Contributors:Antonella Lombardi Costa, Cláubia Pereira, Walter Ambrosini, Francesco D’Auria
Relative power evolution during a period of oscillation of 1.06s.
Contributors:S.A. Galindo-Torres, A. Scheuermann, L. Li, D.M. Pedroso, D.J. Williams
Simulation setup. The no-flow boundary cells of the LBM domain were tagged as solid. The bounce back rule of Eq. (16) were applied to them but with cohesion (Eq. (17)) turned off to mitigate the effects of the boundaries. The water table oscillated with time during the simulation due to the varying pressure head imposed at the bottom boundary.
... Water saturation Sr as a function of dimensionless time (time multiplied by the factor g/H) from simulations with different frequencies (as indicated by the number of fluctuation cycles within the period of the plots).
... Amplitude of the Fourier components |F(ω)| for each frequency for both original (triangles) and filtered signals (squares).
... Amplitude A(ω) of the harmonic component of Sr(t) as a function of ω with a power law fitting (exponent equal to −0.36). Inset: phase angle ϕ representing the lag of the Sr oscillation behind the imposed head fluctuation.
... Imposed hydraulic head fluctuations (h0−h(t))/h0 versus the saturation variations (Sr) for two different frequencies and 4 cycles of equilibrium simulations. The arrows shows the time sequence taking for the equilibrium cycles, first imbibition and then drainage, which also holds for the dynamic simulations.
Contributors:M.M. Dernison, J.M.A.M. Kusters, P.H.J. Peters, W.P.M. van Meerwijk, D.L. Ypey, C.C.A.M. Gielen, E.J.J. van Zoelen, A.P.R. Theuvenet
Changes in intracellular Ca2+/Sr2+ levels of quiescent monolayer NRK cells, upon stimulation with PGF2α inside the ring, at different positions outside, inside and under the ring. Cells inside the ring were stimulation with PGF2α (n=7 experiments). Distribution of the interval time between calcium oscillations is depicted at right panels. (A) Response of 62 cells measured 5mm outside the ring at position A (see inset) after addition inside the ring of 0.8μM PGF2α. (B) Response of 47 cells measured under the ring (position B in inset) in the presence of PGF2α inside the ring. (C) Response of 67 cells measured at the inner edge of the ring (position C in inset) in the presence of PGF2α inside the ring. Individual traces are shown in gray, the mean response of the imaged cells is represented by the black line. Cells outside the ring were perfused with 5mM Sr2+, while inside the ring 1mM Ca2+ was present (see Materials and methods). The lower gray bar indicates presence of PGF2α inside the ring. Inset shows different positions of the imaged regions in relation to the ring location on the monolayer. Time (5min) is indicated by the lower black bar.
... The inset shows a schematic two-dimensional network of 400×400 cells. At the centre of the network cells, within a ring with an inner radius of 1mm (equivalent to 100 cells) have an IP3 concentration randomly distributed within a range between 5 and 15μM. (A) IP3 gradient due to diffusion and degradation of IP3 as described by Eq. (A.4) in Appendix A. For cells under the ring (0.5mm thick) the IP3 concentration decreases according to Eq. (A.4) from 10μM (inner side of the ring) to 0.1μM (outside the ring). Cells outside the ring have an IP3-concentration of 0.1μM and do not exhibit spontaneous calcium oscillations. (B) Membrane potential gradient in the network with (dashed line) and without (solid line) taking into account IP3 diffusion. The solid line shows the average membrane potential if there would be no diffusion of IP3 from the inside of the ring to cells under the ring. The dashed line shows the average membrane potential as a result of simulations for an IP3 distribution in the network according to Eq. (A.4) in Appendix A.
Contributors:Huikun Wang, Tyler Treadway, Daniel P. Covey, Joseph F. Cheer, Carl R. Lupica
Cocaine-Mobilized 2-AG Inhibits GABA Release and Increases DA Release in NAc via Actions in VTA
(A) Acute cocaine (10 μM) perfusion inhibited GABAB IPSCs and this was partially blocked by AM251 (2 μM). Scale bar, 100 ms, 10 pA.
(B) Cocaine inhibition of GABAB IPSCs was reduced by inhibition of DGL with THL, applied either intracellularly via the pipette (intra-THL) or extracellularly, by addition to the aCSF (extra-THL). Scale bar, 100 ms, 10 pA.
(C) Summary of the experiments shows significant reduction of the cocaine inhibition of GABAB IPSCs by AM251 and THL (n = 5; F(3,36) = 6.35, p = 0.0014, one-way ANOVA; ∗p 0.05, paired t test. Scale bar, 100 ms, 10 pA.
(E) In vivo NAc FSCV current (encoded in color) is plotted against the applied potential (ordinate) and the acquisition time (abscissa). Traces above color plots are extracted currents (normalized to concentration) from the potential where DA is oxidized (∼+0.6 V shown in green), when animals are given intravenous cocaine (1 mg/kg), preceded by an i.c.v. vehicle injection.
(F) Effects of cocaine are reduced in vivo by inhibition of 2-AG synthesis by THL in the VTA (750 ng THL in 500 μl, unilateral and ipsilateral to the recording electrode).
(G) Intra-VTA THL reduces DA transient frequency elicited by i.v. cocaine (F (4,10) = 9.395, p = 0.002, one-way ANOVA; n = 3 rats, ∗∗p frequency without intracranial or systemic injections. In other groups, the intra-VTA injection is indicated first, followed by the i.v. injection condition (e.g., intracranial Veh∖intra-VTA Veh). Note that THL alone (THL/Veh) did not alter DA transient frequency, and THL significantly reduced the effect of i.v. cocaine on DA transients (THL/cocaine, p < 0.001, Bonferroni post hoc test).
See also Figure S1.
... Cocaine-Induced Increase in NAc DA Transients Require CB1R Activation in VTA
(A) Voltammetric current (encoded in color) plotted against the applied carbon-fiber electrode potential (ordinate) and the acquisition time (abscissa). Traces above color plots represent current (normalized to concentration) from the potential where DA is oxidized (∼+0.6 V in green), when animals are given an i.v. bolus of cocaine (1 mg/kg), preceded by intra-VTA vehicle infusion.
(B) Systemic effects of cocaine are attenuated following CB1R blockade in VTA (250 ng rimonabant [Rbt] in 500 μl, unilateral and ipsilateral to the recording electrode).
(C) Effects of all treatments on NAc DA transient frequency (F(4,31) = 29.14, p frequency of DA transients without intracranial or systemic injections. In other groups the intra-VTA injection is indicated first, followed by the i.v. injection (e.g., intracranial Veh∖intra-VTA Veh). Note that Rbt alone (Rbt/Veh) did not alter DA transient frequency, and Rbt significantly reduced the effect of i.v. cocaine on DA transients (Rbt/cocaine, ∗∗∗p < 0.0001, Bonferroni post hoc test).
... Cocaine-Induced Calcium Changes in VTA DA Neurons
(A) Superimposed fluorescent and transmitted light images showing the expression of GCaMP6f in VTA DA neurons 2–3 weeks after injection of the AAV- GCaMP6f construct. Scale bar, 500 μm.
(B) Spontaneous slow calcium oscillations in VTA DA neurons. Left: confocal image of the GCaMP6f signal (200×). Scale bar, 50 μm. Right: example calcium oscillations (ΔF/F0) in the same cell indicated in the dashed square at left. Scale bar, 30 s, 20%.
(C) Sample traces of calcium signals (ΔF/F0) in response to cocaine application (10 μM, indicated in gray). Three types of changes were observed: no change, a decrease in spontaneous oscillations, and the initiation of slow oscillations (SO).
(D) Raster plot of oscillation events in 19 neurons imaged as in (B). Each vertical bar denotes the peak of an oscillation event. Each row exhibits the time course of oscillation change in single neurons.
(E) Cumulative frequencies of spontaneous, cocaine-decreased, and cocaine-initiated slow oscillations (cocaine SO) in calcium signal. The curve shifts left to slower frequencies in neurons whose calcium oscillations were decreased by cocaine (osc decrease versus spontaneous, p = 0.17, K-S test). The frequency of cocaine-initiated SO was significantly lower than that of spontaneous oscillations (cocaine-initiated versus spontaneous, p oscillation, n = 43 neurons; oscillation decrease, n = 19 neurons; cocaine SO, n = 29 neurons recorded in eight brain slices from six rats.
(F) Cumulative distribution of half-widths of spontaneous, cocaine-decreased, and cocaine-initiated SO. Cocaine-initiated SO exhibit longer half-widths than spontaneous oscillations. (cocaine SO versus spontaneous, p oscillation, n = 43 neurons; oscillation decrease, n = 19 neurons; cocaine SO, n = 29 neurons recorded in eight brain slices from six rats.
(G) Increased correlation of calcium responses among neurons (same 19 neurons as D) during cocaine perfusion. Cross correlations among all neuron pairs were calculated, and the peak correlation coefficient (r = 0 to 1) is color-coded to form the heat map. The data indicate that VTA DA neuron calcium oscillations are more highly synchronized by cocaine.
(H) Cocaine-induced calcium oscillations depend on mGluR1, α1-adrenergic receptors, and internal calcium stores. The frequency of spontaneous calcium oscillations is reduced by JNJ16259685 (500 nM), but is not altered by HEAT (1 μM), U73122, or thapsigargin (thaps, 2 μM), respectively (F(4,265) = 3.806, p = 0.005, one-way ANOVA; control versus JNJ: p frequency of spontaneous Ca2+ oscillation from one neuron; the box and vertical lines indicate quartiles, minimal, and maximal frequencies. The percentage of neurons exhibiting spontaneous oscillations is shown for each treatment group.
(I) Cumulative distributions of the frequencies of spontaneous oscillations are only affected by JNJ (p = 0.0037, Kolmogorov–Smirnov test).
(J) Summary of the percentage of DA neurons responding to cocaine under control, JNJ16259685, HEAT, U73122, and thapsigargin treatments. Numbers denote the percentage of neurons demonstrating indicated changes upon cocaine treatment. All treatments decreased the cocaine-induced Ca2+ oscillation.
(K) Pre-treatment of slices with thapsigargin (2 μM) significantly attenuates the inhibition of GABAB IPSCs by cocaine (n = 7; ∗p < 0.05, unpaired t test). Inset at right shows averaged electrically evoked GABAB IPSC traces (n = 5) under control conditions (top) and after treatment with thapsigargin. Control sweeps are shown in black; those obtained during cocaine application are shown in gray. Scale bar, 100 ms, 10 pA.
See also Movie S1.
Contributors:L.D. Yépez, J.L. Carrillo, F. Donado, J.M. Sausedo-Solorio, P. Miranda-Romagnoli
The behavior of the average length of the clusters as a function of the frequency of one the fields, keeping the other frequency fixed (see text for more details).
... The average cluster length as a function of the frequency of the vertical rotating field.
... The mean cluster speed as a function of the frequency of the vertical rotating field.
... Plot of the dependence of the average chain-length as a function of the frequency of the rotating field. The effect of the viscous force limiting the cluster size is clearly seen even though the frequency is small. Obviously, the interval of frequency at which the average cluster length drops depends on the liquid viscosity.
... Average Mason number as a function of the frequency. Inset: Average Mason number as a function of the phase shift.
Contributors:Gonzalo J. Revuelta, Subramaniam Uthayathas, Amy E. Wahlquist, Stewart A. Factor, Stella M. Papa
NHP FOG developed in 14 out of 29 monkeys (48%) with stable parkinsonism, as follows: 2 monkeys were from the prospective examination group of 6 animals, and 12 from the retrospective review group of 23 animals (videotapes of NHP FOG were available on 5 cases in retrospective review). NHP FOG were sudden episodes lasting from several seconds to approximately 1min, with clear evidence that the monkeys were able to walk without freezing before and after each episode (see videotapes in Supplementary materials). The frequency of NHP FOG was not documented, however, it was consistently observed in successive morning “off” state evaluations. We could not identify any specific provoking factors, although typical provoking factors for humans were not utilized due to the inherent difficulties of evaluating caged monkeys. In some cases there was evidence of hesitation or trembling of the hind limb. In addition, when the monkey's gait froze, there appeared to be an associated generalized akinesia. NHP FOG could be observed during walking and climbing. A clear relation to starting or reaching the destination could not be established because of our inability to determine the animal's intention to stop suddenly or his predetermined destination. Monkeys with FOG also had a tendency to slowly flex the legs until sitting down after they froze, which does not occur in humans. But in the monkey, sitting is an easily reached position from the standing for quadrupedal gait. The individual demographic characteristics and the MPTP treatment in the FOG monkey group (n=14) are presented in detail in Table 1, and those in the non-FOG monkey group (n=15) in Supplementary materials, Table S1.... Analysis of the evolution of FOG episodes in the MPTP-treated monkey. A and B, recordings of leg movements with an accelerometer placed on the back of the leg during the whole duration of FOG episodes (~15s). Each episode (A and B) has regular oscillations corresponding to tremor before the end of freezing. The freezing episode showed in B also has some initial oscillatory movements that did not qualify as tremor according to the pre-established criteria. Also in B, the end of the freezing episode is followed by gait festination. The traces show raw accelerometry data. C and D, rate meters for the whole duration of the FOG episodes corresponding to A and B, respectively. The peaks correspond to the tremor periods towards the end of the freezing episode when walk restarts. Rate meters used the data produced after detection of full phase oscillations above the threshold. The graphs were constructed with a bin width of 500ms, and smoothed using a Gaussian filter. E, distribution of FOG tremor frequencies. The graph shows the frequencies (Hz) found across 20 recordings of tremor, each in a separate FOG episode. The average rate in the recorded tremors was 7.07Hz (±1.47 STD).
... Variability in the tremor associated with FOG in the MPTP-treated monkey. The oscillatory movements recorded with an accelerometer placed on the back of the leg during 3 episodes of tremor associated with FOG as examples of variability are shown in the three traces. The raster on top of each trace shows the detection of full phase oscillations above the threshold. The frequency and duration of the tremor were calculated on the constructed raster. Tremor frequencies in these episodes were: 6.0, 7.8, and 6.6Hz from top to bottom traces, respectively. Tremor durations in these episodes are shown next to each raster.
Contributors:Xianming Dai, Fanghao Yang, Ronggui Yang, Yung-Cheng Lee, Chen Li
Oscillating flows... Schematic of fluid flow on the micromembrane-enhanced evaporating surfaces in region I. (a) Proposed fluid distribution in heat transfer region. ((b) and (c)) Bubble and meniscus distributions on the surfaces at the heat flux of 9.0W/cm2, respectively. ((d)–(h)) Hypothesized interactions between fluid and vapor inside microchannels. (i) The number of visible bubbles in a single channel, nb, and total number of visible bubbles in active channels, Nc nb, in the low heat flux region. (j) Oscillatingfrequency in a single channel, f, and the total frequency in the channel array, i.e., the product of active channel number and the frequency of a single channel, Nc·f, in the low heat flux region.
... Schematic of fluid flow on the micromembrane-enhanced evaporating surfaces in region III. (a) Hypothesized fluid low and liquid distributions inside the structure. ((b) and (c)) Bubble and meniscus distributions on the surfaces at the heat flux of 61.4W/cm2, respectively. (d) The number of visible bubbles in a single channel, nb, and total number of visible bubbles in active channels, Nc·nb, in the high heat flux region. (d) Bubble growth and collapse frequency, fgc, in the high heat flux region.
The large amplitude vibration of stay cables has been observed in several cable-stayed bridges under the simultaneous occurrence of rain and wind, which is called rain–wind induced vibration (RWIV). During RWIV, the upper rivulet oscillating circumferentially on the inclined cable surface is widely considered to have an important role in this phenomenon. However, the small size of rivulets and high sensitivity to wind flow make the measurement of the rivulet movement challenging. This study proposes a digital image processing method to measure the rivulet movement in wind tunnel tests. RWIV of a cable model was excited during the test and a digital video camera was used to record the video clips of the rivulets, from which the time history of the rivulet movement along the entire cable is identified through image processing. The oscillation amplitude, equilibrium position, and dominant frequency of the upper rivulet are investigated. Results demonstrated that the proposed non-contact, non-intrusive measurement method is cost-effective and has good resolution in measuring the rivulet vibration. Finally the rivulet vibration characteristics were also studied when the cable was fixed. Comparison demonstrates the relation between the upper rivulet and cable vibration.
Contributors:Sandra J. Niederschuh, Hartmut Witte, Manuela Schmidt
Forelimb (“limb”) stride frequency and whisking (“whisk”) frequency. Range, mean value±SD, and speed dependence (F-value and coefficient of determination r2 in %).
... Variation of frequency across the speed range on the continuous (con) and discontinuous (dis) substrate in the presence (vib pres) or absence (carp abs) of carpal vibrissae. (A) Forelimb stride frequency. (B) Whisking frequency.
... Temporal and spatial parameters of forelimb kinematics compared across all subsets of data: all vibrissae present (vp), carpal vibrissae absent (ca), mystacial vibrissae absent (ma), and all vibrissae absent (va). Box plots illustrate the median (bold line), the range between the upper and the lower quartile (box) and maximum and minimum values. (A) Forelimb stride frequency. (B) Forepaw placement relative to the anterior margin of the orbita (=X0). (C) Limb angle at touchdown.
Contributors:Ida Rishal, Naaman Kam, Rotem Ben-Tov Perry, Vera Shinder, Elizabeth M.C. Fisher, Giampietro Schiavo, Mike Fainzilber
Motor-Based Models for Cell-Length Sensing
(A) A gradient-based model wherein length-encoding signals are actively transported by dynein from axon tip to cell body, with a constant rate of signal loss en route. At an early time point (T1), axons are short and signal levels at the cell body are high. At later time points (T2 and T3) the accumulating signal loss along longer tracts will reduce signal levels in the cell body.
(B) Retrograde signal levels at the cell body during axon elongation from simulations of the gradient model at high (blue), medium (red), and low (green) dynein levels, respectively. Reduced dynein levels result in shorter axon lengths (e.g., using threshold indicated by horizontal line in main graph; inset).
(C) A bidirectional mechanism wherein anterograde signals are transported by a kinesin from cell body to axon tip, where they activate dynein-dependent retrograde signaling to the cell body, which then represses the anterograde signal via negative feedback.
(D) The model configuration of (C) generates an oscillating retrograde signal, the frequency of which decreases with axon elongation.
(E and F) If axons stop growing once the signal drops below a certain frequency threshold, the simulations predict that decreasing levels of kinesin, dynein, or both motors together will lead to longer axons, as shown in (F) for growth arrest at a normalized frequency threshold of 0.02.
See also Figure S1 and Movie S1.
... Modeling, Related to Figure 1
(A and B) (A) Kinesin and (B) dynein velocity distributions used for the simulations (Deinhardt et al., 2006; Seitz and Surrey, 2006).
(C and D) A single positive feedback loop model generates a non-informative retrograde signal.
(E and F) A similar model incorporating two positive feedback steps likewise generates a non-informative retrograde signal.
(G) Dominant frequency extraction in signals obtained from the composite negative feedback loop model of Figures 1C and 1D. For further details, see Extended Experimental Procedures.
... Movie S1. Illustration of a Simulation Run for the Frequency-Based Model, Related to Figures 1C and 1D