showed high density and uniform distribution in the DMNV. Scattered terminals and fibers were observed in the AP, ASP, and NTS (particularly the lateral division). The very few fibers were observed in the LVN surrounded the neuronal cell bodies. The present report is part of a study designed to investigate the interaction between neuropeptides and conventional neurotransmitters under conditions producing motion sickness and in the process of sensory-motor adaptation.

  8. Auditorily-induced illusory self-motion: a review.

    PubMed

    Väljamäe, Aleksander

    2009-10-01

    The aim of this paper is to provide a first review of studies related to auditorily-induced self-motion (vection). These studies have been scarce and scattered over the years and over several research communities including clinical audiology, multisensory perception of self-motion and its neural correlates, ergonomics, and virtual reality. The reviewed studies provide evidence that auditorily-induced vection has behavioral, physiological and neural correlates. Although the sound contribution to self-motion perception appears to be weaker than the visual modality, specific acoustic cues appear to be instrumental for a number of domains including posture prosthesis, navigation in unusual gravitoinertial environments (in the air, in space, or underwater), non-visual navigation, and multisensory integration during self-motion. A number of open research questions are highlighted opening avenue for more active and systematic studies in this area.

  9. Wide area Hyperspectral Motion Imaging

    DTIC Science & Technology

    2017-02-03

    LEXINGTON, MASSACHUSETTS 02420-9108 (781) 981-1343 3 February 2017 TO: FROM: Dr. Joseph Lin (joseph.lin@ll.mit.edu), Advanced Imager ...Technology SUBJECT: Wide-area Hyperspectral Motion Imaging Introduction Wide-area motion imaging (WAMI) has received increased attention in...fielded imaging spectrometers use either dispersive or interferometric techniques. A dispersive spectrometer uses a grating or prism to disperse the

  10. Reassessment of area postrema's role in motion sickness and conditioned taste aversion

    NASA Technical Reports Server (NTRS)

    Daunton, Nancy G.; Brizzee, Kenneth R.; Corcoran, Meryl Lee; Crampton, G. H.; Damelio, F.; Elfar, S.; Fox, Robert A.

    1991-01-01

    On the basis of classical studies on the role of the area psotrema (AP) in motion-induced emesis it was generally accepted that the AP is an essential structure for the production of vomiting in response to motion. However, in more recent studies it has been demonstrated that vomiting induced by motion can still occur in animals in which the AP has been destroyed bilaterally. It was inferred from some of these more recent studies that the AP plays no role in motion-induced emesis. From the standpoint of the current understanding of central nervous system (CNS) plasticity, redundancy, remodeling, unmasking, regeneration, and recovery of function, however, it is important to realize the limitations of using ablation procedures to determine the functional role of a given neural structure in a highly integrated, adaptable central nervous system (CNS). For example, the results of our recent investigations in cat and squirrel monkey on the role of the AP in emesis and conditioned taste aversion induced by motion indicate that while AP lesions do not prevent motion-induced emesis when animals are tested 30 days or more after surgery, the lesions do change the latency to emesis. Thus, contradictory findings from lesion studies must be evaluated not only in terms of species difference, differences in lesioning techniques and extent of lesions, and in stimulus parameters, but also in terms of duration of the recovery period, during which significant recovery of function may take place. In our judgment, inadequate consideration of the foregoing factors could lead to erroneous inferences about given structure's role in the behavior of the intact, nonablated animal.

  11. Central Inhibition Ability Modulates Attention-Induced Motion Blindness

    ERIC Educational Resources Information Center

    Milders, Maarten; Hay, Julia; Sahraie, Arash; Niedeggen, Michael

    2004-01-01

    Impaired motion perception can be induced in normal observers in a rapid serial visual presentation task. Essential for this effect is the presence of motion distractors prior to the motion target, and we proposed that this attention-induced motion blindness results from high-level inhibition produced by the distractors. To investigate this, we…

  12. Role of the area postrema in three putative measures of motion sickness in the rat

    NASA Technical Reports Server (NTRS)

    Sutton, Richard L.; Fox, Robert A.; Daunton, Nancy G.

    1991-01-01

    After thermal cauterization of the area postrema in rats, the absence of conditioned taste aversion of sucrose paired with lithium chloride (0.15M, 3.3 ml/kg) was used as a pharmacologic/behavioral index of area postrema damage. In a subsequent experiment the effects of area postrema lesions on three measures proposed as species-relevant measures of motion sickness were studied, using off-vertical rotation at 150 deg/s for either 30 or 90 min. Lesions of area postrema did not alter postrotational suppression of drinking or amount of defecation during motion. The initial acquisition of conditioned taste aversion to a novel cider vinegar solution paired with motion was not affected by lesioning of the area postrema, but these taste aversions extinguished more slowly in lesioned rats than in sham-operates or intact controls. Results are discussed in terms of proposed humoral factors which may induce motion sickness and in light of recent data on the role of the area postrema in similar measures in species possessing the complete emetic reflex.

  13. Can walking motions improve visually induced rotational self-motion illusions in virtual reality?

    PubMed

    Riecke, Bernhard E; Freiberg, Jacob B; Grechkin, Timofey Y

    2015-02-04

    Illusions of self-motion (vection) can provide compelling sensations of moving through virtual environments without the need for complex motion simulators or large tracked physical walking spaces. Here we explore the interaction between biomechanical cues (stepping along a rotating circular treadmill) and visual cues (viewing simulated self-rotation) for providing stationary users a compelling sensation of rotational self-motion (circular vection). When tested individually, biomechanical and visual cues were similarly effective in eliciting self-motion illusions. However, in combination they yielded significantly more intense self-motion illusions. These findings provide the first compelling evidence that walking motions can be used to significantly enhance visually induced rotational self-motion perception in virtual environments (and vice versa) without having to provide for physical self-motion or motion platforms. This is noteworthy, as linear treadmills have been found to actually impair visually induced translational self-motion perception (Ash, Palmisano, Apthorp, & Allison, 2013). Given the predominant focus on linear walking interfaces for virtual-reality locomotion, our findings suggest that investigating circular and curvilinear walking interfaces offers a promising direction for future research and development and can help to enhance self-motion illusions, presence and immersion in virtual-reality systems. © 2015 ARVO.

  14. Relationship of area postrema to three putative measures of motion sickness

    NASA Technical Reports Server (NTRS)

    Sutton, R.; Fox, Robert A.; Daunton, Nancy G.

    1991-01-01

    Although the rat has an incomplete emetic reflex, several species-specific responses to motion were proposed as measures of 'motion sickness' in rats. The purpose was to determine the dependence of these responses on one of several neural structures known to be essential to motion-induced vomiting in species with a complete emetic reflex. The Area Postrema (AP) was shown to play an important role in the production of motion sickness in vomiting species. The effects of thermo-cautery ablations of the AP on three different responses supposedly reflecting motion sickness in the rat were compared: conditioned taste aversion (CTA); drinking suppression; and fecal boli. Efficacy of the ablations was determined by subjecting ablated, sham-operated, and unoperated control animals to a CTA test which is known to require a functional AP. Animals with AP ablations failed to form CTA when 0.15 M LiCl was paired with a 10 percent sucrose solution, while sham-operated control subjects conditioned as well as the unoperated control subjects. The extent of the ablations was evaluated histologically at the end of the experiment. To determine the effects of the ablations on the measures of motion sickness, all animals were subjected to rotation for 30 min or 90 min on a platform displaced 20 deg from earth horizontal. Results indicate that ablation of AP in the rat has no effect on the formation of CTA to a 4 percent solution of cider paired with motion, on the suppression of drinking immediately after exposure to motion, or on the frequency of fecal boli during exposure to motion. This failure of AP ablations to eliminate the effects of motion on any of these responses discourages their use as equivalents of motion-induced vomiting. The appropriateness of other suggested measures, e.g., pica, remains untested but the dependence of such measures on stimulation more severe than commonly used in motion sickness research and the absence of a demonstration of their dependence on neural

  15. Stress Drop and Depth Controls on Ground Motion From Induced Earthquakes

    NASA Astrophysics Data System (ADS)

    Baltay, A.; Rubinstein, J. L.; Terra, F. M.; Hanks, T. C.; Herrmann, R. B.

    2015-12-01

    Induced earthquakes in the central United States pose a risk to local populations, but there is not yet agreement on how to portray their hazard. A large source of uncertainty in the hazard arises from ground motion prediction, which depends on the magnitude and distance of the causative earthquake. However, ground motion models for induced earthquakes may be very different than models previously developed for either the eastern or western United States. A key question is whether ground motions from induced earthquakes are similar to those from natural earthquakes, yet there is little history of natural events in the same region with which to compare the induced ground motions. To address these problems, we explore how earthquake source properties, such as stress drop or depth, affect the recorded ground motion of induced earthquakes. Typically, due to stress drop increasing with depth, ground motion prediction equations model shallower events to have smaller ground motions, when considering the same absolute hypocentral distance to the station. Induced earthquakes tend to occur at shallower depths, with respect to natural eastern US earthquakes, and may also exhibit lower stress drops, which begs the question of how these two parameters interact to control ground motion. Can the ground motions of induced earthquakes simply be understood by scaling our known source-ground motion relations to account for the shallow depth or potentially smaller stress drops of these induced earthquakes, or is there an inherently different mechanism in play for these induced earthquakes? We study peak ground-motion velocity (PGV) and acceleration (PGA) from induced earthquakes in Oklahoma and Kansas, recorded by USGS networks at source-station distances of less than 20 km, in order to model the source effects. We compare these records to those in both the NGA-West2 database (primarily from California) as well as NGA-East, which covers the central and eastern United States and Canada

  16. Neurophysiological responses to stressful motion and anti-motion sickness drugs as mediated by the limbic system

    NASA Technical Reports Server (NTRS)

    Kohl, R. L.; Odell, S.

    1982-01-01

    Performance is characterized in terms of attention and memory, categorizing extrinsic mechanism mediated by ACTH, norepinephrine and dopamine, and intrinsic mechanisms as cholinergic. The cholinergic role in memory and performance was viewed from within the limbic system and related to volitional influences of frontal cortical afferents and behavioral responses of hypothalamic and reticular system efferents. The inhibitory influence of the hippocampus on the autonomic and hormonal responses mediated through the hypothalamus, pituitary, and brain stem are correlated with the actions of such anti-motion sickness drugs as scopolamine and amphetamine. These drugs appear to exert their effects on motion sickness symptomatology through diverse though synergistic neurochemical mechanisms involving the septohippocampal pathway and other limbic system structures. The particular impact of the limbic system on an animal's behavioral and hormonal responses to stress is influenced by ACTH, cortisol, scopolamine, and amphetamine.

  17. Voluntary attention modulates motion-induced mislocalization

    PubMed Central

    Tse, Peter U.; Whitney, David; Anstis, Stuart; Cavanagh, Patrick

    2013-01-01

    When a test is flashed on top of two superimposed, opposing motions, the perceived location of the test is shifted in opposite directions depending on which of the two motions is attended. Because the stimulus remains unchanged as attention switches from one motion to the other, the effect cannot be due to stimulus-driven, low-level motion. A control condition ruled out any contribution from possible attention-induced cyclotorsion of the eyes. This provides the strongest evidence to date for a role of attention in the perception of location, and establishes that what we attend to influences where we perceive objects to be. PMID:21415228

  18. Ground Motion Characteristics of Induced Earthquakes in Central North America

    NASA Astrophysics Data System (ADS)

    Atkinson, G. M.; Assatourians, K.; Novakovic, M.

    2017-12-01

    The ground motion characteristics of induced earthquakes in central North America are investigated based on empirical analysis of a compiled database of 4,000,000 digital ground-motion records from events in induced-seismicity regions (especially Oklahoma). Ground-motion amplitudes are characterized non-parametrically by computing median amplitudes and their variability in magnitude-distance bins. We also use inversion techniques to solve for regional source, attenuation and site response effects. Ground motion models are used to interpret the observations and compare the source and attenuation attributes of induced earthquakes to those of their natural counterparts. Significant conclusions are that the stress parameter that controls the strength of high-frequency radiation is similar for induced earthquakes (depth of h 5 km) and shallow (h 5 km) natural earthquakes. By contrast, deeper natural earthquakes (h 10 km) have stronger high-frequency ground motions. At distances close to the epicenter, a greater focal depth (which increases distance from the hypocenter) counterbalances the effects of a larger stress parameter, resulting in motions of similar strength close to the epicenter, regardless of event depth. The felt effects of induced versus natural earthquakes are also investigated using USGS "Did You Feel It?" reports; 400,000 reports from natural events and 100,000 reports from induced events are considered. The felt reports confirm the trends that we expect based on ground-motion modeling, considering the offsetting effects of the stress parameter versus focal depth in controlling the strength of motions near the epicenter. Specifically, felt intensity for a given magnitude is similar near the epicenter, on average, for all event types and depths. At distances more than 10 km from the epicenter, deeper events are felt more strongly than shallow events. These ground-motion attributes imply that the induced-seismicity hazard is most critical for facilities in

  19. Neural Representation of Motion-In-Depth in Area MT

    PubMed Central

    Sanada, Takahisa M.

    2014-01-01

    Neural processing of 2D visual motion has been studied extensively, but relatively little is known about how visual cortical neurons represent visual motion trajectories that include a component toward or away from the observer (motion in depth). Psychophysical studies have demonstrated that humans perceive motion in depth based on both changes in binocular disparity over time (CD cue) and interocular velocity differences (IOVD cue). However, evidence for neurons that represent motion in depth has been limited, especially in primates, and it is unknown whether such neurons make use of CD or IOVD cues. We show that approximately one-half of neurons in macaque area MT are selective for the direction of motion in depth, and that this selectivity is driven primarily by IOVD cues, with a small contribution from the CD cue. Our results establish that area MT, a central hub of the primate visual motion processing system, contains a 3D representation of visual motion. PMID:25411481

  20. Nanoparticle mediated micromotor motion

    NASA Astrophysics Data System (ADS)

    Liu, Mei; Liu, Limei; Gao, Wenlong; Su, Miaoda; Ge, Ya; Shi, Lili; Zhang, Hui; Dong, Bin; Li, Christopher Y.

    2015-03-01

    In this paper, we report the utilization of nanoparticles to mediate the motion of a polymer single crystal catalytic micromotor. Micromotors have been fabricated by directly self-assembling functional nanoparticles (platinum and iron oxide nanoparticles) onto one or both sides of two-dimensional polymer single crystals. We show that the moving velocity of these micromotors in fluids can be readily tuned by controlling the nanoparticles' surface wettability and catalytic activity. A 3 times velocity increase has been achieved for a hydrophobic micromotor as opposed to the hydrophilic ones. Furthermore, we demonstrate that the catalytic activity of platinum nanoparticles inside the micromotor can be enhanced by their synergetic interactions with iron oxide nanoparticles and an electric field. Both strategies lead to dramatically increased moving velocities, with the highest value reaching ~200 μm s-1. By decreasing the nanoparticles' surface wettability and increasing their catalytic activity, a maximum of a ~10-fold increase in the moving speed of the nanoparticle based micromotor can be achieved. Our results demonstrate the advantages of using nanoparticles in micromotor systems.In this paper, we report the utilization of nanoparticles to mediate the motion of a polymer single crystal catalytic micromotor. Micromotors have been fabricated by directly self-assembling functional nanoparticles (platinum and iron oxide nanoparticles) onto one or both sides of two-dimensional polymer single crystals. We show that the moving velocity of these micromotors in fluids can be readily tuned by controlling the nanoparticles' surface wettability and catalytic activity. A 3 times velocity increase has been achieved for a hydrophobic micromotor as opposed to the hydrophilic ones. Furthermore, we demonstrate that the catalytic activity of platinum nanoparticles inside the micromotor can be enhanced by their synergetic interactions with iron oxide nanoparticles and an electric

  1. Infrasonic induced ground motions

    NASA Astrophysics Data System (ADS)

    Lin, Ting-Li

    On January 28, 2004, the CERI seismic network recorded seismic signals generated by an unknown source. Our conclusion is that the acoustic waves were initiated by an explosive source near the ground surface. The meteorological temperature and effective sound speed profiles suggested existence of an efficient near-surface waveguide that allowed the acoustic disturbance to propagate to large distances. An explosion occurring in an area of forest and farms would have limited the number of eyewitnesses. Resolution of the source might be possible by experiment or by detailed analysis of the ground motion data. A seismo-acoustic array was built to investigate thunder-induced ground motions. Two thunder events with similar N-wave waveforms but different horizontal slownesses are chosen to evaluate the credibility of using thunder as a seismic source. These impulsive acoustic waves excited P and S reverberations in the near surface that depend on both the incident wave horizontal slowness and the velocity structure in the upper 30 meters. Nineteen thunder events were chosen to further investigate the seismo-acoustic coupling. The consistent incident slowness differences between acoustic pressure and ground motions suggest that ground reverberations were first initiated somewhat away from the array. Acoustic and seismic signals were used to generate the time-domain transfer function through the deconvolution technique. Possible non-linear interaction for acoustic propagation into the soil at the surface was observed. The reverse radial initial motions suggest a low Poisson's ratio for the near-surface layer. The acoustic-to-seismic transfer functions show a consistent reverberation series of the Rayleigh wave type, which has a systematic dispersion relation to incident slownesses inferred from the seismic ground velocity. Air-coupled Rayleigh wave dispersion was used to quantitatively constrain the near-surface site structure with constraints afforded by near-surface body

  2. Selectivity to Translational Egomotion in Human Brain Motion Areas

    PubMed Central

    Pitzalis, Sabrina; Sdoia, Stefano; Bultrini, Alessandro; Committeri, Giorgia; Di Russo, Francesco; Fattori, Patrizia; Galletti, Claudio; Galati, Gaspare

    2013-01-01

    The optic flow generated when a person moves through the environment can be locally decomposed into several basic components, including radial, circular, translational and spiral motion. Since their analysis plays an important part in the visual perception and control of locomotion and posture it is likely that some brain regions in the primate dorsal visual pathway are specialized to distinguish among them. The aim of this study is to explore the sensitivity to different types of egomotion-compatible visual stimulations in the human motion-sensitive regions of the brain. Event-related fMRI experiments, 3D motion and wide-field stimulation, functional localizers and brain mapping methods were used to study the sensitivity of six distinct motion areas (V6, MT, MST+, V3A, CSv and an Intra-Parietal Sulcus motion [IPSmot] region) to different types of optic flow stimuli. Results show that only areas V6, MST+ and IPSmot are specialized in distinguishing among the various types of flow patterns, with a high response for the translational flow which was maximum in V6 and IPSmot and less marked in MST+. Given that during egomotion the translational optic flow conveys differential information about the near and far external objects, areas V6 and IPSmot likely process visual egomotion signals to extract information about the relative distance of objects with respect to the observer. Since area V6 is also involved in distinguishing object-motion from self-motion, it could provide information about location in space of moving and static objects during self-motion, particularly in a dynamically unstable environment. PMID:23577096

  3. Thunder-induced ground motions: 1. Observations

    NASA Astrophysics Data System (ADS)

    Lin, Ting-L.; Langston, Charles A.

    2009-04-01

    Acoustic pressure from thunder and its induced ground motions were investigated using a small array consisting of five three-component short-period surface seismometers, a three-component borehole seismometer, and five infrasound microphones. We used the array to constrain wave parameters of the incident acoustic and seismic waves. The incident slowness differences between acoustic pressure and ground motions suggest that ground reverberations were first initiated somewhat away from the array. Using slowness inferred from ground motions is preferable to obtain the seismic source parameters. We propose a source equalization procedure for acoustic/seismic deconvolution to generate the time domain transfer function, a procedure similar to that of obtaining teleseismic earthquake receiver functions. The time domain transfer function removes the incident pressure time history from the seismogram. An additional vertical-to-radial ground motion transfer function was used to identify the Rayleigh wave propagation mode of induced seismic waves complementing that found using the particle motions and amplitude variations in the borehole. The initial motions obtained by the time domain transfer functions suggest a low Poisson's ratio for the near-surface layer. The acoustic-to-seismic transfer functions show a consistent reverberation series at frequencies near 5 Hz. This gives an empirical measure of site resonance that depends on the ratio of the layer velocity to layer thickness for earthquake P and S waves. The time domain transfer function approach by transferring a spectral division into the time domain provides an alternative method for studying acoustic-to-seismic coupling.

  4. Attentive Motion Discrimination Recruits an Area in Inferotemporal Cortex

    PubMed Central

    Stemmann, Heiko

    2016-01-01

    Attentional selection requires the interplay of multiple brain areas. Theoretical accounts of selective attention predict different areas with different functional properties to support endogenous covert attention. To test these predictions, we devised a demanding attention task requiring motion discrimination and spatial selection and performed whole-brain imaging in macaque monkeys. Attention modulated the early visual cortex, motion-selective dorsal stream areas, the lateral intraparietal area, and the frontal eye fields. This pattern of activation supports early selection, feature-based, and biased-competition attention accounts, as well as the frontoparietal theory of attentional control. While high-level motion-selective dorsal stream areas did not exhibit strong attentional modulation, ventral stream areas V4d and the dorsal posterior inferotemporal cortex (PITd) did. The PITd in fact was, consistently across task variations, the most significantly and most strongly attention-modulated area, even though it did not exhibit signs of motion selectivity. Thus the recruitment of the PITd in attention tasks involving different kinds of motion analysis is not predicted by any theoretical account of attention. These functional data, together with known anatomical connections, suggest a general and possibly critical role of the PITd in attentional selection. SIGNIFICANCE STATEMENT Attention is the key cognitive function that selects sensory information relevant to the current goals, relegating other information to the shadows of consciousness. To better understand the neural mechanisms of this interplay between sensory processing and internal cognitive state, we must learn more about the brain areas supporting attentional selection. Here, to test theoretical accounts of attentional selection, we used a novel task requiring sustained attention to motion. We found that, surprisingly, among the most strongly attention-modulated areas is one that is neither selective for

  5. Brain white matter microstructure is associated with susceptibility to motion-induced nausea.

    PubMed

    Napadow, V; Sheehan, J; Kim, J; Dassatti, A; Thurler, A H; Surjanhata, B; Vangel, M; Makris, N; Schaechter, J D; Kuo, B

    2013-05-01

    Nausea is associated with significant morbidity, and there is a wide range in the propensity of individuals to experience nausea. The neural basis of the heterogeneity in nausea susceptibility is poorly understood. Our previous functional magnetic resonance imaging (fMRI) study in healthy adults showed that a visual motion stimulus caused activation in the right MT+/V5 area, and that increased sensation of nausea due to this stimulus was associated with increased activation in the right anterior insula. For the current study, we hypothesized that individual differences in visual motion-induced nausea are due to microstructural differences in the inferior fronto-occipital fasciculus (IFOF), the white matter tract connecting the right visual motion processing area (MT+/V5) and right anterior insula. To test this hypothesis, we acquired diffusion tensor imaging data from 30 healthy adults who were subsequently dichotomized into high and low nausea susceptibility groups based on the Motion Sickness Susceptibility Scale. We quantified diffusion along the IFOF for each subject based on axial diffusivity (AD); radial diffusivity (RD), mean diffusivity (MD) and fractional anisotropy (FA), and evaluated between-group differences in these diffusion metrics. Subjects with high susceptibility to nausea rated significantly (P < 0.001) higher nausea intensity to visual motion stimuli and had significantly (P < 0.05) lower AD and MD along the right IFOF compared to subjects with low susceptibility to nausea. This result suggests that differences in white matter microstructure within tracts connecting visual motion and nausea-processing brain areas may contribute to nausea susceptibility or may have resulted from an increased history of nausea episodes. © 2013 Blackwell Publishing Ltd.

  6. Decoding facial expressions based on face-selective and motion-sensitive areas.

    PubMed

    Liang, Yin; Liu, Baolin; Xu, Junhai; Zhang, Gaoyan; Li, Xianglin; Wang, Peiyuan; Wang, Bin

    2017-06-01

    Humans can easily recognize others' facial expressions. Among the brain substrates that enable this ability, considerable attention has been paid to face-selective areas; in contrast, whether motion-sensitive areas, which clearly exhibit sensitivity to facial movements, are involved in facial expression recognition remained unclear. The present functional magnetic resonance imaging (fMRI) study used multi-voxel pattern analysis (MVPA) to explore facial expression decoding in both face-selective and motion-sensitive areas. In a block design experiment, participants viewed facial expressions of six basic emotions (anger, disgust, fear, joy, sadness, and surprise) in images, videos, and eyes-obscured videos. Due to the use of multiple stimulus types, the impacts of facial motion and eye-related information on facial expression decoding were also examined. It was found that motion-sensitive areas showed significant responses to emotional expressions and that dynamic expressions could be successfully decoded in both face-selective and motion-sensitive areas. Compared with static stimuli, dynamic expressions elicited consistently higher neural responses and decoding performance in all regions. A significant decrease in both activation and decoding accuracy due to the absence of eye-related information was also observed. Overall, the findings showed that emotional expressions are represented in motion-sensitive areas in addition to conventional face-selective areas, suggesting that motion-sensitive regions may also effectively contribute to facial expression recognition. The results also suggested that facial motion and eye-related information played important roles by carrying considerable expression information that could facilitate facial expression recognition. Hum Brain Mapp 38:3113-3125, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Gravity Cues Embedded in the Kinematics of Human Motion Are Detected in Form-from-Motion Areas of the Visual System and in Motor-Related Areas

    PubMed Central

    Cignetti, Fabien; Chabeauti, Pierre-Yves; Menant, Jasmine; Anton, Jean-Luc J. J.; Schmitz, Christina; Vaugoyeau, Marianne; Assaiante, Christine

    2017-01-01

    The present study investigated the cortical areas engaged in the perception of graviceptive information embedded in biological motion (BM). To this end, functional magnetic resonance imaging was used to assess the cortical areas active during the observation of human movements performed under normogravity and microgravity (parabolic flight). Movements were defined by motion cues alone using point-light displays. We found that gravity modulated the activation of a restricted set of regions of the network subtending BM perception, including form-from-motion areas of the visual system (kinetic occipital region, lingual gyrus, cuneus) and motor-related areas (primary motor and somatosensory cortices). These findings suggest that compliance of observed movements with normal gravity was carried out by mapping them onto the observer’s motor system and by extracting their overall form from local motion of the moving light points. We propose that judgment on graviceptive information embedded in BM can be established based on motor resonance and visual familiarity mechanisms and not necessarily by accessing the internal model of gravitational motion stored in the vestibular cortex. PMID:28861024

  8. Nanoparticle mediated micromotor motion.

    PubMed

    Liu, Mei; Liu, Limei; Gao, Wenlong; Su, Miaoda; Ge, Ya; Shi, Lili; Zhang, Hui; Dong, Bin; Li, Christopher Y

    2015-03-21

    In this paper, we report the utilization of nanoparticles to mediate the motion of a polymer single crystal catalytic micromotor. Micromotors have been fabricated by directly self-assembling functional nanoparticles (platinum and iron oxide nanoparticles) onto one or both sides of two-dimensional polymer single crystals. We show that the moving velocity of these micromotors in fluids can be readily tuned by controlling the nanoparticles' surface wettability and catalytic activity. A 3 times velocity increase has been achieved for a hydrophobic micromotor as opposed to the hydrophilic ones. Furthermore, we demonstrate that the catalytic activity of platinum nanoparticles inside the micromotor can be enhanced by their synergetic interactions with iron oxide nanoparticles and an electric field. Both strategies lead to dramatically increased moving velocities, with the highest value reaching ∼200 μm s(-1). By decreasing the nanoparticles' surface wettability and increasing their catalytic activity, a maximum of a ∼10-fold increase in the moving speed of the nanoparticle based micromotor can be achieved. Our results demonstrate the advantages of using nanoparticles in micromotor systems.

  9. Locomotive and reptation motion induced by internal force and friction.

    PubMed

    Sakaguchi, Hidetsugu; Ishihara, Taisuke

    2011-06-01

    We propose a simple mechanical model of locomotion induced by internal force and friction. We first construct a system of two elements as an analog of the bipedal motion. The internal force does not induce a directional motion by itself because of the action-reaction law, but a directional motion becomes possible by the control of the frictional force. The efficiency of these model systems is studied using an analogy to the heat engine. As a modified version of the two-element model, we construct a model that exhibits a bipedal motion similar to kinesin's motion of molecular motor. Next, we propose a linear chain model and a ladder model as an extension of the original two-element model. We find a transition from a straight to a snake-like motion in a ladder model by changing the strength of the internal force.

  10. Ross sea ice motion, area flux, and deformation

    NASA Technical Reports Server (NTRS)

    kwok, Ron

    2005-01-01

    The sea ice motion, area export, and deformation of the Ross Sea ice cover are examined with satellite passive microwave and RADARSAT observations. The record of high-resolution synthetic aperture radar (SAR) data, from 1998 and 2000, allows the estimation of the variability of ice deformation at the small scale (10 km) and to assess the quality of the longer record of passive microwave ice motion. Daily and subdaily deformation fields and RADARSAT imagery highlight the variability of motion and deformation in the Ross Sea. With the passive microwave ice motion, the area export at a flux gate positioned between Cape Adare and Land Bay is estimated. Between 1992 and 2003, a positive trend can be seen in the winter (March-November) ice area flux that has a mean of 990 x 103 km2 and ranges from a low of 600 x 103 km2 in 1992 to a peak of 1600 x 103 km2 in 2001. In the mean, the southern Ross Sea produces almost twice its own area of sea ice during the winter. Cross-gate sea level pressure (SLP) gradients explain 60% of the variance in the ice area flux. A positive trend in this gradient, from reanalysis products, suggests a 'spinup' of the Ross Sea Gyre over the past 12 yr. In both the NCEP-NCAR and ERA-40 surface pressure fields, longer-term trends in this gradient and mean SLP between 1979 and 2002 are explored along with positive anomalies in the monthly cross-gate SLP gradient associated with the positive phase of the Southern Hemisphere annular mode and the extrapolar Southern Oscillation.

  11. Vection and visually induced motion sickness: how are they related?

    PubMed Central

    Keshavarz, Behrang; Riecke, Bernhard E.; Hettinger, Lawrence J.; Campos, Jennifer L.

    2015-01-01

    The occurrence of visually induced motion sickness has been frequently linked to the sensation of illusory self-motion (vection), however, the precise nature of this relationship is still not fully understood. To date, it is still a matter of debate as to whether vection is a necessary prerequisite for visually induced motion sickness (VIMS). That is, can there be VIMS without any sensation of self-motion? In this paper, we will describe the possible nature of this relationship, review the literature that addresses this relationship (including theoretical accounts of vection and VIMS), and offer suggestions with respect to operationally defining and reporting these phenomena in future. PMID:25941509

  12. Enhancement of vortex induced forces and motion through surface roughness control

    DOEpatents

    Bernitsas, Michael M [Saline, MI; Raghavan, Kamaldev [Houston, TX

    2011-11-01

    Roughness is added to the surface of a bluff body in a relative motion with respect to a fluid. The amount, size, and distribution of roughness on the body surface is controlled passively or actively to modify the flow around the body and subsequently the Vortex Induced Forces and Motion (VIFM). The added roughness, when designed and implemented appropriately, affects in a predetermined way the boundary layer, the separation of the boundary layer, the level of turbulence, the wake, the drag and lift forces, and consequently the Vortex Induced Motion (VIM), and the fluid-structure interaction. The goal of surface roughness control is to increase Vortex Induced Forces and Motion. Enhancement is needed in such applications as harnessing of clean and renewable energy from ocean/river currents using the ocean energy converter VIVACE (Vortex Induced Vibration for Aquatic Clean Energy).

  13. Assessing Motion Induced Interruptions Using a Motion Platform

    DTIC Science & Technology

    2013-09-01

    same way that cars have shock absorbers to decrease jolt from potholes and bumps in the road, ships may have the potential to be designed to better...Integration (HSI) seeks to assure human performance to reduce operating costs. This thesis seeks to develop a model for ship design in relation to Motion...Induced Interruptions (MII). The model is based on the premise that MIIs affect specific domains of HSI in an adverse way. Future ship design

  14. The responsiveness of biological motion processing areas to selective attention towards goals.

    PubMed

    Herrington, John; Nymberg, Charlotte; Faja, Susan; Price, Elinora; Schultz, Robert

    2012-10-15

    A growing literature indicates that visual cortex areas viewed as primarily responsive to exogenous stimuli are susceptible to top-down modulation by selective attention. The present study examines whether brain areas involved in biological motion perception are among these areas-particularly with respect to selective attention towards human movement goals. Fifteen participants completed a point-light biological motion study following a two-by-two factorial design, with one factor representing an exogenous manipulation of human movement goals (goal-directed versus random movement), and the other an endogenous manipulation (a goal identification task versus an ancillary color-change task). Both manipulations yielded increased activation in the human homologue of motion-sensitive area MT+ (hMT+) as well as the extrastriate body area (EBA). The endogenous manipulation was associated with increased right posterior superior temporal sulcus (STS) activation, whereas the exogenous manipulation was associated with increased activation in left posterior STS. Selective attention towards goals activated a portion of left hMT+/EBA only during the perception of purposeful movement-consistent with emerging theories associating this area with the matching of visual motion input to known goal-directed actions. The overall pattern of results indicates that attention towards the goals of human movement activates biological motion areas. Ultimately, selective attention may explain why some studies examining biological motion show activation in hMT+ and EBA, even when using control stimuli with comparable motion properties. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. The Responsiveness of Biological Motion Processing Areas to Selective Attention Towards Goals

    PubMed Central

    Herrington, John; Nymberg, Charlotte; Faja, Susan; Price, Elinora; Schultz, Robert

    2012-01-01

    A growing literature indicates that visual cortex areas viewed as primarily responsive to exogenous stimuli are susceptible to top-down modulation by selective attention. The present study examines whether brain areas involved in biological motion perception are among these areas – particularly with respect to selective attention towards human movement goals. Fifteen participants completed a point-light biological motion study following a two-by-two factorial design, with one factor representing an exogenous manipulation of human movement goals (goal-directed versus random movement), and the other an endogenous manipulation (a goal identification task versus an ancillary color-change task). Both manipulations yielded increased activation in the human homologue of motion-sensitive area MT+ (hMT+) as well as the extrastriate body area (EBA). The endogenous manipulation was associated with increased right posterior superior temporal sulcus (STS) activation, whereas the exogenous manipulation was associated with increased activation in left posterior STS. Selective attention towards goals activated portion of left hMT+/EBA only during the perception of purposeful movement consistent with emerging theories associating this area with the matching of visual motion input to known goal-directed actions. The overall pattern of results indicates that attention towards the goals of human movement activates biological motion areas. Ultimately, selective attention may explain why some studies examining biological motion show activation in hMT+ and EBA, even when using control stimuli with comparable motion properties. PMID:22796987

  16. Empirical Ground Motion Characterization of Induced Seismicity in Alberta and Oklahoma

    NASA Astrophysics Data System (ADS)

    Novakovic, M.; Atkinson, G. M.; Assatourians, K.

    2017-12-01

    We develop empirical ground-motion prediction equations (GMPEs) for ground motions from induced earthquakes in Alberta and Oklahoma following the stochastic-model-based method of Atkinson et al. (2015 BSSA). The Oklahoma ground-motion database is compiled from over 13,000 small to moderate seismic events (M 1 to 5.8) recorded at 1600 seismic stations, at distances from 1 to 750 km. The Alberta database is compiled from over 200 small to moderate seismic events (M 1 to 4.2) recorded at 50 regional stations, at distances from 30 to 500 km. A generalized inversion is used to solve for regional source, attenuation and site parameters. The obtained parameters describe the regional attenuation, stress parameter and site amplification. Resolving these parameters allows for the derivation of regionally-calibrated GMPEs that can be used to compare ground motion observations between waste water injection (Oklahoma) and hydraulic fracture induced events (Alberta), and further compare induced observations with ground motions resulting from natural sources (California, NGAWest2). The derived GMPEs have applications for the evaluation of hazards from induced seismicity and can be used to track amplitudes across the regions in real time, which is useful for ground-motion-based alerting systems and traffic light protocols.

  17. Recovery of the vomiting reflex following area postrema ablation in squirrel monkeys

    NASA Technical Reports Server (NTRS)

    Elfar, S.; Brizzee, Kenneth R.; Fox, Robert A.; Corcoran, Meryl Lee; Daunton, Nancy G.; Coleman, J.

    1991-01-01

    The role of the area postrema (AP) in motion-induced emesis was re-assessed recently in several different species. In a few of these studies, the role of the AP in motion-induced conditioned taste aversion (CTA) was also addressed. The purpose was to extend this comparative study to the squirrel monkey, to evaluate further the role of AP in vomiting, and to investigate the dynamics of the recovery process. The AP was ablated bilaterally in 7 motion-susceptible squirrel monkeys which previously had been characterized in terms of their responses to various motion sickness-inducing stimuli. After recovery from surgery all animals were tested at 30-day intervals for a period of 11 months to determine the effects of AP ablations on susceptibility to the same sickness-inducing conditions. In addition, the effectiveness of motion in preducing CTA was evaluated. All pre-ablation motion tests involved stimulation for 30 min., while post-lesion tests were 60 min., in duration. All animals showed significant increases in latencies to vomiting after AP ablations. However, the latencies tended to decrease with time after ablation. All but one animal vomited on at least one of the 10 motion tests occurring after ablation of AP. In addition, CTA was produced by motion used in the conditioning sessions. These results suggest that structures other than AP, and processes other that those mediated through AP, may play an important role in motion-induced emesis.

  18. Motion-induced eddy current thermography for high-speed inspection

    NASA Astrophysics Data System (ADS)

    Wu, Jianbo; Li, Kongjing; Tian, Guiyun; Zhu, Junzhen; Gao, Yunlai; Tang, Chaoqing; Chen, Xiaotian

    2017-08-01

    This letter proposes a novel motion-induced eddy current based thermography (MIECT) for high-speed inspection. In contrast to conventional eddy current thermography (ECT) based on a time-varying magnetic field created by an AC coil, the motion-induced eddy current is induced by the relative motion between magnetic field and inspected objects. A rotating magnetic field created by three-phase windings is used to investigate the heating principle and feasibility of the proposed method. Firstly, based on Faraday's law the distribution of MIEC is investigated, which is then validated by numerical simulation. Further, experimental studies are conducted to validate the proposed method by creating rotating magnetic fields at different speeds from 600 rpm to 6000 rpm, and it is verified that rotating speed will increase MIEC intensity and thereafter improve the heating efficiency. The conclusion can be preliminarily drawn that the proposed MIECT is a platform suitable for high-speed inspection.

  19. The relationship of global form and motion detection to reading fluency.

    PubMed

    Englund, Julia A; Palomares, Melanie

    2012-08-15

    Visual motion processing in typical and atypical readers has suggested aspects of reading and motion processing share a common cortical network rooted in dorsal visual areas. Few studies have examined the relationship between reading performance and visual form processing, which is mediated by ventral cortical areas. We investigated whether reading fluency correlates with coherent motion detection thresholds in typically developing children using random dot kinematograms. As a comparison, we also evaluated the correlation between reading fluency and static form detection thresholds. Results show that both dorsal and ventral visual functions correlated with components of reading fluency, but that they have different developmental characteristics. Motion coherence thresholds correlated with reading rate and accuracy, which both improved with chronological age. Interestingly, when controlling for non-verbal abilities and age, reading accuracy significantly correlated with thresholds for coherent form detection but not coherent motion detection in typically developing children. Dorsal visual functions that mediate motion coherence seem to be related maturation of broad cognitive functions including non-verbal abilities and reading fluency. However, ventral visual functions that mediate form coherence seem to be specifically related to accurate reading in typically developing children. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Psilocybin impairs high-level but not low-level motion perception.

    PubMed

    Carter, Olivia L; Pettigrew, John D; Burr, David C; Alais, David; Hasler, Felix; Vollenweider, Franz X

    2004-08-26

    The hallucinogenic serotonin(1A&2A) agonist psilocybin is known for its ability to induce illusions of motion in otherwise stationary objects or textured surfaces. This study investigated the effect of psilocybin on local and global motion processing in nine human volunteers. Using a forced choice direction of motion discrimination task we show that psilocybin selectively impairs coherence sensitivity for random dot patterns, likely mediated by high-level global motion detectors, but not contrast sensitivity for drifting gratings, believed to be mediated by low-level detectors. These results are in line with those observed within schizophrenic populations and are discussed in respect to the proposition that psilocybin may provide a model to investigate clinical psychosis and the pharmacological underpinnings of visual perception in normal populations.

  1. Reduction of vortex induced forces and motion through surface roughness control

    DOEpatents

    Bernitsas, Michael M; Raghavan, Kamaldev

    2014-04-01

    Roughness is added to the surface of a bluff body in a relative motion with respect to a fluid. The amount, size, and distribution of roughness on the body surface is controlled passively or actively to modify the flow around the body and subsequently the Vortex Induced Forces and Motion (VIFM). The added roughness, when designed and implemented appropriately, affects in a predetermined way the boundary layer, the separation of the boundary layer, the level of turbulence, the wake, the drag and lift forces, and consequently the Vortex Induced Motion (VIM), and the fluid-structure interaction. The goal of surface roughness control is to decrease/suppress Vortex Induced Forces and Motion. Suppression is required when fluid-structure interaction becomes destructive as in VIM of flexible cylinders or rigid cylinders on elastic support, such as underwater pipelines, marine risers, tubes in heat exchangers, nuclear fuel rods, cooling towers, SPAR offshore platforms.

  2. Motion Alters Color Appearance

    PubMed Central

    Hong, Sang-Wook; Kang, Min-Suk

    2016-01-01

    Chromatic induction compellingly demonstrates that chromatic context as well as spectral lights reflected from an object determines its color appearance. Here, we show that when one colored object moves around an identical stationary object, the perceived saturation of the stationary object decreases dramatically whereas the saturation of the moving object increases. These color appearance shifts in the opposite directions suggest that normalization induced by the object’s motion may mediate the shift in color appearance. We ruled out other plausible alternatives such as local adaptation, attention, and transient neural responses that could explain the color shift without assuming interaction between color and motion processing. These results demonstrate that the motion of an object affects both its own color appearance and the color appearance of a nearby object, suggesting a tight coupling between color and motion processing. PMID:27824098

  3. Inattention blindness to motion in area MT

    PubMed Central

    Harrison, Ian T.; Weiner, Katherine F.; Ghose, Geoffrey M.

    2013-01-01

    Subjects naturally form and use expectations to solve familiar tasks, but the accuracy of these expectations, and the neuronal mechanisms by which these expectations enhance behavior, are unclear. We trained animals (Macaca mulatta) in a challenging perceptual task in which the likelihood of a very brief pulse of motion was consistently modulated over time and space. Pulse likelihood had dramatic effects on behavior: unexpected pulses were nearly invisible to the animals. To examine the neuronal basis of such inattention blindness, we recorded from single neurons in the middle temporal (MT) area, an area related to motion perception. Fluctuations in how reliably MT neurons both signaled stimulus events and predicted behavioral choices were highly correlated with changes in performance over the course of individual trials. A simple neuronal pooling model reveals the dramatic behavioral effects of attention in this task can be completely explained by changes in the reliability of a small number of MT neurons. PMID:23658178

  4. Motion induced interplay effects for VMAT radiotherapy.

    PubMed

    Edvardsson, Anneli; Nordström, Fredrik; Ceberg, Crister; Ceberg, Sofie

    2018-04-19

    The purpose of this study was to develop a method to simulate breathing motion induced interplay effects for volumetric modulated arc therapy (VMAT), to verify the proposed method with measurements, and to use the method to investigate how interplay effects vary with different patient- and machine specific parameters. VMAT treatment plans were created on a virtual phantom in a treatment planning system (TPS). Interplay effects were simulated by dividing each plan into smaller sub-arcs using an in-house developed software and shifting the isocenter for each sub-arc to simulate a sin 6 breathing motion in the superior-inferior direction. The simulations were performed for both flattening-filter (FF) and flattening-filter free (FFF) plans and for different breathing amplitudes, period times, initial breathing phases, dose levels, plan complexities, CTV sizes, and collimator angles. The resulting sub-arcs were calculated in the TPS, generating a dose distribution including the effects of motion. The interplay effects were separated from dose blurring and the relative dose differences to 2% and 98% of the CTV volume (ΔD 98% and ΔD 2% ) were calculated. To verify the simulation method, measurements were carried out, both static and during motion, using a quasi-3D phantom and a motion platform. The results of the verification measurements during motion were comparable to the results of the static measurements. Considerable interplay effects were observed for individual fractions, with the minimum ΔD 98% and maximum ΔD 2% being  -16.7% and 16.2%, respectively. The extent of interplay effects was larger for FFF compared to FF and generally increased for higher breathing amplitudes, larger period times, lower dose levels, and more complex treatment plans. Also, the interplay effects varied considerably with the initial breathing phase, and larger variations were observed for smaller CTV sizes. In conclusion, a method to simulate motion induced interplay effects was

  5. Motion induced interplay effects for VMAT radiotherapy

    NASA Astrophysics Data System (ADS)

    Edvardsson, Anneli; Nordström, Fredrik; Ceberg, Crister; Ceberg, Sofie

    2018-04-01

    The purpose of this study was to develop a method to simulate breathing motion induced interplay effects for volumetric modulated arc therapy (VMAT), to verify the proposed method with measurements, and to use the method to investigate how interplay effects vary with different patient- and machine specific parameters. VMAT treatment plans were created on a virtual phantom in a treatment planning system (TPS). Interplay effects were simulated by dividing each plan into smaller sub-arcs using an in-house developed software and shifting the isocenter for each sub-arc to simulate a sin6 breathing motion in the superior–inferior direction. The simulations were performed for both flattening-filter (FF) and flattening-filter free (FFF) plans and for different breathing amplitudes, period times, initial breathing phases, dose levels, plan complexities, CTV sizes, and collimator angles. The resulting sub-arcs were calculated in the TPS, generating a dose distribution including the effects of motion. The interplay effects were separated from dose blurring and the relative dose differences to 2% and 98% of the CTV volume (ΔD98% and ΔD2%) were calculated. To verify the simulation method, measurements were carried out, both static and during motion, using a quasi-3D phantom and a motion platform. The results of the verification measurements during motion were comparable to the results of the static measurements. Considerable interplay effects were observed for individual fractions, with the minimum ΔD98% and maximum ΔD2% being  ‑16.7% and 16.2%, respectively. The extent of interplay effects was larger for FFF compared to FF and generally increased for higher breathing amplitudes, larger period times, lower dose levels, and more complex treatment plans. Also, the interplay effects varied considerably with the initial breathing phase, and larger variations were observed for smaller CTV sizes. In conclusion, a method to simulate motion induced interplay effects was

  6. Thunder-induced ground motions: 2. Site characterization

    NASA Astrophysics Data System (ADS)

    Lin, Ting-L.; Langston, Charles A.

    2009-04-01

    Thunder-induced ground motion, near-surface refraction, and Rayleigh wave dispersion measurements were used to constrain near-surface velocity structure at an unconsolidated sediment site. We employed near-surface seismic refraction measurements to first define ranges for site structure parameters. Air-coupled and hammer-generated Rayleigh wave dispersion curves were used to further constrain the site structure by a grid search technique. The acoustic-to-seismic coupling is modeled as an incident plane P wave in a fluid half-space impinging into a solid layered half-space. We found that the infrasound-induced ground motions constrained substrate velocities and the average thickness and velocities of the near-surface layer. The addition of higher-frequency near-surface Rayleigh waves produced tighter constraints on the near-surface velocities. This suggests that natural or controlled airborne pressure sources can be used to investigate the near-surface site structures for earthquake shaking hazard studies.

  7. The motionally induced back-emf in railguns

    NASA Astrophysics Data System (ADS)

    Graneau, Peter; Thompson, Donald S.; Morrill, Susan L.

    1990-04-01

    Relative motion between armature and rails in the railgun produces induced emf's. The Lorentz force formula correctly predicts the emf present in the armature but it fails to acknowledge the induction of further emf's in the rails which are proportional to the relative velocity. It is easy to confirm the existence of the additional rail emf's behind and ahead of the armature, by voltage measurements across the muzzle and the breech of the railgun. Neumann's forgotten law of induction, which was first proposed in 1845, correctly accounts for the magnitude and position of all motionally induced emf components in the railgun circuit. The velocity dependent back-emf's in the rails coincide with the Ampere recoil forces in the railheads just behind the armature. Electric power extended in overcoming these back-emf's, and associated with the recoil forces, seem to store elastic strain energy in the rails.

  8. Gender differences in motion sickness history and susceptibility to optokinetic rotation-induced motion sickness.

    PubMed

    Park, A H; Hu, S

    1999-11-01

    The present study investigated gender differences in motion sickness history and susceptibility to optokinetic rotation-induced motion sickness. The study included two phases. In Phase 1, 485 subjects filled out a survey of previous incidence of motion sickness. Results indicated that women reported significantly greater incidence of feeling motion sickness than did men on buses, on trains, on planes, in cars, and on amusement rides before the age of 12 yr; and on buses, on trains, on planes, in boats, on ships, in cars, on amusement rides, and on swings between the ages of 12 and 25 yr. Women also reported significantly higher incidence of being actually sick than did men on buses before the age of 12 yr and on buses, on ships, and in cars between the ages of 12 and 25 yr. In Phase 2, each of the 47 subjects viewed an optokinetic rotating-drum for 16 min. Subjects' subjective symptoms of motion sickness (SSMS) were obtained during drum rotation. The results showed that there were no significant differences on SSMS scores between men and women. Although women reported greater incidence in motion sickness history, women did not differ from men in severity of symptoms of motion sickness while viewing a rotating optokinetic drum.

  9. Texture-dependent motion signals in primate middle temporal area

    PubMed Central

    Gharaei, Saba; Tailby, Chris; Solomon, Selina S; Solomon, Samuel G

    2013-01-01

    Neurons in the middle temporal (MT) area of primate cortex provide an important stage in the analysis of visual motion. For simple stimuli such as bars and plaids some neurons in area MT – pattern cells – seem to signal motion independent of contour orientation, but many neurons – component cells – do not. Why area MT supports both types of receptive field is unclear. To address this we made extracellular recordings from single units in area MT of anaesthetised marmoset monkeys and examined responses to two-dimensional images with a large range of orientations and spatial frequencies. Component and pattern cell response remained distinct during presentation of these complex spatial textures. Direction tuning curves were sharpest in component cells when a texture contained a narrow range of orientations, but were similar across all neurons for textures containing all orientations. Response magnitude of pattern cells, but not component cells, increased with the spatial bandwidth of the texture. In addition, response variability in all neurons was reduced when the stimulus was rich in spatial texture. Fisher information analysis showed that component cells provide more informative responses than pattern cells when a texture contains a narrow range of orientations, but pattern cells had more informative responses for broadband textures. Component cells and pattern cells may therefore coexist because they provide complementary and parallel motion signals. PMID:24000175

  10. Effect of Ablation of Area Postrema on Frequency and Latency of Motion Sickness-Induced Emesis in the Squirrel Monkey

    NASA Technical Reports Server (NTRS)

    Brizzee, K. R.; Ordy, J. M.; Mehler, W. R.

    1980-01-01

    Twelve young adult squirrel monkeys of the Bolivian subspecies were subjected to continuous counter-clockwise horizontal rotary motion at 25 rpm, together with a sinusoidal vertical excursion of 6 in. every 2 sec (0.5 Hz). Each animal was exposed to this motion regimen for a period of 60 min once each week for three consecutive weeks. Following the third weekly motion test bilateral ablation of the Area Postrema (AP) was performed in eight of the animals by thermal cautery. Two control animals were sham-operated after the third motion test while two additional controls were given the motion tests as noted above but were not operated. The four controls were considered as a single group for statistical analyses of results of the motion tests. After a recovery period of 30 to 40 days, and at a comparable interval in the non-operated controls, each animal was again tested for motion sensitivity for three consecutive weeks. The brains of all of the animals were then fixed by left ventriculal cardiac perfusion with Bouin's fluid and processed for histological evaluation of the bilateral AP ablation in comparison with the control brains. Five of the AP-ablated animals postoperatively were completely refractory to the motion stimuli, two exhibited a decreased number of emetic responses, and one exhibited the same number of responses before and after the AP lesions. The controls exhibited no significant difference in emetic sensitivity on the second series of three weekly tests than on the first series. The results of this investigation appear to be in agreement with the observations of Wang and Chinn in the dog indicating that the integrity of the AP (CTZ) is essential to the emetic response to motion.

  11. Role of the area postrema in radiation-induced taste aversion learning and emesis in cats

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

    Rabin, B.M.; Hunt, W.A.; Chedester, A.L.

    1986-01-01

    The role of the area postrema in radiation-induced emesis and taste aversion learning and the relationship between these behaviors were studied in cats. The potential involvement of neural factors which might be independent of the area postrema was minimized by using low levels of ionizing radiation (100 rads at a dose rate of 40 rads/min) to elicit a taste aversion, and by using body-only exposures (4500 and 6000 rads at 450 rads/min) to produce emesis. Lesions of the area postrema disrupted both taste aversion learning and emesis following irradiation. These results, which indicate that the area postrema is involved inmore » the mediation of both radiation-induced emesis and taste aversion learning in cats under these experimental conditions, are interpreted as being consistent with the hypotheses that similar mechanisms mediate both responses to exposure to ionizing radiation, and that the taste aversion learning paradigm can therefore serve as a model system for studying radiation-induced emesis.« less

  12. Postural Instability Induced by Visual Motion Stimuli in Patients With Vestibular Migraine

    PubMed Central

    Lim, Yong-Hyun; Kim, Ji-Soo; Lee, Ho-Won; Kim, Sung-Hee

    2018-01-01

    Patients with vestibular migraine are susceptible to motion sickness. This study aimed to determine whether the severity of posture instability is related to the susceptibility to motion sickness. We used a visual motion paradigm with two conditions of the stimulated retinal field and the head posture to quantify postural stability while maintaining a static stance in 18 patients with vestibular migraine and in 13 age-matched healthy subjects. Three parameters of postural stability showed differences between VM patients and controls: RMS velocity (0.34 ± 0.02 cm/s vs. 0.28 ± 0.02 cm/s), RMS acceleration (8.94 ± 0.74 cm/s2 vs. 6.69 ± 0.87 cm/s2), and sway area (1.77 ± 0.22 cm2 vs. 1.04 ± 0.25 cm2). Patients with vestibular migraine showed marked postural instability of the head and neck when visual stimuli were presented in the retinal periphery. The pseudo-Coriolis effect induced by head roll tilt was not responsible for the main differences in postural instability between patients and controls. Patients with vestibular migraine showed a higher visual dependency and low stability of the postural control system when maintaining quiet standing, which may be related to susceptibility to motion sickness. PMID:29930534

  13. Postural Instability Induced by Visual Motion Stimuli in Patients With Vestibular Migraine.

    PubMed

    Lim, Yong-Hyun; Kim, Ji-Soo; Lee, Ho-Won; Kim, Sung-Hee

    2018-01-01

    Patients with vestibular migraine are susceptible to motion sickness. This study aimed to determine whether the severity of posture instability is related to the susceptibility to motion sickness. We used a visual motion paradigm with two conditions of the stimulated retinal field and the head posture to quantify postural stability while maintaining a static stance in 18 patients with vestibular migraine and in 13 age-matched healthy subjects. Three parameters of postural stability showed differences between VM patients and controls: RMS velocity (0.34 ± 0.02 cm/s vs. 0.28 ± 0.02 cm/s), RMS acceleration (8.94 ± 0.74 cm/s 2 vs. 6.69 ± 0.87 cm/s 2 ), and sway area (1.77 ± 0.22 cm 2 vs. 1.04 ± 0.25 cm 2 ). Patients with vestibular migraine showed marked postural instability of the head and neck when visual stimuli were presented in the retinal periphery. The pseudo-Coriolis effect induced by head roll tilt was not responsible for the main differences in postural instability between patients and controls. Patients with vestibular migraine showed a higher visual dependency and low stability of the postural control system when maintaining quiet standing, which may be related to susceptibility to motion sickness.

  14. Enduring stereoscopic motion aftereffects induced by prolonged adaptation.

    PubMed

    Bowd, C; Rose, D; Phinney, R E; Patterson, R

    1996-11-01

    This study investigated the effects of prolonged adaptation on the recovery of the stereoscopic motion aftereffect (adaptation induced by moving binocular disparity information). The adapting and test stimuli were stereoscopic grating patterns created from disparity, embedded in dynamic random-dot stereograms. Motion aftereffects induced by luminance stimuli were included in the study for comparison. Adaptation duration was either 1, 2, 4, 8, 16, 32 or 64 min and the duration of the ensuing aftereffect was the variable of interest. The results showed that aftereffect duration was proportional to the square root of adaptation duration for both stereoscopic and luminance stimuli; on log-log axes, the relation between aftereffect duration and adaptation duration was a power law with the slope near 0.5 in both cases. For both kinds of stimuli, there was no sign of adaptation saturation even at the longest adaptation duration.

  15. Visual stimuli induced by self-motion and object-motion modify odour-guided flight of male moths (Manduca sexta L.).

    PubMed

    Verspui, Remko; Gray, John R

    2009-10-01

    Animals rely on multimodal sensory integration for proper orientation within their environment. For example, odour-guided behaviours often require appropriate integration of concurrent visual cues. To gain a further understanding of mechanisms underlying sensory integration in odour-guided behaviour, our study examined the effects of visual stimuli induced by self-motion and object-motion on odour-guided flight in male M. sexta. By placing stationary objects (pillars) on either side of a female pheromone plume, moths produced self-induced visual motion during odour-guided flight. These flights showed a reduction in both ground and flight speeds and inter-turn interval when compared with flight tracks without stationary objects. Presentation of an approaching 20 cm disc, to simulate object-motion, resulted in interrupted odour-guided flight and changes in flight direction away from the pheromone source. Modifications of odour-guided flight behaviour in the presence of stationary objects suggest that visual information, in conjunction with olfactory cues, can be used to control the rate of counter-turning. We suggest that the behavioural responses to visual stimuli induced by object-motion indicate the presence of a neural circuit that relays visual information to initiate escape responses. These behavioural responses also suggest the presence of a sensory conflict requiring a trade-off between olfactory and visually driven behaviours. The mechanisms underlying olfactory and visual integration are discussed in the context of these behavioural responses.

  16. Vortex-induced vibration (VIV) effects of a drilling riser due to vessel motion

    NASA Astrophysics Data System (ADS)

    Joseph, R. S.; Wang, J.; Ong, M. C.; Jakobsen, J. B.

    2017-12-01

    A marine riser undergoes oscillatory motion in water due to the vessel motions, known as global dynamic response. This to-and-fro motion of the riser will generate an equivalent flow that can cause Vortex-Induced Vibrations (VIVs), even in the absence of the ocean current. In the present work, full-scale measurement data of a drilling riser operating in the Gulf of Mexico are analysed. The VIV occurrences for the riser are identified from the data and the possible excitation sources are discussed. The oscillatory flow due to vessel motion is compared with the ocean current and its possibility to excite VIV is analysed. The full-scale data analysis provides an insight into the vessel motion-induced VIV of marine risers in the actual field environment.

  17. Integrated evaluation of visually induced motion sickness in terms of autonomic nervous regulation.

    PubMed

    Kiryu, Tohru; Tada, Gen; Toyama, Hiroshi; Iijima, Atsuhiko

    2008-01-01

    To evaluate visually-induced motion sickness, we integrated subjective and objective responses in terms of autonomic nervous regulation. Twenty-seven subjects viewed a 2-min-long first-person-view video section five times (total 10 min) continuously. Measured biosignals, the RR interval, respiration, and blood pressure, were used to estimate the indices related to autonomic nervous activity (ANA). Then we determined the trigger points and some sensation sections based on the time-varying behavior of ANA-related indices. We found that there was a suitable combination of biosignals to present the symptoms of visually-induced motion sickness. Based on the suitable combination, integrating trigger points and subjective scores allowed us to represent the time-distribution of subjective responses during visual exposure, and helps us to understand what types of camera motions will cause visually-induced motion sickness.

  18. Stimulus size and eccentricity in visually induced perception of horizontally translational self-motion.

    PubMed

    Nakamura, S; Shimojo, S

    1998-10-01

    The effects of the size and eccentricity of the visual stimulus upon visually induced perception of self-motion (vection) were examined with various sizes of central and peripheral visual stimulation. Analysis indicated the strength of vection increased linearly with the size of the area in which the moving pattern was presented, but there was no difference in vection strength between central and peripheral stimuli when stimulus sizes were the same. Thus, the effect of stimulus size is homogeneous across eccentricities in the visual field.

  19. Pilot-Induced Oscillation Prediction With Three Levels of Simulation Motion Displacement

    NASA Technical Reports Server (NTRS)

    Schroeder, Jeffery A.; Chung, William W. Y.; Tran, Duc T.; Laforce, Soren; Bengford, Norman J.

    2001-01-01

    Simulator motion platform characteristics were examined to determine if the amount of motion affects pilot-induced oscillation (PIO) prediction. Five test pilots evaluated how susceptible 18 different sets of pitch dynamics were to PIOs with three different levels of simulation motion platform displacement: large, small, and none. The pitch dynamics were those of a previous in-flight experiment, some of which elicited PIOs These in-flight results served as truth data for the simulation. As such, the in-flight experiment was replicated as much as possible. Objective and subjective data were collected and analyzed With large motion, PIO and handling qualities ratings matched the flight data more closely than did small motion or no motion. Also, regardless of the aircraft dynamics, large motion increased pilot confidence in assigning handling qualifies ratings, reduced safety pilot trips, and lowered touchdown velocities. While both large and small motion provided a pitch rate cue of high fidelity, only large motion presented the pilot with a high fidelity vertical acceleration cue.

  20. Patterns of fMRI activity dissociate overlapping functional brain areas that respond to biological motion.

    PubMed

    Peelen, Marius V; Wiggett, Alison J; Downing, Paul E

    2006-03-16

    Accurate perception of the actions and intentions of other people is essential for successful interactions in a social environment. Several cortical areas that support this process respond selectively in fMRI to static and dynamic displays of human bodies and faces. Here we apply pattern-analysis techniques to arrive at a new understanding of the neural response to biological motion. Functionally defined body-, face-, and motion-selective visual areas all responded significantly to "point-light" human motion. Strikingly, however, only body selectivity was correlated, on a voxel-by-voxel basis, with biological motion selectivity. We conclude that (1) biological motion, through the process of structure-from-motion, engages areas involved in the analysis of the static human form; (2) body-selective regions in posterior fusiform gyrus and posterior inferior temporal sulcus overlap with, but are distinct from, face- and motion-selective regions; (3) the interpretation of region-of-interest findings may be substantially altered when multiple patterns of selectivity are considered.

  1. Motion-Induced Interruptions and Postural Equilibrium in Linear Lateral Accelerations

    DTIC Science & Technology

    2013-09-01

    model. 50 THIS PAGE INTENTIONALLY LEFT BLANK 51 APPENDIX A. PRE- AND POSTTEST QUESTIONNAIRES Pretest ...Screening and Pretest Q. Midtest Q. Posttest Q. Motion Profile/Noldus Video Researchers’ Data 3001 1-2-3-4 √ √ √ √ √ 3102 * 1-2-3-4...parameters and Motion-Induced Interruptions (MIIs) in a controlled environment, and (b) focus on the effect of the frequency (period) of the

  2. Conditioned taste aversion induced by motion is prevented by selective vagotomy in the rat

    NASA Technical Reports Server (NTRS)

    Fox, Robert A.; Mckenna, Susan

    1991-01-01

    The role of the vagus nerve in motion-induced conditioned taste aversion (CTA) was studied in hooded rats. Animals with complete, selective gastric vagotomy failed to form conditioned taste aversion after multiple conditioning sessions in which the conditioned stimulus (a cider vinegar solution) was drunk immediately before a 30-min exposure to vertical axis rotation at 150 deg/s. Results are discussed with reference to the use of CTA as a measure of motion-induced 'sickness' or gastrointestinal disturbance, and because motion-induced CTA requires that both the vagus nerve and the vestibular apparatus be intact, in light of the possible convergence of vegal and vestibular functions.

  3. Earthquake scenario ground motions for the urban area of Evansville, Indiana

    USGS Publications Warehouse

    Haase, Jennifer S.; Nowack, Robert L.; Cramer, Chris H.; Boyd, Oliver S.; Bauer, Robert A.

    2011-01-01

    The Wabash Valley seismic zone and the New Madrid seismic zone are the closest large earthquake source zones to Evansville, Indiana. The New Madrid earthquakes of 1811-1812, over 180 kilometers (km) from Evansville, produced ground motions with a Modified Mercalli Intensity of VII near Evansville, the highest intensity observed in Indiana. Liquefaction evidence has been documented less than 40 km away from Evansville resulting from two large earthquakes in the past 12,000 years in the Wabash Valley. Two earthquake scenarios are described in this paper that demonstrate the expected ground motions for a 33×42-km region around Evansville based on a repeat earthquake from each of these source regions. We perform a one-dimensional analysis for a grid of sites that takes into account the amplification or deamplification of ground motion in the unconsolidated soil layer using a new three-dimensional model of seismic velocity and bedrock depth. There are significant differences in the calculated amplification from that expected for National Earthquake Hazard Reduction Program site class D conditions, with deamplification at many locations within the ancient bedrock valley underlying Evansville. Ground motions relative to the acceleration of gravity (g) in the Evansville area from a simulation of a magnitude (M) 7.7 New Madrid earthquake range from 0.15 to 0.25 g for peak ground acceleration, 0.14 to 0.7 g for 0.2-second (s) spectral acceleration, and 0.05 to 0.25 g for 1.0-s spectral acceleration. Ground motions from a M6.8 Wabash Valley earthquake centered 40 km northwest of the city produce ground motions that decrease with distance from 1.5 to 0.3 g for 0.2-s spectral acceleration when they reach the main part of Evansville, but then increase in amplitude from 0.3 to 0.6 g south of the city and the Ohio River. The densest urbanization in Evansville and Henderson, Ky., is within the area of preferential amplification at 1.0-s period for both scenarios, but the area

  4. Cryo-tomography Tilt-series Alignment with Consideration of the Beam-induced Sample Motion

    PubMed Central

    Fernandez, Jose-Jesus; Li, Sam; Bharat, Tanmay A. M.; Agard, David A.

    2018-01-01

    Recent evidence suggests that the beam-induced motion of the sample during tilt-series acquisition is a major resolution-limiting factor in electron cryo-tomography (cryoET). It causes suboptimal tilt-series alignment and thus deterioration of the reconstruction quality. Here we present a novel approach to tilt-series alignment and tomographic reconstruction that considers the beam-induced sample motion through the tilt-series. It extends the standard fiducial-based alignment approach in cryoET by introducing quadratic polynomials to model the sample motion. The model can be used during reconstruction to yield a motion-compensated tomogram. We evaluated our method on various datasets with different sample sizes. The results demonstrate that our method could be a useful tool to improve the quality of tomograms and the resolution in cryoET. PMID:29410148

  5. Respiratory-Induced Prostate Motion Using Wavelet Decomposition of the Real-Time Electromagnetic Tracking Signal

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

    Lin, Yuting; Liu, Tian; Yang, Xiaofeng

    2013-10-01

    Purpose: The objective of this work is to characterize and quantify the impact of respiratory-induced prostate motion. Methods and Materials: Real-time intrafraction motion is observed with the Calypso 4-dimensional nonradioactive electromagnetic tracking system (Calypso Medical Technologies, Inc. Seattle, Washington). We report the results from a total of 1024 fractions from 31 prostate cancer patients. Wavelet transform was used to decompose the signal to extract and isolate the respiratory-induced prostate motion from the total prostate displacement. Results: Our results show that the average respiratory motion larger than 0.5 mm can be observed in 68% of the fractions. Fewer than 1% ofmore » the patients showed average respiratory motion of less than 0.2 mm, whereas 99% of the patients showed average respiratory-induced motion ranging between 0.2 and 2 mm. The maximum respiratory range of motion of 3 mm or greater was seen in only 25% of the fractions. In addition, about 2% patients showed anxiety, indicated by a breathing frequency above 24 times per minute. Conclusions: Prostate motion is influenced by respiration in most fractions. Real-time intrafraction data are sensitive enough to measure the impact of respiration by use of wavelet decomposition methods. Although the average respiratory amplitude observed in this study is small, this technique provides a tool that can be useful if one moves to smaller treatment margins (≤5 mm). This also opens ups the possibility of being able to develop patient specific margins, knowing that prostate motion is not unpredictable.« less

  6. A TMS study on the contribution of visual area V5 to the perception of implied motion in art and its appreciation.

    PubMed

    Cattaneo, Zaira; Schiavi, Susanna; Silvanto, Juha; Nadal, Marcos

    2017-01-01

    Over the last decade, researchers have sought to understand the brain mechanisms involved in the appreciation of art. Previous studies reported an increased activity in sensory processing regions for artworks that participants find more appealing. Here we investigated the intriguing possibility that activity in cortical area V5-a region in the occipital cortex mediating physical and implied motion detection-is related not only to the generation of a sense of motion from visual cues used in artworks, but also to the appreciation of those artworks. Art-naïve participants viewed a series of paintings and quickly judged whether or not the paintings conveyed a sense of motion, and whether or not they liked them. Triple-pulse TMS applied over V5 while viewing the paintings significantly decreased the perceived sense of motion, and also significantly reduced liking of abstract (but not representational) paintings. Our data demonstrate that V5 is involved in extracting motion information even when the objects whose motion is implied are pictorial representations (as opposed to photographs or film frames), and even in the absence of any figurative content. Moreover, our study suggests that, in the case of untrained people, V5 activity plays a causal role in the appreciation of abstract but not of representational art.

  7. Prospective motion correction with volumetric navigators (vNavs) reduces the bias and variance in brain morphometry induced by subject motion.

    PubMed

    Tisdall, M Dylan; Reuter, Martin; Qureshi, Abid; Buckner, Randy L; Fischl, Bruce; van der Kouwe, André J W

    2016-02-15

    Recent work has demonstrated that subject motion produces systematic biases in the metrics computed by widely used morphometry software packages, even when the motion is too small to produce noticeable image artifacts. In the common situation where the control population exhibits different behaviors in the scanner when compared to the experimental population, these systematic measurement biases may produce significant confounds for between-group analyses, leading to erroneous conclusions about group differences. While previous work has shown that prospective motion correction can improve perceived image quality, here we demonstrate that, in healthy subjects performing a variety of directed motions, the use of the volumetric navigator (vNav) prospective motion correction system significantly reduces the motion-induced bias and variance in morphometry. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Partners in motion and traffic congestion in the Washington, D.C. metropolitan area

    DOT National Transportation Integrated Search

    2001-01-01

    Partners in Motion is a program aimed at improving the quality, quantity, and availability of travel information to transportation agencies, the media, and the public in the Washington, D.C. metropolitan area. This report evaluates Partners in Motion...

  9. Vection-induced gastric dysrhythmias and motion sickness

    NASA Technical Reports Server (NTRS)

    Koch, K. L.; Stern, R. M.

    1986-01-01

    Gastric electrical and mechanical activity during vection-induced motion sickness was investigated. The contractile events of the antrum and gastric myoelectric activity in healthy subjects exposed to vection were measured simultaneously. Symptomatic and myoelectric responses of subjects with vagotomy and gastric resections during vection stimuli were determined. And laboratory based computer systems for analysis of the myoelectric signal were developed. Gastric myoelectric activity was recorded from cutaneous electrodes, i.e., electrogastrograms (EGGs), and antral contractions were measured with intraluminal pressure transducers. Vection was induced by a rotating drum. gastric electromechanical activity was recorded during three periods: 15 min baseline, 15 min drum rotation (vection), and 15 to 30 min recovery. Preliminary results showed that catecholamine responses in nauseated versus symptom-free subjects were divergent and pretreatment with metoclopramide HC1 (Reglan) prevented vection-induced nausea and reduced tachygastrias in two previously symptomatic subjects.

  10. Blockade of 5-hydroxytryptamine(3) receptors prevents cisplatin-induced but not motion- or xylazine-induced emesis in the cat

    NASA Technical Reports Server (NTRS)

    Lucot, James B.

    1989-01-01

    The effects of the 5-hydroxytryptamine(3) (5-HT-3) antagonists ICS 205-930 and MDL 72222 on the emesis induced by motion or by emetic doses of xylazine (0.66 mg/kg administered SC) or cisplatin (7.5 mg/kg infused over a period of 4-5 min) were investigated in cats. It was found that neither the low (0.1 mg/kg) or the high (1.0 mg.kg) doses of ICS 205-930 or MDL 72222 prevented emesis elicited by screening motion challenges or xylazine. On the other hand, treatment cats by 1.0 mg/kg of ICS 205-930 was effective against cisplatin-induced motion sickness, in agreement with earlier results obtained on other mammals.

  11. Human motion analysis with detection of subpart deformations

    NASA Astrophysics Data System (ADS)

    Wang, Juhui; Lorette, Guy; Bouthemy, Patrick

    1992-06-01

    One essential constraint used in 3-D motion estimation from optical projections is the rigidity assumption. Because of muscle deformations in human motion, this rigidity requirement is often violated for some regions on the human body. Global methods usually fail to bring stable solutions. This paper presents a model-based approach to combating the effect of muscle deformations in human motion analysis. The approach developed is based on two main stages. In the first stage, the human body is partitioned into different areas, where each area is consistent with a general motion model (not necessarily corresponding to a physical existing motion pattern). In the second stage, the regions are eliminated under the hypothesis that they are not induced by a specific human motion pattern. Each hypothesis is generated by making use of specific knowledge about human motion. A global method is used to estimate the 3-D motion parameters in basis of valid segments. Experiments based on a cycling motion sequence are presented.

  12. Motion-induced phase error estimation and correction in 3D diffusion tensor imaging.

    PubMed

    Van, Anh T; Hernando, Diego; Sutton, Bradley P

    2011-11-01

    A multishot data acquisition strategy is one way to mitigate B0 distortion and T2∗ blurring for high-resolution diffusion-weighted magnetic resonance imaging experiments. However, different object motions that take place during different shots cause phase inconsistencies in the data, leading to significant image artifacts. This work proposes a maximum likelihood estimation and k-space correction of motion-induced phase errors in 3D multishot diffusion tensor imaging. The proposed error estimation is robust, unbiased, and approaches the Cramer-Rao lower bound. For rigid body motion, the proposed correction effectively removes motion-induced phase errors regardless of the k-space trajectory used and gives comparable performance to the more computationally expensive 3D iterative nonlinear phase error correction method. The method has been extended to handle multichannel data collected using phased-array coils. Simulation and in vivo data are shown to demonstrate the performance of the method.

  13. Egocentric and Allocentric Localization During Induced Motion

    PubMed Central

    Post, Robert B.; Welch, Robert B.; Whitney, David

    2009-01-01

    This research examined motor measures of the apparent egocentric location and perceptual measures of the apparent allocentric location of a target that was being seen to undergo induced motion (IM). In Experiments 1 and 3, subjects fixated a stationary dot (IM target) while a rectangular surround stimulus (inducing stimulus) oscillated horizontally. The inducing stimulus motion caused the IM target to appear to move in the opposite direction. In Experiment 1, two dots (flashed targets) were flashed above and below the IM target when the surround had reached its leftmost or rightmost displacement from the subject’s midline. Subjects pointed open loop at either the apparent egocentric location of the IM target or at the bottom of the two flashed targets. On separate trials, subjects made judgments of the Vernier alignment of the IM target with the flashed targets at the endpoints of the surround’s oscillation. The pointing responses were displaced in the direction of the previously seen IM for the IM target and to a lesser degree for the bottom flashed target. However, the allocentric Vernier judgments demonstrated no perceptual displacement of the IM target relative to the flashed targets. Thus, IM results in a dissociation of egocentric location measures from allocentric location measures. In Experiment 2, pointing and Vernier measures were obtained with stationary horizontally displaced surrounds and there was no dissociation of egocentric location measures from allocentric location measures. These results indicate that the Roelofs effect did not produce the pattern of results in Experiment 1. In Experiment 3, pointing and Vernier measures were obtained when the surround was at the midpoint of an oscillation. In this case, egocentric pointing responses were displaced in the direction of surround motion (opposite IM) for the IM target and to a greater degree for the bottom flashed target. However, there was no apparent displacement of the IM target relative to

  14. Accelerations induced by body motions during snow skiing

    NASA Astrophysics Data System (ADS)

    Mote, C. D.; Louie, J. K.

    1983-05-01

    Work done by the snow skier during pumping and rocking the center of mass can result in significant accelerations. Pumping and rocking strategies maximizing the velocity of a particle over undulating snow surfaces have been investigated in this paper. The prescribed motions included translation of the particle mass radially from a point contact with the snow surface and rocking of the point contact forward and backward in the vertical plane. The mechanics of the induced velocity variations and the expected magnitude of the velocity variation were of primary interest. The equations of motion were integrated numerically to determine skier-ski model velocity. Positive and negative variations in velocity from 10% to 100% were predicted with pumping strategies over distances of 10-15 m.

  15. 8-OH-DPAT does not interfere with habituation to motion-induced emesis in cats

    NASA Technical Reports Server (NTRS)

    Lucot, James B.; Crampton, George H.

    1991-01-01

    Experiments were performed to determine if suppression of motion-induced emesis (motion sickness) by 8-OH-DPAT altered the development or retention of habituation to the motion stimulus. Cats received 8-OH-DPAT followed by provocative motion on three consecutive treatment days. A drug-free test on the fourth day resulted in an incidence of emesis that was not different from that obtained on the fourth consecutive day of drug-free motion testing. Three consecutive days of treatment with 8-OH-DPAT without motion had no effect on the incidence of motion sickness on the fourth day. It was concluded that suppression of motion sickness by 8-OH-DPAT does not alter the acquisition or retention of habituation.

  16. Micromagnetic analysis of current-induced domain wall motion in a bilayer nanowire with synthetic antiferromagnetic coupling

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

    Komine, Takashi, E-mail: komine@mx.ibaraki.ac.jp; Aono, Tomosuke

    We demonstrate current-induced domain wall motion in bilayer nanowire with synthetic antiferromagnetic (SAF) coupling by modeling two body problems for motion equations of domain wall. The influence of interlayer exchange coupling and magnetostatic interactions on current-induced domain wall motion in SAF nanowires was also investigated. By assuming the rigid wall model for translational motion, the interlayer exchange coupling and the magnetostatic interaction between walls and domains in SAF nanowires enhances domain wall speed without any spin-orbit-torque. The enhancement of domain wall speed was discussed by energy distribution as a function of wall angle configuration in bilayer nanowires.

  17. Electric-field-induced motion of colloid particles in smectic liquid crystals

    NASA Astrophysics Data System (ADS)

    Jakli, Antal

    2005-03-01

    We present the first observations of DC electric-field-induced rotational and translational motion of finite particles in liquid crystals. The electro-rotation is basically identical to the well known Quincke rotation, which triggers the translational motion at higher fields. From the electric field dependence of the angular velocity of the rotation we obtain the viscosity of the liquid crystals. The analysis of the translational motion in smectic liquid crystals indicates elastic responses near the threshold for translation. At increasing fields the speed of the particles is increasing and at sufficiently high speeds the flow of the smectic A and smectic C liquid crystal around the beads become purely viscous. Colloid particles in smectic materials maybe considered as model systems for understanding motion of proteins in cell membranes.

  18. A template-free solvent-mediated synthesis of high surface area boron nitride nanosheets for aerobic oxidative desulfurization.

    PubMed

    Wu, Peiwen; Zhu, Wenshuai; Chao, Yanhong; Zhang, Jinshui; Zhang, Pengfei; Zhu, Huiyuan; Li, Changfeng; Chen, Zhigang; Li, Huaming; Dai, Sheng

    2016-01-04

    Hexagonal boron nitride nanosheets (h-BNNs) with rather high specific surface area (SSA) are important two-dimensional layer-structured materials. Here, a solvent-mediated synthesis of h-BNNs revealed a template-free lattice plane control strategy that induced high SSA nanoporous structured h-BNNs with outstanding aerobic oxidative desulfurization performance.

  19. Auditory motion processing after early blindness

    PubMed Central

    Jiang, Fang; Stecker, G. Christopher; Fine, Ione

    2014-01-01

    Studies showing that occipital cortex responds to auditory and tactile stimuli after early blindness are often interpreted as demonstrating that early blind subjects “see” auditory and tactile stimuli. However, it is not clear whether these occipital responses directly mediate the perception of auditory/tactile stimuli, or simply modulate or augment responses within other sensory areas. We used fMRI pattern classification to categorize the perceived direction of motion for both coherent and ambiguous auditory motion stimuli. In sighted individuals, perceived motion direction was accurately categorized based on neural responses within the planum temporale (PT) and right lateral occipital cortex (LOC). Within early blind individuals, auditory motion decisions for both stimuli were successfully categorized from responses within the human middle temporal complex (hMT+), but not the PT or right LOC. These findings suggest that early blind responses within hMT+ are associated with the perception of auditory motion, and that these responses in hMT+ may usurp some of the functions of nondeprived PT. Thus, our results provide further evidence that blind individuals do indeed “see” auditory motion. PMID:25378368

  20. Postural time-to-contact as a precursor of visually induced motion sickness.

    PubMed

    Li, Ruixuan; Walter, Hannah; Curry, Christopher; Rath, Ruth; Peterson, Nicolette; Stoffregen, Thomas A

    2018-06-01

    The postural instability theory of motion sickness predicts that subjective symptoms of motion sickness will be preceded by unstable control of posture. In previous studies, this prediction has been confirmed with measures of the spatial magnitude and the temporal dynamics of postural activity. In the present study, we examine whether precursors of visually induced motion sickness might exist in postural time-to-contact, a measure of postural activity that is related to the risk of falling. Standing participants were exposed to oscillating visual motion stimuli in a standard laboratory protocol. Both before and during exposure to visual motion stimuli, we monitored the kinematics of the body's center of pressure. We predicted that postural activity would differ between participants who reported motion sickness and those who did not, and that these differences would exist before participants experienced subjective symptoms of motion sickness. During exposure to visual motion stimuli, the multifractality of sway differed between the Well and Sick groups. Postural time-to-contact differed between the Well and Sick groups during exposure to visual motion stimuli, but also before exposure to any motion stimuli. The results provide a qualitatively new type of support for the postural instability theory of motion sickness.

  1. Iterative motion compensation approach for ultrasonic thermal imaging

    NASA Astrophysics Data System (ADS)

    Fleming, Ioana; Hager, Gregory; Guo, Xiaoyu; Kang, Hyun Jae; Boctor, Emad

    2015-03-01

    As thermal imaging attempts to estimate very small tissue motion (on the order of tens of microns), it can be negatively influenced by signal decorrelation. Patient's breathing and cardiac cycle generate shifts in the RF signal patterns. Other sources of movement could be found outside the patient's body, like transducer slippage or small vibrations due to environment factors like electronic noise. Here, we build upon a robust displacement estimation method for ultrasound elastography and we investigate an iterative motion compensation algorithm, which can detect and remove non-heat induced tissue motion at every step of the ablation procedure. The validation experiments are performed on laboratory induced ablation lesions in ex-vivo tissue. The ultrasound probe is either held by the operator's hand or supported by a robotic arm. We demonstrate the ability to detect and remove non-heat induced tissue motion in both settings. We show that removing extraneous motion helps unmask the effects of heating. Our strain estimation curves closely mirror the temperature changes within the tissue. While previous results in the area of motion compensation were reported for experiments lasting less than 10 seconds, our algorithm was tested on experiments that lasted close to 20 minutes.

  2. A template-free solvent-mediated synthesis of high surface area boron nitride nanosheets for aerobic oxidative desulfurization

    DOE PAGES

    Wu, Peiwen; Zhu, Wenshuai; Chao, Yanhong; ...

    2015-10-16

    Hexagonal boron nitride nanosheets (h-BNNs) with rather high specific surface area (SSA) are important two-dimensional layer-structured materials. Here in this study, a solvent-mediated synthesis of h-BNNs revealed a template-free lattice plane control strategy that induced high SSA nanoporous structured h-BNNs with outstanding aerobic oxidative desulfurization performance.

  3. Prostacyclin-induced hyperthermia - Implication of a protein mediator

    NASA Technical Reports Server (NTRS)

    Kandasamy, S. B.; Williams, B. A.

    1982-01-01

    The mechanism of the prostacyclin-linked hyperthermia is studied in rabbits. Results show that intracerebroventricular administration of prostacyclin (PGI2) induces dose-related hyperthermia at room temperature (21 C), as well as at low (4 C) and high (30 C) ambient temperatures. It is found that this PGI2-induced hyperthermia is not mediated by its stable metabolite 6-keto prostaglandin F-1(alpha). Only one of the three anion transport systems, the liver transport system, appears to be important to the central inactivation of pyrogen, prostaglandin E2, and PGI2. Phenoxybenzamine and pimozide have no thermolytic effect on PGI2-induced hyperthermia, while PGI2 still induces hyperthermia after norepinephrine (NE) and dopamine levels are depleted by 6-hydroxydopamine. Indomethacin and SC-19220 (a PG antagonist) do not antagonize PGI2 induced hyperthermia, while theophylline does not accentuate the PGI2-induced hyperthermia. However, the hyperthermic response to PGI2 is attenuated by central administration of the protein synthesis inhibitor, anisomycin. It is concluded that PGI2-induced hyperthermia is not induced by NE, dopamine, or cyclic AMP, but rather that a protein mediator is implicated in the induction of fever by PG12.

  4. PUMA mediates ER stress-induced apoptosis in portal hypertensive gastropathy

    PubMed Central

    Tan, S; Wei, X; Song, M; Tao, J; Yang, Y; Khatoon, S; Liu, H; Jiang, J; Wu, B

    2014-01-01

    Mucosal apoptosis has been demonstrated to be an essential pathological feature in portal hypertensive gastropathy (PHG). p53-upregulated modulator of apoptosis (PUMA) was identified as a BH3-only Bcl-2 family protein that has an essential role in apoptosis induced by a variety of stimuli, including endoplasmic reticulum (ER) stress. However, whether PUMA is involved in mucosal apoptosis in PHG remains unclear, and whether PUMA induces PHG by mediating ER stress remains unknown. The aim of the study is to investigate whether PUMA is involved in PHG by mediating ER stress apoptotic signaling. To identify whether PUMA is involved in PHG by mediating ER stress, gastric mucosal injury and apoptosis were studied in both PHG patients and PHG animal models using PUMA knockout (PUMA-KO) and PUMA wild-type (PUMA-WT) mice. The induction of PUMA expression and ER stress signaling were investigated, and the mechanisms of PUMA-mediated apoptosis were analyzed. GES-1 and SGC7901 cell lines were used to further identify whether PUMA-mediated apoptosis was induced by ER stress in vitro. Epithelial apoptosis and PUMA were markedly induced in the gastric mucosa of PHG patients and mouse PHG models. ER stress had a potent role in the induction of PUMA and apoptosis in PHG models, and the apoptosis was obviously attenuated in PUMA-KO mice. Although the targeted deletion of PUMA did not affect ER stress, mitochondrial apoptotic signaling was downregulated in mice. Meanwhile, PUMA knockdown significantly ameliorated ER stress-induced mitochondria-dependent apoptosis in vitro. These results indicate that PUMA mediates ER stress-induced mucosal epithelial apoptosis through the mitochondrial apoptotic pathway in PHG, and that PUMA is a potentially therapeutic target for PHG. PMID:24625987

  5. Towards motion insensitive EEG-fMRI: Correcting motion-induced voltages and gradient artefact instability in EEG using an fMRI prospective motion correction (PMC) system.

    PubMed

    Maziero, Danilo; Velasco, Tonicarlo R; Hunt, Nigel; Payne, Edwin; Lemieux, Louis; Salmon, Carlos E G; Carmichael, David W

    2016-09-01

    The simultaneous acquisition of electroencephalography and functional magnetic resonance imaging (EEG-fMRI) is a multimodal technique extensively applied for mapping the human brain. However, the quality of EEG data obtained within the MRI environment is strongly affected by subject motion due to the induction of voltages in addition to artefacts caused by the scanning gradients and the heartbeat. This has limited its application in populations such as paediatric patients or to study epileptic seizure onset. Recent work has used a Moiré-phase grating and a MR-compatible camera to prospectively update image acquisition and improve fMRI quality (prospective motion correction: PMC). In this study, we use this technology to retrospectively reduce the spurious voltages induced by motion in the EEG data acquired inside the MRI scanner, with and without fMRI acquisitions. This was achieved by modelling induced voltages from the tracking system motion parameters; position and angles, their first derivative (velocities) and the velocity squared. This model was used to remove the voltages related to the detected motion via a linear regression. Since EEG quality during fMRI relies on a temporally stable gradient artefact (GA) template (calculated from averaging EEG epochs matched to scan volume or slice acquisition), this was evaluated in sessions both with and without motion contamination, and with and without PMC. We demonstrate that our approach is capable of significantly reducing motion-related artefact with a magnitude of up to 10mm of translation, 6° of rotation and velocities of 50mm/s, while preserving physiological information. We also demonstrate that the EEG-GA variance is not increased by the gradient direction changes associated with PMC. Provided a scan slice-based GA template is used (rather than a scan volume GA template) we demonstrate that EEG variance during motion can be supressed towards levels found when subjects are still. In summary, we show that

  6. Effects of Cable Sway, Electrode Surface Area, and Electrode Mass on Electroencephalography Signal Quality during Motion.

    PubMed

    Symeonidou, Evangelia-Regkina; Nordin, Andrew D; Hairston, W David; Ferris, Daniel P

    2018-04-03

    More neuroscience researchers are using scalp electroencephalography (EEG) to measure electrocortical dynamics during human locomotion and other types of movement. Motion artifacts corrupt the EEG and mask underlying neural signals of interest. The cause of motion artifacts in EEG is often attributed to electrode motion relative to the skin, but few studies have examined EEG signals under head motion. In the current study, we tested how motion artifacts are affected by the overall mass and surface area of commercially available electrodes, as well as how cable sway contributes to motion artifacts. To provide a ground-truth signal, we used a gelatin head phantom with embedded antennas broadcasting electrical signals, and recorded EEG with a commercially available electrode system. A robotic platform moved the phantom head through sinusoidal displacements at different frequencies (0-2 Hz). Results showed that a larger electrode surface area can have a small but significant effect on improving EEG signal quality during motion and that cable sway is a major contributor to motion artifacts. These results have implications in the development of future hardware for mobile brain imaging with EEG.

  7. Time-varying behavior of motion vectors in vection-induced images in relation to autonomic regulation.

    PubMed

    Kiryu, Tohru; Yamada, Hiroshi; Jimbo, Masahiro; Bando, Takehiko

    2004-01-01

    Virtual reality (VR) is a promising technology in biomedical engineering, but at the same time enlarges another problem called cybersickness. Aiming at suppression of cybersicknes, we are investigating the influences of vection-induced images on the autonomic regulation quantitatively. We used the motion vectors to quantify image scenes and measured electrocardiogram, blood pressure, and respiration for evaluating the autonomic regulation. Using the estimated motion vectors, we further synthesized random-dot pattern images to survey which component of the global motion vectors seriously affected the autonomic regulation. The results showed that the zoom component with a specific frequency band (0.1-3.0 Hz) would induce sickness.

  8. Anti-inflammatory effects of continuous passive motion on meniscal fibrocartilage

    PubMed Central

    Ferretti, Mario; Srinivasan, Abiraman; Deschner, James; Gassner, Robert; Baliko, Frank; Piesco, Nicholas; Salter, Robert; Agarwal, Sudha

    2016-01-01

    Motion-based therapies have been applied to promote healing of arthritic joints. The goal of the current study was to determine the early molecular events that are responsible for the beneficial actions of motion-based therapies on meniscal fibrocartilage. Rabbit knees with Antigen-Induced-Arthritis (AIA) were exposed to continuous passive motion (CPM) for 24 or 48 h and compared to immobilized knees. The menisci were harvested and glycosaminoglycans (GAG), interleukin-1β (IL-1β), matrix metalloproteinase-1 (MMP-1), cyclooxygenase-2 (COX-2), and interleukin-10 (IL-10) were determined by histochemical analysis. Within 24 h, immobilized knees exhibited marked GAG degradation. The expression of proinflammatory mediators MMP-1, COX-2, and IL-1β was notably increased within 24 h and continued to increase during the next 24 h in immobilized knees. Knees subjected to CPM revealed a rapid and sustained decrease in GAG degradation and the expression of all proinflammatory mediators during the entire period of CPM treatment. More importantly, CPM induced synthesis of the anti-inflammatory cytokine IL-10. The results demonstrate that mechanical signals generated by CPM exert potent anti-inflammatory signals on meniscal fibrochondrocytes. Furthermore, these studies explain the molecular basis of the beneficial effects of CPM observed on articular cartilage and suggest that CPM suppresses the inflammatory process of arthritis more efficiently than immobilization. PMID:16140197

  9. Effect of Induced Charge Electroosmosis on the Dielectrophoretic Motion of Particles

    NASA Astrophysics Data System (ADS)

    Swaminathan, T.; Hu, Howard

    2006-11-01

    Most suspensions involve the formation of ionic double layers next to the surface of particles due to the induced-charge on the surface. These double layers affect the motion of the particle even under AC electric fields. They modify the net dipole moment of the particle and at the same time produce slip velocities on the surfaces of these particles. A method to numerically evaluate the effect of the double layer on the dielectrophoretic motion of particles has been previously developed to study these two effects. The technique involves a matched asymptotic expansion of the electric field near the particle surface, where the double layer is formed, and is written as a jump-boundary-condition for the electric potential when the thickness of the double layer is small compared to the size of the particle. The developed jump-boundary-condition is then used to calculate an effective zeta potential on the particle surface. Unlike classical electroosmosis, this zeta potential is no longer constant on every part of the surface and is dependent on the applied electric field. The effect of the induced-charge electroosmotic slip velocity on the dielectrophoretic motion of particles has been observed using this technique.

  10. Susceptibility of cat and squirrel monkey to motion sickness induced by visual stimulation: Correlation with susceptibility to vestibular stimulation

    NASA Technical Reports Server (NTRS)

    Daunton, N. G.; Fox, R. A.; Crampton, G. H.

    1984-01-01

    Experiments in which the susceptibility of both cats and squirrel monkeys to motion sickness induced by visual stimulation are documented. In addition, it is shown that in both species those individual subjects most highly susceptible to sickness induced by passive motion are also those most likely to become motion sick from visual (optokinetic) stimulation alone.

  11. 20-HETE mediates ozone-induced, neutrophil-independent airway hyper-responsiveness in mice.

    PubMed

    Cooper, Philip R; Mesaros, A Clementina; Zhang, Jie; Christmas, Peter; Stark, Christopher M; Douaidy, Karim; Mittelman, Michael A; Soberman, Roy J; Blair, Ian A; Panettieri, Reynold A

    2010-04-20

    Ozone, a pollutant known to induce airway hyper-responsiveness (AHR), increases morbidity and mortality in patients with obstructive airway diseases and asthma. We postulate oxidized lipids mediate in vivo ozone-induced AHR in murine airways. Male BALB/c mice were exposed to ozone (3 or 6 ppm) or filtered air (controls) for 2 h. Precision cut lung slices (PCLS; 250 microm thickness) containing an intrapulmonary airway ( approximately 0.01 mm(2) lumen area) were prepared immediately after exposure or 16 h later. After 24 h, airways were contracted to carbachol (CCh). Log EC(50) and E(max) values were then calculated by measuring the airway lumen area with respect to baseline. In parallel studies, dexamethasone (2.5 mg/kg), or 1-aminobenzotriazol (ABT) (50 mg/kg) were given intraperitoneal injection to naïve mice 18 h prior to ozone exposure. Indomethacin (10 mg/kg) was administered 2 h prior. Cell counts, cytokine levels and liquid chromatography-mass spectrometry (LC-MS) for lipid analysis were assessed in bronchoalveolar lavage (BAL) fluid from ozone exposed and control mice. Ozone acutely induced AHR to CCh. Dexamethasone or indomethacin had little effect on the ozone-induced AHR; while, ABT, a cytochrome P450 inhibitor, markedly attenuated airway sensitivity. BAL fluid from ozone exposed animals, which did not contain an increase in neutrophils or interleukin (IL)-6 levels, increased airway sensitivity following in vitro incubation with a naïve PCLS. In parallel, significant increases in oxidized lipids were also identified using LC-MS with increases of 20-HETE that were decreased following ABT treatment. These data show that ozone acutely induces AHR to CCh independent of inflammation and is insensitive to steroid treatment or cyclooxygenase (COX) inhibition. BAL fluid from ozone exposed mice mimicked the effects of in vivo ozone exposure that were associated with marked increases in oxidized lipids. 20-HETE plays a pivotal role in mediating acute ozone-induced

  12. Effects of Cable Sway, Electrode Surface Area, and Electrode Mass on Electroencephalography Signal Quality during Motion

    PubMed Central

    Symeonidou, Evangelia-Regkina; Nordin, Andrew D.; Hairston, W. David

    2018-01-01

    More neuroscience researchers are using scalp electroencephalography (EEG) to measure electrocortical dynamics during human locomotion and other types of movement. Motion artifacts corrupt the EEG and mask underlying neural signals of interest. The cause of motion artifacts in EEG is often attributed to electrode motion relative to the skin, but few studies have examined EEG signals under head motion. In the current study, we tested how motion artifacts are affected by the overall mass and surface area of commercially available electrodes, as well as how cable sway contributes to motion artifacts. To provide a ground-truth signal, we used a gelatin head phantom with embedded antennas broadcasting electrical signals, and recorded EEG with a commercially available electrode system. A robotic platform moved the phantom head through sinusoidal displacements at different frequencies (0–2 Hz). Results showed that a larger electrode surface area can have a small but significant effect on improving EEG signal quality during motion and that cable sway is a major contributor to motion artifacts. These results have implications in the development of future hardware for mobile brain imaging with EEG. PMID:29614020

  13. Characteristics of strong ground motion generation areas by fully dynamic earthquake cycles

    NASA Astrophysics Data System (ADS)

    Galvez, P.; Somerville, P.; Ampuero, J. P.; Petukhin, A.; Yindi, L.

    2016-12-01

    During recent subduction zone earthquakes (2010 Mw 8.8 Maule and 2011 Mw 9.0 Tohoku), high frequency ground motion radiation has been detected in deep regions of seismogenic zones. By semblance analysis of wave packets, Kurahashi & Irikura (2013) found strong ground motion generation areas (SMGAs) located in the down dip region of the 2011 Tohoku rupture. To reproduce the rupture sequence of SMGA's and replicate their rupture time and ground motions, we extended previous work on dynamic rupture simulations with slip reactivation (Galvez et al, 2016). We adjusted stresses on the most southern SMGAs of Kurahashi & Irikura (2013) model to reproduce the observed peak ground velocity recorded at seismic stations along Japan for periods up to 5 seconds. To generate higher frequency ground motions we input the rupture time, final slip and slip velocity of the dynamic model into the stochastic ground motion generator of Graves & Pitarka (2010). Our results are in agreement with the ground motions recorded at the KiK-net and K-NET stations.While we reproduced the recorded ground motions of the 2011 Tohoku event, it is unknown whether the characteristics and location of SMGA's will persist in future large earthquakes in this region. Although the SMGA's have large peak slip velocities, the areas of largest final slip are located elsewhere. To elucidate whether this anti-correlation persists in time, we conducted earthquake cycle simulations and analysed the spatial correlation of peak slip velocities, stress drops and final slip of main events. We also investigated whether or not the SMGA's migrate to other regions of the seismic zone.To perform this study, we coupled the quasi-dynamic boundary element solver QDYN (Luo & Ampuero, 2015) and the dynamic spectral element solver SPECFEM3D (Galvez et al., 2014; 2016). The workflow alternates between inter-seismic periods solved with QDYN and coseismic periods solved with SPECFEM3D, with automated switch based on slip rate

  14. THE MEDIAL PREOPTIC AREA MODULATES COCAINE-INDUCED LOCOMOTION IN MALE RATS

    PubMed Central

    Will, Ryan G.; Martz, Julia R.; Dominguez, Juan M.

    2016-01-01

    Cocaine-induced locomotion is mediated by dopamine in the nucleus accumbens (NAc). Recent evidence indicates that the medial preoptic area (mPOA), a region in the rostral hypothalamus, modulates cocaine-induced dopamine in the NAc. Specifically, rats with lesions of the mPOA experienced a greater increase in dopamine following cocaine administration than rats with sham lesions. Whether the mPOA similarly influences cocaine-induced locomotion is not known. Here we examined whether radiofrequency or neurotoxic lesions of the mPOA in male rats influence changes in locomotion that follow cocaine administration. Locomotion was measured following cocaine administration in male rats with neurotoxic, radiofrequency, or sham lesions of the mPOA. Results indicate that bilateral lesions of the mPOA facilitated cocaine-induced locomotion. This facilitation was independent of lesion type, as increased locomotion was observed with either approach. These findings support a role for the mPOA as an integral region in the processing of cocaine-induced behavioral response, in this case locomotor activity. PMID:26947755

  15. Alterations to global but not local motion processing in long-term ecstasy (MDMA) users.

    PubMed

    White, Claire; Brown, John; Edwards, Mark

    2014-07-01

    Growing evidence indicates that the main psychoactive ingredient in the illegal drug "ecstasy" (methylendioxymethamphetamine) causes reduced activity in the serotonin and gamma-aminobutyric acid (GABA) systems in humans. On the basis of substantial serotonin input to the occipital lobe, recent research investigated visual processing in long-term users and found a larger magnitude of the tilt aftereffect, interpreted to reflect broadened orientation tuning bandwidths. Further research found higher orientation discrimination thresholds and reduced long-range interactions in the primary visual area of ecstasy users. The aim of the present research was to investigate whether serotonin-mediated V1 visual processing deficits in ecstasy users extend to motion processing mechanisms. Forty-five participants (21 controls, 24 drug users) completed two psychophysical studies: A direction discrimination study directly measured local motion processing in V1, while a motion coherence task tested global motion processing in area V5/MT. "Primary" ecstasy users (n = 18), those without substantial polydrug use, had significantly lower global motion thresholds than controls [p = 0.027, Cohen's d = 0.78 (large)], indicating increased sensitivity to global motion stimuli, but no difference in local motion processing (p = 0.365). These results extend on previous research investigating the long-term effects of illicit drugs on visual processing. Two possible explanations are explored: defuse attentional processes may be facilitating spatial pooling of motion signals in users. Alternatively, it may be that a GABA-mediated disruption to V5/MT processing is reducing spatial suppression and therefore improving global motion perception in ecstasy users.

  16. Perception of linear horizontal self-motion induced by peripheral vision /linearvection/ - Basic characteristics and visual-vestibular interactions

    NASA Technical Reports Server (NTRS)

    Berthoz, A.; Pavard, B.; Young, L. R.

    1975-01-01

    The basic characteristics of the sensation of linear horizontal motion have been studied. Objective linear motion was induced by means of a moving cart. Visually induced linear motion perception (linearvection) was obtained by projection of moving images at the periphery of the visual field. Image velocity and luminance thresholds for the appearance of linearvection have been measured and are in the range of those for image motion detection (without sensation of self motion) by the visual system. Latencies of onset are around 1 sec and short term adaptation has been shown. The dynamic range of the visual analyzer as judged by frequency analysis is lower than the vestibular analyzer. Conflicting situations in which visual cues contradict vestibular and other proprioceptive cues show, in the case of linearvection a dominance of vision which supports the idea of an essential although not independent role of vision in self motion perception.

  17. Suppression of motion-induced streak artifacts along chords in fan-beam BPF-reconstructions of motion-contaminated projection data

    NASA Astrophysics Data System (ADS)

    King, Martin; Xia, Dan; Yu, Lifeng; Pan, Xiaochuan; Giger, Maryellen

    2006-03-01

    Usage of the backprojection filtration (BPF) algorithm for reconstructing images from motion-contaminated fan-beam data may result in motion-induced streak artifacts, which appear in the direction of the chords on which images are reconstructed. These streak artifacts, which are most pronounced along chords tangent to the edges of the moving object, may be suppressed by use of the weighted BPF (WBPF) algorithm, which can exploit the inherent redundancies in fan-beam data. More specifically, reconstructions using full-scan and short-scan data can allow for substantial suppression of these streaks, whereas those using reduced-scan data can allow for partial suppression. Since multiple different reconstructions of the same chord can be obtained by varying the amount of redundant data used, we have laid the groundwork for a possible method to characterize the amount of motion encoded within the data used for reconstructing an image on a particular chord. Furthermore, since motion artifacts in WBPF reconstructions using full-scan and short-scan data appear similar to those in corresponding fan-beam filtered backprojection (FFBP) reconstructions for the cases performed in this study, the BPF and WBPF algorithms potentially may be used to arrive at a more fundamental characterization of how motion artifacts appear in FFBP reconstructions.

  18. Foliage motion under wind, from leaf flutter to branch buffeting.

    PubMed

    Tadrist, Loïc; Saudreau, Marc; Hémon, Pascal; Amandolese, Xavier; Marquier, André; Leclercq, Tristan; de Langre, Emmanuel

    2018-05-01

    The wind-induced motion of the foliage in a tree is an important phenomenon both for biological issues (photosynthesis, pathogens development or herbivory) and for more subtle effects such as on wi-fi transmission or animal communication. Such foliage motion results from a combination of the motion of the branches that support the leaves, and of the motion of the leaves relative to the branches. Individual leaf dynamics relative to the branch, and branch dynamics have usually been studied separately. Here, in an experimental study on a whole tree in a large-scale wind tunnel, we present the first empirical evidence that foliage motion is actually dominated by individual leaf flutter at low wind velocities, and by branch turbulence buffeting responses at higher velocities. The transition between the two regimes is related to a weak dependence of leaf flutter on wind velocity, while branch turbulent buffeting is strongly dependent on it. Quantitative comparisons with existing engineering-based models of leaf and branch motion confirm the prevalence of these two mechanisms. Simultaneous measurements of the wind-induced drag on the tree and of the light interception by the foliage show the role of an additional mechanism, reconfiguration, whereby leaves bend and overlap, limiting individual leaf flutter. We then discuss the consequences of these findings on the role of wind-mediated phenomena. © 2018 The Author(s).

  19. Towards a real-time wide area motion imagery system

    NASA Astrophysics Data System (ADS)

    Young, R. I.; Foulkes, S. B.

    2015-10-01

    It is becoming increasingly important in both the defence and security domains to conduct persistent wide area surveillance (PWAS) of large populations of targets. Wide Area Motion Imagery (WAMI) is a key technique for achieving this wide area surveillance. The recent development of multi-million pixel sensors has provided sensors with wide field of view replete with sufficient resolution for detection and tracking of objects of interest to be achieved across these extended areas of interest. WAMI sensors simultaneously provide high spatial and temporal resolutions, giving extreme pixel counts over large geographical areas. The high temporal resolution is required to enable effective tracking of targets. The provision of wide area coverage with high frame rates generates data deluge issues; these are especially profound if the sensor is mounted on an airborne platform, with finite data-link bandwidth and processing power that is constrained by size, weight and power (SWAP) limitations. These issues manifest themselves either as bottlenecks in the transmission of the imagery off-board or as latency in the time taken to analyse the data due to limited computational processing power.

  20. Directional bias of illusory stream caused by relative motion adaptation.

    PubMed

    Tomimatsu, Erika; Ito, Hiroyuki

    2016-07-01

    Enigma is an op-art painting that elicits an illusion of rotational streaming motion. In the present study, we tested whether adaptation to various motion configurations that included relative motion components could be reflected in the directional bias of the illusory stream. First, participants viewed the center of a rotating Enigma stimulus for adaptation. There was no physical motion on the ring area. During the adaptation period, the illusory stream on the ring was mainly seen in the direction opposite to that of the physical rotation. After the physical rotation stopped, the illusory stream on the ring was mainly seen in the same direction as that of the preceding physical rotation. Moreover, adapting to strong relative motion induced a strong bias in the illusory motion direction in the subsequently presented static Enigma stimulus. The results suggest that relative motion detectors corresponding to the ring area may produce the illusory stream of Enigma. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. A margin model to account for respiration-induced tumour motion and its variability

    NASA Astrophysics Data System (ADS)

    Coolens, Catherine; Webb, Steve; Shirato, H.; Nishioka, K.; Evans, Phil M.

    2008-08-01

    In order to reduce the sensitivity of radiotherapy treatments to organ motion, compensation methods are being investigated such as gating of treatment delivery, tracking of tumour position, 4D scanning and planning of the treatment, etc. An outstanding problem that would occur with all these methods is the assumption that breathing motion is reproducible throughout the planning and delivery process of treatment. This is obviously not a realistic assumption and is one that will introduce errors. A dynamic internal margin model (DIM) is presented that is designed to follow the tumour trajectory and account for the variability in respiratory motion. The model statistically describes the variation of the breathing cycle over time, i.e. the uncertainty in motion amplitude and phase reproducibility, in a polar coordinate system from which margins can be derived. This allows accounting for an additional gating window parameter for gated treatment delivery as well as minimizing the area of normal tissue irradiated. The model was illustrated with abdominal motion for a patient with liver cancer and tested with internal 3D lung tumour trajectories. The results confirm that the respiratory phases around exhale are most reproducible and have the smallest variation in motion amplitude and phase (approximately 2 mm). More importantly, the margin area covering normal tissue is significantly reduced by using trajectory-specific margins (as opposed to conventional margins) as the angular component is by far the largest contributor to the margin area. The statistical approach to margin calculation, in addition, offers the possibility for advanced online verification and updating of breathing variation as more data become available.

  2. Estimation of Source and Attenuation Parameters from Ground Motion Observations for Induced Seismicity in Alberta

    NASA Astrophysics Data System (ADS)

    Novakovic, M.; Atkinson, G. M.

    2015-12-01

    We use a generalized inversion to solve for site response, regional source and attenuation parameters, in order to define a region-specific ground-motion prediction equation (GMPE) from ground motion observations in Alberta, following the method of Atkinson et al. (2015 BSSA). The database is compiled from over 200 small to moderate seismic events (M 1 to 4.2) recorded at ~50 regional stations (distances from 30 to 500 km), over the last few years; almost all of the events have been identified as being induced by oil and gas activity. We remove magnitude scaling and geometric spreading functions from observed ground motions and invert for stress parameter, regional attenuation and site amplification. Resolving these parameters allows for the derivation of a regionally-calibrated GMPE that can be used to accurately predict amplitudes across the region in real time, which is useful for ground-motion-based alerting systems and traffic light protocols. The derived GMPE has further applications for the evaluation of hazards from induced seismicity.

  3. Distinct fMRI Responses to Self-Induced versus Stimulus Motion during Free Viewing in the Macaque

    PubMed Central

    Kaneko, Takaaki; Saleem, Kadharbatcha S.; Berman, Rebecca A.; Leopold, David A.

    2016-01-01

    Visual motion responses in the brain are shaped by two distinct sources: the physical movement of objects in the environment and motion resulting from one's own actions. The latter source, termed visual reafference, stems from movements of the head and body, and in primates from the frequent saccadic eye movements that mark natural vision. To study the relative contribution of reafferent and stimulus motion during natural vision, we measured fMRI activity in the brains of two macaques as they freely viewed >50 hours of naturalistic video footage depicting dynamic social interactions. We used eye movements obtained during scanning to estimate the level of reafferent retinal motion at each moment in time. We also estimated the net stimulus motion by analyzing the video content during the same time periods. Mapping the responses to these distinct sources of retinal motion, we found a striking dissociation in the distribution of visual responses throughout the brain. Reafferent motion drove fMRI activity in the early retinotopic areas V1, V2, V3, and V4, particularly in their central visual field representations, as well as lateral aspects of the caudal inferotemporal cortex (area TEO). However, stimulus motion dominated fMRI responses in the superior temporal sulcus, including areas MT, MST, and FST as well as more rostral areas. We discuss this pronounced separation of motion processing in the context of natural vision, saccadic suppression, and the brain's utilization of corollary discharge signals. SIGNIFICANCE STATEMENT Visual motion arises not only from events in the external world, but also from the movements of the observer. For example, even if objects are stationary in the world, the act of walking through a room or shifting one's eyes causes motion on the retina. This “reafferent” motion propagates into the brain as signals that must be interpreted in the context of real object motion. The delineation of whole-brain responses to stimulus versus self

  4. Influence of Visual Motion, Suggestion, and Illusory Motion on Self-Motion Perception in the Horizontal Plane.

    PubMed

    Rosenblatt, Steven David; Crane, Benjamin Thomas

    2015-01-01

    A moving visual field can induce the feeling of self-motion or vection. Illusory motion from static repeated asymmetric patterns creates a compelling visual motion stimulus, but it is unclear if such illusory motion can induce a feeling of self-motion or alter self-motion perception. In these experiments, human subjects reported the perceived direction of self-motion for sway translation and yaw rotation at the end of a period of viewing set visual stimuli coordinated with varying inertial stimuli. This tested the hypothesis that illusory visual motion would influence self-motion perception in the horizontal plane. Trials were arranged into 5 blocks based on stimulus type: moving star field with yaw rotation, moving star field with sway translation, illusory motion with yaw, illusory motion with sway, and static arrows with sway. Static arrows were used to evaluate the effect of cognitive suggestion on self-motion perception. Each trial had a control condition; the illusory motion controls were altered versions of the experimental image, which removed the illusory motion effect. For the moving visual stimulus, controls were carried out in a dark room. With the arrow visual stimulus, controls were a gray screen. In blocks containing a visual stimulus there was an 8s viewing interval with the inertial stimulus occurring over the final 1s. This allowed measurement of the visual illusion perception using objective methods. When no visual stimulus was present, only the 1s motion stimulus was presented. Eight women and five men (mean age 37) participated. To assess for a shift in self-motion perception, the effect of each visual stimulus on the self-motion stimulus (cm/s) at which subjects were equally likely to report motion in either direction was measured. Significant effects were seen for moving star fields for both translation (p = 0.001) and rotation (p<0.001), and arrows (p = 0.02). For the visual motion stimuli, inertial motion perception was shifted in the

  5. Light effects in the atomic-motion-induced Ramsey narrowing of dark resonances in wall-coated cells

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

    Breschi, E.; Schori, C.; Di Domenico, G.

    2010-12-15

    We report on light shift and broadening in the atomic-motion-induced Ramsey narrowing of dark resonances prepared in alkali-metal vapors contained in wall-coated cells without buffer gas. The atomic-motion-induced Ramsey narrowing is due to the free motion of the polarized atomic spins in and out of the optical interaction region before spin relaxation. As a consequence of this effect, we observe a narrowing of the dark resonance linewidth as well as a reduction of the ground states' light shift when the volume of the interaction region decreases at constant optical intensity. The results can be intuitively interpreted as a dilution ofmore » the intensity effect similar to a pulsed interrogation due to the atomic motion. Finally the influence of this effect on the performance of compact atomic clocks is discussed.« less

  6. Nitric oxide-mediated bystander signal transduction induced by heavy-ion microbeam irradiation

    NASA Astrophysics Data System (ADS)

    Tomita, Masanori; Matsumoto, Hideki; Funayama, Tomoo; Yokota, Yuichiro; Otsuka, Kensuke; Maeda, Munetoshi; Kobayashi, Yasuhiko

    2015-07-01

    In general, a radiation-induced bystander response is known to be a cellular response induced in non-irradiated cells after receiving bystander signaling factors released from directly irradiated cells within a cell population. Bystander responses induced by high-linear energy transfer (LET) heavy ions at low fluence are an important health problem for astronauts in space. Bystander responses are mediated via physical cell-cell contact, such as gap-junction intercellular communication (GJIC) and/or diffusive factors released into the medium in cell culture conditions. Nitric oxide (NO) is a well-known major initiator/mediator of intercellular signaling within culture medium during bystander responses. In this study, we investigated the NO-mediated bystander signal transduction induced by high-LET argon (Ar)-ion microbeam irradiation of normal human fibroblasts. Foci formation by DNA double-strand break repair proteins was induced in non-irradiated cells, which were co-cultured with those irradiated by high-LET Ar-ion microbeams in the same culture plate. Foci formation was suppressed significantly by pretreatment with an NO scavenger. Furthermore, NO-mediated reproductive cell death was also induced in bystander cells. Phosphorylation of NF-κB and Akt were induced during NO-mediated bystander signaling in the irradiated and bystander cells. However, the activation of these proteins depended on the incubation time after irradiation. The accumulation of cyclooxygenase-2 (COX-2), a downstream target of NO and NF-κB, was observed in the bystander cells 6 h after irradiation but not in the directly irradiated cells. Our findings suggest that Akt- and NF-κB-dependent signaling pathways involving COX-2 play important roles in NO-mediated high-LET heavy-ion-induced bystander responses. In addition, COX-2 may be used as a molecular marker of high-LET heavy-ion-induced bystander cells to distinguish them from directly irradiated cells, although this may depend on the time

  7. Partners In Motion And Customer Satisfaction In The Washington Dc Metropolitan Area

    DOT National Transportation Integrated Search

    1999-06-01

    PARTNERS IN MOTION IS A PROGRAM AIMED AT IMPROVING THE QUALITY, QUANTITY, AND AVAILABILITY OF TRAVEL INFORMATION TO TRANSPORTATION AGENCIES, THE MEDIA, AND, ULTIMATELY, TO THE TRAVELER IN THE WASHINGTON, D.C. METROPOLITAN AREA. THE PROGRAM WAS INITIA...

  8. Distinct fMRI Responses to Self-Induced versus Stimulus Motion during Free Viewing in the Macaque.

    PubMed

    Russ, Brian E; Kaneko, Takaaki; Saleem, Kadharbatcha S; Berman, Rebecca A; Leopold, David A

    2016-09-14

    Visual motion responses in the brain are shaped by two distinct sources: the physical movement of objects in the environment and motion resulting from one's own actions. The latter source, termed visual reafference, stems from movements of the head and body, and in primates from the frequent saccadic eye movements that mark natural vision. To study the relative contribution of reafferent and stimulus motion during natural vision, we measured fMRI activity in the brains of two macaques as they freely viewed >50 hours of naturalistic video footage depicting dynamic social interactions. We used eye movements obtained during scanning to estimate the level of reafferent retinal motion at each moment in time. We also estimated the net stimulus motion by analyzing the video content during the same time periods. Mapping the responses to these distinct sources of retinal motion, we found a striking dissociation in the distribution of visual responses throughout the brain. Reafferent motion drove fMRI activity in the early retinotopic areas V1, V2, V3, and V4, particularly in their central visual field representations, as well as lateral aspects of the caudal inferotemporal cortex (area TEO). However, stimulus motion dominated fMRI responses in the superior temporal sulcus, including areas MT, MST, and FST as well as more rostral areas. We discuss this pronounced separation of motion processing in the context of natural vision, saccadic suppression, and the brain's utilization of corollary discharge signals. Visual motion arises not only from events in the external world, but also from the movements of the observer. For example, even if objects are stationary in the world, the act of walking through a room or shifting one's eyes causes motion on the retina. This "reafferent" motion propagates into the brain as signals that must be interpreted in the context of real object motion. The delineation of whole-brain responses to stimulus versus self-generated retinal motion

  9. Dihydroartemisinin induces apoptosis preferentially via a Bim-mediated intrinsic pathway in hepatocarcinoma cells.

    PubMed

    Qin, Guiqi; Zhao, ChuBiao; Zhang, Lili; Liu, Hongyu; Quan, Yingyao; Chai, Liuying; Wu, Shengnan; Wang, Xiaoping; Chen, Tongsheng

    2015-08-01

    This report is designed to dissect the detail molecular mechanism by which dihydroartemisinin (DHA), a derivative of artemisinin, induces apoptosis in human hepatocellular carcinoma (HCC) cells. DHA induced a loss of the mitochondrial transmemberane potential (ΔΨm), release of cytochrome c, activation of caspases, and externalization of phosphatidylserine indicative of apoptosis induction. Compared with the modest inhibitory effects of silencing Bax, silencing Bak largely prevented DHA-induced ΔΨm collapse and apoptosis though DHA induced a commensurable activation of Bax and Bak, demonstrating a key role of the Bak-mediated intrinsic apoptosis pathway. DHA did not induce Bid cleavage and translocation from cytoplasm to mitochondria and had little effects on the expressions of Puma and Noxa, but did increase Bim and Bak expressions and decrease Mcl-1 expression. Furthermore, the cytotoxicity of DHA was remarkably reduced by silencing Bim, and modestly but significantly reduced by silencing Puma or Noxa. Silencing Bim or Noxa preferentially reduced DHA-induced Bak activation, while silencing Puma preferentially reduced DHA-induced Bax activation, demonstrating that Bim and to a lesser extent Noxa act as upstream mediators to trigger the Bak-mediated intrinsic apoptosis pathway. In addition, silencing Mcl-1 enhanced DHA-induced Bak activation and apoptosis. Taken together, our data demonstrate a crucial role of Bim in preferentially regulating the Bak/Mcl-1 rheostat to mediate DHA-induced apoptosis in HCC cells.

  10. Motion-induced error reduction by combining Fourier transform profilometry with phase-shifting profilometry.

    PubMed

    Li, Beiwen; Liu, Ziping; Zhang, Song

    2016-10-03

    We propose a hybrid computational framework to reduce motion-induced measurement error by combining the Fourier transform profilometry (FTP) and phase-shifting profilometry (PSP). The proposed method is composed of three major steps: Step 1 is to extract continuous relative phase maps for each isolated object with single-shot FTP method and spatial phase unwrapping; Step 2 is to obtain an absolute phase map of the entire scene using PSP method, albeit motion-induced errors exist on the extracted absolute phase map; and Step 3 is to shift the continuous relative phase maps from Step 1 to generate final absolute phase maps for each isolated object by referring to the absolute phase map with error from Step 2. Experiments demonstrate the success of the proposed computational framework for measuring multiple isolated rapidly moving objects.

  11. Stroboscopic Vision as a Treatment for Retinal Slip Induced Motion Sickness

    NASA Technical Reports Server (NTRS)

    Reschke, M. F.; Somers, J. T.; Ford, G.; Krnavek, J. M.; Hwang, E. J.; Leigh, R. J.; Estrada, A.

    2007-01-01

    Motion sickness in the general population is a significant problem driven by the increasingly more sophisticated modes of transportation, visual displays, and virtual reality environments. It is important to investigate non-pharmacological alternatives for the prevention of motion sickness for individuals who cannot tolerate the available anti-motion sickness drugs, or who are precluded from medication because of different operational environments. Based on the initial work of Melvill Jones, in which post hoc results indicated that motion sickness symptoms were prevented during visual reversal testing when stroboscopic vision was used to prevent retinal slip, we have evaluated stroboscopic vision as a method of preventing motion sickness in a number of different environments. Specifically, we have undertaken a five part study that was designed to investigate the effect of stroboscopic vision (either with a strobe light or LCD shutter glasses) on motion sickness while: (1) using visual field reversal, (2) reading while riding in a car (with or without external vision present), (3) making large pitch head movements during parabolic flight, (4) during exposure to rough seas in a small boat, and (5) seated and reading in the cabin area of a UH60 Black Hawk Helicopter during 20 min of provocative flight patterns.

  12. In vitro performance of the fixed and adjustable gravity-assisted unit with and without motion-evidence of motion-induced flow.

    PubMed

    Kimura, Takaoki; Schulz, Matthias; Shimoji, Kazuaki; Miyajima, Masakazu; Arai, Hajime; Thomale, Ulrich-Wilhelm

    2016-10-01

    Anti-siphon devices and gravitational-assisted valves have been introduced to counteract the effects of overdrainage after implantation of a shunt system. The study examined the flow performance of two gravitational-assisted valves (shunt assistant - SA and programmable shunt assistant - proSA, Miethke & Co. KG, Potsdam, Germany) in an in vitro shunt laboratory with and without motion. An in vitro laboratory setup was used to model the cerebrospinal fluid (CSF) drainage conditions similar to a ventriculo-peritoneal shunt and to test the SA (resistance of +20 cmH2O in 90°) and proSA (adjustable resistance of 0 to +40 cmH2O in 90°). The differential pressure (DP) through the simulated shunt and tested valve was adjusted between 0 and 60 cmH2O by combinations of different inflow pressures (40, 30, 20, 10, and 0 cmH2O) and the hydrostatic negative outflow pressure (0, -20, and -40 cmH2O) in several differing device positions (0°, 30°, 60°, and 90°). In addition, the two devices were tested under vertical motion with movement frequencies of 2, 3, and 4 Hz. Both gravity-assisted units effectively counteract the hydrostatic effect in relation to the chosen differential pressure. The setting the proSA resulted in flow reductions in the 90° position according to the chosen resistance of the device. Angulation-related flow changes were similar in the two devices in 30-90° position, however, in the 0-30° position, a higher flow is seen in the proSA. Repeated vertical movement significantly increased flow through both devices. While with the proSA a 2-Hz motion was not able to induce additional flow (0.006 ± 0.05 ml/min), 3- and 4-Hz motion significantly induced higher flow values (3 Hz: +0.56 ± 0.12 ml/min, 4 Hz: +0.54 ± 0.04 ml/min). The flow through the SA was not induced by vertical movements at a low DP of 10 cmH2O at all frequencies, but at DPs of 30 cmH2O and higher, all frequencies significantly induced higher flow values (2 Hz: +0

  13. Mechanisms mediating Nitroglycerin-induced Delayed Onset Hyperalgesia in the Rat

    PubMed Central

    Ferrari, Luiz F.; Levine, Jon D.; Green, Paul G.

    2016-01-01

    Nitroglycerin (glycerol trinitrate, GTN) induces headache in migraineurs, an effect that has been used both diagnostically and in the study of the pathophysiology of this neurovascular pain syndrome. An important feature of this headache is a delay from the administration of GTN to headache onset that, because of GTN’s very rapid metabolism, cannot be due to its pharmacokinetic profile. It has recently been suggested that activation of perivascular mast cells, which has been implicated in the pathophysiology of migraine, may contribute to this delay. We reported that hyperalgesia induced by intradermal GTN has a delay to onset of ~30 min in male and ~45 min in female rats. This hyperalgesia was greater in females, was prevented by pretreatment with the anti-migraine drug, sumatriptan, as well as by chronic pretreatment with the mast cell degranulator, compound 48/80. The acute administration of GTN and compound 48/80 both induced hyperalgesia that was prevented by pretreatment with octoxynol-9, which attenuates endothelial function, suggesting that GTN and mast cell-mediated hyperalgesia are endothelial cell-dependent. Furthermore, A-317491, a P2X3 antagonist, which inhibits endothelial cell-dependent hyperalgesia, also prevents GTN and mast cell-mediated hyperalgesia. We conclude that delayed onset mechanical hyperalgesia induced by GTN is mediated by activation of mast cells, which in turn release mediators that stimulate endothelial cells to release ATP, to act on P2X3, a ligand-gated ion channel, in perivascular nociceptors. A role of the mast and endothelial cell in GTN-induced hyperalgesia suggest potential novel risk factors and targets for the treatment of migraine. PMID:26779834

  14. Mechanisms mediating nitroglycerin-induced delayed-onset hyperalgesia in the rat.

    PubMed

    Ferrari, L F; Levine, J D; Green, P G

    2016-03-11

    Nitroglycerin (glycerol trinitrate, GTN) induces headache in migraineurs, an effect that has been used both diagnostically and in the study of the pathophysiology of this neurovascular pain syndrome. An important feature of this headache is a delay from the administration of GTN to headache onset that, because of GTN's very rapid metabolism, cannot be due to its pharmacokinetic profile. It has recently been suggested that activation of perivascular mast cells, which has been implicated in the pathophysiology of migraine, may contribute to this delay. We reported that hyperalgesia induced by intradermal GTN has a delay to onset of ∼ 30 min in male and ∼ 45 min in female rats. This hyperalgesia was greater in females, was prevented by pretreatment with the anti-migraine drug, sumatriptan, as well as by chronic pretreatment with the mast cell degranulator, compound 48/80. The acute administration of GTN and compound 48/80 both induced hyperalgesia that was prevented by pretreatment with octoxynol-9, which attenuates endothelial function, suggesting that GTN and mast cell-mediated hyperalgesia are endothelial cell-dependent. Furthermore, A-317491, a P2X3 antagonist, which inhibits endothelial cell-dependent hyperalgesia, also prevents GTN and mast cell-mediated hyperalgesia. We conclude that delayed-onset mechanical hyperalgesia induced by GTN is mediated by activation of mast cells, which in turn release mediators that stimulate endothelial cells to release ATP, to act on P2X3, a ligand-gated ion channel, in perivascular nociceptors. A role of the mast and endothelial cell in GTN-induced hyperalgesia suggests potential novel risk factors and targets for the treatment of migraine. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. A benchmark for vehicle detection on wide area motion imagery

    NASA Astrophysics Data System (ADS)

    Catrambone, Joseph; Amzovski, Ismail; Liang, Pengpeng; Blasch, Erik; Sheaff, Carolyn; Wang, Zhonghai; Chen, Genshe; Ling, Haibin

    2015-05-01

    Wide area motion imagery (WAMI) has been attracting an increased amount of research attention due to its large spatial and temporal coverage. An important application includes moving target analysis, where vehicle detection is often one of the first steps before advanced activity analysis. While there exist many vehicle detection algorithms, a thorough evaluation of them on WAMI data still remains a challenge mainly due to the lack of an appropriate benchmark data set. In this paper, we address a research need by presenting a new benchmark for wide area motion imagery vehicle detection data. The WAMI benchmark is based on the recently available Wright-Patterson Air Force Base (WPAFB09) dataset and the Temple Resolved Uncertainty Target History (TRUTH) associated target annotation. Trajectory annotations were provided in the original release of the WPAFB09 dataset, but detailed vehicle annotations were not available with the dataset. In addition, annotations of static vehicles, e.g., in parking lots, are also not identified in the original release. Addressing these issues, we re-annotated the whole dataset with detailed information for each vehicle, including not only a target's location, but also its pose and size. The annotated WAMI data set should be useful to community for a common benchmark to compare WAMI detection, tracking, and identification methods.

  16. Orientation of selective effects of body tilt on visually induced perception of self-motion.

    PubMed

    Nakamura, S; Shimojo, S

    1998-10-01

    We examined the effect of body posture upon visually induced perception of self-motion (vection) with various angles of observer's tilt. The experiment indicated that the tilted body of observer could enhance perceived strength of vertical vection, while there was no effect of body tilt on horizontal vection. This result suggests that there is an interaction between the effects of visual and vestibular information on perception of self-motion.

  17. Visual motion integration by neurons in the middle temporal area of a New World monkey, the marmoset

    PubMed Central

    Solomon, Selina S; Tailby, Chris; Gharaei, Saba; Camp, Aaron J; Bourne, James A; Solomon, Samuel G

    2011-01-01

    Abstract The middle temporal area (MT/V5) is an anatomically distinct region of primate visual cortex that is specialized for the processing of image motion. It is generally thought that some neurons in area MT are capable of signalling the motion of complex patterns, but this has only been established in the macaque monkey. We made extracellular recordings from single units in area MT of anaesthetized marmosets, a New World monkey. We show through quantitative analyses that some neurons (35 of 185; 19%) are capable of signalling pattern motion (‘pattern cells’). Across several dimensions, the visual response of pattern cells in marmosets is indistinguishable from that of pattern cells in macaques. Other neurons respond to the motion of oriented contours in a pattern (‘component cells’) or show intermediate properties. In addition, we encountered a subset of neurons (22 of 185; 12%) insensitive to sinusoidal gratings but very responsive to plaids and other two-dimensional patterns and otherwise indistinguishable from pattern cells. We compared the response of each cell class to drifting gratings and dot fields. In pattern cells, directional selectivity was similar for gratings and dot fields; in component cells, directional selectivity was weaker for dot fields than gratings. Pattern cells were more likely to have stronger suppressive surrounds, prefer lower spatial frequencies and prefer higher speeds than component cells. We conclude that pattern motion sensitivity is a feature of some neurons in area MT of both New and Old World monkeys, suggesting that this functional property is an important stage in motion analysis and is likely to be conserved in humans. PMID:21946851

  18. Motion sickness increases functional connectivity between visual motion and nausea-associated brain regions.

    PubMed

    Toschi, Nicola; Kim, Jieun; Sclocco, Roberta; Duggento, Andrea; Barbieri, Riccardo; Kuo, Braden; Napadow, Vitaly

    2017-01-01

    The brain networks supporting nausea not yet understood. We previously found that while visual stimulation activated primary (V1) and extrastriate visual cortices (MT+/V5, coding for visual motion), increasing nausea was associated with increasing sustained activation in several brain areas, with significant co-activation for anterior insula (aIns) and mid-cingulate (MCC) cortices. Here, we hypothesized that motion sickness also alters functional connectivity between visual motion and previously identified nausea-processing brain regions. Subjects prone to motion sickness and controls completed a motion sickness provocation task during fMRI/ECG acquisition. We studied changes in connectivity between visual processing areas activated by the stimulus (MT+/V5, V1), right aIns and MCC when comparing rest (BASELINE) to peak nausea state (NAUSEA). Compared to BASELINE, NAUSEA reduced connectivity between right and left V1 and increased connectivity between right MT+/V5 and aIns and between left MT+/V5 and MCC. Additionally, the change in MT+/V5 to insula connectivity was significantly associated with a change in sympathovagal balance, assessed by heart rate variability analysis. No state-related connectivity changes were noted for the control group. Increased connectivity between a visual motion processing region and nausea/salience brain regions may reflect increased transfer of visual/vestibular mismatch information to brain regions supporting nausea perception and autonomic processing. We conclude that vection-induced nausea increases connectivity between nausea-processing regions and those activated by the nauseogenic stimulus. This enhanced low-frequency coupling may support continual, slowly evolving nausea perception and shifts toward sympathetic dominance. Disengaging this coupling may be a target for biobehavioral interventions aimed at reducing motion sickness severity. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Resveratrol inhibits estrogen-induced breast carcinogenesis through induction of NRF2-mediated protective pathways

    PubMed Central

    Singh, Bhupendra; Shoulson, Rivka; Chatterjee, Anwesha; Ronghe, Amruta; Bhat, Nimee K.; Dim, Daniel C.; Bhat, Hari K.

    2014-01-01

    The importance of estrogens in the etiology of breast cancer is widely recognized. Estrogen-induced oxidative stress has been implicated in this carcinogenic process. Resveratrol (Res), a natural antioxidant phytoestrogen has chemopreventive effects against a variety of illnesses including cancer. The objective of the present study was to characterize the mechanism(s) of Res-mediated protection against estrogen-induced breast carcinogenesis. Female August Copenhagen Irish rats were treated with 17β-estradiol (E2), Res and Res + E2 for 8 months. Cotreatment of rats with Res and E2 inhibited E2-mediated proliferative changes in mammary tissues and significantly increased tumor latency and reduced E2-induced breast tumor development. Resveratrol treatment alone or in combination with E2 significantly upregulated expression of nuclear factor erythroid 2-related factor 2 (NRF2) in mammary tissues. Expression of NRF2-regulated antioxidant genes NQO1, SOD3 and OGG1 that are involved in protection against oxidative DNA damage was increased in Res- and Res + E2-treated mammary tissues. Resveratrol also prevented E2-mediated inhibition of detoxification genes AOX1 and FMO1. Inhibition of E2-mediated alterations in NRF2 promoter methylation and expression of NRF2 targeting miR-93 after Res treatment indicated Res-mediated epigenetic regulation of NRF2 during E2-induced breast carcinogenesis. Resveratrol treatment also induced apoptosis and inhibited E2-mediated increase in DNA damage in mammary tissues. Increased apoptosis and decreased DNA damage, cell migration, colony and mammosphere formation in Res- and Res + E2-treated MCF-10A cells suggested a protective role of Res against E2-induced mammary carcinogenesis. Small-interfering RNA-mediated silencing of NRF2 inhibited Res-mediated preventive effects on the colony and mammosphere formation. Taken together, these results suggest that Res inhibits E2-induced breast carcinogenesis via induction of NRF2-mediated protective

  20. A 2 epoch proper motion catalogue from the UKIDSS Large Area Survey

    NASA Astrophysics Data System (ADS)

    Smith, Leigh; Lucas, Phil; Burningham, Ben; Jones, Hugh; Pinfield, David; Smart, Ricky; Andrei, Alexandre

    2013-04-01

    The UKIDSS Large Area Survey (LAS) began in 2005, with the start of the UKIDSS program as a 7 year effort to survey roughly 4000 square degrees at high galactic latitudes in Y, J, H and K bands. The survey also included a significant quantity of 2-epoch J band observations, with epoch baselines ranging from 2 to 7 years. We present a proper motion catalogue for the 1500 square degrees of the 2 epoch LAS data, which includes some 800,000 sources with motions detected above the 5σ level. We developed a bespoke proper motion pipeline which applies a source-unique second order polynomial transformation to UKIDSS array coordinates of each source to counter potential local non-uniformity in the focal plane. Our catalogue agrees well with the proper motion data supplied in the current WFCAM Science Archive (WSA) DR9 catalogue where there is overlap, and in various optical catalogues, but it benefits from some improvements. One improvement is that we provide absolute proper motions, using LAS galaxies for the relative to absolute correction. Also, by using unique, local, 2nd order polynomial tranformations, as opposed to the linear transformations in the WSA, we correct better for any local distortions in the focal plane, not including the radial distortion that is removed by their pipeline.

  1. Catecholaminergic responses to stressful motion stimuli, scopolamine plus amphetamine, and dexamethasone

    NASA Technical Reports Server (NTRS)

    Kohl, R. L.; Chelen, W. E.

    1992-01-01

    Peripheral levels of epinephrine (EPI) and neoepinephrine (NE) generally rise following stressful motion stimuli. Effective anti-motion sickness drugs, scopolamine plus, d-amphetamine (S/D) and dexamthasone (DEX) modulate release of EPI and NE. This modulation may be of etiological relevance. Methods: Severe nausea was induced by exposure to coriolis simulation using a rotating chair. Chronic administration of S/D (0.4 and 5 mg/da) DEX (3 mg/day) and placebo preceded coriolis simulation. EPI and NE were measured immediately before and after simulation. A double-blind crossover design was used. Results: Nausea-induced elevations of EPI (2.5 fold, p less than .01) and NE were not diminished upon repeated exposure and adaptation to the stressor. Subjects with more pronounced elevations of EPI following simulation displayed higher resistance to stressful motion (p less .05). Alteration of peripheral catechlomaine levels following drug suggested that motion sickness was not mediated by peripheral catechlolamine receptor simulation. EPI and NE levels were 2.8 and 3.6-fold higher (p less than .03 and .01) after nausea without DEX treatment. DEX loading halved pre-stress levels of EPI and NE (p less than .05). Conclusions: Marked differences were noted in individual responses to drug and systematic responses of EPI and NE. It is possible that the responses of EPI to motion sickness may predict resistance to stressful motion and represent a peripheral manifestation of some as yet unknown central event of etiologic relevance.

  2. Micro-valve using induced-charge electrokinetic motion of Janus particle.

    PubMed

    Daghighi, Yasaman; Li, Dongqing

    2011-09-07

    A new micro-valve using the electrokinetic motion of a Janus particle is introduced in this paper. A Janus particle with a conducting hemisphere and a non-conducting hemisphere is placed in a junction of several microchannels. Under an applied electric field, the induced-charge electrokinetic flow around the conducting side of the Janus particle forms vortices. The vortices push the particle moving forwards to block the entrance of a microchannel. By switching the direction of the applied electric field, the motion of the Janus particle can be changed to block different microchannels. This paper develops a theoretical model and conducts numerical simulations of the three-dimensional transient motion of the Janus particle. The results show that this Janus particle-based micro-valve is feasible for switching and controlling the flow rate in a microfluidic chip. This method is simple in comparison with other types of micro-valve methods. It is easy for fabrication, for operation control, and has a fast response time. To better understand the micro-valve functions, comparisons with a non-conducting particle and a fully conducting particle were made. Results proved that only a Janus particle can fulfill the requirements of such a micro-valve.

  3. Observation and analysis of high-speed human motion with frequent occlusion in a large area

    NASA Astrophysics Data System (ADS)

    Wang, Yuru; Liu, Jiafeng; Liu, Guojun; Tang, Xianglong; Liu, Peng

    2009-12-01

    The use of computer vision technology in collecting and analyzing statistics during sports matches or training sessions is expected to provide valuable information for tactics improvement. However, the measurements published in the literature so far are either unreliably documented to be used in training planning due to their limitations or unsuitable for studying high-speed motion in large area with frequent occlusions. A sports annotation system is introduced in this paper for tracking high-speed non-rigid human motion over a large playing area with the aid of motion camera, taking short track speed skating competitions as an example. The proposed system is composed of two sub-systems: precise camera motion compensation and accurate motion acquisition. In the video registration step, a distinctive invariant point feature detector (probability density grads detector) and a global parallax based matching points filter are used, to provide reliable and robust matching across a large range of affine distortion and illumination change. In the motion acquisition step, a two regions' relationship constrained joint color model and Markov chain Monte Carlo based joint particle filter are emphasized, by dividing the human body into two relative key regions. Several field tests are performed to assess measurement errors, including comparison to popular algorithms. With the help of the system presented, the system obtains position data on a 30 m × 60 m large rink with root-mean-square error better than 0.3975 m, velocity and acceleration data with absolute error better than 1.2579 m s-1 and 0.1494 m s-2, respectively.

  4. Evaluation of adaptation to visually induced motion sickness based on the maximum cross-correlation between pulse transmission time and heart rate.

    PubMed

    Sugita, Norihiro; Yoshizawa, Makoto; Abe, Makoto; Tanaka, Akira; Watanabe, Takashi; Chiba, Shigeru; Yambe, Tomoyuki; Nitta, Shin-ichi

    2007-09-28

    Computer graphics and virtual reality techniques are useful to develop automatic and effective rehabilitation systems. However, a kind of virtual environment including unstable visual images presented to wide field screen or a head mounted display tends to induce motion sickness. The motion sickness induced in using a rehabilitation system not only inhibits effective training but also may harm patients' health. There are few studies that have objectively evaluated the effects of the repetitive exposures to these stimuli on humans. The purpose of this study is to investigate the adaptation to visually induced motion sickness by physiological data. An experiment was carried out in which the same video image was presented to human subjects three times. We evaluated changes of the intensity of motion sickness they suffered from by a subjective score and the physiological index rho(max), which is defined as the maximum cross-correlation coefficient between heart rate and pulse wave transmission time and is considered to reflect the autonomic nervous activity. The results showed adaptation to visually-induced motion sickness by the repetitive presentation of the same image both in the subjective and the objective indices. However, there were some subjects whose intensity of sickness increased. Thus, it was possible to know the part in the video image which related to motion sickness by analyzing changes in rho(max) with time. The physiological index, rho(max), will be a good index for assessing the adaptation process to visually induced motion sickness and may be useful in checking the safety of rehabilitation systems with new image technologies.

  5. Inducing Tropical Cyclones to Undergo Brownian Motion

    NASA Astrophysics Data System (ADS)

    Hodyss, D.; McLay, J.; Moskaitis, J.; Serra, E.

    2014-12-01

    Stochastic parameterization has become commonplace in numerical weather prediction (NWP) models used for probabilistic prediction. Here, a specific stochastic parameterization will be related to the theory of stochastic differential equations and shown to be affected strongly by the choice of stochastic calculus. From an NWP perspective our focus will be on ameliorating a common trait of the ensemble distributions of tropical cyclone (TC) tracks (or position), namely that they generally contain a bias and an underestimate of the variance. With this trait in mind we present a stochastic track variance inflation parameterization. This parameterization makes use of a properly constructed stochastic advection term that follows a TC and induces its position to undergo Brownian motion. A central characteristic of Brownian motion is that its variance increases with time, which allows for an effective inflation of an ensemble's TC track variance. Using this stochastic parameterization we present a comparison of the behavior of TCs from the perspective of the stochastic calculi of Itô and Stratonovich within an operational NWP model. The central difference between these two perspectives as pertains to TCs is shown to be properly predicted by the stochastic calculus and the Itô correction. In the cases presented here these differences will manifest as overly intense TCs, which, depending on the strength of the forcing, could lead to problems with numerical stability and physical realism.

  6. ENDOTHELIAL CONTRACTION INDUCED BY HISTAMINE-TYPE MEDIATORS

    PubMed Central

    Majno, Guido; Shea, Stephen M.; Leventhal, Monika

    1969-01-01

    Previous work has shown that endogenous chemical mediators, of which histamine is the prototype, increase the permeability of blood vessels by causing gaps to appear between endothelial cells. In the present paper, morphologic and statistical evidence is presented, to suggest that endothelial cells contract under the influence of mediators, and that this contraction causes the formation of intercellular gaps. Histamine, serotonin, and bradykinin were injected subcutaneously into the scrotum of the rat, and the vessels of the underlying cremaster muscle were examined by electron microscopy. To eliminate the vascular collapse induced by routine fixation, in one series of animals (including controls) the root of the cremaster was constricted for 2–4 min prior to sacrifice, and the tissues were fixed under conditions of mild venous congestion. Electron micrographs were taken of 599 nuclei from the endothelium of small blood vessels representing the various experimental situations. Nuclear deformations were classified into four types of increasing tightness (notches, foldsl closing folds, and pinches. In the latter the apposed surfaces of the nuclear membrane are in contact). It was found that: (1) venous congestion tends to straighten the nuclei in al groups; (2) mediators cause a highly significant increase in the number of pinches (P < 0.001), also if the vessels are distended by venous congestion; (3) fixation without venous congestion causes vascular collapse. The degree of endothelial recoil, as measured by nuclear pinches, is very different from that caused by mediators (P < 0.001). (4) Pinched nuclei are more frequent in leaking vessels, and in cells adjacent to gaps (P < 0.001); (5) mediators also induce, in the endothelium, cytoplasmic changes suggestive of contraction, and similar to those of contracted smooth muscle; (6) there is no evidence of pericyte contraction under the conditions tested. Occasional pericytes appeared to receive fine nerve endings

  7. Critical role of foreground stimuli in perceiving visually induced self-motion (vection).

    PubMed

    Nakamura, S; Shimojo, S

    1999-01-01

    The effects of a foreground stimulus on vection (illusory perception of self-motion induced by a moving background stimulus) were examined in two experiments. The experiments reveal that the presentation of a foreground pattern with a moving background stimulus may affect vection. The foreground stimulus facilitated vection strength when it remained stationary or moved slowly in the opposite direction to that of the background stimulus. On the other hand, there was a strong inhibition of vection when the foreground stimulus moved slowly with, or quickly against, the background. These results suggest that foreground stimuli, as well as background stimuli, play an important role in perceiving self-motion.

  8. Summary of methods in Wide-Area Motion Imagery (WAMI)

    NASA Astrophysics Data System (ADS)

    Blasch, Erik; Seetharaman, Guna; Suddarth, Steve; Palaniappan, Kannappan; Chen, Genshe; Ling, Haibin; Basharat, Arlsan

    2014-06-01

    In the last decade, there have been numerous developments in wide-area motion imagery (WAMI) from the sensor design to data exploitation. In this paper, we summarize the published literature on WAMI results in an effort to organize the techniques, discuss the developments, and determine the state-of-the-art. Using the organization of developments, we see the variations in approaches and relations to the data sets available. The literature summary provides and anthology of many of the developers in the last decade and their associated techniques. In our use case, we showcase current methods and products that enable future WAMI exploitation developments.

  9. [Evaluation of Motion Sickness Induced by 3D Video Clips].

    PubMed

    Matsuura, Yasuyuki; Takada, Hiroki

    2016-01-01

    The use of stereoscopic images has been spreading rapidly. Nowadays, stereoscopic movies are nothing new to people. Stereoscopic systems date back to 280 A.D. when Euclid first recognized the concept of depth perception by humans. Despite the increase in the production of three-dimensional (3D) display products and many studies on stereoscopic vision, the effect of stereoscopic vision on the human body has been insufficiently understood. However, symptoms such as eye fatigue and 3D sickness have been the concerns when viewing 3D films for a prolonged period of time; therefore, it is important to consider the safety of viewing virtual 3D contents as a contribution to society. It is generally explained to the public that accommodation and convergence are mismatched during stereoscopic vision and that this is the main reason for the visual fatigue and visually induced motion sickness (VIMS) during 3D viewing. We have devised a method to simultaneously measure lens accommodation and convergence. We used this simultaneous measurement device to characterize 3D vision. Fixation distance was compared between accommodation and convergence during the viewing of 3D films with repeated measurements. Time courses of these fixation distances and their distributions were compared in subjects who viewed 2D and 3D video clips. The results indicated that after 90 s of continuously viewing 3D images, the accommodative power does not correspond to the distance of convergence. In this paper, remarks on methods to measure the severity of motion sickness induced by viewing 3D films are also given. From the epidemiological viewpoint, it is useful to obtain novel knowledge for reduction and/or prevention of VIMS. We should accumulate empirical data on motion sickness, which may contribute to the development of relevant fields in science and technology.

  10. Calcium-mediated signaling and calmodulin-dependent kinase regulate hepatocyte-inducible nitric oxide synthase expression.

    PubMed

    Zhang, Baochun; Crankshaw, Will; Nesemeier, Ryan; Patel, Jay; Nweze, Ikenna; Lakshmanan, Jaganathan; Harbrecht, Brian G

    2015-02-01

    Induced nitric oxide synthase (iNOS) is induced in hepatocytes by shock and inflammatory stimuli. Excessive NO from iNOS mediates shock-induced hepatic injury and death, so understanding the regulation of iNOS will help elucidate the pathophysiology of septic shock. In vitro, cytokines induce iNOS expression through activation of signaling pathways including mitogen-activated protein kinases and nuclear factor κB. Cytokines also induce calcium (Ca(2+)) mobilization and activate calcium-mediated intracellular signaling pathways, typically through activation of calmodulin-dependent kinases (CaMK). Calcium regulates NO production in macrophages but the role of calcium and calcium-mediated signaling in hepatocyte iNOS expression has not been defined. Primary rat hepatocytes were isolated, cultured, and induced to produce NO with proinflammatory cytokines. Calcium mobilization and Ca(2+)-mediated signaling were altered with ionophore, Ca(2+) channel blockers, and inhibitors of CaMK. The Ca(2+) ionophore A23187 suppressed cytokine-stimulated NO production, whereas Ethylene glycol tetraacetic acid and nifedipine increased NO production, iNOS messenger RNA, and iNOS protein expression. Inhibition of CaMK with KN93 and CBD increased NO production but the calcineurin inhibitor FK 506 decreased iNOS expression. These data demonstrate that calcium-mediated signaling regulates hepatocyte iNOS expression and does so through a mechanism independent of calcineurin. Changes in intracellular calcium levels may regulate iNOS expression during hepatic inflammation induced by proinflammatory cytokines. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Interleukin-1 receptor (IL-1R) mediates epilepsy-induced sleep disruption.

    PubMed

    Huang, Tzu-Rung; Jou, Shuo-Bin; Chou, Yu-Ju; Yi, Pei-Lu; Chen, Chun-Jen; Chang, Fang-Chia

    2016-11-22

    Sleep disruptions are common in epilepsy patients. Our previous study demonstrates that homeostatic factors and circadian rhythm may mediate epilepsy-induced sleep disturbances when epilepsy occurs at different zeitgeber hours. The proinflammatory cytokine, interleukin-1 (IL-1), is a somnogenic cytokine and may also be involved in epileptogenesis; however, few studies emphasize the effect of IL-1 in epilepsy-induced sleep disruption. We herein hypothesized that IL-1 receptor type 1 (IL-1R1) mediates the pathogenesis of epilepsy and epilepsy-induced sleep disturbances. We determined the role of IL-1R1 by using IL-1R1 knockout (IL-1R1 -/- KO) mice. Our results elucidated the decrease of non-rapid eye movement (NREM) sleep during the light period in IL-1R -/- mice and confirmed the somnogenic role of IL-1R1. Rapid electrical amygdala kindling was performed to induce epilepsy at the particular zeitgeber time (ZT) point, ZT13. Our results demonstrated that seizure thresholds induced by kindling stimuli, such as the after-discharge threshold and successful kindling rates, were not altered in IL-1R -/- mice when compared to those obtained from the wildtype mice (IL-1R +/+ mice). This result suggests that IL-1R1 is not involved in kindling-induced epileptogenesis. During sleep, ZT13 kindling stimulation significantly enhanced NREM sleep during the subsequent 6 h (ZT13-18) in wildtype mice, and sleep returned to the baseline the following day. However, the kindling-induced sleep alteration was absent in the IL-1R -/- KO mice. These results indicate that the IL-1 signal mediates epilepsy-induced sleep disturbance, but dose not participate in kindling-induced epileptogenesis.

  12. A Bio-Inspired, Motion-Based Analysis of Crowd Behavior Attributes Relevance to Motion Transparency, Velocity Gradients, and Motion Patterns

    PubMed Central

    Raudies, Florian; Neumann, Heiko

    2012-01-01

    The analysis of motion crowds is concerned with the detection of potential hazards for individuals of the crowd. Existing methods analyze the statistics of pixel motion to classify non-dangerous or dangerous behavior, to detect outlier motions, or to estimate the mean throughput of people for an image region. We suggest a biologically inspired model for the analysis of motion crowds that extracts motion features indicative for potential dangers in crowd behavior. Our model consists of stages for motion detection, integration, and pattern detection that model functions of the primate primary visual cortex area (V1), the middle temporal area (MT), and the medial superior temporal area (MST), respectively. This model allows for the processing of motion transparency, the appearance of multiple motions in the same visual region, in addition to processing opaque motion. We suggest that motion transparency helps to identify “danger zones” in motion crowds. For instance, motion transparency occurs in small exit passages during evacuation. However, motion transparency occurs also for non-dangerous crowd behavior when people move in opposite directions organized into separate lanes. Our analysis suggests: The combination of motion transparency and a slow motion speed can be used for labeling of candidate regions that contain dangerous behavior. In addition, locally detected decelerations or negative speed gradients of motions are a precursor of danger in crowd behavior as are globally detected motion patterns that show a contraction toward a single point. In sum, motion transparency, image speeds, motion patterns, and speed gradients extracted from visual motion in videos are important features to describe the behavioral state of a motion crowd. PMID:23300930

  13. Cocaine induces astrocytosis through ER stress-mediated activation of autophagy

    PubMed Central

    Periyasamy, Palsamy; Guo, Ming-Lei; Buch, Shilpa

    2016-01-01

    ABSTRACT Cocaine is known to induce inflammation, thereby contributing in part, to the pathogenesis of neurodegeneration. A recent study from our lab has revealed a link between macroautophagy/autophagy and microglial activation. The current study was aimed at investigating whether cocaine could also mediate activation of astrocytes and, whether this process involved induction of autophagy. Our findings demonstrated that cocaine mediated the activation of astrocytes by altering the levels of autophagy markers, such as BECN1, ATG5, MAP1LC3B-II, and SQSTM1 in both human A172 astrocytoma cells and primary human astrocytes. Furthermore, cocaine treatment resulted in increased formation of endogenous MAP1LC3B puncta in human astrocytes. Additionally, astrocytes transfected with the GFP-MAP1LC3B plasmid also demonstrated cocaine-mediated upregulation of the green fluorescent MAP1LC3B puncta. Cocaine-mediated induction of autophagy involved upstream activation of ER stress proteins such as EIF2AK3, ERN1, ATF6 since blockage of autophagy using either pharmacological or gene-silencing approaches, had no effect on cocaine-mediated induction of ER stress. Using both pharmacological and gene-silencing approaches to block either ER stress or autophagy, our findings demonstrated that cocaine-induced activation of astrocytes (measured by increased levels of GFAP) involved sequential activation of ER stress and autophagy. Cocaine-mediated-increased upregulation of GFAP correlated with increased expression of proinflammatory mediators such as TNF, IL1B, and IL6. In conclusion, these findings reveal an association between ER stress-mediated autophagy and astrogliosis in cocaine-treated astrocytes. Intervention of ER stress and/or autophagy signaling would thus be promising therapeutic targets for abrogating cocaine-mediated neuroinflammation. PMID:27337297

  14. Cocaine induces astrocytosis through ER stress-mediated activation of autophagy.

    PubMed

    Periyasamy, Palsamy; Guo, Ming-Lei; Buch, Shilpa

    2016-08-02

    Cocaine is known to induce inflammation, thereby contributing in part, to the pathogenesis of neurodegeneration. A recent study from our lab has revealed a link between macroautophagy/autophagy and microglial activation. The current study was aimed at investigating whether cocaine could also mediate activation of astrocytes and, whether this process involved induction of autophagy. Our findings demonstrated that cocaine mediated the activation of astrocytes by altering the levels of autophagy markers, such as BECN1, ATG5, MAP1LC3B-II, and SQSTM1 in both human A172 astrocytoma cells and primary human astrocytes. Furthermore, cocaine treatment resulted in increased formation of endogenous MAP1LC3B puncta in human astrocytes. Additionally, astrocytes transfected with the GFP-MAP1LC3B plasmid also demonstrated cocaine-mediated upregulation of the green fluorescent MAP1LC3B puncta. Cocaine-mediated induction of autophagy involved upstream activation of ER stress proteins such as EIF2AK3, ERN1, ATF6 since blockage of autophagy using either pharmacological or gene-silencing approaches, had no effect on cocaine-mediated induction of ER stress. Using both pharmacological and gene-silencing approaches to block either ER stress or autophagy, our findings demonstrated that cocaine-induced activation of astrocytes (measured by increased levels of GFAP) involved sequential activation of ER stress and autophagy. Cocaine-mediated-increased upregulation of GFAP correlated with increased expression of proinflammatory mediators such as TNF, IL1B, and IL6. In conclusion, these findings reveal an association between ER stress-mediated autophagy and astrogliosis in cocaine-treated astrocytes. Intervention of ER stress and/or autophagy signaling would thus be promising therapeutic targets for abrogating cocaine-mediated neuroinflammation.

  15. Dexras1 mediates glucocorticoid-associated adipogenesis and diet-induced obesity

    PubMed Central

    Cha, Jiyoung Y.; Kim, Hyo Jung; Yu, Jung Hwan; Xu, Jing; Kim, Daham; Paul, Bindu D.; Choi, Hyeonjin; Kim, Seyun; Lee, Yoo Jeong; Ho, Gary P.; Rao, Feng; Snyder, Solomon H.; Kim, Jae-woo

    2013-01-01

    Adipogenesis, the conversion of precursor cells into adipocytes, is associated with obesity and is mediated by glucocorticoids acting via hitherto poorly characterized mechanisms. Dexras1 is a small G protein of the Ras family discovered on the basis of its marked induction by the synthetic glucocorticoid dexamethasone. We show that Dexras1 mediates adipogenesis and diet-induced obesity. Adipogenic differentiation of 3T3-L1 cells is abolished with Dexras1 depletion, whereas overexpression of Dexras1 elicits adipogenesis. Adipogenesis is markedly reduced in mouse embryonic fibroblasts from Dexras1-deleted mice, whereas adiposity and diet-induced weight gain are diminished in the mutant mice. PMID:24297897

  16. An Animal Model of Abacavir-Induced HLA-Mediated Liver Injury.

    PubMed

    Song, Binbin; Aoki, Shigeki; Liu, Cong; Susukida, Takeshi; Ito, Kousei

    2018-04-01

    Genome-wide association studies indicate that several idiosyncratic adverse drug reactions are highly associated with specific human leukocyte antigen (HLA) alleles. For instance, abacavir, a human immunodeficiency virus reverse transcriptase inhibitor, induces multiorgan toxicity exclusively in patients carrying the HLA-B*57:01 allele. However, the underlying mechanism is unclear due to a lack of appropriate animal models. Previously, we developed HLA-B*57:01 transgenic mice and found that topical application of abacavir to the ears induced proliferation of CD8+ lymphocytes in local lymph nodes. Here, we attempted to reproduce abacavir-induced liver injury in these mice. However, oral administration of abacavir alone to HLA-B*57:01 transgenic mice did not increase levels of the liver injury marker alanine aminotransferase. Considering the importance of innate immune activation in mouse liver, we treated mice with CpG oligodeoxynucleotide, a toll-like receptor 9 agonist, plus abacavir. This resulted in a marked increase in alanine aminotransferase, pathological changes in liver, increased numbers of activated CD8+ T cells, and tissue infiltration by immune cells exclusively in HLA-B*57:01 transgenic mice. These results indicate that CpG oligodeoxynucleotide-induced inflammatory reactions and/or innate immune activation are necessary for abacavir-induced HLA-mediated liver injury characterized by infiltration of CD8+ T cells. Thus, we developed the first mouse model of HLA-mediated abacavir-induced idiosyncratic liver injury. Further investigation will show that the proposed HLA-mediated liver injury model can be applied to other combinations of drugs and HLA types, thereby improving drug development and contributing to the development of personalized medicine.

  17. Ghrelin mediates stress-induced food-reward behavior in mice

    PubMed Central

    Chuang, Jen-Chieh; Perello, Mario; Sakata, Ichiro; Osborne-Lawrence, Sherri; Savitt, Joseph M.; Lutter, Michael; Zigman, Jeffrey M.

    2011-01-01

    The popular media and personal anecdotes are rich with examples of stress-induced eating of calorically dense “comfort foods.” Such behavioral reactions likely contribute to the increased prevalence of obesity in humans experiencing chronic stress or atypical depression. However, the molecular substrates and neurocircuits controlling the complex behaviors responsible for stress-based eating remain mostly unknown, and few animal models have been described for probing the mechanisms orchestrating this response. Here, we describe a system in which food-reward behavior, assessed using a conditioned place preference (CPP) task, is monitored in mice after exposure to chronic social defeat stress (CSDS), a model of prolonged psychosocial stress, featuring aspects of major depression and posttraumatic stress disorder. Under this regime, CSDS increased both CPP for and intake of high-fat diet, and stress-induced food-reward behavior was dependent on signaling by the peptide hormone ghrelin. Also, signaling specifically in catecholaminergic neurons mediated not only ghrelin’s orexigenic, antidepressant-like, and food-reward behavioral effects, but also was sufficient to mediate stress-induced food-reward behavior. Thus, this mouse model has allowed us to ascribe a role for ghrelin-engaged catecholaminergic neurons in stress-induced eating. PMID:21701068

  18. Ghrelin mediates stress-induced food-reward behavior in mice.

    PubMed

    Chuang, Jen-Chieh; Perello, Mario; Sakata, Ichiro; Osborne-Lawrence, Sherri; Savitt, Joseph M; Lutter, Michael; Zigman, Jeffrey M

    2011-07-01

    The popular media and personal anecdotes are rich with examples of stress-induced eating of calorically dense "comfort foods." Such behavioral reactions likely contribute to the increased prevalence of obesity in humans experiencing chronic stress or atypical depression. However, the molecular substrates and neurocircuits controlling the complex behaviors responsible for stress-based eating remain mostly unknown, and few animal models have been described for probing the mechanisms orchestrating this response. Here, we describe a system in which food-reward behavior, assessed using a conditioned place preference (CPP) task, is monitored in mice after exposure to chronic social defeat stress (CSDS), a model of prolonged psychosocial stress, featuring aspects of major depression and posttraumatic stress disorder. Under this regime, CSDS increased both CPP for and intake of high-fat diet, and stress-induced food-reward behavior was dependent on signaling by the peptide hormone ghrelin. Also, signaling specifically in catecholaminergic neurons mediated not only ghrelin's orexigenic, antidepressant-like, and food-reward behavioral effects, but also was sufficient to mediate stress-induced food-reward behavior. Thus, this mouse model has allowed us to ascribe a role for ghrelin-engaged catecholaminergic neurons in stress-induced eating.

  19. Perceived state of self during motion can differentially modulate numerical magnitude allocation.

    PubMed

    Arshad, Q; Nigmatullina, Y; Roberts, R E; Goga, U; Pikovsky, M; Khan, S; Lobo, R; Flury, A-S; Pettorossi, V E; Cohen-Kadosh, R; Malhotra, P A; Bronstein, A M

    2016-09-01

    Although a direct relationship between numerical allocation and spatial attention has been proposed, recent research suggests that these processes are not directly coupled. In keeping with this, spatial attention shifts induced either via visual or vestibular motion can modulate numerical allocation in some circumstances but not in others. In addition to shifting spatial attention, visual or vestibular motion paradigms also (i) elicit compensatory eye movements which themselves can influence numerical processing and (ii) alter the perceptual state of 'self', inducing changes in bodily self-consciousness impacting upon cognitive mechanisms. Thus, the precise mechanism by which motion modulates numerical allocation remains unknown. We sought to investigate the influence that different perceptual experiences of motion have upon numerical magnitude allocation while controlling for both eye movements and task-related effects. We first used optokinetic visual motion stimulation (OKS) to elicit the perceptual experience of either 'visual world' or 'self'-motion during which eye movements were identical. In a second experiment, we used a vestibular protocol examining the effects of perceived and subliminal angular rotations in darkness, which also provoked identical eye movements. We observed that during the perceptual experience of 'visual world' motion, rightward OKS-biased judgments towards smaller numbers, whereas leftward OKS-biased judgments towards larger numbers. During the perceptual experience of 'self-motion', judgments were biased towards larger numbers irrespective of the OKS direction. Contrastingly, vestibular motion perception was found not to modulate numerical magnitude allocation, nor was there any differential modulation when comparing 'perceived' vs. 'subliminal' rotations. We provide a novel demonstration that numerical magnitude allocation can be differentially modulated by the perceptual state of self during visual but not vestibular mediated motion

  20. Dynamics of the functional link between area MT LFPs and motion detection

    PubMed Central

    Smith, Jackson E. T.; Beliveau, Vincent; Schoen, Alan; Remz, Jordana; Zhan, Chang'an A.

    2015-01-01

    The evolution of a visually guided perceptual decision results from multiple neural processes, and recent work suggests that signals with different neural origins are reflected in separate frequency bands of the cortical local field potential (LFP). Spike activity and LFPs in the middle temporal area (MT) have a functional link with the perception of motion stimuli (referred to as neural-behavioral correlation). To cast light on the different neural origins that underlie this functional link, we compared the temporal dynamics of the neural-behavioral correlations of MT spikes and LFPs. Wide-band activity was simultaneously recorded from two locations of MT from monkeys performing a threshold, two-stimuli, motion pulse detection task. Shortly after the motion pulse occurred, we found that high-gamma (100–200 Hz) LFPs had a fast, positive correlation with detection performance that was similar to that of the spike response. Beta (10–30 Hz) LFPs were negatively correlated with detection performance, but their dynamics were much slower, peaked late, and did not depend on stimulus configuration or reaction time. A late change in the correlation of all LFPs across the two recording electrodes suggests that a common input arrived at both MT locations prior to the behavioral response. Our results support a framework in which early high-gamma LFPs likely reflected fast, bottom-up, sensory processing that was causally linked to perception of the motion pulse. In comparison, late-arriving beta and high-gamma LFPs likely reflected slower, top-down, sources of neural-behavioral correlation that originated after the perception of the motion pulse. PMID:25948867

  1. Ghrelin signaling in the ventral tegmental area mediates both reward-based feeding and fasting-induced hyperphagia on high-fat diet.

    PubMed

    Wei, X J; Sun, B; Chen, K; Lv, B; Luo, X; Yan, J Q

    2015-08-06

    Ghrelin is a potent orexigenic hormone that acts in the central nervous system to stimulate food intake via the growth hormone secretagogue receptor (GHSR) that is abundantly expressed in the ventral tegmental area (VTA). Not only does ghrelin modulate feeding behavior via a homeostatic mechanism, but numerous studies have identified ghrelin as a key regulator of reward-based hedonic feeding behaviors. Nutritional states influence ghrelin and GHSR expression as well as the behavioral sensitivity to reward-inducing stimuli. In the current study, we examined the role of ghrelin at the VTA level in food intake in two different nutritional states, satiety and hunger, by using a restricted feeding model. In this model, rats were conditioned to a daily 3-h (h) feeding session on standard chow for 10days and a high-fat diet (HFD) was supplied either in the third hour after 2h of chow diet intake, or at the beginning of a daily meal on the test day. We found that intra-VTA microinjection of 1, 2, and 4μg of ghrelin, induced a dose-related increase of 1h of reward-based feeding on HFD in sated rats, as well as a 24-h body weight gain. The overconsumption stimulated by ghrelin could be attenuated by 10μg of direct infusion of the ghrelin receptor antagonist D-Lys3-GHRP-6 into the VTA. Moreover, our data showed that the injection of 1, 2, and 4μg of ghrelin in the VTA, enhanced fasting-induced hyperphagia on HFD in a dose-related manner following a 21-h food restriction as well as a 24-h body weight gain. Conversely, hyperphagia on HFD that is potentiated by ghrelin could be blocked by pretreatment with a 10-μg D-Lys3-GHRP-6 intra-VTA microinjection. Collectively, these data demonstrate that ghrelin signaling at the VTA level mediates both reward-based eating and fasting-induced hyperphagia and provides a primary target for the control of the intake of rewarding food. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Standards for efficient employment of wide-area motion imagery (WAMI) sensors

    NASA Astrophysics Data System (ADS)

    Randall, L. Scott; Maenner, Paul F.

    2013-05-01

    Airborne Wide Area Motion Imagery (WAMI) sensors provide the opportunity for continuous high-resolution surveillance of geographic areas covering tens of square kilometers. This is both a blessing and a curse. Data volumes from "gigapixel-class" WAMI sensors are orders of magnitude greater than for traditional "megapixel-class" video sensors. The amount of data greatly exceeds the capacities of downlinks to ground stations, and even if this were not true, the geographic coverage is too large for effective human monitoring. Although collected motion imagery is recorded on the platform, typically only small "windows" of the full field of view are transmitted to the ground; the full set of collected data can be retrieved from the recording device only after the mission has concluded. Thus, the WAMI environment presents several difficulties: (1) data is too massive for downlink; (2) human operator selection and control of the video windows may not be effective; (3) post-mission storage and dissemination may be limited by inefficient file formats; and (4) unique system implementation characteristics may thwart exploitation by available analysis tools. To address these issues, the National Geospatial-Intelligence Agency's Motion Imagery Standards Board (MISB) is developing relevant standard data exchange formats: (1) moving target indicator (MTI) and tracking metadata to support tipping and cueing of WAMI windows using "watch boxes" and "trip wires"; (2) control channel commands for positioning the windows within the full WAMI field of view; and (3) a full-field-of-view spatiotemporal tiled file format for efficient storage, retrieval, and dissemination. The authors previously provided an overview of this suite of standards. This paper describes the latest progress, with specific concentration on a detailed description of the spatiotemporal tiled file format.

  3. Vehicle tracking in wide area motion imagery from an airborne platform

    NASA Astrophysics Data System (ADS)

    van Eekeren, Adam W. M.; van Huis, Jasper R.; Eendebak, Pieter T.; Baan, Jan

    2015-10-01

    Airborne platforms, such as UAV's, with Wide Area Motion Imagery (WAMI) sensors can cover multiple square kilometers and produce large amounts of video data. Analyzing all data for information need purposes becomes increasingly labor-intensive for an image analyst. Furthermore, the capacity of the datalink in operational areas may be inadequate to transfer all data to the ground station. Automatic detection and tracking of people and vehicles enables to send only the most relevant footage to the ground station and assists the image analysts in effective data searches. In this paper, we propose a method for detecting and tracking vehicles in high-resolution WAMI images from a moving airborne platform. For the vehicle detection we use a cascaded set of classifiers, using an Adaboost training algorithm on Haar features. This detector works on individual images and therefore does not depend on image motion stabilization. For the vehicle tracking we use a local template matching algorithm. This approach has two advantages. In the first place, it does not depend on image motion stabilization and it counters the inaccuracy of the GPS data that is embedded in the video data. In the second place, it can find matches when the vehicle detector would miss a certain detection. This results in long tracks even when the imagery is of low frame-rate. In order to minimize false detections, we also integrate height information from a 3D reconstruction that is created from the same images. By using the locations of buildings and roads, we are able to filter out false detections and increase the performance of the tracker. In this paper we show that the vehicle tracks can also be used to detect more complex events, such as traffic jams and fast moving vehicles. This enables the image analyst to do a faster and more effective search of the data.

  4. Perception of Elasticity in the Kinetic Illusory Object with Phase Differences in Inducer Motion

    PubMed Central

    Masuda, Tomohiro; Sato, Kazuki; Murakoshi, Takuma; Utsumi, Ken; Kimura, Atsushi; Shirai, Nobu; Kanazawa, So; Yamaguchi, Masami K.; Wada, Yuji

    2013-01-01

    Background It is known that subjective contours are perceived even when a figure involves motion. However, whether this includes the perception of rigidity or deformation of an illusory surface remains unknown. In particular, since most visual stimuli used in previous studies were generated in order to induce illusory rigid objects, the potential perception of material properties such as rigidity or elasticity in these illusory surfaces has not been examined. Here, we elucidate whether the magnitude of phase difference in oscillation influences the visual impressions of an object's elasticity (Experiment 1) and identify whether such elasticity perceptions are accompanied by the shape of the subjective contours, which can be assumed to be strongly correlated with the perception of rigidity (Experiment 2). Methodology/Principal Findings In Experiment 1, the phase differences in the oscillating motion of inducers were controlled to investigate whether they influenced the visual impression of an illusory object's elasticity. The results demonstrated that the impression of the elasticity of an illusory surface with subjective contours was systematically flipped with the degree of phase difference. In Experiment 2, we examined whether the subjective contours of a perceived object appeared linear or curved using multi-dimensional scaling analysis. The results indicated that the contours of a moving illusory object were perceived as more curved than linear in all phase-difference conditions. Conclusions/Significance These findings suggest that the phase difference in an object's motion is a significant factor in the material perception of motion-related elasticity. PMID:24205281

  5. Delay feedback induces a spontaneous motion of two-dimensional cavity solitons in driven semiconductor microcavities

    NASA Astrophysics Data System (ADS)

    Tlidi, M.; Averlant, E.; Vladimirov, A.; Panajotov, K.

    2012-09-01

    We consider a broad area vertical-cavity surface-emitting laser (VCSEL) operating below the lasing threshold and subject to optical injection and time-delayed feedback. We derive a generalized delayed Swift-Hohenberg equation for the VCSEL system, which is valid close to the nascent optical bistability. We first characterize the stationary-cavity solitons by constructing their snaking bifurcation diagram and by showing clustering behavior within the pinning region of parameters. Then, we show that the delayed feedback induces a spontaneous motion of two-dimensional (2D) cavity solitons in an arbitrary direction in the transverse plane. We characterize moving cavity solitons by estimating their threshold and calculating their velocity. Numerical 2D solutions of the governing semiconductor laser equations are in close agreement with those obtained from the delayed generalized Swift-Hohenberg equation.

  6. Enhanced Ultrasound Visualization of Bracytherapy Seeds by a Novel Magnetically Induced Motion Imaging Method

    DTIC Science & Technology

    2008-04-01

    We report our progress in developing Magnetically Induced Motion Imaging (MIMI) for unambiguous identification and localization brachytherapy seeds ...in ultrasound images. Coupled finite element and ultrasound imaging simulations have been performed to demonstrate that seeds are detectable with MIMI

  7. Gain Modulation as a Mechanism for Coding Depth from Motion Parallax in Macaque Area MT

    PubMed Central

    Kim, HyungGoo R.; Angelaki, Dora E.

    2017-01-01

    Observer translation produces differential image motion between objects that are located at different distances from the observer's point of fixation [motion parallax (MP)]. However, MP can be ambiguous with respect to depth sign (near vs far), and this ambiguity can be resolved by combining retinal image motion with signals regarding eye movement relative to the scene. We have previously demonstrated that both extra-retinal and visual signals related to smooth eye movements can modulate the responses of neurons in area MT of macaque monkeys, and that these modulations generate neural selectivity for depth sign. However, the neural mechanisms that govern this selectivity have remained unclear. In this study, we analyze responses of MT neurons as a function of both retinal velocity and direction of eye movement, and we show that smooth eye movements modulate MT responses in a systematic, temporally precise, and directionally specific manner to generate depth-sign selectivity. We demonstrate that depth-sign selectivity is primarily generated by multiplicative modulations of the response gain of MT neurons. Through simulations, we further demonstrate that depth can be estimated reasonably well by a linear decoding of a population of MT neurons with response gains that depend on eye velocity. Together, our findings provide the first mechanistic description of how visual cortical neurons signal depth from MP. SIGNIFICANCE STATEMENT Motion parallax is a monocular cue to depth that commonly arises during observer translation. To compute from motion parallax whether an object appears nearer or farther than the point of fixation requires combining retinal image motion with signals related to eye rotation, but the neurobiological mechanisms have remained unclear. This study provides the first mechanistic account of how this interaction takes place in the responses of cortical neurons. Specifically, we show that smooth eye movements modulate the gain of responses of neurons

  8. Transient Receptor Potential Vanilloid 1 Expression Mediates Capsaicin-Induced Cell Death.

    PubMed

    Ramírez-Barrantes, Ricardo; Córdova, Claudio; Gatica, Sebastian; Rodriguez, Belén; Lozano, Carlo; Marchant, Ivanny; Echeverria, Cesar; Simon, Felipe; Olivero, Pablo

    2018-01-01

    The transient receptor potential (TRP) ion channel family consists of a broad variety of non-selective cation channels that integrate environmental physicochemical signals for dynamic homeostatic control. Involved in a variety of cellular physiological processes, TRP channels are fundamental to the control of the cell life cycle. TRP channels from the vanilloid (TRPV) family have been directly implicated in cell death. TRPV1 is activated by pain-inducing stimuli, including inflammatory endovanilloids and pungent exovanilloids, such as capsaicin (CAP). TRPV1 activation by high doses of CAP (>10 μM) leads to necrosis, but also exhibits apoptotic characteristics. However, CAP dose-response studies are lacking in order to determine whether CAP-induced cell death occurs preferentially via necrosis or apoptosis. In addition, it is not known whether cytosolic Ca 2+ and mitochondrial dysfunction participates in CAP-induced TRPV1-mediated cell death. By using TRPV1-transfected HeLa cells, we investigated the underlying mechanisms involved in CAP-induced TRPV1-mediated cell death, the dependence of CAP dose, and the participation of mitochondrial dysfunction and cytosolic Ca 2+ increase. Together, our results contribute to elucidate the pathophysiological steps that follow after TRPV1 stimulation with CAP. Low concentrations of CAP (1 μM) induce cell death by a mechanism involving a TRPV1-mediated rapid and transient intracellular Ca 2+ increase that stimulates plasma membrane depolarization, thereby compromising plasma membrane integrity and ultimately leading to cell death. Meanwhile, higher doses of CAP induce cell death via a TRPV1-independent mechanism, involving a slow and persistent intracellular Ca 2+ increase that induces mitochondrial dysfunction, plasma membrane depolarization, plasma membrane loss of integrity, and ultimately, cell death.

  9. Perception of object motion in three-dimensional space induced by cast shadows.

    PubMed

    Katsuyama, Narumi; Usui, Nobuo; Nose, Izuru; Taira, Masato

    2011-01-01

    Cast shadows can be salient depth cues in three-dimensional (3D) vision. Using a motion illusion in which a ball is perceived to roll in depth on the bottom or to flow in the front plane depending on the slope of the trajectory of its cast shadow, we investigated cortical mechanisms underlying 3D vision based on cast shadows using fMRI techniques. When modified versions of the original illusion, in which the slope of the shadow trajectory (shadow slope) was changed in 5 steps from the same one as the ball trajectory to the horizontal, were presented to participants, their perceived ball trajectory shifted gradually from rolling on the bottom to floating in the front plane as the change of the shadow slope. This observation suggests that the perception of the ball trajectory in this illusion is strongly affected by the motion of the cast shadow. In the fMRI study, cortical activity during observation of the movies of the illusion was investigated. We found that the bilateral posterior-occipital sulcus (POS) and right ventral precuneus showed activation related to the perception of the ball trajectory induced by the cast shadows in the illusion. Of these areas, it was suggested that the right POS may be involved in the inferring of the ball trajectory by the given spatial relation between the ball and the shadow. Our present results suggest that the posterior portion of the medial parietal cortex may be involved in 3D vision by cast shadows. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Role of orientation reference selection in motion sickness

    NASA Technical Reports Server (NTRS)

    Peterka, Robert J.; Black, F. Owen

    1992-01-01

    The overall objective of this proposal is to understand the relationship between human orientation control and motion sickness susceptibility. Three areas related to orientation control will be investigated. These three areas are (1) reflexes associated with the control of eye movements and posture, (2) the perception of body rotation and position with respect to gravity, and (3) the strategies used to resolve sensory conflict situations which arise when different sensory systems provide orientation cues which are not consistent with one another or with previous experience. Of particular interest is the possibility that a subject may be able to ignore an inaccurate sensory modality in favor of one or more other sensory modalities which do provide accurate orientation reference information. We refer to this process as sensory selection. This proposal will attempt to quantify subjects' sensory selection abilities and determine if this ability confers some immunity to the development of motion sickness symptoms. Measurements of reflexes, motion perception, sensory selection abilities, and motion sickness susceptibility will concentrate on pitch and roll motions since these seem most relevant to the space motion sickness problem. Vestibulo-ocular (VOR) and oculomotor reflexes will be measured using a unique two-axis rotation device developed in our laboratory over the last seven years. Posture control reflexes will be measured using a movable posture platform capable of independently altering proprioceptive and visual orientation cues. Motion perception will be quantified using closed loop feedback technique developed by Zacharias and Young (Exp Brain Res, 1981). This technique requires a subject to null out motions induced by the experimenter while being exposed to various confounding sensory orientation cues. A subject's sensory selection abilities will be measured by the magnitude and timing of his reactions to changes in sensory environments. Motion sickness

  11. Muscarinic receptors mediate cold stress-induced detrusor overactivity in type 2 diabetes mellitus rats.

    PubMed

    Imamura, Tetsuya; Ishizuka, Osamu; Ogawa, Teruyuki; Yamagishi, Takahiro; Yokoyama, Hitoshi; Minagawa, Tomonori; Nakazawa, Masaki; Gautam, Sudha Silwal; Nishizawa, Osamu

    2014-10-01

    This study determined if muscarinic receptors could mediate the cold stress-induced detrusor overactivity induced in type 2 diabetes mellitus rats. Ten-week-old female Goto-Kakizaki diabetic rats (n = 12) and Wister Kyoto non-diabetic rats (n = 12) were maintained on a high-fat diet for 4 weeks. Cystometric investigations of the unanesthetized rats were carried out at room temperature (27 ± 2°C) for 20 min. They were intravenously administered imidafenacin (0.3 mg/kg, n = 6) or vehicle (n = 6). After 5 min, the rats were transferred to a low temperature (4 ± 2°C) for 40 min where the cystometry was continued. The rats were then returned to room temperature for the final cystometric measurements. Afterwards, expressions of bladder muscarinic receptor M3 and M2 messenger ribonucleic acids and proteins were assessed by reverse transcription polymerase chain reaction and immunohistochemistry. In non-diabetic Wister Kyoto rats, imidafenacin did not reduce cold stress-induced detrusor overactivity. In diabetic Goto-Kakizaki rats, just after transfer to a low temperature, the cold stress-induced detrusor overactivity in imidafenacin-treated rats was reduced compared with vehicle-treated rats. Within the urinary bladders, the ratio of M3 to M2 receptor messenger ribonucleic acid in the diabetic Goto-Kakizaki rats was significantly higher than that of the non-diabetic Wister Kyoto rats. The proportion of muscarinic M3 receptor-positive area within the detrusor in diabetic Goto-Kakizaki rats was also significantly higher than that in non-diabetic Wister Kyoto rats. Imidafenacin partially inhibits cold stress-induced detrusor overactivity in diabetic Goto-Kakizaki rats. In this animal model, muscarinic M3 receptors partially mediate cold stress-induced detrusor overactivity. © 2014 The Japanese Urological Association.

  12. Quantification of respiration-induced esophageal tumor motion using fiducial markers and four-dimensional computed tomography.

    PubMed

    Jin, Peng; Hulshof, Maarten C C M; de Jong, Rianne; van Hooft, Jeanin E; Bel, Arjan; Alderliesten, Tanja

    2016-03-01

    Respiration-induced tumor motion is an important geometrical uncertainty in esophageal cancer radiation therapy. The aim of this study was to quantify this motion using fiducial markers and four-dimensional computed tomography (4DCT). Twenty esophageal cancer patients underwent endoscopy-guided marker implantation in the tumor volume and 4DCT acquisition. The 4DCT data were sorted into 10 breathing phases and the end-of-inhalation phase was selected as reference. We quantified for each visible marker (n=60) the motion in each phase and derived the peak-to-peak motion magnitude throughout the breathing cycle. The motion was quantified and analyzed for four different regions and in three orthogonal directions. The median(interquartile range) of the peak-to-peak magnitudes of the respiration-induced marker motion (left-right/anterior-posterior/cranial-caudal) was 1.5(0.5)/1.6(0.5)/2.9(1.4) mm for the proximal esophagus (n=6), 1.5(1.4)/1.4(1.3)/3.7(2.6) mm for the middle esophagus (n=12), 2.6(1.3)/3.3(1.8)/5.4(2.9) mm for the distal esophagus (n=25), and 3.7(2.1)/5.3(1.8)/8.2(3.1) mm for the proximal stomach (n=17). The variations in the results between the three directions, four regions, and patients suggest the need of individualized region-dependent anisotropic internal margins. Therefore, we recommend using markers with 4DCT to patient-specifically adapt the internal target volume (ITV). Without 4DCT, 3DCTs at the end-of-inhalation and end-of-exhalation phases could be alternatively applied for ITV individualization. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Detection of cyclic-fold bifurcation in electrostatic MEMS transducers by motion-induced current

    NASA Astrophysics Data System (ADS)

    Park, Sangtak; Khater, Mahmoud; Effa, David; Abdel-Rahman, Eihab; Yavuz, Mustafa

    2017-08-01

    This paper presents a new detection method of cyclic-fold bifurcations in electrostatic MEMS transducers based on a variant of the harmonic detection of resonance method. The electrostatic transducer is driven by an unbiased harmonic signal at half its natural frequency, ω a   =  1/2 ω o . The response of the transducer consists of static displacement and a series of harmonics at 2 ω a , 4 ω a , and so on. Its motion-induced current is shifted by the excitation frequency, ω a , to appear at 3 ω a , 5 ω a , and higher odd harmonics, providing higher sensitivity to the measurement of harmonic motions. With this method, we successfully detected the variation in the location of the cyclic-fold bifurcation of an encapsulated electrostatic MEMS transducer. We also detected a regime of tapping mode motions subsequent to the bifurcation.

  14. People can understand descriptions of motion without activating visual motion brain regions

    PubMed Central

    Dravida, Swethasri; Saxe, Rebecca; Bedny, Marina

    2013-01-01

    What is the relationship between our perceptual and linguistic neural representations of the same event? We approached this question by asking whether visual perception of motion and understanding linguistic depictions of motion rely on the same neural architecture. The same group of participants took part in two language tasks and one visual task. In task 1, participants made semantic similarity judgments with high motion (e.g., “to bounce”) and low motion (e.g., “to look”) words. In task 2, participants made plausibility judgments for passages describing movement (“A centaur hurled a spear … ”) or cognitive events (“A gentleman loved cheese …”). Task 3 was a visual motion localizer in which participants viewed animations of point-light walkers, randomly moving dots, and stationary dots changing in luminance. Based on the visual motion localizer we identified classic visual motion areas of the temporal (MT/MST and STS) and parietal cortex (inferior and superior parietal lobules). We find that these visual cortical areas are largely distinct from neural responses to linguistic depictions of motion. Motion words did not activate any part of the visual motion system. Motion passages produced a small response in the right superior parietal lobule, but none of the temporal motion regions. These results suggest that (1) as compared to words, rich language stimuli such as passages are more likely to evoke mental imagery and more likely to affect perceptual circuits and (2) effects of language on the visual system are more likely in secondary perceptual areas as compared to early sensory areas. We conclude that language and visual perception constitute distinct but interacting systems. PMID:24009592

  15. Controlled surface-induced flows from the motion of self-assembled colloidal walkers.

    PubMed

    Sing, Charles E; Schmid, Lothar; Schneider, Matthias F; Franke, Thomas; Alexander-Katz, Alfredo

    2010-01-12

    Biological flows at the microscopic scale are important for the transport of nutrients, locomotion, and differentiation. Here, we present a unique approach for creating controlled, surface-induced flows inspired by a ubiquitous biological system, cilia. Our design is based on a collection of self-assembled colloidal rotors that "walk" along surfaces in the presence of a rotating magnetic field. These rotors are held together solely by magnetic forces that allow for reversible assembly and disassembly of the chains. Furthermore, rotation of the magnetic field allows for straightforward manipulation of the shape and motion of these chains. This system offers a simple and versatile approach for designing microfluidic devices as well as for studying fundamental questions in cooperative-driven motion and transport at the microscopic level.

  16. Effect decomposition in the presence of an exposure-induced mediator-outcome confounder

    PubMed Central

    VanderWeele, Tyler J.; Vansteelandt, Stijn; Robins, James M.

    2014-01-01

    Methods from causal mediation analysis have generalized the traditional approach to direct and indirect effects in the epidemiologic and social science literature by allowing for interaction and non-linearities. However, the methods from the causal inference literature have themselves been subject to a major limitation in that the so-called natural direct and indirect effects that are employed are not identified from data whenever there is a variable that is affected by the exposure, which also confounds the relationship between the mediator and the outcome. In this paper we describe three alternative approaches to effect decomposition that give quantities that can be interpreted as direct and indirect effects, and that can be identified from data even in the presence of an exposure-induced mediator-outcome confounder. We describe a simple weighting-based estimation method for each of these three approaches, illustrated with data from perinatal epidemiology. The methods described here can shed insight into pathways and questions of mediation even when an exposure-induced mediator-outcome confounder is present. PMID:24487213

  17. Sphingosine kinase 1 mediates AGEs-induced fibronectin upregulation in diabetic nephropathy.

    PubMed

    Chen, Cheng; Gong, Wenyan; Li, Changzheng; Xiong, Fengxiao; Wang, Shaogui; Huang, Junying; Wang, Yu; Chen, Zhiquan; Chen, Qiuhong; Liu, Peiqing; Lan, Tian; Huang, Heqing

    2017-10-03

    Activation of sphingosine kinase 1 (SphK1) signaling pathway mediates fibronectin (FN) upregulation in glomerular mesangial cells (GMCs) under high glucose (HG) condition. However, the roles of SphK1 in advanced glycation end products (AGEs)-induced DN have not been elucidated. Here we show that AGEs upregulated FN and SphK1 and SphK1 activity. Inhibition of SphK1 signaling attenuated AGEs-induced FN synthesis in GMCs. Inhibition of AGE receptor (RAGE) signaling reduced the upregulation of FN and SphK1 and SphK1 activity in GMCs induced by AGEs. Treatment of aminoguanidine ameliorates the renal injury and fibrosis in STZ-induced diabetic mice and attenuated SphK1 expression and activity in diabetic mouse kidneys. The renal injury and fibrosis in diabetic SphK1 -/- mice was significantly attenuated than WT mice. Furthermore, AGEs upregulated SphK1 by reducing its degradation and prolonging its half-life. SphK1 mediates AGEs-induced FN synthesis in GMCs and diabetic mice under hyperglycemic condition .

  18. Sphingosine kinase 1 mediates AGEs-induced fibronectin upregulation in diabetic nephropathy

    PubMed Central

    Chen, Cheng; Gong, Wenyan; Li, Changzheng; Xiong, Fengxiao; Wang, Shaogui; Huang, Junying; Wang, Yu; Chen, Zhiquan; Chen, Qiuhong; Liu, Peiqing; Lan, Tian; Huang, Heqing

    2017-01-01

    Activation of sphingosine kinase 1 (SphK1) signaling pathway mediates fibronectin (FN) upregulation in glomerular mesangial cells (GMCs) under high glucose (HG) condition. However, the roles of SphK1 in advanced glycation end products (AGEs)-induced DN have not been elucidated. Here we show that AGEs upregulated FN and SphK1 and SphK1 activity. Inhibition of SphK1 signaling attenuated AGEs-induced FN synthesis in GMCs. Inhibition of AGE receptor (RAGE) signaling reduced the upregulation of FN and SphK1 and SphK1 activity in GMCs induced by AGEs. Treatment of aminoguanidine ameliorates the renal injury and fibrosis in STZ-induced diabetic mice and attenuated SphK1 expression and activity in diabetic mouse kidneys. The renal injury and fibrosis in diabetic SphK1-/- mice was significantly attenuated than WT mice. Furthermore, AGEs upregulated SphK1 by reducing its degradation and prolonging its half-life. Conclusion: SphK1 mediates AGEs-induced FN synthesis in GMCs and diabetic mice under hyperglycemic condition. PMID:29108256

  19. Dynamic RSA for the evaluation of inducible micromotion of Oxford UKA during step-up and step-down motion.

    PubMed

    Horsager, Kristian; Kaptein, Bart L; Rømer, Lone; Jørgensen, Peter B; Stilling, Maiken

    2017-06-01

    Background and purpose - Implant inducible micromotions have been suggested to reflect the quality of the fixation interface. We investigated the usability of dynamic RSA for evaluation of inducible micromotions of the Oxford Unicompartmental Knee Arthroplasty (UKA) tibial component, and evaluated factors that have been suggested to compromise the fixation, such as fixation method, component alignment, and radiolucent lines (RLLs). Patients and methods - 15 patients (12 men) with a mean age of 69 (55-86) years, with an Oxford UKA (7 cemented), were studied after a mean time in situ of 4.4 (3.6-5.1) years. 4 had tibial RLLs. Each patient was recorded with dynamic RSA (10 frames/second) during a step-up/step-down motion. Inducible micromotions were calculated for the tibial component with respect to the tibia bone. Postoperative component alignment was measured with model-based RSA and RLLs were measured on screened radiographs. Results - All tibial components showed inducible micromotions as a function of the step-cycle motion with a mean subsidence of up to -0.06 mm (95% CI: -0.10 to -0.03). Tibial component inducible micromotions were similar for cemented fixation and cementless fixation. Patients with tibial RLLs had 0.5° (95% CI: 0.18-0.81) greater inducible medio-lateral tilt of the tibial component. There was a correlation between postoperative posterior slope of the tibial plateau and inducible anterior-posterior tilt. Interpretation - All patients had inducible micromotions of the tibial component during step-cycle motion. RLLs and a high posterior slope increased the magnitude of inducible micromotions. This suggests that dynamic RSA is a valuable clinical tool for the evaluation of functional implant fixation.

  20. Overlapping striatal sites mediate scopolamine-induced feeding suppression and mu-opioid-mediated hyperphagia in the rat.

    PubMed

    Perry, Michelle L; Pratt, Wayne E; Baldo, Brian A

    2014-03-01

    Intra-striatal infusions of the muscarinic antagonist, scopolamine, markedly suppress feeding; however, the underlying mechanisms are unclear. Recent findings suggest that scopolamine influences opioid-dependent mechanisms of feeding modulation. Robust mu-opioid-mediated feeding responses are obtained in anterior, ventral sectors of the striatum with progressively weaker effects posteriorly and dorsally. One might therefore expect the effects of scopolamine to conform to similar boundaries, but a systematic mapping of scopolamine-induced feeding suppression has not yet been undertaken. This study aimed to assess the overlap between the striatal sites mediating scopolamine-induced feeding suppression and mu-opioid-induced hyperphagia. Dose-effect functions for scopolamine (0, 1, 5, and 10 μg) were obtained in the nucleus accumbens (Acb), anterior dorsal striatum (ADS), and posterior dorsal striatum (PDS) in three different groups of rats. In the same subjects, the mu-opioid receptor agonist (D-Ala2-N-MePhe4, Glyol)-enkephalin (DAMGO; 0.25 μg) was infused on a separate test day. The dependent variables were food and water intake, ambulation, and rearing. The greatest dose sensitivity for scopolamine-induced feeding suppression was observed in the Acb. Only the highest dose was effective in the ADS, and no effects were seen in the PDS. Water intake and general motor activity were not altered by scopolamine in any site. DAMGO infusions produced hyperphagia only in the Acb. These results support a model in which the behavioral effects of muscarinic blockade are limited by the same anatomical constraints that govern mu-opioid receptor-mediated control of feeding. These constraints are likely imposed by the topographic arrangement of feeding-related afferent inputs and efferent projections of the striatum.

  1. Mitochondrial damage elicits a TCDD-inducible poly(ADP-ribose) polymerase-mediated antiviral response

    PubMed Central

    Kozaki, Tatsuya; Komano, Jun; Kanbayashi, Daiki; Takahama, Michihiro; Misawa, Takuma; Satoh, Takashi; Takeuchi, Osamu; Kawai, Taro; Shimizu, Shigeomi; Matsuura, Yoshiharu; Akira, Shizuo; Saitoh, Tatsuya

    2017-01-01

    The innate immune system senses RNA viruses by pattern recognition receptors (PRRs) and protects the host from virus infection. PRRs mediate the production of immune modulatory factors and direct the elimination of RNA viruses. Here, we show a unique PRR that mediates antiviral response. Tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP ribose) polymerase (TIPARP), a Cysteine3 Histidine (CCCH)-type zinc finger-containing protein, binds to Sindbis virus (SINV) RNA via its zinc finger domain and recruits an exosome to induce viral RNA degradation. TIPARP typically localizes in the nucleus, but it accumulates in the cytoplasm after SINV infection, allowing targeting of cytoplasmic SINV RNA. Redistribution of TIPARP is induced by reactive oxygen species (ROS)-dependent oxidization of the nuclear pore that affects cytoplasmic-nuclear transport. BCL2-associated X protein (BAX) and BCL2 antagonist/killer 1 (BAK1), B-cell leukemia/lymphoma 2 (BCL2) family members, mediate mitochondrial damage to generate ROS after SINV infection. Thus, TIPARP is a viral RNA-sensing PRR that mediates antiviral responses triggered by BAX- and BAK1-dependent mitochondrial damage. PMID:28213497

  2. Tile prediction schemes for wide area motion imagery maps in GIS

    NASA Astrophysics Data System (ADS)

    Michael, Chris J.; Lin, Bruce Y.

    2017-11-01

    Wide-area surveillance, traffic monitoring, and emergency management are just several of many applications benefiting from the incorporation of Wide-Area Motion Imagery (WAMI) maps into geographic information systems. Though the use of motion imagery as a GIS base map via the Web Map Service (WMS) standard is not a new concept, effectively streaming imagery is particularly challenging due to its large scale and the multidimensionally interactive nature of clients that use WMS. Ineffective streaming from a server to one or more clients can unnecessarily overwhelm network bandwidth and cause frustratingly large amounts of latency in visualization to the user. Seamlessly streaming WAMI through GIS requires good prediction to accurately guess the tiles of the video that will be traversed in the near future. In this study, we present an experimental framework for such prediction schemes by presenting a stochastic interaction model that represents a human user's interaction with a GIS video map. We then propose several algorithms by which the tiles of the stream may be predicted. Results collected both within the experimental framework and using human analyst trajectories show that, though each algorithm thrives under certain constraints, the novel Markovian algorithm yields the best results overall. Furthermore, we make the argument that the proposed experimental framework is sufficient for the study of these prediction schemes.

  3. Heme oxygenase-1 mediates BAY 11-7085 induced ferroptosis.

    PubMed

    Chang, Ling-Chu; Chiang, Shih-Kai; Chen, Shuen-Ei; Yu, Yung-Luen; Chou, Ruey-Hwang; Chang, Wei-Chao

    2018-03-01

    Ferroptosis is a form of oxidative cell death and has become a chemotherapeutic target for cancer treatment. BAY 11-7085 (BAY), which is a well-known IκBα inhibitor, suppressed viability in cancer cells via induction of ferroptotic death in an NF-κB-independent manner. Reactive oxygen species scavenging, relief of lipid peroxidation, replenishment of glutathione and thiol-containing agents, as well as iron chelation, rescued BAY-induced cell death. BAY upregulated a variety of Nrf2 target genes related to redox regulation, particularly heme oxygenase-1 (HO-1). Studies with specific inhibitors and shRNA interventions suggested that the hierarchy of induction is Nrf2-SLC7A11-HO-1. SLC7A11 inhibition by erastin, sulfasalazine, or shRNA interference sensitizes BAY-induced cell death. Overexperession of SLC7A11 attenuated BAY-inhibited cell viability. The ferroptotic process induced by hHO-1 overexpression further indicated that HO-1 is a key mediator of BAY-induced ferroptosis that operates through cellular redox regulation and iron accumulation. BAY causes compartmentalization of HO-1 into the nucleus and mitochondrion, and followed mitochondrial dysfunctions, leading to lysosome targeting for mitophagy. In this study, we first discovered that BAY induced ferroptosis via Nrf2-SLC7A11-HO-1 pathway and HO-1 is a key mediator by responding to the cellular redox status. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Characterizing spatiotemporal information loss in sparse-sampling-based dynamic MRI for monitoring respiration-induced tumor motion in radiotherapy.

    PubMed

    Arai, Tatsuya J; Nofiele, Joris; Madhuranthakam, Ananth J; Yuan, Qing; Pedrosa, Ivan; Chopra, Rajiv; Sawant, Amit

    2016-06-01

    Sparse-sampling and reconstruction techniques represent an attractive strategy to achieve faster image acquisition speeds, while maintaining adequate spatial resolution and signal-to-noise ratio in rapid magnetic resonance imaging (MRI). The authors investigate the use of one such sequence, broad-use linear acquisition speed-up technique (k-t BLAST) in monitoring tumor motion for thoracic and abdominal radiotherapy and examine the potential trade-off between increased sparsification (to increase imaging speed) and the potential loss of "true" information due to greater reliance on a priori information. Lung tumor motion trajectories in the superior-inferior direction, previously recorded from ten lung cancer patients, were replayed using a motion phantom module driven by an MRI-compatible motion platform. Eppendorf test tubes filled with water which serve as fiducial markers were placed in the phantom. The modeled rigid and deformable motions were collected in a coronal image slice using balanced fast field echo in conjunction with k-t BLAST. Root mean square (RMS) error was used as a metric of spatial accuracy as measured trajectories were compared to input data. The loss of spatial information was characterized for progressively increasing acceleration factor from 1 to 16; the resultant sampling frequency was increased approximately from 2.5 to 19 Hz when the principal direction of the motion was set along frequency encoding direction. In addition to the phantom study, respiration-induced tumor motions were captured from two patients (kidney tumor and lung tumor) at 13 Hz over 49 s to demonstrate the impact of high speed motion monitoring over multiple breathing cycles. For each subject, the authors compared the tumor centroid trajectory as well as the deformable motion during free breathing. In the rigid and deformable phantom studies, the RMS error of target tracking at the acquisition speed of 19 Hz was approximately 0.3-0.4 mm, which was smaller than the

  5. Enhanced Ultrasound Visualization of Brachytherapy Seeds by a Novel Magnetically Induced Motion Imaging Method

    DTIC Science & Technology

    2007-04-01

    We report our progress in developing Magnetically Induced Motion Imaging (MIMI) for unambiguous identification and localization brachytherapy seeds ...tail artifacts in segmented seed images. The second is a method for joining ends of seeds in segmented seed images based on the phase of the detected

  6. A 1500 deg2 near infrared proper motion catalogue from the UKIDSS Large Area Survey

    NASA Astrophysics Data System (ADS)

    Smith, Leigh; Lucas, P. W.; Burningham, B.; Jones, H. R. A.; Smart, R. L.; Andrei, A. H.; Catalán, S.; Pinfield, D. J.

    2014-02-01

    The United Kingdom Infrared Deep Sky Survey (UKIDSS) Large Area Survey (LAS) began in 2005, with the start of the UKIDSS programme as a 7 year effort to survey roughly 4000 deg2 at high Galactic latitudes in Y, J, H and K bands. The survey also included a significant quantity of two epoch J band observations, with an epoch baseline greater than 2 years to calculate proper motions. We present a near-infrared proper motion catalogue for the 1500 deg2 of the two epoch LAS data, which includes 135 625 stellar sources and a further 88 324 with ambiguous morphological classifications, all with motions detected above the 5σ level. We developed a custom proper motion pipeline which we describe here. Our catalogue agrees well with the proper motion data supplied for a 300 deg2 subset in the current Wide Field Camera Science Archive (WSA) 10th data release (DR10) catalogue, and in various optical catalogues, but it benefits from a larger matching radius and hence a larger upper proper motion detection limit. We provide absolute proper motions, using LAS galaxies for the relative to absolute correction. By using local second-order polynomial transformations, as opposed to linear transformations in the WSA, we correct better for any local distortions in the focal plane, not including the radial distortion that is removed by the UKIDSS pipeline. We present the results of proper motion searches for new brown dwarfs and white dwarfs. We discuss 41 sources in the WSA DR10 overlap with our catalogue with proper motions >300 mas yr-1, several of which are new detections. We present 15 new candidate ultracool dwarf binary systems.

  7. Effects of eating on vection-induced motion sickness, cardiac vagal tone, and gastric myoelectric activity

    NASA Technical Reports Server (NTRS)

    Uijtdehaage, S. H.; Stern, R. M.; Koch, K. L.

    1992-01-01

    This study investigated the effect of food ingestion on motion sickness severity and its physiological mechanisms. Forty-six fasted subjects were assigned either to a meal group or to a no-meal group. Electrogastrographic (EGG) indices (normal 3 cpm activity and abnormal 4-9 cpm tachyarrhythmia) and respiratory sinus arrhythmia (RSA) were measured before and after a meal and during a subsequent exposure to a rotating drum in which illusory self-motion was induced. The results indicated that food intake enhanced cardiac parasympathetic tone (RSA) and increased gastric 3 cpm activity. Postprandial effects on motion sickness severity remain equivocal due to group differences in RSA baseline levels. During drum rotation, dysrhythmic activity of the stomach (tachyarrhythmia) and vagal withdrawal were observed. Furthermore, high levels of vagal tone prior to drum rotation predicted a low incidence of motion sickness symptoms, and were associated positively with gastric 3 cpm activity and negatively with tachyarrhythmia. These data suggest that enhanced levels of parasympathetic activity can alleviate motion sickness symptoms by suppressing, in part, its dysrhythmic gastric underpinnings.

  8. Source mechanism inversion and ground motion modeling of induced earthquakes in Kuwait - A Bayesian approach

    NASA Astrophysics Data System (ADS)

    Gu, C.; Toksoz, M. N.; Marzouk, Y.; Al-Enezi, A.; Al-Jeri, F.; Buyukozturk, O.

    2016-12-01

    The increasing seismic activity in the regions of oil/gas fields due to fluid injection/extraction and hydraulic fracturing has drawn new attention in both academia and industry. Source mechanism and triggering stress of these induced earthquakes are of great importance for understanding the physics of the seismic processes in reservoirs, and predicting ground motion in the vicinity of oil/gas fields. The induced seismicity data in our study are from Kuwait National Seismic Network (KNSN). Historically, Kuwait has low local seismicity; however, in recent years the KNSN has monitored more and more local earthquakes. Since 1997, the KNSN has recorded more than 1000 earthquakes (Mw < 5). In 2015, two local earthquakes - Mw4.5 in 03/21/2015 and Mw4.1 in 08/18/2015 - have been recorded by both the Incorporated Research Institutions for Seismology (IRIS) and KNSN, and widely felt by people in Kuwait. These earthquakes happen repeatedly in the same locations close to the oil/gas fields in Kuwait (see the uploaded image). The earthquakes are generally small (Mw < 5) and are shallow with focal depths of about 2 to 4 km. Such events are very common in oil/gas reservoirs all over the world, including North America, Europe, and the Middle East. We determined the location and source mechanism of these local earthquakes, with the uncertainties, using a Bayesian inversion method. The triggering stress of these earthquakes was calculated based on the source mechanisms results. In addition, we modeled the ground motion in Kuwait due to these local earthquakes. Our results show that most likely these local earthquakes occurred on pre-existing faults and were triggered by oil field activities. These events are generally smaller than Mw 5; however, these events, occurring in the reservoirs, are very shallow with focal depths less than about 4 km. As a result, in Kuwait, where oil fields are close to populated areas, these induced earthquakes could produce ground accelerations high

  9. Developmental Regulation of NO-Mediated VEGF-Induced Effects in the Lung

    PubMed Central

    Bhandari, Vineet; Choo-Wing, Rayman; Lee, Chun G.; Yusuf, Kamran; Nedrelow, Jonathan H.; Ambalavanan, Namasivayam; Malkus, Herbert; Homer, Robert J.; Elias, Jack A.

    2008-01-01

    Vascular endothelial growth factor (VEGF) is known to have a pivotal role in lung development and in a variety of pathologic conditions in the adult lung. Our earlier studies have shown that NO is a critical mediator of VEGF-induced vascular and extravascular effects in the adult murine lung. As significant differences have been reported in the cytokine responses in the adult versus the neonatal lung, we hypothesized that there may be significant differences in VEGF-induced alterations in the developing as opposed to the mature lung. Furthermore, nitric oxide (NO) mediation of these VEGF-induced effects may be developmentally regulated. Using a novel externally regulatable lung-targeted transgenic murine model, we found that VEGF-induced pulmonary hemorrhage was mediated by NO-dependent mechanisms in adults and newborns. VEGF enhanced surfactant production in adults as well as increased surfactant and lung development in newborns, via an NO-independent mechanism. While the enhanced survival in hyperoxia in the adult was partly NO-dependent, there was enhanced hyperoxia-induced lung injury in the newborn. In addition, human amniotic fluid VEGF levels correlated positively with surfactant phospholipids. Tracheal aspirate VEGF levels had an initial spike, followed by a decline, and then a subsequent rise, in human neonates with an outcome of bronchopulmonary dysplasia or death. Our data show that VEGF can have injurious as well as potentially beneficial developmental effects, of which some are NO dependent, others NO independent. This opens up the possibility of selective manipulation of any VEGF-based intervention using NO inhibitors for maximal potential clinical benefit. PMID:18441284

  10. Developmental regulation of NO-mediated VEGF-induced effects in the lung.

    PubMed

    Bhandari, Vineet; Choo-Wing, Rayman; Lee, Chun G; Yusuf, Kamran; Nedrelow, Jonathan H; Ambalavanan, Namasivayam; Malkus, Herbert; Homer, Robert J; Elias, Jack A

    2008-10-01

    Vascular endothelial growth factor (VEGF) is known to have a pivotal role in lung development and in a variety of pathologic conditions in the adult lung. Our earlier studies have shown that NO is a critical mediator of VEGF-induced vascular and extravascular effects in the adult murine lung. As significant differences have been reported in the cytokine responses in the adult versus the neonatal lung, we hypothesized that there may be significant differences in VEGF-induced alterations in the developing as opposed to the mature lung. Furthermore, nitric oxide (NO) mediation of these VEGF-induced effects may be developmentally regulated. Using a novel externally regulatable lung-targeted transgenic murine model, we found that VEGF-induced pulmonary hemorrhage was mediated by NO-dependent mechanisms in adults and newborns. VEGF enhanced surfactant production in adults as well as increased surfactant and lung development in newborns, via an NO-independent mechanism. While the enhanced survival in hyperoxia in the adult was partly NO-dependent, there was enhanced hyperoxia-induced lung injury in the newborn. In addition, human amniotic fluid VEGF levels correlated positively with surfactant phospholipids. Tracheal aspirate VEGF levels had an initial spike, followed by a decline, and then a subsequent rise, in human neonates with an outcome of bronchopulmonary dysplasia or death. Our data show that VEGF can have injurious as well as potentially beneficial developmental effects, of which some are NO dependent, others NO independent. This opens up the possibility of selective manipulation of any VEGF-based intervention using NO inhibitors for maximal potential clinical benefit.

  11. Identifying natural and anthropogenically-induced geohazards from satellite ground motion and geospatial data: Stoke-on-Trent, UK

    NASA Astrophysics Data System (ADS)

    Jordan, Hannah; Cigna, Francesca; Bateson, Luke

    2017-12-01

    Determining the location and nature of hazardous ground motion resulting from natural and anthropogenic processes such as landslides, tectonic movement and mining is essential for hazard mitigation and sustainable resource use. Ground motion estimates from satellite ERS-1/2 persistent scatterer interferometry (PSI) were combined with geospatial data to identify areas of observed geohazards in Stoke-on-Trent, UK. This investigation was performed within the framework of the EC FP7-SPACE PanGeo project which aimed to provide free and open access to geohazard information for 52 urban areas across Europe. Geohazards identified within the city of Stoke-on-Trent and neighbouring rural areas are presented here alongside an examination of the PanGeo methodology. A total of 14 areas experiencing ground instability caused by natural and anthropogenic processes have been defined, covering 122.35 km2. These are attributed to a range of geohazards, including landslides, ground dissolution, made ground and mining activities. The dominant geohazard (by area) is ground movement caused by post-mining groundwater recharge and mining-related subsidence (93.19% of total geohazard area), followed by landsliding (5.81%). Observed ground motions along the satellite line-of-sight reach maxima of +35.23 mm/yr and -22.57 mm/yr. A combination of uplift, subsidence and downslope movement is displayed. 'Construction sites' and 'continuous urban fabric' (European Urban Atlas land use types) form the land uses most affected (by area) by ground motion and 'discontinuous very low density urban fabric' the least. Areas of 'continuous urban fabric' also show the highest average velocity towards the satellite (5.08 mm/yr) and the highest PS densities (1262.92 points/km2) along with one of the lowest standard deviations. Rural land uses tend to result in lower PS densities and higher standard deviations, a consequence of fewer suitable reflectors in these regions. PSI is also limited in its ability to

  12. Autonomic changes induced by provocative motion in rats bred for high (HAB) and low (LAB) anxiety-related behavior: Paradoxical responses in LAB animals.

    PubMed

    Carnevali, Luca; Andrews, Paul L; Neumann, Inga D; Nalivaiko, Eugene; Sgoifo, Andrea

    2016-12-01

    In humans, associations between anxiety and nausea (including motion-induced) are reported but the underlying mechanisms are not known. Hypothermia is proposed to be an index of nausea in rats. Utilising hypothermia and heart rate as outcome measures we investigated the response to provocative motion in rats selectively bred for high (HAB) and low (LAB) anxiety-related behaviors and in non-selected (NAB) rats to further elucidate the potential relationship between hypothermia and nausea-like state. Core temperature and electrocardiogram were monitored in each group (n=10 per group) using telemetry, with or without circular motion (40min; 0.75Hz) and vehicle or diazepam (2mg/kg, i.p.) pre-treatment. Heart rate and time- and frequency-domain parameters of heart rate variability were derived from the electrocardiogram. There was no baseline difference in core temperature between the three groups (mean 38.0±0.1°C), but HAB animals had a significantly lower resting heart rate (330±7bpm) compared to LAB (402±5bpm) and NAB (401±9bpm). Animals in all groups exhibited hypothermia during motion (HAB: 36.3±0.1°C; NAB: 36.4±0.1°C; LAB: 34.9±0.2°C) with the magnitude (area under the curve, AUC) of the response during 40-min motion being greater in LAB compared to NAB and HAB rats, and this was also the case for the motion-induced bradycardia. Diazepam had minimal effects on baseline temperature and heart rate in all groups, but significantly reduced the hypothermia response (AUC) to motion in all groups by ~30%. Breeding for extremes in anxiety-related behavior unexpectedly selects animals with low trait anxiety that have enhanced bradycardia and hypothermic responses to motion; consequently, this animal model appears to be not suitable for exploring relationships between anxiety and autonomic correlates of nausea. Thermal and cardiovascular responses to motion were little different between HAB and NAB rats indicating that either hypothermia is not an index of a

  13. Multibuilding Block Janus Synthesized by Seed-Mediated Self-Assembly for Enhanced Photothermal Effects and Colored Brownian Motion in an Optical Trap.

    PubMed

    Sansanaphongpricha, Kanokwan; DeSantis, Michael C; Chen, Hongwei; Cheng, Wei; Sun, Kai; Wen, Bo; Sun, Duxin

    2017-02-01

    The asymmetrical features and unique properties of multibuilding block Janus nanostructures (JNSs) provide superior functions for biomedical applications. However, their production process is very challenging. This problem has hampered the progress of JNS research and the exploration of their applications. In this study, an asymmetrical multibuilding block gold/iron oxide JNS has been generated to enhance photothermal effects and display colored Brownian motion in an optical trap. JNS is formed by seed-mediated self-assembly of nanoparticle-loaded thermocleavable micelles, where the hydrophobic backbones of the polymer are disrupted at high temperatures, resulting in secondary self-assembly and structural rearrangement. The JNS significantly enhances photothermal effects compared to their homogeneous counterpart after near-infrared (NIR) light irradiation. The asymmetrical distribution of gold and iron oxide within JNS also generates uneven thermophoretic force to display active colored Brownian rotational motion in a single-beam gradient optical trap. These properties indicate that the asymmetrical JNS could be employed as a strong photothermal therapy mediator and a fuel-free nanoscale Janus motor under NIR light. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Pleasant music as a countermeasure against visually induced motion sickness.

    PubMed

    Keshavarz, Behrang; Hecht, Heiko

    2014-05-01

    Visually induced motion sickness (VIMS) is a well-known side-effect in virtual environments or simulators. However, effective behavioral countermeasures against VIMS are still sparse. In this study, we tested whether music can reduce the severity of VIMS. Ninety-three volunteers were immersed in an approximately 14-minute-long video taken during a bicycle ride. Participants were randomly assigned to one of four experimental groups, either including relaxing music, neutral music, stressful music, or no music. Sickness scores were collected using the Fast Motion Sickness Scale and the Simulator Sickness Questionnaire. Results showed an overall trend for relaxing music to reduce the severity of VIMS. When factoring in the subjective pleasantness of the music, a significant reduction of VIMS occurred only when the presented music was perceived as pleasant, regardless of the music type. In addition, we found a gender effect with women reporting more sickness than men. We assume that the presentation of pleasant music can be an effective, low-cost, and easy-to-administer method to reduce VIMS. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  15. Early Blindness Results in Developmental Plasticity for Auditory Motion Processing within Auditory and Occipital Cortex

    PubMed Central

    Jiang, Fang; Stecker, G. Christopher; Boynton, Geoffrey M.; Fine, Ione

    2016-01-01

    Early blind subjects exhibit superior abilities for processing auditory motion, which are accompanied by enhanced BOLD responses to auditory motion within hMT+ and reduced responses within right planum temporale (rPT). Here, by comparing BOLD responses to auditory motion in hMT+ and rPT within sighted controls, early blind, late blind, and sight-recovery individuals, we were able to separately examine the effects of developmental and adult visual deprivation on cortical plasticity within these two areas. We find that both the enhanced auditory motion responses in hMT+ and the reduced functionality in rPT are driven by the absence of visual experience early in life; neither loss nor recovery of vision later in life had a discernable influence on plasticity within these areas. Cortical plasticity as a result of blindness has generally be presumed to be mediated by competition across modalities within a given cortical region. The reduced functionality within rPT as a result of early visual loss implicates an additional mechanism for cross modal plasticity as a result of early blindness—competition across different cortical areas for functional role. PMID:27458357

  16. Transformations of visual memory induced by implied motions of pattern elements.

    PubMed

    Finke, R A; Freyd, J J

    1985-10-01

    Four experiments measured distortions in short-term visual memory induced by displays depicting independent translations of the elements of a pattern. In each experiment, observers saw a sequence of 4 dot patterns and were instructed to remember the third pattern and to compare it with the fourth. The first three patterns depicted translations of the dots in consistent, but separate directions. Error rates and reaction times for rejecting the fourth pattern as different from the third were substantially higher when the dots in that pattern were displaced slightly forward, in the same directions as the implied motions, compared with when the dots were displaced in the opposite, backward directions. These effects showed little variation across interstimulus intervals ranging from 250 to 2,000 ms, and did not depend on whether the displays gave rise to visual apparent motion. However, they were eliminated when the dots in the fourth pattern were displaced by larger amounts in each direction, corresponding to the dot positions in the next and previous patterns in the same inducing sequence. These findings extend our initial report of the phenomenon of "representational momentum" (Freyd & Finke, 1984a), and help to rule out alternatives to the proposal that visual memories tend to undergo, at least to some extent, the transformations implied by a prior sequence of observed events.

  17. Ionophore-A23187-induced cellular cytotoxicity: a cell fragment mediated process.

    PubMed Central

    Nash, G S; Niedt, G W; MacDermott, R P

    1980-01-01

    Calcium ionophore A23187 was found to induce human white blood cells to kill human red blood cells. Optimal conditions for ionophore-induced cellular cytotoxicity (IICC) included an 18 h time period, an incubation temperature of 25 degrees, a 25:1 or 50:1 killer:target cell ratio,and a final ionophore concentration of 2 . 5 microgram/ml. WBC or granulocytes which were either frozen and thawed three times or sonicated were capable of mediating IICC. As intact cells, granulocytes (67 . 2% cytotoxicity), monocytes (34 . 8%), B cells (22 . 0%) and Null cells (19 . 3%) were effector cells but T cells (7 . 4%) were not. After fragmenting these cells, all cell types including T cells were able to mediate IICC. When cell lines (K562, Chang, and NCTC) were used as effectors, none would mediate IICC when intact. After freezing and thawing, Chang and NCTC would not mediate IICC, whereas K562 cells did. These studies may be indicative of a calcium-dependent, membrane-localized mechanism in cellular cytotoxic processes, and may provide a useful indicator system for isolation of the enzyme systems involved in cellular cytotoxicity. PMID:6773881

  18. TRPM8 and RAAS-mediated hypertension is critical for cold-induced immunosuppression in mice

    PubMed Central

    Lien, Te-Sheng; Chang, Hsin-Hou

    2018-01-01

    Mechanisms underlying cold-induced immunosuppression remain unclear. Here we found that cold exposure leads to transient receptor potential melastatin 8 (TRPM8)-dependent, renin–angiotensin–aldosterone system (RAAS)-mediated hypertension, which subsequently induces small molecule and fluid extravasation, increases plasma Ig levels, and elicits immunosuppression. An effect is similar to the clinically-used immunosuppressive treatments of intravenous immunoglobulin (IVIg) against various inflammatory diseases, such as immune thrombocytopenia (ITP). Essential roles of TRPM8 and Ig in cold-induced immunosuppression are supported by the cold-mediated amelioration of ITP and the cold-mediated suppression of bacterial clearance, which were observed in wild-type mice but not in Ig- and TRPM8-deficient mutants. Treatment with antihypertensive drugs aliskiren and losartan drastically reversed high plasma Ig levels and ameliorated cold-induced immunosuppression, indicating the involvement of the RAAS and hypertension. These results indicated that the natively increased plasma Ig level is associated with immunosuppression during periods of cold exposure, and antihypertensive drugs can be useful to manage cold-induced immunosuppression. PMID:29560109

  19. TRPM8 and RAAS-mediated hypertension is critical for cold-induced immunosuppression in mice.

    PubMed

    Chan, Hao; Huang, Hsuan-Shun; Sun, Der-Shan; Lee, Chung-Jen; Lien, Te-Sheng; Chang, Hsin-Hou

    2018-02-27

    Mechanisms underlying cold-induced immunosuppression remain unclear. Here we found that cold exposure leads to transient receptor potential melastatin 8 (TRPM8)-dependent, renin-angiotensin-aldosterone system (RAAS)-mediated hypertension, which subsequently induces small molecule and fluid extravasation, increases plasma Ig levels, and elicits immunosuppression. An effect is similar to the clinically-used immunosuppressive treatments of intravenous immunoglobulin (IVIg) against various inflammatory diseases, such as immune thrombocytopenia (ITP). Essential roles of TRPM8 and Ig in cold-induced immunosuppression are supported by the cold-mediated amelioration of ITP and the cold-mediated suppression of bacterial clearance, which were observed in wild-type mice but not in Ig- and TRPM8-deficient mutants. Treatment with antihypertensive drugs aliskiren and losartan drastically reversed high plasma Ig levels and ameliorated cold-induced immunosuppression, indicating the involvement of the RAAS and hypertension. These results indicated that the natively increased plasma Ig level is associated with immunosuppression during periods of cold exposure, and antihypertensive drugs can be useful to manage cold-induced immunosuppression.

  20. Overlapping striatal sites mediate scopolamine-induced feeding suppression and mu-opioid-mediated hyperphagia in the rat

    PubMed Central

    Perry, Michelle L.; Pratt, Wayne E.; Baldo, Brian A.

    2013-01-01

    Rationale Intra-striatal infusions of the muscarinic antagonist, scopolamine, markedly suppress feeding; however, the underlying mechanisms are unclear. Recent findings suggest that scopolamine influences opioid-dependent mechanisms of feeding modulation. Robust mu-opioid-mediated feeding responses are obtained in anterior, ventral sectors of the striatum with progressively weaker effects posteriorly and dorsally. One might therefore expect the effects of scopolamine to conform to similar boundaries, but a systematic mapping of scopolamine-induced feeding suppression has not yet been undertaken. Objective This study aimed to assess the overlap between the striatal sites mediating scopolamine-induced feeding suppression and mu-opioid-induced hyperphagia. Methods Dose–effect functions for scopolamine (0, 1, 5, and 10 μg) were obtained in the nucleus accumbens (Acb), anterior dorsal striatum (ADS), and posterior dorsal striatum (PDS) in three different groups of rats. In the same subjects, the mu-opioid receptor agonist (d-Ala2-N-MePhe4, Glyol)-enkephalin (DAMGO; 0.25 μg) was infused on a separate test day. The dependent variables were food and water intake, ambulation, and rearing. Results The greatest dose sensitivity for scopolamine-induced feeding suppression was observed in the Acb. Only the highest dose was effective in the ADS, and no effects were seen in the PDS. Water intake and general motor activity were not altered by scopolamine in any site. DAMGO infusions produced hyperphagia only in the Acb. Conclusions These results support a model in which the behavioral effects of muscarinic blockade are limited by the same anatomical constraints that govern mu-opioid receptor-mediated control of feeding. These constraints are likely imposed by the topographic arrangement of feeding-related afferent inputs and efferent projections of the striatum. PMID:24190586

  1. Cigarette Smoke–Induced CXCR3 Receptor Up-Regulation Mediates Endothelial Apoptosis

    PubMed Central

    Green, Linden A.; Petrusca, Daniela; Rajashekhar, Gangaraju; Gianaris, Tom; Schweitzer, Kelly S.; Wang, Liang; Justice, Matthew J.; Petrache, Irina

    2012-01-01

    Endothelial monocyte–activating polypeptide II (EMAP II) and interferon-inducible protein (IP)–10 are proinflammatory mediators, which in addition to their chemokine activities, selectively induce apoptosis in endothelial cells and are up-regulated in the lungs of cigarette smoke–exposed humans. Previously, we showed that EMAP II is an essential mediator of cigarette smoke–induced lung emphysema in mice linking endothelial cell apoptosis with inflammation. Here we addressed the role of the CXCR3 receptor in EMAP II–induced and IP-10–induced apoptosis in endothelial cells and its regulation by cigarette smoke. We found that both neutralizing antibodies and small inhibitory RNA to CXCR3 abrogated EMAP II–induced and IP-10–induced endothelial caspase-3 activation and DNA fragmentation. CXCR3 receptor surface expression in human lung microvascular endothelial cells and in lung tissue endothelium was up-regulated by exposure to cigarette smoke. In tissue culture conditions, EMAP II–induced and IP-10–induced apoptosis was enhanced by preincubation with cigarette smoke extract. Interestingly, serum starvation also induced CXCR3 up-regulation and enhanced EMAP II–induced endothelial apoptosis. Signal transduction via p38 mitogen-activated protein kinase activation was essential for CXCR3-induced cell death, but not for CXCR3 receptor up-regulation by cigarette smoke. In turn, protein nitration was required for CXCR3 receptor up-regulation by cigarette smoke and consequently for subsequent CXCR3-induced cell death. In conclusion, the concerted up-regulation of proinflammatory EMAP II, IP-10, and CXCR3 by cigarette smoke could sustain a cascade of cell death that may promote the alveolar tissue loss noted in human emphysema. PMID:22936405

  2. Spatiotemporal motion boundary detection and motion boundary velocity estimation for tracking moving objects with a moving camera: a level sets PDEs approach with concurrent camera motion compensation.

    PubMed

    Feghali, Rosario; Mitiche, Amar

    2004-11-01

    The purpose of this study is to investigate a method of tracking moving objects with a moving camera. This method estimates simultaneously the motion induced by camera movement. The problem is formulated as a Bayesian motion-based partitioning problem in the spatiotemporal domain of the image quence. An energy functional is derived from the Bayesian formulation. The Euler-Lagrange descent equations determine imultaneously an estimate of the image motion field induced by camera motion and an estimate of the spatiotemporal motion undary surface. The Euler-Lagrange equation corresponding to the surface is expressed as a level-set partial differential equation for topology independence and numerically stable implementation. The method can be initialized simply and can track multiple objects with nonsimultaneous motions. Velocities on motion boundaries can be estimated from geometrical properties of the motion boundary. Several examples of experimental verification are given using synthetic and real-image sequences.

  3. Investigation of optimal method for inducing harmonic motion in tissue using a linear ultrasound phased array--a simulation study.

    PubMed

    Heikkilä, Janne; Hynynen, Kullervo

    2006-04-01

    Many noninvasive ultrasound techniques have been developed to explore mechanical properties of soft tissues. One of these methods, Localized Harmonic Motion Imaging (LHMI), has been proposed to be used for ultrasound surgery monitoring. In LHMI, dynamic ultrasound radiation-force stimulation induces displacements in a target that can be measured using pulse-echo imaging and used to estimate the elastic properties of the target. In this initial, simulation study, the use of a one-dimensional phased array is explored for the induction of the tissue motion. The study compares three different dual-frequency and amplitude-modulated single-frequency methods for the inducing tissue motion. Simulations were computed in a homogeneous soft-tissue volume. The Rayleigh integral was used in the simulations of the ultrasound fields and the tissue displacements were computed using a finite-element method (FEM). The simulations showed that amplitude-modulated sonication using a single frequency produced the largest vibration amplitude of the target tissue. These simulations demonstrate that the properties of the tissue motion are highly dependent on the sonication method and that it is important to consider the full three-dimensional distribution of the ultrasound field for controlling the induction of tissue motion.

  4. Amyloid β-Mediated Zn2+ Influx into Dentate Granule Cells Transiently Induces a Short-Term Cognitive Deficit

    PubMed Central

    Takeda, Atsushi; Nakamura, Masatoshi; Fujii, Hiroaki; Uematsu, Chihiro; Minamino, Tatsuya; Adlard, Paul A.; Bush, Ashley I.; Tamano, Haruna

    2014-01-01

    We examined an idea that short-term cognition is transiently affected by a state of confusion in Zn2+ transport system due to a local increase in amyloid-β (Aβ) concentration. A single injection of Aβ (25 pmol) into the dentate gyrus affected dentate gyrus long-term potentiation (LTP) 1 h after the injection, but not 4 h after the injection. Simultaneously, 1-h memory of object recognition was affected when the training was performed 1 h after the injection, but not 4 h after the injection. Aβ-mediated impairments of LTP and memory were rescued in the presence of zinc chelators, suggesting that Zn2+ is involved in Aβ action. When Aβ was injected into the dentate gyrus, intracellular Zn2+ levels were increased only in the injected area in the dentate gyrus, suggesting that Aβ induces the influx of Zn2+ into cells in the injected area. When Aβ was added to hippocampal slices, Aβ did not increase intracellular Zn2+ levels in the dentate granule cell layer in ACSF without Zn2+, but in ACSF containing Zn2+. The increase in intracellular Zn2+ levels was inhibited in the presence of CaEDTA, an extracellular zinc chelator, but not in the presence of CNQX, an AMPA receptor antagonist. The present study indicates that Aβ-mediated Zn2+ influx into dentate granule cells, which may occur without AMPA receptor activation, transiently induces a short-term cognitive deficit. Extracellular Zn2+ may play a key role for transiently Aβ-induced cognition deficits. PMID:25536033

  5. Amyloid β-mediated Zn2+ influx into dentate granule cells transiently induces a short-term cognitive deficit.

    PubMed

    Takeda, Atsushi; Nakamura, Masatoshi; Fujii, Hiroaki; Uematsu, Chihiro; Minamino, Tatsuya; Adlard, Paul A; Bush, Ashley I; Tamano, Haruna

    2014-01-01

    We examined an idea that short-term cognition is transiently affected by a state of confusion in Zn2+ transport system due to a local increase in amyloid-β (Aβ) concentration. A single injection of Aβ (25 pmol) into the dentate gyrus affected dentate gyrus long-term potentiation (LTP) 1 h after the injection, but not 4 h after the injection. Simultaneously, 1-h memory of object recognition was affected when the training was performed 1 h after the injection, but not 4 h after the injection. Aβ-mediated impairments of LTP and memory were rescued in the presence of zinc chelators, suggesting that Zn2+ is involved in Aβ action. When Aβ was injected into the dentate gyrus, intracellular Zn2+ levels were increased only in the injected area in the dentate gyrus, suggesting that Aβ induces the influx of Zn2+ into cells in the injected area. When Aβ was added to hippocampal slices, Aβ did not increase intracellular Zn2+ levels in the dentate granule cell layer in ACSF without Zn2+, but in ACSF containing Zn2+. The increase in intracellular Zn2+ levels was inhibited in the presence of CaEDTA, an extracellular zinc chelator, but not in the presence of CNQX, an AMPA receptor antagonist. The present study indicates that Aβ-mediated Zn2+ influx into dentate granule cells, which may occur without AMPA receptor activation, transiently induces a short-term cognitive deficit. Extracellular Zn2+ may play a key role for transiently Aβ-induced cognition deficits.

  6. Parallel search for conjunctions with stimuli in apparent motion.

    PubMed

    Casco, C; Ganis, G

    1999-01-01

    A series of experiments was conducted to determine whether apparent motion tends to follow the similarity rule (i.e. is attribute-specific) and to investigate the underlying mechanism. Stimulus duration thresholds were measured during a two-alternative forced-choice task in which observers detected either the location or the motion direction of target groups defined by the conjunction of size and orientation. Target element positions were randomly chosen within a nominally defined rectangular subregion of the display (target region). The target region was presented either statically (followed by a 250 ms duration mask) or dynamically, displaced by a small distance (18 min of arc) from frame to frame. In the motion display, the position of both target and background elements was changed randomly from frame to frame within the respective areas to abolish spatial correspondence over time. Stimulus duration thresholds were lower in the motion than in the static task, indicating that target detection in the dynamic condition does not rely on the explicit identification of target elements in each static frame. Increasing the distractor-to-target ratio was found to reduce detectability in the static, but not in the motion task. This indicates that the perceptual segregation of the target is effortless and parallel with motion but not with static displays. The pattern of results holds regardless of the task or search paradigm employed. The detectability in the motion condition can be improved by increasing the number of frames and/or by reducing the width of the target area. Furthermore, parallel search in the dynamic condition can be conducted with both short-range and long-range motion stimuli. Finally, apparent motion of conjunctions is insufficient on its own to support location decision and is disrupted by random visual noise. Overall, these findings show that (i) the mechanism underlying apparent motion is attribute-specific; (ii) the motion system mediates temporal

  7. Analysis of opioid receptor subtype antagonist effects upon mu opioid agonist-induced feeding elicited from the ventral tegmental area of rats.

    PubMed

    Lamonte, Nicole; Echo, Joyce A; Ackerman, Tsippa F; Christian, Garrison; Bodnar, Richard J

    2002-03-01

    The present study examined opioid receptor(s) mediation of feeding elicited by mu opioid agonists in the ventral tegmental area using general or selective opioid antagonist pretreatment. Naltrexone as well as equimolar doses of selective mu and kappa, but not delta opioid antagonists in the ventral tegmental area significantly reduced mu agonist-induced feeding, indicating a pivotal role for these receptor subtypes in the full expression of this response.

  8. Quantitative assessment of tumor angiogenesis using real-time motion-compensated contrast-enhanced ultrasound imaging

    PubMed Central

    Pysz, Marybeth A.; Guracar, Ismayil; Foygel, Kira; Tian, Lu; Willmann, Jürgen K.

    2015-01-01

    Purpose To develop and test a real-time motion compensation algorithm for contrast-enhanced ultrasound imaging of tumor angiogenesis on a clinical ultrasound system. Materials and methods The Administrative Institutional Panel on Laboratory Animal Care approved all experiments. A new motion correction algorithm measuring the sum of absolute differences in pixel displacements within a designated tracking box was implemented in a clinical ultrasound machine. In vivo angiogenesis measurements (expressed as percent contrast area) with and without motion compensated maximum intensity persistence (MIP) ultrasound imaging were analyzed in human colon cancer xenografts (n = 64) in mice. Differences in MIP ultrasound imaging signal with and without motion compensation were compared and correlated with displacements in x- and y-directions. The algorithm was tested in an additional twelve colon cancer xenograft-bearing mice with (n = 6) and without (n = 6) anti-vascular therapy (ASA-404). In vivo MIP percent contrast area measurements were quantitatively correlated with ex vivo microvessel density (MVD) analysis. Results MIP percent contrast area was significantly different (P < 0.001) with and without motion compensation. Differences in percent contrast area correlated significantly (P < 0.001) with x- and y-displacements. MIP percent contrast area measurements were more reproducible with motion compensation (ICC = 0.69) than without (ICC = 0.51) on two consecutive ultrasound scans. Following anti-vascular therapy, motion-compensated MIP percent contrast area significantly (P = 0.03) decreased by 39.4 ± 14.6 % compared to non-treated mice and correlated well with ex vivo MVD analysis (Rho = 0.70; P = 0.05). Conclusion Real-time motion-compensated MIP ultrasound imaging allows reliable and accurate quantification and monitoring of angiogenesis in tumors exposed to breathing-induced motion artifacts. PMID:22535383

  9. Quantitative assessment of tumor angiogenesis using real-time motion-compensated contrast-enhanced ultrasound imaging.

    PubMed

    Pysz, Marybeth A; Guracar, Ismayil; Foygel, Kira; Tian, Lu; Willmann, Jürgen K

    2012-09-01

    To develop and test a real-time motion compensation algorithm for contrast-enhanced ultrasound imaging of tumor angiogenesis on a clinical ultrasound system. The Administrative Institutional Panel on Laboratory Animal Care approved all experiments. A new motion correction algorithm measuring the sum of absolute differences in pixel displacements within a designated tracking box was implemented in a clinical ultrasound machine. In vivo angiogenesis measurements (expressed as percent contrast area) with and without motion compensated maximum intensity persistence (MIP) ultrasound imaging were analyzed in human colon cancer xenografts (n = 64) in mice. Differences in MIP ultrasound imaging signal with and without motion compensation were compared and correlated with displacements in x- and y-directions. The algorithm was tested in an additional twelve colon cancer xenograft-bearing mice with (n = 6) and without (n = 6) anti-vascular therapy (ASA-404). In vivo MIP percent contrast area measurements were quantitatively correlated with ex vivo microvessel density (MVD) analysis. MIP percent contrast area was significantly different (P < 0.001) with and without motion compensation. Differences in percent contrast area correlated significantly (P < 0.001) with x- and y-displacements. MIP percent contrast area measurements were more reproducible with motion compensation (ICC = 0.69) than without (ICC = 0.51) on two consecutive ultrasound scans. Following anti-vascular therapy, motion-compensated MIP percent contrast area significantly (P = 0.03) decreased by 39.4 ± 14.6 % compared to non-treated mice and correlated well with ex vivo MVD analysis (Rho = 0.70; P = 0.05). Real-time motion-compensated MIP ultrasound imaging allows reliable and accurate quantification and monitoring of angiogenesis in tumors exposed to breathing-induced motion artifacts.

  10. JNK1 Mediates Lipopolysaccharide-Induced CD14 and SR-AI Expression and Macrophage Foam Cell Formation.

    PubMed

    An, Dong; Hao, Feng; Hu, Chen; Kong, Wei; Xu, Xuemin; Cui, Mei-Zhen

    2017-01-01

    Foam cell formation is the key process in the development of atherosclerosis. The uptake of oxidized low-density lipoprotein (oxLDL) converts macrophages into foam cells. We recently reported that lipopolysaccharide (LPS)-induced foam cell formation is regulated by CD14 and scavenger receptor AI (SR-AI). In this study, we employed pharmaceutical and gene knockdown approaches to determine the upstream molecular mediators, which control LPS-induced foam cell formation. Our results demonstrated that the specific c-Jun N-terminal kinase (JNK) pathway inhibitor, SP600125, but neither the specific inhibitor of extracellular signaling-regulated kinase (ERK) kinase MEK1/2, U0126, nor the specific inhibitor of p38 MAPK, SB203580, significantly blocks LPS-induced oxLDL uptake, suggesting that the JNK pathway is the upstream mediator of LPS-induced oxLDL uptake/foam cell formation. To address whether JNK pathway mediates LPS-induced oxLDL uptake is due to JNK pathway-regulated CD14 and SR-AI expression, we assessed whether the pharmaceutical inhibitor of JNK influences LPS-induced expression of CD14 and SR-AI. Our results indicate that JNK pathway mediates LPS-induced CD14 and SR-AI expression. To conclusively address the isoform role of JNK family, we depleted JNK isoforms using the JNK isoform-specific siRNA. Our data showed that the depletion of JNK1, but not JNK2 blocked LPS-induced CD14/SR-AI expression and foam cell formation. Taken together, our results reveal for the first time that JNK1 is the key mediator of LPS-induced CD14 and SR-AI expression in macrophages, leading to LPS-induced oxLDL uptake/foam cell formation. We conclude that the novel JNK1/CD14/SR-AI pathway controls macrophage oxLDL uptake/foam cell formation.

  11. Atorvastatin-induced cardioprotection is mediated by increasing inducible nitric oxide synthase and consequent S-nitrosylation of cyclooxygenase-2.

    PubMed

    Atar, Shaul; Ye, Yumei; Lin, Yu; Freeberg, Sheldon Y; Nishi, Shawn P; Rosanio, Salvatore; Huang, Ming-He; Uretsky, Barry F; Perez-Polo, Jose R; Birnbaum, Yochai

    2006-05-01

    We determined the effects of cyclooxygenase-1 (COX-1; SC-560), COX-2 (SC-58125), and inducible nitric oxide synthase (iNOS; 1400W) inhibitors on atorvastatin (ATV)-induced myocardial protection and whether iNOS mediates the ATV-induced increases in COX-2. Sprague-Dawley rats received 10 mg ATV.kg(-1).day(-1) added to drinking water or water alone for 3 days and received intravenous SC-58125, SC-560, 1400W, or vehicle alone. Anesthesia was induced with ketamine and xylazine and maintained with isoflurane. Fifteen minutes after intravenous injection rats underwent 30-min myocardial ischemia followed by 4-h reperfusion [infarct size (IS) protocol], or the hearts were explanted for biochemical analysis and immunoblotting. Left ventricular weight and area at risk (AR) were comparable among groups. ATV reduced IS to 12.7% (SD 3.1) of AR, a reduction of 64% vs. 35.1% (SD 7.6) in the sham-treated group (P < 0.001). SC-58125 and 1400W attenuated the protective effect without affecting IS in the non-ATV-treated rats. ATV increased calcium-independent NOS (iNOS) [11.9 (SD 0.8) vs. 3.9 (SD 0.1) x 1,000 counts/min; P < 0.001] and COX-2 [46.7 (SD 1.1) vs. 6.5 (SD 1.4) pg/ml of 6-keto-PGF(1alpha); P < 0.001] activity. Both SC-58125 and 1400W attenuated this increase. SC-58125 did not affect iNOS activity, whereas 1400W blocked iNOS activity. COX-2 was S-nitrosylated in ATV-treated but not sham-treated rats or rats pretreated with 1400W. COX-2 immunoprecipitated with iNOS but not with endothelial nitric oxide synthase. We conclude that ATV reduced IS by increasing the activity of iNOS and COX-2, iNOS is upstream to COX-2, and iNOS activates COX-2 by S-nitrosylation. These results are consistent with the hypothesis that preconditioning effects are mediated via PG.

  12. Stretch-Induced Hypertrophy Activates NFkB-Mediated VEGF Secretion in Adult Cardiomyocytes

    PubMed Central

    Leychenko, Anna; Konorev, Eugene; Jijiwa, Mayumi; Matter, Michelle L.

    2011-01-01

    Hypertension and myocardial infarction are associated with the onset of hypertrophy. Hypertrophy is a compensatory response mechanism to increases in mechanical load due to pressure or volume overload. It is characterized by extracellular matrix remodeling and hypertrophic growth of adult cardiomyocytes. Production of Vascular Endothelial Growth Factor (VEGF), which acts as an angiogenic factor and a modulator of cardiomyocyte function, is regulated by mechanical stretch. Mechanical stretch promotes VEGF secretion in neonatal cardiomyocytes. Whether this effect is retained in adult cells and the molecular mechanism mediating stretch-induced VEGF secretion has not been elucidated. Our objective was to investigate whether cyclic mechanical stretch induces VEGF secretion in adult cardiomyocytes and to identify the molecular mechanism mediating VEGF secretion in these cells. Isolated primary adult rat cardiomyocytes (ARCMs) were subjected to cyclic mechanical stretch at an extension level of 10% at 30 cycles/min that induces hypertrophic responses. Cyclic mechanical stretch induced a 3-fold increase in VEGF secretion in ARCMs compared to non-stretch controls. This increase in stretch-induced VEGF secretion correlated with NFkB activation. Cyclic mechanical stretch-mediated VEGF secretion was blocked by an NFkB peptide inhibitor and expression of a dominant negative mutant IkBα, but not by inhibitors of the MAPK/ERK1/2 or PI3K pathways. Chromatin immunoprecipitation assays demonstrated an interaction of NFkB with the VEGF promoter in stretched primary cardiomyocytes. Moreover, VEGF secretion is increased in the stretched myocardium during pressure overload-induced hypertrophy. These findings are the first to demonstrate that NFkB activation plays a role in mediating VEGF secretion upon cyclic mechanical stretch in adult cardiomyocytes. Signaling by NFkB initiated in response to cyclic mechanical stretch may therefore coordinate the hypertrophic response in adult

  13. The perception of object versus objectless motion.

    PubMed

    Hock, Howard S; Nichols, David F

    2013-05-01

    Wertheimer, M. (Zeitschrift für Psychologie und Physiologie der Sinnesorgane, 61:161-265, 1912) classical distinction between beta (object) and phi (objectless) motion is elaborated here in a series of experiments concerning competition between two qualitatively different motion percepts, induced by sequential changes in luminance for two-dimensional geometric objects composed of rectangular surfaces. One of these percepts is of spreading-luminance motion that continuously sweeps across the entire object; it exhibits shape invariance and is perceived most strongly for fast speeds. Significantly for the characterization of phi as objectless motion, the spreading luminance does not involve surface boundaries or any other feature; the percept is driven solely by spatiotemporal changes in luminance. Alternatively, and for relatively slow speeds, a discrete series of edge motions can be perceived in the direction opposite to spreading-luminance motion. Akin to beta motion, the edges appear to move through intermediate positions within the object's changing surfaces. Significantly for the characterization of beta as object motion, edge motion exhibits shape dependence and is based on the detection of oppositely signed changes in contrast (i.e., counterchange) for features essential to the determination of an object's shape, the boundaries separating its surfaces. These results are consistent with area MT neurons that differ with respect to speed preference Newsome et al (Journal of Neurophysiology, 55:1340-1351, 1986) and shape dependence Zeki (Journal of Physiology, 236:549-573, 1974).

  14. Characterizing spatiotemporal information loss in sparse-sampling-based dynamic MRI for monitoring respiration-induced tumor motion in radiotherapy

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

    Arai, Tatsuya J.; Nofiele, Joris; Yuan, Qing

    Purpose: Sparse-sampling and reconstruction techniques represent an attractive strategy to achieve faster image acquisition speeds, while maintaining adequate spatial resolution and signal-to-noise ratio in rapid magnetic resonance imaging (MRI). The authors investigate the use of one such sequence, broad-use linear acquisition speed-up technique (k-t BLAST) in monitoring tumor motion for thoracic and abdominal radiotherapy and examine the potential trade-off between increased sparsification (to increase imaging speed) and the potential loss of “true” information due to greater reliance on a priori information. Methods: Lung tumor motion trajectories in the superior–inferior direction, previously recorded from ten lung cancer patients, were replayed usingmore » a motion phantom module driven by an MRI-compatible motion platform. Eppendorf test tubes filled with water which serve as fiducial markers were placed in the phantom. The modeled rigid and deformable motions were collected in a coronal image slice using balanced fast field echo in conjunction with k-t BLAST. Root mean square (RMS) error was used as a metric of spatial accuracy as measured trajectories were compared to input data. The loss of spatial information was characterized for progressively increasing acceleration factor from 1 to 16; the resultant sampling frequency was increased approximately from 2.5 to 19 Hz when the principal direction of the motion was set along frequency encoding direction. In addition to the phantom study, respiration-induced tumor motions were captured from two patients (kidney tumor and lung tumor) at 13 Hz over 49 s to demonstrate the impact of high speed motion monitoring over multiple breathing cycles. For each subject, the authors compared the tumor centroid trajectory as well as the deformable motion during free breathing. Results: In the rigid and deformable phantom studies, the RMS error of target tracking at the acquisition speed of 19 Hz was approximately 0

  15. Characterizing spatiotemporal information loss in sparse-sampling-based dynamic MRI for monitoring respiration-induced tumor motion in radiotherapy

    PubMed Central

    Arai, Tatsuya J.; Nofiele, Joris; Madhuranthakam, Ananth J.; Yuan, Qing; Pedrosa, Ivan; Chopra, Rajiv; Sawant, Amit

    2016-01-01

    Purpose: Sparse-sampling and reconstruction techniques represent an attractive strategy to achieve faster image acquisition speeds, while maintaining adequate spatial resolution and signal-to-noise ratio in rapid magnetic resonance imaging (MRI). The authors investigate the use of one such sequence, broad-use linear acquisition speed-up technique (k-t BLAST) in monitoring tumor motion for thoracic and abdominal radiotherapy and examine the potential trade-off between increased sparsification (to increase imaging speed) and the potential loss of “true” information due to greater reliance on a priori information. Methods: Lung tumor motion trajectories in the superior–inferior direction, previously recorded from ten lung cancer patients, were replayed using a motion phantom module driven by an MRI-compatible motion platform. Eppendorf test tubes filled with water which serve as fiducial markers were placed in the phantom. The modeled rigid and deformable motions were collected in a coronal image slice using balanced fast field echo in conjunction with k-t BLAST. Root mean square (RMS) error was used as a metric of spatial accuracy as measured trajectories were compared to input data. The loss of spatial information was characterized for progressively increasing acceleration factor from 1 to 16; the resultant sampling frequency was increased approximately from 2.5 to 19 Hz when the principal direction of the motion was set along frequency encoding direction. In addition to the phantom study, respiration-induced tumor motions were captured from two patients (kidney tumor and lung tumor) at 13 Hz over 49 s to demonstrate the impact of high speed motion monitoring over multiple breathing cycles. For each subject, the authors compared the tumor centroid trajectory as well as the deformable motion during free breathing. Results: In the rigid and deformable phantom studies, the RMS error of target tracking at the acquisition speed of 19 Hz was approximately 0.3–0

  16. Molecular Dynamics Study of Thermally Augmented Nanodroplet Motion on Chemical Energy Induced Wettability Gradient Surfaces.

    PubMed

    Chakraborty, Monojit; Chowdhury, Anamika; Bhusan, Richa; DasGupta, Sunando

    2015-10-20

    Droplet motion on a surface with chemical energy induced wettability gradient has been simulated using molecular dynamics (MD) simulation to highlight the underlying physics of molecular movement near the solid-liquid interface including the contact line friction. The simulations mimic experiments in a comprehensive manner wherein microsized droplets are propelled by the surface wettability gradient against forces opposed to motion. The liquid-wall Lennard-Jones interaction parameter and the substrate temperature are varied to explore their effects on the three-phase contact line friction coefficient. The contact line friction is observed to be a strong function of temperature at atomistic scales, confirming their experimentally observed inverse functionality. Additionally, the MD simulation results are successfully compared with those from an analytical model for self-propelled droplet motion on gradient surfaces.

  17. Knee extension range of motion and self-report physical function in total knee arthroplasty: mediating effects of knee extensor strength

    PubMed Central

    2013-01-01

    Background Knee extensor strength and knee extension range of motion (ROM) are important predictors of physical function in patients with a total knee arthroplasty (TKA). However, the relationship between the two knee measures remains unclear. The purpose of this study was to examine whether changes in knee extensor strength mediate the association between changes in knee extension ROM and self-report physical function. Methods Data from 441 patients with a TKA were collected preoperatively and 6 months postoperatively. Self-report measure of physical function was assessed by the Short Form 36 (SF-36) questionnaire. Knee extensor strength was measured by handheld dynamometry and knee extension ROM by goniometry. A bootstrapped cross product of coefficients approach was used to evaluate mediation effects. Results Mediation analyses, adjusted for clinicodemographic measures, revealed that the association between changes in knee extension ROM and SF-36 physical function was mediated by changes in knee extensor strength. Conclusions In patients with TKA, knee extensor strength mediated the influence of knee extension ROM on physical function. These results suggest that interventions to improve the range of knee extension may be useful in improving knee extensor performance. PMID:23332039

  18. Visual motion modulates pattern sensitivity ahead, behind, and beside motion

    PubMed Central

    Arnold, Derek H.; Marinovic, Welber; Whitney, David

    2014-01-01

    Retinal motion can modulate visual sensitivity. For instance, low contrast drifting waveforms (targets) can be easier to detect when abutting the leading edges of movement in adjacent high contrast waveforms (inducers), rather than the trailing edges. This target-inducer interaction is contingent on the adjacent waveforms being consistent with one another – in-phase as opposed to out-of-phase. It has been suggested that this happens because there is a perceptually explicit predictive signal at leading edges of motion that summates with low contrast physical input – a ‘predictive summation’. Another possible explanation is a phase sensitive ‘spatial summation’, a summation of physical inputs spread across the retina (not predictive signals). This should be non-selective in terms of position – it should be evident at leading, adjacent, and at trailing edges of motion. To tease these possibilities apart, we examined target sensitivity at leading, adjacent, and trailing edges of motion. We also examined target sensitivity adjacent to flicker, and for a stimulus that is less susceptible to spatial summation, as it sums to grey across a small retinal expanse. We found evidence for spatial summation in all but the last condition. Finally, we examined sensitivity to an absence of signal at leading and trailing edges of motion, finding greater sensitivity at leading edges. These results are inconsistent with the existence of a perceptually explicit predictive signal in advance of drifting waveforms. Instead, we suggest that phase-contingent target-inducer modulations of sensitivity are explicable in terms of a directionally modulated spatial summation. PMID:24699250

  19. Feedback Synthesizes Neural Codes for Motion.

    PubMed

    Clarke, Stephen E; Maler, Leonard

    2017-05-08

    In senses as diverse as vision, hearing, touch, and the electrosense, sensory neurons receive bottom-up input from the environment, as well as top-down input from feedback loops involving higher brain regions [1-4]. Through connectivity with local inhibitory interneurons, these feedback loops can exert both positive and negative control over fundamental aspects of neural coding, including bursting [5, 6] and synchronous population activity [7, 8]. Here we show that a prominent midbrain feedback loop synthesizes a neural code for motion reversal in the hindbrain electrosensory ON- and OFF-type pyramidal cells. This top-down mechanism generates an accurate bidirectional encoding of object position, despite the inability of the electrosensory afferents to generate a consistent bottom-up representation [9, 10]. The net positive activity of this midbrain feedback is additionally regulated through a hindbrain feedback loop, which reduces stimulus-induced bursting and also dampens the ON and OFF cell responses to interfering sensory input [11]. We demonstrate that synthesis of motion representations and cancellation of distracting signals are mediated simultaneously by feedback, satisfying an accepted definition of spatial attention [12]. The balance of excitatory and inhibitory feedback establishes a "focal" distance for optimized neural coding, whose connection to a classic motion-tracking behavior provides new insight into the computational roles of feedback and active dendrites in spatial localization [13, 14]. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Potential of mechanical metamaterials to induce their own global rotational motion

    NASA Astrophysics Data System (ADS)

    Dudek, K. K.; Wojciechowski, K. W.; Dudek, M. R.; Gatt, R.; Mizzi, L.; Grima, J. N.

    2018-05-01

    The potential of several classes of mechanical metamaterials to induce their own overall rotational motion through the individual rotation of their subunits is examined. Using a theoretical approach, we confirm that for various rotating rigid unit systems, if by design the sum of angular momentum of subunits rotating in different directions is made to be unequal, then the system will experience an overall rotation, the extent of which may be controlled through careful choice of the geometric parameters defining these systems. This phenomenon of self-induced rotation is also confirmed experimentally. Furthermore, we discuss how these systems can be designed in a special way so as to permit extended rotations which allows them to overcome geometric lockage and the relevance of this concept in applications ranging from satellites to spacecraft and telescopes employed in space.

  1. Vibrationally induced flip motion of a hydroxyl dimer on Cu(110)

    NASA Astrophysics Data System (ADS)

    Ootsuka, Yasuhiro; Frederiksen, Thomas; Ueba, Hiromu; Paulsson, Magnus

    2011-11-01

    Recent low-temperature scanning-tunneling microscopy experiments [T. Kumagai , Phys. Rev. BPLRBAQ0556-280510.1103/PhysRevB.79.035423 79, 035423 (2009)] observed the vibrationally induced flip motion of a hydroxyl dimer (OD)2 on Cu(110). We propose a model to describe two-level fluctuations and current-voltage characteristics of nanoscale systems that undergo vibrationally induced switching. The parameters of the model are based on comprehensive density functional calculations of the system’s vibrational properties. For the dimer (OD)2, the calculated population of the high- and low-conductance states, the I-V, dI/dV, and d2I/dV2 curves are in good agreement with the experimental results and underline the different roles played by the free and shared OD stretch modes of the dimer.

  2. Default perception of high-speed motion

    PubMed Central

    Wexler, Mark; Glennerster, Andrew; Cavanagh, Patrick; Ito, Hiroyuki; Seno, Takeharu

    2013-01-01

    When human observers are exposed to even slight motion signals followed by brief visual transients—stimuli containing no detectable coherent motion signals—they perceive large and salient illusory jumps. This visually striking effect, which we call “high phi,” challenges well-entrenched assumptions about the perception of motion, namely the minimal-motion principle and the breakdown of coherent motion perception with steps above an upper limit called dmax. Our experiments with transients, such as texture randomization or contrast reversal, show that the magnitude of the jump depends on spatial frequency and transient duration—but not on the speed of the inducing motion signals—and the direction of the jump depends on the duration of the inducer. Jump magnitude is robust across jump directions and different types of transient. In addition, when a texture is actually displaced by a large step beyond the upper step size limit of dmax, a breakdown of coherent motion perception is expected; however, in the presence of an inducer, observers again perceive coherent displacements at or just above dmax. In summary, across a large variety of stimuli, we find that when incoherent motion noise is preceded by a small bias, instead of perceiving little or no motion—as suggested by the minimal-motion principle—observers perceive jumps whose amplitude closely follows their own dmax limits. PMID:23572578

  3. Recovery of biological motion perception and network plasticity after cerebellar tumor removal.

    PubMed

    Sokolov, Arseny A; Erb, Michael; Grodd, Wolfgang; Tatagiba, Marcos S; Frackowiak, Richard S J; Pavlova, Marina A

    2014-10-01

    Visual perception of body motion is vital for everyday activities such as social interaction, motor learning or car driving. Tumors to the left lateral cerebellum impair visual perception of body motion. However, compensatory potential after cerebellar damage and underlying neural mechanisms remain unknown. In the present study, visual sensitivity to point-light body motion was psychophysically assessed in patient SL with dysplastic gangliocytoma (Lhermitte-Duclos disease) to the left cerebellum before and after neurosurgery, and in a group of healthy matched controls. Brain activity during processing of body motion was assessed by functional magnetic resonance imaging (MRI). Alterations in underlying cerebro-cerebellar circuitry were studied by psychophysiological interaction (PPI) analysis. Visual sensitivity to body motion in patient SL before neurosurgery was substantially lower than in controls, with significant improvement after neurosurgery. Functional MRI in patient SL revealed a similar pattern of cerebellar activation during biological motion processing as in healthy participants, but located more medially, in the left cerebellar lobules III and IX. As in normalcy, PPI analysis showed cerebellar communication with a region in the superior temporal sulcus, but located more anteriorly. The findings demonstrate a potential for recovery of visual body motion processing after cerebellar damage, likely mediated by topographic shifts within the corresponding cerebro-cerebellar circuitry induced by cerebellar reorganization. The outcome is of importance for further understanding of cerebellar plasticity and neural circuits underpinning visual social cognition.

  4. SET mediates TCE-induced liver cell apoptosis through dephosphorylation and upregulation of nucleolin

    PubMed Central

    Ren, Xiaohu; Huang, Xinfeng; Yang, Xifei; Liu, Yungang; Liu, Wei; Huang, Haiyan; Wu, Desheng; Zou, Fei; Liu, Jianjun

    2017-01-01

    Trichloroethylene (TCE) is an occupational and environmental chemical that can cause severe hepatotoxicity. While our previous studies showed that the phosphatase inhibitor SET is a key mediator of TCE-induced liver cell apoptosis, the molecular mechanisms remain elusive. Using quantitative phosphoproteomic analysis, we report here that nucleolin is a SET-regulated phosphoprotein in human liver HL-7702 cells. Functional analysis suggested that SET promoted dephosphorylation of nucleolin, decreased its binding to its transcriptional activator, c-myc, and upregulated nucleolin expression in TCE-treated cells. Importantly, TCE-induced hepatocyte apoptosis was significantly attenuated when nucleolin was downregulated with specific siRNAs. These findings indicate that TCE may induce hepatocyte apoptosis via SET-mediated dephosphorylation and overexpression of nucleolin. PMID:28402964

  5. SET mediates TCE-induced liver cell apoptosis through dephosphorylation and upregulation of nucleolin.

    PubMed

    Ren, Xiaohu; Huang, Xinfeng; Yang, Xifei; Liu, Yungang; Liu, Wei; Huang, Haiyan; Wu, Desheng; Zou, Fei; Liu, Jianjun

    2017-06-20

    Trichloroethylene (TCE) is an occupational and environmental chemical that can cause severe hepatotoxicity. While our previous studies showed that the phosphatase inhibitor SET is a key mediator of TCE-induced liver cell apoptosis, the molecular mechanisms remain elusive. Using quantitative phosphoproteomic analysis, we report here that nucleolin is a SET-regulated phosphoprotein in human liver HL-7702 cells. Functional analysis suggested that SET promoted dephosphorylation of nucleolin, decreased its binding to its transcriptional activator, c-myc, and upregulated nucleolin expression in TCE-treated cells. Importantly, TCE-induced hepatocyte apoptosis was significantly attenuated when nucleolin was downregulated with specific siRNAs. These findings indicate that TCE may induce hepatocyte apoptosis via SET-mediated dephosphorylation and overexpression of nucleolin.

  6. Attraction of posture and motion-trajectory elements of conspecific biological motion in medaka fish.

    PubMed

    Shibai, Atsushi; Arimoto, Tsunehiro; Yoshinaga, Tsukasa; Tsuchizawa, Yuta; Khureltulga, Dashdavaa; Brown, Zuben P; Kakizuka, Taishi; Hosoda, Kazufumi

    2018-06-05

    Visual recognition of conspecifics is necessary for a wide range of social behaviours in many animals. Medaka (Japanese rice fish), a commonly used model organism, are known to be attracted by the biological motion of conspecifics. However, biological motion is a composite of both body-shape motion and entire-field motion trajectory (i.e., posture or motion-trajectory elements, respectively), and it has not been revealed which element mediates the attractiveness. Here, we show that either posture or motion-trajectory elements alone can attract medaka. We decomposed biological motion of the medaka into the two elements and synthesized visual stimuli that contain both, either, or none of the two elements. We found that medaka were attracted by visual stimuli that contain at least one of the two elements. In the context of other known static visual information regarding the medaka, the potential multiplicity of information regarding conspecific recognition has further accumulated. Our strategy of decomposing biological motion into these partial elements is applicable to other animals, and further studies using this technique will enhance the basic understanding of visual recognition of conspecifics.

  7. [Locally administered lentivirus-mediated siRNA inhibits wear debris-induced inflammation].

    PubMed

    Peng, Xiao-chun; Zhang, Xian-long; Tao, Kun; Cheng, Tao; Zhu, Jun-feng; Zeng, Bing-fang

    2009-03-01

    To determine the safety and efficacy of local administration of lentivirus-mediated small interfering RNA (siRNA) targeting tumor necrosis factor-alpha (TNF-alpha) in murine air pouch model. From May 2007 to April 2008 a siRNA targeting TNF-alpha and a missense siRNA were designed, and recombine lentivirus which coexpressed the green fluorescent protein (GFP) as a marker gene was constructed. Air pouches were established and stimulated by Ti-6Al-4V particles. Pouches were divided into 3 groups randomly. Lentivirus-mediated siRNA targeting TNF-alpha (TNF-alpha group) or lentivirus-mediated missense siRNA (MS group), or virus-free saline (control group) were injected into pouches respectively. Pouch membrane, peripheral blood, heart, liver, spleen, kidney, lung and brain were harvested at 28 d after transfection, and assayed for markers of inflammation using histological, molecular, immunological techniques and Xenogen in vivo imaging system (IVIS) 50 vivo bioluminescent assay system. Xenogen IVIS 50 vivo image revealed strong expression of GFP localized in pouch areas and no expression in other parts of mice both in TNF-alpha group and MS group at 4 weeks after transfection, while no expression of GFP was found in control group. By RT-PCR and ELISA, the mRNA and protein levels of TNF-alpha in TNF-alpha group decreased by 81.6% and 82.6% respectively compared to control group (P < 0.01), and decreased by 78.9% and 84.0% respectively compared to MS group (P < 0.01), whereas TNF-alpha level in peripheral blood, heart, liver, spleen, kidney, lung and brain remained invariant (P > 0.05). Less inflammatory responses (thinner pouch membrane and decreased cellular infiltration) were observed in TNF-alpha group. Efficient local delivery of lentivirus-mediated siRNA targeting TNF-alpha into modified murine air pouch can inhibit debris-induced inflammation effectively, with no systemic adverse effects.

  8. Role of endothelial nitric oxide synthase as a trigger and mediator of isoflurane-induced delayed preconditioning in rabbit myocardium.

    PubMed

    Chiari, Pascal C; Bienengraeber, Martin W; Weihrauch, Dorothee; Krolikowski, John G; Kersten, Judy R; Warltier, David C; Pagel, Paul S

    2005-07-01

    Isoflurane produces delayed preconditioning in vivo. The authors tested the hypothesis that endothelial, inducible, or neuronal nitric oxide synthase (NOS) is a trigger or mediator of this protective effect. In the absence or presence of exposure to isoflurane (1.0 minimum alveolar concentration) 24 h before experimentation, pentobarbital-anesthetized rabbits (n = 128) instrumented for hemodynamic measurement received 0.9% saline (control), the nonselective NOS inhibitor N-nitro-l-arginine methyl ester (10 mg/kg), one of two of the selective inducible NOS antagonists aminoguanidine (300 mg/kg) or 1400W (0.5 mg/kg), or the selective neuronal NOS inhibitor 7-nitroindazole (50 mg/kg) administered before exposure to isoflurane (trigger; day 1) or left anterior descending coronary artery occlusion (mediator; day 2). All rabbits underwent 30 min of coronary occlusion followed by 3 h of reperfusion. Tissue samples for reverse-transcription polymerase chain reaction and immunohistochemistry were also obtained in the presence or absence of N-nitro-l-arginine methyl ester with or without isoflurane pretreatment. Isoflurane significantly (P < 0.05) reduced infarct size (23 +/- 5% [mean +/- SD] of the left ventricular area at risk; triphenyltetrazolium chloride staining) as compared with control (42 +/- 7%). N-nitro-l-arginine methyl ester administered before isoflurane or coronary occlusion abolished protection (49 +/- 7 and 43 +/- 10%, respectively). Aminoguanidine, 1400W, and 7-nitroindazole did not alter infarct size or affect isoflurane-induced delayed preconditioning. Isoflurane increased endothelial but not inducible NOS messenger RNA transcription and protein translation immediately and 24 h after administration of the volatile agent. Pretreatment with N-nitro-l-arginine methyl ester attenuated isoflurane-induced increases in endothelial NOS expression. The results suggest that endothelial NOS but not inducible or neuronal NOS is a trigger and mediator of delayed

  9. 34 CFR 81.13 - Mediation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Mediation. 81.13 Section 81.13 Education Office of the... Mediation. (a) Voluntary mediation is available for proceedings that are pending before the OALJ. (b) A... mediation by filing a motion with the ALJ assigned to the case. The OALJ arranges for a mediator if the...

  10. Spin-orbit-torque-induced magnetic domain wall motion in Ta/CoFe nanowires with sloped perpendicular magnetic anisotropy.

    PubMed

    Zhang, Yue; Luo, Shijiang; Yang, Xiaofei; Yang, Chang

    2017-05-17

    In materials with the gradient of magnetic anisotropy, spin-orbit-torque-induced magnetization behaviour has attracted attention because of its intriguing scientific principle and potential application. Most of the magnetization behaviours microscopically originate from magnetic domain wall motion, which can be precisely depicted using the standard cooperative coordinate method (CCM). However, the domain wall motion in materials with the gradient of magnetic anisotropy using the CCM remains lack of investigation. In this paper, by adopting CCM, we established a set of equations to quantitatively depict the spin-orbit-torque-induced motion of domain walls in a Ta/CoFe nanotrack with weak Dzyaloshinskii-Moriya interaction and magnetic anisotropy gradient. The equations were solved numerically, and the solutions are similar to those of a micromagnetic simulation. The results indicate that the enhanced anisotropy along the track acts as a barrier to inhibit the motion of the domain wall. In contrast, the domain wall can be pushed to move in a direction with reduced anisotropy, with the velocity being accelerated by more than twice compared with that for the constant anisotropy case. This substantial velocity manipulation by anisotropy engineering is important in designing novel magnetic information devices with high reading speeds.

  11. Examining Rotational Ground Motion Induced by Tornados

    NASA Astrophysics Data System (ADS)

    Kessler, Elijah; Dunn, Robert

    2016-03-01

    Ring lasers are well known for their ability to detect rotation and to serve as replacements for mechanical gyroscopes. The sensitivity of large ring lasers to various forms of ground motion is less familiar. Since ring lasers preferentially measure rotational ground motion and a standard seismograph is designed to measure translational and vertical ground motion, each device responds to different aspects of ground movement. Therefore, the two instruments will be used to explore responses to microseisms, earthquake generated shear waves, and in particular tornado generated ground movement. On April 27, 2014 an EF4 tornado devastated Vilonia, AR a small town ~ 21 km from the Hendrix College ring laser. The proximity of the tornado's path to the ring laser interferometer and to a seismograph located in Vilonia provided the opportunity to examine the response of these instruments to tornadic generated ground motion. Our measurements suggest tornadic weather systems can produce both rotational and lateral ground motion. This contention is supported by an after the fact damage survey which found that the tornado flattened a forest in which trees were uprooted and laid down in a pair of converging arcs with the centerline pointed in the direction of the tornado's path.

  12. Effect of vertical ground motion on earthquake-induced derailment of railway vehicles over simply-supported bridges

    NASA Astrophysics Data System (ADS)

    Jin, Zhibin; Pei, Shiling; Li, Xiaozhen; Liu, Hongyan; Qiang, Shizhong

    2016-11-01

    The running safety of railway vehicles on bridges can be negatively affected by earthquake events. This phenomenon has traditionally been investigated with only the lateral ground excitation component considered. This paper presented results from a numerical investigation on the contribution of vertical ground motion component to the derailment of vehicles on simply-supported bridges. A full nonlinear wheel-rail contact model was used in the investigation together with the Hertzian contact theory and nonlinear creepage theory, which allows the wheel to jump vertically and separate from the rail. The wheel-rail relative displacement was used as the criterion for derailment events. A total of 18 ground motion records were used in the analysis to account for the uncertainty of ground motions. The results showed that inclusion of vertical ground motion will likely increase the chance of derailment. It is recommended to include vertical ground motion component in earthquake induced derailment analysis to ensure conservative estimations. The derailment event on bridges was found to be more closely related to the deck acceleration rather than the ground acceleration.

  13. Moment tensor inversion of ground motion from mining-induced earthquakes, Trail Mountain, Utah

    USGS Publications Warehouse

    Fletcher, Joe B.; McGarr, A.

    2005-01-01

    A seismic network was operated in the vicinity of the Trail Mountain mine, central Utah, from the summer of 2000 to the spring of 2001 to investigate the seismic hazard to a local dam from mining-induced events that we expect to be triggered by future coal mining in this area. In support of efforts to develop groundmotion prediction relations for this situation, we inverted ground-motion recordings for six mining-induced events to determine seismic moment tensors and then to estimate moment magnitudes M for comparison with the network coda magnitudes Mc. Six components of the tensor were determined, for an assumed point source, following the inversion method of McGarr (1992a), which uses key measurements of amplitude from obvious features of the displacement waveforms. When the resulting moment tensors were decomposed into implosive and deviatoric components, we found that four of the six events showed a substantial volume reduction, presumably due to coseismic closure of the adjacent mine openings. For these four events, the volume reduction ranges from 27% to 55% of the shear component (fault area times average slip). Radiated seismic energy, computed from attenuation-corrected body-wave spectra, ranged from 2.4 ?? 105 to 2.4 ?? 106 J for events with M from 1.3 to 1.8, yielding apparent stresses from 0.02 to 0.06 MPa. The energy released for each event, approximated as the product of volume reduction and overburden stress, when compared with the corresponding seismic energies, revealed seismic efficiencies ranging from 0.5% to 7%. The low apparent stresses are consistent with the shallow focal depths of 0.2 to 0.6 km and rupture in a low stress/low strength regime compared with typical earthquake source regions at midcrustal depths.

  14. Dynamic modeling of injection-induced fault reactivation and ground motion and impact on surface structures and human perception

    DOE PAGES

    Rutqvist, Jonny; Cappa, Frederic; Rinaldi, Antonio P.; ...

    2014-12-31

    We summarize recent modeling studies of injection-induced fault reactivation, seismicity, and its potential impact on surface structures and nuisance to the local human population. We used coupled multiphase fluid flow and geomechanical numerical modeling, dynamic wave propagation modeling, seismology theories, and empirical vibration criteria from mining and construction industries. We first simulated injection-induced fault reactivation, including dynamic fault slip, seismic source, wave propagation, and ground vibrations. From co-seismic average shear displacement and rupture area, we determined the moment magnitude to about M w = 3 for an injection-induced fault reactivation at a depth of about 1000 m. We then analyzedmore » the ground vibration results in terms of peak ground acceleration (PGA), peak ground velocity (PGV), and frequency content, with comparison to the U.S. Bureau of Mines’ vibration criteria for cosmetic damage to buildings, as well as human-perception vibration limits. For the considered synthetic M w = 3 event, our analysis showed that the short duration, high frequency ground motion may not cause any significant damage to surface structures, and would not cause, in this particular case, upward CO 2 leakage, but would certainly be felt by the local population.« less

  15. Sodium fluoride induces apoptosis in mouse embryonic stem cells through ROS-dependent and caspase- and JNK-mediated pathways

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

    Nguyen Ngoc, Tam Dan; Son, Young-Ok; Lim, Shin-Saeng

    2012-03-15

    Sodium fluoride (NaF) is used as a source of fluoride ions in diverse applications. Fluoride salt is an effective prophylactic for dental caries and is an essential element required for bone health. However, fluoride is known to cause cytotoxicity in a concentration-dependent manner. Further, no information is available on the effects of NaF on mouse embryonic stem cells (mESCs). We investigated the mode of cell death induced by NaF and the mechanisms involved. NaF treatment greater than 1 mM reduced viability and DNA synthesis in mESCs and induced cell cycle arrest in the G{sub 2}/M phase. The addition of NaFmore » induced cell death mainly by apoptosis rather than necrosis. Catalase (CAT) treatment significantly inhibited the NaF-mediated cell death and also suppressed the NaF-mediated increase in phospho-c-Jun N-terminal kinase (p-JNK) levels. Pre-treatment with SP600125 or z-VAD-fmk significantly attenuated the NaF-mediated reduction in cell viability. In contrast, intracellular free calcium chelator, but not of sodium or calcium ion channel blockers, facilitated NaF-induced toxicity in the cells. A JNK specific inhibitor (SP600125) prevented the NaF-induced increase in growth arrest and the DNA damage-inducible protein 45α. Further, NaF-mediated loss of mitochondrial membrane potential was apparently inhibited by pifithrin-α or CAT inhibitor. These findings suggest that NaF affects viability of mESCs in a concentration-dependent manner, where more than 1 mM NaF causes apoptosis through hydroxyl radical-dependent and caspase- and JNK-mediated pathways. -- Highlights: ► The mode of NaF-induced cell death and the mechanisms involved were examined. ► NaF induced mainly apoptotic death of mouse embryonic stem cells (mESCs). ► NaF induced mitochondrial-mediated and caspase-dependent apoptosis. ► JNK- and p53-mediated pathways are involved in NaF-mediated apoptosis in the cells. ► ROS are the up-stream effector in NaF-mediated activation of JNK and p53

  16. Cadmium-induced teratogenicity: Association with ROS-mediated endoplasmic reticulum stress in placenta

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

    Wang, Zhen; Wang, Hua; Xu, Zhong Mei

    The placenta is essential for sustaining the growth of the fetus. An increased endoplasmic reticulum (ER) stress has been associated with the impaired placental and fetal development. Cadmium (Cd) is a potent teratogen that caused fetal malformation and growth restriction. The present study investigated the effects of maternal Cd exposure on placental and fetal development. The pregnant mice were intraperitoneally injected with CdCl{sub 2} (4.5 mg/kg) on gestational day 9. As expected, maternal Cd exposure during early limb development significantly increased the incidences of forelimb ectrodactyly in fetuses. An obvious impairment in the labyrinth, a highly developed tissue of bloodmore » vessels, was observed in placenta of mice treated with CdCl{sub 2}. In addition, maternal Cd exposure markedly repressed cell proliferation and increased apoptosis in placenta. An additional experiment showed that maternal Cd exposure significantly upregulated the expression of GRP78, an ER chaperone. Moreover, maternal Cd exposure induced the phosphorylation of placental eIF2α, a downstream molecule of PERK signaling. In addition, maternal Cd exposure significantly increased the level of placental CHOP, another target of PERK signaling, indicating that the unfolded protein response (UPR) signaling was activated in placenta of mice treated with CdCl{sub 2}. Interestingly, alpha-phenyl-N-t-butylnitrone, a free radical spin-trapping agent, significantly alleviated Cd-induced placental ER stress and UPR. Taken together, these results suggest that reactive oxygen species (ROS)-mediated ER stress might be involved in Cd-induced impairment on placental and fetal development. Antioxidants may be used as pharmacological agents to protect against Cd-induced fetal malformation and growth restriction. -- Highlights: ► Cd induces fetal malformation and growth restriction. ► Cd induced placental ER stress and UPR. ► PBN alleviates Cd-induced ER stress and UPR in placenta. ► ROS-mediated

  17. Thrombin Induces Inositol Trisphosphate-Mediated Spatially Extensive Responses in Lung Microvessels.

    PubMed

    Escue, Rachel; Kandasamy, Kathirvel; Parthasarathi, Kaushik

    2017-04-01

    Activation of plasma membrane receptors initiates compartmentalized second messenger signaling. Whether this compartmentalization facilitates the preferential intercellular diffusion of specific second messengers is unclear. Toward this, the receptor-mediated agonist, thrombin, was instilled into microvessels in a restricted region of isolated blood-perfused mouse lungs. Subsequently, the thrombin-induced increase in endothelial F-actin was determined using confocal fluorescence microscopy. Increased F-actin was evident in microvessels directly treated with thrombin and in those located in adjoining thrombin-free regions. This increase was abrogated by inhibiting inositol trisphosphate-mediated calcium release with Xestospongin C (XeC). XeC also inhibited the thrombin-induced increase in the amplitude of endothelial cytosolic Ca 2+ oscillations. Instillation of thrombin and XeC into adjacent restricted regions increased F-actin in microvessels in the thrombin-treated and adjacent regions but not in those in the XeC-treated region. Thus, inositol trisphosphate, and not calcium, diffused interendothelially to the spatially remote thrombin-free microvessels. Thus, activation of plasma membrane receptors increased the ambit of inflammatory responses via a second messenger different from that used by stimuli that induce cell-wide increases in second messengers. Thrombin however failed to induce the spatially extensive response in microvessels of mice lacking endothelial connexin43, suggesting a role for connexin43 gap junctions. Compartmental second messenger signaling and interendothelial communication define the specific second messenger involved in exacerbating proinflammatory responses to receptor-mediated agonists. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  18. 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.

  19. Effect of stationary objects on illusory forward self-motion induced by a looming display.

    PubMed

    Ohmi, M; Howard, I P

    1988-01-01

    It has previously been shown that when a moving and a stationary display are superimposed, illusory self-rotation (circular vection) is induced only when the moving display appears as the background. Three experiments are reported on the extent to which illusory forward self-motion (forward vection) induced by a looming display is inhibited by a superimposed stationary display as a function of the size and location of the stationary display and of the depth between the stationary and looming displays. Results showed that forward vection was controlled by the display that was perceived as the background, and background stationary displays suppressed forward vection by about the same amount whatever their size and eccentricity. Also, the perception of foreground-background properties of competing displays determined which controlled forward vection, and this control was not tied to specific depth cues. The inhibitory effect of a stationary background on forward vection was, however, weaker than that found with circular vection. This difference makes sense because, for forward body motion, the image of a distant scene is virtually stationary whereas, when the body rotates, it is not.

  20. Endoplasmic reticulum stress mediates withaferin A-induced apoptosis in human renal carcinoma cells.

    PubMed

    Choi, Min Jung; Park, Eun Jung; Min, Kyoung Jin; Park, Jong-Wook; Kwon, Taeg Kyu

    2011-04-01

    The accumulation of misfolded proteins in the lumen of the endoplasmic reticulum (ER) results in cellular stress that initiates a specialized response designated as the unfolded protein response. ER stress has been implicated in a variety of common diseases, such as diabetes, ischemia and neurodegenerative disorders. Withaferin A, a major chemical constituent of Withania somnifera, has been reported to inhibit tumor cell growth. We show that withaferin A induced a dose-dependent apoptotic cell death in several types of human cancer cells, as measured by FACS analysis and PARP cleavage. Treatment of Caki cells with withaferin A induced a number of signature ER stress markers, including phosphorylation of eukaryotic initiation factor-2α (eIF-2 α), ER stress-specific XBP1 splicing, and up-regulation of glucose-regulated protein (GRP)-78. In addition, withaferin A caused up-regulation of CAAT/enhancer-binding protein-homologous protein (CHOP), suggesting the induction of ER stress. Pretreatment with N-acetyl cysteine (NAC) significantly inhibited withaferin A-mediated ER stress proteins and cell death, suggesting that reactive oxygen species (ROS) mediate withaferin A-induced ER stress. Furthermore, CHOP siRNA or inhibition of caspase-4 activity attenuated withaferin A-induced apoptosis. Taken together, the present study provides strong evidence supporting an important role of the ER stress response in mediating withaferin A-induced apoptosis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Apoptosis-inducing factor (Aif1) mediates anacardic acid-induced apoptosis in Saccharomyces cerevisiae.

    PubMed

    Muzaffar, Suhail; Chattoo, Bharat B

    2017-03-01

    Anacardic acid is a medicinal phytochemical that inhibits proliferation of fungal as well as several types of cancer cells. It induces apoptotic cell death in various cell types, but very little is known about the mechanism involved in the process. Here, we used budding yeast Saccharomyces cerevisiae as a model to study the involvement of some key elements of apoptosis in the anacardic acid-induced cell death. Plasma membrane constriction, chromatin condensation, DNA degradation, and externalization of phosphatidylserine (PS) indicated that anacardic acid induces apoptotic cell death in S. cerevisiae. However, the exogenous addition of broad-spectrum caspase inhibitor Z-VAD-FMK or deletion of the yeast caspase Yca1 showed that the anacardic acid-induced cell death is caspase independent. Apoptosis-inducing factor (AIF1) deletion mutant was resistant to the anacardic acid-induced cell death, suggesting a key role of Aif1. Overexpression of Aif1 made cells highly susceptible to anacardic acid, further confirming that Aif1 mediates anacardic acid-induced apoptosis. Interestingly, instead of the increase in the intracellular reactive oxygen species (ROS) normally observed during apoptosis, anacardic acid caused a decrease in the intracellular ROS levels. Quantitative real-time PCR analysis showed downregulation of the BIR1 survivin mRNA expression during the anacardic acid-induced apoptosis.

  2. Motion Sickness-Induced Food Aversions in the Squirrel Monkey

    NASA Technical Reports Server (NTRS)

    Roy, M. Aaron; Brizzee, Kenneth R.

    1979-01-01

    Conditioned aversions to colored, flavored water were established in Squirrel monkeys (Saimiri sciureus) by following consumption with 90 min of simultaneous rotational and vertical stimulation. The experimental group (N= 13) drank significantly less of the green, almond-flavored test solution than did the control group (N=14) during three post-treatment preference testing days. Individual differences were noted in that two experimental monkeys readily drank the test solution after rotational stimulation. Only two of the experimental monkeys showed emesis during rotation, yet 10 monkeys in this group developed an aversion. These results suggest that: (1) motion sickness can be readily induced in Squirrel monkeys with simultaneous rotational and vertical stimulation, and (2) that conditioned food aversions are achieved in the absence of emesis in this species.

  3. Ventral and dorsal streams processing visual motion perception (FDG-PET study)

    PubMed Central

    2012-01-01

    Background Earlier functional imaging studies on visually induced self-motion perception (vection) disclosed a bilateral network of activations within primary and secondary visual cortex areas which was combined with signal decreases, i.e., deactivations, in multisensory vestibular cortex areas. This finding led to the concept of a reciprocal inhibitory interaction between the visual and vestibular systems. In order to define areas involved in special aspects of self-motion perception such as intensity and duration of the perceived circular vection (CV) or the amount of head tilt, correlation analyses of the regional cerebral glucose metabolism, rCGM (measured by fluorodeoxyglucose positron-emission tomography, FDG-PET) and these perceptual covariates were performed in 14 healthy volunteers. For analyses of the visual-vestibular interaction, the CV data were compared to a random dot motion stimulation condition (not inducing vection) and a control group at rest (no stimulation at all). Results Group subtraction analyses showed that the visual-vestibular interaction was modified during CV, i.e., the activations within the cerebellar vermis and parieto-occipital areas were enhanced. The correlation analysis between the rCGM and the intensity of visually induced vection, experienced as body tilt, showed a relationship for areas of the multisensory vestibular cortical network (inferior parietal lobule bilaterally, anterior cingulate gyrus), the medial parieto-occipital cortex, the frontal eye fields and the cerebellar vermis. The “earlier” multisensory vestibular areas like the parieto-insular vestibular cortex and the superior temporal gyrus did not appear in the latter analysis. The duration of perceived vection after stimulus stop was positively correlated with rCGM in medial temporal lobe areas bilaterally, which included the (para-)hippocampus, known to be involved in various aspects of memory processing. The amount of head tilt was found to be positively

  4. NLRP3 Inflammasome Mediates Aldosterone-Induced Vascular Damage.

    PubMed

    Bruder-Nascimento, Thiago; Ferreira, Nathanne S; Zanotto, Camila Z; Ramalho, Fernanda; Pequeno, Isabela O; Olivon, Vania C; Neves, Karla B; Alves-Lopes, Rheure; Campos, Eduardo; Silva, Carlos Alberto A; Fazan, Rubens; Carlos, Daniela; Mestriner, Fabiola L; Prado, Douglas; Pereira, Felipe V; Braga, Tarcio; Luiz, Joao Paulo M; Cau, Stefany B; Elias, Paula C; Moreira, Ayrton C; Câmara, Niels O; Zamboni, Dario S; Alves-Filho, Jose Carlos; Tostes, Rita C

    2016-12-06

    Inflammation is a key feature of aldosterone-induced vascular damage and dysfunction, but molecular mechanisms by which aldosterone triggers inflammation remain unclear. The NLRP3 inflammasome is a pivotal immune sensor that recognizes endogenous danger signals triggering sterile inflammation. We analyzed vascular function and inflammatory profile of wild-type (WT), NLRP3 knockout (NLRP3 -/- ), caspase-1 knockout (Casp-1 -/- ), and interleukin-1 receptor knockout (IL-1R -/- ) mice treated with vehicle or aldosterone (600 µg·kg -1 ·d -1 for 14 days through osmotic mini-pump) while receiving 1% saline to drink. Here, we show that NLRP3 inflammasome plays a central role in aldosterone-induced vascular dysfunction. Long-term infusion of aldosterone in mice resulted in elevation of plasma interleukin-1β levels and vascular abnormalities. Mice lacking the IL-1R or the inflammasome components NLRP3 and caspase-1 were protected from aldosterone-induced vascular damage. In vitro, aldosterone stimulated NLRP3-dependent interleukin-1β secretion by bone marrow-derived macrophages by activating nuclear factor-κB signaling and reactive oxygen species generation. Moreover, chimeric mice reconstituted with NLRP3-deficient hematopoietic cells showed that NLRP3 in immune cells mediates aldosterone-induced vascular damage. In addition, aldosterone increased the expression of NLRP3, active caspase-1, and mature interleukin-1β in human peripheral blood mononuclear cells. Hypertensive patients with hyperaldosteronism or normal levels of aldosterone exhibited increased activity of NLRP3 inflammasome, suggesting that the effect of hyperaldosteronism on the inflammasome may be mediated through high blood pressure. Together, these data demonstrate that NLRP3 inflammasome, through activation of IL-1R, is critically involved in the deleterious vascular effects of aldosterone, placing NLRP3 as a potential target for therapeutic interventions in conditions with high aldosterone levels.

  5. SIRT1 activation mediates heat-induced survival of UVB damaged Keratinocytes.

    PubMed

    Calapre, Leslie; Gray, Elin S; Kurdykowski, Sandrine; David, Anthony; Descargues, Pascal; Ziman, Mel

    2017-06-10

    Exposure to heat stress after UVB irradiation induces a reduction of apoptosis, resulting in survival of DNA damaged human keratinocytes. This heat-mediated evasion of apoptosis appears to be mediated by activation of SIRT1 and inactivation of p53 signalling. In this study, we assessed the role of SIRT1 in the inactivation of p53 signalling and impairment of DNA damage response in UVB plus heat exposed keratinocytes. Activation of SIRT1 after multiple UVB plus heat exposures resulted in increased p53 deacetylation at K382, which is known to affect its binding to specific target genes. Accordingly, we noted decreased apoptosis and down regulation of the p53 targeted pro-apoptotic gene BAX and the DNA repair genes ERCC1 and XPC after UVB plus heat treatments. In addition, UVB plus heat induced increased expression of the cell survival gene Survivin and the proliferation marker Ki67. Notably, keratinocytes exposed to UVB plus heat in the presence of the SIRT1 inhibitor, Ex-527, showed a similar phenotype to those exposed to UV alone; i.e. an increase in p53 acetylation, increased apoptosis and low levels of Survivin. This study demonstrate that heat-induced SIRT1 activation mediates survival of DNA damaged keratinocytes through deacetylation of p53 after exposure to UVB plus heat.

  6. Bacopa monnieri-Induced Protective Autophagy Inhibits Benzo[a]pyrene-Mediated Apoptosis.

    PubMed

    Das, Durgesh Nandini; Naik, Prajna Paramita; Nayak, Aditi; Panda, Prashanta Kumar; Mukhopadhyay, Subhadip; Sinha, Niharika; Bhutia, Sujit K

    2016-11-01

    Benzo[a]pyrene (B[a]P) is capable of inducing oxidative stress and cellular injuries leading to cell death and associates with a significant risk of cancer development. Prevention of B[a]P-induced cellular toxicity with herbal compound through regulation of mitochondrial oxidative stress might protect cell death and have therapeutic benefit to human health. In this study, we demonstrated the cytoprotective role of Bacopa monnieri (BM) against B[a]P-induced apoptosis through autophagy induction. Pretreatment with BM rescued the reduction in cell viability in B[a]P-treated human keratinocytes (HaCaT) cells indicating the cytoprotective potential of BM against B[a]P. Moreover, BM was found to inhibit B[a]P-mediated reactive oxygen species (ROS)-induced apoptosis activation in HaCaT cells. Furthermore, BM was found to preserve mitochondrial membrane potential and inhibited release of cytochrome c in B[a]P-treated HaCaT cells. Bacopa monnieri induced protective autophagy; we knocked down Beclin-1, and data showed that BM was unable to protect from B[a]P-induced mitochondrial ROS-mediated apoptosis in Beclin-1-deficient HaCaT cells. Moreover, we established that B[a]P-induced damaged mitochondria were found to colocalize and degraded within autolysosomes in order to protect HaCaT cells from mitochondrial injury. In conclusion, B[a]P-induced apoptosis was rescued by BM treatment and provided cytoprotection through Beclin-1-dependent autophagy activation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  7. Effects of auditory information on self-motion perception during simultaneous presentation of visual shearing motion

    PubMed Central

    Tanahashi, Shigehito; Ashihara, Kaoru; Ujike, Hiroyasu

    2015-01-01

    Recent studies have found that self-motion perception induced by simultaneous presentation of visual and auditory motion is facilitated when the directions of visual and auditory motion stimuli are identical. They did not, however, examine possible contributions of auditory motion information for determining direction of self-motion perception. To examine this, a visual stimulus projected on a hemisphere screen and an auditory stimulus presented through headphones were presented separately or simultaneously, depending on experimental conditions. The participant continuously indicated the direction and strength of self-motion during the 130-s experimental trial. When the visual stimulus with a horizontal shearing rotation and the auditory stimulus with a horizontal one-directional rotation were presented simultaneously, the duration and strength of self-motion perceived in the opposite direction of the auditory rotation stimulus were significantly longer and stronger than those perceived in the same direction of the auditory rotation stimulus. However, the auditory stimulus alone could not sufficiently induce self-motion perception, and if it did, its direction was not consistent within each experimental trial. We concluded that auditory motion information can determine perceived direction of self-motion during simultaneous presentation of visual and auditory motion information, at least when visual stimuli moved in opposing directions (around the yaw-axis). We speculate that the contribution of auditory information depends on the plausibility and information balance of visual and auditory information. PMID:26113828

  8. Ablation of synovial pannus using microbubble-mediated ultrasonic cavitation in antigen-induced arthritis in rabbits.

    PubMed

    Qiu, Li; Jiang, Yong; Zhang, Lingyan; Wang, Lei; Luo, Yan

    2012-12-01

    To investigate the ablative effectiveness of microbubble-mediated ultrasonic cavitation for treating synovial pannus and to determine a potential mechanism using the antigen-induced arthritis model (AIA). Ultrasonic ablation was performed on the knee joints of AIA rabbits using optimal ultrasonic ablative parameters. Rabbits with antigen-induced arthritis were randomly assigned to 4 groups: (1) the ultrasound (US) + microbubble group; (2) the US only group; (3) the microbubble only group, and (4) the control group. At 1 h and 14 days after the first ablation, contrast-enhanced ultrasonography (CEUS) monitoring and pathology synovitis score were used to evaluate the therapeutic effects. Synovial necrosis and microvascular changes were also measured. After the ablation treatment, the thickness of synovium and parameters of time intensity curve including derived peak intensity and area under curve were measured using CEUS, and the pathology synovitis score in the ultrasound + microbubble group was significantly lower than that found in the remaining groups. No damage was observed in the surrounding normal tissues. The mechanism underlying the ultrasonic ablation was related to microthrombosis and microvascular rupture that resulted in synovial necrosis. The results suggest that microbubble-mediated ultrasonic cavitation should be applied as a non-invasive strategy for the treatment of synovial pannus in arthritis under optimal conditions.

  9. The effect of internal and external fields of view on visually induced motion sickness.

    PubMed

    Bos, Jelte E; de Vries, Sjoerd C; van Emmerik, Martijn L; Groen, Eric L

    2010-07-01

    Field of view (FOV) is said to affect visually induced motion sickness. FOV, however, is characterized by an internal setting used by the graphics generator (iFOV) and an external factor determined by screen size and viewing distance (eFOV). We hypothesized that especially the incongruence between iFOV and eFOV would lead to sickness. To that end we used a computer game environment with different iFOV and eFOV settings, and found the opposite effect. We speculate that the relative large differences between iFOV and eFOV used in this experiment caused the discrepancy, as may be explained by assuming an observer model controlling body motion. Copyright 2009 Elsevier Ltd. All rights reserved.

  10. The endocannabinoid system mediates aerobic exercise-induced antinociception in rats.

    PubMed

    Galdino, Giovane; Romero, Thiago R L; Silva, José Felipe P; Aguiar, Daniele C; de Paula, Ana Maria; Cruz, Jader S; Parrella, Cosimo; Piscitelli, Fabiana; Duarte, Igor D; Di Marzo, Vincenzo; Perez, Andrea C

    2014-02-01

    Exercise-induced antinociception is widely described in the literature, but the mechanisms involved in this phenomenon are poorly understood. Systemic (s.c.) and central (i.t., i.c.v.) pretreatment with CB₁ and CB₂ cannabinoid receptor antagonists (AM251 and AM630) blocked the antinociception induced by an aerobic exercise (AE) protocol in both mechanical and thermal nociceptive tests. Western blot analysis revealed an increase and activation of CB₁ receptors in the rat brain, and immunofluorescence analysis demonstrated an increase of activation and expression of CB₁ receptors in neurons of the periaqueductal gray matter (PAG) after exercise. Additionally, pretreatment (s.c., i.t. and i.c.v.) with endocannabinoid metabolizing enzyme inhibitors (MAFP and JZL184) and an anandamide reuptake inhibitor (VDM11) prolonged and intensified this antinociceptive effect. These results indicate that exercise could activate the endocannabinoid system, producing antinociception. Supporting this hypothesis, liquid-chromatography/mass-spectrometry measurements demonstrated that plasma levels of endocannabinoids (anandamide and 2-arachidonoylglycerol) and of anandamide-related mediators (palmitoylethanolamide and oleoylethanolamide) were increased after AE. Therefore, these results suggest that the endocannabinoid system mediates aerobic exercise-induced antinociception at peripheral and central levels. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Sensory conflict in motion sickness: An observer theory approach

    NASA Technical Reports Server (NTRS)

    Oman, Charles M.

    1989-01-01

    Motion sickness is the general term describing a group of common nausea syndromes originally attributed to motion-induced cerebral ischemia, stimulation of abdominal organ afferent, or overstimulation of the vestibular organs of the inner ear. Sea-, car-, and airsicknesses are the most commonly experienced examples. However, the discovery of other variants such as Cinerama-, flight simulator-, spectacle-, and space sickness in which the physical motion of the head and body is normal or absent has led to a succession of sensory conflict theories which offer a more comprehensive etiologic perspective. Implicit in the conflict theory is the hypothesis that neutral and/or humoral signals originate in regions of the brain subversing spatial orientation, and that these signals somehow traverse to other centers mediating sickness symptoms. Unfortunately, the present understanding of the neurophysiological basis of motion sickness is far from complete. No sensory conflict neuron or process has yet been physiologically identified. To what extent can the existing theory be reconciled with current knowledge of the physiology and pharmacology of nausea and vomiting. The stimuli which causes sickness, synthesizes a contemporary Observer Theory view of the Sensory Conflict hypothesis are reviewed, and a revised model for the dynamic coupling between the putative conflict signals and nausea magnitude estimates is presented. The use of quantitative models for sensory conflict offers a possible new approach to improving the design of visual and motion systems for flight simulators and other virtual environment display systems.

  12. Chinese hyper-susceptibility to vection-induced motion sickness

    NASA Technical Reports Server (NTRS)

    Stern, Robert M.; Hu, Senqi; Leblanc, Ree; Koch, Kenneth L.

    1993-01-01

    Little is known about the factors that control individual differences in susceptible to motion sickness. A serendipitous observation in our laboratory that most Chinese subjects become motion sick prompted this study. We used a rotating optokinetic drum to provoke motion sickness and compared gastric responses and symptom reports of Chinese, European-American, and African-American subjects. There was no difference in the responses of European-American and African-American subjects; however, Chinese subjects showed significantly greater disturbances in gastric activity and reported significantly more severe symptoms. We suggest that this hypersusceptibility presents a natural model for the study of physiological mechanisms of nausea and other symptoms of motion sickness.

  13. Simulations with current constraints of ELM-induced tungsten melt motion in ASDEX Upgrade

    NASA Astrophysics Data System (ADS)

    Thorén, E.; Bazylev, B.; Ratynskaia, S.; Tolias, P.; Krieger, K.; Pitts, R. A.; Pestchanyi, S.; Komm, M.; Sieglin, B.; the EUROfusion MST1 Team; the ASDEX Upgrade Team

    2017-12-01

    Melt motion simulations of recent ASDEX Upgrade experiments on transient-induced melting of a tungsten leading edge during ELMing H-mode are performed with the incompressible fluid dynamics code MEMOS 3D. The total current flowing through the sample was measured in these experiments providing an important constraint for the simulations since thermionic emission is considered to be responsible for the replacement current driving melt motion. To allow for a reliable comparison, the description of the space-charge limited regime of thermionic emission has been updated in the code. The effect of non-periodic aspects of the spatio-temporal heat flux in the temperature distribution and melt characteristics as well as the importance of current limitation are investigated. The results are compared with measurements of the total current and melt profile.

  14. Correlation-based motion vector processing with adaptive interpolation scheme for motion-compensated frame interpolation.

    PubMed

    Huang, Ai-Mei; Nguyen, Truong

    2009-04-01

    In this paper, we address the problems of unreliable motion vectors that cause visual artifacts but cannot be detected by high residual energy or bidirectional prediction difference in motion-compensated frame interpolation. A correlation-based motion vector processing method is proposed to detect and correct those unreliable motion vectors by explicitly considering motion vector correlation in the motion vector reliability classification, motion vector correction, and frame interpolation stages. Since our method gradually corrects unreliable motion vectors based on their reliability, we can effectively discover the areas where no motion is reliable to be used, such as occlusions and deformed structures. We also propose an adaptive frame interpolation scheme for the occlusion areas based on the analysis of their surrounding motion distribution. As a result, the interpolated frames using the proposed scheme have clearer structure edges and ghost artifacts are also greatly reduced. Experimental results show that our interpolated results have better visual quality than other methods. In addition, the proposed scheme is robust even for those video sequences that contain multiple and fast motions.

  15. Interactions between radiation and amphetamine in taste aversion learning and the role of the area postrema in amphetamine-induced conditioned taste aversions

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

    Rabin, B.M.; Hunt, W.A.; Lee, J.

    1987-08-01

    Three experiments were run to assess the role of the area postrema in taste aversion learning resulting from combined treatment with subthreshold unconditioned stimuli and in the acquisition of an amphetamine-induced taste aversion. In the first experiment, it was shown that combined treatment with subthreshold radiation (15 rad) and subthreshold amphetamine (0.5 mg/kg, IP) resulted in the acquisition of a taste aversion. The second experiment showed that lesions of the area postrema blocked taste aversion learning produced by two subthreshold doses of amphetamine. In the third experiment, which looked at the dose-response curve for amphetamine-induced taste aversion learning in intactmore » rats and rats with area postrema lesions, it was shown that both groups of rats acquired taste aversions following injection of amphetamine, although the rats with lesions showed a less severe aversion than the intact rats. The results are interpreted as indicating that amphetamine-induced taste aversion learning may involve area postrema-mediated mechanisms, particularly at the lower doses, but that an intact area postrema is not a necessary condition for the acquisition of an amphetamine-induced taste aversion.« less

  16. Sphingosine-1-phosphate mediates epidermal growth factor-induced muscle satellite cell activation

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

    Nagata, Yosuke, E-mail: cynagata@mail.ecc.u-tokyo.ac.jp; Ohashi, Kazuya; Wada, Eiji

    2014-08-01

    Skeletal muscle can regenerate repeatedly due to the presence of resident stem cells, called satellite cells. Because satellite cells are usually quiescent, they must be activated before participating in muscle regeneration in response to stimuli such as injury, overloading, and stretch. Although satellite cell activation is a crucial step in muscle regeneration, little is known of the molecular mechanisms controlling this process. Recent work showed that the bioactive lipid sphingosine-1-phosphate (S1P) plays crucial roles in the activation, proliferation, and differentiation of muscle satellite cells. We investigated the role of growth factors in S1P-mediated satellite cell activation. We found that epidermalmore » growth factor (EGF) in combination with insulin induced proliferation of quiescent undifferentiated mouse myoblast C2C12 cells, which are also known as reserve cells, in serum-free conditions. Sphingosine kinase activity increased when reserve cells were stimulated with EGF. Treatment of reserve cells with the D-erythro-N,N-dimethylsphingosine, Sphingosine Kinase Inhibitor, or siRNA duplexes specific for sphingosine kinase 1, suppressed EGF-induced C2C12 activation. We also present the evidence showing the S1P receptor S1P2 is involved in EGF-induced reserve cell activation. Moreover, we demonstrated a combination of insulin and EGF promoted activation of satellite cells on single myofibers in a manner dependent on SPHK and S1P2. Taken together, our observations show that EGF-induced satellite cell activation is mediated by S1P and its receptor. - Highlights: • EGF in combination with insulin induces proliferation of quiescent C2C12 cells. • Sphingosine kinase activity increases when reserve cells are stimulated with EGF. • EGF-induced activation of reserve cells is dependent on sphingosine kinase and ERK. • The S1P receptor S1P2 is involved in EGF-induced reserve cell activation. • EGF-induced reserve cell activation is mediated by S1P and

  17. Ferroelectric domain wall motion induced by polarized light

    PubMed Central

    Rubio-Marcos, Fernando; Del Campo, Adolfo; Marchet, Pascal; Fernández, Jose F.

    2015-01-01

    Ferroelectric materials exhibit spontaneous and stable polarization, which can usually be reoriented by an applied external electric field. The electrically switchable nature of this polarization is at the core of various ferroelectric devices. The motion of the associated domain walls provides the basis for ferroelectric memory, in which the storage of data bits is achieved by driving domain walls that separate regions with different polarization directions. Here we show the surprising ability to move ferroelectric domain walls of a BaTiO3 single crystal by varying the polarization angle of a coherent light source. This unexpected coupling between polarized light and ferroelectric polarization modifies the stress induced in the BaTiO3 at the domain wall, which is observed using in situ confocal Raman spectroscopy. This effect potentially leads to the non-contact remote control of ferroelectric domain walls by light. PMID:25779918

  18. Human-motion energy harvester for autonomous body area sensors

    NASA Astrophysics Data System (ADS)

    Geisler, M.; Boisseau, S.; Perez, M.; Gasnier, P.; Willemin, J.; Ait-Ali, I.; Perraud, S.

    2017-03-01

    This paper reports on a method to optimize an electromagnetic energy harvester converting the low-frequency body motion and aimed at powering wireless body area sensors. This method is based on recorded accelerations, and mechanical and transduction models that enable an efficient joint optimization of the structural parameters. An optimized prototype of 14.8 mmØ × 52 mm, weighting 20 g, has generated up to 4.95 mW in a resistive load when worn at the arm during a run, and 6.57 mW when hand-shaken. Among the inertial electromagnetic energy harvesters reported so far, this one exhibits one of the highest power densities (up to 730 μW cm-3). The energy harvester was finally used to power a bluetooth low energy wireless sensor node with accelerations measurements at 25 Hz.

  19. ATP mediates flow-induced NO production in thick ascending limbs

    PubMed Central

    Hong, Nancy J.; Garvin, Jeffrey L.

    2012-01-01

    Mechanical stimulation caused by increasing flow induces nucleotide release from many cells. Luminal flow and extracellular ATP stimulate production of nitric oxide (NO) in thick ascending limbs. However, the factors that mediate flow-induced NO production are unknown. We hypothesized that luminal flow stimulates thick ascending limb NO production via ATP. We measured NO in isolated, perfused rat thick ascending limbs using the fluorescent dye DAF FM. The rate of increase in dye fluorescence reflects NO accumulation. Increasing luminal flow from 0 to 20 nl/min stimulated NO production from 17 ± 16 to 130 ± 37 arbitrary units (AU)/min (P < 0.02). Increasing flow from 0 to 20 nl/min raised ATP release from 4 ± 1 to 21 ± 6 AU/min (P < 0.04). Hexokinase (10 U/ml) plus glucose, which consumes ATP, completely prevented the measured increase in ATP. Luminal flow did not increase NO production in the presence of luminal and basolateral hexokinase (10 U/ml). When flow was increased with the ATPase apyrase in both luminal and basolateral solutions (5 U/ml), NO levels did not change significantly. The P2 receptor antagonist suramin (300 μmol/l) reduced flow-induced NO production by 83 ± 25% (P < 0.03) when added to both and basolateral sides. Luminal hexokinase decreased flow-induced NO production from 205.6 ± 85.6 to 36.6 ± 118.6 AU/min (P < 0.02). Basolateral hexokinase also reduced flow-induced NO production. The P2X receptor-selective antagonist NF023 (200 μmol/l) prevented flow-induced NO production when added to the basolateral side but not the luminal side. We conclude that ATP mediates flow-induced NO production in the thick ascending limb likely via activation of P2Y receptors in the luminal and P2X receptors in the basolateral membrane. PMID:22496412

  20. Caspase-8-mediated intracellular acidification precedes mitochondrial dysfunction in somatostatin-induced apoptosis.

    PubMed

    Liu, D; Martino, G; Thangaraju, M; Sharma, M; Halwani, F; Shen, S H; Patel, Y C; Srikant, C B

    2000-03-31

    Activation of initiator and effector caspases, mitochondrial changes involving a reduction in its membrane potential and release of cytochrome c (cyt c) into the cytosol, are characteristic features of apoptosis. These changes are associated with cell acidification in some models of apoptosis. The hierarchical relationship between these events has, however, not been deciphered. We have shown that somatostatin (SST), acting via the Src homology 2 bearing tyrosine phosphatase SHP-1, exerts cytotoxic action in MCF-7 cells, and triggers cell acidification and apoptosis. We investigated the temporal sequence of apoptotic events linking caspase activation, acidification, and mitochondrial dysfunction in this system and report here that (i) SHP-1-mediated caspase-8 activation is required for SST-induced decrease in pH(i). (ii) Effector caspases are induced only when there is concomitant acidification. (iii) Decrease in pH(i) is necessary to induce reduction in mitochondrial membrane potential, cyt c release and caspase-9 activation and (iv) depletion of ATP ablates SST-induced cyt c release and caspase-9 activation, but not its ability to induce effector caspases and apoptosis. These data reveal that SHP-1-/caspase-8-mediated acidification occurs at a site other than the mitochondrion and that SST-induced apoptosis is not dependent on disruption of mitochondrial function and caspase-9 activation.

  1. Using structures of the August 24, 2016 Amatrice earthquake affected area as seismoscopes for assessing ground motion characteristics and parameters of the main shock and its largest aftershocks

    NASA Astrophysics Data System (ADS)

    Carydis, Panayotis; Lekkas, Efthymios; Mavroulis, Spyridon

    2017-04-01

    On August 24, 2016 an Mw 6.0 earthquake struck Central Apennines (Italy) resulting in 299 fatalities, 388 injuries and about 3000 homeless in Amatrice wider area. Normal faulting surface ruptures along the western slope of Mt Vettore along with provided focal mechanisms demonstrated a NW-SE striking and SE dipping causative normal fault. The dominant building types in the affected area are unreinforced masonry (URM) and reinforced concrete (RC) buildings. Based on our macroseismic survey in the affected area immediately after the earthquake, RC buildings suffered non-structural damage including horizontal cracking of infill and internal partition walls, detachment of infill walls from the surrounding RC frame and detachment of large plaster pieces from infill walls as well as structural damage comprising soft story failure, symmetrical buckling of rods, compression damage at midheight of columns and bursting of over-stressed columns resulting in partial or total collapse. Damage in RC buildings was due to poor quality of concrete, inadequacy of reinforcement, inappropriate foundation close to the edge of slopes leading to differential settlements, poor workmanship and the destructive effect of vertical ground motions. Damage in URM buildings ranged from cracks and detachment of large plaster pieces from load-bearing walls to destruction due to poor workmanship with randomly placed materials bound by low-strength mortars, the effect of the vertical ground motion, inadequate repair and/or strengthening after previous earthquakes as well as inadequate interventions, additions and extensions to older URM buildings. During field surveying, the authors had the opportunity to observe damage induced not only by the main shock but also by its largest aftershocks (Mw 4.5-5.3) during the first three days of the aftershock sequence (August 24-26). Bearing in mind that: (a) soil conditions in foundations of the affected villages were more or less similar, (b) building damage

  2. Processing Motion Signals in Complex Environments

    NASA Technical Reports Server (NTRS)

    Verghese, Preeti

    2000-01-01

    Motion information is critical for human locomotion and scene segmentation. Currently we have excellent neurophysiological models that are able to predict human detection and discrimination of local signals. Local motion signals are insufficient by themselves to guide human locomotion and to provide information about depth, object boundaries and surface structure. My research is aimed at understanding the mechanisms underlying the combination of motion signals across space and time. A target moving on an extended trajectory amidst noise dots in Brownian motion is much more detectable than the sum of signals generated by independent motion energy units responding to the trajectory segments. This result suggests that facilitation occurs between motion units tuned to similar directions, lying along the trajectory path. We investigated whether the interaction between local motion units along the motion direction is mediated by contrast. One possibility is that contrast-driven signals from motion units early in the trajectory sequence are added to signals in subsequent units. If this were the case, then units later in the sequence would have a larger signal than those earlier in the sequence. To test this possibility, we compared contrast discrimination thresholds for the first and third patches of a triplet of sequentially presented Gabor patches, aligned along the motion direction. According to this simple additive model, contrast increment thresholds for the third patch should be higher than thresholds for the first patch.The lack of a measurable effect on contrast thresholds for these various manipulations suggests that the pooling of signals along a trajectory is not mediated by contrast-driven signals. Instead, these results are consistent with models that propose that the facilitation of trajectory signals is achieved by a second-level network that chooses the strongest local motion signals and combines them if they occur in a spatio-temporal sequence consistent

  3. Investigating the possible effect of electrode support structure on motion artifact in wearable bioelectric signal monitoring.

    PubMed

    Cömert, Alper; Hyttinen, Jari

    2015-05-15

    With advances in technology and increasing demand, wearable biosignal monitoring is developing and new applications are emerging. One of the main challenges facing the widespread use of wearable monitoring systems is the motion artifact. The sources of the motion artifact lie in the skin-electrode interface. Reducing the motion and deformation at this interface should have positive effects on signal quality. In this study, we aim to investigate whether the structure supporting the electrode can be designed to reduce the motion artifact with the hypothesis that this can be achieved by stabilizing the skin deformations around the electrode. We compare four textile electrodes with different support structure designs: a soft padding larger than the electrode area, a soft padding larger than the electrode area with a novel skin deformation restricting design, a soft padding the same size as the electrode area, and a rigid support the same size as the electrode. With five subjects and two electrode locations placed over different kinds of tissue at various mounting forces, we simultaneously measured the motion artifact, a motion affected ECG, and the real-time skin-electrode impedance during the application of controlled motion to the electrodes. The design of the electrode support structure has an effect on the generated motion artifact; good design with a skin stabilizing structure makes the electrodes physically more motion artifact resilient, directly affecting signal quality. Increasing the applied mounting force shows a positive effect up to 1,000 gr applied force. The properties of tissue under the electrode are an important factor in the generation of the motion artifact and the functioning of the electrodes. The relationship of motion artifact amplitude to the electrode movement magnitude is seen to be linear for smaller movements. For larger movements, the increase of motion generated a disproportionally larger artifact. The motion artifact and the induced

  4. Hindbrain GLP-1 receptor mediation of cisplatin-induced anorexia and nausea.

    PubMed

    De Jonghe, Bart C; Holland, Ruby A; Olivos, Diana R; Rupprecht, Laura E; Kanoski, Scott E; Hayes, Matthew R

    2016-01-01

    While chemotherapy-induced nausea and vomiting are clinically controlled in the acute (<24 h) phase following treatment, the anorexia, nausea, fatigue, and other illness-type behaviors during the delayed phase (>24 h) of chemotherapy are largely uncontrolled. As the hindbrain glucagon-like peptide-1 (GLP-1) system contributes to energy balance and mediates aversive and stressful stimuli, here we examine the hypothesis that hindbrain GLP-1 signaling mediates aspects of chemotherapy-induced nausea and reductions in feeding behavior in rats. Specifically, hindbrain GLP-1 receptor (GLP-1R) blockade, via 4th intracerebroventricular (ICV) exendin-(9-39) injections, attenuates the anorexia, body weight reduction, and pica (nausea-induced ingestion of kaolin clay) elicited by cisplatin chemotherapy during the delayed phase (48 h) of chemotherapy-induced nausea. Additionally, the present data provide evidence that the central GLP-1-producing preproglucagon neurons in the nucleus tractus solitarius (NTS) of the caudal brainstem are activated by cisplatin during the delayed phase of chemotherapy-induced nausea, as cisplatin led to a significant increase in c-Fos immunoreactivity in NTS GLP-1-immunoreactive neurons. These data support a growing body of literature suggesting that the central GLP-1 system may be a potential pharmaceutical target for adjunct anti-emetics used to treat the delayed-phase of nausea and emesis, anorexia, and body weight loss that accompany chemotherapy treatments. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Ground motions from induced earthquakes in Oklahoma and Kansas and the implications for seismic hazard

    NASA Astrophysics Data System (ADS)

    Moschetti, M. P.; Rennolet, S.; Thompson, E.; Yeck, W.; McNamara, D. E.; Herrmann, R. B.; Powers, P.; Hoover, S. M.

    2016-12-01

    Recent efforts to characterize the seismic hazard resulting from increased seismicity rates in Oklahoma and Kansas highlight the need for a regionalized ground motion characterization. To support these efforts, we measure and compile strong ground motions and compare these average ground motions intensity measures (IMs) with existing ground motion prediction equations (GMPEs). IMs are computed for available broadband and strong-motion records from M≥3 earthquakes occurring January 2009-April 2016, using standard strong motion processing guidelines. We verified our methods by comparing results from specific earthquakes to other standard procedures such as the USGS Shakemap system. The large number of records required an automated processing scheme, which was complicated by the extremely high rate of small-magnitude earthquakes 2014-2016. Orientation-independent IMs include peak ground motions (acceleration and velocity) and pseudo-spectral accelerations (5 percent damping, 0.1-10 s period). Metadata for the records included relocated event hypocenters. The database includes more than 160,000 records from about 3200 earthquakes. Estimates of the mean and standard deviation of the IMs are computed by distance binning at intervals of 2 km. Mean IMs exhibit a clear break in geometrical attenuation at epicentral distances of about 50-70 km, which is consistent with previous studies in the CEUS. Comparisons of these ground motions with modern GMPEs provide some insight into the relative IMs of induced earthquakes in Oklahoma and Kansas relative to the western U.S. and the central and eastern U.S. The site response for these stations is uncertain because very little is known about shallow seismic velocity in the region, and we make no attempt to correct observed IMs to a reference site conditions. At close distances, the observed IMs are lower than the predictions of the seed GMPEs of the NGA-East project (and about consistent with NGA-West-2 ground motions). This ground

  6. Interfractional variability of respiration-induced esophageal tumor motion quantified using fiducial markers and four-dimensional cone-beam computed tomography.

    PubMed

    Jin, Peng; Hulshof, Maarten C C M; van Wieringen, Niek; Bel, Arjan; Alderliesten, Tanja

    2017-07-01

    To investigate the interfractional variability of respiration-induced esophageal tumor motion using fiducial markers and four-dimensional cone-beam computed tomography (4D-CBCT) and assess if a 4D-CT is sufficient for predicting the motion during the treatment. Twenty-four patients with 63 markers visible in the retrospectively reconstructed 4D-CBCTs were included. For each marker, we calculated the amplitude and trajectory of the respiration-induced motion. Possible time trends of the amplitude over the treatment course and the interfractional variability of amplitudes and trajectory shapes were assessed. Further, the amplitudes measured in the 4D-CT were compared to those in the 4D-CBCTs. The amplitude was largest in the cranial-caudal direction of the distal esophagus (mean: 7.1mm) and proximal stomach (mean: 7.8mm). No time trend was observed in the amplitude over the treatment course. The interfractional variability of amplitudes and trajectory shapes was limited (mean: ≤1.4mm). Moreover, small and insignificant deviation was found between the amplitudes quantified in the 4D-CT and in the 4D-CBCT (mean absolute difference: ≤1.0mm). The limited interfractional variability of amplitudes and trajectory shapes and small amplitude difference between 4D-CT-based and 4D-CBCT-based measurements imply that a single 4D-CT would be sufficient for predicting the respiration-induced esophageal tumor motion during the treatment course. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. A slowly moving foreground can capture an observer's self-motion--a report of a new motion illusion: inverted vection.

    PubMed

    Nakamura, S; Shimojo, S

    2000-01-01

    We investigated interactions between foreground and background stimuli during visually induced perception of self-motion (vection) by using a stimulus composed of orthogonally moving random-dot patterns. The results indicated that, when the foreground moves with a slower speed, a self-motion sensation with a component in the same direction as the foreground is induced. We named this novel component of self-motion perception 'inverted vection'. The robustness of inverted vection was confirmed using various measures of self-motion sensation and under different stimulus conditions. The mechanism underlying inverted vection is discussed with regard to potentially relevant factors, such as relative motion between the foreground and background, and the interaction between the mis-registration of eye-movement information and self-motion perception.

  8. Motion direction discrimination training reduces perceived motion repulsion.

    PubMed

    Jia, Ke; Li, Sheng

    2017-04-01

    Participants often exaggerate the perceived angular separation between two simultaneously presented motion stimuli, which is referred to as motion repulsion. The overestimation helps participants differentiate between the two superimposed motion directions, yet it causes the impairment of direction perception. Since direction perception can be refined through perceptual training, we here attempted to investigate whether the training of a direction discrimination task changes the amount of motion repulsion. Our results showed a direction-specific learning effect, which was accompanied by a reduced amount of motion repulsion both for the trained and the untrained directions. The reduction of the motion repulsion disappeared when the participants were trained on a luminance discrimination task (control experiment 1) or a speed discrimination task (control experiment 2), ruling out any possible interpretation in terms of adaptation or training-induced attentional bias. Furthermore, training with a direction discrimination task along a direction 150° away from both directions in the transparent stimulus (control experiment 3) also had little effect on the amount of motion repulsion, ruling out the contribution of task learning. The changed motion repulsion observed in the main experiment was consistent with the prediction of the recurrent model of perceptual learning. Therefore, our findings demonstrate that training in direction discrimination can benefit the precise direction perception of the transparent stimulus and provide new evidence for the recurrent model of perceptual learning.

  9. Insulin induces long-term depression of VTA dopamine neurons via an endocannabinoid-mediated mechanism

    PubMed Central

    Labouèbe, Gwenaël; Liu, Shuai; Dias, Carine; Zou, Haiyan; Wong, Jovi C.Y.; Karunakaran, Subashini; Clee, Susanne M.; Phillips, Anthony; Boutrel, Benjamin; Borgland, Stephanie L.

    2014-01-01

    The prevalence of obesity has drastically increased over the last few decades. Exploration into how hunger and satiety signals influence the reward system can help us to understand non-homeostatic mechanisms of feeding. Evidence suggests that insulin may act in the ventral tegmental area (VTA), a critical site for reward-seeking behavior, to suppress feeding. However, the neural mechanisms underlying insulin effects in the VTA remain unknown. We demonstrate that insulin, a circulating catabolic peptide that inhibits feeding, can induce a long-term depression (LTD) of excitatory synapses onto VTA dopamine neurons. This effect requires endocannabinoid-mediated presynaptic inhibition of glutamate release. Furthermore, after a sweetened high fat meal, which elevates endogenous insulin levels, insulin-induced LTD is occluded. Finally, insulin in the VTA reduces food anticipatory behavior and conditioned place preference for food. Taken together, these results suggest that insulin in the VTA suppresses excitatory synaptic transmission and reduces salience of food-related cues. PMID:23354329

  10. Mental Rotation Meets the Motion Aftereffect: The Role of hV5/MT+ in Visual Mental Imagery

    ERIC Educational Resources Information Center

    Seurinck, Ruth; de Lange, Floris P.; Achten, Erik; Vingerhoets, Guy

    2011-01-01

    A growing number of studies show that visual mental imagery recruits the same brain areas as visual perception. Although the necessity of hV5/MT+ for motion perception has been revealed by means of TMS, its relevance for motion imagery remains unclear. We induced a direction-selective adaptation in hV5/MT+ by means of an MAE while subjects…

  11. High-Resolution Multi-Shot Spiral Diffusion Tensor Imaging with Inherent Correction of Motion-Induced Phase Errors

    PubMed Central

    Truong, Trong-Kha; Guidon, Arnaud

    2014-01-01

    Purpose To develop and compare three novel reconstruction methods designed to inherently correct for motion-induced phase errors in multi-shot spiral diffusion tensor imaging (DTI) without requiring a variable-density spiral trajectory or a navigator echo. Theory and Methods The first method simply averages magnitude images reconstructed with sensitivity encoding (SENSE) from each shot, whereas the second and third methods rely on SENSE to estimate the motion-induced phase error for each shot, and subsequently use either a direct phase subtraction or an iterative conjugate gradient (CG) algorithm, respectively, to correct for the resulting artifacts. Numerical simulations and in vivo experiments on healthy volunteers were performed to assess the performance of these methods. Results The first two methods suffer from a low signal-to-noise ratio (SNR) or from residual artifacts in the reconstructed diffusion-weighted images and fractional anisotropy maps. In contrast, the third method provides high-quality, high-resolution DTI results, revealing fine anatomical details such as a radial diffusion anisotropy in cortical gray matter. Conclusion The proposed SENSE+CG method can inherently and effectively correct for phase errors, signal loss, and aliasing artifacts caused by both rigid and nonrigid motion in multi-shot spiral DTI, without increasing the scan time or reducing the SNR. PMID:23450457

  12. Perceived spatial displacement of motion-defined contours in peripheral vision.

    PubMed

    Fan, Zhao; Harris, John

    2008-12-01

    The perceived displacement of motion-defined contours in peripheral vision was examined in four experiments. In Experiment 1, in line with Ramachandran and Anstis' finding [Ramachandran, V. S., & Anstis, S. M. (1990). Illusory displacement of equiluminous kinetic edges. Perception, 19, 611-616], the border between a field of drifting dots and a static dot pattern was apparently displaced in the same direction as the movement of the dots. When a uniform dark area was substituted for the static dots, a similar displacement was found, but this was smaller and statistically insignificant. In Experiment 2, the border between two fields of dots moving in opposite directions was displaced in the direction of motion of the dots in the more eccentric field, so that the location of a boundary defined by a diverging pattern is perceived as more eccentric, and that defined by a converging as less eccentric. Two explanations for this effect (that the displacement reflects a greater weight given to the more eccentric motion, or that the region containing stronger centripetal motion components expands perceptually into that containing centrifugal motion) were tested in Experiment 3, by varying the velocity of the more eccentric region. The results favoured the explanation based on the expansion of an area in centripetal motion. Experiment 4 showed that the difference in perceived location was unlikely to be due to differences in the discriminability of contours in diverging and converging patterns, and confirmed that this effect is due to a difference between centripetal and centrifugal motion rather than motion components in other directions. Our result provides new evidence for a bias towards centripetal motion in human vision, and suggests that the direction of motion-induced displacement of edges is not always in the direction of an adjacent moving pattern.

  13. Cold Active Motion: How Time-Independent Disorder Affects the Motion of Self-Propelled Agents

    NASA Astrophysics Data System (ADS)

    Peruani, Fernando; Aranson, Igor S.

    2018-06-01

    Assemblages of self-propelled particles, often termed active matter, exhibit collective behavior due to competition between neighbor alignment and noise-induced decoherence. However, very little is known of how the quenched (i.e., time-independent) disorder impacts active motion. Here we report on the effects of quenched disorder on the dynamics of self-propelled point particles. We identified three major types of quenched disorder relevant in the context of active matter: random torque, force, and stress. We demonstrate that even in the absence of external fluctuations ("cold active matter"), quenched disorder results in nontrivial dynamic phases not present in their "hot" counterpart. In particular, by analyzing when the equations of motion exhibit a Hamiltonian structure and when attractors may be present, we identify in which scenarios particle trapping, i.e., the asymptotic convergence of particle trajectories to bounded areas in space ("traps"), can and cannot occur. Our study provides new fundamental insights into active systems realized by self-propelled particles on natural and synthetic disordered substrates.

  14. Full Range of Motion Induces Greater Muscle Damage Than Partial Range of Motion in Elbow Flexion Exercise With Free Weights.

    PubMed

    Baroni, Bruno M; Pompermayer, Marcelo G; Cini, Anelize; Peruzzolo, Amanda S; Radaelli, Régis; Brusco, Clarissa M; Pinto, Ronei S

    2017-08-01

    Baroni, BM, Pompermayer, MG, Cini, A, Peruzzolo, AS, Radaelli, R, Brusco, CM, and Pinto, RS. Full range of motion induces greater muscle damage than partial range of motion in elbow flexion exercise with free weights. J Strength Cond Res 31(8): 2223-2230, 2017-Load and range of motion (ROM) applied in resistance training (RT) affect the muscle damage magnitude and the recovery time-course. Because exercises performed with partial ROM allow a higher load compared with those with full ROM, this study investigated the acute effect of a traditional RT exercise using full ROM or partial ROM on muscle damage markers. Fourteen healthy men performed 4 sets of 10 concentric-eccentric repetitions of unilateral elbow flexion on the Scott bench. Arms were randomly assigned to partial-ROM (50-100°) and full-ROM (0-130°) conditions, and load was determined as 80% of 1 repetition maximum (1RM) in the full- and partial-ROM tests. Muscle damage markers were assessed preexercise, immediately, and 24, 48, and 72 hours after exercise. Primary outcomes were peak torque, muscle soreness during palpation and elbow extension, arm circumference, and joint ROM. The load lifted in the partial-ROM condition (1RM = 19.1 ± 3.0 kg) was 40 ± 18% higher compared with the full-ROM condition (1RM = 13.7 ± 2.2 kg). Seventy-two hours after exercise, the full-ROM condition led to significant higher soreness sensation during elbow extension (1.3-4.1 cm vs. 1.0-1.9 cm) and smaller ROM values (97.5-106.1° vs. 103.6-115.7°). Peak torque, soreness from palpation, and arm circumference were statistically similar between conditions, although mean values in all time points of these outcomes have suggested more expressive muscle damage for the full-ROM condition. In conclusion, elbow flexion exercise with full ROM seems to induce greater muscle damage than partial-ROM exercises, even though higher absolute load was achieved with partial ROM.

  15. Towards a wire-mediated coupling of trapped ions

    NASA Astrophysics Data System (ADS)

    Clark, Robert; Lee, Tony; Daniilidis, Nikos; Sankaranarayanan, S.; Häffner, Hartmut

    2008-03-01

    Most schemes for ion trap quantum computation rely upon the exchange of information between ion-qubits in the same trap region, mediated by their shared vibrational mode. An alternative way to achieve this coupling is via the image charges induced in a conducting wire that connects different traps. This was shown to be theoretically possible by Heinzen and Wineland in 1990, but some important practical questions have remained unaddressed. Among these are how the presence of such a wire modifies the motional frequencies and heating rates of trapped ions. We thus have realized this system as a 1 mm-scale planar segmented rf ion trap combined with an electrically floating gold wire of 25 microns diameter and length 1 cm. This wire is placed close to trapped ions using a set of piezoelectric nanopositioners. We present here experimental measurements of the motional frequencies and heating rates of a single trapped calcium ion as the wire is moved from 3.0 mm to 0.2 mm away from the ion. We discuss the implications of these results for achieving wire-mediated coupling in the present apparatus, as well as in future improved setups.

  16. Heptachlor induced mitochondria-mediated cell death via impairing electron transport chain complex III

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

    Hong, Seokheon; Kim, Joo Yeon; Hwang, Joohyun

    Highlights: •Heptachlor inhibited mitochondrial electron transport chain complex III activity. •Heptachlor promoted generation of reactive oxygen species. •Heptachlor induced Bax activation. •Heptachlor induced mitochondria-mediated and caspase-dependent apoptosis. -- Abstract: Environmental toxins like pesticides have been implicated in the pathogenesis of Parkinson’s disease (PD). Epidemiological studies suggested that exposures to organochlorine pesticides have an association with an increased PD risk. In the present study, we examined the mechanism of toxicity induced by an organochlorine pesticide heptachlor. In a human dopaminergic neuroblastoma SH-SY5Y cells, heptachlor induced both morphological and functional damages in mitochondria. Interestingly, the compound inhibited mitochondrial electron transport chain complexmore » III activity. Rapid generation of reactive oxygen species and the activation of Bax were then detected. Subsequently, mitochondria-mediated, caspase-dependent apoptosis followed. Our results raise a possibility that an organochlorine pesticide heptachlor can act as a neurotoxicant associated with PD.« less

  17. Representation of particle motion in the auditory midbrain of a developing anuran.

    PubMed

    Simmons, Andrea Megela

    2015-07-01

    In bullfrog tadpoles, a "deaf period" of lessened responsiveness to the pressure component of sounds, evident during the end of the late larval period, has been identified in the auditory midbrain. But coding of underwater particle motion in the vestibular medulla remains stable over all of larval development, with no evidence of a "deaf period." Neural coding of particle motion in the auditory midbrain was assessed to determine if a "deaf period" for this mode of stimulation exists in this brain area in spite of its absence from the vestibular medulla. Recording sites throughout the developing laminar and medial principal nuclei show relatively stable thresholds to z-axis particle motion, up until the "deaf period." Thresholds then begin to increase from this point up through the rest of metamorphic climax, and significantly fewer responsive sites can be located. The representation of particle motion in the auditory midbrain is less robust during later compared to earlier larval stages, overlapping with but also extending beyond the restricted "deaf period" for pressure stimulation. The decreased functional representation of particle motion in the auditory midbrain throughout metamorphic climax may reflect ongoing neural reorganization required to mediate the transition from underwater to amphibious life.

  18. Brief report: altered horizontal binding of single dots to coherent motion in autism.

    PubMed

    David, Nicole; Rose, Michael; Schneider, Till R; Vogeley, Kai; Engel, Andreas K

    2010-12-01

    Individuals with autism often show a fragmented way of perceiving their environment, suggesting a disorder of information integration, possibly due to disrupted communication between brain areas. We investigated thirteen individuals with high-functioning autism (HFA) and thirteen healthy controls using the metastable motion quartet, a stimulus consisting of two dots alternately presented at four locations of a hypothetical square, thereby inducing an apparent motion percept. This percept is vertical or horizontal, the latter requiring binding of motion signals across cerebral hemispheres. Decreasing the horizontal distance between dots could facilitate horizontal percepts. We found evidence for altered horizontal binding in HFA: Individuals with HFA needed stronger facilitation to experience horizontal motion. These data are interpreted in light of reduced cross-hemispheric communication.

  19. Thermal-induced domain wall motion of tip-inverted micro/nanodomains in near-stoichiometric LiNbO3 crystals

    NASA Astrophysics Data System (ADS)

    Liu, X. Y.; Kitamura, K.; Liu, Y. M.; Ohuchi, F. S.; Li, J. Y.

    2011-09-01

    Thermal-induced domain wall motion of tip-inverted micro/nanodomains in near-stoichiometric LiNbO3 single crystals was investigated using piezoresponse force microscopy (PFM). The domain wall motion was observed in PFM phase and amplitude images at room temperature after the sample was subjected to a thermal process at a heating temperature higher than 100 °C. In hexagonal domains with only y walls, predetermined nucleation with layer-by-layer growth is the main mechanism for the domain wall motion. In the domains composed of both x walls and y walls, the x walls are more mobile than the y walls, and the domain wall motion starts from the random nucleation of steps along the x walls that finally grow into y walls. The domain wall motion in the near-stoichiometric LiNbO3 crystal is attributed to the energy-preferable domain wall orientation, the pyroelectric effect, and the screening charge variation caused by the thermal process.

  20. Chk2 mediates RITA-induced apoptosis.

    PubMed

    de Lange, J; Verlaan-de Vries, M; Teunisse, A F A S; Jochemsen, A G

    2012-06-01

    Reactivation of the p53 tumor-suppressor protein by small molecules like Nutlin-3 and RITA (reactivation of p53 and induction of tumor cell apoptosis) is a promising strategy for cancer therapy. The molecular mechanisms involved in the responses to RITA remain enigmatic. Several groups reported the induction of a p53-dependent DNA damage response. Furthermore, the existence of a p53-dependent S-phase checkpoint has been suggested, involving the checkpoint kinase Chk1. We have recently shown synergistic induction of apoptosis by RITA in combination with Nutlin-3, and we observed concomitant Chk2 phosphorylation. Therefore, we investigated whether Chk2 contributes to the cellular responses to RITA. Strikingly, the induction of apoptosis seemed entirely Chk2 dependent. Transcriptional activity of p53 in response to RITA required the presence of Chk2. A partial rescue of apoptosis observed in Noxa knockdown cells emphasized the relevance of p53 transcriptional activity for RITA-induced apoptosis. In addition, we observed an early p53- and Chk2-dependent block of DNA replication upon RITA treatment. Replicating cells seemed more prone to entering RITA-induced apoptosis. Furthermore, the RITA-induced DNA damage response, which was not a secondary effect of apoptosis induction, was strongly attenuated in cells lacking p53 or Chk2. In conclusion, we identified Chk2 as an essential mediator of the cellular responses to RITA.

  1. IB4(+) nociceptors mediate persistent muscle pain induced by GDNF.

    PubMed

    Alvarez, Pedro; Chen, Xiaojie; Bogen, Oliver; Green, Paul G; Levine, Jon D

    2012-11-01

    Skeletal muscle is a well-known source of glial cell line-derived neurotrophic factor (GDNF), which can produce mechanical hyperalgesia. Since some neuromuscular diseases are associated with both increased release of GDNF and intense muscle pain, we explored the role of GDNF as an endogenous mediator in muscle pain. Intramuscularly injected GDNF induced a dose-dependent (0.1-10 ng/20 μl) persistent (up to 3 wk) mechanical hyperalgesia in the rat. Once hyperalgesia subsided, injection of prostaglandin E(2) at the site induced a prolonged mechanical hyperalgesia (>72 h) compared with naïve rats (<4 h; hyperalgesic priming). Selective neurotoxic destruction of IB4(+) nociceptors attenuated both GDNF hyperalgesia and hyperalgesic priming. Ergonomic muscular injury induced by eccentric exercise or mechanical vibration increased muscle GDNF levels at 24 h, a time point where rats also exhibited marked muscle hyperalgesia. Intrathecal antisense oligodeoxynucleotides to mRNA encoding GFRα1, the canonical binding receptor for GDNF, reversibly inhibited eccentric exercise- and mechanical vibration-induced muscle hyperalgesia. Finally, electrophysiological recordings from nociceptors innervating the gastrocnemius muscle in anesthetized rats, revealed significant increase in response to sustained mechanical stimulation after local GDNF injection. In conclusion, these data indicate that GDNF plays a role as an endogenous mediator in acute and induction of chronic muscle pain, an effect likely to be produced by GDNF action at GFRα1 receptors located in IB4(+) nociceptors.

  2. Analysis of intra-uterine fluid motion induced by uterine contractions.

    PubMed

    Eytan, O; Elad, D

    1999-03-01

    Evaluation of the fluid flow pattern in a non-pregnant uterus is important for understanding embryo transport in the uterus. Fertilization occurs in the fallopian tube and the embryo (fertilized ovum) enters the uterine cavity within 3 days of ovulation. In the uterus, the embryo is conveyed by the uterine fluid for another 3 to 4 days to a successful implantation site at the upper part of the uterus. Fluid movements within the uterus may be induced by several mechanisms, but they seem to be dominated by myometrial contractions. Intra-uterine fluid transport in a sagittal cross-section of the uterus was simulated by a model of wall-induced fluid motion within a two-dimensional channel. The time-dependent fluid pattern was studied by employing the lubrication theory. A comprehensive analysis of peristaltic transport resulting from symmetric and asymmetric contractions is presented for various displacement waves on the channel walls. The results provide information on the flow field and possible trajectories by which an embryo may be transported before implantation at the uterine wall.

  3. Vasopressin and motion sickness in cats

    NASA Technical Reports Server (NTRS)

    Fox, R. A.; Keil, L. C.; Daunton, N. G.; Crampton, G. H.; Lucot, J.

    1987-01-01

    Levels of arginine vasopressin (AVP) in blood plasma and cerebrospinal fluid (CSF) were measured in cats under several motion-sickness-inducing conditions. Plasma AVP increased significantly in both susceptible and resistant animals exposed to motion. When vomiting occurred, levels of plasma AVP were drmatically elevated (up to 27 times resting levels). There was no difference in resting levels of AVP of susceptible and resistant cats. Levels of CSF-AVP were not elevated immediately after vomiting, but the testing levels of CSF-AVP were lower in animals that vomited during motion than in those animals which did not vomit during motion. The results of these experiments show that changes in systemic AVP are directly related to vomiting induced by motion, however, CSF-AVP apparently does not change in association with vomiting. CSF-AVP does appear to be lower in animals that reach frank vomiting during motion stimulation than in animals which do not vomit.

  4. Pressure-overload-induced angiotensin-mediated early remodeling in mouse heart

    PubMed Central

    Kim, Jeremy H.; Jiang, Ya-Ping; Cohen, Ira S.; Lin, Richard Z.; Mathias, Richard T.

    2017-01-01

    Our previous work on angiotensin II-mediated electrical-remodeling in canine left ventricle, in connection with a long history of other studies, suggested the hypothesis: increases in mechanical load induce autocrine secretion of angiotensin II (A2), which coherently regulates a coterie of membrane ion transporters in a manner that increases contractility. However, the relation between load and A2 secretion was correlative. We subsequently showed a similar or identical system was present in murine heart. To investigate whether the relation between mechanical load and A2-mediated electrical remodeling was causal, we employed transverse aortic constriction in mice to subject the left ventricle to pressure overload for short-term (1 to 2 days) or long-term (1 to 2 weeks) periods. Heart-to-body weight ratios and cell capacitance measurements were used to determine hypertrophy. Whole-cell patch clamp recordings of the predominant repolarization currents Ito,fast and IK,slow were used to assess electrical remodeling. Hearts or myocytes subjected to long-term load displayed significant hypertrophy, which was not evident in short-term load. However, short-term load induced significant reductions in Ito,fast and IK,slow. Incubation of these myocytes with the angiotensin II type 1 receptor inhibitor saralasin for 2 hours restored Ito,fast and IK,slow to control levels. The number of Ito.fast or IK,slow channels did not change with A2 or long-term load, however the hypertrophic increase in membrane area reduced the current densities for both channels. For Ito,fast but not IK,slow there was an additional reduction that was reversed by inhibition of angiotensin receptors. These results suggest increased load activates an endogenous renin angiotensin system that initially reduces Ito,fast and IK,slow prior to the onset of hypertrophic growth. However, there are functional interactions between electrical and anatomical remodeling. First, hypertrophy tends to reduce all current

  5. An Inducible Endothelial Cell Surface Glycoprotein Mediates Melanoma Adhesion

    NASA Astrophysics Data System (ADS)

    Rice, G. Edgar; Bevilacqua, Michael P.

    1989-12-01

    Hematogenous metastasis requires the arrest and extravasation of blood-borne tumor cells, possibly involving direct adhesive interactions with vascular endothelium. Cytokine activation of cultured human endothelium increases adhesion of melanoma and carcinoma cell lines. An inducible 110-kD endothelial cell surface glycoprotein, designated INCAM-110, appears to mediate adhesion of melanoma cells. In addition, an inducible endothelial receptor for neutrophils, ELAM-1, supports the adhesion of a human colon carcinoma cell line. Thus, activation of vascular endothelium in vivo that results in increased expression of INCAM-110 and ELAM-1 may promote tumor cell adhesion and affect the incidence and distribution of metastases.

  6. The use of EEG to measure cerebral changes during computer-based motion-sickness-inducing tasks

    NASA Astrophysics Data System (ADS)

    Strychacz, Christopher; Viirre, Erik; Wing, Shawn

    2005-05-01

    Motion sickness (MS) is a stressor commonly attributed with causing serious navigational and performance errors. The distinct nature of MS suggests this state may have distinct neural markers distinguishable from other states known to affect performance (e.g., stress, fatigue, sleep deprivation, high workload). This pilot study used new high-resolution electro-encephalograph (EEG) technologies to identify distinct neuronal activation changes that occur during MS. Brain EEG activity was monitored while subjects performed a ball-tracking task and viewed stimuli on a projection screen intended to induce motion sickness/spatial disorientation. Results show the presence of EEG spectral changes in all subjects who developed motion sickness when compared to baseline levels. These changes included: 1) low frequency (1 to 10 Hz) changes that may reflect oculomotor movements rather than intra-cerebral sources; 2) increased spectral power across all frequencies (attributable to increased scalp conductivity related to sweating), 3) local increases of power spectra in the 20-50 Hz range (likely attributable to external muscles on the skull) and; 4) a central posterior (occipital) independent component that shows suppression of a 20 Hz peak in the MS condition when compared to baseline. Further research is necessary to refine neural markers, characterize their origin and physiology, to distinguish between motion sickness and other states and to enable markers to be used for operator state monitoring and the designing of interventions for motion sickness.

  7. 13 CFR 134.806 - Mediation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... attorney to serve as a mediator. If the parties reach a settlement through mediation, they may file a joint motion to dismiss the appeal based on that settlement. If the parties do not reach a settlement, the...

  8. Respiration Induced Heart Motion and Indications of Gated Delivery for Left-Sided Breast Irradiation

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

    Qi, X. Sharon, E-mail: xiangrong.qi@ucdenver.edu; Hu, Angela; Wang Kai

    Purpose: To investigate respiration-induced heart motion for left-sided breast irradiation using a four-dimensional computed tomography (4DCT) technique and to determine novel indications to assess heart motion and identify breast patients who may benefit from a gated treatment. Methods and Materials: Images of 4DCT acquired during free breathing for 20 left-sided breast cancer patients, who underwent whole breast irradiation with or without regional nodal irradiation, were analyzed retrospectively. Dose distributions were reconstructed in the phases of 0%, 20%, and 50%. The intrafractional heart displacement was measured in three selected transverse CT slices using D{sub LAD} (the distance from left ascending aortamore » to a fixed line [connecting middle point of sternum and the body] drawn on each slice) and maximum heart depth (MHD, the distance of the forefront of the heart to the line). Linear regression analysis was used to correlate these indices with mean heart dose and heart dose volume at different breathing phases. Results: Respiration-induced heart displacement resulted in observable variations in dose delivered to the heart. During a normal free-breathing cycle, heart-induced motion D{sub LAD} and MHD changed up to 9 and 11 mm respectively, resulting in up to 38% and 39% increases of mean doses and V{sub 25.2} for the heart. MHD and D{sub LAD} were positively correlated with mean heart dose and heart dose volume. Respiratory-adapted gated treatment may better spare heart and ipsilateral-lung compared with the conventional non-gated plan in a subset of patients with large D{sub LAD} or MHD variations. Conclusion: Proposed indices offer novel assessment of heart displacement based on 4DCT images. MHD and D{sub LAD} can be used independently or jointly as selection criteria for respiratory gating procedure before treatment planning. Patients with great intrafractional MHD variations or tumor(s) close to the diaphragm may particularly benefit from the

  9. Neurogenic mediators contribute to local edema induced by Micrurus lemniscatus venom

    PubMed Central

    2017-01-01

    Background/Aims Micrurus is one of the four snake genera of medical importance in Brazil. Coral snakes have a broad geographic distribution from the southern United States to Argentina. Micrurine envenomation is characterized by neurotoxic symptoms leading to dyspnea and death. Moreover, various local manifestations, including edema formation, have been described in patients bitten by different species of Micrurus. Thus, we investigated the ability of Micrurus lemniscatus venom (MLV) to induce local edema. We also explored mechanisms underlying this effect, focusing on participation of neuropeptides and mast cells. Methodology/Principal findings Intraplantar injection of MLV (1–10 μg/paw) in rats caused dose- and time-dependent edema with a peak between 15 min and 1 h after injection. MLV also induced degranulation of peritoneal mast cells (MCs). MC depletion by compound 48/80 markedly reduced MLV-induced edema. Pre-treatment (30 min) of rats with either promethazine a histamine H1 receptor antagonist or methysergide, a nonselective 5-HT receptor antagonist, reduced MLV-induced edema. However, neither thioperamide, a histamine H3/H4 receptor antagonist, nor co-injection of MLV with HOE-140, a BK2 receptor antagonist, altered the response. Depletion of neuropeptides by capsaicin or treatment of animals with NK1- and NK2-receptor antagonists (SR 140333 and SR 48968, respectively) markedly reduced MLV-induced edema. Conclusions/Significance In conclusion, MLV induces paw edema in rats by mechanisms involving activation of mast cells and substance P-releasing sensory C-fibers. Tachykinins NKA and NKB, histamine, and serotonin are major mediators of the MLV-induced edematogenic response. Targeting mast cell- and sensory C-fiber-derived mediators should be considered as potential therapeutic approaches to interrupt development of local edema induced by Micrurus venoms. PMID:29161255

  10. Hypoxia-inducible factor 1α is a critical downstream mediator for hypoxia-induced mitogenic factor (FIZZ1/RELMα)-induced pulmonary hypertension

    PubMed Central

    Johns, Roger A.; Takimoto, Eiki; Meuchel, Lucas W.; Elsaigh, Esra; Zhang, Ailan; Heller, Nicola M.; Semenza, Gregg L.; Yamaji-Kegan, Kazuyo

    2017-01-01

    Objective Pulmonary hypertension (PH) is characterized by progressive elevation of pulmonary vascular resistance, right ventricular failure, and ultimately death. We have shown that in rodents, hypoxia-induced mitogenic factor (HIMF; also known as FIZZ1 or RELMα) causes PH by initiating lung vascular inflammation. We hypothesized that hypoxia-inducible factor-1 (HIF-1) is a critical downstream signal mediator of HIMF during PH development. Approach and Results In this study, we compared the degree of HIMF-induced pulmonary vascular remodeling and PH development in wild-type (HIF-1α+/+) and HIF-1α heterozygous null (HIF-1α+/−) mice. HIMF-induced PH was significantly diminished in HIF-1α+/− mice and was accompanied by a dysregulated VEGF-A–VEGF receptor 2 pathway. HIF-1α was critical for bone marrow-derived cell migration and vascular tube formation in response to HIMF. Furthermore, HIMF and its human homolog, resistin-like molecule-β (RELMβ), significantly increased IL-6 in macrophages and lung resident cells through a mechanism dependent on HIF-1α and, at least to some extent, on nuclear factor κB. Conclusions Our results suggest that HIF-1α is a critical downstream transcription factor for HIMF-induced pulmonary vascular remodeling and PH development. Importantly, both HIMF and human RELMβ significantly increased IL-6 in lung resident cells and increased perivascular accumulation of IL-6–expressing macrophages in the lungs of mice. These data suggest that HIMF can induce HIF-1, VEGF-A, and interleukin-6, which are critical mediators of both hypoxic inflammation and PH pathophysiology. PMID:26586659

  11. Study on Vortex-Induced Motions of A New Type of Deep Draft Multi-Columns FDPSO

    NASA Astrophysics Data System (ADS)

    Gu, Jia-yang; Xie, Yu-lin; Zhao, Yuan; Li, Wen-juan; Tao, Yan-wu; Huang, Xiang-hong

    2018-03-01

    A numerical simulation and an experimental study on vortex-induced motion (VIM) of a new type of deep draft multi-columns floating drilling production, storage and offloading (FDPSO) are presented in this paper. The main dimension, the special variable cross-section column and the cabin arrangement of the octagonal pontoon are introduced based on the result. The numerical simulation is adapted to study the effects of current incidence angles and reduced velocities on this platform's sway motion response. The 300 m water depth equivalent truncated mooring system is adopted for the model tests. The model tests are carried out to check the reliability of numerical simulation. The results consist of surge, sway and yaw motions, as well as motion trajectories. The maximum sway amplitudes for different types of offshore platform is also studied. The main results show that the peak frequencies of sway motion under different current incidence angles and reduced velocities vary around the natural frequency. The analysis result of flow field indicates that the change of distribution of vortex in vertical presents significant influences on the VIM of platform. The trend of sway amplitude ratio curve of this new type FDPSO differs from the other types of platform. Under 45° current incidence angle, the sway amplitude of this new type of FDPSO is much smaller than those of other types of offshore platform at 4.4 ≤ V r ≤ 8.9. The typical `8' shape trajectory does not appear in the platform's motion trajectories.

  12. URBAN PARTICLE-INDUCED PULMONARY ARTERY CONSTRUCTION IS MEDIATED BY SUPEROXIDE PRODUCTION

    EPA Science Inventory

    URBAN PARTICLE-INDUCED PULMONARY ARTERY CONSTRICTION IS MEDIATED BY SUPEROXIDE PRODUCTION.Jacqueline D. Carter, Zhuowei Li, Lisa A. Dailey, Yuh-Chin T. Huang. CEMALB, University of North Carolina, and ORD, US EPA, Chapel Hill, North Carolina.

    Exposure to particulate matter...

  13. Allergen-Induced Dermatitis Causes Alterations in Cutaneous Retinoid-Mediated Signaling in Mice

    PubMed Central

    Gericke, Janine; Ittensohn, Jan; Mihály, Johanna; Dubrac, Sandrine; Rühl, Ralph

    2013-01-01

    Nuclear receptor-mediated signaling via RARs and PPARδ is involved in the regulation of skin homeostasis. Moreover, activation of both RAR and PPARδ was shown to alter skin inflammation. Endogenous all-trans retinoic acid (ATRA) can activate both receptors depending on specific transport proteins: Fabp5 initiates PPARδ signaling whereas Crabp2 promotes RAR signaling. Repetitive topical applications of ovalbumin (OVA) in combination with intraperitoneal injections of OVA or only intraperitoneal OVA applications were used to induce allergic dermatitis. In our mouse model, expression of IL-4, and Hbegf increased whereas expression of involucrin, Abca12 and Spink5 decreased in inflamed skin, demonstrating altered immune response and epidermal barrier homeostasis. Comprehensive gene expression analysis showed alterations of the cutaneous retinoid metabolism and retinoid-mediated signaling in allergic skin immune response. Notably, ATRA synthesis was increased as indicated by the elevated expression of retinaldehyde dehydrogenases and increased levels of ATRA. Consequently, the expression pattern of genes downstream to RAR was altered. Furthermore, the increased ratio of Fabp5 vs. Crabp2 may indicate an up-regulation of the PPARδ pathway in allergen-induced dermatitis in addition to the altered RAR signaling. Thus, our findings suggest that ATRA levels, RAR-mediated signaling and signaling involved in PPARδ pathways are mainly increased in allergen-induced dermatitis and may contribute to the development and/or maintenance of allergic skin diseases. PMID:23977003

  14. Allergen-induced dermatitis causes alterations in cutaneous retinoid-mediated signaling in mice.

    PubMed

    Gericke, Janine; Ittensohn, Jan; Mihály, Johanna; Dubrac, Sandrine; Rühl, Ralph

    2013-01-01

    Nuclear receptor-mediated signaling via RARs and PPARδ is involved in the regulation of skin homeostasis. Moreover, activation of both RAR and PPARδ was shown to alter skin inflammation. Endogenous all-trans retinoic acid (ATRA) can activate both receptors depending on specific transport proteins: Fabp5 initiates PPARδ signaling whereas Crabp2 promotes RAR signaling. Repetitive topical applications of ovalbumin (OVA) in combination with intraperitoneal injections of OVA or only intraperitoneal OVA applications were used to induce allergic dermatitis. In our mouse model, expression of IL-4, and Hbegf increased whereas expression of involucrin, Abca12 and Spink5 decreased in inflamed skin, demonstrating altered immune response and epidermal barrier homeostasis. Comprehensive gene expression analysis showed alterations of the cutaneous retinoid metabolism and retinoid-mediated signaling in allergic skin immune response. Notably, ATRA synthesis was increased as indicated by the elevated expression of retinaldehyde dehydrogenases and increased levels of ATRA. Consequently, the expression pattern of genes downstream to RAR was altered. Furthermore, the increased ratio of Fabp5 vs. Crabp2 may indicate an up-regulation of the PPARδ pathway in allergen-induced dermatitis in addition to the altered RAR signaling. Thus, our findings suggest that ATRA levels, RAR-mediated signaling and signaling involved in PPARδ pathways are mainly increased in allergen-induced dermatitis and may contribute to the development and/or maintenance of allergic skin diseases.

  15. Saturated phosphatidic acids mediate saturated fatty acid-induced vascular calcification and lipotoxicity.

    PubMed

    Masuda, Masashi; Miyazaki-Anzai, Shinobu; Keenan, Audrey L; Okamura, Kayo; Kendrick, Jessica; Chonchol, Michel; Offermanns, Stefan; Ntambi, James M; Kuro-O, Makoto; Miyazaki, Makoto

    2015-10-26

    Recent evidence indicates that saturated fatty acid-induced (SFA-induced) lipotoxicity contributes to the pathogenesis of cardiovascular and metabolic diseases; however, the molecular mechanisms that underlie SFA-induced lipotoxicity remain unclear. Here, we have shown that repression of stearoyl-CoA desaturase (SCD) enzymes, which regulate the intracellular balance of SFAs and unsaturated FAs, and the subsequent accumulation of SFAs in vascular smooth muscle cells (VSMCs), are characteristic events in the development of vascular calcification. We evaluated whether SMC-specific inhibition of SCD and the resulting SFA accumulation plays a causative role in the pathogenesis of vascular calcification and generated mice with SMC-specific deletion of both Scd1 and Scd2. Mice lacking both SCD1 and SCD2 in SMCs displayed severe vascular calcification with increased ER stress. Moreover, we employed shRNA library screening and radiolabeling approaches, as well as in vitro and in vivo lipidomic analysis, and determined that fully saturated phosphatidic acids such as 1,2-distearoyl-PA (18:0/18:0-PA) mediate SFA-induced lipotoxicity and vascular calcification. Together, these results identify a key lipogenic pathway in SMCs that mediates vascular calcification.

  16. Asparagine deprivation mediated by Salmonella asparaginase causes suppression of activation-induced T cell metabolic reprogramming.

    PubMed

    Torres, AnnMarie; Luke, Joanna D; Kullas, Amy L; Kapilashrami, Kanishk; Botbol, Yair; Koller, Antonius; Tonge, Peter J; Chen, Emily I; Macian, Fernando; van der Velden, Adrianus W M

    2016-02-01

    Salmonellae are pathogenic bacteria that induce immunosuppression by mechanisms that remain largely unknown. Previously, we showed that a putative type II l-asparaginase produced by Salmonella Typhimurium inhibits T cell responses and mediates virulence in a murine model of infection. Here, we report that this putative L-asparaginase exhibits L-asparagine hydrolase activity required for Salmonella Typhimurium to inhibit T cells. We show that L-asparagine is a nutrient important for T cell activation and that L-asparagine deprivation, such as that mediated by the Salmonella Typhimurium L-asparaginase, causes suppression of activation-induced mammalian target of rapamycin signaling, autophagy, Myc expression, and L-lactate secretion. We also show that L-asparagine deprivation mediated by the Salmonella Typhimurium L-asparaginase causes suppression of cellular processes and pathways involved in protein synthesis, metabolism, and immune response. Our results advance knowledge of a mechanism used by Salmonella Typhimurium to inhibit T cell responses and mediate virulence, and provide new insights into the prerequisites of T cell activation. We propose a model in which l-asparagine deprivation inhibits T cell exit from quiescence by causing suppression of activation-induced metabolic reprogramming. © Society for Leukocyte Biology.

  17. Extrinsic grouping factors in motion-induced blindness

    PubMed Central

    2018-01-01

    We investigated how various grouping factors altered subjective disappearances of the individual targets in the motion-induced blindness display. The latter relies on a moving mask to render highly salient static targets temporarily subjectively invisible. Specifically, we employed two extrinsic grouping factors, the connectedness and the common region, and examined whether their presence would make targets more resilient against the suppression. In addition, we investigated whether the presence of an illusory Kanizsa triangle would affect the suppression of the inducing Pac-Man elements. We quantified the perceptual dynamics using the proportion of the disappearance time (this indicates whether targets became more resilient against the suppression), and the proportion of simultaneous disappearance and reappearance events (characterizes the tendency for the targets to disappear or reappear as a group). We report that a single mask that encompassed all targets (a common region grouping) significantly increased the proportion of simultaneous disappearance and reappearance events, but had no effect on the proportion of the disappearance time. In contrast, a line that connected two targets significantly decreased the total invisibility time, but had no impact on the simultaneity of the disappearance and reappearance events. We found no statistically significant effect of the presence of the illusory Kanizsa triangle on either measure. Finally, we found no interaction either between the common region and the connectedness or between the common region and the presence of the illusory Kanizsa triangle. Our results indicate that extrinsic grouping factors might influence the perception differently than the intrinsic ones and highlight the importance of using several measures to characterize the perceptual dynamics, as various grouping factors might affect it differentially. PMID:29381747

  18. A framework for activity detection in wide-area motion imagery

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

    Porter, Reid B; Ruggiero, Christy E; Morrison, Jack D

    2009-01-01

    Wide-area persistent imaging systems are becoming increasingly cost effective and now large areas of the earth can be imaged at relatively high frame rates (1-2 fps). The efficient exploitation of the large geo-spatial-temporal datasets produced by these systems poses significant technical challenges for image and video analysis and data mining. In recent years there has been significant progress made on stabilization, moving object detection and tracking and automated systems now generate hundreds to thousands of vehicle tracks from raw data, with little human intervention. However, the tracking performance at this scale, is unreliable and average track length is much smallermore » than the average vehicle route. This is a limiting factor for applications which depend heavily on track identity, i.e. tracking vehicles from their points of origin to their final destination. In this paper we propose and investigate a framework for wide-area motion imagery (W AMI) exploitation that minimizes the dependence on track identity. In its current form this framework takes noisy, incomplete moving object detection tracks as input, and produces a small set of activities (e.g. multi-vehicle meetings) as output. The framework can be used to focus and direct human users and additional computation, and suggests a path towards high-level content extraction by learning from the human-in-the-loop.« less

  19. Motion-Matching: A Challenge Game to Generate Motion Concepts

    ERIC Educational Resources Information Center

    Schuster, David; Adams, Betty; Brookes, David; Milner-Bolotin, Marina; Undreiu, Adriana

    2009-01-01

    Motion is a topic that is taught from elementary grades through to university at various levels of sophistication. It is an area that can be challenging for learning in a conceptually meaningful way, and formal kinematics instruction can sometimes seem dry and boring. Thus, the nature of students' initial introduction to motion is important in…

  20. Filling-in visual motion with sounds.

    PubMed

    Väljamäe, A; Soto-Faraco, S

    2008-10-01

    Information about the motion of objects can be extracted by multiple sensory modalities, and, as a consequence, object motion perception typically involves the integration of multi-sensory information. Often, in naturalistic settings, the flow of such information can be rather discontinuous (e.g. a cat racing through the furniture in a cluttered room is partly seen and partly heard). This study addressed audio-visual interactions in the perception of time-sampled object motion by measuring adaptation after-effects. We found significant auditory after-effects following adaptation to unisensory auditory and visual motion in depth, sampled at 12.5 Hz. The visually induced (cross-modal) auditory motion after-effect was eliminated if visual adaptors flashed at half of the rate (6.25 Hz). Remarkably, the addition of the high-rate acoustic flutter (12.5 Hz) to this ineffective, sparsely time-sampled, visual adaptor restored the auditory after-effect to a level comparable to what was seen with high-rate bimodal adaptors (flashes and beeps). Our results suggest that this auditory-induced reinstatement of the motion after-effect from the poor visual signals resulted from the occurrence of sound-induced illusory flashes. This effect was found to be dependent both on the directional congruency between modalities and on the rate of auditory flutter. The auditory filling-in of time-sampled visual motion supports the feasibility of using reduced frame rate visual content in multisensory broadcasting and virtual reality applications.

  1. 6% magnetic-field-induced strain by twin-boundary motion in ferromagnetic Ni-Mn-Ga

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

    Murray, S. J.; Marioni, M.; Allen, S. M.

    2000-08-07

    Field-induced strains of 6% are reported in ferromagnetic Ni-Mn-Ga martensites at room temperature. The strains are the result of twin boundary motion driven largely by the Zeeman energy difference across the twin boundary. The strain measured parallel to the applied magnetic field is negative in the sample/field geometry used here. The strain saturates in fields of order 400 kA/m and is blocked by a compressive stress of order 2 MPa applied orthogonal to the magnetic field. The strain versus field curves exhibit appreciable hysteresis associated with the motion of the twin boundaries. A simple model accounts quantitatively for the dependencemore » of strain on magnetic field and external stress using as input parameters only measured quantities. (c) 2000 American Institute of Physics.« less

  2. Orientation Preferences and Motion Sickness Induced in a Virtual Reality Environment.

    PubMed

    Chen, Wei; Chao, Jian-Gang; Zhang, Yan; Wang, Jin-Kun; Chen, Xue-Wen; Tan, Cheng

    2017-10-01

    Astronauts' orientation preferences tend to correlate with their susceptibility to space motion sickness (SMS). Orientation preferences appear universally, since variable sensory cue priorities are used between individuals. However, SMS susceptibility changes after proper training, while orientation preferences seem to be intrinsic proclivities. The present study was conducted to investigate whether orientation preferences change if susceptibility is reduced after repeated exposure to a virtual reality (VR) stimulus environment that induces SMS. A horizontal supine posture was chosen to create a sensory context similar to weightlessness, and two VR devices were used to produce a highly immersive virtual scene. Subjects were randomly allocated to an experimental group (trained through exposure to a provocative rotating virtual scene) and a control group (untrained). All subjects' orientation preferences were measured twice with the same interval, but the experimental group was trained three times during the interval, while the control group was not. Trained subjects were less susceptible to SMS, with symptom scores reduced by 40%. Compared with untrained subjects, trained subjects' orientation preferences were significantly different between pre- and posttraining assessments. Trained subjects depended less on visual cues, whereas few subjects demonstrated the opposite tendency. Results suggest that visual information may be inefficient and unreliable for body orientation and stabilization in a rotating visual scene, while reprioritizing preferences for different sensory cues was dynamic and asymmetric between individuals. The present findings should facilitate customization of efficient and proper training for astronauts with different sensory prioritization preferences and dynamic characteristics.Chen W, Chao J-G, Zhang Y, Wang J-K, Chen X-W, Tan C. Orientation preferences and motion sickness induced in a virtual reality environment. Aerosp Med Hum Perform. 2017

  3. Pitch body orientation influences the perception of self-motion direction induced by optic flow.

    PubMed

    Bourrelly, A; Vercher, J-L; Bringoux, L

    2010-10-04

    We studied the effect of static pitch body tilts on the perception of self-motion direction induced by a visual stimulus. Subjects were seated in front of a screen on which was projected a 3D cluster of moving dots visually simulating a forward motion of the observer with upward or downward directional biases (relative to a true earth horizontal direction). The subjects were tilted at various angles relative to gravity and were asked to estimate the direction of the perceived motion (nose-up, as during take-off or nose-down, as during landing). The data showed that body orientation proportionally affected the amount of error in the reported perceived direction (by 40% of body tilt magnitude in a range of +/-20 degrees) and these errors were systematically recorded in the direction of body tilt. As a consequence, a same visual stimulus was differently interpreted depending on body orientation. While the subjects were required to perform the task in a geocentric reference frame (i.e., relative to a gravity-related direction), they were obviously influenced by egocentric references. These results suggest that the perception of self-motion is not elaborated within an exclusive reference frame (either egocentric or geocentric) but rather results from the combined influence of both. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  4. Sensitivity of neurons in the middle temporal area of marmoset monkeys to random dot motion.

    PubMed

    Chaplin, Tristan A; Allitt, Benjamin J; Hagan, Maureen A; Price, Nicholas S C; Rajan, Ramesh; Rosa, Marcello G P; Lui, Leo L

    2017-09-01

    Neurons in the middle temporal area (MT) of the primate cerebral cortex respond to moving visual stimuli. The sensitivity of MT neurons to motion signals can be characterized by using random-dot stimuli, in which the strength of the motion signal is manipulated by adding different levels of noise (elements that move in random directions). In macaques, this has allowed the calculation of "neurometric" thresholds. We characterized the responses of MT neurons in sufentanil/nitrous oxide-anesthetized marmoset monkeys, a species that has attracted considerable recent interest as an animal model for vision research. We found that MT neurons show a wide range of neurometric thresholds and that the responses of the most sensitive neurons could account for the behavioral performance of macaques and humans. We also investigated factors that contributed to the wide range of observed thresholds. The difference in firing rate between responses to motion in the preferred and null directions was the most effective predictor of neurometric threshold, whereas the direction tuning bandwidth had no correlation with the threshold. We also showed that it is possible to obtain reliable estimates of neurometric thresholds using stimuli that were not highly optimized for each neuron, as is often necessary when recording from large populations of neurons with different receptive field concurrently, as was the case in this study. These results demonstrate that marmoset MT shows an essential physiological similarity to macaque MT and suggest that its neurons are capable of representing motion signals that allow for comparable motion-in-noise judgments. NEW & NOTEWORTHY We report the activity of neurons in marmoset MT in response to random-dot motion stimuli of varying coherence. The information carried by individual MT neurons was comparable to that of the macaque, and the maximum firing rates were a strong predictor of sensitivity. Our study provides key information regarding the neural

  5. Sirtuins-mediators of maternal obesity-induced complications in offspring?

    PubMed

    Nguyen, Long T; Chen, Hui; Pollock, Carol A; Saad, Sonia

    2016-04-01

    Obesity is a complex metabolic disease, attributed to diverse and interactive genetic and environmental factors. The associated health consequences of obesity are pleiotropic, with individuals being more susceptible to chronic diseases such as type 2 diabetes mellitus, hypertension, and lipotoxicity-related chronic diseases. The contribution of maternal obesity to the offspring's predisposition to both obesity and its complications is increasingly recognized. Understanding the mechanisms underlying these "transmissible" effects is critical to develop therapeutic interventions to reduce the risk for "programmed" obesity. Sirtuins (SIRTs), particularly SIRT1 and SIRT3, are NAD(+)-dependent deacetylases that regulate metabolic balance and stress responses in both central and peripheral tissues, of which dysregulation is a well-established mediator for the development and effects of obesity. Nevertheless, their implication in the transmissible effects of maternal obesity across generations remains largely elusive. In this review, we examine multiple pathways and systems that are likely to mediate such effects, with particular emphasis on the role of SIRTs.-Nguyen, L. T., Chen, H., Pollock, C. A., Saad, S. Sirtuins-mediators of maternal obesity-induced complications in offspring? © FASEB.

  6. Polyphosphate induces matrix metalloproteinase-3-mediated proliferation of odontoblast-like cells derived from induced pluripotent stem cells

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

    Ozeki, Nobuaki; Hase, Naoko; Yamaguchi, Hideyuki

    2015-05-01

    Inorganic polyphosphate [Poly(P)] may represent a physiological source of phosphate and has the ability to induce bone differentiation in osteoblasts. We previously reported that cytokine-induced matrix metalloproteinase (MMP)-3 accelerates the proliferation of purified odontoblast-like cells. In this study, MMP-3 small interfering RNA (siRNA) was transfected into odontoblast-like cells derived from induced pluripotent stem cells to investigate whether MMP-3 activity is induced by Poly(P) and/or is associated with cell proliferation and differentiation into odontoblast-like cells. Treatment with Poly(P) led to an increase in both cell proliferation and additional odontoblastic differentiation. Poly(P)-treated cells showed a small but significant increase in dentin sialophosphoproteinmore » (DSPP) and dentin matrix protein-1 (DMP-1) mRNA expression, which are markers of mature odontoblasts. The cells also acquired additional odontoblast-specific properties including adoption of an odontoblastic phenotype typified by high alkaline phosphatase (ALP) activity and a calcification capacity. In addition, Poly(P) induced expression of MMP-3 mRNA and protein, and increased MMP-3 activity. MMP-3 siRNA-mediated disruption of the expression of these effectors potently suppressed the expression of odontoblastic biomarkers ALP, DSPP, and DMP-1, and blocked calcification. Interestingly, upon siRNA-mediated silencing of MMP-3, we noted a potent and significant decrease in cell proliferation. Using specific siRNAs, we revealed that a unique signaling cascade, Poly(P)→MMP-3→DSPP and/or DMP-1, was intimately involved in the proliferation of odontoblast-like cells. - Highlights: • Polyphosphate increases proliferation of iPS cell-derived odontoblast-like cells. • Polyphosphate-induced MMP-3 results in an increase of cell proliferation. • Induced cell proliferation involves MMP-3, DSPP, and/or DMP-1 sequentially. • Induced MMP-3 also results in an increase of

  7. Image motion compensation by area correlation and centroid tracking of solar surface features

    NASA Technical Reports Server (NTRS)

    Nein, M. E.; Mcintosh, W. R.; Cumings, N. P.

    1983-01-01

    An experimental solar correlation tracker was tested and evaluated on a ground-based solar magnetograph. Using sunspots as fixed targets, tracking error signals were derived by which the telescope image was stabilized against wind induced perturbations. Two methods of stabilization were investigated; mechanical stabilization of the image by controlled two-axes motion of an active optical element in the telescope beam, and electronic stabilization by biasing of the electron scan in the recording camera. Both approaches have demonstrated telescope stability of about 0.6 arc sec under random perturbations which can cause the unstabilized image to move up to 120 arc sec at frequencies up to 30 Hz.

  8. Unsteady motion of laser ablation plume by vortex induced by the expansion of curved shock wave

    NASA Astrophysics Data System (ADS)

    Tran, D. T.; Mori, K.

    2017-02-01

    There are a number of industrial applications of laser ablation in a gas atmosphere. When an intense pulsed laser beam is irradiated on a solid surface in the gas atmosphere, the surface material is ablated and expands into the atmosphere. At the same time, a spherical shock wave is launched by the ablation jet to induce the unsteady flow around the target surface. The ablated materials, luminously working as tracer, exhibit strange unsteady motions depending on the experimental conditions. By using a high-speed video camera (HPV-X2), unsteady motion ablated materials are visualized at the frame rate more than 106 fps, and qualitatively characterized.

  9. Blockade of 5-hydroxytryptamine3 receptors prevents cisplatin-induced but not motion- or xylazine-induced emesis in the cat

    NASA Technical Reports Server (NTRS)

    Lucot, J. B.

    1989-01-01

    5-Hydroxytryptamine3 antagonists have been reported to prevent emesis elicited by cisplatin and radiation. This study investigated the possibility that drugs with this mechanism of action may be useful in preventing emesis elicited by other stimuli. The drugs ICS 205-930 (0.1 and 1.0 mg/kg) and MDL 72222 (0.1 and 1.0 mg/kg) were administered SC to cats before challenging them with either provocative motion or an emetic dose of xylazine. In no instance was a significant reduction in emesis evident. Zacopride was also administered before motion testing (0.01 to 10.0 mg/kg) and found to not have efficacy. To test the possibility that species or route of administration were factors in the negative results, 1.0 mg/kg of ICS 205-930 was administered SC before IV infusion of 7.5 mg/kg of cisplatin. There was a total suppression of emesis for the duration of the six-hour observation periods. This result verifies other work which found 5-hydroxytryptamine3 antagonists to be effective in preventing emesis elicited by cancer chemotherapeutic treatments. However, there is no evidence that they are effective in other syndromes, such as motion sickness and xylazine-induced emesis.

  10. Chk2 mediates RITA-induced apoptosis

    PubMed Central

    de Lange, J; Verlaan-de Vries, M; Teunisse, A F A S; Jochemsen, A G

    2012-01-01

    Reactivation of the p53 tumor-suppressor protein by small molecules like Nutlin-3 and RITA (reactivation of p53 and induction of tumor cell apoptosis) is a promising strategy for cancer therapy. The molecular mechanisms involved in the responses to RITA remain enigmatic. Several groups reported the induction of a p53-dependent DNA damage response. Furthermore, the existence of a p53-dependent S-phase checkpoint has been suggested, involving the checkpoint kinase Chk1. We have recently shown synergistic induction of apoptosis by RITA in combination with Nutlin-3, and we observed concomitant Chk2 phosphorylation. Therefore, we investigated whether Chk2 contributes to the cellular responses to RITA. Strikingly, the induction of apoptosis seemed entirely Chk2 dependent. Transcriptional activity of p53 in response to RITA required the presence of Chk2. A partial rescue of apoptosis observed in Noxa knockdown cells emphasized the relevance of p53 transcriptional activity for RITA-induced apoptosis. In addition, we observed an early p53- and Chk2-dependent block of DNA replication upon RITA treatment. Replicating cells seemed more prone to entering RITA-induced apoptosis. Furthermore, the RITA-induced DNA damage response, which was not a secondary effect of apoptosis induction, was strongly attenuated in cells lacking p53 or Chk2. In conclusion, we identified Chk2 as an essential mediator of the cellular responses to RITA. PMID:22158418

  11. The MAP kinase JNK2 mediates cigarette smoke-induced arterial thrombosis.

    PubMed

    Breitenstein, Alexander; Stämpfli, Simon F; Reiner, Martin F; Shi, Yi; Keller, Stephan; Akhmedov, Alexander; Schaub Clerigué, Ariane; Spescha, Remo D; Beer, Hans-Jürg; Lüscher, Thomas F; Tanner, Felix C; Camici, Giovanni G

    2017-01-05

    Despite public awareness of its deleterious effects, smoking remains a major cause of death. Indeed, it is a risk factor for atherothrombotic complications and in line with this, the introduction of smoking ban in public areas reduced smoking-associated cardiovascular complications. Nonetheless, smoking remains a major concern, and molecular mechanisms by which it causes cardiovascular disease are not known. Peripheral blood monocytes from healthy smokers displayed increased JNK2 and tissue factor (TF) gene expression compared to non-smokers (n=15, p<0.05). Similarly, human aortic endothelial cells exposed to cigarette smoke total particulate matter (CS-TPM) revealed increased TF expression mediated by JNK2 (n=4; p<0.05). Wild-type and JNK2 -/- mice were exposed to cigarette smoke for two weeks after which arterial thrombosis was investigated. Wild-type mice exposed to smoke displayed reduced time to thrombotic arterial occlusion (n=8; p<0.05) and increased tissue factor activity (n=7; p<0.05) as compared to wild-type controls (n=6), while JNK2 -/- mice exposed to smoke maintained an unaltered thrombotic potential (n=8; p=NS) and tissue factor activity (n=8) comparable to that of JNK2 -/- and wild-type controls (n=6; p=NS). Smoking caused an increased production of reactive oxygen species (ROS) in wild-type but not in JNK2 -/- mice (n=7; p<0.05 for wild-type mice and n=5-6; p=NS for JNK2 -/- mice). In conclusion, the MAP kinase JNK2 mediates cigarette smoke-induced TF activation, arterial thrombosis and ROS production. These results underscore a major role of JNK2 in smoke-mediated thrombus formation and may offer an attractive target to prevent smoke-related thrombosis in those subjects which do not manage quitting.

  12. Long period nodal motion of sun synchronous orbits

    NASA Technical Reports Server (NTRS)

    Duck, K. I.

    1975-01-01

    An approximative model is formulated for assessing these perturbations that significantly affect long term modal motion of sun synchronous orbits. Computer simulations with several independent computer programs consider zonal and tesseral gravitational harmonics, third body gravitational disturbances induced by the sun and the moon, and atmospheric drag. A pendulum model consisting of evenzonal harmonics through order 4 and solar gravity dominated nodal motion approximation. This pendulum motion results from solar gravity inducing an inclination oscillation which couples into the nodal precession induced by the earth's oblateness. The pendulum model correlated well with simulations observed flight data.

  13. Epidermal growth factor receptor signaling mediates aldosterone-induced profibrotic responses in kidney

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

    Sheng, Lili; Yang, Min; Ding, Wei

    Aldosterone has been recognized as a risk factor for the development of chronic kidney disease (CKD). Studies have indicated that enhanced activation of epidermal growth factor receptor (EGFR) is associated with the development and progression of renal fibrosis. But if EGFR is involved in aldosterone-induced renal fibrosis is less investigated. In the present study, we examined the effect of erlotinib, an inhibitor of EGFR tyrosine kinase activity, on the progression of aldosterone-induced renal profibrotic responses in a murine model underwent uninephrectomy. Erlotinib-treated rats exhibited relieved structural lesion comparing with rats treated with aldosterone alone, as characterized by glomerular hypertrophy, mesangialmore » cell proliferation and expansion. Also, erlotinib inhibited the expression of TGF-β, α-SMA and mesangial matrix proteins such as collagen Ⅳ and fibronectin. In cultured mesangial cells, inhibition of EGFR also abrogated aldosterone-induced expression of extracellular matrix proteins, cell proliferation and migration. We also demonstrated that aldosterone induced the phosphorylation of EGFR through generation of ROS. And the activation of EGFR resulted in the phosphorylation of ERK1/2, leading to the activation of profibrotic pathways. Taken together, we concluded that aldosterone-mediated tissue fibrosis relies on ROS induced EGFR/ERK activation, highlighting EGFR as a potential therapeutic target for modulating renal fibrosis. - Highlights: • EGFR was involved in aldosterone-induced renal profibrotic responses. • Aldosterone-induced EGFR activation was mediated by MR-dependent ROS generation. • EGFR activated the MAPK/ERK1/2 signaling to promote renal fibrosis.« less

  14. Development of enhanced piezoelectric energy harvester induced by human motion.

    PubMed

    Minami, Y; Nakamachi, E

    2012-01-01

    In this study, a high frequency piezoelectric energy harvester converted from the human low vibrated motion energy was newly developed. This hybrid energy harvester consists of the unimorph piezoelectric cantilever and a couple of permanent magnets. One magnet was attached at the end of cantilever, and the counterpart magnet was set at the end of the pendulum. The mechanical energy provided through the human walking motion, which is a typical ubiquitous presence of vibration, is converted to the electric energy via the piezoelectric cantilever vibration system. At first, we studied the energy convert mechanism and the performance of our energy harvester, where the resonance free vibration of unimorph cantilever with one permanent magnet under a rather high frequency was induced by the artificial low frequency vibration. The counterpart magnet attached on the pendulum. Next, we equipped the counterpart permanent magnet pendulum, which was fluctuated under a very low frequency by the human walking, and the piezoelectric cantilever, which had the permanent magnet at the end. The low-to-high frequency convert "hybrid system" can be characterized as an enhanced energy harvest one. We examined and obtained maximum values of voltage and power in this system, as 1.2V and 1.2 µW. Those results show the possibility to apply for the energy harvester in the portable and implantable Bio-MEMS devices.

  15. Scavengers modifying the phototoxicity induced by ALA-mediated photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Casas, Adriana; Perotti, Christian; Fukuda, Haydee; Batlle, Alcira

    2001-04-01

    The exogenously stimulated formation of intracellularly generated Protoporphyrin IX, a precursor of heme, is becoming one of the fastest developing areas in the field of Photodynamic Therapy (PDT). We have examined the degree of protection of several scavengers, aminoacids and compounds related to glutathione metabolism, to the photodamage induced by 5-aminolevulinic acid (ALA)-mediated PDT, employing the LM2 cell line, derived from a mammary murine adenocarcinoma. We have exposed the cells to different concentrations of the scavengers, 24 before PDT, during PDT, and 19 hr after treatment. We defined the protection grade (PG) as the ratio between cell survival after ALA-PDT treatment in the presence of the protector and cell survival after ALA-PDT treatment. We found that L-tryptophan (PG=8.3 at 2mM), N-acetyl-L-cysteine (PG= 7.9 at 30 mM), L-cysteine (PG=7.81 at 8mM), S-adenosyl-L-methionine (PG= 7.86 at 8mM), melatonin (PG=6.81 at 8mM) and glycine (PG=6.8 at 40 mM) are the best protectors to PDT damage, followed by L-methionine (PG=4.38 at 0.8 mM), mannitol (PG=2.32 at 2 mM) and reduced glutathione (PG=3.41 at 0.8 mM), whereas oxidized glutathione does not exert any protection. The implications of these results in the photodamage induced by ALA-PDT is discussed.

  16. Comparison of different detection methods for persistent multiple hypothesis tracking in wide area motion imagery

    NASA Astrophysics Data System (ADS)

    Hartung, Christine; Spraul, Raphael; Schuchert, Tobias

    2017-10-01

    Wide area motion imagery (WAMI) acquired by an airborne multicamera sensor enables continuous monitoring of large urban areas. Each image can cover regions of several square kilometers and contain thousands of vehicles. Reliable vehicle tracking in this imagery is an important prerequisite for surveillance tasks, but remains challenging due to low frame rate and small object size. Most WAMI tracking approaches rely on moving object detections generated by frame differencing or background subtraction. These detection methods fail when objects slow down or stop. Recent approaches for persistent tracking compensate for missing motion detections by combining a detection-based tracker with a second tracker based on appearance or local context. In order to avoid the additional complexity introduced by combining two trackers, we employ an alternative single tracker framework that is based on multiple hypothesis tracking and recovers missing motion detections with a classifierbased detector. We integrate an appearance-based similarity measure, merge handling, vehicle-collision tests, and clutter handling to adapt the approach to the specific context of WAMI tracking. We apply the tracking framework on a region of interest of the publicly available WPAFB 2009 dataset for quantitative evaluation; a comparison to other persistent WAMI trackers demonstrates state of the art performance of the proposed approach. Furthermore, we analyze in detail the impact of different object detection methods and detector settings on the quality of the output tracking results. For this purpose, we choose four different motion-based detection methods that vary in detection performance and computation time to generate the input detections. As detector parameters can be adjusted to achieve different precision and recall performance, we combine each detection method with different detector settings that yield (1) high precision and low recall, (2) high recall and low precision, and (3) best f

  17. Recovery of Near-Fault Ground Motion by Introducing Rotational Motions

    NASA Astrophysics Data System (ADS)

    Chiu, H. C.

    2014-12-01

    Near-fault ground motion is the key data to seismologists for revealing the seismic faulting and earthquake physics and strong-motion data is the only near-fault seismogram that can keep on-scale recording in a major earthquake. Unfortunately, this type of data might be contaminated by the rotation induced effects such as the centrifugal acceleration and the gravity effects. We analyze these effects based on a set of collocated rotation-translation data of small to moderate earthquakes. Results show these rotation effects could be negligible in small ground motion, but they might have a radical growing in the near-fault/extremely large ground motions. In order to extract more information from near-fault seismogram for improving our understating of seismic faulting and earthquake physics, it requires six-component collocated rotation-translation records to reduce or remove these effects.

  18. Inducible nitric oxide synthase is key to peroxynitrite-mediated, LPS-induced protein radical formation in murine microglial BV2 cells

    PubMed Central

    Kumar, Ashutosh; Chen, Shih-Heng; Kadiiska, Maria B.; Hong, Jau-Shyong; Zielonka, Jacek; Kalyanaraman, Balaraman; Mason, Ronald P.

    2014-01-01

    Microglia are the resident immune cells in the brain. Microglial activation is characteristic of several inflammatory and neurodegenerative diseases including Alzheimer’s disease, multiple sclerosis, and Parkinson’s disease. Though LPS-induced microglial activation in models of Parkinson’s disease (PD) is well documented, the free radical-mediated protein radical formation and its underlying mechanism during LPS-induced microglial activation is not known. Here we have used immuno-spin trapping and RNA interference to investigate the role of inducible nitric oxide synthase (iNOS) in peroxynitrite-mediated protein radical formation in murine microglial BV2 cells treated with LPS. Treatment of BV2 cells with LPS resulted in morphological changes, induction of iNOS and increased protein radical formation. Pretreatments with FeTPPS (a peroxynitrite decomposition catalyst), L-NAME (total NOS inhibitor), 1400W (iNOS inhibitor) and apocynin significantly attenuated LPS-induced protein radical formation and tyrosine nitration. Results obtained with coumarin-7-boronic acid, a highly specific probe for peroxynitrite detection, correlated with LPS-induced tyrosine nitration, which demonstrated involvement of peroxynitrite in protein radical formation. A similar degree of protection conferred by 1400W and L-NAME led us to conclude that only iNOS, and no other forms of NOS, are involved in LPS-induced peroxynitrite formation. Subsequently, siRNA for iNOS, the iNOS-specific inhibitor 1400W, the NF-kB inhibitor PDTC and the P38 MAPK inhibitor SB202190 were used to inhibit iNOS directly or indirectly. Inhibition of iNOS precisely correlated with decreased protein radical formation in LPS-treated BV2 cells. The time course of protein radical formation also matched the time course of iNOS expression. Taken together, these results prove the role of iNOS in peroxynitrite-mediated protein radical formation in LPS-treated microglial BV2 cells. PMID:24746617

  19. Gq protein mediates UVB-induced cyclooxygenase-2 expression by stimulating HB-EGF secretion from HaCaT human keratinocytes

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

    Seo, MiRan; Juhnn, Yong-Sung, E-mail: juhnn@snu.ac.kr

    Ultraviolet (UV) radiation induces cyclooxygenase-2 expression to produce cellular responses including aging and carcinogenesis in skin. We hypothesised that heterotrimeric G proteins mediate UV-induced COX-2 expression by stimulating secretion of soluble HB-EGF (sHB-EGF). In this study, we aimed to elucidate the role and underlying mechanism of the {alpha} subunit of Gq protein (G{alpha}q) in UVB-induced HB-EGF secretion and COX-2 induction. We found that expression of constitutively active G{alpha}q (G{alpha}qQL) augmented UVB-induced HB-EGF secretion, which was abolished by knockdown of G{alpha}q with shRNA in HaCaT human keratinocytes. G{alpha}q was found to mediate the UVB-induced HB-EGF secretion by sequential activation of phospholipasemore » C (PLC), protein kinase C{delta} (PKC{delta}), and matrix metaloprotease-2 (MMP-2). Moreover, G{alpha}qQL mediated UVB-induced COX-2 expression in an HB-EGF-, EGFR-, and p38-dependent manner. From these results, we concluded that G{alpha}q mediates UV-induced COX-2 expression through activation of EGFR by HB-EGF, of which ectodomain shedding was stimulated through sequential activation of PLC, PKC{delta} and MMP-2 in HaCaT cells.« less

  20. Sulforaphane-induced autophagy flux prevents prion protein-mediated neurotoxicity through AMPK pathway.

    PubMed

    Lee, J-H; Jeong, J-K; Park, S-Y

    2014-10-10

    Prion diseases are neurodegenerative and infectious disorders that involve accumulation of misfolded scrapie prion protein, and which are characterized by spongiform degeneration. Autophagy, a major homeostatic process responsible for the degradation of cytoplasmic components, has garnered attention as the potential target for neurodegenerative diseases such as prion disease. We focused on protective effects of sulforaphane found in cruciferous vegetables on prion-mediated neurotoxicity and the mechanism of sulforaphane related to autophagy. In human neuroblastoma cells, sulforaphane protected prion protein (PrP) (106-126)-mediated neurotoxicity and increased autophagy flux marker microtubule-associated protein 1 light chain 3-II protein levels, following a decrease of p62 protein level. Pharmacological and genetical inhibition of autophagy by 3MA, wortmannin and knockdown of autophagy-related 5 (ATG5) led to block the effect of sulforaphane against PrP (106-126)-induced neurotoxicity. Furthermore we demonstrated that both sulforaphane-induced autophagy and protective effect of sulforaphane against PrP (106-126)-induced neurotoxicity are dependent on the AMP-activated protein kinase (AMPK) signaling. The present results indicated that sulforaphane of cruciferous vegetables enhanced autophagy flux led to the protection effects against prion-mediated neurotoxicity, which was regulated by AMPK signaling pathways in human neuron cells. Our data also suggest that sulforaphane has a potential value as a therapeutic tool in neurodegenerative disease including prion diseases. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. SNX10 mediates alcohol-induced liver injury and steatosis by regulating the activation of chaperone-mediated autophagy.

    PubMed

    You, Yan; Li, Wan-Zhen; Zhang, Sulin; Hu, Bin; Li, Yue-Xuan; Li, Hai-Dong; Tang, Huan-Huan; Li, Qian-Wen; Guan, Yun-Yun; Liu, Li-Xin; Bao, Wei-Lian; Shen, Xiaoyan

    2018-07-01

    Alcoholic liver disease (ALD) is a major cause of morbidity and mortality worldwide. However, the cellular defense mechanisms underlying ALD are not well understood. Recent studies highlighted the involvement of chaperone-mediated autophagy (CMA) in regulating hepatic lipid metabolism. Sorting nexin (SNX)-10 has a regulatory function in endolysosomal trafficking and stabilisation. Here, we investigated the roles of SNX10 in CMA activation and in the pathogenesis of alcohol-induced liver injury and steatosis. Snx10 knockout (Snx10 KO) mice and their wild-type (WT) littermates fed either the Lieber-DeCarli liquid alcohol diet or a control liquid diet, and primary cultured WT and Snx10 KO hepatocytes stimulated with ethanol, were used as in vivo and in vitro ALD models, respectively. Activation of CMA, liver injury parameters, inflammatory cytokines, oxidative stress and lipid metabolism were measured. Compared with WT littermates, Snx10 KO mice exhibited a significant amelioration in ethanol-induced liver injury and hepatic steatosis. Both in vivo and in vitro studies showed that SNX10 deficiency upregulated lysosome-associated membrane protein type 2A (LAMP-2A) expression and CMA activation, which could be reversed by SNX10 overexpression in vitro. LAMP-2A interference confirmed that the upregulation of Nrf2 and AMPK signalling pathways induced by SNX10 deficiency relied on CMA activation. Pull-down assays revealed an interaction between SNX10 and cathepsin A (CTSA), a key enzyme involved in LAMP-2A degradation. Deficiency in SNX10 inhibited CTSA maturation and increased the stability of LAMP-2A, resulting in an increase in CMA activity. SNX10 controls CMA activity by mediating CTSA maturation, and, thus, has an essential role in alcohol-induced liver injury and steatosis. Our results provide evidence for SNX10 as a potential promising therapeutic target for preventing or ameliorating liver injury in ALD. Alcoholic liver disease is a major cause of morbidity and

  2. Prolonged asymmetric vestibular stimulation induces opposite, long-term effects on self-motion perception and ocular responses.

    PubMed

    Pettorossi, V E; Panichi, R; Botti, F M; Kyriakareli, A; Ferraresi, A; Faralli, M; Schieppati, M; Bronstein, A M

    2013-04-01

    Self-motion perception and the vestibulo-ocular reflex (VOR) were investigated in healthy subjects during asymmetric whole body yaw plane oscillations while standing on a platform in the dark. Platform oscillation consisted of two half-sinusoidal cycles of the same amplitude (40°) but different duration, featuring a fast (FHC) and a slow half-cycle (SHC). Rotation consisted of four or 20 consecutive cycles to probe adaptation further with the longer duration protocol. Self-motion perception was estimated by subjects tracking with a pointer the remembered position of an earth-fixed visual target. VOR was measured by electro-oculography. The asymmetric stimulation pattern consistently induced a progressive increase of asymmetry in motion perception, whereby the gain of the tracking response gradually increased during FHCs and decreased during SHCs. The effect was observed already during the first few cycles and further increased during 20 cycles, leading to a totally distorted location of the initial straight-ahead. In contrast, after some initial interindividual variability, the gain of the slow phase VOR became symmetric, decreasing for FHCs and increasing for SHCs. These oppositely directed adaptive effects in motion perception and VOR persisted for nearly an hour. Control conditions using prolonged but symmetrical stimuli produced no adaptive effects on either motion perception or VOR. These findings show that prolonged asymmetric activation of the vestibular system leads to opposite patterns of adaptation of self-motion perception and VOR. The results provide strong evidence that semicircular canal inputs are processed centrally by independent mechanisms for perception of body motion and eye movement control. These divergent adaptation mechanisms enhance awareness of movement toward the faster body rotation, while improving the eye stabilizing properties of the VOR.

  3. Mechanisms and mediators of hypertension induced by erythropoietin and related molecules.

    PubMed

    Agarwal, Rajiv

    2017-12-08

    Hypertension is a common but frequently overlooked adverse effect of erythropoietin (EPO) therapy. Underreporting of hypertension with EPO is likely due to either more aggressively managing hypertension through the prescription of antihypertensive drugs or closer attention to dry weight. The purpose and focus of this review is to critically evaluate the mechanisms of EPO-induced hypertension. Preclinical data are considered first, followed by clinical data where available. Mediated by a variety of molecules, there is an imbalance in the vascular tone favoring net vasoconstriction that mediates EPO-induced hypertension. Animal studies show the primary importance of chronic kidney disease in the genesis of EPO-induced hypertension. Preclinical studies show deranged regulation of the nitric oxide, endothelins and porstanoids and the sympathoadrenal and renin-angiotensin pathways as causes of EPO-induced hypertension. Human studies suggest that EPO administration is also associated with increased responsiveness to catecholamines and angiotensin II on vascular tissue; in addition, hypoxia-induced vasodilation may be impaired in those with EPO-induced hypertension. There is little evidence for EPO as a direct vasoconstrictor or its effect on blood viscosity as a mechanism of EPO-induced hypertension. EPO-induced hypertension, at least in part, appears to be independent of an increase in hemoglobin, because experiments show that hemoglobin may be increased by EPO without an increase in blood pressure (BP) by simply treating the animals with EPO-binding protein and that treatment with EPO in the setting of iron deficiency may not increase hemoglobin but may still increase BP. However, experimental data are not consistent across studies and better mechanistic designs are needed, especially in patients with chronic kidney disease, to dissect the precise mechanism of EPO-induced hypertension. Animal studies suggest that hypoxia-inducible factor stablizers may induce

  4. Form and motion make independent contributions to the response to biological motion in occipitotemporal cortex.

    PubMed

    Thompson, James C; Baccus, Wendy

    2012-01-02

    Psychophysical and computational studies have provided evidence that both form and motion cues are used in the perception of biological motion. However, neuroimaging and neurophysiological studies have suggested that the neural processing of actions in temporal cortex might rely on form cues alone. Here we examined the contribution of form and motion to the spatial pattern of response to biological motion in ventral and lateral occipitotemporal cortex, using functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis (MVPA). We found that selectivity to intact versus scrambled biological motion in lateral occipitotemporal cortex was correlated with selectivity for bodies and not for motion. However, this appeared to be due to the fact that subtracting scrambled from intact biological motion removes any contribution of local motion cues. Instead, we found that form and motion made independent contributions to the spatial pattern of responses to biological motion in lateral occipitotemporal regions MT, MST, and the extrastriate body area. The motion contribution was position-dependent, and consistent with the representation of contra- and ipsilateral visual fields in MT and MST. In contrast, only form contributed to the response to biological motion in the fusiform body area, with a bias towards central versus peripheral presentation. These results indicate that the pattern of response to biological motion in ventral and lateral occipitotemporal cortex reflects the linear combination of responses to form and motion. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Methamphetamine-induced neurotoxicity and microglial activation are not mediated by fractalkine receptor signaling

    PubMed Central

    Thomas, David M.; Francescutti-Verbeem, Dina M.; Kuhn, Donald M.

    2009-01-01

    Methamphetamine (METH) damages dopamine (DA) nerve endings by a process that has been linked to microglial activation but the signaling pathways that mediate this response have not yet been delineated. Cardona et al. [Nat. Neurosci. 9 (2006), 917] recently identified the microglial-specific fractalkine receptor (CX3CR1) as an important mediator of MPTP-induced neurodegeneration of DA neurons. Because the CNS damage caused by METH and MPTP is highly selective for the DA neuronal system in mouse models of neurotoxicity, we hypothesized that the CX3CR1 plays a role in METH-induced neurotoxicity and microglial activation. Mice in which the CX3CR1 gene has been deleted and replaced with a cDNA encoding enhanced green fluorescent protein (eGFP) were treated with METH and examined for striatal neurotoxicity. METH depleted DA, caused microglial activation, and increased body temperature in CX3CR1 knockout mice to the same extent and over the same time course seen in wild-type controls. The effects of METH in CX3CR1 knockout mice were not gender-dependent and did not extend beyond the striatum. Striatal microglia expressing eGFP constitutively show morphological changes after METH that are characteristic of activation. This response was restricted to the striatum and contrasted sharply with unresponsive eGFP-microglia in surrounding brain areas that are not damaged by METH. We conclude from these studies that CX3CR1 signaling does not modulate METH neurotoxicity or microglial activation. Furthermore, it appears that striatal-resident microglia respond to METH with an activation cascade and then return to a surveying state without undergoing apoptosis or migration. PMID:18410508

  6. Methamphetamine-induced neurotoxicity and microglial activation are not mediated by fractalkine receptor signaling.

    PubMed

    Thomas, David M; Francescutti-Verbeem, Dina M; Kuhn, Donald M

    2008-07-01

    Methamphetamine (METH) damages dopamine (DA) nerve endings by a process that has been linked to microglial activation but the signaling pathways that mediate this response have not yet been delineated. Cardona et al. [Nat. Neurosci. 9 (2006), 917] recently identified the microglial-specific fractalkine receptor (CX3CR1) as an important mediator of MPTP-induced neurodegeneration of DA neurons. Because the CNS damage caused by METH and MPTP is highly selective for the DA neuronal system in mouse models of neurotoxicity, we hypothesized that the CX3CR1 plays a role in METH-induced neurotoxicity and microglial activation. Mice in which the CX3CR1 gene has been deleted and replaced with a cDNA encoding enhanced green fluorescent protein (eGFP) were treated with METH and examined for striatal neurotoxicity. METH depleted DA, caused microglial activation, and increased body temperature in CX3CR1 knockout mice to the same extent and over the same time course seen in wild-type controls. The effects of METH in CX3CR1 knockout mice were not gender-dependent and did not extend beyond the striatum. Striatal microglia expressing eGFP constitutively show morphological changes after METH that are characteristic of activation. This response was restricted to the striatum and contrasted sharply with unresponsive eGFP-microglia in surrounding brain areas that are not damaged by METH. We conclude from these studies that CX3CR1 signaling does not modulate METH neurotoxicity or microglial activation. Furthermore, it appears that striatal-resident microglia respond to METH with an activation cascade and then return to a surveying state without undergoing apoptosis or migration.

  7. Menadione induces the formation of reactive oxygen species and depletion of GSH-mediated apoptosis and inhibits the FAK-mediated cell invasion.

    PubMed

    Kim, Yun Jeong; Shin, Yong Kyoo; Sohn, Dong Suep; Lee, Chung Soo

    2014-09-01

    Menadione induces apoptosis in tumor cells. However, the mechanism of apoptosis in ovarian cancer cells exposed to menadione is not clear. In addition, it is unclear whether menadione-induced apoptosis is mediated by the depletion of glutathione (GSH) contents that is associated with the formation of reactive oxygen species. Furthermore, the effect of menadione on the invasion and migration of human epithelial ovarian cancer cells has not been studied. Therefore, we investigated the effects of menadione exposure on apoptosis, cell adhesion, and cell migration using the human epithelial ovarian carcinoma cell lines OVCAR-3 and SK-OV-3. The results suggest that menadione may induce apoptotic cell death in ovarian carcinoma cell lines by activating the mitochondrial pathway and the caspase-8- and Bid-dependent pathways. The apoptotic effect of menadione appears to be mediated by the formation of reactive oxygen species and the depletion of GSH. Menadione inhibited fetal-bovine-serum-induced cell adhesion and migration of OVCAR-3 cells, possibly through the suppression the focal adhesion kinase (FAK)-dependent activation of cytoskeletal-associated components. Therefore, menadione might be beneficial in the treatment of epithelial ovarian adenocarcinoma and combination therapy.

  8. CHOP Contributes to, But Is Not the Only Mediator of, IAPP Induced β-Cell Apoptosis.

    PubMed

    Gurlo, T; Rivera, J F; Butler, A E; Cory, M; Hoang, J; Costes, S; Butler, Peter C

    2016-04-01

    The islet in type 2 diabetes is characterized by β-cell loss, increased β-cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). When protein misfolding protective mechanisms are overcome, human IAPP (h-IAPP) forms membrane permeant toxic oligomers that induce β-cell dysfunction and apoptosis. In humans with type 2 diabetes (T2D) and mice transgenic for h-IAPP, endoplasmic reticulum (ER) stress has been inferred from nuclear translocation of CCAAT/enhancer-binding protein homologous protein (CHOP), an established mediator of ER stress. To establish whether h-IAPP toxicity is mediated by ER stress, we evaluated diabetes onset and β-cell mass in h-IAPP transgenic (h-TG) mice with and without deletion of CHOP in comparison with wild-type controls. Diabetes was delayed in h-TG CHOP(-/-) mice, with relatively preserved β-cell mass and decreased β-cell apoptosis. Deletion of CHOP attenuates dysfunction of the autophagy/lysosomal pathway in β-cells of h-TG mice, uncovering a role for CHOP in mediating h-IAPP-induced dysfunction of autophagy. As deletion of CHOP delayed but did not prevent h-IAPP-induced β-cell loss and diabetes, we examined CHOP-independent stress pathways. JNK, a target of the IRE-1pTRAF2 complex, and the Bcl-2 family proapoptotic mediator BIM, a target of ATF4, were comparably activated by h-IAPP expression in the presence and absence of CHOP. Therefore, although these studies affirm that CHOP is a mediator of h-IAPP-induced ER stress, it is not the only one. Therefore, suppression of CHOP alone is unlikely to be a durable therapeutic strategy to protect against h-IAPP toxicity because multiple stress pathways are activated.

  9. Role of Alpha-Band Oscillations in Spatial Updating across Whole Body Motion

    PubMed Central

    Gutteling, Tjerk P.; Medendorp, W. P.

    2016-01-01

    When moving around in the world, we have to keep track of important locations in our surroundings. In this process, called spatial updating, we must estimate our body motion and correct representations of memorized spatial locations in accordance with this motion. While the behavioral characteristics of spatial updating across whole body motion have been studied in detail, its neural implementation lacks detailed study. Here we use electroencephalography (EEG) to distinguish various spectral components of this process. Subjects gazed at a central body-fixed point in otherwise complete darkness, while a target was briefly flashed, either left or right from this point. Subjects had to remember the location of this target as either moving along with the body or remaining fixed in the world while being translated sideways on a passive motion platform. After the motion, subjects had to indicate the remembered target location in the instructed reference frame using a mouse response. While the body motion, as detected by the vestibular system, should not affect the representation of body-fixed targets, it should interact with the representation of a world-centered target to update its location relative to the body. We show that the initial presentation of the visual target induced a reduction of alpha band power in contralateral parieto-occipital areas, which evolved to a sustained increase during the subsequent memory period. Motion of the body led to a reduction of alpha band power in central parietal areas extending to lateral parieto-temporal areas, irrespective of whether the targets had to be memorized relative to world or body. When updating a world-fixed target, its internal representation shifts hemispheres, only when subjects’ behavioral responses suggested an update across the body midline. Our results suggest that parietal cortex is involved in both self-motion estimation and the selective application of this motion information to maintaining target

  10. Activation of G proteins mediates flow-induced prostaglandin E2 production in osteoblasts

    NASA Technical Reports Server (NTRS)

    Reich, K. M.; McAllister, T. N.; Gudi, S.; Frangos, J. A.

    1997-01-01

    Interstitial fluid flow may play a role in load-induced bone remodeling. Previously, we have shown that fluid flow stimulates osteoblast production of cAMP inositol trisphosphate (IP3), and PGE2. Flow-induced increases in cAMP and IP3 were shown to be a result of PG production. Thus, PGE2 production appears to be an important component in fluid flow induced signal transduction. In the present study, we investigated the mechanism of flow-induced PGE2 synthesis. Flow-induced a 20-fold increase in PGE2 production in osteoblasts. Increases were also observed with ALF4-(10mM) (98-fold), an activator of guanidine nucleotide-binding proteins (G proteins), and calcium ionophore A23187 (2 microM) (100-fold) in stationary cells. We then investigated whether flow stimulation is mediated by G proteins and increases in intracellular calcium. Flow-induced PGE2 production was inhibited by the G protein inhibitors GDP beta S (100 microM) and pertussis toxin (1 microgram/ml) by 83% and 72%, respectively. Chelation of extracellular calcium by EGTA (2 mM) and intracellular calcium by quin-2/AM (30 microM) blocked flow stimulation by 87% and 67%, respectively. These results suggest that G proteins and calcium play an important role in mediating mechanochemical signal transduction in osteoblasts.

  11. Is Diaphragm Motion a Good Surrogate for Liver Tumor Motion?

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

    Yang, Juan; School of Information Science and Engineering, Shandong University, Jinan, Shandong; Cai, Jing

    Purpose: To evaluate the relationship between liver tumor motion and diaphragm motion. Methods and Materials: Fourteen patients with hepatocellular carcinoma (10 of 14) or liver metastases (4 of 14) undergoing radiation therapy were included in this study. All patients underwent single-slice cine–magnetic resonance imaging simulations across the center of the tumor in 3 orthogonal planes. Tumor and diaphragm motion trajectories in the superior–inferior (SI), anterior–posterior (AP), and medial–lateral (ML) directions were obtained using an in-house-developed normalized cross-correlation–based tracking technique. Agreement between the tumor and diaphragm motion was assessed by calculating phase difference percentage, intraclass correlation coefficient, and Bland-Altman analysis (Diff).more » The distance between the tumor and tracked diaphragm area was analyzed to understand its impact on the correlation between the 2 motions. Results: Of all patients, the mean (±standard deviation) phase difference percentage values were 7.1% ± 1.1%, 4.5% ± 0.5%, and 17.5% ± 4.5% in the SI, AP, and ML directions, respectively. The mean intraclass correlation coefficient values were 0.98 ± 0.02, 0.97 ± 0.02, and 0.08 ± 0.06 in the SI, AP, and ML directions, respectively. The mean Diff values were 2.8 ± 1.4 mm, 2.4 ± 1.1 mm, and 2.2 ± 0.5 mm in the SI, AP, and ML directions, respectively. Tumor and diaphragm motions had high concordance when the distance between the tumor and tracked diaphragm area was small. Conclusions: This study showed that liver tumor motion had good correlation with diaphragm motion in the SI and AP directions, indicating diaphragm motion in the SI and AP directions could potentially be used as a reliable surrogate for liver tumor motion.« less

  12. NLRP3 inflammasome activation mediates radiation-induced pyroptosis in bone marrow-derived macrophages

    PubMed Central

    Liu, Yan-gang; Chen, Ji-kuai; Zhang, Zi-teng; Ma, Xiu-juan; Chen, Yong-chun; Du, Xiu-ming; Liu, Hong; Zong, Ying; Lu, Guo-cai

    2017-01-01

    A limit to the clinical benefit of radiotherapy is not an incapacity to eliminate tumor cells but rather a limit on its capacity to do so without destroying normal tissue and inducing inflammation. Recent evidence reveals that the inflammasome is essential for mediating radiation-induced cell and tissue damage. In this study, using primary cultured bone marrow-derived macrophages (BMDM) and a mouse radiation model, we explored the role of NLRP3 inflammasome activation and the secondary pyroptosis underlying radiation-induced immune cell death. We observed an increasing proportion of pyroptosis and elevating Caspase-1 activation in 10 and 20 Gy radiation groups. Nlrp3 knock out significantly diminished the quantity of cleaved-Caspase-1 (p10) and IL-1β as well as the proportion of pyroptosis. Additionally, in vivo research shows that 9.5 Gy of radiation promotes Caspase-1 activation in marginal zone cells and induces death in mice, both of which can be significantly inhibited by knocking out Nlrp3. Thus, based on these findings, we conclude that the NLRP3 inflammasome activation mediates radiation-induced pyroptosis in BMDMs. Targeting NLRP3 inflammasome and pyroptosis may serve as effective strategies to diminish injury caused by radiation. PMID:28151471

  13. Urban dogs in rural areas: Human-mediated movement defines dog populations in southern Chile.

    PubMed

    Villatoro, Federico J; Sepúlveda, Maximiliano A; Stowhas, Paulina; Silva-Rodríguez, Eduardo A

    2016-12-01

    Management strategies for dog populations and their diseases include reproductive control, euthanasia and vaccination, among others. However, the effectiveness of these strategies can be severely affected by human-mediated dog movement. If immigration is important, then the location of origin of dogs imported by humans will be fundamental to define the spatial scales over which population management and research should apply. In this context, the main objective of our study was to determine the spatial extent of dog demographic processes in rural areas and the proportion of dogs that could be labeled as immigrants at multiple spatial scales. To address our objective we conducted surveys in households located in a rural landscape in southern Chile. Interviews allowed us to obtain information on the demographic characteristics of dogs in these rural settings, human influence on dog mortality and births, the localities of origin of dogs living in rural areas, and the spatial extent of human-mediated dog movement. We found that most rural dogs (64.1%) were either urban dogs that had been brought to rural areas (40.0%), or adopted dogs that had been previously abandoned in rural roads (24.1%). Some dogs were brought from areas located as far as ∼700km away from the study area. Human-mediated movement of dogs, especially from urban areas, seems to play a fundamental role in the population dynamics of dogs in rural areas. Consequently, local scale efforts to manage dog populations or their diseases are unlikely to succeed if implemented in isolation, simply because dogs can be brought from surrounding urban areas or even distant locations. We suggest that efforts to manage or study dog populations and related diseases should be implemented using a multi-scale approach. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Sphingosine kinase-1 mediates androgen-induced osteoblast cell growth

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

    Martin, Claire; Universite de Toulouse, UPS, IPBS, Toulouse F-31000; Lafosse, Jean-Michel

    Herein we report that the lipid kinase sphingosine kinase-1 (SphK1) is instrumental in mediating androgen-induced cell proliferation in osteoblasts. Dihydrotestosterone (DHT) triggered cell growth in steroid-deprived MC3T3 cells, which was associated with a rapid stimulation of SphK1 and activation of both Akt and ERK signaling pathways. This mechanism relied on functional androgen receptor/PI3K/Akt nongenotropic signaling as pharmacological antagonists could block SphK1 stimulation by DHT and its consequences. Finally, SphK1 inhibition not only abrogated DHT-induced ERK activation but also blocked cell proliferation, while ERK inhibition had no impact, suggesting that SphK1 was critical for DHT signaling yet independently of the ERK.

  15. Nickel chloride-induced apoptosis via mitochondria- and Fas-mediated caspase-dependent pathways in broiler chickens.

    PubMed

    Guo, Hongrui; Cui, Hengmin; Fang, Jing; Zuo, Zhicai; Deng, Junliang; Wang, Xun; Zhao, Ling; Wu, Bangyuan; Chen, Kejie; Deng, Jie

    2016-11-29

    Ni, a metal with industrial and commercial uses, poses a serious hazard to human and animal health. In the present study, we used flow cytometry, immunohistochemistry and qRT-PCR to investigate the mechanisms of NiCl2-induced apoptosis in kidney cells. After treating 280 broiler chickens with 0, 300, 600 or 900 mg/kg NiCl2 for 42 days, we found that two caspase-dependent pathways were involved in the induced renal tubular cell apoptosis. In the mitochondria-mediated caspase-dependent apoptotic pathway, cyt-c, HtrA2/Omi, Smac/Diablo, apaf-1, PARP, and caspase-9, 3, 6 and 7 were all increased, while. XIAP transcription was decreased. Concurrently, in the Fas-mediated caspase-dependent apoptotic pathway, Fas, FasL, caspase-8, caspase-10 and Bid levels were all increased. These results indicate that dietary NiCl2 at 300+ mg/kg induces renal tubular cell apoptosis in broiler chickens, involving both mitochondrial and Fas-mediated caspase-dependent apoptotic pathways. Our results provide novel insight into Ni and Ni-compound toxicology evaluated in vitro and in vivo.

  16. Nickel chloride-induced apoptosis via mitochondria- and Fas-mediated caspase-dependent pathways in broiler chickens

    PubMed Central

    Guo, Hongrui; Cui, Hengmin; Fang, Jing; Zuo, Zhicai; Deng, Junliang; Wang, Xun; Zhao, Ling; Wu, Bangyuan; Chen, Kejie; Deng, Jie

    2016-01-01

    Ni, a metal with industrial and commercial uses, poses a serious hazard to human and animal health. In the present study, we used flow cytometry, immunohistochemistry and qRT-PCR to investigate the mechanisms of NiCl2-induced apoptosis in kidney cells. After treating 280 broiler chickens with 0, 300, 600 or 900 mg/kg NiCl2 for 42 days, we found that two caspase-dependent pathways were involved in the induced renal tubular cell apoptosis. In the mitochondria-mediated caspase-dependent apoptotic pathway, cyt-c, HtrA2/Omi, Smac/Diablo, apaf-1, PARP, and caspase-9, 3, 6 and 7 were all increased, while. XIAP transcription was decreased. Concurrently, in the Fas-mediated caspase-dependent apoptotic pathway, Fas, FasL, caspase-8, caspase-10 and Bid levels were all increased. These results indicate that dietary NiCl2 at 300+ mg/kg induces renal tubular cell apoptosis in broiler chickens, involving both mitochondrial and Fas-mediated caspase-dependent apoptotic pathways. Our results provide novel insight into Ni and Ni-compound toxicology evaluated in vitro and in vivo. PMID:27806327

  17. Electrical acustimulation relieves vection-induced motion sickness

    NASA Technical Reports Server (NTRS)

    Hu, S.; Stern, R. M.; Koch, K. L.

    1992-01-01

    The aim of this study was to examine the effects of electrical acustimulation on gastric myoelectric activity and severity of symptoms of motion sickness. In experiment 1, 16 Chinese subjects received electrical acustimulation in one of two sessions. In experiment 2, 45 white and black American subjects were randomly divided into three groups: acustimulation, sham acustimulation, and control. Each subject sat in an optokinetic drum for 15 minutes baseline and 15 minutes of drum rotation. Subjects' electrogastrograms and subjective symptoms of motion sickness were obtained. In experiment 1, the mean symptom score and tachyarrhythmia during acustimulation sessions were significantly lower than during no-acustimulation sessions. In experiment 2, the mean symptom score of the acustimulation group was significantly lower than that of the sham-stimulation group and the control group; tachyarrhythmia in the acustimulation group was significantly less than that of the control group but not the sham-stimulation group. In conclusion, electrical acustimulation reduces the severity of symptoms of motion sickness and appears to decrease gastric tachyarrhythmia.

  18. Central apelin mediates stress-induced gastrointestinal motor dysfunction in rats.

    PubMed

    Bülbül, Mehmet; İzgüt-Uysal, V Nimet; Sinen, Osman; Birsen, İlknur; Tanrıöver, Gamze

    2016-02-15

    Apelin, an endogenous ligand for APJ receptor, has been reported to be upregulated in paraventricular nucleus (PVN) following stress. Central apelin is known to stimulate release of corticotropin-releasing factor (CRF) via APJ receptor. We tested the hypothesis that stress-induced gastrointestinal (GI) dysfunction is mediated by central apelin. We also assessed the effect of exogenous apelin on GI motility under nonstressed (NS) conditions in conscious rats. Prior to solid gastric emptying (GE) and colon transit (CT) measurements, APJ receptor antagonist F13A was centrally administered under NS conditions and following acute stress (AS), chronic homotypic stress (CHS), and chronic heterotypic stress (CHeS). Plasma corticosterone was assayed. Strain gage transducers were implanted on serosal surfaces of antrum and distal colon to record postprandial motility. Stress exposure induced coexpression of c-Fos and apelin in hypothalamic PVN. Enhanced hypothalamic apelin and CRF levels in microdialysates were detected following AS and CHeS, which were negatively and positively correlated with GE and CT, respectively. Central F13A administration abolished delayed GE and accelerated CT induced by AS and CHeS. Central apelin-13 administration increased the plasma corticosterone and inhibited GE and CT by attenuating antral and colonic contractions. The inhibitory effect elicited by apelin-13 was abolished by central pretreatment of CRF antagonist CRF9-41 in antrum, but not in distal colon. Central endogenous apelin mediates stress-induced changes in gastric and colonic motor functions through APJ receptor. The inhibitory effects of central exogenous apelin-13 on GI motility appear to be partly CRF dependent. Apelin-13 inhibits colon motor functions through a CRF-independent pathway. Copyright © 2016 the American Physiological Society.

  19. Predictive local receptive fields based respiratory motion tracking for motion-adaptive radiotherapy.

    PubMed

    Yubo Wang; Tatinati, Sivanagaraja; Liyu Huang; Kim Jeong Hong; Shafiq, Ghufran; Veluvolu, Kalyana C; Khong, Andy W H

    2017-07-01

    Extracranial robotic radiotherapy employs external markers and a correlation model to trace the tumor motion caused by the respiration. The real-time tracking of tumor motion however requires a prediction model to compensate the latencies induced by the software (image data acquisition and processing) and hardware (mechanical and kinematic) limitations of the treatment system. A new prediction algorithm based on local receptive fields extreme learning machines (pLRF-ELM) is proposed for respiratory motion prediction. All the existing respiratory motion prediction methods model the non-stationary respiratory motion traces directly to predict the future values. Unlike these existing methods, the pLRF-ELM performs prediction by modeling the higher-level features obtained by mapping the raw respiratory motion into the random feature space of ELM instead of directly modeling the raw respiratory motion. The developed method is evaluated using the dataset acquired from 31 patients for two horizons in-line with the latencies of treatment systems like CyberKnife. Results showed that pLRF-ELM is superior to that of existing prediction methods. Results further highlight that the abstracted higher-level features are suitable to approximate the nonlinear and non-stationary characteristics of respiratory motion for accurate prediction.

  20. Directed motion of spheres induced by unbiased driving forces in viscous fluids beyond the Stokes' law regime

    NASA Astrophysics Data System (ADS)

    Casado-Pascual, Jesús

    2018-03-01

    The emergence of directed motion is investigated in a system consisting of a sphere immersed in a viscous fluid and subjected to time-periodic forces of zero average. The directed motion arises from the combined action of a nonlinear drag force and the applied driving forces, in the absence of any periodic substrate potential. Necessary conditions for the existence of such directed motion are obtained and an analytical expression for the average terminal velocity is derived within the adiabatic approximation. Special attention is paid to the case of two mutually perpendicular forces with sinusoidal time dependence, one with twice the period of the other. It is shown that, although neither of these two forces induces directed motion when acting separately, when added together, the resultant force generates directed motion along the direction of the force with the shortest period. The dependence of the average terminal velocity on the system parameters is analyzed numerically and compared with that obtained using the adiabatic approximation. Among other results, it is found that, for appropriate parameter values, the direction of the average terminal velocity can be reversed by varying the forcing strength. Furthermore, certain aspects of the observed phenomenology are explained by means of symmetry arguments.

  1. Differential Responses to a Visual Self-Motion Signal in Human Medial Cortical Regions Revealed by Wide-View Stimulation

    PubMed Central

    Wada, Atsushi; Sakano, Yuichi; Ando, Hiroshi

    2016-01-01

    Vision is important for estimating self-motion, which is thought to involve optic-flow processing. Here, we investigated the fMRI response profiles in visual area V6, the precuneus motion area (PcM), and the cingulate sulcus visual area (CSv)—three medial brain regions recently shown to be sensitive to optic-flow. We used wide-view stereoscopic stimulation to induce robust self-motion processing. Stimuli included static, randomly moving, and coherently moving dots (simulating forward self-motion). We varied the stimulus size and the presence of stereoscopic information. A combination of univariate and multi-voxel pattern analyses (MVPA) revealed that fMRI responses in the three regions differed from each other. The univariate analysis identified optic-flow selectivity and an effect of stimulus size in V6, PcM, and CSv, among which only CSv showed a significantly lower response to random motion stimuli compared with static conditions. Furthermore, MVPA revealed an optic-flow specific multi-voxel pattern in the PcM and CSv, where the discrimination of coherent motion from both random motion and static conditions showed above-chance prediction accuracy, but that of random motion from static conditions did not. Additionally, while area V6 successfully classified different stimulus sizes regardless of motion pattern, this classification was only partial in PcM and was absent in CSv. This may reflect the known retinotopic representation in V6 and the absence of such clear visuospatial representation in CSv. We also found significant correlations between the strength of subjective self-motion and univariate activation in all examined regions except for primary visual cortex (V1). This neuro-perceptual correlation was significantly higher for V6, PcM, and CSv when compared with V1, and higher for CSv when compared with the visual motion area hMT+. Our convergent results suggest the significant involvement of CSv in self-motion processing, which may give rise to its

  2. Electric field control of magnon-induced magnetization dynamics in multiferroics

    PubMed Central

    Risinggård, Vetle; Kulagina, Iryna; Linder, Jacob

    2016-01-01

    We consider theoretically the effect of an inhomogeneous magnetoelectric coupling on the magnon-induced dynamics of a ferromagnet. The magnon-mediated magnetoelectric torque affects both the homogeneous magnetization and magnon-driven domain wall motion. In the domains, we predict a reorientation of the magnetization, controllable by the applied electric field, which is almost an order of magnitude larger than that observed in other physical systems via the same mechanism. The applied electric field can also be used to tune the domain wall speed and direction of motion in a linear fashion, producing domain wall velocities several times the zero field velocity. These results show that multiferroic systems offer a promising arena to achieve low-dissipation magnetization rotation and domain wall motion by exciting spin-waves. PMID:27554064

  3. Electric field control of magnon-induced magnetization dynamics in multiferroics.

    PubMed

    Risinggård, Vetle; Kulagina, Iryna; Linder, Jacob

    2016-08-24

    We consider theoretically the effect of an inhomogeneous magnetoelectric coupling on the magnon-induced dynamics of a ferromagnet. The magnon-mediated magnetoelectric torque affects both the homogeneous magnetization and magnon-driven domain wall motion. In the domains, we predict a reorientation of the magnetization, controllable by the applied electric field, which is almost an order of magnitude larger than that observed in other physical systems via the same mechanism. The applied electric field can also be used to tune the domain wall speed and direction of motion in a linear fashion, producing domain wall velocities several times the zero field velocity. These results show that multiferroic systems offer a promising arena to achieve low-dissipation magnetization rotation and domain wall motion by exciting spin-waves.

  4. Fas- and Mitochondria-Mediated Signaling Pathway Involved in Osteoblast Apoptosis Induced by AlCl3.

    PubMed

    Xu, Feibo; Ren, Limin; Song, Miao; Shao, Bing; Han, Yanfei; Cao, Zheng; Li, Yanfei

    2018-07-01

    Aluminum (Al) is known to induce apoptosis of osteoblasts (OBs). However, the mechanism is not yet established. To investigate the apoptotic mechanism of OBs induced by aluminum trichloride (AlCl 3 ), the primary OBs from the craniums of fetal Wistar rats were exposed to 0 mg/mL (control group, CG), 0.06 mg/mL (low-dose group, LG), 0.12 mg/mL (mid-dose group, MG), and 0.24 mg/mL (high-dose group, HG) AlCl 3 for 24 h, respectively. We observed that AlCl 3 induced OB apoptosis with the appearance of apoptotic morphology and increase of apoptosis rate. Additionally, AlCl 3 treatment activated mitochondrial-mediated signaling pathway, accompanied by mitochondrial membrane potential (ΔΨm) depolarization, release of cytochrome c from the mitochondria to the cytoplasm, as well as survival signal-related factor caspase-9 and caspase-3 activation. AlCl 3 exposure also activated Fas/Fas ligand signaling pathway, presented as Fas, Fas ligand, and Fas-associated death domain expression enhancement and caspase-8 activation, as well as the hydrolysis of Bid to truncated Bid, suggesting that the Fas-mediated signaling pathway might aggravate mitochondria-mediated OB apoptosis through hydrolyzing Bid. Furthermore, AlCl 3 exposure inhibited Bcl-2 protein expression and increased the expressions of Bax, Bak, and Bim in varying degrees. These results indicated that AlCl 3 exposure induced OB apoptosis through activating Fas- and mitochondria-mediated signaling pathway and disrupted B-cell lymphoma-2 family proteins.

  5. Fiber-Mediated Nourishment of Gut Microbiota Protects against Diet-Induced Obesity by Restoring IL-22-Mediated Colonic Health.

    PubMed

    Zou, Jun; Chassaing, Benoit; Singh, Vishal; Pellizzon, Michael; Ricci, Matthew; Fythe, Michael D; Kumar, Matam Vijay; Gewirtz, Andrew T

    2018-01-10

    Dietary supplementation with fermentable fiber suppresses adiposity and the associated parameters of metabolic syndrome. Microbiota-generated fiber-derived short-chain fatty acids (SCFAs) and free fatty acid receptors including GPR43 are thought to mediate these effects. We find that while fermentable (inulin), but not insoluble (cellulose), fiber markedly protected mice against high-fat diet (HFD)-induced metabolic syndrome, the effect was not significantly impaired by either inhibiting SCFA production or genetic ablation of GPR43. Rather, HFD decimates gut microbiota, resulting in loss of enterocyte proliferation, leading to microbiota encroachment, low-grade inflammation (LGI), and metabolic syndrome. Enriching HFD with inulin restored microbiota loads, interleukin-22 (IL-22) production, enterocyte proliferation, and antimicrobial gene expression in a microbiota-dependent manner, as assessed by antibiotic and germ-free approaches. Inulin-induced IL-22 expression, which required innate lymphoid cells, prevented microbiota encroachment and protected against LGI and metabolic syndrome. Thus, fermentable fiber protects against metabolic syndrome by nourishing microbiota to restore IL-22-mediated enterocyte function. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Ultra-low frequency vibration data acquisition concerns in operating flight simulators. [Motion sickness inducing vibrations in flight simulators

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

    Van Hoy, B.W.

    1988-01-01

    The measurement of ultra-low frequency vibration (.01 to 1.0 Hz) in motion based flight simulators was undertaken to quantify the energy and frequencies of motion present during operation. Methods of measurement, the selection of transducers, recorders, and analyzers and the development of a test plan, as well as types of analysis are discussed. Analysis of the data using a high-speed minicomputer and a comparison of the computer analysis with standard FFT analysis are also discussed. Measurement of simulator motion with the pilot included as part of the control dynamics had not been done up to this time. The data aremore » being used to evaluate the effect of low frequency energy on the vestibular system of the air crew, and the incidence of simulator induced sickness. 11 figs.« less

  7. The motional stark effect with laser-induced fluorescence diagnostic

    NASA Astrophysics Data System (ADS)

    Foley, E. L.; Levinton, F. M.

    2010-05-01

    The motional Stark effect (MSE) diagnostic is the worldwide standard technique for internal magnetic field pitch angle measurements in magnetized plasmas. Traditionally, it is based on using polarimetry to measure the polarization direction of light emitted from a hydrogenic species in a neutral beam. As the beam passes through the magnetized plasma at a high velocity, in its rest frame it perceives a Lorentz electric field. This field causes the H-alpha emission to be split and polarized. A new technique under development adds laser-induced fluorescence (LIF) to a diagnostic neutral beam (DNB) for an MSE measurement that will enable radially resolved magnetic field magnitude as well as pitch angle measurements in even low-field (<1 T) experiments. An MSE-LIF system will be installed on the National Spherical Torus Experiment (NSTX) at the Princeton Plasma Physics Laboratory. It will enable reconstructions of the plasma pressure, q-profile and current as well as, in conjunction with the existing MSE system, measurements of radial electric fields.

  8. Prolonged asymmetric vestibular stimulation induces opposite, long-term effects on self-motion perception and ocular responses

    PubMed Central

    Pettorossi, V E; Panichi, R; Botti, F M; Kyriakareli, A; Ferraresi, A; Faralli, M; Schieppati, M; Bronstein, A M

    2013-01-01

    Self-motion perception and the vestibulo-ocular reflex (VOR) were investigated in healthy subjects during asymmetric whole body yaw plane oscillations while standing on a platform in the dark. Platform oscillation consisted of two half-sinusoidal cycles of the same amplitude (40°) but different duration, featuring a fast (FHC) and a slow half-cycle (SHC). Rotation consisted of four or 20 consecutive cycles to probe adaptation further with the longer duration protocol. Self-motion perception was estimated by subjects tracking with a pointer the remembered position of an earth-fixed visual target. VOR was measured by electro-oculography. The asymmetric stimulation pattern consistently induced a progressive increase of asymmetry in motion perception, whereby the gain of the tracking response gradually increased during FHCs and decreased during SHCs. The effect was observed already during the first few cycles and further increased during 20 cycles, leading to a totally distorted location of the initial straight-ahead. In contrast, after some initial interindividual variability, the gain of the slow phase VOR became symmetric, decreasing for FHCs and increasing for SHCs. These oppositely directed adaptive effects in motion perception and VOR persisted for nearly an hour. Control conditions using prolonged but symmetrical stimuli produced no adaptive effects on either motion perception or VOR. These findings show that prolonged asymmetric activation of the vestibular system leads to opposite patterns of adaptation of self-motion perception and VOR. The results provide strong evidence that semicircular canal inputs are processed centrally by independent mechanisms for perception of body motion and eye movement control. These divergent adaptation mechanisms enhance awareness of movement toward the faster body rotation, while improving the eye stabilizing properties of the VOR. PMID:23318876

  9. TRPC3-Nox2 complex mediates doxorubicin-induced myocardial atrophy

    PubMed Central

    Shimauchi, Tsukasa; Numaga-Tomita, Takuro; Ito, Tomoya; Nishimura, Akiyuki; Matsukane, Ryosuke; Oda, Sayaka; Hoka, Sumio; Ide, Tomomi; Koitabashi, Norimichi; Uchida, Koji; Sumimoto, Hideki; Mori, Yasuo

    2017-01-01

    Myocardial atrophy is a wasting of cardiac muscle due to hemodynamic unloading. Doxorubicin is a highly effective anticancer agent but also induces myocardial atrophy through a largely unknown mechanism. Here, we demonstrate that inhibiting transient receptor potential canonical 3 (TRPC3) channels abolishes doxorubicin-induced myocardial atrophy in mice. Doxorubicin increased production of ROS in rodent cardiomyocytes through hypoxic stress–mediated upregulation of NADPH oxidase 2 (Nox2), which formed a stable complex with TRPC3. Cardiomyocyte-specific expression of TRPC3 C-terminal minipeptide inhibited TRPC3-Nox2 coupling and suppressed doxorubicin-induced reduction of myocardial cell size and left ventricular (LV) dysfunction, along with its upregulation of Nox2 and oxidative stress, without reducing hypoxic stress. Voluntary exercise, an effective treatment to prevent doxorubicin-induced cardiotoxicity, also downregulated the TRPC3-Nox2 complex and promoted volume load–induced LV compliance, as demonstrated in TRPC3-deficient hearts. These results illustrate the impact of TRPC3 on LV compliance and flexibility and, focusing on the TRPC3-Nox2 complex, provide a strategy for prevention of doxorubicin-induced cardiomyopathy. PMID:28768915

  10. Site-Directed Spin Labeling Reveals Pentameric Ligand-Gated Ion Channel Gating Motions

    PubMed Central

    Dellisanti, Cosma D.; Ghosh, Borna; Hanson, Susan M.; Raspanti, James M.; Grant, Valerie A.; Diarra, Gaoussou M.; Schuh, Abby M.; Satyshur, Kenneth; Klug, Candice S.; Czajkowski, Cynthia

    2013-01-01

    Pentameric ligand-gated ion channels (pLGICs) are neurotransmitter-activated receptors that mediate fast synaptic transmission. In pLGICs, binding of agonist to the extracellular domain triggers a structural rearrangement that leads to the opening of an ion-conducting pore in the transmembrane domain and, in the continued presence of neurotransmitter, the channels desensitize (close). The flexible loops in each subunit that connect the extracellular binding domain (loops 2, 7, and 9) to the transmembrane channel domain (M2–M3 loop) are essential for coupling ligand binding to channel gating. Comparing the crystal structures of two bacterial pLGIC homologues, ELIC and the proton-activated GLIC, suggests channel gating is associated with rearrangements in these loops, but whether these motions accurately predict the motions in functional lipid-embedded pLGICs is unknown. Here, using site-directed spin labeling (SDSL) electron paramagnetic resonance (EPR) spectroscopy and functional GLIC channels reconstituted into liposomes, we examined if, and how far, the loops at the ECD/TMD gating interface move during proton-dependent gating transitions from the resting to desensitized state. Loop 9 moves ∼9 Å inward toward the channel lumen in response to proton-induced desensitization. Loop 9 motions were not observed when GLIC was in detergent micelles, suggesting detergent solubilization traps the protein in a nonactivatable state and lipids are required for functional gating transitions. Proton-induced desensitization immobilizes loop 2 with little change in position. Proton-induced motion of the M2–M3 loop was not observed, suggesting its conformation is nearly identical in closed and desensitized states. Our experimentally derived distance measurements of spin-labeled GLIC suggest ELIC is not a good model for the functional resting state of GLIC, and that the crystal structure of GLIC does not correspond to a desensitized state. These findings advance our

  11. TRPA1 channel mediates organophosphate-induced delayed neuropathy

    PubMed Central

    Ding, Qiang; Fang, Sui; Chen, Xueqin; Wang, Youxin; Li, Jian; Tian, Fuyun; Xu, Xiang; Attali, Bernard; Xie, Xin; Gao, Zhaobing

    2017-01-01

    The organophosphate-induced delayed neuropathy (OPIDN), often leads to paresthesias, ataxia and paralysis, occurs in the late-stage of acute poisoning or after repeated exposures to organophosphate (OP) insecticides or nerve agents, and may contribute to the Gulf War Syndrome. The acute phase of OP poisoning is often attributed to acetylcholinesterase inhibition. However, the underlying mechanism for the delayed neuropathy remains unknown and no treatment is available. Here we demonstrate that TRPA1 channel (Transient receptor potential cation channel, member A1) mediates OPIDN. A variety of OPs, exemplified by malathion, activates TRPA1 but not other neuronal TRP channels. Malathion increases the intracellular calcium levels and upregulates the excitability of mouse dorsal root ganglion neurons in vitro. Mice with repeated exposures to malathion also develop local tissue nerve injuries and pain-related behaviors, which resembles OPIDN. Both the neuropathological changes and the nocifensive behaviors can be attenuated by treatment of TRPA1 antagonist HC030031 or abolished by knockout of Trpa1 gene. In the classic hens OPIDN model, malathion causes nerve injuries and ataxia to a similar level as the positive inducer tri-ortho-cresyl phosphate (TOCP), which also activates TRPA1 channel. Treatment with HC030031 reduces the damages caused by malathion or tri-ortho-cresyl phosphate. Duloxetine and Ketotifen, two commercially available drugs exhibiting TRPA1 inhibitory activity, show neuroprotective effects against OPIDN and might be used in emergency situations. The current study suggests TRPA1 is the major mediator of OPIDN and targeting TRPA1 is an effective way for the treatment of OPIDN. PMID:28894590

  12. Combination therapies in adjuvant with topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions

    NASA Astrophysics Data System (ADS)

    Yang, Deng-Fu; Hsu, Yih-Chih

    2012-03-01

    In Taiwan, oral cancer has becomes the fastest growth male cancer disease due to the betel nut chewing habit combing with smoking and alcohol-drinking lifestyle of people. In order to eliminate the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch precancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when ALA reached its peak level in the lesional epithelial cells after topical application of ALA gel. We found that ALA reached its peak level in precancerous lesions about 2.5 hrs after topical application of ALA gel. The cancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 150 J/cm2 using LED 635 nm fiber-guided light device. Visual examination demonstrated that adjuvant topical ALA -mediated PDT group has shown better therapeutic results in compared to those of non-adjuvant topical ALA-mediated PDT group for DMBA-induced hamster buccal pouch precancerous lesions.

  13. Thioredoxin-mediated denitrosylation regulates cytokine-induced nuclear factor κB (NF-κB) activation.

    PubMed

    Kelleher, Zachary T; Sha, Yonggang; Foster, Matthew W; Foster, W Michael; Forrester, Michael T; Marshall, Harvey E

    2014-01-31

    S-nitrosylation of nuclear factor κB (NF-κB) on the p65 subunit of the p50/p65 heterodimer inhibits NF-κB DNA binding activity. We have recently shown that p65 is constitutively S-nitrosylated in the lung and that LPS-induced injury elicits a decrease in SNO-p65 levels concomitant with NF-κB activation in the respiratory epithelium and initiation of the inflammatory response. Here, we demonstrate that TNFα-mediated activation of NF-κB in the respiratory epithelium similarly induces p65 denitrosylation. This process is mediated by the denitrosylase thioredoxin (Trx), which becomes activated upon cytokine-induced degradation of thioredoxin-interacting protein (Txnip). Similarly, inhibition of Trx activity in the lung attenuates LPS-induced SNO-p65 denitrosylation, NF-κB activation, and airway inflammation, supporting a pathophysiological role for this mechanism in lung injury. These data thus link stimulus-coupled activation of NF-κB to a specific, protein-targeted denitrosylation mechanism and further highlight the importance of S-nitrosylation in the regulation of the immune response.

  14. Safe-Taipei a Program Project for Strong Motions, Active Faults, and Earthquakes in the Taipei Metropolitan Area

    NASA Astrophysics Data System (ADS)

    Wang, Jeen-Hwa

    Strong collision between the Eurasian and Philippine Sea Plates causes high seismicity in the Taiwan region, which is often attacked by large earthquakes. Several cities, including three mega-cities, i.e., Taipei, Taichung, and Kaoshung, have been constructed on western Taiwan, where is lying on thick sediments. These cities, with a high-population density, are usually a regional center of culture, economics, and politics. Historically, larger-sized earthquakes, e.g. the 1935 Hsingchu—Taichung earthquake and the 1999 Chi—Chi earthquake, often caused serious damage on the cities. Hence, urban seismology must be one of the main subjects of Taiwan's seismological community. Since 2005, a program project, sponsored by Academia Sinica, has been launched to investigate seismological problems in the Taipei Metropolitan Area. This program project is performed during the 2005—2007 period. The core research subjects are: (1) the deployment of the Taipei Down-hole Seismic Array; (2) the properties of earthquakes and active faults in the area; (3) the seismogenic-zone structures, including the 3-D velocity and Q structures, of the area; (4) the characteristics of strong-motions and sites affects; and (5) strong-motion prediction. In addition to academic goals, the results obtained from the program project will be useful for seismic hazard mitigation not only for the area but also for others.

  15. Glucose Deprivation Induces ATF4-Mediated Apoptosis through TRAIL Death Receptors

    PubMed Central

    Iurlaro, Raffaella; Püschel, Franziska; León-Annicchiarico, Clara Lucía; O'Connor, Hazel; Martin, Seamus J.; Palou-Gramón, Daniel; Lucendo, Estefanía

    2017-01-01

    ABSTRACT Metabolic stress occurs frequently in tumors and in normal tissues undergoing transient ischemia. Nutrient deprivation triggers, among many potential cell death-inducing pathways, an endoplasmic reticulum (ER) stress response with the induction of the integrated stress response transcription factor ATF4. However, how this results in cell death remains unknown. Here we show that glucose deprivation triggered ER stress and induced the unfolded protein response transcription factors ATF4 and CHOP. This was associated with the nontranscriptional accumulation of TRAIL receptor 1 (TRAIL-R1) (DR4) and with the ATF4-mediated, CHOP-independent induction of TRAIL-R2 (DR5), suggesting that cell death in this context may involve death receptor signaling. Consistent with this, the ablation of TRAIL-R1, TRAIL-R2, FADD, Bid, and caspase-8 attenuated cell death, although the downregulation of TRAIL did not, suggesting ligand-independent activation of TRAIL receptors. These data indicate that stress triggered by glucose deprivation promotes the ATF4-dependent upregulation of TRAIL-R2/DR5 and TRAIL receptor-mediated cell death. PMID:28242652

  16. GPR30 mediates anorectic estrogen-induced STAT3 signaling in the hypothalamus.

    PubMed

    Kwon, Obin; Kang, Eun Seok; Kim, Insook; Shin, Sora; Kim, Mijung; Kwon, Somin; Oh, So Ra; Ahn, Young Soo; Kim, Chul Hoon

    2014-11-01

    Estrogen plays an important role in the control of energy balance in the hypothalamus. Leptin-independent STAT3 activation (i.e., tyrosine(705)-phosphorylation of STAT3, pSTAT3) in the hypothalamus is hypothesized as the primary mechanism of the estrogen-induced anorexic response. However, the type of estrogen receptor that mediates this regulation is unknown. We investigated the role of the G protein-coupled receptor 30 (GPR30) in estradiol (E2)-induced STAT3 activation in the hypothalamus. Regulation of STAT3 activation by E2, G-1, a specific agonist of GPR30 and G-15, a specific antagonist of GPR30 was analyzed in vitro and in vivo. Effect of GPR30 activation on eating behavior was analyzed in vivo. E2 stimulated pSTAT3 in cells expressing GPR30, but not expressing estrogen receptor ERα and ERβ. G-1 induced pSTAT3, and G-15 inhibited E2-induced pSTAT3 in primary cultures of hypothalamic neurons. A cerebroventricular injection of G-1 increased pSTAT3 in the arcuate nucleus of mice, which was associated with a decrease in food intake and body weight gain. These results suggest that GPR30 is the estrogen receptor that mediates the anorectic effect of estrogen through the STAT3 pathway in the hypothalamus. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Connective tissue growth factor mediates TGF-β1-induced low-grade serous ovarian tumor cell apoptosis.

    PubMed

    Cheng, Jung-Chien; Chang, Hsun-Ming; Leung, Peter C K

    2017-10-17

    Ovarian low-grade serous carcinoma (LGSC) is a rare disease and is now considered to be a distinct entity from high-grade serous carcinoma (HGSC), which is the most common and malignant form of epithelial ovarian cancer. Connective tissue growth factor (CTGF) is a secreted matricellular protein that has been shown to modulate many biological functions by interacting with multiple molecules in the microenvironment. Increasing evidence indicates that aberrant expression of CTGF is associated with cancer development and progression. Transforming growth factor-β1 (TGF-β1) is a well-known molecule that can strongly up-regulate CTGF expression in different types of normal and cancer cells. Our previous study demonstrated that TGF-β1 induces apoptosis of LGSC cells. However, the effect of TGF-β1 on CTGF expression in LGSC needs to be defined. In addition, whether CTGF mediates TGF-β1-induced LGSC cell apoptosis remains unknown. In the present study, we show that TGF-β1 treatment up-regulates CTGF expression by activating SMAD3 signaling in two human LGSC cell lines. Additionally, siRNA-mediated CTGF knockdown attenuates TGF-β1-induced cell apoptosis. Moreover, our results show that the inhibitory effect of the CTGF knockdown on TGF-β1-induced cell apoptosis is mediated by down-regulating SMAD3 expression. This study demonstrates an important role for CTGF in mediating the pro-apoptotic effects of TGF-β1 on LGCS.

  18. Redox control of molecular motion in switchable artificial nanoscale devices.

    PubMed

    Credi, Alberto; Semeraro, Monica; Silvi, Serena; Venturi, Margherita

    2011-03-15

    The design, synthesis, and operation of molecular-scale systems that exhibit controllable motions of their component parts is a topic of great interest in nanoscience and a fascinating challenge of nanotechnology. The development of this kind of species constitutes the premise to the construction of molecular machines and motors, which in a not-too-distant future could find applications in fields such as materials science, information technology, energy conversion, diagnostics, and medicine. In the past 25 years the development of supramolecular chemistry has enabled the construction of an interesting variety of artificial molecular machines. These devices operate via electronic and molecular rearrangements and, like the macroscopic counterparts, they need energy to work as well as signals to communicate with the operator. Here we outline the design principles at the basis of redox switching of molecular motion in artificial nanodevices. Redox processes, chemically, electrically, or photochemically induced, can indeed supply the energy to bring about molecular motions. Moreover, in the case of electrically and photochemically induced processes, electrochemical and photochemical techniques can be used to read the state of the system, and thus to control and monitor the operation of the device. Some selected examples are also reported to describe the most representative achievements in this research area.

  19. Sharpened cortical tuning and enhanced cortico-cortical communication contribute to the long-term neural mechanisms of visual motion perceptual learning.

    PubMed

    Chen, Nihong; Bi, Taiyong; Zhou, Tiangang; Li, Sheng; Liu, Zili; Fang, Fang

    2015-07-15

    Much has been debated about whether the neural plasticity mediating perceptual learning takes place at the sensory or decision-making stage in the brain. To investigate this, we trained human subjects in a visual motion direction discrimination task. Behavioral performance and BOLD signals were measured before, immediately after, and two weeks after training. Parallel to subjects' long-lasting behavioral improvement, the neural selectivity in V3A and the effective connectivity from V3A to IPS (intraparietal sulcus, a motion decision-making area) exhibited a persistent increase for the trained direction. Moreover, the improvement was well explained by a linear combination of the selectivity and connectivity increases. These findings suggest that the long-term neural mechanisms of motion perceptual learning are implemented by sharpening cortical tuning to trained stimuli at the sensory processing stage, as well as by optimizing the connections between sensory and decision-making areas in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. TLR4 activation of TRPC6-dependent calcium signaling mediates endotoxin-induced lung vascular permeability and inflammation

    PubMed Central

    Tauseef, Mohammad; Knezevic, Nebojsa; Chava, Koteswara R.; Smith, Monica; Sukriti, Sukriti; Gianaris, Nicholas; Obukhov, Alexander G.; Vogel, Stephen M.; Schraufnagel, Dean E.; Dietrich, Alexander; Birnbaumer, Lutz; Malik, Asrar B.

    2012-01-01

    Lung vascular endothelial barrier disruption and the accompanying inflammation are primary pathogenic features of acute lung injury (ALI); however, the basis for the development of both remains unclear. Studies have shown that activation of transient receptor potential canonical (TRPC) channels induces Ca2+ entry, which is essential for increased endothelial permeability. Here, we addressed the role of Toll-like receptor 4 (TLR4) intersection with TRPC6-dependent Ca2+ signaling in endothelial cells (ECs) in mediating lung vascular leakage and inflammation. We find that the endotoxin (lipopolysaccharide; LPS) induces Ca2+ entry in ECs in a TLR4-dependent manner. Moreover, deletion of TRPC6 renders mice resistant to endotoxin-induced barrier dysfunction and inflammation, and protects against sepsis-induced lethality. TRPC6 induces Ca2+ entry in ECs, which is secondary to the generation of diacylglycerol (DAG) induced by LPS. Ca2+ entry mediated by TRPC6, in turn, activates the nonmuscle myosin light chain kinase (MYLK), which not only increases lung vascular permeability but also serves as a scaffold to promote the interaction of myeloid differentiation factor 88 and IL-1R–associated kinase 4, which are required for NF-κB activation and lung inflammation. Our findings suggest that TRPC6-dependent Ca2+ entry into ECs, secondary to TLR4-induced DAG generation, participates in mediating both lung vascular barrier disruption and inflammation induced by endotoxin. PMID:23045603

  1. Propelling a water drop with the vapor-mediated Marangoni effect

    NASA Astrophysics Data System (ADS)

    Kim, Seungho; Kim, Ho-Young

    2013-11-01

    We show that a water drop on solid surfaces can be propelled just by placing a volatile alcohol drop nearby. It is found to be because the water-air interface near the alcohol drop mixes with alcohol vapor, thereby locally lowering the surface tension. The surface-tension-gradient induces the motion of the water drop, enabling the trajectory control of water drops through the motion of remote alcohol drops. This vapor-mediated Marangoni effect also gives rise to other interesting interfacial flow phenomena, such as nucleation of holes on a water film and ballooning of a water drop hanging from a syringe needle with the approach of an alcohol drop. We visualize such interfacial dynamics with a high-speed camera and rationalize their salient features by scaling analysis. This work was supported by the National Research Foundation of Korea (grant no. 2012-008023).

  2. Role of oxidative stress in methamphetamine-induced dopaminergic toxicity mediated by protein kinase Cδ

    PubMed Central

    Nguyen, Xuan-Khanh Thi; Li, Zhengyi; Bing, Guoying; Bach, Jae-Hyung; Park, Dae Hun; Nakayama, Keiichi; Ali, Syed F.; Kanthasamy, Anumantha G.; Cadet, Jean Lud; Nabeshima, Toshitaka; Kim, Hyoung-Chun

    2014-01-01

    This study examined the role of protein kinase C (PKC) isozymes in methamphetamine (MA)-induced dopaminergic toxicity. Multiple-dose administration of MA did not significantly alter PKCα, PKCβI, PKCβII, or PKCζ expression in the striatum, but did significantly increase PKCδ expression. Gö6976 (a co-inhibitor of PKCα and -β), hispidin (PKCβ inhibitor), and PKCζ pseudosubstrate inhibitor (PKCζ inhibitor) did not significantly alter MA-induced behavioral impairments. However, rottlerin (PKCδ inhibitor) significantly attenuated behavioral impairments in a dose-dependent manner. In addition, MA-induced behavioral impairments were not apparent in PKCδ knockout (–/–) mice. MA-induced oxidative stress (i.e., lipid peroxidation and protein oxidation) was significantly attenuated in rottlerin-treated mice and was not apparent in PKCδ (–/–) mice. Consistent with this, MA-induced apoptosis (i.e., terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive apoptotic cells) was significantly attenuated in rottlerin-treated mice. Furthermore, MA-induced increases in the dopamine (DA) turnover rate and decreases in tyrosine hydroxylase (TH) activity and the expression of TH, dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2) were not significantly observed in rottlerin-treated or PKCδ (–/–) mice. Our results suggest that PKCδ gene expression is a key mediator of oxidative stress and dopaminergic damage induced by MA. Thus, inhibition of PKCδ may be a useful target for protection against MA-induced neurotoxicity. PMID:22512859

  3. Role of oxidative stress in methamphetamine-induced dopaminergic toxicity mediated by protein kinase Cδ.

    PubMed

    Shin, Eun-Joo; Duong, Chu Xuan; Nguyen, Xuan-Khanh Thi; Li, Zhengyi; Bing, Guoying; Bach, Jae-Hyung; Park, Dae Hun; Nakayama, Keiichi; Ali, Syed F; Kanthasamy, Anumantha G; Cadet, Jean Lud; Nabeshima, Toshitaka; Kim, Hyoung-Chun

    2012-06-15

    This study examined the role of protein kinase C (PKC) isozymes in methamphetamine (MA)-induced dopaminergic toxicity. Multiple-dose administration of MA did not significantly alter PKCα, PKCβI, PKCβII, or PKCζ expression in the striatum, but did significantly increase PKCδ expression. Gö6976 (a co-inhibitor of PKCα and -β), hispidin (PKCβ inhibitor), and PKCζ pseudosubstrate inhibitor (PKCζ inhibitor) did not significantly alter MA-induced behavioral impairments. However, rottlerin (PKCδ inhibitor) significantly attenuated behavioral impairments in a dose-dependent manner. In addition, MA-induced behavioral impairments were not apparent in PKCδ knockout (-/-) mice. MA-induced oxidative stress (i.e., lipid peroxidation and protein oxidation) was significantly attenuated in rottlerin-treated mice and was not apparent in PKCδ (-/-) mice. Consistent with this, MA-induced apoptosis (i.e., terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive apoptotic cells) was significantly attenuated in rottlerin-treated mice. Furthermore, MA-induced increases in the dopamine (DA) turnover rate and decreases in tyrosine hydroxylase (TH) activity and the expression of TH, dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2) were not significantly observed in rottlerin-treated or PKCδ (-/-) mice. Our results suggest that PKCδ gene expression is a key mediator of oxidative stress and dopaminergic damage induced by MA. Thus, inhibition of PKCδ may be a useful target for protection against MA-induced neurotoxicity. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Amphiregulin mediates hCG-induced StAR expression and progesterone production in human granulosa cells.

    PubMed

    Fang, Lanlan; Yu, Yiping; Zhang, Ruizhe; He, Jingyan; Sun, Ying-Pu

    2016-04-26

    Progesterone plays critical roles in maintaining a successful pregnancy at the early embryonic stage. Human chorionic gonadotropin (hCG) rapidly induces amphiregulin (AREG) expression. However, it remains unknown whether AREG mediates hCG-induced progesterone production. Thus, the objective of this study was to investigate the role of AREG in hCG-induced progesterone production and the underlying molecular mechanism in human granulosa cells; primary cells were used as the experimental model. We demonstrated that the inhibition of EGFR and the knockdown of AREG abolished hCG-induced steroidogenic acute regulatory protein (StAR) expression and progesterone production. Importantly, follicular fluid AREG levels were positively correlated with progesterone levels in the follicular fluid and serum. Treatment with AREG increased StAR expression and progesterone production, and these stimulatory effects were abolished by EGFR inhibition. Moreover, activation of ERK1/2, but not PI3K/Akt, signaling was required for the AREG-induced up-regulation of StAR expression and progesterone production. Our results demonstrate that AREG mediates hCG-induced StAR expression and progesterone production in human granulosa cells, providing novel evidence for the role of AREG in the regulation of steroidogenesis.

  5. NAD(P)H oxidase mediates the endothelial barrier dysfunction induced by TNF-alpha.

    PubMed

    Gertzberg, Nancy; Neumann, Paul; Rizzo, Victor; Johnson, Arnold

    2004-01-01

    We tested the hypothesis that the NAD(P)H oxidase-dependent generation of superoxide anion (O2-*) mediates tumor necrosis factor-alpha (TNF)-induced alterations in the permeability of pulmonary microvessel endothelial monolayers (PMEM). The permeability of PMEM was assessed by the clearance rate of Evans blue-labeled albumin. The NAD(P)H oxidase subcomponents p47phox and p22phox were assessed by immunofluorescent microscopy and Western blot. The reactive oxygen species O2-* was measured by the fluorescence of 6-carboxy-2',7'-dichlorodihydrofluorescein diacetatedi(acetoxymethyl ester), 5 (and 6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate-acetyl ester, and dihydroethidium. TNF treatment (50 ng/ml for 4.0 h) induced 1) p47phox translocation, 2) an increase in p22phox protein, 3) increased localization of p47phox with p22phox, 4) O2-* generation, and 5) increased permeability to albumin. p22phox antisense oligonucleotide prevented the TNF-induced effect on p22phox, p47phox, O2-*, and permeability. The scrambled nonsense oligonucleotide had no effect. The TNF-induced increase in O2-* and permeability to albumin was also prevented by the O2-* scavenger Cu-Zn superoxide dismutase (100 U/ml). The results indicate that the activation of NAD(P)H oxidase, via the generation of O2-*, mediates TNF-induced barrier dysfunction in PMEM.

  6. Static and Dynamic Water Motion-Induced Instability in Oxide Thin-Film Transistors and Its Suppression by Using Low-k Fluoropolymer Passivation.

    PubMed

    Choi, Seungbeom; Jo, Jeong-Wan; Kim, Jaeyoung; Song, Seungho; Kim, Jaekyun; Park, Sung Kyu; Kim, Yong-Hoon

    2017-08-09

    Here, we report static and dynamic water motion-induced instability in indium-gallium-zinc-oxide (IGZO) thin-film transistors (TFTs) and its effective suppression with the use of a simple, solution-processed low-k (ε ∼ 1.9) fluoroplastic resin (FPR) passivation layer. The liquid-contact electrification effect, in which an undesirable drain current modulation is induced by a dynamic motion of a charged liquid such as water, can cause a significant instability in IGZO TFTs. It was found that by adopting a thin (∼44 nm) FPR passivation layer for IGZO TFTs, the current modulation induced by the water-contact electrification was greatly reduced in both off- and on-states of the device. In addition, the FPR-passivated IGZO TFTs exhibited an excellent stability to static water exposure (a threshold voltage shift of +0.8 V upon 3600 s of water soaking), which is attributed to the hydrophobicity of the FPR passivation layer. Here, we discuss the origin of the current instability caused by the liquid-contact electrification as well as various static and dynamic stability tests for IGZO TFTs. On the basis of our findings, we believe that the use of a thin, solution-processed FPR passivation layer is effective in suppressing the static and dynamic water motion-induced instabilities, which may enable the realization of high-performance and environment-stable oxide TFTs for emerging wearable and skin-like electronics.

  7. Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

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

    Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy

    We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91{sup st} day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOSmore » and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E{sub max} of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce

  8. Perceptual learning modifies the functional specializations of visual cortical areas.

    PubMed

    Chen, Nihong; Cai, Peng; Zhou, Tiangang; Thompson, Benjamin; Fang, Fang

    2016-05-17

    Training can improve performance of perceptual tasks. This phenomenon, known as perceptual learning, is strongest for the trained task and stimulus, leading to a widely accepted assumption that the associated neuronal plasticity is restricted to brain circuits that mediate performance of the trained task. Nevertheless, learning does transfer to other tasks and stimuli, implying the presence of more widespread plasticity. Here, we trained human subjects to discriminate the direction of coherent motion stimuli. The behavioral learning effect substantially transferred to noisy motion stimuli. We used transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms underlying the transfer of learning. The TMS experiment revealed dissociable, causal contributions of V3A (one of the visual areas in the extrastriate visual cortex) and MT+ (middle temporal/medial superior temporal cortex) to coherent and noisy motion processing. Surprisingly, the contribution of MT+ to noisy motion processing was replaced by V3A after perceptual training. The fMRI experiment complemented and corroborated the TMS finding. Multivariate pattern analysis showed that, before training, among visual cortical areas, coherent and noisy motion was decoded most accurately in V3A and MT+, respectively. After training, both kinds of motion were decoded most accurately in V3A. Our findings demonstrate that the effects of perceptual learning extend far beyond the retuning of specific neural populations for the trained stimuli. Learning could dramatically modify the inherent functional specializations of visual cortical areas and dynamically reweight their contributions to perceptual decisions based on their representational qualities. These neural changes might serve as the neural substrate for the transfer of perceptual learning.

  9. Investigation of visually induced motion sickness in dynamic 3D contents based on subjective judgment, heart rate variability, and depth gaze behavior.

    PubMed

    Wibirama, Sunu; Hamamoto, Kazuhiko

    2014-01-01

    Visually induced motion sickness (VIMS) is an important safety issue in stereoscopic 3D technology. Accompanying subjective judgment of VIMS with objective measurement is useful to identify not only biomedical effects of dynamic 3D contents, but also provoking scenes that induce VIMS, duration of VIMS, and user behavior during VIMS. Heart rate variability and depth gaze behavior are appropriate physiological indicators for such objective observation. However, there is no information about relationship between subjective judgment of VIMS, heart rate variability, and depth gaze behavior. In this paper, we present a novel investigation of VIMS based on simulator sickness questionnaire (SSQ), electrocardiography (ECG), and 3D gaze tracking. Statistical analysis on SSQ data shows that nausea and disorientation symptoms increase as amount of dynamic motions increases (nausea: p<;0.005; disorientation: p<;0.05). To reduce VIMS, SSQ and ECG data suggest that user should perform voluntary gaze fixation at one point when experiencing vertical motion (up or down) and horizontal motion (turn left and right) in dynamic 3D contents. Observation of 3D gaze tracking data reveals that users who experienced VIMS tended to have unstable depth gaze than ones who did not experience VIMS.

  10. Swimming Motility Mediates the Formation of Neutrophil Extracellular Traps Induced by Flagellated Pseudomonas aeruginosa

    PubMed Central

    Sil, Payel; Chassaing, Benoit; Yoo, Dae-goon; Gewirtz, Andrew T.; Goldberg, Joanna B.; McCarter, Linda L.; Rada, Balázs

    2016-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen causing severe infections often characterized by robust neutrophilic infiltration. Neutrophils provide the first line of defense against P. aeruginosa. Aside from their defense conferred by phagocytic activity, neutrophils also release neutrophil extracellular traps (NETs) to immobilize bacteria. Although NET formation is an important antimicrobial process, the details of its mechanism are largely unknown. The identity of the main components of P. aeruginosa responsible for triggering NET formation is unclear. In this study, our focus was to identify the main bacterial factors mediating NET formation and to gain insight into the underlying mechanism. We found that P. aeruginosa in its exponential growth phase promoted strong NET formation in human neutrophils while its NET-inducing ability dramatically decreased at later stages of bacterial growth. We identified the flagellum as the primary component of P. aeruginosa responsible for inducing NET extrusion as flagellum-deficient bacteria remained seriously impaired in triggering NET formation. Purified P. aeruginosa flagellin, the monomeric component of the flagellum, does not stimulate NET formation in human neutrophils. P. aeruginosa-induced NET formation is independent of the flagellum-sensing receptors TLR5 and NLRC4 in both human and mouse neutrophils. Interestingly, we found that flagellar motility, not flagellum binding to neutrophils per se, mediates NET release induced by flagellated bacteria. Immotile, flagellar motor-deficient bacterial strains producing paralyzed flagella did not induce NET formation. Forced contact between immotile P. aeruginosa and neutrophils restored their NET-inducing ability. Both the motAB and motCD genetic loci encoding flagellar motor genes contribute to maximal NET release; however the motCD genes play a more important role. Phagocytosis of P. aeruginosa and superoxide production by neutrophils were also largely dependent upon

  11. PINK1/Parkin-mediated mitophagy play a protective role in manganese induced apoptosis in SH-SY5Y cells.

    PubMed

    Zhang, Hong-Tao; Mi, Lan; Wang, Ting; Yuan, Lan; Li, Xue-Hui; Dong, Li-Sha; Zhao, Peng; Fu, Juan-Ling; Yao, Bi-Yun; Zhou, Zong-Can

    2016-08-01

    Manganese (Mn) as an environmental risk factor of Parkinson's disease (PD) is considered to cause manganism. Mitophagy is thought to play a key role in elimination the injured mitochondria. The goal of this paper was to explore whether the PINK1/Parkin-mediated mitophagy is activated and its role in Mn-induced mitochondrial dysfunction and cell death in SH-SY5Y cells. Here, we investigated effects of MnCl2 on ROS generation, mitochondrial membrane potential (MMP/ΔΨm) and apoptosis by FACS and examined PINK1/Parkin-mediated mitophagy by western-blotting and the co-localization of mitochondria and acidic lysosomes. Further, we explore the role of mitophagy in Mn-induced apoptosis by inhibition the mitophagy by knockdown Parkin level. Results show that MnCl2 dose-dependently caused ΔΨm decrease, ROS generation and apoptosis of dopaminergic SH-SY5Y cells. Moreover, Mn could induce mitophagy and PINK1/Parkin-mediated pathway was activated in SH-SY5Y cells. Transient transfection of Parkin siRNA knockdown the expressing level of parkin inhibited Mn-induced mitophagy and aggravated apoptosis of SH-SY5Y cells. In conclusion, our study demonstrated that Mn may induce PINK1/Parkin-mediated mitophagy, which may exert significant neuro-protective effect against Mn-induced dopaminergic neuronal cells apoptosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Quantitative inference of population response properties across eccentricity from motion-induced maps in macaque V1

    PubMed Central

    Chen, Ming; Wu, Si; Lu, Haidong D.; Roe, Anna W.

    2013-01-01

    Interpreting population responses in the primary visual cortex (V1) remains a challenge especially with the advent of techniques measuring activations of large cortical areas simultaneously with high precision. For successful interpretation, a quantitatively precise model prediction is of great importance. In this study, we investigate how accurate a spatiotemporal filter (STF) model predicts average response profiles to coherently drifting random dot motion obtained by optical imaging of intrinsic signals in V1 of anesthetized macaques. We establish that orientation difference maps, obtained by subtracting orthogonal axis-of-motion, invert with increasing drift speeds, consistent with the motion streak effect. Consistent with perception, the speed at which the map inverts (the critical speed) depends on cortical eccentricity and systematically increases from foveal to parafoveal. We report that critical speeds and response maps to drifting motion are excellently reproduced by the STF model. Our study thus suggests that the STF model is quantitatively accurate enough to be used as a first model of choice for interpreting responses obtained with intrinsic imaging methods in V1. We show further that this good quantitative correspondence opens the possibility to infer otherwise not easily accessible population receptive field properties from responses to complex stimuli, such as drifting random dot motions. PMID:23197457

  13. Food portion size area mediates energy effects on expected anxiety in anorexia nervosa.

    PubMed

    Herzog, Musya; Douglas, Christopher R; Kissileff, Harry R; Brunstrom, Jeffrey M; Halmi, Katherine Ann

    2017-05-01

    A study in which adolescent patients with anorexia nervosa (n = 24) rated their expected food-anxiety in response to images of portions of food (potatoes, rice pizza, and M&Ms) showed that lower energy-dense foods elicited higher expected anxiety per kilocalorie than higher energy-dense foods. However, the area of the portion sizes could be an unmeasured variable driving the anxiety response. To test the hypothesis that area mediates the effects of energy content on expected anxiety, the same images of portions were measured in area (cm 2 ), and standardized values of expected anxiety were regressed from standardized values of energy and area of portions. With regression of expected anxiety from portion size in area, M&Ms, which had the highest energy density of the four foods, elicited the highest expected anxiety slope (β = 1.75), which was significantly different from the expected anxiety slopes of the other three foods (β range = 0.67 - 0.96). Area was confirmed as a mediator of energy effects from loss of significance of the slopes when area was added to the regression of expected anxiety from energy x food. When expected anxiety was regressed from food, area, energy and area by energy interaction, area accounted for 5.7 times more variance than energy, and β for area (0.7) was significantly larger (by 0.52, SE = 0.15, t = 3.4, p = 0.0007) than β for energy (0.19). Area could be a learned cue for the energy content of food portions, and thus, for weight gain potential, which triggers anxiety in patients with anorexia nervosa. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  14. Audio–visual interactions for motion perception in depth modulate activity in visual area V3A

    PubMed Central

    Ogawa, Akitoshi; Macaluso, Emiliano

    2013-01-01

    Multisensory signals can enhance the spatial perception of objects and events in the environment. Changes of visual size and auditory intensity provide us with the main cues about motion direction in depth. However, frequency changes in audition and binocular disparity in vision also contribute to the perception of motion in depth. Here, we presented subjects with several combinations of auditory and visual depth-cues to investigate multisensory interactions during processing of motion in depth. The task was to discriminate the direction of auditory motion in depth according to increasing or decreasing intensity. Rising or falling auditory frequency provided an additional within-audition cue that matched or did not match the intensity change (i.e. intensity-frequency (IF) “matched vs. unmatched” conditions). In two-thirds of the trials, a task-irrelevant visual stimulus moved either in the same or opposite direction of the auditory target, leading to audio–visual “congruent vs. incongruent” between-modalities depth-cues. Furthermore, these conditions were presented either with or without binocular disparity. Behavioral data showed that the best performance was observed in the audio–visual congruent condition with IF matched. Brain imaging results revealed maximal response in visual area V3A when all cues provided congruent and reliable depth information (i.e. audio–visual congruent, IF-matched condition including disparity cues). Analyses of effective connectivity revealed increased coupling from auditory cortex to V3A specifically in audio–visual congruent trials. We conclude that within- and between-modalities cues jointly contribute to the processing of motion direction in depth, and that they do so via dynamic changes of connectivity between visual and auditory cortices. PMID:23333414

  15. Hypothalamic mTOR pathway mediates thyroid hormone-induced hyperphagia in hyperthyroidism.

    PubMed

    Varela, Luis; Martínez-Sánchez, Noelia; Gallego, Rosalía; Vázquez, María J; Roa, Juan; Gándara, Marina; Schoenmakers, Erik; Nogueiras, Rubén; Chatterjee, Krishna; Tena-Sempere, Manuel; Diéguez, Carlos; López, Miguel

    2012-06-01

    Hyperthyroidism is characterized in rats by increased energy expenditure and marked hyperphagia. Alterations of thermogenesis linked to hyperthyroidism are associated with dysregulation of hypothalamic AMPK and fatty acid metabolism; however, the central mechanisms mediating hyperthyroidism-induced hyperphagia remain largely unclear. Here, we demonstrate that hyperthyroid rats exhibit marked up-regulation of the hypothalamic mammalian target of rapamycin (mTOR) signalling pathway associated with increased mRNA levels of agouti-related protein (AgRP) and neuropeptide Y (NPY), and decreased mRNA levels of pro-opiomelanocortin (POMC) in the arcuate nucleus of the hypothalamus (ARC), an area where mTOR co-localizes with thyroid hormone receptor-α (TRα). Central administration of thyroid hormone (T3) or genetic activation of thyroid hormone signalling in the ARC recapitulated hyperthyroidism effects on feeding and the mTOR pathway. In turn, central inhibition of mTOR signalling with rapamycin in hyperthyroid rats reversed hyperphagia and normalized the expression of ARC-derived neuropeptides, resulting in substantial body weight loss. The data indicate that in the hyperthyroid state, increased feeding is associated with thyroid hormone-induced up-regulation of mTOR signalling. Furthermore, our findings that different neuronal modulations influence food intake and energy expenditure in hyperthyroidism pave the way for a more rational design of specific and selective therapeutic compounds aimed at reversing the metabolic consequences of this disease. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  16. Encodings of implied motion for animate and inanimate object categories in the two visual pathways.

    PubMed

    Lu, Zhengang; Li, Xueting; Meng, Ming

    2016-01-15

    Previous research has proposed two separate pathways for visual processing: the dorsal pathway for "where" information vs. the ventral pathway for "what" information. Interestingly, the middle temporal cortex (MT) in the dorsal pathway is involved in representing implied motion from still pictures, suggesting an interaction between motion and object related processing. However, the relationship between how the brain encodes implied motion and how the brain encodes object/scene categories is unclear. To address this question, fMRI was used to measure activity along the two pathways corresponding to different animate and inanimate categories of still pictures with different levels of implied motion speed. In the visual areas of both pathways, activity induced by pictures of humans and animals was hardly modulated by the implied motion speed. By contrast, activity in these areas correlated with the implied motion speed for pictures of inanimate objects and scenes. The interaction between implied motion speed and stimuli category was significant, suggesting different encoding mechanisms of implied motion for animate-inanimate distinction. Further multivariate pattern analysis of activity in the dorsal pathway revealed significant effects of stimulus category that are comparable to the ventral pathway. Moreover, still pictures of inanimate objects/scenes with higher implied motion speed evoked activation patterns that were difficult to differentiate from those evoked by pictures of humans and animals, indicating a functional role of implied motion in the representation of object categories. These results provide novel evidence to support integrated encoding of motion and object categories, suggesting a rethink of the relationship between the two visual pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Phytochromes A and B mediate red-light-induced positive phototropism in roots

    NASA Technical Reports Server (NTRS)

    Kiss, John Z.; Mullen, Jack L.; Correll, Melanie J.; Hangarter, Roger P.

    2003-01-01

    The interaction of tropisms is important in determining the final growth form of the plant body. In roots, gravitropism is the predominant tropistic response, but phototropism also plays a role in the oriented growth of roots in flowering plants. In blue or white light, roots exhibit negative phototropism that is mediated by the phototropin family of photoreceptors. In contrast, red light induces a positive phototropism in Arabidopsis roots. Because this red-light-induced response is weak relative to both gravitropism and negative phototropism, we used a novel device to study phototropism without the complications of a counteracting gravitational stimulus. This device is based on a computer-controlled system using real-time image analysis of root growth and a feedback-regulated rotatable stage. Our data show that this system is useful to study root phototropism in response to red light, because in wild-type roots, the maximal curvature detected with this apparatus is 30 degrees to 40 degrees, compared with 5 degrees to 10 degrees without the feedback system. In positive root phototropism, sensing of red light occurs in the root itself and is not dependent on shoot-derived signals resulting from light perception. Phytochrome (Phy)A and phyB were severely impaired in red-light-induced phototropism, whereas the phyD and phyE mutants were normal in this response. Thus, PHYA and PHYB play a key role in mediating red-light-dependent positive phototropism in roots. Although phytochrome has been shown to mediate phototropism in some lower plant groups, this is one of the few reports indicating a phytochrome-dependent phototropism in flowering plants.

  18. Phytochromes A and B mediate red-light-induced positive phototropism in roots.

    PubMed

    Kiss, John Z; Mullen, Jack L; Correll, Melanie J; Hangarter, Roger P

    2003-03-01

    The interaction of tropisms is important in determining the final growth form of the plant body. In roots, gravitropism is the predominant tropistic response, but phototropism also plays a role in the oriented growth of roots in flowering plants. In blue or white light, roots exhibit negative phototropism that is mediated by the phototropin family of photoreceptors. In contrast, red light induces a positive phototropism in Arabidopsis roots. Because this red-light-induced response is weak relative to both gravitropism and negative phototropism, we used a novel device to study phototropism without the complications of a counteracting gravitational stimulus. This device is based on a computer-controlled system using real-time image analysis of root growth and a feedback-regulated rotatable stage. Our data show that this system is useful to study root phototropism in response to red light, because in wild-type roots, the maximal curvature detected with this apparatus is 30 degrees to 40 degrees, compared with 5 degrees to 10 degrees without the feedback system. In positive root phototropism, sensing of red light occurs in the root itself and is not dependent on shoot-derived signals resulting from light perception. Phytochrome (Phy)A and phyB were severely impaired in red-light-induced phototropism, whereas the phyD and phyE mutants were normal in this response. Thus, PHYA and PHYB play a key role in mediating red-light-dependent positive phototropism in roots. Although phytochrome has been shown to mediate phototropism in some lower plant groups, this is one of the few reports indicating a phytochrome-dependent phototropism in flowering plants.

  19. Synthesis of High-Frequency Ground Motion Using Information Extracted from Low-Frequency Ground Motion

    NASA Astrophysics Data System (ADS)

    Iwaki, A.; Fujiwara, H.

    2012-12-01

    Broadband ground motion computations of scenario earthquakes are often based on hybrid methods that are the combinations of deterministic approach in lower frequency band and stochastic approach in higher frequency band. Typical computation methods for low-frequency and high-frequency (LF and HF, respectively) ground motions are the numerical simulations, such as finite-difference and finite-element methods based on three-dimensional velocity structure model, and the stochastic Green's function method, respectively. In such hybrid methods, LF and HF wave fields are generated through two different methods that are completely independent of each other, and are combined at the matching frequency. However, LF and HF wave fields are essentially not independent as long as they are from the same event. In this study, we focus on the relation among acceleration envelopes at different frequency bands, and attempt to synthesize HF ground motion using the information extracted from LF ground motion, aiming to propose a new method for broad-band strong motion prediction. Our study area is Kanto area, Japan. We use the K-NET and KiK-net surface acceleration data and compute RMS envelope at four frequency bands: 0.5-1.0 Hz, 1.0-2.0 Hz, 2.0-4.0 Hz, .0-8.0 Hz, and 8.0-16.0 Hz. Taking the ratio of the envelopes of adjacent bands, we find that the envelope ratios have stable shapes at each site. The empirical envelope-ratio characteristics are combined with low-frequency envelope of the target earthquake to synthesize HF ground motion. We have applied the method to M5-class earthquakes and a M7 target earthquake that occurred in the vicinity of Kanto area, and successfully reproduced the observed HF ground motion of the target earthquake. The method can be applied to a broad band ground motion simulation for a scenario earthquake by combining numerically-computed low-frequency (~1 Hz) ground motion with the empirical envelope ratio characteristics to generate broadband ground motion

  20. [Endoplasmic reticulum stress mediates lipopolysaccharide-induced apoptosis in rat hepatocyte].

    PubMed

    Ji, Ying-Lei; Yan, Jun; Wang, Yan-Sha; Liu, Yi-Chang; Gu, Zhen-Yong

    2014-02-01

    To investigate the role of endoplasmic reticulum stress (ERS) in lipopolysaccharide (LPS)-induced hepatocyte apoptosis. Cells of the rat hepatocyte line BRL were cultured. The hepatocytes were treated with LPS, ERS inducer thapsigargin (TG), and ERS inhibitor 4-phenylbutyric acid (4-PBA), respectively or in their different combination. The cell viability was measured by MTT assay. The cyto-nuclear morphological changes of apoptosis cells were detected by the fluorescent dye Hoechst 33258. The apoptosis rate was assessed by flow cytometry with Annexin V-FITC/PI double-staining. Expressions of GRP78 as ERS marker protein, CHOP, caspase-12 and cleaved-caspase-3 as ERS related protein were detected by Western blotting. LPS could cause a decrease in cell viability and an increase in apoptosis rate in a dose- and time-dependent manner. The expression of GRP78, CHOP, caspase-12 and cleaved-caspase-3 proteins were significantly increased with LPS treatment. TG led to a marked decrease in cell viability and an increase in apoptosis rate, which aggravated the hepatocyte injury induced by LPS; whereas 4-PBA alleviated LPS-induced apoptosis. ERS mediates LPS-induced hepatocyte injuries, indicating that ERS may play a vital role in the pathogenesis of LPS-induced hepatocyte injuries.

  1. Seismic Wavefield Imaging of Long-Period Ground Motion in the Tokyo Metropolitan Area, Japan

    NASA Astrophysics Data System (ADS)

    Nagao, H.; Kano, M.; Nagata, K.; Ito, S. I.; Sakai, S.; Nakagawa, S.; Hori, M.; Hirata, N.

    2017-12-01

    Long-period ground motions due to large earthquakes can cause devastating disasters, especially in urbanized areas located on sedimentary basins. To assess and mitigate such damage, it is essential to rapidly evaluate seismic hazards for infrastructures, which can be simulated by seismic response analyses that use waveforms at the base of each infrastructure as an input ground motion. The present study reconstructs the seismic wavefield in the Tokyo metropolitan area located on the Kanto sedimentary basin, Japan, from seismograms of the Metropolitan Seismic Observation network (MeSO-net). The obtained wavefield fully explains the observed waveforms in the frequency band of 0.10-0.20 Hz. This is attributed to the seismic wavefield imaging technique proposed by Kano et al. (2017), which implements the replica exchange Monte Carlo method to simultaneously estimate model parameters related to the subsurface structure and source information. Further investigation shows that the reconstructed seismic wavefield lower than 0.30 Hz is of high quality in terms of variance reduction (VR), which quantifies a misfit in waveforms but that the VR rapidly worsens in higher frequencies. Meanwhile, the velocity response spectra show good agreement with observations up to 0.90 Hz in terms of the combined goodness of fit (CGOF), which is a measure of misfit in the velocity response spectra. Inputting the reconstructed wavefield into seismic response analyses, we can rapidly assess the overall damage to infrastructures immediately after a large earthquake.

  2. Thon rings from amorphous ice and implications of beam-induced Brownian motion in single particle electron cryo-microscopy.

    PubMed

    McMullan, G; Vinothkumar, K R; Henderson, R

    2015-11-01

    We have recorded dose-fractionated electron cryo-microscope images of thin films of pure flash-frozen amorphous ice and pre-irradiated amorphous carbon on a Falcon II direct electron detector using 300 keV electrons. We observe Thon rings [1] in both the power spectrum of the summed frames and the sum of power spectra from the individual frames. The Thon rings from amorphous carbon images are always more visible in the power spectrum of the summed frames whereas those of amorphous ice are more visible in the sum of power spectra from the individual frames. This difference indicates that while pre-irradiated carbon behaves like a solid during the exposure, amorphous ice behaves like a fluid with the individual water molecules undergoing beam-induced motion. Using the measured variation in the power spectra amplitude with number of electrons per image we deduce that water molecules are randomly displaced by a mean squared distance of ∼1.1 Å(2) for every incident 300 keV e(-)/Å(2). The induced motion leads to an optimal exposure with 300 keV electrons of 4.0 e(-)/Å(2) per image with which to observe Thon rings centred around the strong 3.7 Å scattering peak from amorphous ice. The beam-induced movement of the water molecules generates pseudo-Brownian motion of embedded macromolecules. The resulting blurring of single particle images contributes an additional term, on top of that from radiation damage, to the minimum achievable B-factor for macromolecular structure determination. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  3. The neural basis of form and form-motion integration from static and dynamic translational Glass patterns: A rTMS investigation.

    PubMed

    Pavan, Andrea; Ghin, Filippo; Donato, Rita; Campana, Gianluca; Mather, George

    2017-08-15

    A long-held view of the visual system is that form and motion are independently analysed. However, there is physiological and psychophysical evidence of early interaction in the processing of form and motion. In this study, we used a combination of Glass patterns (GPs) and repetitive Transcranial Magnetic Stimulation (rTMS) to investigate in human observers the neural mechanisms underlying form-motion integration. GPs consist of randomly distributed dot pairs (dipoles) that induce the percept of an oriented stimulus. GPs can be either static or dynamic. Dynamic GPs have both a form component (i.e., orientation) and a non-directional motion component along the orientation axis. GPs were presented in two temporal intervals and observers were asked to discriminate the temporal interval containing the most coherent GP. rTMS was delivered over early visual area (V1/V2) and over area V5/MT shortly after the presentation of the GP in each interval. The results showed that rTMS applied over early visual areas affected the perception of static GPs, but the stimulation of area V5/MT did not affect observers' performance. On the other hand, rTMS was delivered over either V1/V2 or V5/MT strongly impaired the perception of dynamic GPs. These results suggest that early visual areas seem to be involved in the processing of the spatial structure of GPs, and interfering with the extraction of the global spatial structure also affects the extraction of the motion component, possibly interfering with early form-motion integration. However, visual area V5/MT is likely to be involved only in the processing of the motion component of dynamic GPs. These results suggest that motion and form cues may interact as early as V1/V2. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Eupafolin enhances TRAIL-mediated apoptosis through cathepsin S-induced down-regulation of Mcl-1 expression and AMPK-mediated Bim up-regulation in renal carcinoma Caki cells.

    PubMed

    Han, Min Ae; Min, Kyoung-Jin; Woo, Seon Min; Seo, Bo Ram; Kwon, Taeg Kyu

    2016-10-04

    Eupafolin, a flavone found in Artemisia princeps, has been reported for its anti-tumor activity in several cancer cells. In this study, we examined whether eupafolin could sensitize TRAIL-mediated apoptosis in human renal carcinoma Caki cells. We found that eupafolin alone and TRAIL alone had no effect on apoptosis. However, combined treatment with eupafolin and TRAIL markedly induced apoptosis in human renal carcinoma (Caki) cells, glioma cells (U251MG), and prostate cancer cells (DU145), but not normal cells [mesangial cells (MC) and normal mouse kidney cells (TCMK-1)]. Eupafolin induced down-regulation of Mcl-1 expression at the post-translational levels in cathepsin S-dependent manner, and over-expression of Mcl-1 markedly blocked apoptosis induced by combined treatment with eupafolin and TRAIL. In addition, eupafolin increased Bim expression at the post-translational levels via AMP-activated protein kinase (AMPK)-mediated inhibition of proteasome activity. Knock-down of Bim expression by siRNA inhibited eupafolin plus TRAIL-induced apoptosis. Furthermore, combined treatment with eupafolin and TRAIL reduced tumor growth in xenograft models. Taken together, these results suggest that eupafolin enhanced TRAIL-mediated apoptosis via down-regulation of Mcl-1 and up-regulation of Bim in renal carcinoma Caki cells.

  5. Eupafolin enhances TRAIL-mediated apoptosis through cathepsin S-induced down-regulation of Mcl-1 expression and AMPK-mediated Bim up-regulation in renal carcinoma Caki cells

    PubMed Central

    Woo, Seon Min; Seo, Bo Ram; Kwon, Taeg Kyu

    2016-01-01

    Eupafolin, a flavone found in Artemisia princeps, has been reported for its anti-tumor activity in several cancer cells. In this study, we examined whether eupafolin could sensitize TRAIL-mediated apoptosis in human renal carcinoma Caki cells. We found that eupafolin alone and TRAIL alone had no effect on apoptosis. However, combined treatment with eupafolin and TRAIL markedly induced apoptosis in human renal carcinoma (Caki) cells, glioma cells (U251MG), and prostate cancer cells (DU145), but not normal cells [mesangial cells (MC) and normal mouse kidney cells (TCMK-1)]. Eupafolin induced down-regulation of Mcl-1 expression at the post-translational levels in cathepsin S-dependent manner, and over-expression of Mcl-1 markedly blocked apoptosis induced by combined treatment with eupafolin and TRAIL. In addition, eupafolin increased Bim expression at the post-translational levels via AMP-activated protein kinase (AMPK)-mediated inhibition of proteasome activity. Knock-down of Bim expression by siRNA inhibited eupafolin plus TRAIL-induced apoptosis. Furthermore, combined treatment with eupafolin and TRAIL reduced tumor growth in xenograft models. Taken together, these results suggest that eupafolin enhanced TRAIL-mediated apoptosis via down-regulation of Mcl-1 and up-regulation of Bim in renal carcinoma Caki cells. PMID:27582546

  6. Differential effect of visual motion adaption upon visual cortical excitability.

    PubMed

    Lubeck, Astrid J A; Van Ombergen, Angelique; Ahmad, Hena; Bos, Jelte E; Wuyts, Floris L; Bronstein, Adolfo M; Arshad, Qadeer

    2017-03-01

    The objectives of this study were 1 ) to probe the effects of visual motion adaptation on early visual and V5/MT cortical excitability and 2 ) to investigate whether changes in cortical excitability following visual motion adaptation are related to the degree of visual dependency, i.e., an overreliance on visual cues compared with vestibular or proprioceptive cues. Participants were exposed to a roll motion visual stimulus before, during, and after visual motion adaptation. At these stages, 20 transcranial magnetic stimulation (TMS) pulses at phosphene threshold values were applied over early visual and V5/MT cortical areas from which the probability of eliciting a phosphene was calculated. Before and after adaptation, participants aligned the subjective visual vertical in front of the roll motion stimulus as a marker of visual dependency. During adaptation, early visual cortex excitability decreased whereas V5/MT excitability increased. After adaptation, both early visual and V5/MT excitability were increased. The roll motion-induced tilt of the subjective visual vertical (visual dependence) was not influenced by visual motion adaptation and did not correlate with phosphene threshold or visual cortex excitability. We conclude that early visual and V5/MT cortical excitability is differentially affected by visual motion adaptation. Furthermore, excitability in the early or late visual cortex is not associated with an increase in visual reliance during spatial orientation. Our findings complement earlier studies that have probed visual cortical excitability following motion adaptation and highlight the differential role of the early visual cortex and V5/MT in visual motion processing. NEW & NOTEWORTHY We examined the influence of visual motion adaptation on visual cortex excitability and found a differential effect in V1/V2 compared with V5/MT. Changes in visual excitability following motion adaptation were not related to the degree of an individual's visual

  7. New principle for measuring arterial blood oxygenation, enabling motion-robust remote monitoring.

    PubMed

    van Gastel, Mark; Stuijk, Sander; de Haan, Gerard

    2016-12-07

    Finger-oximeters are ubiquitously used for patient monitoring in hospitals worldwide. Recently, remote measurement of arterial blood oxygenation (SpO 2 ) with a camera has been demonstrated. Both contact and remote measurements, however, require the subject to remain static for accurate SpO 2 values. This is due to the use of the common ratio-of-ratios measurement principle that measures the relative pulsatility at different wavelengths. Since the amplitudes are small, they are easily corrupted by motion-induced variations. We introduce a new principle that allows accurate remote measurements even during significant subject motion. We demonstrate the main advantage of the principle, i.e. that the optimal signature remains the same even when the SNR of the PPG signal drops significantly due to motion or limited measurement area. The evaluation uses recordings with breath-holding events, which induce hypoxemia in healthy moving subjects. The events lead to clinically relevant SpO 2 levels in the range 80-100%. The new principle is shown to greatly outperform current remote ratio-of-ratios based methods. The mean-absolute SpO 2 -error (MAE) is about 2 percentage-points during head movements, where the benchmark method shows a MAE of 24 percentage-points. Consequently, we claim ours to be the first method to reliably measure SpO 2 remotely during significant subject motion.

  8. Peer-Mediated Procedures to Induce Swallowing and Food Acceptance in Young Children.

    ERIC Educational Resources Information Center

    Greer, R. Douglas; And Others

    1991-01-01

    A peer modeling procedure was shown to induce swallowing in a young child with dysphagia, and to increase food acceptance in a young child who consistently declined food. A peer-mediated procedure, consisting of rotated opportunities to consume food with a peer, increased consumption more than did modeling alone. (Author/JDD)

  9. Motion Compensation in Extremity Cone-Beam CT Using a Penalized Image Sharpness Criterion

    PubMed Central

    Sisniega, A.; Stayman, J. W.; Yorkston, J.; Siewerdsen, J. H.; Zbijewski, W.

    2017-01-01

    Cone-beam CT (CBCT) for musculoskeletal imaging would benefit from a method to reduce the effects of involuntary patient motion. In particular, the continuing improvement in spatial resolution of CBCT may enable tasks such as quantitative assessment of bone microarchitecture (0.1 mm – 0.2 mm detail size), where even subtle, sub-mm motion blur might be detrimental. We propose a purely image based motion compensation method that requires no fiducials, tracking hardware or prior images. A statistical optimization algorithm (CMA-ES) is used to estimate a motion trajectory that optimizes an objective function consisting of an image sharpness criterion augmented by a regularization term that encourages smooth motion trajectories. The objective function is evaluated using a volume of interest (VOI, e.g. a single bone and surrounding area) where the motion can be assumed to be rigid. More complex motions can be addressed by using multiple VOIs. Gradient variance was found to be a suitable sharpness metric for this application. The performance of the compensation algorithm was evaluated in simulated and experimental CBCT data, and in a clinical dataset. Motion-induced artifacts and blurring were significantly reduced across a broad range of motion amplitudes, from 0.5 mm to 10 mm. Structure Similarity Index (SSIM) against a static volume was used in the simulation studies to quantify the performance of the motion compensation. In studies with translational motion, the SSIM improved from 0.86 before compensation to 0.97 after compensation for 0.5 mm motion, from 0.8 to 0.94 for 2 mm motion and from 0.52 to 0.87 for 10 mm motion (~70% increase). Similar reduction of artifacts was observed in a benchtop experiment with controlled translational motion of an anthropomorphic hand phantom, where SSIM (against a reconstruction of a static phantom) improved from 0.3 to 0.8 for 10 mm motion. Application to a clinical dataset of a lower extremity showed dramatic reduction of streaks

  10. 111 years of Brownian motion.

    PubMed

    Bian, Xin; Kim, Changho; Karniadakis, George Em

    2016-08-14

    We consider the Brownian motion of a particle and present a tutorial review over the last 111 years since Einstein's paper in 1905. We describe Einstein's model, Langevin's model and the hydrodynamic models, with increasing sophistication on the hydrodynamic interactions between the particle and the fluid. In recent years, the effects of interfaces on the nearby Brownian motion have been the focus of several investigations. We summarize various results and discuss some of the controversies associated with new findings about the changes in Brownian motion induced by the interface.

  11. 111 years of Brownian motion

    PubMed Central

    Kim, Changho

    2017-01-01

    We consider the Brownian motion of a particle and present a tutorial review over the last 111 years since Einstein’s paper in 1905. We describe Einstein’s model, Langevin’s model and the hydrodynamic models, with increasing sophistication on the hydrodynamic interactions between the particle and the fluid. In recent years, the effects of interfaces on the nearby Brownian motion have been the focus of several investigations. We summarize various results and discuss some of the controversies associated with new findings about the changes in Brownian motion induced by the interface. PMID:27396746

  12. Second-order motions contribute to vection.

    PubMed

    Gurnsey, R; Fleet, D; Potechin, C

    1998-09-01

    First- and second-order motions differ in their ability to induce motion aftereffects (MAEs) and the kinetic depth effect (KDE). To test whether second-order stimuli support computations relating to motion-in-depth we examined the vection illusion (illusory self motion induced by image flow) using a vection stimulus (V, expanding concentric rings) that depicted a linear path through a circular tunnel. The set of vection stimuli contained differing amounts of first- and second-order motion energy (ME). Subjects reported the duration of the perceived MAEs and the duration of their vection percept. In Experiment 1 both MAEs and vection durations were longest when the first-order (Fourier) components of V were present in the stimulus. In Experiment 2, V was multiplicatively combined with static noise carriers having different check sizes. The amount of first-order ME associated with V increases with check size. MAEs were found to increase with check size but vection durations were unaffected. In general MAEs depend on the amount of first-order ME present in the signal. Vection, on the other hand, appears to depend on a representation of image flow that combines first- and second-order ME.

  13. Protein disulfide isomerase mediates glutathione depletion-induced cytotoxicity.

    PubMed

    Okada, Kazushi; Fukui, Masayuki; Zhu, Bao-Ting

    2016-08-26

    Glutathione depletion is a distinct cause underlying many forms of pathogenesis associated with oxidative stress and cytotoxicity. Earlier studies showed that glutamate-induced glutathione depletion in immortalized murine HT22 hippocampal neuronal cells leads to accumulation of reactive oxygen species (ROS) and ultimately cell death, but the precise mechanism underlying these processes is not clear. Here we show that during the induction of glutathione depletion, nitric oxide (NO) accumulation precedes ROS accumulation. While neuronal NO synthase (nNOS) in untreated HT22 cells exists mostly as a monomer, glutathione depletion results in increased formation of the dimer nNOS, accompanied by increases in the catalytic activity. We identified that nNOS dimerization is catalyzed by protein disulfide isomerase (PDI). Inhibition of PDI's isomerase activity effectively abrogates glutathione depletion-induced conversion of monomer nNOS into dimer nNOS, accumulation of NO and ROS, and cytotoxicity. Furthermore, we found that PDI is present in untreated cells in an inactive S-nitrosylated form, which becomes activated following glutathione depletion via S-denitrosylation. These results reveal a novel role for PDI in mediating glutathione depletion-induced oxidative cytotoxicity, as well as its role as a valuable therapeutic target for protection against oxidative cytotoxicity. Copyright © 2016. Published by Elsevier Inc.

  14. Polysaccharide peptides from COV-1 strain of Coriolus versicolor induce hyperalgesia via inflammatory mediator release in the mouse.

    PubMed

    Chan, Siu-Lung; Yeung, John H K

    2006-04-18

    Polysaccharide peptide (PSP), isolated from Coriolus versicolor COV-1, has been widely used as an adjunct to cancer chemotherapy and as an immuno-stimulator in China. In this study, the anti-nociceptive effects of PSP were investigated in two different pain models in the mouse. In the acetic acid-induced writhing model, initial studies showed that PSP decreased the number of acetic acid-induced writhing by 92.9%, which, by definition, would constitute an analgesic effect. However, further studies showed that PSP itself induced a dose-dependent writhing response. Studies on inflammatory mediator release showed that PSP increased the release of prostaglandin E2, tumor necrosis factor-alpha, interleukin-1beta, and histamine in mouse peritoneal macrophages and mast cells both in vitro and in vivo. The role of inflammatory mediator release in PSP-induced writhing was confirmed when diclofenac and dexamethasone decreased the number of writhing responses by 54% and 58.5%, respectively. Diphenhydramine totally inhibited the PSP-induced writhing. In the hot-plate test, PSP dose-dependently shortened the hind paw withdrawal latency, indicative of a hyperalgesic effect. The hyperalgesic effect was reduced by pretreatment with the anti-inflammatory drugs. In conclusion, the PSP-induced hyperalgesia was related to activation of peritoneal resident cells and an increase in the release of inflammatory mediators.

  15. 2',5'-Dihydroxychalcone-induced glutathione is mediated by oxidative stress and kinase signaling pathways.

    PubMed

    Kachadourian, Remy; Pugazhenthi, Subbiah; Velmurugan, Kalpana; Backos, Donald S; Franklin, Christopher C; McCord, Joe M; Day, Brian J

    2011-09-15

    Hydroxychalcones are naturally occurring compounds that continue to attract considerable interest because of their anti-inflammatory and antiangiogenic properties. They have been reported to inhibit the synthesis of the inducible nitric oxide synthase and to induce the expression of heme oxygenase-1. This study examines the mechanisms by which 2',5'-dihydroxychalcone (2',5'-DHC) induces an increase in cellular glutathione (GSH) levels using a cell line stably expressing a luciferase reporter gene driven by antioxidant-response elements (MCF-7/AREc32). The 2',5'-DHC-induced increase in cellular GSH levels was partially inhibited by the catalytic antioxidant MnTDE-1,3-IP(5+), suggesting that reactive oxygen species (ROS) mediate the antioxidant adaptive response. 2',5'-DHC treatment induced phosphorylation of the c-Jun N-terminal kinase (JNK) pathway, which was also inhibited by MnTDE-1,3-IP(5+). These findings suggest a ROS-dependent activation of the AP-1 transcriptional response. However, whereas 2',5'-DHC triggered the NF-E2-related factor 2 (Nrf2) transcriptional response, cotreatment with MnTDE-1,3-IP(5+) did not decrease 2',5'-DHC-induced Nrf2/ARE activity, showing that this pathway is not dependent on ROS. Moreover, pharmacological inhibitors of mitogen-activated protein kinase (MAPK) pathways showed a role for JNK and p38MAPK in mediating the 2',5'-DHC-induced Nrf2 response. These findings suggest that the 2',5'-DHC-induced increase in GSH levels results from a combination of ROS-dependent and ROS-independent pathways. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Motion Driven by Strain Gradient Fields

    PubMed Central

    Wang, Chao; Chen, Shaohua

    2015-01-01

    A new driving mechanism for direction-controlled motion of nano-scale objects is proposed, based on a model of stretching a graphene strip linked to a rigid base with linear springs of identical stiffness. We find that the potential energy difference induced by the strain gradient field in the graphene strip substrate can generate sufficient force to overcome the static and kinetic friction forces between the nano-flake and the strip substrate, resulting in the nanoscale flake motion in the direction of gradient reduction. The dynamics of the nano-flake can be manipulated by tuning the stiffness of linear springs, stretching velocity and the flake size. This fundamental law of directional motion induced by strain gradient could be very useful for promising designs of nanoscale manipulation, transportation and smart surfaces. PMID:26323603

  17. Vection is the main contributor to motion sickness induced by visual yaw rotation: Implications for conflict and eye movement theories

    PubMed Central

    Pretto, Paolo; Oberfeld, Daniel; Hecht, Heiko; Bülthoff, Heinrich H.

    2017-01-01

    This study investigated the role of vection (i.e., a visually induced sense of self-motion), optokinetic nystagmus (OKN), and inadvertent head movements in visually induced motion sickness (VIMS), evoked by yaw rotation of the visual surround. These three elements have all been proposed as contributing factors in VIMS, as they can be linked to different motion sickness theories. However, a full understanding of the role of each factor is still lacking because independent manipulation has proven difficult in the past. We adopted an integrative approach to the problem by obtaining measures of potentially relevant parameters in four experimental conditions and subsequently combining them in a linear mixed regression model. To that end, participants were exposed to visual yaw rotation in four separate sessions. Using a full factorial design, the OKN was manipulated by a fixation target (present/absent), and vection strength by introducing a conflict in the motion direction of the central and peripheral field of view (present/absent). In all conditions, head movements were minimized as much as possible. Measured parameters included vection strength, vection variability, OKN slow phase velocity, OKN frequency, the number of inadvertent head movements, and inadvertent head tilt. Results show that VIMS increases with vection strength, but that this relation varies among participants (R2 = 0.48). Regression parameters for vection variability, head and eye movement parameters were not significant. These results may seem to be in line with the Sensory Conflict theory on motion sickness, but we argue that a more detailed definition of the exact nature of the conflict is required to fully appreciate the relationship between vection and VIMS. PMID:28380077

  18. Cytoplasmic motion induced by cytoskeleton stretching and its effect on cell mechanics.

    PubMed

    Zhang, T

    2011-09-01

    Cytoplasmic motion assumed as a steady state laminar flow induced by cytoskeleton stretching in a cell is determined and its effect on the mechanical behavior of the cell under externally applied forces is demonstrated. Non-Newtonian fluid is assumed for the multiphase cytoplasmic fluid and the analytical velocity field around the macromolecular chain is obtained by solving the reduced nonlinear momentum equation using homotopy technique. The entropy generation by the fluid internal friction is calculated and incorporated into the entropic elasticity based 8-chain constitutive relations. Numerical examples showed strengthening behavior of cells in response to externally applied mechanical stimuli. The spatial distribution of the stresses within a cell under externally applied fluid flow forces were also studied.

  19. Linearized motion estimation for articulated planes.

    PubMed

    Datta, Ankur; Sheikh, Yaser; Kanade, Takeo

    2011-04-01

    In this paper, we describe the explicit application of articulation constraints for estimating the motion of a system of articulated planes. We relate articulations to the relative homography between planes and show that these articulations translate into linearized equality constraints on a linear least-squares system, which can be solved efficiently using a Karush-Kuhn-Tucker system. The articulation constraints can be applied for both gradient-based and feature-based motion estimation algorithms and to illustrate this, we describe a gradient-based motion estimation algorithm for an affine camera and a feature-based motion estimation algorithm for a projective camera that explicitly enforces articulation constraints. We show that explicit application of articulation constraints leads to numerically stable estimates of motion. The simultaneous computation of motion estimates for all of the articulated planes in a scene allows us to handle scene areas where there is limited texture information and areas that leave the field of view. Our results demonstrate the wide applicability of the algorithm in a variety of challenging real-world cases such as human body tracking, motion estimation of rigid, piecewise planar scenes, and motion estimation of triangulated meshes.

  20. Ground Motion Modeling in the Eastern Caucasus

    DOE PAGES

    Pitarka, Arben; Gok, Rengin; Yetirmishli, Gurban; ...

    2016-05-13

    In this paper, we analyzed the performance of a preliminary three-dimensional (3D) velocity model of the Eastern Caucasus covering most of the Azerbaijan. The model was developed in support to long-period ground motion simulations and seismic hazard assessment from regional earthquakes in Azerbaijan. The model’s performance was investigated by simulating ground motion from the damaging Mw 5.9, 2012 Zaqatala earthquake, which was well recorded throughout the region by broadband seismic instruments. In our simulations, we use a parallelized finite-difference method of fourth-order accuracy. The comparison between the simulated and recorded ground motion velocity in the modeled period range of 3–20more » s shows that in general, the 3D velocity model performs well. Areas in which the model needs improvements are located mainly in the central part of the Kura basin and in the Caspian Sea coastal areas. Comparisons of simulated ground motion using our 3D velocity model and corresponding 1D regional velocity model were used to locate areas with strong 3D wave propagation effects. In areas with complex underground structure, the 1D model fails to produce the observed ground motion amplitude and duration, and spatial extend of ground motion amplification caused by wave propagation effects.« less

  1. Lipid emulsions enhance the norepinephrine-mediated reversal of local anesthetic-induced vasodilation at toxic doses.

    PubMed

    Lee, Soo Hee; Sung, Hui-Jin; Ok, Seong-Ho; Yu, Jongsun; Choi, Mun-Jeoung; Lim, Jin Soo; Sohn, Ju-Tae

    2013-11-01

    Intravenous lipid emulsions have been used to treat the systemic toxicity of local anesthetics. The goal of this in vitro study was to examine the effects of lipid emulsions on the norepinephrine-mediated reversal of vasodilation induced by high doses of levobupivacaine, ropivacaine, and mepivacaine in isolated endothelium-denuded rat aorta, and to determine whether such effects are associated with the lipid solubility of local anesthetics. The effects of lipid emulsions (0.30, 0.49, 1.40, and 2.61%) on norepinephrine concentration-responses in high-dose local anesthetic (6×10(-4) M levobupivacaine, 2×10(-3) M ropivacaine, and 7×10(-3) M mepivacaine)-induced vasodilation of isolated aorta precontracted with 60 mM KCl were assessed. The effects of lipid emulsions on local anesthetic- and diltiazem-induced vasodilation in isolated aorta precontracted with phenylephrine were also assessed. Lipid emulsions (0.30%) enhanced norepinephrine-induced contraction in levobupivacaine-induced vasodilation, whereas 1.40 and 2.61% lipid emulsions enhanced norepinephrine-induced contraction in both ropivacaine- and mepivacaine-induced vasodilation, respectively. Lipid emulsions (0.20, 0.49 and 1.40%) inhibited vasodilation induced by levobupivacaine and ropivacaine, whereas 1.40 and 2.61% lipid emulsions slightly attenuated mepivacaine (3×10(-3) M)-induced vasodilation. In addition, lipid emulsions attenuated diltiazem-induced vasodilation. Lipid emulsions enhanced norepinephrine-induced contraction in endothelium-denuded aorta without pretreatment with local anesthetics. Taken together, these results suggest that lipid emulsions enhance the norepinephrine-mediated reversal of local anesthetic-induced vasodilation at toxic anesthetic doses and inhibit local anesthetic-induced vasodilation in a manner correlated with the lipid solubility of a particular local anesthetic.

  2. Neural network architecture for form and motion perception (Abstract Only)

    NASA Astrophysics Data System (ADS)

    Grossberg, Stephen

    1991-08-01

    Evidence is given for a new neural network theory of biological motion perception, a motion boundary contour system. This theory clarifies why parallel streams V1 yields V2 and V1 yields MT exist for static form and motion form processing among the areas V1, V2, and MT of visual cortex. The motion boundary contour system consists of several parallel copies, such that each copy is activated by a different range of receptive field sizes. Each copy is further subdivided into two hierarchically organized subsystems: a motion oriented contrast (MOC) filter, for preprocessing moving images; and a cooperative-competitive feedback (CC) loop, for generating emergent boundary segmentations of the filtered signals. The present work uses the MOC filter to explain a variety of classical and recent data about short-range and long- range apparent motion percepts that have not yet been explained by alternative models. These data include split motion; reverse-contrast gamma motion; delta motion; visual inertia; group motion in response to a reverse-contrast Ternus display at short interstimulus intervals; speed- up of motion velocity as interflash distance increases or flash duration decreases; dependence of the transition from element motion to group motion on stimulus duration and size; various classical dependencies between flash duration, spatial separation, interstimulus interval, and motion threshold known as Korte''s Laws; and dependence of motion strength on stimulus orientation and spatial frequency. These results supplement earlier explanations by the model of apparent motion data that other models have not explained; a recent proposed solution of the global aperture problem including explanations of motion capture and induced motion; an explanation of how parallel cortical systems for static form perception and motion form perception may develop, including a demonstration that these parallel systems are variations on a common cortical design; an explanation of why the

  3. Acid mediates a prolonged antinociception via substance P signaling in acid-induced chronic widespread pain.

    PubMed

    Chen, Wei-Nan; Chen, Chih-Cheng

    2014-05-21

    Substance P is an important neuropeptide released from nociceptors to mediate pain signals. We recently revealed antinociceptive signaling by substance P in acid-sensing ion channel 3 (ASIC3)-expressing muscle nociceptors in a mouse model of acid-induced chronic widespread pain. However, methods to specifically trigger the substance P antinociception were still lacking. Here we show that acid could induce antinociceptive signaling via substance P release in muscle. We prevented the intramuscular acid-induced hyperalgesia by pharmacological inhibition of ASIC3 and transient receptor potential V1 (TRPV1). The antinociceptive effect of non-ASIC3, non-TRPV1 acid signaling lasted for 2 days. The non-ASIC3, non-TRPV1 acid antinociception was largely abolished in mice lacking substance P. Moreover, pretreatment with substance P in muscle mimicked the acid antinociceptive effect and prevented the hyperalgesia induced by next-day acid injection. Acid could mediate a prolonged antinociceptive signaling via the release of substance P from muscle afferent neurons in a non-ASIC3, non-TRPV1 manner.

  4. Single-neuron labeling with inducible cre-mediated knockout in transgenic mice

    PubMed Central

    Young, Paul; Qiu, Li; Wang, Dongqing; Zhao, Shengli; Gross, James; Feng, Guoping

    2011-01-01

    To facilitate functional analysis of neuronal connectivity in a mammalian nervous system tightly packed with billions of cells, we developed a new technique that allows inducible genetic manipulations within fluorescently labeled single neurons in mice. We term this technique SLICK for Single-neuron Labeling with Inducible Cre-mediated Knockout. SLICK is achieved by co-expressing a drug-inducible form of cre recombinase and a fluorescent protein within the same small subsets of neurons. Thus, SLICK combines the powerful cre recombinase system for conditional genetic manipulation and the fluorescent labeling of single neurons for imaging. We demonstrate efficient inducible genetic manipulation in several types of neurons using SLICK. Furthermore, we apply SLICK to eliminate synaptic transmission in a small subset of neuromuscular junctions. Our results provide evidence for the long-term stability of inactive neuromuscular synapses in adult animals. More broadly, these studies demonstrate a cre-LoxP compatible system for dissecting gene functions in single identifiable neurons. PMID:18454144

  5. Sulforaphane protects Microcystin-LR-induced toxicity through activation of the Nrf2-mediated defensive response

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

    Gan Nanqin; Mi Lixin; Sun Xiaoyun

    2010-09-01

    Microcystins (MCs), a cyclic heptapeptide hepatotoxins, are mainly produced by the bloom-forming cyanobacerium Microcystis, which has become an environmental hazard worldwide. Long term consumption of MC-contaminated water may induce liver damage, liver cancer, and even human death. Therefore, in addition to removal of MCs in drinking water, novel strategies that prevent health damages are urgently needed. Sulforaphane (SFN), a natural-occurring isothiocyanate from cruciferous vegetables, has been reported to reduce and eliminate toxicities from xenobiotics and carcinogens. The purpose of the present study was to provide mechanistic insights into the SFN-induced antioxidative defense system against MC-LR-induced cytotoxicity. We performed cell viabilitymore » assays, including MTS assay, colony formation assay and apoptotic cell sorting, to study MC-LR-induced cellular damage and the protective effects by SFN. The results showed that SFN protected MC-LR-induced damages at a nontoxic and physiological relevant dose in HepG2, BRL-3A and NIH 3 T3 cells. The protection was Nrf2-mediated as evident by transactivation of Nrf2 and activation of its downstream genes, including NQO1 and HO-1, and elevated intracellular GSH level. Results of our studies indicate that pretreatment of cells with 10 {mu}M SFN for 12 h significantly protected cells from MC-LR-induced damage. SFN-induced protective response was mediated through Nrf2 pathway.« less

  6. PINK1/Parkin-mediated mitophagy alleviates chlorpyrifos-induced apoptosis in SH-SY5Y cells.

    PubMed

    Dai, Hongmei; Deng, Yuanying; Zhang, Jie; Han, Hailong; Zhao, Mingyi; Li, Ying; Zhang, Chen; Tian, Jing; Bing, Guoying; Zhao, Lingling

    2015-08-06

    Chlorpyrifos (CPF) is one of the most widely used organophosphorous insecticides. There are links between CPF exposure and neurological disorders. Mitochondrial damage has been implicated to play a key role in CPF-induced neurotoxicity. Mitophagy, the selective autophagic elimination of mitochondria, is an important mitochondrial quality control mechanism. However, the role of mitophagy in CPF-induced neurotoxicity remains unclear. In this study, CPF-caused mitochondrial damage, role and mechanism of mitophagy on CPF-induced neuroapoptosis were extensively studied by using SH-SY5Y cells. We showed that CPF treatment caused mitochondrial fragmentation, excessive ROS generation and mitochondrial depolarization, thus led to cell apoptosis. Moreover, CPF treatment also resulted in increased colocalizaton of mitochondria with LC3, decreased levels of mitochondrial proteins, PINK1 stabilization and mitochondrial accumulation of Parkin. These data suggested that CPF treatment induced PINK1/Parkin-mediated mitophagy in SH-SY5Y cells. Furthermore, knockdown of Parkin dramatically increased CPF-induced neuroapoptosis. On the other hand, overexpression of Parkin markedly alleviated CPF-induced SH-SY5Y cell apoptosis. Together, these findings implicate a protective role of PINK1/Parkin-mediated mitophagy against neuroapoptosis and that enhancing mitophagy provides a potential therapeutic strategy for CPF-induced neurological disorders. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  7. STAT3-mediated SMAD3 activation underlies Oncostatin M-induced Senescence

    PubMed Central

    Junk, Damian J.; Cipriano, Rocky; Jackson, Mark W.

    2017-01-01

    ABSTRACT Cytokines in the developing tumor microenvironment (TME) can drive transformation and subsequent progression toward metastasis. Elevated levels of the Interleukin-6 (IL-6) family cytokine Oncostatin M (OSM) in the breast TME correlate with aggressive, metastatic cancers, increased tumor recurrence, and poor patient prognosis. Paradoxically, OSM engages a tumor-suppressive, Signal Transducer and Activator of Transcription 3 (STAT3)-dependent senescence response in normal and non-transformed human mammary epithelial cells (HMEC). Here, we identify a novel link between OSM-activated STAT3 signaling and the Transforming Growth Factor-β (TGF-β) signaling pathway that engages senescence in HMEC. Inhibition of functional TGF-β/SMAD signaling by expressing a dominant-negative TGF-β receptor, treating with a TGF-β receptor inhibitor, or suppressing SMAD3 expression using a SMAD3-shRNA prevented OSM-induced senescence. OSM promoted a protein complex involving activated-STAT3 and SMAD3, induced the nuclear localization of SMAD3, and enhanced SMAD3-mediated transcription responsible for senescence. In contrast, expression of MYC (c-MYC) from a constitutive promoter abrogated senescence and strikingly, cooperated with OSM to promote a transformed phenotype, epithelial-mesenchymal transition (EMT), and invasiveness. Our findings suggest that a novel STAT3/SMAD3-signaling axis is required for OSM-mediated senescence that is coopted during the transformation process to confer aggressive cancer cell properties. Understanding how developing cancer cells bypass OSM/STAT3/SMAD3-mediated senescence may help identify novel targets for future “pro-senescence” therapies aiming to reengage this hidden tumor-suppressive response. PMID:27892764

  8. Antiproliferative and apoptosis inducing effects of citral via p53 and ROS-induced mitochondrial-mediated apoptosis in human colorectal HCT116 and HT29 cell lines.

    PubMed

    Sheikh, Bassem Y; Sarker, Md Moklesur Rahman; Kamarudin, Muhamad Noor Alfarizal; Mohan, Gokula

    2017-12-01

    Despite various anticancer reports, antiproliferative and apoptosis inducing activity of citral in HCT116 and HT29 cells have never been reported. This study aimed to evaluate the cytotoxic and apoptosis inducing effects of citral in colorectal cancer cell lines. The citral-treated cells were subjected to MTT assay followed by flow cytometric Annexin V-FITC/PI, mitochondrial membrane potential and intracellular reactive oxygen species (ROS) determination. The apoptotic proteins expression was investigated by Western blot analysis. Citral inhibited the growth of HCT116 and HT29 cells by dose- and time-dependent manner without inducing cytotoxicity in CCD841-CoN normal colon cells. Flow cytometric analysis showed that citral (50-200μM; 24-48h) induced the externalization of phoshpotidylserine and reduced the mitochondrial membrane potential in HCT116 and HT29 cells. Citral elevated intracellular ROS level while attenuating GSH levels in HCT116 and HT29 cells which were reversed with N-acetycysteine (2mM) pre-treatment indicating that citral induced mitochondrial-mediated apoptosis via augmentation of intracellular ROS. Citral induced the phosphorylation of p53 protein and the expression of Bax while decreasing Bc-2 and Bcl-xL expression which promoted the cleavage of caspase-3. Collectively, our data suggest that citral induced p53 and ROS-mediated mitochondrial-mediated apoptosis in human colorectal cancer HCT116 and HT29 cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Tumor necrosis factor and interleukin 1 as mediators of endotoxin-induced beneficial effects

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

    Urbaschek, R.; Urbaschek, B.

    Bacterial lipopolysaccharides or endotoxins are known to induce tumor necrosis; enhanced nonspecific resistance to bacterial, viral, and parasitic infections and to radiation sickness; and tolerance to lethal doses of endotoxin. These beneficial effects are achieved by pretreatment with minute amounts of endotoxin. Recombinant tumor necrosis factor (TNF) and interleukin 1 (IL-1) are among the mediators capable of invoking radioprotection or resistance to the consequences of cecal ligation and puncture. Both cytokines are potent inducers of serum colony-stimulating factor (CSF) in C3H/HeJ mice (low responders to endotoxin). The number of splenic granulocyte-macrophage precursors was found to increase 5 days after injectionmore » of TNF in these mice. Although with IL-1 no increase in the number of granulocyte-macrophage colonies occurred in culture in the presence of serum CSF, a marked stimulation was observed when TNF was added. This stimulation of myelopoiesis observed in vivo and in vitro may be related to the radioprotective effect of TNF. The data presented suggest that TNF and IL-1 released after injection of endotoxin participate in the mediation of endotoxin-induced enhancement of nonspecific resistance and stimulation of hematopoiesis. 76 references.« less

  10. Neck proprioception shapes body orientation and perception of motion.

    PubMed

    Pettorossi, Vito Enrico; Schieppati, Marco

    2014-01-01

    This review article deals with some effects of neck muscle proprioception on human balance, gait trajectory, subjective straight-ahead (SSA), and self-motion perception. These effects are easily observed during neck muscle vibration, a strong stimulus for the spindle primary afferent fibers. We first remind the early findings on human balance, gait trajectory, SSA, induced by limb, and neck muscle vibration. Then, more recent findings on self-motion perception of vestibular origin are described. The use of a vestibular asymmetric yaw-rotation stimulus for emphasizing the proprioceptive modulation of motion perception from the neck is mentioned. In addition, an attempt has been made to conjointly discuss the effects of unilateral neck proprioception on motion perception, SSA, and walking trajectory. Neck vibration also induces persistent aftereffects on the SSA and on self-motion perception of vestibular origin. These perceptive effects depend on intensity, duration, side of the conditioning vibratory stimulation, and on muscle status. These effects can be maintained for hours when prolonged high-frequency vibration is superimposed on muscle contraction. Overall, this brief outline emphasizes the contribution of neck muscle inflow to the construction and fine-tuning of perception of body orientation and motion. Furthermore, it indicates that tonic neck-proprioceptive input may induce persistent influences on the subject's mental representation of space. These plastic changes might adapt motion sensitiveness to lasting or permanent head positional or motor changes.

  11. Specific LPA receptor subtype mediation of LPA-induced hypertrophy of cardiac myocytes and involvement of Akt and NFkappaB signal pathways.

    PubMed

    Chen, Jinghai; Chen, Yuefeng; Zhu, Weiquan; Han, Yu; Han, Bianmei; Xu, Ruixia; Deng, Linzi; Cai, Yan; Cong, Xiangfeng; Yang, Yuejing; Hu, Shengshou; Chen, Xi

    2008-04-15

    Lysophosphatidic acid (LPA) is a bioactive phospholipid with diverse functions mediated via G-protein-coupled receptors (GPCRs). In view of the elevated levels of LPA in acute myocardial infarction (MI) patients we have conducted studies aimed at identifying specific LPA receptor subtypes and signaling events that may mediate its actions in hypertrophic remodeling. Experiments were carried out in cultured neonatal rat cardiomyocytes (NRCMs) exposed to LPA and in a rat MI model. In NRCMs, LPA-induced hypertrophic growth was completely abrogated by DGPP, an LPA1/LPA3 antagonist. The LPA3 agonist OMPT, but not the LPA2 agonist dodecylphosphate, promoted hypertrophy as examined by 3[H]-Leucine incorporation, ANF-luciferase expression and cell area. In in vivo experiments, LPA1, LPA2 and LPA3 mRNA levels as well as LPA1 and LPA3 protein levels increased together with left ventricular remodeling (LVRM) after MI. In addition, LPA stimulated the phosphorylation of Akt and p65 protein and activated NF-kappaB-luciferase expression. Inhibitors of PI3K (wortmannin), mTOR (rapamycin), and NF-kappaB (PDTC or SN50) effectively prevented LPA-induced 3[H]-Leucine incorporation and ANF-luciferase expression. Furthermore, ERK inhibitors (U0126 and PD98059) suppressed LPA-stimulated activation of NF-kappaB and p65 phosphorylation whereas wortmannin showed no effect on NF-kappaB activation. Our findings indicate that LPA3 and/or LPA1 mediate LPA-induced hypertrophy of NRCMs and that LPA1 and LPA3 may be involved in LVRM of MI rats. Moreover, Akt and NF-kappaB signaling pathways independently implicate in LPA-stimulated myocardial hypertrophic growth.

  12. Nuclear Membranes ETB Receptors Mediate ET-1-induced Increase of Nuclear Calcium in Human Left Ventricular Endocardial Endothelial Cells.

    PubMed

    Jules, Farah; Avedanian, Levon; Al-Khoury, Johny; Keita, Ramatoulaye; Normand, Alexandre; Bkaily, Ghassan; Jacques, Danielle

    2015-07-01

    In fetal human left ventricular endocardial endothelial cells (EECLs), both plasma membrane (PM) ET(A)R and ET(B)R were reported to mediate ET-1-induced increase of intracellular calcium [Ca](i); however, this effect was mediated by ET(A)R in right EECs (EECRs). In this study, we verified whether, as for the PM, nuclear membranes (NMs) ET-1 receptors activation in EECLs and EECRs induce an increase of nuclear calcium ([Ca](n)) and if this effect is mediated through the same receptor type as in PM. Using a plasmalemma-perforated technique and 3D confocal microscopy, our results showed that, as in PM intact cells, superfusion of nuclei of both cell types with cytosolic ET-1 induced a concentration-dependent sustained increase of [Ca](n). In EECRs, the ET(A)R antagonist prevented the effect of ET-1 on [Ca](n) without affecting EECLs. However, in both cell types, the effect of cytosolic ET-1 on [Ca](n) was prevented by the ETBR antagonist. In conclusion, both NMs' ET(A)R and ET(B)R mediated the effect of cytosolic ET-1 on [Ca](n) in EECRs. In contrast, only NMs' ET(B)R activation mediated the effect of cytosolic ET-1 in EECLs. Hence, the type of NMs' receptors mediating the effect of ET-1 on [Ca](n) are different from those of PM mediating the increase in [Ca](i).

  13. Optokinetic motion sickness - Attenuation of visually-induced apparent self-rotation by passive head movements

    NASA Technical Reports Server (NTRS)

    Teixeira, R. A.; Lackner, J. R.

    1979-01-01

    An experimental study was conducted on seven normal subjects to evaluate the effectiveness of passive head movements in suppressing the optokinetically-induced illusory self-rotation. Visual simulation was provided by a servo-controlled optokinetic drum. Each subject participated in two experimental sessions. In one condition, the subject's head remained stationary while he gazed passively at a moving stripe pattern. In the other, he gazed passively and relaxed his neck muscles while his head was rotated from side to side. It appears that suppression of optokinetically-induced illusory self-rotation with passive head movements results from the operation of a spatial constancy mechanism interrelating visual, vestibular, and kinesthetic information on ongoing body orientation. The results support the view that optokinetic 'motion sickness' is related, at least in part, to an oculomotor disturbance rather than a visually triggered disturbance of specifically vestibular etiology.

  14. Mast cells mediate the immune suppression induced by dermal exposure to JP-8 jet fuel.

    PubMed

    Limón-Flores, Alberto Y; Chacón-Salinas, Rommel; Ramos, Gerardo; Ullrich, Stephen E

    2009-11-01

    Applying jet propulsion-8 (JP-8) jet fuel to the skin of mice induces immune suppression. Applying JP-8 to the skin of mice suppresses T-cell-mediated immune reactions including, contact hypersensitivity (CHS) delayed-type hypersensitivity and T-cell proliferation. Because dermal mast cells play an important immune regulatory role in vivo, we tested the hypothesis that mast cells mediate jet fuel-induced immune suppression. When we applied JP-8 to the skin of mast cell deficient mice CHS was not suppressed. Reconstituting mast cell deficient mice with wild-type bone marrow derived mast cells (mast cell "knock-in mice") restored JP-8-induced immune suppression. When, however, mast cells from prostaglandin E(2) (PGE(2))-deficient mice were used, the ability of JP-8 to suppress CHS was not restored, indicating that mast cell-derived PGE(2) was activating immune suppression. Examining the density of mast cells in the skin and lymph nodes of JP-8-treated mice indicated that jet fuel treatment caused an initial increase in mast cell density in the skin, followed by increased numbers of mast cells in the subcutaneous space and then in draining lymph nodes. Applying JP-8 to the skin increased mast cell expression of CXCR4, and increased the expression of CXCL12 by draining lymph node cells. Because CXCL12 is a chemoattractant for CXCR4+ mast cells, we treated JP-8-treated mice with AMD3100, a CXCR4 antagonist. AMD3100 blocked the mobilization of mast cells to the draining lymph node and inhibited JP-8-induced immune suppression. Our findings demonstrate the importance of mast cells in mediating jet fuel-induced immune suppression.

  15. Cebpd Is Essential for Gamma-Tocotrienol Mediated Protection against Radiation-Induced Hematopoietic and Intestinal Injury

    PubMed Central

    Banerjee, Sudip; Shah, Sumit K.; Melnyk, Stepan B.; Hauer-Jensen, Martin

    2018-01-01

    Gamma-tocotrienol (GT3) confers protection against ionizing radiation (IR)-induced injury. However, the molecular targets that underlie the protective functions of GT3 are not yet known. We have reported that mice lacking CCAAT enhancer binding protein delta (Cebpd−/−) display increased mortality to IR due to injury to the hematopoietic and intestinal tissues and that Cebpd protects from IR-induced oxidative stress and cell death. The purpose of this study was to investigate whether Cebpd mediates the radio protective functions of GT3. We found that GT3-treated Cebpd−/− mice showed partial recovery of white blood cells compared to GT3-treated Cebpd+/+ mice at 2 weeks post-IR. GT3-treated Cebpd−/− mice showed an increased loss of intestinal crypt colonies, which correlated with increased expression of inflammatory cytokines and chemokines, increased levels of oxidized glutathione (GSSG), S-nitrosoglutathione (GSNO) and 3-nitrotyrosine (3-NT) after exposure to IR compared to GT3-treated Cebpd+/+ mice. Cebpd is induced by IR as well as a combination of IR and GT3 in the intestine. Studies have shown that granulocyte-colony stimulating factor (G-CSF), mediates the radioprotective functions of GT3. Interestingly, we found that IR alone as well as the combination of IR and GT3 caused robust augmentation of plasma G-CSF in both Cebpd+/+ and Cebpd−/− mice. These results identify a novel role for Cebpd in GT3-mediated protection against IR-induced injury, in part via modulation of IR-induced inflammation and oxidative/nitrosative stress, which is independent of G-CSF. PMID:29642403

  16. BH3-Only Protein BIM Mediates Heat Shock-Induced Apoptosis

    PubMed Central

    Mahajan, Indra M.; Chen, Miao-Der; Muro, Israel; Robertson, John D.; Wright, Casey W.; Bratton, Shawn B.

    2014-01-01

    Acute heat shock can induce apoptosis through a canonical pathway involving the upstream activation of caspase-2, followed by BID cleavage and stimulation of the intrinsic pathway. Herein, we report that the BH3-only protein BIM, rather than BID, is essential to heat shock-induced cell death. We observed that BIM-deficient cells were highly resistant to heat shock, exhibiting short and long-term survival equivalent to Bax−/−Bak−/− cells and better than either Bid−/− or dominant-negative caspase-9-expressing cells. Only Bim−/− and Bax−/−Bak−/− cells exhibited resistance to mitochondrial outer membrane permeabilization and loss of mitochondrial inner membrane potential. Moreover, while dimerized caspase-2 failed to induce apoptosis in Bid−/− cells, it readily did so in Bim−/− cells, implying that caspase-2 kills exclusively through BID, not BIM. Finally, BIM reportedly associates with MCL-1 following heat shock, and Mcl-1−/− cells were indeed sensitized to heat shock-induced apoptosis. However, pharmacological inhibition of BCL-2 and BCL-XL with ABT-737 also sensitized cells to heat shock, most likely through liberation of BIM. Thus, BIM mediates heat shock-induced apoptosis through a BAX/BAK-dependent pathway that is antagonized by antiapoptotic BCL-2 family members. PMID:24427286

  17. Motion-induced blindness and microsaccades: cause and effect

    PubMed Central

    Bonneh, Yoram S.; Donner, Tobias H.; Sagi, Dov; Fried, Moshe; Cooperman, Alexander; Heeger, David J; Arieli, Amos

    2010-01-01

    It has been suggested that subjective disappearance of visual stimuli results from a spontaneous reduction of microsaccade rate causing image stabilization, enhanced adaptation and a consequent fading. In motion-induced-blindness (MIB) salient visual targets disappear intermittently when surrounded by a moving pattern. We investigated whether changes in microsaccade rate can account for MIB. We first determined that the moving mask does not affect microsaccade metrics (rate, magnitude, and temporal distribution). We then compared the dynamics of microsaccades during reported illusory disappearance (MIB) and physical disappearance (Replay) of a salient peripheral target. We found large modulations of microsaccade rate following perceptual transitions, whether illusory (MIB) or real (Replay). For MIB, the rate also decreased prior to disappearance and increased prior to reappearance. Importantly, MIB persisted in the presence of microsaccades although sustained microsaccade rate was lower during invisible than visible periods. These results suggest that the microsaccade system reacts to changes in visibility, but microsaccades also modulate MIB. The latter modulation is well described by a Poisson model of the perceptual transitions assuming that the probability for reappearance and disappearance is modulated following a microsaccade. Our results show that microsaccades counteract disappearance, but are neither necessary nor sufficient to account for MIB. PMID:21172899

  18. Direct observation of X-ray induced atomic motion using scanning tunneling microscope combined with synchrotron radiation.

    PubMed

    Saito, Akira; Tanaka, Takehiro; Takagi, Yasumasa; Hosokawa, Hiromasa; Notsu, Hiroshi; Ohzeki, Gozo; Tanaka, Yoshihito; Kohmura, Yoshiki; Akai-Kasaya, Megumi; Ishikawa, Tetsuya; Kuwahara, Yuji; Kikuta, Seishi; Aono, Masakazu

    2011-04-01

    X-ray induced atomic motion on a Ge(111)-c(2 x 8) clean surface at room temperature was directly observed with atomic resolution using a synchrotron radiation (SR)-based scanning tunneling microscope (STM) system under ultra high vacuum condition. The atomic motion was visualized as a tracking image by developing a method to merge the STM images before and after X-ray irradiation. Using the tracking image, the atomic mobility was found to be strongly affected by defects on the surface, but was not dependent on the incident X-ray energy, although it was clearly dependent on the photon density. The atomic motion can be attributed to surface diffusion, which might not be due to core-excitation accompanied with electronic transition, but a thermal effect by X-ray irradiation. The crystal surface structure was possible to break even at a lower photon density than the conventionally known barrier. These results can alert X-ray studies in the near future about sample damage during measurements, while suggesting the possibility of new applications. Also the obtained results show a new availability of the in-situ SR-STM system.

  19. Phospholipase D and phosphatidic acid mediate heat stress induced secondary metabolism in Ganoderma lucidum.

    PubMed

    Liu, Yong-Nan; Lu, Xiao-Xiao; Chen, Dai; Lu, Ya-Ping; Ren, Ang; Shi, Liang; Zhu, Jing; Jiang, Ai-Liang; Yu, Han-Shou; Zhao, Ming-Wen

    2017-11-01

    Phospholipid-mediated signal transduction plays a key role in responses to environmental changes, but little is known about the role of phospholipid signalling in microorganisms. Heat stress (HS) is one of the most important environmental factors. Our previous study found that HS could induce the biosynthesis of the secondary metabolites, ganoderic acids (GA). Here, we performed a comprehensive mass spectrometry-based analysis to investigate HS-induced lipid remodelling in Ganoderma lucidum. In particular, we observed a significant accumulation of phosphatidic acid (PA) on HS. Further genetic tests in which pld-silencing strains were constructed demonstrated that the accumulation of PA is dependent on HS-activated phospholipase D (PLD) hydrolysing phosphatidylethanolamine. Furthermore, we determined the role of PLD and PA in HS-induced secondary metabolism in G. lucidum. Exogenous 1-butanol, which decreased PLD-mediated formation of PA, reverses the increased GA biosynthesis that was elicited by HS. The pld-silenced strains partly blocked HS-induced GA biosynthesis, and this block can be reversed by adding PA. Taken together, our results suggest that PLD and PA are involved in the regulation of HS-induced secondary metabolism in G. lucidum. Our findings provide key insights into how microorganisms respond to heat stress and then consequently accumulate secondary metabolites by phospholipid remodelling. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  20. Depletion force induced collective motion of microtubules driven by kinesin

    NASA Astrophysics Data System (ADS)

    Inoue, Daisuke; Mahmot, Bulbul; Kabir, Arif Md. Rashedul; Farhana, Tamanna Ishrat; Tokuraku, Kiyotaka; Sada, Kazuki; Konagaya, Akihiko; Kakugo, Akira

    2015-10-01

    Collective motion is a fascinating example of coordinated behavior of self-propelled objects, which is often associated with the formation of large scale patterns. Nowadays, the in vitro gliding assay is being considered a model system to experimentally investigate various aspects of group behavior and pattern formation by self-propelled objects. In the in vitro gliding assay, cytoskeletal filaments F-actin or microtubules are driven by the surface immobilized associated biomolecular motors myosin or dynein respectively. Although the F-actin/myosin or microtubule/dynein system was found to be promising in understanding the collective motion and pattern formation by self-propelled objects, the most widely used biomolecular motor system microtubule/kinesin could not be successfully employed so far in this regard. Failure in exhibiting collective motion by kinesin driven microtubules is attributed to the intrinsic properties of kinesin, which was speculated to affect the behavior of individual gliding microtubules and mutual interactions among them. In this work, for the first time, we have demonstrated the collective motion of kinesin driven microtubules by regulating the mutual interaction among the gliding microtubules, by employing a depletion force among them. Proper regulation of the mutual interaction among the gliding microtubules through the employment of the depletion force was found to allow the exhibition of collective motion and stream pattern formation by the microtubules. This work offers a universal means for demonstrating the collective motion using the in vitro gliding assay of biomolecular motor systems and will help obtain a meticulous understanding of the fascinating coordinated behavior and pattern formation by self-propelled objects.Collective motion is a fascinating example of coordinated behavior of self-propelled objects, which is often associated with the formation of large scale patterns. Nowadays, the in vitro gliding assay is being

  1. Plasticity Beyond V1: Reinforcement of Motion Perception upon Binocular Central Retinal Lesions in Adulthood.

    PubMed

    Burnat, Kalina; Hu, Tjing-Tjing; Kossut, Małgorzata; Eysel, Ulf T; Arckens, Lutgarde

    2017-09-13

    postlesion time. Only the motion-sensitive area V5/PMLS shows no decrease, and even a significant activity increase at 3 months post-retinal lesion. Behavioral tests of motion perception found no impairment and even better sensitivity to higher random dot stimulus velocities. We demonstrate that the loss of central vision induces functional mobilization of motion-sensitive visual cortex, resulting in enhanced perception of moving stimuli. Copyright © 2017 the authors 0270-6474/17/378989-11$15.00/0.

  2. Peroxynitrite mediates testosterone-induced vasodilation of microvascular resistance vessels.

    PubMed

    Puttabyatappa, Yashoda; Stallone, John N; Ergul, Adviye; El-Remessy, Azza B; Kumar, Sanjiv; Black, Stephen; Johnson, Maribeth; Owen, Mary P; White, Richard E

    2013-04-01

    Our knowledge of how androgens influence the cardiovascular system is far from complete, and this lack of understanding is especially true of how androgens affect resistance vessels. Our aim was to identify the signaling mechanisms stimulated by testosterone (TES) in microvascular arteries and to understand how these mechanisms mediate TES-induced vasodilation. Mesenteric microvessels were isolated from male Sprague-Dawley rats. Tension studies demonstrated a rapid, concentration-dependent, vasodilatory response to TES that did not involve protein synthesis or aromatization to 17β-estradiol. Dichlorofluorescein fluorescence and nitrotyrosine immunoblot experiments indicated that TES stimulated peroxynitrite formation in microvessels, and functional studies demonstrated that TES-induced vasodilation was inhibited by scavenging peroxynitrite. As predicted, TES enhanced the production of both peroxynitrite precursors (i.e., superoxide and nitic oxide), and xanthine oxidase was identified as the likely source of TES-stimulated superoxide production. Functional and biochemical studies indicated that TES signaling involved activity of the phosphoinositide 3 (PI3) kinase-protein kinase B (Akt) cascade initiated by activation of the androgen receptor and culminated in enhanced production of cGMP and microvascular vasodilation. These findings, derived from a variety of analytical and functional approaches, provide evidence for a novel nongenomic signaling mechanism for androgen action in the microvasculature: TES-stimulated vasodilation mediated primarily by peroxynitrite formed from xanthine oxidase-generated superoxide and NO. This response was associated with activation of the PI3 kinase-Akt signaling cascade initiated by activation of the androgen receptor. We propose this mechanism could account for TES-stimulated cGMP production in microvessels and, ultimately, vasodilation.

  3. Peroxynitrite Mediates Testosterone-Induced Vasodilation of Microvascular Resistance Vessels

    PubMed Central

    Puttabyatappa, Yashoda; Stallone, John N.; Ergul, Adviye; El-Remessy, Azza B.; Kumar, Sanjiv; Black, Stephen; Johnson, Maribeth; Owen, Mary P.

    2013-01-01

    Our knowledge of how androgens influence the cardiovascular system is far from complete, and this lack of understanding is especially true of how androgens affect resistance vessels. Our aim was to identify the signaling mechanisms stimulated by testosterone (TES) in microvascular arteries and to understand how these mechanisms mediate TES-induced vasodilation. Mesenteric microvessels were isolated from male Sprague-Dawley rats. Tension studies demonstrated a rapid, concentration-dependent, vasodilatory response to TES that did not involve protein synthesis or aromatization to 17β-estradiol. Dichlorofluorescein fluorescence and nitrotyrosine immunoblot experiments indicated that TES stimulated peroxynitrite formation in microvessels, and functional studies demonstrated that TES-induced vasodilation was inhibited by scavenging peroxynitrite. As predicted, TES enhanced the production of both peroxynitrite precursors (i.e., superoxide and nitic oxide), and xanthine oxidase was identified as the likely source of TES-stimulated superoxide production. Functional and biochemical studies indicated that TES signaling involved activity of the phosphoinositide 3 (PI3) kinase-protein kinase B (Akt) cascade initiated by activation of the androgen receptor and culminated in enhanced production of cGMP and microvascular vasodilation. These findings, derived from a variety of analytical and functional approaches, provide evidence for a novel nongenomic signaling mechanism for androgen action in the microvasculature: TES-stimulated vasodilation mediated primarily by peroxynitrite formed from xanthine oxidase-generated superoxide and NO. This response was associated with activation of the PI3 kinase-Akt signaling cascade initiated by activation of the androgen receptor. We propose this mechanism could account for TES-stimulated cGMP production in microvessels and, ultimately, vasodilation. PMID:23318471

  4. Seizure-mediated neuronal activation induces DREAM gene expression in the mouse brain.

    PubMed

    Matsu-ura, Toru; Konishi, Yoshiyuki; Aoki, Tsutomu; Naranjo, Jose R; Mikoshiba, Katsuhiko; Tamura, Taka-aki

    2002-12-30

    Various transcriptional activators are induced in neurons concomitantly with long-lasting neural activity, whereas only a few transcription factors are known to act as neural activity-inducible transcription repressors. In this study, mRNA of DREAM (DRE-antagonizing modulator), a Ca(2+)-modulated transcriptional repressor, was demonstrated to accumulate in the mouse brain after pentylenetetrazol (PTZ)-induced seizures. Accumulation in the mouse hippocampus reached maximal level in the late phase (at 7-8 h) after PTZ injection. Kainic acid induced the same response. Interestingly, the late induction of DREAM expression required new protein synthesis and was blocked by MK801 suggesting that Ca(2+)-influx via NMDA receptors is necessary for the PTZ-mediated DREAM expression. In situ hybridization revealed that PTZ-induced DREAM mRNA accumulation was observed particularly in the dentate gyrus, cerebral cortex, and piriform cortex. The results of the present study demonstrate that DREAM is a neural activity-stimulated late gene and suggest its involvement in adaptation to long-lasting neuronal activity.

  5. Effect of intrafractional prostate motion on simultaneous boost intensity-modulated radiotherapy to the prostate: A simulation study based on intrafractional motion in the prone position

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

    Ikeda, Itaru; Mizowaki, Takashi, E-mail: mizo@kuhp.kyoto-u.ac.jp; Ono, Tomohiro

    2015-01-01

    Although the prostate displacement of patients in the prone position is affected by respiration-induced motion, the effect of intrafractional prostate motion in the prone position during “simultaneous integrated boost intensity-modulated radiotherapy” (SIB-IMRT) is unclear. The purpose of this study was to evaluate the dosimetric effects of intrafractional motion on SIB-IMRT to a dominant intraprostatic lesion (IPL) using measured motion data of patients in a prone position, fixed with a thermoplastic shell. We obtained 2 orthogonal x-ray fluoroscopic images at the same moment every 0.2 seconds for 30 seconds before and after treatment, once weekly, from 7 patients with localized prostatemore » cancer with detectable prostatic calcification. Prostate displacements in the left-right (LR), anteroposterior (AP), and superoinferior (SI) directions were calculated using the prostatic calcification as a fiducial marker. We defined the displacement between pretreatment and posttreatment as baseline drift (BD). An SIB-IMRT plan was generated in which each IPL + 3 mm received a dose of 94.5 Gy, whereas the remainder of the prostate + 7 mm received a dose of 75.6 Gy in 9 fields. A simulated plan of dose blurring was generated by the convolution of isocenter-shifted plans using measured motion data in 30 seconds and motion in 30 seconds + distance between pretreatment and posttreatment position (BD) for each of the 7 patients. The motion in 30 seconds mainly reflected respiration-induced motion. The mean displacements of BD were 1.4 mm (− 3.1 to 8.2 mm), − 2.2 mm (− 9.1 to 1.5 mm), and − 0.3 mm (− 5.0 to 1.8 mm) in the AP, SI, and LR directions, respectively. The differences in the target coverage with V{sub 90%} of the IPL and V{sub 100%} of the prostate between the simulated plan and original plan were − 3.9% to − 0.3% and − 0.6% to 1.1% for respiration-induced motion and 3.1% to − 67.8% and 3.6% to − 13.3% for BD with respiration-induced motion

  6. Hypothalamic CaMKKβ mediates glucagon anorectic effect and its diet-induced resistance.

    PubMed

    Quiñones, Mar; Al-Massadi, Omar; Gallego, Rosalía; Fernø, Johan; Diéguez, Carlos; López, Miguel; Nogueiras, Ruben

    2015-12-01

    Glucagon receptor antagonists and humanized glucagon antibodies are currently studied as promising therapies for obesity and type II diabetes. Among its variety of actions, glucagon reduces food intake, but the molecular mechanisms mediating this effect as well as glucagon resistance are totally unknown. Glucagon and adenoviral vectors were administered in specific hypothalamic nuclei of lean and diet-induced obese rats. The expression of neuropeptides controlling food intake was performed by in situ hybridization. The regulation of factors of the glucagon signaling pathway was assessed by western blot. The central injection of glucagon decreased feeding through a hypothalamic pathway involving protein kinase A (PKA)/Ca(2+)-calmodulin-dependent protein kinase kinase β (CaMKKβ)/AMP-activated protein kinase (AMPK)-dependent mechanism. More specifically, the central injection of glucagon increases PKA activity and reduces protein levels of CaMKKβ and its downstream target phosphorylated AMPK in the hypothalamic arcuate nucleus (ARC). Consistently, central glucagon significantly decreased AgRP expression. Inhibition of PKA and genetic activation of AMPK in the ARC blocked glucagon-induced anorexia in lean rats. Genetic down-regulation of glucagon receptors in the ARC stimulates fasting-induced hyperphagia. Although glucagon was unable to decrease food intake in DIO rats, glucagon sensitivity was restored after inactivation of CaMKKβ, specifically in the ARC. Thus, glucagon decreases food intake acutely via PKA/CaMKKβ/AMPK dependent pathways in the ARC, and CaMKKβ mediates its obesity-induced hypothalamic resistance. This work reveals the molecular underpinnings by which glucagon controls feeding that may lead to a better understanding of disease states linked to anorexia and cachexia.

  7. Effects of Second-Order Sum- and Difference-Frequency Wave Forces on the Motion Response of a Tension-Leg Platform Considering the Set-down Motion

    NASA Astrophysics Data System (ADS)

    Wang, Bin; Tang, Yougang; Li, Yan; Cai, Runbo

    2018-04-01

    This paper presents a study on the motion response of a tension-leg platform (TLP) under first- and second-order wave forces, including the mean-drift force, difference and sum-frequency forces. The second-order wave force is calculated using the full-field quadratic transfer function (QTF). The coupled effect of the horizontal motions, such as surge, sway and yaw motions, and the set-down motion are taken into consideration by the nonlinear restoring matrix. The time-domain analysis with 50-yr random sea state is performed. A comparison of the results of different case studies is made to assess the influence of second-order wave force on the motions of the platform. The analysis shows that the second-order wave force has a major impact on motions of the TLP. The second-order difference-frequency wave force has an obvious influence on the low-frequency motions of surge and sway, and also will induce a large set-down motion which is an important part of heave motion. Besides, the second-order sum-frequency force will induce a set of high-frequency motions of roll and pitch. However, little influence of second-order wave force is found on the yaw motion.

  8. The binding protein BiP attenuates stress-induced cell death in soybean via modulation of the N-rich protein-mediated signaling pathway.

    PubMed

    Reis, Pedro A A; Rosado, Gustavo L; Silva, Lucas A C; Oliveira, Luciana C; Oliveira, Lucas B; Costa, Maximiller D L; Alvim, Fátima C; Fontes, Elizabeth P B

    2011-12-01

    The molecular chaperone binding protein (BiP) participates in the constitutive function of the endoplasmic reticulum (ER) and protects the cell against stresses. In this study, we investigated the underlying mechanism by which BiP protects plant cells from stress-induced cell death. We found that enhanced expression of BiP in soybean (Glycine max) attenuated ER stress- and osmotic stress-mediated cell death. Ectopic expression of BiP in transgenic lines attenuated the leaf necrotic lesions that are caused by the ER stress inducer tunicamycin and also maintained shoot turgidity upon polyethylene glycol-induced dehydration. BiP-mediated attenuation of stress-induced cell death was confirmed by the decreased percentage of dead cell, the reduced induction of the senescence-associated marker gene GmCystP, and reduced DNA fragmentation in BiP-overexpressing lines. These phenotypes were accompanied by a delay in the induction of the cell death marker genes N-RICH PROTEIN-A (NRP-A), NRP-B, and GmNAC6, which are involved in transducing a cell death signal generated by ER stress and osmotic stress through the NRP-mediated signaling pathway. The prosurvival effect of BiP was associated with modulation of the ER stress- and osmotic stress-induced NRP-mediated cell death signaling, as determined in transgenic tobacco (Nicotiana tabacum) lines with enhanced (sense) and suppressed (antisense) BiP levels. Enhanced expression of BiP prevented NRP- and NAC6-mediated chlorosis and the appearance of senescence-associated markers, whereas silencing of endogenous BiP accelerated the onset of leaf senescence mediated by NRPs and GmNAC6. Collectively, these results implicate BiP as a negative regulator of the stress-induced NRP-mediated cell death response.

  9. The Impact of Motion Induced Interruptions on Cognitive Performance

    DTIC Science & Technology

    2014-07-23

    found that even participants presenting with minor physiological effects of motion experienced a decline in multitasking performance. Further, Yu...literature has investigated the impact of task based interruptions such as being inter- rupted by a phone call or writing an email . In these...Engineers Journal. 102 (2) 65-72. Matsangas, P. (2013). The Effect of Mild Motion Sickness and Sopite Syndrome on Multitasking Cognitive Performance

  10. Crew activity and motion effects on the space station

    NASA Technical Reports Server (NTRS)

    Rochon, Brian V.; Scheer, Steven A.

    1987-01-01

    Among the significant sources of internal disturbances that must be considered in the design of space station vibration control systems are the loads induced on the structure from various crew activities. Flight experiment T013, flown on the second manned mission of Skylab, measured force and moment time histories for a range of preplanned crew motions and activities. This experiment has proved itself invaluable as a source of on-orbit crew induced loads that has allowed a space station forcing function data base to be built. This will enable forced response such as acceleration and deflections, attributable to crew activity, to be calculated. The flight experiment, resultant database and structural model pre-processor, analysis examples and areas of combined research shall be described.

  11. CFTR mediates noradrenaline-induced ATP efflux from DRG neurons.

    PubMed

    Kanno, Takeshi; Nishizaki, Tomoyuki

    2011-09-24

    In our earlier study, noradrenaline (NA) stimulated ATP release from dorsal root ganglion (DRG) neurons as mediated via β(3) adrenoceptors linked to G(s) protein involving protein kinase A (PKA) activation, to cause allodynia. The present study was conducted to understand how ATP is released from DRG neurons. In an outside-out patch-clamp configuration from acutely dissociated rat DRG neurons, single-channel currents, sensitive to the P2X receptor inhibitor PPADS, were evoked by approaching the patch-electrode tip close to a neuron, indicating that ATP is released from DRG neurons, to activate P2X receptor. NA increased the frequency of the single-channel events, but such NA effect was not found for DRG neurons transfected with the siRNA to silence the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In the immunocytochemical study using acutely dissociated rat DRG cells, CFTR was expressed in neurons alone, but not satellite cells, fibroblasts, or Schwann cells. It is concluded from these results that CFTR mediates NA-induced ATP efflux from DRG neurons as an ATP channel.

  12. TRPV3 channels mediate strontium-induced mouse egg activation

    PubMed Central

    Carvacho, Ingrid; Lee, Hoi Chang; Fissore, Rafael A.; Clapham, David E.

    2014-01-01

    SUMMARY In mammals, calcium influx is required for oocyte maturation and egg activation. The molecular identities of the calcium-permeant channels that underlie the initiation of embryonic development are not established. Here, we describe a Transient Receptor Potential (TRP) ion channel current activated by TRP agonists that is absent in TrpV3−/− eggs. TRPV3 current is differentially expressed during oocyte maturation, reaching a peak of maximum density and activity at metaphase of meiosis II (MII), the stage of fertilization. Selective activation of TRPV3 channels provokes egg activation by mediating massive calcium entry. Widely used to activate eggs, strontium application is known to yield normal offspring in combination with somatic cell nuclear transfer. We show that TRPV3 is required for strontium influx, as TrpV3−/− eggs failed to permeate Sr2+ or undergo strontium-induced activation. We propose that TRPV3 is the major mediator of calcium influx in mouse eggs and is a putative target for artificial egg activation. PMID:24316078

  13. A neural model of motion processing and visual navigation by cortical area MST.

    PubMed

    Grossberg, S; Mingolla, E; Pack, C

    1999-12-01

    Cells in the dorsal medial superior temporal cortex (MSTd) process optic flow generated by self-motion during visually guided navigation. A neural model shows how interactions between well-known neural mechanisms (log polar cortical magnification, Gaussian motion-sensitive receptive fields, spatial pooling of motion-sensitive signals and subtractive extraretinal eye movement signals) lead to emergent properties that quantitatively simulate neurophysiological data about MSTd cell properties and psychophysical data about human navigation. Model cells match MSTd neuron responses to optic flow stimuli placed in different parts of the visual field, including position invariance, tuning curves, preferred spiral directions, direction reversals, average response curves and preferred locations for stimulus motion centers. The model shows how the preferred motion direction of the most active MSTd cells can explain human judgments of self-motion direction (heading), without using complex heading templates. The model explains when extraretinal eye movement signals are needed for accurate heading perception, and when retinal input is sufficient, and how heading judgments depend on scene layouts and rotation rates.

  14. Ground-motion modeling of Hayward fault scenario earthquakes, part II: Simulation of long-period and broadband ground motions

    USGS Publications Warehouse

    Aagaard, Brad T.; Graves, Robert W.; Rodgers, Arthur; Brocher, Thomas M.; Simpson, Robert W.; Dreger, Douglas; Petersson, N. Anders; Larsen, Shawn C.; Ma, Shuo; Jachens, Robert C.

    2010-01-01

    We simulate long-period (T>1.0–2.0 s) and broadband (T>0.1 s) ground motions for 39 scenario earthquakes (Mw 6.7–7.2) involving the Hayward, Calaveras, and Rodgers Creek faults. For rupture on the Hayward fault, we consider the effects of creep on coseismic slip using two different approaches, both of which reduce the ground motions, compared with neglecting the influence of creep. Nevertheless, the scenario earthquakes generate strong shaking throughout the San Francisco Bay area, with about 50% of the urban area experiencing modified Mercalli intensity VII or greater for the magnitude 7.0 scenario events. Long-period simulations of the 2007 Mw 4.18 Oakland earthquake and the 2007 Mw 5.45 Alum Rock earthquake show that the U.S. Geological Survey’s Bay Area Velocity Model version 08.3.0 permits simulation of the amplitude and duration of shaking throughout the San Francisco Bay area for Hayward fault earthquakes, with the greatest accuracy in the Santa Clara Valley (San Jose area). The ground motions for the suite of scenarios exhibit a strong sensitivity to the rupture length (or magnitude), hypocenter (or rupture directivity), and slip distribution. The ground motions display a much weaker sensitivity to the rise time and rupture speed. Peak velocities, peak accelerations, and spectral accelerations from the synthetic broadband ground motions are, on average, slightly higher than the Next Generation Attenuation (NGA) ground-motion prediction equations. We attribute much of this difference to the seismic velocity structure in the San Francisco Bay area and how the NGA models account for basin amplification; the NGA relations may underpredict amplification in shallow sedimentary basins. The simulations also suggest that the Spudich and Chiou (2008) directivity corrections to the NGA relations could be improved by increasing the areal extent of rupture directivity with period.

  15. Doxorubicin-induced necrosis is mediated by poly-(ADP-ribose) polymerase 1 (PARP1) but is independent of p53.

    PubMed

    Shin, Hyeon-Jun; Kwon, Hyuk-Kwon; Lee, Jae-Hyeok; Gui, Xiangai; Achek, Asma; Kim, Jae-Ho; Choi, Sangdun

    2015-11-02

    Necrosis, unregulated cell death, is characterized by plasma membrane rupture as well as nuclear and cellular swelling. However, it has recently been reported that necrosis is a regulated form of cell death mediated by poly-(ADP-ribose) polymerase 1 (PARP1). PARP1 is thought to mediate necrosis by inducing DNA damage, although this remains unconfirmed. In this study, we examined the mechanisms of PARP1-mediated necrosis following doxorubicin (DOX)-induced DNA damage in human kidney proximal tubular (HK-2) cells. DOX initiated DNA damage response (DDR) and upregulated PARP1 and p53 expression, resulting in morphological changes similar to those observed during necrosis. Additionally, DOX induced mitochondrial hyper-activation, as evidenced by increased mitochondrial respiration and cytosolic ATP (cATP) production. However, DOX affected mitochondrial mass. DOX-induced DNA damage, cytosolic reactive oxygen species (cROS) generation, and mitochondrial hyper-activation decreased in cells with inhibited PARP1 expression, while generation of nitric oxide (NO) and mitochondrial ROS (mROS) remained unaffected. Moreover, DOX-induced DNA damage, cell cycle changes, and oxidative stress were not affected by p53 inhibition. These findings suggest that DNA damage induced necrosis through a PARP1-dependent and p53-independent pathway.

  16. Doxorubicin-induced necrosis is mediated by poly-(ADP-ribose) polymerase 1 (PARP1) but is independent of p53

    PubMed Central

    Shin, Hyeon-Jun; Kwon, Hyuk-Kwon; Lee, Jae-Hyeok; Gui, Xiangai; Achek, Asma; Kim, Jae-Ho; Choi, Sangdun

    2015-01-01

    Necrosis, unregulated cell death, is characterized by plasma membrane rupture as well as nuclear and cellular swelling. However, it has recently been reported that necrosis is a regulated form of cell death mediated by poly-(ADP-ribose) polymerase 1 (PARP1). PARP1 is thought to mediate necrosis by inducing DNA damage, although this remains unconfirmed. In this study, we examined the mechanisms of PARP1-mediated necrosis following doxorubicin (DOX)-induced DNA damage in human kidney proximal tubular (HK-2) cells. DOX initiated DNA damage response (DDR) and upregulated PARP1 and p53 expression, resulting in morphological changes similar to those observed during necrosis. Additionally, DOX induced mitochondrial hyper-activation, as evidenced by increased mitochondrial respiration and cytosolic ATP (cATP) production. However, DOX affected mitochondrial mass. DOX-induced DNA damage, cytosolic reactive oxygen species (cROS) generation, and mitochondrial hyper-activation decreased in cells with inhibited PARP1 expression, while generation of nitric oxide (NO) and mitochondrial ROS (mROS) remained unaffected. Moreover, DOX-induced DNA damage, cell cycle changes, and oxidative stress were not affected by p53 inhibition. These findings suggest that DNA damage induced necrosis through a PARP1-dependent and p53-independent pathway. PMID:26522181

  17. Aeroelastic impact of above-rated wave-induced structural motions on the near-wake stability of a floating offshore wind turbine rotor

    NASA Astrophysics Data System (ADS)

    Rodriguez, Steven; Jaworski, Justin

    2017-11-01

    The impact of above-rated wave-induced motions on the stability of floating offshore wind turbine near-wakes is studied numerically. The rotor near-wake is generated using a lifting-line free vortex wake method, which is strongly coupled to a finite element solver for kinematically nonlinear blade deformations. A synthetic time series of relatively high-amplitude/high-frequency representative of above-rated conditions of the NREL 5MW referece wind turbine is imposed on the rotor structure. To evaluate the impact of these above-rated conditions, a linear stability analysis is first performed on the near wake generated by a fixed-tower wind turbine configuration at above-rated inflow conditions. The platform motion is then introduced via synthetic time series, and a stability analysis is performed on the wake generated by the floating offshore wind turbine at the same above-rated inflow conditions. The stability trends (disturbance modes versus the divergence rate of vortex structures) of the two analyses are compared to identify the impact that above-rated wave-induced structural motions have on the stability of the floating offshore wind turbine wake.

  18. GSK-3 mediates the okadaic acid-induced modification of collapsin response mediator protein-2 in human SK-N-SH neuroblastoma cells.

    PubMed

    Ni, Mei-Hui; Wu, Chih-Ching; Chan, Wen-Hsiung; Chien, Kun-Yi; Yu, Jau-Song

    2008-04-15

    Collapsin response mediator protein-2 (CRMP-2), a phosphoprotein involved in axonal outgrowth and microtubule dynamics, is aberrantly phosphorylated in Alzheimer's disease (AD) brain. Alteration of glycogen synthase kinase-3 (GSK-3) activity is associated with the pathogenesis of AD. Here, we show that CRMP-2 is one of the major substrates for GSK-3 in pig brain extracts. Both GSK-3alpha and 3beta phosphorylate purified pig brain CRMP-2 and significantly alter its mobility in SDS-gels, resembling the CRMP-2 modification observed in AD brain. Interestingly, this modification can be detected in SK-N-SH neuroblastoma cells treated with a phosphatase inhibitor, okadaic acid (OA), and GSK-3 inhibitors completely block this OA-induced event. Knockdown of both GSK-3alpha and 3beta, but not either kinase alone, impairs OA-induced modification of CRMP-2. Mutation of Ser-518 or Ser-522 of CRMP-2, which are highly phosphorylated in AD brain, to Ala blocks the OA-induced modification of CRMP-2 in SK-N-SH cells. Ser-522 prephosphorylated by Cdk5 is required for subsequent GSK-3alpha-mediated phosphorylation of CRMP-2 in vitro. Collectively, our results demonstrate for the first time that OA can induce phosphorylation of CRMP-2 in SK-N-SH cells at sites aberrantly phosphorylated in AD brain, and both GSK-3alpha and 3beta and Ser-522 kinase(s) are involved in this process.

  19. Motion perception: behavior and neural substrate.

    PubMed

    Mather, George

    2011-05-01

    Visual motion perception is vital for survival. Single-unit recordings in primate primary visual cortex (V1) have revealed the existence of specialized motion sensing neurons; perceptual effects such as the motion after-effect demonstrate their importance for motion perception. Human psychophysical data on motion detection can be explained by a computational model of cortical motion sensors. Both psychophysical and physiological data reveal at least two classes of motion sensor capable of sensing motion in luminance-defined and texture-defined patterns, respectively. Psychophysical experiments also reveal that motion can be seen independently of motion sensor output, based on attentive tracking of visual features. Sensor outputs are inherently ambiguous, due to the problem of univariance in neural responses. In order to compute stimulus direction and speed, the visual system must compare the responses of many different sensors sensitive to different directions and speeds. Physiological data show that this computation occurs in the visual middle temporal (MT) area. Recent psychophysical studies indicate that information about spatial form may also play a role in motion computations. Adaptation studies show that the human visual system is selectively sensitive to large-scale optic flow patterns, and physiological studies indicate that cells in the middle superior temporal (MST) area derive this sensitivity from the combined responses of many MT cells. Extraretinal signals used to control eye movements are an important source of signals to cancel out the retinal motion responses generated by eye movements, though visual information also plays a role. A number of issues remain to be resolved at all levels of the motion-processing hierarchy. WIREs Cogni Sci 2011 2 305-314 DOI: 10.1002/wcs.110 For further resources related to this article, please visit the WIREs website Additional Supporting Information may be found in http://www.lifesci.sussex.ac.uk/home/George_Mather/Motion

  20. Dynamic motion of red blood cells in simple shear flow

    NASA Astrophysics Data System (ADS)

    Sui, Y.; Chew, Y. T.; Roy, P.; Cheng, Y. P.; Low, H. T.

    2008-11-01

    A three-dimensional numerical model is proposed to simulate the dynamic motion of red blood cells (RBCs) in simple shear flow. The RBCs are approximated by ghost cells consisting of Newtonian liquid drops enclosed by Skalak membranes which take into account the membrane shear elasticity and the membrane area incompressibility. The RBCs have an initially biconcave discoid resting shape, and the internal liquid is assumed to have the same physical properties as the matrix fluid. The simulation is based on a hybrid method, in which the immersed boundary concept is introduced into the framework of the lattice Boltzmann method, and a finite element model is incorporated to obtain the forces acting on the nodes of the cell membrane which is discretized into flat triangular elements. The dynamic motion of RBCs is investigated in simple shear flow under a broad range of shear rates. At large shear rates, the cells are found to carry out a swinging motion, in which periodic inclination oscillation and shape deformation superimpose on the membrane tank treading motion. With the shear rate decreasing, the swinging amplitude of the cell increases, and finally triggers a transition to tumbling motion. This is the first direct numerical simulation that predicts both the swinging motion of the RBCs and the shear rate induced transition, which have been observed in a recent experiment. It is also found that as the mode changes from swinging to tumbling, the apparent viscosity of the suspension increases monotonically.

  1. Neck Proprioception Shapes Body Orientation and Perception of Motion

    PubMed Central

    Pettorossi, Vito Enrico; Schieppati, Marco

    2014-01-01

    This review article deals with some effects of neck muscle proprioception on human balance, gait trajectory, subjective straight-ahead (SSA), and self-motion perception. These effects are easily observed during neck muscle vibration, a strong stimulus for the spindle primary afferent fibers. We first remind the early findings on human balance, gait trajectory, SSA, induced by limb, and neck muscle vibration. Then, more recent findings on self-motion perception of vestibular origin are described. The use of a vestibular asymmetric yaw-rotation stimulus for emphasizing the proprioceptive modulation of motion perception from the neck is mentioned. In addition, an attempt has been made to conjointly discuss the effects of unilateral neck proprioception on motion perception, SSA, and walking trajectory. Neck vibration also induces persistent aftereffects on the SSA and on self-motion perception of vestibular origin. These perceptive effects depend on intensity, duration, side of the conditioning vibratory stimulation, and on muscle status. These effects can be maintained for hours when prolonged high-frequency vibration is superimposed on muscle contraction. Overall, this brief outline emphasizes the contribution of neck muscle inflow to the construction and fine-tuning of perception of body orientation and motion. Furthermore, it indicates that tonic neck-proprioceptive input may induce persistent influences on the subject’s mental representation of space. These plastic changes might adapt motion sensitiveness to lasting or permanent head positional or motor changes. PMID:25414660

  2. Phytochromes A and B Mediate Red-Light-Induced Positive Phototropism in Roots1

    PubMed Central

    Kiss, John Z.; Mullen, Jack L.; Correll, Melanie J.; Hangarter, Roger P.

    2003-01-01

    The interaction of tropisms is important in determining the final growth form of the plant body. In roots, gravitropism is the predominant tropistic response, but phototropism also plays a role in the oriented growth of roots in flowering plants. In blue or white light, roots exhibit negative phototropism that is mediated by the phototropin family of photoreceptors. In contrast, red light induces a positive phototropism in Arabidopsis roots. Because this red-light-induced response is weak relative to both gravitropism and negative phototropism, we used a novel device to study phototropism without the complications of a counteracting gravitational stimulus. This device is based on a computer-controlled system using real-time image analysis of root growth and a feedback-regulated rotatable stage. Our data show that this system is useful to study root phototropism in response to red light, because in wild-type roots, the maximal curvature detected with this apparatus is 30° to 40°, compared with 5° to 10° without the feedback system. In positive root phototropism, sensing of red light occurs in the root itself and is not dependent on shoot-derived signals resulting from light perception. Phytochrome (Phy)A and phyB were severely impaired in red-light-induced phototropism, whereas the phyD and phyE mutants were normal in this response. Thus, PHYA and PHYB play a key role in mediating red-light-dependent positive phototropism in roots. Although phytochrome has been shown to mediate phototropism in some lower plant groups, this is one of the few reports indicating a phytochrome-dependent phototropism in flowering plants. PMID:12644690

  3. A Framework for the Validation of Probabilistic Seismic Hazard Analysis Maps Using Strong Ground Motion Data

    NASA Astrophysics Data System (ADS)

    Bydlon, S. A.; Beroza, G. C.

    2015-12-01

    Recent debate on the efficacy of Probabilistic Seismic Hazard Analysis (PSHA), and the utility of hazard maps (i.e. Stein et al., 2011; Hanks et al., 2012), has prompted a need for validation of such maps using recorded strong ground motion data. Unfortunately, strong motion records are limited spatially and temporally relative to the area and time windows hazard maps encompass. We develop a framework to test the predictive powers of PSHA maps that is flexible with respect to a map's specified probability of exceedance and time window, and the strong motion receiver coverage. Using a combination of recorded and interpolated strong motion records produced through the ShakeMap environment, we compile a record of ground motion intensity measures for California from 2002-present. We use this information to perform an area-based test of California PSHA maps inspired by the work of Ward (1995). Though this framework is flexible in that it can be applied to seismically active areas where ShakeMap-like ground shaking interpolations have or can be produced, this testing procedure is limited by the relatively short lifetime of strong motion recordings and by the desire to only test with data collected after the development of the PSHA map under scrutiny. To account for this, we use the assumption that PSHA maps are time independent to adapt the testing procedure for periods of recorded data shorter than the lifetime of a map. We note that accuracy of this testing procedure will only improve as more data is collected, or as the time-horizon of interest is reduced, as has been proposed for maps of areas experiencing induced seismicity. We believe that this procedure can be used to determine whether PSHA maps are accurately portraying seismic hazard and whether discrepancies are localized or systemic.

  4. Shared Sensory Estimates for Human Motion Perception and Pursuit Eye Movements

    PubMed Central

    Mukherjee, Trishna; Battifarano, Matthew; Simoncini, Claudio

    2015-01-01

    Are sensory estimates formed centrally in the brain and then shared between perceptual and motor pathways or is centrally represented sensory activity decoded independently to drive awareness and action? Questions about the brain's information flow pose a challenge because systems-level estimates of environmental signals are only accessible indirectly as behavior. Assessing whether sensory estimates are shared between perceptual and motor circuits requires comparing perceptual reports with motor behavior arising from the same sensory activity. Extrastriate visual cortex both mediates the perception of visual motion and provides the visual inputs for behaviors such as smooth pursuit eye movements. Pursuit has been a valuable testing ground for theories of sensory information processing because the neural circuits and physiological response properties of motion-responsive cortical areas are well studied, sensory estimates of visual motion signals are formed quickly, and the initiation of pursuit is closely coupled to sensory estimates of target motion. Here, we analyzed variability in visually driven smooth pursuit and perceptual reports of target direction and speed in human subjects while we manipulated the signal-to-noise level of motion estimates. Comparable levels of variability throughout viewing time and across conditions provide evidence for shared noise sources in the perception and action pathways arising from a common sensory estimate. We found that conditions that create poor, low-gain pursuit create a discrepancy between the precision of perception and that of pursuit. Differences in pursuit gain arising from differences in optic flow strength in the stimulus reconcile much of the controversy on this topic. PMID:26041919

  5. Prevention of doxorubicin-induced cardiomyopathy using targeted MaFGF mediated by nanoparticles combined with ultrasound-targeted MB destruction

    PubMed Central

    Zheng, Lei; ZhuGe, De-Li; Chen, Bin; Lu, Cui-Tao; Yuan, Jian-Jun; Zhao, Ying-Zheng

    2017-01-01

    The present study seeks to observe the preventive effects of doxorubicin-induced cardiomyopathy (DOX-CM) in rats using targeted non-mitogenic acidic fibroblast growth factor (MaFGF) mediated by nanoparticles (NP) combined with ultrasound-targeted MB destruction (UTMD). DOX-CM rats were induced by intraperitoneally injected doxorubicin. Six weeks after intervention, the indices from the transthoracic echocardiography and velocity vector imaging showed that the left ventricular function in the MaFGF-loaded NP (MaFGF-NP) + UTMD group was significantly improved compared with the DOX-CM group. The increased malondialdehyde and decreased superoxide dismutase were observed in the DOX-CM group, while a significant increase in superoxide dismutase and a decrease in malondialdehyde were detected in the groups treated with MaFGF-NP + UTMD. From the Masson staining, the MaFGF-NP + UTMD group showed a significant difference from the DOX-CM group. The cardiac collagen volume fraction and the ratio of the perivascular collagen area to the luminal area number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling positive cells in the MaFGF-NP + UTMD group decreased to 8.9%, 0.55-fold, compared with the DOX-CM group (26.5%, 1.7-fold). From terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling staining, the results showed the strongest inhibition of apoptosis progress in MaFGF-NP + UTMD group. The immunohistochemical staining of the TGF-β1 in MaFGF-NP + UTMD group reached 3.6%, which was much lower than that of the DOX-CM group (12.6%). These results confirmed that the abnormalities, including left ventricular dysfunction, myocardial fibrosis, cardiomyocytes apoptosis and oxidative stress, could be suppressed by twice weekly MaFGF treatments for 6 consecutive weeks (free MaFGF or MaFGF-NP+/UTMD), with the strongest improvements observed in the MaFGF-NP + UTMD group. Western blot analyses of the heart

  6. Mast Cells Mediate the Immune Suppression Induced by Dermal Exposure to JP-8 Jet Fuel

    PubMed Central

    Limón-Flores, Alberto Y.; Chacón-Salinas, Rommel; Ramos, Gerardo; Ullrich, Stephen E.

    2009-01-01

    Applying jet propulsion-8 (JP-8) jet fuel to the skin of mice induces immune suppression. Applying JP-8 to the skin of mice suppresses T-cell–mediated immune reactions including, contact hypersensitivity (CHS) delayed-type hypersensitivity and T-cell proliferation. Because dermal mast cells play an important immune regulatory role in vivo, we tested the hypothesis that mast cells mediate jet fuel–induced immune suppression. When we applied JP-8 to the skin of mast cell deficient mice CHS was not suppressed. Reconstituting mast cell deficient mice with wild-type bone marrow derived mast cells (mast cell “knock-in mice”) restored JP-8–induced immune suppression. When, however, mast cells from prostaglandin E2 (PGE2)–deficient mice were used, the ability of JP-8 to suppress CHS was not restored, indicating that mast cell–derived PGE2 was activating immune suppression. Examining the density of mast cells in the skin and lymph nodes of JP-8-treated mice indicated that jet fuel treatment caused an initial increase in mast cell density in the skin, followed by increased numbers of mast cells in the subcutaneous space and then in draining lymph nodes. Applying JP-8 to the skin increased mast cell expression of CXCR4, and increased the expression of CXCL12 by draining lymph node cells. Because CXCL12 is a chemoattractant for CXCR4+ mast cells, we treated JP-8-treated mice with AMD3100, a CXCR4 antagonist. AMD3100 blocked the mobilization of mast cells to the draining lymph node and inhibited JP-8–induced immune suppression. Our findings demonstrate the importance of mast cells in mediating jet fuel–induced immune suppression. PMID:19726579

  7. MotionFlow: Visual Abstraction and Aggregation of Sequential Patterns in Human Motion Tracking Data.

    PubMed

    Jang, Sujin; Elmqvist, Niklas; Ramani, Karthik

    2016-01-01

    Pattern analysis of human motions, which is useful in many research areas, requires understanding and comparison of different styles of motion patterns. However, working with human motion tracking data to support such analysis poses great challenges. In this paper, we propose MotionFlow, a visual analytics system that provides an effective overview of various motion patterns based on an interactive flow visualization. This visualization formulates a motion sequence as transitions between static poses, and aggregates these sequences into a tree diagram to construct a set of motion patterns. The system also allows the users to directly reflect the context of data and their perception of pose similarities in generating representative pose states. We provide local and global controls over the partition-based clustering process. To support the users in organizing unstructured motion data into pattern groups, we designed a set of interactions that enables searching for similar motion sequences from the data, detailed exploration of data subsets, and creating and modifying the group of motion patterns. To evaluate the usability of MotionFlow, we conducted a user study with six researchers with expertise in gesture-based interaction design. They used MotionFlow to explore and organize unstructured motion tracking data. Results show that the researchers were able to easily learn how to use MotionFlow, and the system effectively supported their pattern analysis activities, including leveraging their perception and domain knowledge.

  8. Management of Respiration-Induced Motion With 4-Dimensional Computed Tomography (4DCT) for Pancreas Irradiation

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

    Tai, An, E-mail: atai@mcw.edu; Liang, Zhiwen; Radiation Oncology Center, Wuhan Union Hospital, Huazhong University of Science and Technology, Wuhan

    2013-08-01

    Purpose: The purposes of this study were to quantify respiration-induced organ motions for pancreatic cancer patients and to explore strategies to account for these motions. Methods and Materials: Both 3-dimensional computed tomography (3DCT) and 4-dimensional computed tomography (4DCT) scans were acquired sequentially for 15 pancreatic cancer patients, including 10 randomly selected patients and 5 patients selected from a subgroup of patients with large tumor respiratory motions. 3DCTs were fused with 2 sets of 4DCT data at the end of exhale phase (50%) and the end of inhale phase (0%). The target was delineated on the 50% and 0% phase CTmore » sets, and the organs at risk were drawn on the 3DCT. These contours were populated to the CT sets at other respiratory phases based on deformable image registration. Internal target volumes (ITV) were generated by tracing the target contours of all phases (ITV{sub 10}), 3 phases of 0%, 20% and 50% (ITV{sub 3}), and 2 phases of 0% and 50% (ITV{sub 2}). ITVs generated from phase images were compared using percentage of volume overlap, Dice coefficient, geometric centers, and average surface distance. Results: Volume variations of pancreas, kidneys, and liver as a function of respiratory phases were small (<5%) during respiration. For the 10 randomly selected patients, peak-to-peak amplitudes of liver, left kidney, right kidney, and the target along the superior-inferior (SI) direction were 7.9 ± 3.2 mm, 7.1 ± 3.1 mm, 5.7 ± 3.2 mm, and 5.9 ± 2.8 mm, respectively. The percentage of volume overlap and Dice coefficient were 92% ± 1% and 96% ± 1% between ITV{sub 10} and ITV{sub 2} and 96% ± 1% and 98% ± 1% between ITV{sub 10} and ITV{sub 3}, respectively. The percentage of volume overlap between ITV{sub 10} and ITV{sub 3} was 93.6 ± 1.1 for patients with tumor motion >8 mm. Conclusions: Appropriate motion management strategies are proposed for radiation treatment planning of pancreatic tumors based on magnitudes of

  9. Cardiac hypertrophy induced by active Raf depends on Yorkie-mediated transcription

    PubMed Central

    Yu, Lin; Daniels, Joseph P.; Wu, Huihui; Wolf, Matthew J.

    2015-01-01

    Organ hypertrophy can result from enlargement of individual cells or from cell proliferation or both. Activating mutations in the serine-threonine kinase Raf cause cardiac hypertrophy and contribute to Noonan syndrome in humans. Cardiac-specific expression of activated Raf also causes hypertrophy in Drosophila melanogaster. We found that Yorkie (Yki), a transcriptional coactivator in the Hippo pathway that regulates organ size, is required for Raf-induced cardiac hypertrophy in flies. Although aberrant activation of Yki orthologs stimulates cardiac hyperplasia in mice, cardiac-specific expression of an activated mutant form of Yki in fruit flies caused cardiac hypertrophy without hyperplasia. Knockdown of Yki caused cardiac dilation without loss of cardiomyocytes and prevented Raf-induced cardiac hypertrophy. In flies, Yki-induced cardiac hypertrophy required the TEA domain–containing transcription factor Scalloped, and, in mammalian cells, expression of mouse RafL613V, an activated form of Raf with a Noonan syndrome mutation, increased Yki-induced Scalloped activity. Furthermore, overexpression of Tgi (a Tondu domain–containing Scalloped-binding corepressor) in the fly heart abrogated Yki- or Raf-induced cardiac hypertrophy. Thus, crosstalk between Raf and Yki occurs in the heart and can influence Raf-mediated cardiac hypertrophy. PMID:25650441

  10. Anthocyanins protect against LPS-induced oxidative stress-mediated neuroinflammation and neurodegeneration in the adult mouse cortex.

    PubMed

    Khan, Muhammad Sohail; Ali, Tahir; Kim, Min Woo; Jo, Myeung Hoon; Jo, Min Gi; Badshah, Haroon; Kim, Myeong Ok

    2016-11-01

    Several studies provide evidence that reactive oxygen species (ROS) are key mediators of various neurological disorders. Anthocyanins are polyphenolic compounds and are well known for their anti-oxidant and neuroprotective effects. In this study, we investigated the neuroprotective effects of anthocyanins (extracted from black soybean) against lipopolysaccharide (LPS)-induced ROS-mediated neuroinflammation and neurodegeneration in the adult mouse cortex. Intraperitoneal injection of LPS (250 μg/kg) for 7 days triggers elevated ROS and oxidative stress, which induces neuroinflammation and neurodegeneration in the adult mouse cortex. Treatment with 24 mg/kg/day of anthocyanins for 14 days in LPS-injected mice (7 days before and 7 days co-treated with LPS) attenuated elevated ROS and oxidative stress compared to mice that received LPS-injection alone. The immunoblotting results showed that anthocyanins reduced the level of the oxidative stress kinase phospho-c-Jun N-terminal Kinase 1 (p-JNK). The immunoblotting and morphological results showed that anthocyanins treatment significantly reduced LPS-induced-ROS-mediated neuroinflammation through inhibition of various inflammatory mediators, such as IL-1β, TNF-α and the transcription factor NF- k B. Anthocyanins treatment also reduced activated astrocytes and microglia in the cortex of LPS-injected mice, as indicated by reductions in GFAP and Iba-1, respectively. Anthocyanins also prevent overexpression of various apoptotic markers, i.e., Bax, cytosolic cytochrome C, cleaved caspase-3 and PARP-1. Immunohistochemical fluoro-jade B (FJB) and Nissl staining indicated that anthocyanins prevent LPS-induced neurodegeneration in the mouse cortex. Our results suggest that dietary flavonoids, such as anthocyanins, have antioxidant and neuroprotective activities that could be beneficial to various neurological disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. The Development of Wireless Body Area Network for Motion Sensing Application

    NASA Astrophysics Data System (ADS)

    Puspitaningayu, P.; Widodo, A.; Yundra, E.; Ramadhany, F.; Arianto, L.; Habibie, D.

    2018-04-01

    The information era has driven the society into the digitally-controlled lifestyle. Wireless body area networks (WBAN) as the specific scope of wireless sensor networks (WSN) is consistently growing into bigger applications. Currently, people are able to monitor their medical parameters by simply using small electronics devices attached to their body and connected to the authorities. On top of that, this time, smart phones are typically equipped with sensors such as accelerometer, gyroscope, barometric pressure, heart rate monitor, etc. It means that the sensing yet the signal processing can be performed by a single device. Moreover, Android opens lot wider opportunities for new applications as the most popular open-sourced smart phone platform. This paper is intended to show the development of motion sensing application which focused on analysing data from accelerometer and gyroscope. Beside reads the sensors, this application also has the ability to convert the sensors’ numerical value into graphs.

  12. Activation of the Human MT Complex by Motion in Depth Induced by a Moving Cast Shadow

    PubMed Central

    Katsuyama, Narumi; Usui, Nobuo; Taira, Masato

    2016-01-01

    A moving cast shadow is a powerful monocular depth cue for motion perception in depth. For example, when a cast shadow moves away from or toward an object in a two-dimensional plane, the object appears to move toward or away from the observer in depth, respectively, whereas the size and position of the object are constant. Although the cortical mechanisms underlying motion perception in depth by cast shadow are unknown, the human MT complex (hMT+) is likely involved in the process, as it is sensitive to motion in depth represented by binocular depth cues. In the present study, we examined this possibility by using a functional magnetic resonance imaging (fMRI) technique. First, we identified the cortical regions sensitive to the motion of a square in depth represented via binocular disparity. Consistent with previous studies, we observed significant activation in the bilateral hMT+, and defined functional regions of interest (ROIs) there. We then investigated the activity of the ROIs during observation of the following stimuli: 1) a central square that appeared to move back and forth via a moving cast shadow (mCS); 2) a segmented and scrambled cast shadow presented beside the square (sCS); and 3) no cast shadow (nCS). Participants perceived motion of the square in depth in the mCS condition only. The activity of the hMT+ was significantly higher in the mCS compared with the sCS and nCS conditions. Moreover, the hMT+ was activated equally in both hemispheres in the mCS condition, despite presentation of the cast shadow in the bottom-right quadrant of the stimulus. Perception of the square moving in depth across visual hemifields may be reflected in the bilateral activation of the hMT+. We concluded that the hMT+ is involved in motion perception in depth induced by moving cast shadow and by binocular disparity. PMID:27597999

  13. Topical photosan-mediated photodynamic therapy for DMBA-induced hamster buccal pouch early cancer lesions: an in vivo study

    NASA Astrophysics Data System (ADS)

    Hsu, Yih-Chih; Chang, Walter Hong-Shong; Chang, Junn-Liang; Liu, Kuang-Ting; Chiang, Chun-Pin; Liu, Chung-Ji; Chen, Chih-Ping

    2011-03-01

    Oral cancer has becomes the most prominent cancer disease in recent years in Taiwan. The reason is the betel nut chewing habit combing with smoking and alcohol-drinking lifestyle of people results in oral cancer becomes the fastest growth incident cancer amongst other major cancer diseases. In previous studies showed that photosan, haematoporphyrin derivative (HPD), has demonstrated effective PDT results on human head and neck disease studies. To avoid the systemic phototoxic effect of photosan, this study was designed to use a topical photosan-mediated PDT for treatment of DMBA-induced hamster buccal pouch cancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical photosan-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when photosan reached its peak level in the lesional epithelial cells after topical application of photosan gel. We found that photosan reached its peak level in cancerous lesions about 13.5 min after topical application of photosan gel. The cancerous lesions in hamsters were then treated with topical photosan-mediated PDT (fluence rate: 600 mW/cm2; light exposure dose 200 J/cm2) using the portable Lumacare 635 nm fiber-guided light device. Visual examination demonstrated that topical photosan-mediated PDT was an applicable treatment modality for DMBA-induced hamster buccal pouch cancerous lesions.

  14. Involvement of Bim in Photofrin-mediated photodynamically induced apoptosis.

    PubMed

    Wang, Xianwang; He, Xiaobing; Hu, Shujuan; Sun, Anbang; Lu, Chengbiao

    2015-01-01

    Photodynamic therapy (PDT) is a promising noninvasive technique, which has been successfully applied to the treatment of human cancers. Studies have shown that the Bcl-2 family proteins play important roles in PDT-induced apoptosis. However, whether Bcl-2-interacting mediator of cell death (Bim) is involved in photodynamic treatment remains unknown. In this study, we attempt to determine the effect of Bim on Photofrin photodynamic treatment (PPT)-induced apoptosis in human lung adenocarcinoma ASTC-a-1 cells. The translocation of Bim/Bax of the cells were monitored by laser confocal scanning microscope. The levels of Bim protein and activated caspase-3 in cells were detected by western blot assay. Caspase-3 activities were measured by Caspase-3 Fluorogenic Substrate (Ac-DEVD-AFC) analysis. The induction of apoptosis was detected by Hoechst 33258 and PI staining as well as flow cytometry analysis. The effect of Bim on PPT-induced apoptosis was determined by RNAi. BimL translocated to mitochondria in response to PPT, similar to the downstream pro-apoptotic protein Bax activation. PPT increased the level of Bim and activated caspase-3 in cells and that knockdown of Bim by RNAi significantly protected against caspase-3 activity. PPT-induced apoptosis were suppressed in cells transfected with shRNA-Bim. We demonstrated the involvement of Bim in PPT-induced apoptosis in human ASTC-a-1 lung adenocarcinoma cells and suggested that enhancing Bim activity might be a potential strategy for treating human cancers. © 2015 S. Karger AG, Basel.

  15. The long- and short-term variability of breathing induced tumor motion in lung and liver over the course of a radiotherapy treatment.

    PubMed

    Dhont, Jennifer; Vandemeulebroucke, Jef; Burghelea, Manuela; Poels, Kenneth; Depuydt, Tom; Van Den Begin, Robbe; Jaudet, Cyril; Collen, Christine; Engels, Benedikt; Reynders, Truus; Boussaer, Marlies; Gevaert, Thierry; De Ridder, Mark; Verellen, Dirk

    2018-02-01

    To evaluate the short and long-term variability of breathing induced tumor motion. 3D tumor motion of 19 lung and 18 liver lesions captured over the course of an SBRT treatment were evaluated and compared to the motion on 4D-CT. An implanted fiducial could be used for unambiguous motion information. Fast orthogonal fluoroscopy (FF) sequences, included in the treatment workflow, were used to evaluate motion during treatment. Several motion parameters were compared between different FF sequences from the same fraction to evaluate the intrafraction variability. To assess interfraction variability, amplitude and hysteresis were compared between fractions and with the 3D tumor motion registered by 4D-CT. Population based margins, necessary on top of the ITV to capture all motion variability, were calculated based on the motion captured during treatment. Baseline drift in the cranio-caudal (CC) or anterior-poster (AP) direction is significant (ie. >5 mm) for a large group of patients, in contrary to intrafraction amplitude and hysteresis variability. However, a correlation between intrafraction amplitude variability and mean motion amplitude was found (Pearson's correlation coefficient, r = 0.72, p < 10 -4 ). Interfraction variability in amplitude is significant for 46% of all lesions. As such, 4D-CT accurately captures the motion during treatment for some fractions but not for all. Accounting for motion variability during treatment increases the PTV margins in all directions, most significantly in CC from 5 mm to 13.7 mm for lung and 8.0 mm for liver. Both short-term and day-to-day tumor motion variability can be significant, especially for lesions moving with amplitudes above 7 mm. Abandoning passive motion management strategies in favor of more active ones is advised. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Morphological changes of plasma membrane and protein assembly during clathrin-mediated endocytosis

    PubMed Central

    Yoshida, Aiko; Sakai, Nobuaki; Uekusa, Yoshitsugu; Imaoka, Yuka; Itagaki, Yoshitsuna; Suzuki, Yuki

    2018-01-01

    Clathrin-mediated endocytosis (CME) proceeds through a series of morphological changes of the plasma membrane induced by a number of protein components. Although the spatiotemporal assembly of these proteins has been elucidated by fluorescence-based techniques, the protein-induced morphological changes of the plasma membrane have not been fully clarified in living cells. Here, we visualize membrane morphology together with protein localizations during CME by utilizing high-speed atomic force microscopy (HS-AFM) combined with a confocal laser scanning unit. The plasma membrane starts to invaginate approximately 30 s after clathrin starts to assemble, and the aperture diameter increases as clathrin accumulates. Actin rapidly accumulates around the pit and induces a small membrane swelling, which, within 30 s, rapidly covers the pit irreversibly. Inhibition of actin turnover abolishes the swelling and induces a reversible open–close motion of the pit, indicating that actin dynamics are necessary for efficient and irreversible pit closure at the end of CME. PMID:29723197

  17. Sensitivity analysis for direct and indirect effects in the presence of exposure-induced mediator-outcome confounders

    PubMed Central

    Chiba, Yasutaka

    2014-01-01

    Questions of mediation are often of interest in reasoning about mechanisms, and methods have been developed to address these questions. However, these methods make strong assumptions about the absence of confounding. Even if exposure is randomized, there may be mediator-outcome confounding variables. Inference about direct and indirect effects is particularly challenging if these mediator-outcome confounders are affected by the exposure because in this case these effects are not identified irrespective of whether data is available on these exposure-induced mediator-outcome confounders. In this paper, we provide a sensitivity analysis technique for natural direct and indirect effects that is applicable even if there are mediator-outcome confounders affected by the exposure. We give techniques for both the difference and risk ratio scales and compare the technique to other possible approaches. PMID:25580387

  18. Receptor Interacting Protein 3-Mediated Necroptosis Promotes Lipopolysaccharide-Induced Inflammation and Acute Respiratory Distress Syndrome in Mice.

    PubMed

    Wang, Linlin; Wang, Tingting; Li, Haobo; Liu, Qing; Zhang, Zhongjun; Xie, Wanli; Feng, Yinglu; Socorburam, Tumenjavkhlan; Wu, Gui; Xia, Zhengyuan; Wu, Qingping

    2016-01-01

    Necrosis amplifies inflammation and plays important roles in acute respiratory distress syndrome (ARDS). Necroptosis is a newly identified programmed necrosis that is mediated by receptor interacting protein 3 (RIP3). However, the potential involvement and impact of necroptosis in lipopolysaccharide (LPS)-induced ARDS remains unknown. We therefore explored the role and mechanism of RIP3-mediated necroptosis in LPS-induced ARDS. Mice were instilled with increasing doses of LPS intratracheally to induce different degrees of ARDS. Lung tissues were harvested for histological and TUNEL staining and western blot for RIP3, p-RIP3, X-linked inhibitor of apoptosis protein (XIAP), mixed lineage kinase domain-like protein (MLKL), total and cleaved caspases-3/8. Then, wild-type and RIP3 knock-out mice were induced ARDS with 30 mg/kg LPS. Pulmonary cellular necrosis was labeled by the propidium Iodide (PI) staining. Levels of TNF-a, Interleukin (IL)-1β, IL-6, IL-1α, IL-10 and HMGB1, tissue myeloperoxidase (MPO) activity, neutrophil counts and total protein concentration were measured. Results showed that in high dose LPS (30mg/kg and 40mg/kg) -induced severe ARDS, RIP3 protein was increased significantly, accompanied by increases of p-RIP3 and MLKL, while in low dose LPS (10mg/kg and 20mg/kg) -induced mild ARDS, apoptosis was remarkably increased. In LPS-induced severe ARDS, RIP3 knock-out alleviated the hypothermia symptom, increased survival rate and ameliorated the lung tissue injury RIP3 depletion also attenuated LPS-induced increase in IL-1α/β, IL-6 and HMGB1 release, decreased tissue MPO activity, and reduced neutrophil influx and total protein concentration in BALF in severe ARDS. Further, RIP3 depletion reduced the necrotic cells in the lung and decreased the expression of MLKL, but had no impact on cleaved caspase-3 in LPS-induced ARDS. It is concluded that RIP3-mediated necroptosis is a major mechanism of enhanced inflammation and lung tissue injury in high dose

  19. Receptor Interacting Protein 3-Mediated Necroptosis Promotes Lipopolysaccharide-Induced Inflammation and Acute Respiratory Distress Syndrome in Mice

    PubMed Central

    Li, Haobo; Liu, Qing; Zhang, Zhongjun; Xie, Wanli; Feng, Yinglu; Socorburam, Tumenjavkhlan; Wu, Gui; Xia, Zhengyuan; Wu, Qingping

    2016-01-01

    Necrosis amplifies inflammation and plays important roles in acute respiratory distress syndrome (ARDS). Necroptosis is a newly identified programmed necrosis that is mediated by receptor interacting protein 3 (RIP3). However, the potential involvement and impact of necroptosis in lipopolysaccharide (LPS)-induced ARDS remains unknown. We therefore explored the role and mechanism of RIP3-mediated necroptosis in LPS-induced ARDS. Mice were instilled with increasing doses of LPS intratracheally to induce different degrees of ARDS. Lung tissues were harvested for histological and TUNEL staining and western blot for RIP3, p-RIP3, X-linked inhibitor of apoptosis protein (XIAP), mixed lineage kinase domain-like protein (MLKL), total and cleaved caspases-3/8. Then, wild-type and RIP3 knock-out mice were induced ARDS with 30 mg/kg LPS. Pulmonary cellular necrosis was labeled by the propidium Iodide (PI) staining. Levels of TNF-a, Interleukin (IL)-1β, IL-6, IL-1α, IL-10 and HMGB1, tissue myeloperoxidase (MPO) activity, neutrophil counts and total protein concentration were measured. Results showed that in high dose LPS (30mg/kg and 40mg/kg) -induced severe ARDS, RIP3 protein was increased significantly, accompanied by increases of p-RIP3 and MLKL, while in low dose LPS (10mg/kg and 20mg/kg) -induced mild ARDS, apoptosis was remarkably increased. In LPS-induced severe ARDS, RIP3 knock-out alleviated the hypothermia symptom, increased survival rate and ameliorated the lung tissue injury RIP3 depletion also attenuated LPS-induced increase in IL-1α/β, IL-6 and HMGB1 release, decreased tissue MPO activity, and reduced neutrophil influx and total protein concentration in BALF in severe ARDS. Further, RIP3 depletion reduced the necrotic cells in the lung and decreased the expression of MLKL, but had no impact on cleaved caspase-3 in LPS-induced ARDS. It is concluded that RIP3-mediated necroptosis is a major mechanism of enhanced inflammation and lung tissue injury in high dose

  20. Simple motion correction strategy reduces respiratory-induced motion artifacts for k-t accelerated and compressed-sensing cardiovascular magnetic resonance perfusion imaging.

    PubMed

    Zhou, Ruixi; Huang, Wei; Yang, Yang; Chen, Xiao; Weller, Daniel S; Kramer, Christopher M; Kozerke, Sebastian; Salerno, Michael

    2018-02-01

    Cardiovascular magnetic resonance (CMR) stress perfusion imaging provides important diagnostic and prognostic information in coronary artery disease (CAD). Current clinical sequences have limited temporal and/or spatial resolution, and incomplete heart coverage. Techniques such as k-t principal component analysis (PCA) or k-t sparcity and low rank structure (SLR), which rely on the high degree of spatiotemporal correlation in first-pass perfusion data, can significantly accelerate image acquisition mitigating these problems. However, in the presence of respiratory motion, these techniques can suffer from significant degradation of image quality. A number of techniques based on non-rigid registration have been developed. However, to first approximation, breathing motion predominantly results in rigid motion of the heart. To this end, a simple robust motion correction strategy is proposed for k-t accelerated and compressed sensing (CS) perfusion imaging. A simple respiratory motion compensation (MC) strategy for k-t accelerated and compressed-sensing CMR perfusion imaging to selectively correct respiratory motion of the heart was implemented based on linear k-space phase shifts derived from rigid motion registration of a region-of-interest (ROI) encompassing the heart. A variable density Poisson disk acquisition strategy was used to minimize coherent aliasing in the presence of respiratory motion, and images were reconstructed using k-t PCA and k-t SLR with or without motion correction. The strategy was evaluated in a CMR-extended cardiac torso digital (XCAT) phantom and in prospectively acquired first-pass perfusion studies in 12 subjects undergoing clinically ordered CMR studies. Phantom studies were assessed using the Structural Similarity Index (SSIM) and Root Mean Square Error (RMSE). In patient studies, image quality was scored in a blinded fashion by two experienced cardiologists. In the phantom experiments, images reconstructed with the MC strategy had higher

  1. Macrophage-induced angiogenesis is mediated by tumour necrosis factor-alpha.

    PubMed

    Leibovich, S J; Polverini, P J; Shepard, H M; Wiseman, D M; Shively, V; Nuseir, N

    Macrophages are important in the induction of new blood vessel growth during wound repair, inflammation and tumour growth. We show here that tumour necrosis factor-alpha (TNF-alpha), a secretory product of activated macrophages that is believed to mediate tumour cytotoxicity, is a potent inducer of new blood vessel growth (angiogenesis). In vivo, TNF-alpha induces capillary blood vessel formation in the rat cornea and the developing chick chorioallantoic membrane at very low doses. In vitro, TNF-alpha stimulates chemotaxis of bovine adrenal capillary endothelial cells and induces cultures of these cells grown on type-1 collagen gels to form capillary-tube-like structures. The angiogenic activity produced by activated murine peritoneal macrophages is completely neutralized by a polyclonal antibody to TNF-alpha, suggesting immunological features are common to TNF-alpha and the protein responsible for macrophage-derived angiogenic activity. In inflammation and wound repair, TNF-alpha could augment repair by stimulating new blood vessel growth; in tumours, TNF-alpha might both stimulate tumour development by promoting vessel growth and participate in tumour destruction by direct cytotoxicity.

  2. Wave induced coastal cliff top ground motions and infragravity wave dissipation under high energy wave conditions.

    NASA Astrophysics Data System (ADS)

    Earlie, C. S.; le Dantec, N.; Young, A.

    2016-12-01

    Coastal cliff erosion is a widespread problem that threatens property and infrastructure globally. The prediction of this risk calls for robust understanding of the processes and mechanisms involved in causing coastal cliff failure. Over the last decade, a number of geomorphological studies have highlighted the importance of the relationship between the offshore wave climate and cliff-toe water levels, and the resultant coastal response in terms of cliff-top ground motion and erosion. Field-based studies of instantaneous cliff response to direct wave impact have shown that wave-induced loading of the foreshore leads to cliff-top ground motions that may have the potential to weaken the integrity of the rocks and prepare them for failure. In order to understand wave-cliff interaction and how beach morphodynamics influences cliff-top ground motion and cliff erosion, two field experiments were carried out simultaneously at two locations in Northern Brittany (France). This three-month long winter field campaign (Jan-Mar 2016) included, for the first time, a comparison of cliff-top ground motion and cliff erosion at sites fronted by different beach morphologies (reflective/dissipative), along with monitoring of hydrodynamic forcing and beach topography. The magnitude of cliff-top displacements at both sites were dependent on tidal stage and free water surface elevation at the cliff toe, with the greatest contributions of cliff-top ground motions found at infragravity frequencies (0.05-0.005 Hz). Vertical displacements at infragravity and incident sea-swell (0.1-0.5 Hz) frequencies were greater at the dissipative site, apart from during spring high tide and energetic wave conditions, where displacements were two times that at the reflective site. Combining these wave-cliff interaction data with beach morphology and nearshore bathymetry will be key to understanding the spatial variability in cliff erosion under a variety of environmental settings and forcing conditions.

  3. Silver Nanoparticles Induce HePG-2 Cells Apoptosis Through ROS-Mediated Signaling Pathways

    NASA Astrophysics Data System (ADS)

    Zhu, Bing; Li, Yinghua; Lin, Zhengfang; Zhao, Mingqi; Xu, Tiantian; Wang, Changbing; Deng, Ning

    2016-04-01

    Recently, silver nanoparticles (AgNPs) have been shown to provide a novel approach to overcome tumors, especially those of hepatocarcinoma. However, the anticancer mechanism of silver nanoparticles is unclear. Thus, the purpose of this study was to estimate the effect of AgNPs on proliferation and activation of ROS-mediated signaling pathway on human hepatocellular carcinoma HePG-2 cells. A simple chemical method for preparing AgNPs with superior anticancer activity has been showed in this study. AgNPs were detected by transmission electronic microscopy (TEM) and energy dispersive X-ray (EDX). The size distribution and zeta potential of silver nanoparticles were detected by Zetasizer Nano. The average size of AgNPs (2 nm) observably increased the cellular uptake by endocytosis. AgNPs markedly inhibited the proliferation of HePG-2 cells through induction of apoptosis with caspase-3 activation and PARP cleavage. AgNPs with dose-dependent manner significantly increased the apoptotic cell population (sub-G1). Furthermore, AgNP-induced apoptosis was found dependent on the overproduction of reactive oxygen species (ROS) and affecting of MAPKs and AKT signaling and DNA damage-mediated p53 phosphorylation to advance HePG-2 cells apoptosis. Therefore, our results show that the mechanism of ROS-mediated signaling pathways may provide useful information in AgNP-induced HePG-2 cell apoptosis.

  4. 2'-Hydroxycinnamaldehyde induces apoptosis through HSF1-mediated BAG3 expression.

    PubMed

    Nguyen, Hai-Anh; Kim, Soo-A

    2017-01-01

    BAG3, a member of BAG co-chaperone family, is induced by stressful stimuli such as heat shock and heavy metals. Through interaction with various binding partners, BAG3 is thought to play a role in cellular adaptive responses against stressful conditions in normal and neoplastic cells. 2'-Hydroxycinnamaldehyde (HCA) is a natural derivative of cinnamaldehyde and has antitumor activity in various cancer cells. In the present study, for the first time, we identified that HCA induced BAG3 expression and BAG3-mediated apoptosis in cancer cells. The apoptotic cell death induced by HCA was demonstrated by caspase-7, -9 and PARP activation, and confirmed by Annexin V staining in both SW480 and SW620 colon cancer cells. Notably, both the mRNA and protein levels of BAG3 were largely induced by HCA in a dose- and time-dependent manner. By showing transcription factor HSF1 activation, we demonstrated that HCA induces the expression of BAG3 through HSF1 activation. More importantly, knockdown of BAG3 expression using siRNA largely inhibited HCA-induced apoptosis, suggesting that BAG3 is actively involved in HCA-induced cancer cell death. Considering the importance of the stress response mechanism in cancer progression, our results strongly suggest that BAG3 could be a potential target for anticancer therapy.

  5. Robust dynamic 3-D measurements with motion-compensated phase-shifting profilometry

    NASA Astrophysics Data System (ADS)

    Feng, Shijie; Zuo, Chao; Tao, Tianyang; Hu, Yan; Zhang, Minliang; Chen, Qian; Gu, Guohua

    2018-04-01

    Phase-shifting profilometry (PSP) is a widely used approach to high-accuracy three-dimensional shape measurements. However, when it comes to moving objects, phase errors induced by the movement often result in severe artifacts even though a high-speed camera is in use. From our observations, there are three kinds of motion artifacts: motion ripples, motion-induced phase unwrapping errors, and motion outliers. We present a novel motion-compensated PSP to remove the artifacts for dynamic measurements of rigid objects. The phase error of motion ripples is analyzed for the N-step phase-shifting algorithm and is compensated using the statistical nature of the fringes. The phase unwrapping errors are corrected exploiting adjacent reliable pixels, and the outliers are removed by comparing the original phase map with a smoothed phase map. Compared with the three-step PSP, our method can improve the accuracy by more than 95% for objects in motion.

  6. Nitric oxide mediates angiogenesis induced in vivo by platelet-activating factor and tumor necrosis factor-alpha.

    PubMed Central

    Montrucchio, G.; Lupia, E.; de Martino, A.; Battaglia, E.; Arese, M.; Tizzani, A.; Bussolino, F.; Camussi, G.

    1997-01-01

    We evaluated the role of an endogenous production of nitric oxide (NO) in the in vitro migration of endothelial cells and in the in vivo angiogenic response elicited by platelet-activating factor (PAF), tumor necrosis factor-alpha (TNF), and basic fibroblast growth factor (bFGF). The NO synthase inhibitor, N omega-nitro-L-arginine-methyl ester (L-NAME), but not its enantiomer D-NAME, prevented chemotaxis of endothelial cells induced in vitro by PAF and by TNF. The motogenic activity of TNF was also inhibited by WEB 2170, a specific PAF-receptor antagonist. In contrast, chemotaxis induced by bFGF was not prevented by L-NAME or by WEB 2170. Angiogenesis was studied in vivo in a murine model in which Matrigel was used as a vehicle for the delivery of mediators. In this model, the angiogenesis induced by PAF and TNF was inhibited by WEB 2170 and L-NAME but not by D-NAME. In contrast, angiogenesis induced by bFGF was not affected by L-NAME or by WEB 2170. TNF, but not bFGF, induced PAF synthesis within Matrigel. These results suggest that NO mediates the angiogenesis induced by PAF as well as that induced by TNF, which is dependent on the production of PAF. In contrast, the angiogenic effect of bFGF appears to be both PAF and NO independent. Images Figure 3 Figure 4 PMID:9250168

  7. Stimulation of serotonin-1A receptors in mammals to alleviate motion sickness and emesis induced by chemical agents

    NASA Technical Reports Server (NTRS)

    Lucot, James B. (Inventor); Crampton, George H. (Inventor)

    1990-01-01

    A method for the alleviation of both motion sickness and chemically-induced emesis is provided which includes the administration of a nontoxic, therapeutically effective amount of a composition which stimulates serotonin-1A receptors in a mammal in need of such treatment. The preferred compounds for use are buspirone and 8-hydroxy-2(di-n-propylamino)-tetralin (8-OH-DPAT).

  8. Mast cell mediators in citric acid-induced airway constriction of guinea pigs

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

    Lin, C.-H.; Lai, Y.-L.

    2005-08-15

    We demonstrated previously that mast cells play an important role in citric acid (CA)-induced airway constriction. In this study, we further investigated the underlying mediator(s) for this type of airway constriction. At first, to examine effects caused by blocking agents, 67 young Hartley guinea pigs were divided into 7 groups: saline + CA; methysergide (serotonin receptor antagonist) + CA; MK-886 (leukotriene synthesis inhibitor) + CA; mepyramine (histamine H{sub 1} receptor antagonist) + CA; indomethacin (cyclooxygenase inhibitor) + CA; cromolyn sodium (mast cell stabilizer) + CA; and compound 48/80 (mast cell degranulating agent) + CA. Then, we tested whether leukotriene C{submore » 4} (LTC{sub 4}) or histamine enhances CA-induced airway constriction in compound 48/80-pretreated guinea pigs. We measured dynamic respiratory compliance (Crs) and forced expiratory volume in 0.1 s (FEV{sub 0.1}) during either baseline or recovery period. In addition, we detected histamine level, an index of pulmonary mast cell degranulation, in bronchoalveolar lavage (BAL) samples. Citric acid aerosol inhalation caused decreases in Crs and FEV{sub 0.1}, indicating airway constriction in the control group. This airway constriction was significantly attenuated by MK-886, mepyramine, cromolyn sodium, and compound 48/80, but not by either methysergide or indomethacin. Both LTC{sub 4} and histamine infusion significantly increased the magnitude of CA-induced airway constriction in compound 48/80-pretreated guinea pigs. Citric acid inhalation caused significant increase in histamine level in the BAL sample, which was significantly suppressed by compound 48/80. These results suggest that leukotrienes and histamine originating from mast cells play an important role in CA inhalation-induced noncholinergic airway constriction.« less

  9. Hypothalamic CaMKKβ mediates glucagon anorectic effect and its diet-induced resistance

    PubMed Central

    Quiñones, Mar; Al-Massadi, Omar; Gallego, Rosalía; Fernø, Johan; Diéguez, Carlos; López, Miguel; Nogueiras, Ruben

    2015-01-01

    Objective Glucagon receptor antagonists and humanized glucagon antibodies are currently studied as promising therapies for obesity and type II diabetes. Among its variety of actions, glucagon reduces food intake, but the molecular mechanisms mediating this effect as well as glucagon resistance are totally unknown. Methods Glucagon and adenoviral vectors were administered in specific hypothalamic nuclei of lean and diet-induced obese rats. The expression of neuropeptides controlling food intake was performed by in situ hybridization. The regulation of factors of the glucagon signaling pathway was assessed by western blot. Results The central injection of glucagon decreased feeding through a hypothalamic pathway involving protein kinase A (PKA)/Ca2+-calmodulin-dependent protein kinase kinase β (CaMKKβ)/AMP-activated protein kinase (AMPK)-dependent mechanism. More specifically, the central injection of glucagon increases PKA activity and reduces protein levels of CaMKKβ and its downstream target phosphorylated AMPK in the hypothalamic arcuate nucleus (ARC). Consistently, central glucagon significantly decreased AgRP expression. Inhibition of PKA and genetic activation of AMPK in the ARC blocked glucagon-induced anorexia in lean rats. Genetic down-regulation of glucagon receptors in the ARC stimulates fasting-induced hyperphagia. Although glucagon was unable to decrease food intake in DIO rats, glucagon sensitivity was restored after inactivation of CaMKKβ, specifically in the ARC. Thus, glucagon decreases food intake acutely via PKA/CaMKKβ/AMPK dependent pathways in the ARC, and CaMKKβ mediates its obesity-induced hypothalamic resistance. Conclusions This work reveals the molecular underpinnings by which glucagon controls feeding that may lead to a better understanding of disease states linked to anorexia and cachexia. PMID:26909312

  10. Rolling motion of an elastic cylinder induced by elastic strain gradients

    NASA Astrophysics Data System (ADS)

    Chen, Lei; Chen, Shaohua

    2014-10-01

    Recent experiment shows that an elastic strain gradient field can be utilized to transport spherical particles on a stretchable substrate by rolling, inspired by which a generalized plane-strain Johnson-Kendall-Roberts model is developed in this paper in order to verify possible rolling of an elastic cylinder adhering on an elastic substrate subject to a strain gradient. With the help of contact mechanics, closed form solutions of interface tractions, stress intensity factors, and corresponding energy release rates in the plane-strain contact model are obtained, based on which a possible rolling motion of an elastic cylinder induced by strain gradients is found and the criterion for the initiation of rolling is established. The theoretical prediction is consistent well with the existing experimental observation. The result should be helpful for understanding biological transport mechanisms through muscle contractions and the design of transport systems with strain gradient.

  11. Aag DNA Glycosylase Promotes Alkylation-Induced Tissue Damage Mediated by Parp1

    PubMed Central

    Calvo, Jennifer A.; Moroski-Erkul, Catherine A.; Lake, Annabelle; Eichinger, Lindsey W.; Shah, Dharini; Jhun, Iny; Limsirichai, Prajit; Bronson, Roderick T.; Christiani, David C.; Meira, Lisiane B.; Samson, Leona D.

    2013-01-01

    Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER) is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG) mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag −/− mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage. PMID:23593019

  12. Activation of mitochondria-mediated apoptotic pathway in tri-ortho-cresyl phosphate-induced delayed neuropathy.

    PubMed

    Zou, Chaoshuang; Kou, Ruirui; Gao, Yuan; Xie, Keqin; Song, Fuyong

    2013-06-01

    Previous studies suggest that abnormal neurons death has been implicated in organophosphate-induced delayed neuropathy (OPIDN). However, the precise mechanism of neuronal death in OPIDN remains largely unknown. In this study, adult hens were treated with a dosage of 750 mg/kg tri-ortho-cresyl phosphate (TOCP) by gavage, and then sacrificed on the time-points of 1, 5, 10, and 21 days after dosing TOCP, respectively. The apoptotic change of spinal cord neurons induced by TOCP was examined, and the role of mitochondria-mediated apoptosis of neurons during OPIDN was investigated. TUNEL assays showed that apoptotic neurons in hen spinal cords began to appear on day 5 following TOCP exposure. Immunohistochemistry and western blot analysis revealed a translocation of cytochrome C from mitochondria to cytoplasm after dosing TOCP. Moreover, the level of Bcl-2, Bcl-xl, Pro-caspase3 and Pro-caspase9 in hen spinal cord was significantly decreased, whereas that of Bax and cleaved-PARP was significantly elevated. Taken together, these findings indicate that the administration of TOCP can induce neuron apoptosis in hen spinal cords, which might be mediated by the activation of mitochondrial apoptotic pathway. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. DNA–PKcs–SIN1 complexation mediates low-dose X-ray irradiation (LDI)-induced Akt activation and osteoblast differentiation

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

    Xu, Yong; Fang, Shi-ji; Zhu, Li-juan

    Highlights: • LDI increases ALP activity, promotes type I collagen (Col I)/Runx2 mRNA expression. • LDI induces DNA–PKcs activation, which is required for osteoblast differentiation. • Akt activation mediates LDI-induced ALP activity and Col I/Runx2 mRNA increase. • DNA–PKcs–SIN1 complexation mediates LDI-induced Akt Ser-473 phosphorylation. • DNA–PKcs–SIN1 complexation is important for osteoblast differentiation. - Abstract: Low-dose irradiation (LDI) induces osteoblast differentiation, however the underlying mechanisms are not fully understood. In this study, we explored the potential role of DNA-dependent protein kinase catalytic subunit (DNA–PKcs)–Akt signaling in LDI-induced osteoblast differentiation. We confirmed that LDI promoted mouse calvarial osteoblast differentiation, which wasmore » detected by increased alkaline phosphatase (ALP) activity as well as mRNA expression of type I collagen (Col I) and runt-related transcription factor 2 (Runx2). In mouse osteoblasts, LDI (1 Gy) induced phosphorylation of DNA–PKcs and Akt (mainly at Ser-473). The kinase inhibitors against DNA–PKcs (NU-7026 and NU-7441) or Akt (LY294002, perifosine and MK-2206), as well as partial depletion of DNA–PKcs or Akt1 by targeted-shRNA, dramatically inhibited LDI-induced Akt activation and mouse osteoblast differentiation. Further, siRNA-knockdown of SIN1, a key component of mTOR complex 2 (mTORC2), also inhibited LDI-induced Akt Ser-473 phosphorylation as well as ALP activity increase and Col I/Runx2 expression in mouse osteoblasts. Co-immunoprecipitation (Co-IP) assay results demonstrated that LDI-induced DNA–PKcs–SIN1 complexation, which was inhibited by NU-7441 or SIN1 siRNA-knockdown in mouse osteoblasts. In summary, our data suggest that DNA–PKcs–SIN1 complexation-mediated Akt activation (Ser-473 phosphorylation) is required for mouse osteoblast differentiation.« less

  14. Stress-induced decrease of uterine blood flow in sheep is mediated by alpha 1-adrenergic receptors.

    PubMed

    Dreiling, Michelle; Bischoff, Sabine; Schiffner, Rene; Rupprecht, Sven; Kiehntopf, Michael; Schubert, Harald; Witte, Otto W; Nathanielsz, Peter W; Schwab, Matthias; Rakers, Florian

    2016-09-01

    Prenatal maternal stress can be transferred to the fetus via a catecholamine-dependent decrease of uterine blood flow (UBF). However, it is unclear which group of adrenergic receptors mediates this mechanism of maternal-fetal stress transfer. We hypothesized that in sheep, alpha 1-adrenergic receptors may play a key role in catecholamine mediated UBF decrease, as these receptors are mainly involved in peripheral vasoconstriction and are present in significant number in the uterine vasculature. After chronic instrumentation at 125 ± 1 days of gestation (dGA; term 150 dGA), nine pregnant sheep were exposed at 130 ± 1 dGA to acute isolation stress for one hour without visual, tactile, or auditory contact with their flockmates. UBF, blood pressure (BP), heart rate (HR), stress hormones, and blood gases were determined before and during this isolation challenge. Twenty-four hours later, experiments were repeated during alpha 1-adrenergic receptor blockage induced by a continuous intravenous infusion of urapidil. In both experiments, ewes reacted to isolation with an increase in serum norepinephrine, cortisol, BP, and HR as typical signs of activation of sympatho-adrenal and the hypothalamic-pituitary-adrenal axis. Stress-induced UBF decrease was prevented by alpha 1-adrenergic receptor blockage. We conclude that UBF decrease induced by maternal stress in sheep is mediated by alpha 1-adrenergic receptors. Future studies investigating prevention strategies of impact of prenatal maternal stress on fetal health should consider selective blockage of alpha 1-receptors to interrupt maternal-fetal stress transfer mediated by utero-placental malperfusion.

  15. Lack of TXNIP protects against mitochondria-mediated apoptosis but not against fatty acid-induced ER stress-mediated beta-cell death.

    PubMed

    Chen, Junqin; Fontes, Ghislaine; Saxena, Geetu; Poitout, Vincent; Shalev, Anath

    2010-02-01

    We have previously shown that lack of thioredoxin-interacting protein (TXNIP) protects against diabetes and glucotoxicity-induced beta-cell apoptosis. Because the role of TXNIP in lipotoxicity is unknown, the goal of the present study was to determine whether TXNIP expression is regulated by fatty acids and whether TXNIP deficiency also protects beta-cells against lipoapoptosis. RESARCH DESIGN AND METHODS: To determine the effects of fatty acids on beta-cell TXNIP expression, INS-1 cells and isolated islets were incubated with/without palmitate and rats underwent cyclic infusions of glucose and/or Intralipid prior to islet isolation and analysis by quantitative real-time RT-PCR and immunoblotting. Using primary wild-type and TXNIP-deficient islets, we then assessed the effects of palmitate on apoptosis (transferase-mediated dUTP nick-end labeling [TUNEL]), mitochondrial death pathway (cytochrome c release), and endoplasmic reticulum (ER) stress (binding protein [BiP], C/EBP homologous protein [CHOP]). Effects of TXNIP deficiency were also tested in the context of staurosporine (mitochondrial damage) or thapsigargin (ER stress). Glucose elicited a dramatic increase in islet TXNIP expression both in vitro and in vivo, whereas fatty acids had no such effect and, when combined with glucose, even abolished the glucose effect. We also found that TXNIP deficiency does not effectively protect against palmitate or thapsigargin-induced beta-cell apoptosis, but specifically prevents staurosporine- or glucose-induced toxicity. Our results demonstrate that unlike glucose, fatty acids do not induce beta-cell expression of proapoptotic TXNIP. They further reveal that TXNIP deficiency specifically inhibits the mitochondrial death pathway underlying beta-cell glucotoxicity, whereas it has very few protective effects against ER stress-mediated lipoapoptosis.

  16. Gefitinib enhances human colon cancer cells to TRAIL-induced apoptosis of via autophagy- and JNK-mediated death receptors upregulation.

    PubMed

    Chen, Lei; Meng, Yue; Guo, Xiaoqing; Sheng, Xiaotong; Tai, Guihua; Zhang, Fenglei; Cheng, Hairong; Zhou, Yifa

    2016-11-01

    Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a potent cancer cell-specific apoptosis-inducing cytokine with little toxicity to most normal cells. Here, we report that gefitinib and TRAIL in combination produce a potent synergistic effect on TRAIL-sensitive human colon cancer HCT116 cells and an additive effect on TRAIL-resistant HT-29 cells. Interestingly, gefitinib increases the expression of cell surface receptors DR4 and DR5, possibly explaining the synergistic effect. Knockdown of DR4 and DR5 by siRNA significantly decreases gefitinib- and TRAIL-mediated cell apoptosis, supporting this idea. Because the inhibition of gefitinib-induced autophagy by 3-MA significantly decreases DR4 and DR5 upregulation, as well as reduces gefitinib- and TRAIL-induced apoptosis, we conclude that death receptor upregulation is autophagy mediated. Furthermore, our results indicate that death receptor expression may also be regulated by JNK activation, because pre-treatment of cells with JNK inhibitor SP600125 significantly decreases gefitinib-induced death receptor upregulation. Interestingly, SP600125 also inhibits the expression CHOP, yet CHOP has no impact on death receptor expressions. We also find here that phosphorylation of Akt and ERK might also be required for TRAIL sensitization. In summary, our results indicate that gefitinib effectively enhances TRAIL-induced apoptosis, likely via autophagy and JNK- mediated death receptor expression and phosphorylation of Akt and ERK.

  17. Improved pertussis vaccines based on adjuvants that induce cell-mediated immunity.

    PubMed

    Allen, Aideen C; Mills, Kingston H G

    2014-10-01

    Bordetella pertussis is a Gram-negative bacterium that causes the severe and sometimes lethal respiratory disease whooping cough in infants and children. There has been a recent resurgence in the number of cases of pertussis in several countries with high vaccine coverage. This has been linked with waning or ineffective immunity induced by current acellular pertussis vaccines. These acellular pertussis vaccines are formulated with alum as the adjuvant, which promotes strong antibody responses but is less effective at inducing Th1-type responses crucial for effective bacterial clearance. Studies in animal models have demonstrated that replacing alum with alternative adjuvants, such as toll-like receptor agonists, can promote more robust cell-mediated immunity and confer a high level of protection against infection following respiratory challenge.

  18. The implication of non-cyclic intrafractional longitudinal motion in SBRT by TomoTherapy

    NASA Astrophysics Data System (ADS)

    Yang, Wensha; Van Ausdal, Ray; Read, Paul; Larner, James; Benedict, Stan; Sheng, Ke

    2009-05-01

    To determine the dosimetric impact of non-cyclic longitudinal intrafractional motion, TomoTherapy plans with different field sizes were interrupted during a phantom delivery, and a displacement between -5 mm and 5 mm was induced prior to the delivery of the completion procedure. The planar dose was measured by film and a cylindrical phantom, and under-dosed or over-dosed volume was observed for either positive or negative displacement. For a 2.5 cm field, there was a 4% deviation for every mm of motion and for a 1 cm field, the deviation was 8% per mm. The dimension of the under/over-dosed area was independent of the motion but dependent on the field size. The results have significant implication in small-field high-dose treatments (i.e. stereotactic body radiation therapy (SBRT)) that deliver doses in only a few fractions. Our studies demonstrate that a small longitudinal motion may cause a dose error that is difficult to compensate; however, dividing a SBRT fraction into smaller passes is helpful to reduce such adverse effects.

  19. CRH engagement of the locus coeruleus noradrenergic system mediates stress-induced anxiety

    PubMed Central

    McCall, Jordan G.; Al-Hasani, Ream; Siuda, Edward R.; Hong, Daniel Y.; Norris, Aaron J.; Ford, Christopher P.; Bruchas, Michael R.

    2015-01-01

    Summary The locus coeruleus noradrenergic (LC-NE) system is one of the first systems engaged following a stressful event. While numerous groups have demonstrated that LC-NE neurons are activated by many different stressors, the underlying neural circuitry and the role of this activity in generating stress-induced anxiety has not been elucidated. Using a combination of in vivo chemogenetics, optogenetics, and retrograde tracing we determine that increased tonic activity of the LC-NE system is necessary and sufficient for stress-induced anxiety and aversion. Selective inhibition of LC-NE neurons during stress prevents subsequent anxiety-like behavior. Exogenously increasing tonic, but not phasic, activity of LC-NE neurons is alone sufficient for anxiety-like and aversive behavior. Furthermore, endogenous corticotropin releasing hormone+ (CRH+) LC inputs from the amygdala increase tonic LC activity, inducing anxiety-like behaviors. These studies position the LC-NE system as a critical mediator of acute stress-induced anxiety and offer a potential intervention for preventing stress-related affective disorders. PMID:26212712

  20. Artemisinin induces ROS-mediated caspase3 activation in ASTC-a-1 cells

    NASA Astrophysics Data System (ADS)

    Xiao, Feng-Lian; Chen, Tong-Sheng; Qu, Jun-Le; Liu, Cheng-Yi

    2010-02-01

    Artemisinin (ART), an antimalarial phytochemical from the sweet wormwood plant or a naturally occurring component of Artemisia annua, has been shown a potential anticancer activity by apoptotic pathways. In our report, cell counting kit (CCK-8) assay showed that treatment of human lung adenocarcinoma (ASTC-a-1) cells with ART effectively increase cell death by inducing apoptosis in a time- and dose-dependent fashion. Hoechst 33258 staining was used to detect apoptosis as well. Reactive oxygen species (ROS) generation was observed in cells exposed to ART at concentrations of 400 μM for 48 h. N-acetyl-L-cysteine (NAC), an oxygen radical scavenger, suppressed the rate of ROS generation and inhibited the ART-induced apoptosis. Moreover, AFC assay (Fluorometric assay for Caspase3 activity) showed that ROS was involved in ART-induced caspase3 acitvation. Taken together, our data indicate that ART induces ROS-mediated caspase3 activation in a time-and dose-dependent way in ASCT-a-1 cells.

  1. Toll-like receptor 4 mediates lipopolysaccharide-induced muscle catabolism via coordinate activation of ubiquitin-proteasome and autophagy-lysosome pathways

    PubMed Central

    Doyle, Alexander; Zhang, Guohua; Abdel Fattah, Elmoataz A.; Eissa, N. Tony; Li, Yi-Ping

    2011-01-01

    Cachectic muscle wasting is a frequent complication of many inflammatory conditions, due primarily to excessive muscle catabolism. However, the pathogenesis and intervention strategies against it remain to be established. Here, we tested the hypothesis that Toll-like receptor 4 (TLR4) is a master regulator of inflammatory muscle catabolism. We demonstrate that TLR4 activation by lipopolysaccharide (LPS) induces C2C12 myotube atrophy via up-regulating autophagosome formation and the expression of ubiquitin ligase atrogin-1/MAFbx and MuRF1. TLR4-mediated activation of p38 MAPK is necessary and sufficient for the up-regulation of atrogin1/MAFbx and autophagosomes, resulting in myotube atrophy. Similarly, LPS up-regulates muscle autophagosome formation and ubiquitin ligase expression in mice. Importantly, autophagy inhibitor 3-methyladenine completely abolishes LPS-induced muscle proteolysis, while proteasome inhibitor lactacystin partially blocks it. Furthermore, TLR4 knockout or p38 MAPK inhibition abolishes LPS-induced muscle proteolysis. Thus, TLR4 mediates LPS-induced muscle catabolism via coordinate activation of the ubiquitin-proteasome and the autophagy-lysosomal pathways.—Doyle, A., Zhang, G., Abdel Fattah, E. A., Eissa, N. T., Li, Y.-P. Toll-like receptor 4 mediates lipopolysaccharide-induced muscle catabolism via coordinate activation of ubiquitin-proteasome and autophagy-lysosome pathways. PMID:20826541

  2. Maresin 1, a Proresolving Lipid Mediator, Mitigates Carbon Tetrachloride-Induced Liver Injury in Mice

    PubMed Central

    Li, Ruidong; Wang, Yaxin; Zhao, Ende; Wu, Ke; Li, Wei; Shi, Liang; Wang, Di; Xie, Gengchen; Yin, Yuping; Deng, Meizhou; Zhang, Peng; Tao, Kaixiong

    2016-01-01

    Maresin 1 (MaR 1) was recently reported to have protective properties in several different animal models of acute inflammation by inhibiting inflammatory response. However, its function in acute liver injury is still unknown. To address this question, we induced liver injury in BALB/c mice with intraperitoneal injection of carbon tetrachloride with or without treatment of MaR 1. Our data showed that MaR 1 attenuated hepatic injury, oxidative stress, and lipid peroxidation induced by carbon tetrachloride, as evidenced by increased thiobarbituric acid reactive substances and reactive oxygen species levels were inhibited by treatment of MaR 1. Furthermore, MaR 1 increased activities of antioxidative mediators in carbon tetrachloride-treated mice liver. MaR 1 decreased indices of inflammatory mediators such as tumor necrosis factor-α, interleukin-6, interleukin-1β, monocyte chemotactic protein 1, myeloperoxidase, cyclooxygenase-2, and inducible nitric oxide synthase. Administration of MaR 1 inhibited activation of nuclear factor kappa B (NF-κb) and mitogen-activated protein kinases (MAPKs) in the liver of CCl4 treated mice. In conclusion, these results suggested the antioxidative, anti-inflammatory properties of MaR 1 in CCl4 induced liver injury. The possible mechanism is partly implicated in its abilities to inhibit ROS generation and activation of NF-κb and MAPK pathway. PMID:26881046

  3. Comparsion of light dose on topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions

    NASA Astrophysics Data System (ADS)

    Yang, Deng-Fu; Tseng, Meng-Ke; Liu, Chung-Ji; Hsu, Yih-Chih

    2012-03-01

    Oral cancer has becomes the most prominent male cancer disease due to the local betel nut chewing habit combing with smoking and alcohol-drinking lifestyle. In order to minimize the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch cancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 8 to 10 weeks. Precancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA -mediated PDT. We found that ALA reached its peak level in cancerous lesions about 2.5 hrs after topical application of ALA gel. The precancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 75 and 100 J/cm2 using LED 635 nm Wonderlight device. It is suggesting that optimization of the given light dose is critical to the success of PDT results.

  4. Greenland ice sheet motion insensitive to exceptional meltwater forcing.

    PubMed

    Tedstone, Andrew J; Nienow, Peter W; Sole, Andrew J; Mair, Douglas W F; Cowton, Thomas R; Bartholomew, Ian D; King, Matt A

    2013-12-03

    Changes to the dynamics of the Greenland ice sheet can be forced by various mechanisms including surface-melt-induced ice acceleration and oceanic forcing of marine-terminating glaciers. We use observations of ice motion to examine the surface melt-induced dynamic response of a land-terminating outlet glacier in southwest Greenland to the exceptional melting observed in 2012. During summer, meltwater generated on the Greenland ice sheet surface accesses the ice sheet bed, lubricating basal motion and resulting in periods of faster ice flow. However, the net impact of varying meltwater volumes upon seasonal and annual ice flow, and thus sea level rise, remains unclear. We show that two extreme melt events (98.6% of the Greenland ice sheet surface experienced melting on July 12, the most significant melt event since 1889, and 79.2% on July 29) and summer ice sheet runoff ~3.9 σ above the 1958-2011 mean resulted in enhanced summer ice motion relative to the average melt year of 2009. However, despite record summer melting, subsequent reduced winter ice motion resulted in 6% less net annual ice motion in 2012 than in 2009. Our findings suggest that surface melt-induced acceleration of land-terminating regions of the ice sheet will remain insignificant even under extreme melting scenarios.

  5. Reinforcement of integrin-mediated T-Lymphocyte adhesion by TNF-induced Inside-out Signaling

    NASA Astrophysics Data System (ADS)

    Li, Qian; Huth, Steven; Adam, Dieter; Selhuber-Unkel, Christine

    2016-07-01

    Integrin-mediated leukocyte adhesion to endothelial cells is a crucial step in immunity against pathogens. Whereas the outside-in signaling pathway in response to the pro-inflammatory cytokine tumour necrosis factor (TNF) has already been studied in detail, little knowledge exists about a supposed TNF-mediated inside-out signaling pathway. In contrast to the outside-in signaling pathway, which relies on the TNF-induced upregulation of surface molecules on endothelium, inside-out signaling should also be present in an endothelium-free environment. Using single-cell force spectroscopy, we show here that stimulating Jurkat cells with TNF significantly reinforces their adhesion to fibronectin in a biomimetic in vitro assay for cell-surface contact times of about 1.5 seconds, whereas for larger contact times the effect disappears. Analysis of single-molecule ruptures further demonstrates that TNF strengthens sub-cellular single rupture events at short cell-surface contact times. Hence, our results provide quantitative evidence for the significant impact of TNF-induced inside-out signaling in the T-lymphocyte initial adhesion machinery.

  6. Topological dynamics and current-induced motion in a skyrmion lattice

    NASA Astrophysics Data System (ADS)

    Martinez, J. C.; Jalil, M. B. A.

    2016-03-01

    We study the Thiele equation for current-induced motion in a skyrmion lattice through two soluble models of the pinning potential. Comprised by a Magnus term, a dissipative term and a pinning force, Thiele’s equation resembles Newton’s law but in virtue of the topological character to the first, it differs significantly from Newtonian mechanics and because the Magnus force is dominant, unlike its mechanical counterpart—the Coriolis force—skyrmion trajectories do not necessarily have mechanical counterparts. This is important if we are to understand skyrmion dynamics and tap into its potential for data-storage technology. We identify a pinning threshold velocity for the one-dimensional pinning potential and for a two-dimensional attractive potential we find a pinning point and the skyrmion trajectories toward that point are spirals whose frequency (compare Kepler’s second law) and amplitude-decay depend only on the Gilbert constant and potential at the pinning point. Other scenarios, e.g. other choices of initial spin velocity, a repulsive potential, etc are also investigated.

  7. Boundary Avoidance Tracking for Instigating Pilot Induced Oscillations

    NASA Technical Reports Server (NTRS)

    Craun, Robert W.; Acosta, Diana M.; Beard, Steven D.; Hardy, Gordon H.; Leonard, Michael W.; Weinstein, Michael

    2013-01-01

    In order to advance research in the area of pilot induced oscillations, a reliable method to create PIOs in a simulated environment is necessary. Using a boundary avoidance tracking task, researchers performing an evaluation of control systems were able to create PIO events in 42% of cases using a nominal aircraft, and 91% of cases using an aircraft with reduced actuator rate limits. The simulator evaluation took place in the NASA Ames Vertical Motion Simulator, a high-fidelity motion-based simulation facility.

  8. Drug-Induced Alterations of Endocannabinoid-Mediated Plasticity in Brain Reward Regions.

    PubMed

    Zlebnik, Natalie E; Cheer, Joseph F

    2016-10-05

    The endocannabinoid (eCB) system has emerged as one of the most important mediators of physiological and pathological reward-related synaptic plasticity. eCBs are retrograde messengers that provide feedback inhibition, resulting in the suppression of neurotransmitter release at both excitatory and inhibitory synapses, and they serve a critical role in the spatiotemporal regulation of both short- and long-term synaptic plasticity that supports adaptive learning of reward-motivated behaviors. However, mechanisms of eCB-mediated synaptic plasticity in reward areas of the brain are impaired following exposure to drugs of abuse. Because of this, it is theorized that maladaptive eCB signaling may contribute to the development and maintenance of addiction-related behavior. Here we review various forms of eCB-mediated synaptic plasticity present in regions of the brain involved in reward and reinforcement and explore the potential physiological relevance of maladaptive eCB signaling to addiction vulnerability. Copyright © 2016 the authors 0270-6474/16/3610230-09$15.00/0.

  9. Normalization of flow-mediated dilation to shear stress area under the curve eliminates the impact of variable hyperemic stimulus.

    PubMed

    Padilla, Jaume; Johnson, Blair D; Newcomer, Sean C; Wilhite, Daniel P; Mickleborough, Timothy D; Fly, Alyce D; Mather, Kieren J; Wallace, Janet P

    2008-09-04

    Normalization of brachial artery flow-mediated dilation (FMD) to individual shear stress area under the curve (peak FMD:SSAUC ratio) has recently been proposed as an approach to control for the large inter-subject variability in reactive hyperemia-induced shear stress; however, the adoption of this approach among researchers has been slow. The present study was designed to further examine the efficacy of FMD normalization to shear stress in reducing measurement variability. Five different magnitudes of reactive hyperemia-induced shear stress were applied to 20 healthy, physically active young adults (25.3 +/- 0. 6 yrs; 10 men, 10 women) by manipulating forearm cuff occlusion duration: 1, 2, 3, 4, and 5 min, in a randomized order. A venous blood draw was performed for determination of baseline whole blood viscosity and hematocrit. The magnitude of occlusion-induced forearm ischemia was quantified by dual-wavelength near-infrared spectrometry (NIRS). Brachial artery diameters and velocities were obtained via high-resolution ultrasound. The SSAUC was individually calculated for the duration of time-to-peak dilation. One-way repeated measures ANOVA demonstrated distinct magnitudes of occlusion-induced ischemia (volume and peak), hyperemic shear stress, and peak FMD responses (all p < 0.0001) across forearm occlusion durations. Differences in peak FMD were abolished when normalizing FMD to SSAUC (p = 0.785). Our data confirm that normalization of FMD to SSAUC eliminates the influences of variable shear stress and solidifies the utility of FMD:SSAUC ratio as an index of endothelial function.

  10. Block Tectonic Motion on Venus

    NASA Astrophysics Data System (ADS)

    Byrne, P. K.; Ghail, R.; Sengor, A. M. C.; Klimczak, C.; Solomon, S. C.

    2017-12-01

    Despite close similarities in mass and bulk composition to Earth, Venus apparently shows no evidence for Earth-like plate tectonics, except perhaps for limited plume-induced subduction. We use Magellan radar data to survey numerous examples of low-lying areas infilled with plains lavas and delimited by networks of narrow belts of substantial tectonic deformation; such sites include those at Lavinia and Llorona Planitiæ and to the north of Helen Planitia. This deformation is locally extensional or shortening in style but very often also includes structures that denote substantial lateral motion. Cross-cutting relations suggest that this motion occurred both before and after the lavas were emplaced. Together, these observations imply that many of the belt-bounded areas have acted as relatively rigid blocks that experienced considerable horizontal movement relative to each other, in a manner similar to blocks that constitute parts of the Terran continental lithosphere. On Earth, continental deformation is enabled by the low strength of the lower crust and/or upper mantle. On Venus, the shallow brittle-ductile transition (BDT), a result of the planet's elevated surface temperature, likely acts in a similar way to decouple the upper and lower crust. Subcrustal lid rejuvenation, a recently proposed mechanism for renewal of the mantle portion of Venus' stagnant lithospheric lid through thinning and recycling, could drive the horizontal movement of these rigid blocks. It may be, then, that the blocks move as continental blocks do on Earth, with mantle motion transferred to the surface and manifest as narrow zones of tectonic deformation akin to, for example, the Tian Shan and Altin Tagh ranges that bound the Tarim Basin in northwestern China. The shallow BDT on Venus precludes the blocks from subducting, and so their fate is to shorten, lengthen, or retain their geometry at the expense of adjacent blocks. We suggest that this behavior is analogous to plate

  11. Topical chlorophyll-pheophytin derivative-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premaligant lesions: an in vivo study

    NASA Astrophysics Data System (ADS)

    Hsu, Yih-Chih; Chiang, Chung-Pin; Chen, Jian Wen; Lee, Jeng-Woei; How, Mon-Hsin

    2010-02-01

    In Taiwan, oral cancer has become a prominent cancer because of its highest annual increase rate among all cancer diseases. Betel quid chewing habit is a major risk factor for oral precancerous and cancerous lesions and there are more than two million people who have this habit in Taiwan. Our previous studies showed that chlorophyll-pheophytin derivative (CPD)-mediated PDT is very effective for killing of SCC-4 cell lines in vitro. In order to decrease the systemic phototoxic effect of CPD, this study was designed to use a topical CPD-mediated PDT for treatment of DMBA-induced hamster buccal pouch precancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 8 to 10 weeks. Precancerous lesions of moderate to severe dysplasia were induced and proven by histological examination. These induced precancerous lesions were used for testing the efficacy of topical CPD-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when CPD reached its peak level in the lesional epithelial cells after topical application of CPD gel. We found that CPD reached its peak level in precancerous lesions about 1 hour (range, 0 to 30 hours) after topical application of CPD gel. The precancerous lesions in hamsters were then treated with topical CPD-mediated PDT (fluence rate: 200 mW/cm2; light exposure dose 100 J/cm2) using the portable WonderLight LED 635 nm fiber-guided light device once or twice a week. Visual and histological examination demonstrated that topical CPD-mediated PDT was partially effective treatment modality for DMBA-induced hamster buccal pouch precancerous lesions.

  12. Spatial task performance, sex differences, and motion sickness susceptibility.

    PubMed

    Levine, Max E; Stern, Robert M

    2002-10-01

    There are substantial individual differences in susceptibility to motion sickness, yet little is known about what mediates these differences. Spatial ability and sex have been suggested as possible factors in this relationship. 89 participants (57 women) were administered a Motion Sickness Questionnaire that assesses motion sickness susceptibility, a Water-level Task that gauges sensitivity to gravitational upright, and a Mental Rotation Task that tests an individual's awareness of how objects typically move in space. Significant sex differences were observed in performance of both the Water-level Task (p<.01), and the Mental Rotation Task (p<.005), with women performing less accurately than men. Women also had significantly higher scores on the Motion Sickness Questionnaire (p<.005). Among men, but not women, significant negative relationships were observed between Water-level Task performance and Motion Sickness Questionnaire score (p<.001) and between Mental Rotation Task performance and Motion Sickness Questionnaire score (p<.005). In conclusion, women performed significantly more poorly than men did on the spatial ability tasks and reported significantly more bouts of motion sickness. In addition, men showed a significant negative relationship between spatial ability and motion sickness susceptibility.

  13. Simvastatin may induce insulin resistance through a novel fatty acid mediated cholesterol independent mechanism

    PubMed Central

    Kain, Vasundhara; Kapadia, Bandish; Misra, Parimal; Saxena, Uday

    2015-01-01

    Statins are a class of oral drugs that are widely used for treatment of hypercholesterolemia. Recent clinical data suggest that chronic use of these drugs increases the frequency of new onset diabetes. Studies to define the risks of statin-induced diabetes and its underlying mechanisms are clearly necessary. We explored the possible mechanism of statin induced insulin resistance using a well-established cell based model and simvastatin as a prototype statin. Our data show that simvastatin induces insulin resistance in a cholesterol biosynthesis inhibition independent fashion but does so by a fatty acid mediated effect on insulin signaling pathway. These data may help design strategies for prevention of statin induced insulin resistance and diabetes in patients with hypercholesterolemia. PMID:26345110

  14. Large scale track analysis for wide area motion imagery surveillance

    NASA Astrophysics Data System (ADS)

    van Leeuwen, C. J.; van Huis, J. R.; Baan, J.

    2016-10-01

    Wide Area Motion Imagery (WAMI) enables image based surveillance of areas that can cover multiple square kilometers. Interpreting and analyzing information from such sources, becomes increasingly time consuming as more data is added from newly developed methods for information extraction. Captured from a moving Unmanned Aerial Vehicle (UAV), the high-resolution images allow detection and tracking of moving vehicles, but this is a highly challenging task. By using a chain of computer vision detectors and machine learning techniques, we are capable of producing high quality track information of more than 40 thousand vehicles per five minutes. When faced with such a vast number of vehicular tracks, it is useful for analysts to be able to quickly query information based on region of interest, color, maneuvers or other high-level types of information, to gain insight and find relevant activities in the flood of information. In this paper we propose a set of tools, combined in a graphical user interface, which allows data analysts to survey vehicles in a large observed area. In order to retrieve (parts of) images from the high-resolution data, we developed a multi-scale tile-based video file format that allows to quickly obtain only a part, or a sub-sampling of the original high resolution image. By storing tiles of a still image according to a predefined order, we can quickly retrieve a particular region of the image at any relevant scale, by skipping to the correct frames and reconstructing the image. Location based queries allow a user to select tracks around a particular region of interest such as landmark, building or street. By using an integrated search engine, users can quickly select tracks that are in the vicinity of locations of interest. Another time-reducing method when searching for a particular vehicle, is to filter on color or color intensity. Automatic maneuver detection adds information to the tracks that can be used to find vehicles based on their

  15. Severe Hypoglycemia–Induced Lethal Cardiac Arrhythmias Are Mediated by Sympathoadrenal Activation

    PubMed Central

    Reno, Candace M.; Daphna-Iken, Dorit; Chen, Y. Stefanie; VanderWeele, Jennifer; Jethi, Krishan; Fisher, Simon J.

    2013-01-01

    For people with insulin-treated diabetes, severe hypoglycemia can be lethal, though potential mechanisms involved are poorly understood. To investigate how severe hypoglycemia can be fatal, hyperinsulinemic, severe hypoglycemic (10–15 mg/dL) clamps were performed in Sprague-Dawley rats with simultaneous electrocardiogram monitoring. With goals of reducing hypoglycemia-induced mortality, the hypotheses tested were that: 1) antecedent glycemic control impacts mortality associated with severe hypoglycemia; 2) with limitation of hypokalemia, potassium supplementation could limit hypoglycemia-associated deaths; 3) with prevention of central neuroglycopenia, brain glucose infusion could prevent hypoglycemia-associated arrhythmias and deaths; and 4) with limitation of sympathoadrenal activation, adrenergic blockers could prevent hypoglycemia-induced arrhythmic deaths. Severe hypoglycemia–induced mortality was noted to be worsened by diabetes, but recurrent antecedent hypoglycemia markedly improved the ability to survive an episode of severe hypoglycemia. Potassium supplementation tended to reduce mortality. Severe hypoglycemia caused numerous cardiac arrhythmias including premature ventricular contractions, tachycardia, and high-degree heart block. Intracerebroventricular glucose infusion reduced severe hypoglycemia–induced arrhythmias and overall mortality. β-Adrenergic blockade markedly reduced cardiac arrhythmias and completely abrogated deaths due to severe hypoglycemia. Under conditions studied, sudden deaths caused by insulin-induced severe hypoglycemia were mediated by lethal cardiac arrhythmias triggered by brain neuroglycopenia and the marked sympathoadrenal response. PMID:23835337

  16. XB130 translocation to microfilamentous structures mediates NNK-induced migration of human bronchial epithelial cells.

    PubMed

    Wu, Qifei; Nadesalingam, Jeya; Moodley, Serisha; Bai, Xiaohui; Liu, Mingyao

    2015-07-20

    Cigarette smoking contributes to the pathogenesis of chronic obstructive pulmonary disease and lung cancer. Nicotine-derived nitrosamine ketone (NNK) is the most potent carcinogen among cigarette smoking components, and is known to enhance migration of cancer cells. However, the effect of NNK on normal human bronchial epithelial cells is not well studied. XB130 is a member of actin filament associated protein family and is involved in cell morphology changes, cytoskeletal rearrangement and outgrowth formation, as well as cell migration. We hypothesized that XB130 mediates NNK-induced migration of normal human bronchial epithelial cells. Our results showed that, after NNK stimulation, XB130 was translocated to the cell periphery and enriched in cell motility-associated structures, such as lamellipodia, in normal human bronchial epithelial BEAS2B cells. Moreover, overexpression of XB130 significantly enhanced NNK-induced migration, which requires both the N- and C-termini of XB130. Overexpression of XB130 enhanced NNK-induced protein tyrosine phosphorylation and promoted matrix metalloproteinase-14 translocation to cell motility-associated cellular structures after NNK stimulation. XB130-mediated NNK-induced cell migration may contribute to airway epithelial repair; however, it may also be involved in cigarette smoking-related chronic obstructive pulmonary disease and lung cancer.

  17. Ultraviolet radiation-induced interleukin 6 release in HeLa cells is mediated via membrane events in a DNA damage-independent way.

    PubMed

    Kulms, D; Pöppelmann, B; Schwarz, T

    2000-05-19

    Evidence exists that ultraviolet radiation (UV) affects molecular targets in the nucleus or at the cell membrane. UV-induced apoptosis was found to be mediated via DNA damage and activation of death receptors, suggesting that nuclear and membrane effects are not mutually exclusive. To determine whether participation of nuclear and membrane components is also essential for other UV responses, we studied the induction of interleukin-6 (IL-6) by UV. Exposing HeLa cells to UV at 4 degrees C, which inhibits activation of surface receptors, almost completely prevented IL-6 release. Enhanced repair of UV-mediated DNA damage by addition of the DNA repair enzyme photolyase did not affect UV-induced IL-6 production, suggesting that in this case membrane events predominant over nuclear effects. UV-induced IL-6 release is mediated via NFkappaB since the NFkappaB inhibitor MG132 or transfection of cells with a super-repressor form of the NFkappaB inhibitor IkappaB reduced IL-6 release. Transfection with a dominant negative mutant of the signaling protein TRAF-2 reduced IL-6 release upon exposure to UV, indicating that UV-induced IL-6 release is mediated by activation of the tumor necrosis factor receptor-1. These data demonstrate that UV can exert biological effects mainly by affecting cell surface receptors and that this is independent of its ability to induce nuclear DNA damage.

  18. Stellar motion induced by gravitational instabilities in protoplanetary discs

    NASA Astrophysics Data System (ADS)

    Michael, Scott; Durisen, R. H.

    2010-07-01

    We test the effect of assumptions about stellar motion on the behaviour of gravitational instabilities (GIs) in protoplanetary discs around solar-type stars by performing two simulations that are identical in all respects except the treatment of the star. In one simulation, the star is assumed to remain fixed at the centre of the inertial reference frame. In the other, stellar motion is handled properly by including an indirect potential in the hydrodynamic equations to model the star's reference frame as one which is accelerated by star/disc interactions. The discs in both simulations orbit a solar mass star, initially extend from 2.3 to 40 au with a ϖ-1/2 surface density profile, and have a total mass of 0.14 Msolar. The γ = 5/3 ideal gas is assumed to cool everywhere with a constant cooling time of two outer rotation periods. The overall behaviour of the disc evolution is similar, except for weakening in various measures of GI activity by about at most tens of per cent for the indirect potential case. Overall conclusions about disc evolution in earlier papers by our group, where the star was always assumed to be fixed in an inertial frame, remain valid. There is no evidence for independent one-armed instabilities, like the Stimulation by the Long-range Interaction of Newtonian Gravity (SLING), in either simulation. On the other hand, the stellar motion about the system centre of mass (COM) in the simulation with the indirect potential is substantial, up to 0.25 au during the burst phase, as GIs initiate, and averaging about 0.9 au during the asymptotic phase, when the GIs reach an overall balance of heating and cooling. These motions appear to be a stellar response to non-linear interactions between discrete global spiral modes in both the burst and asymptotic phases of the evolution, and the star's orbital motion about the COM reflects the orbit periods of disc material near the corotation radii of the dominant spiral waves. This motion is, in principle

  19. Differential responses in dorsal visual cortex to motion and disparity depth cues

    PubMed Central

    Arnoldussen, David M.; Goossens, Jeroen; van den Berg, Albert V.

    2013-01-01

    We investigated how interactions between monocular motion parallax and binocular cues to depth vary in human motion areas for wide-field visual motion stimuli (110 × 100°). We used fMRI with an extensive 2 × 3 × 2 factorial blocked design in which we combined two types of self-motion (translational motion and translational + rotational motion), with three categories of motion inflicted by the degree of noise (self-motion, distorted self-motion, and multiple object-motion), and two different view modes of the flow patterns (stereo and synoptic viewing). Interactions between disparity and motion category revealed distinct contributions to self- and object-motion processing in 3D. For cortical areas V6 and CSv, but not the anterior part of MT+ with bilateral visual responsiveness (MT+/b), we found a disparity-dependent effect of rotational flow and noise: When self-motion perception was degraded by adding rotational flow and moderate levels of noise, the BOLD responses were reduced compared with translational self-motion alone, but this reduction was cancelled by adding stereo information which also rescued the subject's self-motion percept. At high noise levels, when the self-motion percept gave way to a swarm of moving objects, the BOLD signal strongly increased compared to self-motion in areas MT+/b and V6, but only for stereo in the latter. BOLD response did not increase for either view mode in CSv. These different response patterns indicate different contributions of areas V6, MT+/b, and CSv to the processing of self-motion perception and the processing of multiple independent motions. PMID:24339808

  20. Thermally Induced Lateral Motion of α-Zirconium Phosphate Layers Intercalated with Hexadecylamines

    NASA Astrophysics Data System (ADS)

    Char, Kookheon

    2005-03-01

    Well-defined intercalated structure, either interdigitated layers or bilayers, of hexadecylamines (HDAs) in a confined space of a highly-functionalized layered material, α- zirconium phosphate (α-ZrP), was prepared and these two distinct intercalated structures can serve as model systems to investigate the interaction of the two monolayers whose amphiphilic tails are adjacent to each other. Acidic functional groups (-POH) on the α-ZrP are in well-ordered array and the number of functional group is quite high (i.e., cationic exchange capacity (CEC) = 664 mmole/100 g, area per one charge site = 0.24 nm^2) enough to realize the bilayers (i.e., discrete two monolayers) of HDAs within the α-ZrP interlayer. We employed the two-step intercalation mechanism for the preparation of well- ordered interdigitated layers as well as the bilayers of alkyl chains attached to both sides of the α-ZrP intergallery. An intriguing lateral motion of the α-ZrP sheets was observed with in-situ SAXS measurements for the interdigitated layer during heating and cooling cycle and verified with TEM. This lateral motion is believed to be due to the transition from the tilted to the untilted conformation of the interdigitated HDA chains and this transition is found to be thermally reversible.

  1. Improving Understanding of Hydraulic Fracturing-Related Induced Seismicity: A Case for Regulating based on Ground Motion

    NASA Astrophysics Data System (ADS)

    Urbancic, T.; Bosman, K.; Baig, A. M.; Viegas, G. F.

    2016-12-01

    on ground motion. Due to the extreme difficulty of predicting the source characteristics of future induced events, regulating based on magnitude alone appears to be an overly simplistic approach. Regulations incorporating observed ground motion provide a more appropriate method of assessing the potential damage resulting from induced seismicity.

  2. New insights into the effects of onion consumption on lipid mediators using a diet-induced model of hypercholesterolemia.

    PubMed

    González-Peña, Diana; Checa, Antonio; de Ancos, Begoña; Wheelock, Craig E; Sánchez-Moreno, Concepción

    2017-04-01

    The levels and roles of lipid mediators can be modified in response to nutritional stimuli. The aim of this study was to investigate shifts in oxylipin and sphingolipid profiles stimulated by a hypercholesterolemic (HC) diet along with the modulating effects of onion introduced as an antioxidant functional ingredient characterized in the diet (HCO). Oxylipin and sphingolipid profiles were determined in plasma and tissues from Wistar rats using LC-MS/MS. Plasma ω-3 and ω-6 PUFA-derived oxylipins decreased in rats after 7 weeks of HC feeding, but did not evidence a further shift with HCO diet. Onion ingredient supplementation modulated the hepatic concentrations of prostaglandins and enhanced ω-3 oxylipins in the liver of HCO-fed rats relative to the HC group. The HC diet induced shifts in plasma sphingolipids, increasing sphingoid bases, dihydroceramides and ceramides, whilst the sphingomyelin, hexosylceramide and lactosylceramide families decreased. The HCO diet modified some HC diet-induced changes in sphingolipids in liver and spleen tissue. Onion supplementation effected changes in lipid mediator levels in diet-induced hypercholesterolemic Wistar rats. The potential of onion as regulator of pro-inflammatory mediators, and possible enhancer of pro-resolution pathways, warrants further study of the interaction of functional ingredients with bioactive lipid mediators and their potential impact on inflammation, oxidative stress and organ dysfunction. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Motion-Induced Blindness and Troxler Fading: Common and Different Mechanisms

    PubMed Central

    Bonneh, Yoram S.; Donner, Tobias H.; Cooperman, Alexander; Heeger, David J.; Sagi, Dov

    2014-01-01

    Extended stabilization of gaze leads to disappearance of dim visual targets presented peripherally. This phenomenon, known as Troxler fading, is thought to result from neuronal adaptation. Intense targets also disappear intermittently when surrounded by a moving pattern (the “mask”), a phenomenon known as motion-induced blindness (MIB). The similar phenomenology and dynamics of these disappearances may suggest that also MIB is, likewise, solely due to adaptation, which may be amplified by the presence of the mask. Here we directly compared the dependence of both phenomena on target contrast. Observers reported the disappearance and reappearance of a target of varying intensity (contrast levels: 8%–80%). MIB was induced by adding a mask that moved at one of various different speeds. The results revealed a lawful effect of contrast in both MIB and Troxler fading, but with opposite trends. Increasing target contrast increased (doubled) the rate of disappearance events for MIB, but decreased the disappearance rate to half in Troxler fading. The target mean invisible period decreased equally strongly with target contrast in MIB and in Troxler fading. The results suggest that both MIB and Troxler are equally affected by contrast adaptation, but that the rate of MIB is governed by an additional mechanism, possibly involving antagonistic processes between neuronal populations processing target and mask. Our results link MIB to other bi-stable visual phenomena that involve neuronal competition (such as binocular rivalry), which exhibit an analogous dependency on the strength of the competing stimulus components. PMID:24658600

  4. Hepcidin mediates transcriptional changes that modulate acute cytokine-induced inflammatory responses in mice

    PubMed Central

    De Domenico, Ivana; Zhang, Tian Y.; Koening, Curry L.; Branch, Ryan W.; London, Nyall; Lo, Eric; Daynes, Raymond A.; Kushner, James P.; Li, Dean; Ward, Diane M.; Kaplan, Jerry

    2010-01-01

    Hepcidin is a peptide hormone that regulates iron homeostasis and acts as an antimicrobial peptide. It is expressed and secreted by a variety of cell types in response to iron loading and inflammation. Hepcidin mediates iron homeostasis by binding to the iron exporter ferroportin, inducing its internalization and degradation via activation of the protein kinase Jak2 and the subsequent phosphorylation of ferroportin. Here we have shown that hepcidin-activated Jak2 also phosphorylates the transcription factor Stat3, resulting in a transcriptional response. Hepcidin treatment of ferroportin-expressing mouse macrophages showed changes in mRNA expression levels of a wide variety of genes. The changes in transcript levels for half of these genes were a direct effect of hepcidin, as shown by cycloheximide insensitivity, and dependent on the presence of Stat3. Hepcidin-mediated transcriptional changes modulated LPS-induced transcription in both cultured macrophages and in vivo mouse models, as demonstrated by suppression of IL-6 and TNF-α transcript and secreted protein. Hepcidin-mediated transcription in mice also suppressed toxicity and morbidity due to single doses of LPS, poly(I:C), and turpentine, which is used to model chronic inflammatory disease. Most notably, we demonstrated that hepcidin pretreatment protected mice from a lethal dose of LPS and that hepcidin-knockout mice could be rescued from LPS toxicity by injection of hepcidin. The results of our study suggest a new function for hepcidin in modulating acute inflammatory responses. PMID:20530874

  5. Glial cell-expressed mechanosensitive channel TRPV4 mediates infrasound-induced neuronal impairment.

    PubMed

    Shi, Ming; Du, Fang; Liu, Yang; Li, Li; Cai, Jing; Zhang, Guo-Feng; Xu, Xiao-Fei; Lin, Tian; Cheng, Hao-Ran; Liu, Xue-Dong; Xiong, Li-Ze; Zhao, Gang

    2013-11-01

    Vibroacoustic disease, a progressive and systemic disease, mainly involving the central nervous system, is caused by excessive exposure to low-frequency but high-intensity noise generated by various heavy transportations and machineries. Infrasound is a type of low-frequency noise. Our previous studies demonstrated that infrasound at a certain intensity caused neuronal injury in rats but the underlying mechanism(s) is still largely unknown. Here, we showed that glial cell-expressed TRPV4, a Ca(2+)-permeable mechanosensitive channel, mediated infrasound-induced neuronal injury. Among different frequencies and intensities, infrasound at 16 Hz and 130 dB impaired rat learning and memory abilities most severely after 7-14 days exposure, a time during which a prominent loss of hippocampal CA1 neurons was evident. Infrasound also induced significant astrocytic and microglial activation in hippocampal regions following 1- to 7-day exposure, prior to neuronal apoptosis. Moreover, pharmacological inhibition of glial activation in vivo protected against neuronal apoptosis. In vitro, activated glial cell-released proinflammatory cytokines IL-1β and TNF-α were found to be key factors for this neuronal apoptosis. Importantly, infrasound induced an increase in the expression level of TRPV4 both in vivo and in vitro. Knockdown of TRPV4 expression by siRNA or pharmacological inhibition of TRPV4 in cultured glial cells decreased the levels of IL-1β and TNF-α, attenuated neuronal apoptosis, and reduced TRPV4-mediated Ca(2+) influx and NF-κB nuclear translocation. Finally, using various antagonists we revealed that calmodulin and protein kinase C signaling pathways were involved in TRPV4-triggered NF-κB activation. Thus, our results provide the first evidence that glial cell-expressed TRPV4 is a potential key factor responsible for infrasound-induced neuronal impairment.

  6. Reading Emotion From Mouse Cursor Motions: Affective Computing Approach.

    PubMed

    Yamauchi, Takashi; Xiao, Kunchen

    2018-04-01

    Affective computing research has advanced emotion recognition systems using facial expressions, voices, gaits, and physiological signals, yet these methods are often impractical. This study integrates mouse cursor motion analysis into affective computing and investigates the idea that movements of the computer cursor can provide information about emotion of the computer user. We extracted 16-26 trajectory features during a choice-reaching task and examined the link between emotion and cursor motions. Participants were induced for positive or negative emotions by music, film clips, or emotional pictures, and they indicated their emotions with questionnaires. Our 10-fold cross-validation analysis shows that statistical models formed from "known" participants (training data) could predict nearly 10%-20% of the variance of positive affect and attentiveness ratings of "unknown" participants, suggesting that cursor movement patterns such as the area under curve and direction change help infer emotions of computer users. Copyright © 2017 Cognitive Science Society, Inc.

  7. Disorders of motion and depth.

    PubMed

    Nawrot, Mark

    2003-08-01

    Damage to the human homologue of area MT produces a motion perception deficit similar to that found in the monkey with MT lesions. Even temporary disruption of MT processing with transcranial magnetic stimulation can produce a temporary akinetopsia [127]. Motion perception deficits, however, also are found with a variety of subcortical lesions and other neurologic disorders that can best be described as causing a disconnection within the motion processing stream. The precise role of these subcortical structures, such as the cerebellum, remains to be determined. Simple motion perception, moreover, is only a part of MT function. It undoubtedly has an important role in the perception of depth from motion and stereopsis [112]. Psychophysical studies using aftereffects in normal observers suggest a link between stereo mechanisms and the perception of depth from motion [9-11]. There is even a simple correlation between stereo acuity and the perception of depth from motion [128]. Future studies of patients with cortical lesions will take a closer look at depth perception in association with motion perception and should provide a better understanding of how motion and depth are processed together.

  8. Shared sensory estimates for human motion perception and pursuit eye movements.

    PubMed

    Mukherjee, Trishna; Battifarano, Matthew; Simoncini, Claudio; Osborne, Leslie C

    2015-06-03

    Are sensory estimates formed centrally in the brain and then shared between perceptual and motor pathways or is centrally represented sensory activity decoded independently to drive awareness and action? Questions about the brain's information flow pose a challenge because systems-level estimates of environmental signals are only accessible indirectly as behavior. Assessing whether sensory estimates are shared between perceptual and motor circuits requires comparing perceptual reports with motor behavior arising from the same sensory activity. Extrastriate visual cortex both mediates the perception of visual motion and provides the visual inputs for behaviors such as smooth pursuit eye movements. Pursuit has been a valuable testing ground for theories of sensory information processing because the neural circuits and physiological response properties of motion-responsive cortical areas are well studied, sensory estimates of visual motion signals are formed quickly, and the initiation of pursuit is closely coupled to sensory estimates of target motion. Here, we analyzed variability in visually driven smooth pursuit and perceptual reports of target direction and speed in human subjects while we manipulated the signal-to-noise level of motion estimates. Comparable levels of variability throughout viewing time and across conditions provide evidence for shared noise sources in the perception and action pathways arising from a common sensory estimate. We found that conditions that create poor, low-gain pursuit create a discrepancy between the precision of perception and that of pursuit. Differences in pursuit gain arising from differences in optic flow strength in the stimulus reconcile much of the controversy on this topic. Copyright © 2015 the authors 0270-6474/15/358515-16$15.00/0.

  9. TMEM16A mediates the hypersecretion of mucus induced by Interleukin-13

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

    Lin, Jiachen; Jiang, Youfan; Li, Li

    2015-06-10

    Previous studies showed that the Ca{sup 2+}-activated Cl{sup −} channel (CaCC) was involved in the pathogenesis of mucus hypersecretion induced by Interleukin-13 (IL-13). However, the mechanisms underlying the process were unknown. Recently, transmembrane protein 16A (TMEM16A) was identified as the channel underlying the CaCC current. The aim of the current study was to investigate whether the TMEM16A channel is part of the mechanism underlying IL-13-induced mucus hypersecretion. We observed that both TMEM16A mRNA and protein expression were significantly up-regulated after treatment with IL-13 in human bronchial epithelial 16 (HBE 16) cells, which correlated with an increase in mucus production. Additionally,more » mucus hypersecretion in rat airways was induced by intratracheal instillation of IL-13 and similar increases were observed in the expression of TMEM16A mRNA and protein in the bronchial epithelium. Niflumic acid (NA), a selective antagonist of CaCC, markedly blocked IL-13-induced mucin (MUC) 5AC mRNA and protein production in vivo and in vitro. Further investigation with HBE16 cells revealed that TMEM16A overexpression clearly promoted mucus production, IκBα phosphorylation, and p65 accumulation in the nucleus. The loss of TMEM16A resulted in inhibition of mucus production, and the TMEM16A-mediated production of MUC5AC was significantly blocked by a nuclear factor-kappa B (NF-κB) inhibitor. Therefore, the TMEM16A channel acts upstream of NF-κB in the regulation of mucus production. This is the first demonstration that the TMEM16A-NF-κB pathway is positively involved in IL-13-induced mucus production, which provides novel insight into the molecular mechanism of mucin overproduction. - Highlights: • TMEM16A acts as downstream events of IL-13 signaling pathway. • Established the link between TMEM16A and mucus hypersecretion. • NF-κB activation might be responsible for TMEM16A mediated mucus secretion.« less

  10. Endothelin Induces Rapid, Dynamin-mediated Budding of Endothelial Caveolae Rich in ET-B*

    PubMed Central

    Oh, Phil; Horner, Thierry; Witkiewicz, Halina; Schnitzer, Jan E.

    2012-01-01

    Clathrin-independent trafficking pathways for internalizing G protein-coupled receptors (GPCRs) remain undefined. Clathrin-mediated endocytosis of receptors including ligand-engaged GPCRs can be very rapid and comprehensive (<10 min). Caveolae-mediated endocytosis of ligands and antibodies has been reported to be much slower in cell culture (≫10 min). Little is known about the role of physiological ligands and specific GPCRs in regulating caveolae trafficking. Here, we find that one receptor for endothelin, ET-B but not ET-A, resides on endothelial cell surfaces in both tissue and cell culture primarily concentrated within caveolae. Reconstituted cell-free budding assays show that endothelins (ETs) induce the fission of caveolae from endothelial plasma membranes purified from rat lungs. Electron microcopy of lung tissue sections and tissue subcellular fractionation both show that endothelin administered intravascularly in rats also induces a significant loss of caveolae at the luminal surface of lung vascular endothelium. Endothelial cells in culture show that ET stimulates very rapid internalization of caveolae and cargo including caveolin, caveolae-targeting antibody, and itself. The ET-B inhibitor BQ788, but not the ET-A inhibitor BQ123, blocks the ET-induced budding of caveolae. Both the pharmacological inhibitor Dynasore and the genetic dominant negative K44A mutant of dynamin prevent this induced budding and internalization of caveolae. Also shRNA lentivirus knockdown of caveolin-1 expression prevents rapid internalization of ET and ET-B. It appears that endothelin can engage ET-B already highly concentrated in caveolae of endothelial cells to induce very rapid caveolae fission and endocytosis. This transport requires active dynamin function. Caveolae trafficking may occur more rapidly than previously documented when it is stimulated by a specific ligand to signaling receptors already located in caveolae before ligand engagement. PMID:22457360

  11. IL-13 is a central mediator of chemical-induced airway hyperreactivity in mice

    PubMed Central

    Devos, Fien C.; Pollaris, Lore; Cremer, Jonathan; Seys, Sven; Hoshino, Tomoaki; Ceuppens, Jan; Talavera, Karel; Nemery, Benoit; Hoet, Peter H. M.

    2017-01-01

    Background While the importance of the Th2 cytokine IL-13 as a central mediator of airway hyperreactivity (AHR) has been described in allergic protein-induced asthma, this has never been investigated in chemical-induced asthma. Objective We examined the importance of IL-13 in a mouse model of chemical-induced AHR, using toluene-2,4-diisocyanate (TDI). Methods In a first set-up, wild type (WT) and IL-13 knockout (KO) C57Bl/6 mice were dermally treated on days 1 and 8 with 1% TDI or vehicle (acetone/olive oil) on both ears. On day 15, mice received an intranasal instillation with 0.1% TDI or vehicle. In a second set-up, WT mice sensitized with 1% TDI or vehicle, received i.v. either anti-IL-13 or control antibody prior to the intranasal challenge. Results TDI-sensitized and TDI-challenged WT mice showed AHR to methacholine, in contrast to TDI-sensitized and TDI-challenged IL-13 KO mice, which also showed lower levels of total serum IgE. TDI-sensitized and TDI-challenged IL-13 KO mice had lower numbers of T-cells in the auricular lymph nodes. TDI-treated WT mice, receiving anti-IL-13, showed no AHR, in contrast to those receiving control antibody, despite increased levels of IgE. Anti-IL-13 treatment in TDI-treated WT mice resulted in lower levels of serum IL-13, but did not induce changes in T- and B-cell numbers, and in the cytokine production profile. Conclusion and clinical relevance We conclude that IL-13 plays a critical role in the effector phase of chemical-induced, immune-mediated AHR. This implicates that anti-IL-13 treatment could have a beneficial effect in patients with this asthma phenotype. PMID:28704401

  12. Does corticosterone mediate predator-induced responses of larval Hylarana indica?

    PubMed

    Joshi, A M; Wadekar, N V; Gramapurohit, N P

    2017-09-15

    Prey-predator interactions have been studied extensively in terms of morphological and behavioural responses of prey to predation risk using diverse model systems. However, the underlying physiological changes associated with morphological, behavioural or life historical responses have been rarely investigated. Herein, we studied the effect of chronic predation risk on larval growth and metamorphosis of Hylarana indica and the underlying physiological changes in prey tadpoles. In the first experiment, tadpoles were exposed to a caged predator from Gosner stage 25-42 to record growth and metamorphosis. Further, whole body corticosterone (CORT) was measured to determine the physiological changes underlying morphological and life historical responses of these prey tadpoles. Surprisingly, tadpoles experiencing continuous predation risk grew and developed faster and metamorphosed at a larger size. Interestingly, these tadpoles had significantly lower CORT levels. In the second experiment, tadpoles were exposed to predation risk (PR) or PR+CORT from stage 25-42 to determine the role of CORT in mediating predator-induced responses of H. indica. Tadpoles facing continuous predation risk grew and developed faster and metamorphosed at a larger size reinforcing the results of the first experiment. However, when CORT was administered along with predation risk, tadpoles grew and developed slowly leading to delayed metamorphosis. Interestingly, growth and metamorphic traits of tadpoles exposed to PR+CORT were comparable to those of the control group indicating that exogenous CORT nullified the positive effect of predation risk. Apparently, CORT mediates predator-induced morphological responses of H. indica tadpoles by regulating their physiology. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Quantitative framework for prospective motion correction evaluation.

    PubMed

    Pannetier, Nicolas A; Stavrinos, Theano; Ng, Peter; Herbst, Michael; Zaitsev, Maxim; Young, Karl; Matson, Gerald; Schuff, Norbert

    2016-02-01

    Establishing a framework to evaluate performances of prospective motion correction (PMC) MRI considering motion variability between MRI scans. A framework was developed to obtain quantitative comparisons between different motion correction setups, considering that varying intrinsic motion patterns between acquisitions can induce bias. Intrinsic motion was considered by replaying in a phantom experiment the recorded motion trajectories from subjects. T1-weighted MRI on five volunteers and two different marker fixations (mouth guard and nose bridge fixations) were used to test the framework. Two metrics were investigated to quantify the improvement of the image quality with PMC. Motion patterns vary between subjects as well as between repeated scans within a subject. This variability can be approximated by replaying the motion in a distinct phantom experiment and used as a covariate in models comparing motion corrections. We show that considering the intrinsic motion alters the statistical significance in comparing marker fixations. As an example, two marker fixations, a mouth guard and a nose bridge, were evaluated in terms of their effectiveness for PMC. A mouth guard achieved better PMC performance. Intrinsic motion patterns can bias comparisons between PMC configurations and must be considered for robust evaluations. A framework for evaluating intrinsic motion patterns in PMC is presented. © 2015 Wiley Periodicals, Inc.

  14. Increased CRF signaling in a ventral tegmental area-interpeduncular nucleus-medial habenula circuit induces anxiety during nicotine withdrawal

    PubMed Central

    Zhao-Shea, Rubing; DeGroot, Steven R.; Liu, Liwang; Vallaster, Markus; Pang, Xueyan; Su, Qin; Gao, Guangping; Rando, Oliver J.; Martin, Gilles E.; George, Olivier; Gardner, Paul D.; Tapper, Andrew R.

    2015-01-01

    Increased anxiety is a predominant withdrawal symptom in abstinent smokers, yet the neuroanatomical and molecular bases underlying it are unclear. Here, we show that withdrawal-induced anxiety increases activity of neurons in the interpeduncular intermediate (IPI), a subregion of the interpeduncular nucleus (IPN). IPI activation during nicotine withdrawal was mediated by increased corticotropin releasing factor (CRF) receptor-1 expression and signaling, which modulated glutamatergic input from the medial habenula (MHb). Pharmacological blockade of IPN CRF1 receptors or optogenetic silencing of MHb input reduced IPI activation and alleviated withdrawal-induced anxiety; whereas IPN CRF infusion in mice increased anxiety. We identified a meso-interpeduncular circuit, consisting of ventral tegmental area (VTA) dopaminergic neurons projecting to the IPN, as a potential source of CRF. Knock-down of CRF synthesis in the VTA prevented IPI activation and anxiety during nicotine withdrawal. These data indicate that increased CRF receptor signaling within a VTA-IPN-MHb circuit triggers anxiety during nicotine withdrawal. PMID:25898242

  15. WE-G-18C-06: Is Diaphragm Motion a Good Surrogate for Liver Tumor Motion?

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

    Yang, J; School of Information Science and Engineering, Shandong University, Jinan, Shandong; Cai, J

    2014-06-15

    Purpose: To investigate whether diaphragm motion is a good surrogate for liver tumor motion by comparing their motion trajectories obtained from cine-MRI. Methods: Fourteen patients with hepatocellular carcinoma (10/14) or liver metastases (4/14) undergoing radiation therapy were included in this study. All patients underwent single-slice 2D cine-MRI simulations across the center of the tumor in three orthogonal planes. Tumor and diaphragm motion trajectories in the superior-inferior (SI), anteriorposterior (AP), and medial-lateral (ML) directions were obtained using the normalized cross-correlation based tracking technique. Agreement between tumor and diaphragm motions was assessed by calculating the phase difference percentage (PDP), intra-class correlation coefficientmore » (ICC), Bland-Altman analysis (Diffs) and paired t-test. The distance (D) between tumor and tracked diaphragm area was analyzed to understand its impact on the correlation between tumor and diaphragm motions. Results: Of all patients, the means (±standard deviations) of PDP were 7.1 (±1.1)%, 4.5 (±0.5)% and 17.5 (±4.5)% in the SI, AP and ML directions, respectively. The means of ICC were 0.98 (±0.02), 0.97 (±0.02), and 0.08 (±0.06) in the SI, AP and ML directions, respectively. The Diffs were 2.8 (±1.4) mm, 2.4 (±1.1) mm, and 2.2 (±0.5) mm in the SI, AP and ML directions, respectively. The p-values derived from the paired t-test were < 0.02 in SI and AP directions, whereas were > 0.58 in ML direction primarily due to the small motion in ML direction. Tumor and diaphragmatic motion had high concordance when the distance between the tumor and tracked diaphragm areas was small. Conclusion: Preliminary results showed that liver tumor motion had good correlations with diaphragm motion in the SI and AP directions, indicating diaphragm motion in the SI and AP directions could potentially be a reliable surrogate for liver tumor motion. NIH (1R21CA165384-01A1), Golfers Against Cancer (GAC

  16. Fluoride induces oxidative damage and SIRT1/autophagy through ROS-mediated JNK signaling.

    PubMed

    Suzuki, Maiko; Bandoski, Cheryl; Bartlett, John D

    2015-12-01

    Fluoride is an effective caries prophylactic, but at high doses can also be an environmental health hazard. Acute or chronic exposure to high fluoride doses can result in dental enamel and skeletal and soft tissue fluorosis. Dental fluorosis is manifested as mottled, discolored, porous enamel that is susceptible to dental caries. Fluoride induces cell stress, including endoplasmic reticulum stress and oxidative stress, which leads to impairment of ameloblasts responsible for dental enamel formation. Recently we reported that fluoride activates SIRT1 and autophagy as an adaptive response to protect cells from stress. However, it still remains unclear how SIRT1/autophagy is regulated in dental fluorosis. In this study, we demonstrate that fluoride exposure generates reactive oxygen species (ROS) and the resulting oxidative damage is counteracted by SIRT1/autophagy induction through c-Jun N-terminal kinase (JNK) signaling in ameloblasts. In the mouse-ameloblast-derived cell line LS8, fluoride induced ROS, mitochondrial damage including cytochrome-c release, up-regulation of UCP2, attenuation of ATP synthesis, and H2AX phosphorylation (γH2AX), which is a marker of DNA damage. We evaluated the effects of the ROS inhibitor N-acetylcysteine (NAC) and the JNK inhibitor SP600125 on fluoride-induced SIRT1/autophagy activation. NAC decreased fluoride-induced ROS generation and attenuated JNK and c-Jun phosphorylation. NAC decreased SIRT1 phosphorylation and formation of the autophagy marker LC3II, which resulted in an increase in the apoptosis mediators γH2AX and cleaved/activated caspase-3. SP600125 attenuated fluoride-induced SIRT1 phosphorylation, indicating that fluoride activates SIRT1/autophagy via the ROS-mediated JNK pathway. In enamel organs from rats or mice treated with 50, 100, or 125 ppm fluoride for 6 weeks, cytochrome-c release and the DNA damage markers 8-oxoguanine, p-ATM, and γH2AX were increased compared to those in controls (0 ppm fluoride). These

  17. Fluoride induces oxidative damage and SIRT1/autophagy through ROS-mediated JNK signaling

    PubMed Central

    Suzuki, Maiko; Bandoski, Cheryl; Bartlett, John D.

    2015-01-01

    Fluoride is an effective caries prophylactic, but at high doses can also be an environmental health hazard. Acute or chronic exposure to high fluoride doses can result in dental enamel and skeletal and soft tissue fluorosis. Dental fluorosis is manifested as mottled, discolored, porous enamel that is susceptible to dental caries. Fluoride induces cell stress, including endoplasmic reticulum stress and oxidative stress, which leads to impairment of ameloblasts responsible for dental enamel formation. Recently we reported that fluoride activates SIRT1 and autophagy as an adaptive response to protect cells from stress. However, it still remains unclear how SIRT1/autophagy is regulated in dental fluorosis. In this study, we demonstrate that fluoride exposure generates reactive oxygen species (ROS) and the resulting oxidative damage is counteracted by SIRT1/autophagy induction through c-Jun N-terminal kinase (JNK) signaling in ameloblasts. In the mouse-ameloblast-derived cell line LS8, fluoride induced ROS, mitochondrial damage including cytochrome-c release, up-regulation of UCP2, attenuation of ATP synthesis, and H2AX phosphorylation (γH2AX), which is a marker of DNA damage. We evaluated the effects of the ROS inhibitor N-acetylcysteine (NAC) and the JNK inhibitor SP600125 on fluoride-induced SIRT1/autophagy activation. NAC decreased fluoride-induced ROS generation and attenuated JNK and c-Jun phosphorylation. NAC decreased SIRT1 phosphorylation and formation of the autophagy marker LC3II, which resulted in an increase in the apoptosis mediators γH2AX and cleaved/activated caspase-3. SP600125 attenuated fluoride-induced SIRT1 phosphorylation, indicating that fluoride activates SIRT1/autophagy via the ROS-mediated JNK pathway. In enamel organs from rats or mice treated with 50, 100, or 125 ppm fluoride for 6 weeks, cytochrome-c release and the DNA damage markers 8-oxoguanine, p-ATM, and γH2AX were increased compared to those in controls (0 ppm fluoride). These

  18. Distinct roles of NF-{kappa}B p50 in the regulation of acetaminophen-induced inflammatory mediator production and hepatotoxicity

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

    Dambach, Donna M.; Pharmaceutical Research Institute, Bristol-Myers Squibb, Princeton, NJ 08543; Durham, Stephen K.

    2006-03-01

    Oxidative stress plays an important role in acetaminophen (APAP)-induced hepatotoxicity. In addition to inducing direct cellular damage, oxidants can activate transcription factors including NF-{kappa}B, which regulate the production of inflammatory mediators implicated in hepatotoxicity. Here, we investigated the role of APAP-induced oxidative stress and NF-{kappa}B in inflammatory mediator production. Treatment of mice with APAP (300 mg/kg, i.p.) resulted in centrilobular hepatic necrosis and increased serum aminotransferase levels. This was correlated with depletion of hepatic glutathione and CuZn superoxide dismutase (SOD). APAP administration also increased expression of the proinflammatory mediators, interleukin-1{beta} (IL-1{beta}), tumor necrosis factor-{alpha} (TNF{alpha}), macrophage chemotactic protein-1 (MCP-1), andmore » KC/gro, and the anti-inflammatory cytokine, interleukin-10 (IL-10). Pretreatment of mice with the antioxidant, N-acetylcysteine (NAC) prevented APAP-induced depletion of glutathione and CuZnSOD, as well as hepatotoxicity. NAC also abrogated APAP-induced increases in TNF{alpha}, KC/gro, and IL-10, but augmented expression of the anti-inflammatory cytokines interleukin-4 (IL-4) and transforming growth factor-{beta} (TGF{beta}). No effects were observed on IL-1{beta} or MCP-1 expression. To determine if NF-{kappa}B plays a role in regulating mediator production, we used transgenic mice with a targeted disruption of the gene for NF-{kappa}B p50. As observed with NAC pretreatment, the loss of NF-{kappa}B p50 was associated with decreased ability of APAP to upregulate TNF{alpha}, KC/gro, and IL-10 expression and increased expression of IL-4 and TGF{beta}. However, in contrast to NAC pretreatment, the loss of p50 had no effect on APAP-induced hepatotoxicity. These data demonstrate that APAP-induced cytokine expression in the liver is influenced by oxidative stress and that this is dependent, in part, on NF-{kappa}B. However, NF-{kappa}B p50

  19. Increased expression of matrix metalloproteinases mediates thromboxane A2-induced invasion in lung cancer cells.

    PubMed

    Li, Xiuling; Tai, Hsin-Hsiung

    2012-07-01

    Thromboxane A(2) receptor (TP) has been shown to play an important role in multiple aspects of cancer development including regulation of tumor growth, survival and metastasis. Here we report that TP mediates cancer cell invasion by inducing expression of matrix metalloproteinases (MMPs). TP agonist, I-BOP, significantly elevated MMP-1, MMP-3, MMP-9 and MMP-10 mRNA levels in A549 human lung adenocarcinoma cells overexpressing TPα or TPβ. The secretion of MMP-1 and MMP-9 in conditioned media was determined using Western blot analysis and zymographic assay. Signaling pathways of I-BOP-induced MMP-1 expression were examined in further detail as a model system for MMPs induction. Signaling molecules involved in I-BOP-induced MMP-1 expression were identified by using specific inhibitors including small interfering (si)-RNAs of signaling molecules and promoter reporter assay. The results indicate that I-BOP-induced MMP-1 expression is mediated by protein kinase C (PKC), extracellular signal-regulated kinase (ERK)-activator protein-1(AP-1) and ERK-CCAAT/enhancer-binding protein β (C/EBPβ) pathways. I-BOP-induced cellular invasiveness of A549 cells expressing TPα or TPβ was determined by invasion assay. GM6001, a general inhibitor of MMPs, decreased basal and I-BOP-induced cell invasion. Knockdown of MMP-1 and MMP-9 by their respective siRNA partially reduced I-BOP-stimulated cell invasion suggesting that other MMPs induced by I-BOP were also involved. Our studies establish the relationship between TP and MMPs in cancer cell invasion and suggest that the thromboxane A(2) (TXA(2))-TP signaling is a potential therapeutic target for cancer invasion and metastasis.

  20. Mycobacterium tuberculosis ESAT6 induces IFN-β gene expression in Macrophages via TLRs-mediated signaling.

    PubMed

    Jang, Ah-Ra; Choi, Joo-Hee; Shin, Sung Jae; Park, Jong-Hwan

    2018-04-01

    Mycobacterium tuberculosis is a highly virulent bacterium that causes tuberculosis. It infects about one third of the world's population. Type I interferons (IFNs) play a detrimental role in host defense against M. tuberculosis infection. Proteins secreted by M. tuberculosis through ESX-1 secretion system contribute to type I IFNs production. However, the precise mechanism by which 6-kDa early secretory antigen target (ESAT6), one of ESX-1-mediated secretory proteins, induces type I IFNs production in host cells is currently unclear. Therefore, the objective of the present study was to determine the underlying molecular mechanism regulating ESAT6-mediated gene expression of IFN-β in macrophages. Recombinant ESAT6 produced from E. coli expression system induced IFN-β gene expression in various types of macrophages such as mouse bone marrow-derived macrophages (BMDMs), peritoneal macrophages, and MH-S cells (murine alveolar macrophage cell line). Deficiency of TLR4 and TRIF absolutely abrogated ESAT6-induced IFN-β gene expression. TLR2 and MyD88 were partially involved in IFN-β gene expression in response to low dose of ESAT6. Another recombinant ESAT6 produced from baculovirus system also upregulated IFN-β gene expression via TLR4-dependent pathway. Polymyxin B (PMB) treatment impaired LPS-induced IFN-β expression. However, IFN-β expression induced by ESAT6 was not influenced by PMB. This suggests that ESAT6-mediated IFN-β expression is not due to LPS contamination. Treatment with ESAT6 resulted in activation of TBK1 and IRF3 in macrophages. Such activation was abolished in TLR4- and TRIF-deficient cells. Moreover, inhibition of IRF3 and TBK1 suppressed IFN-β gene expression in response to ESAT6. Our results suggest that ESAT6 might contribute to virulence of M. tuberculosis by regulating type I IFNs production through TLR4-TRIF signaling pathway. Copyright © 2017 Elsevier Ltd. All rights reserved.