Soft-Clamped Silicon Nitride String Resonators at Millikelvin Temperatures.

We demonstrate that soft-clamped silicon nitride strings with a large aspect ratio can be operated at mK temperatures. The quality factors (Q) of two measured devices show consistent dependency on the cryostat temperature, with soft-clamped mechanical modes reaching Q>10^{9} at roughly 46 mK. For low optical readout power, Q is found to saturate, indicating good thermalization between the sample and the stage it is mounted on. Our best device exhibits a calculated force sensitivity of 9.6 zN/sqrt[Hz] and a thermal decoherence time of 0.38 s, which bode well for future applications such as nanomechanical force sensing.

Strong Parametric Coupling between Two Ultracoherent Membrane Modes.

We demonstrate parametric coupling between two modes of a silicon nitride membrane. We achieve the coupling by applying an oscillating voltage to a sharp metal tip that approaches the membrane surface to within a few 100 nm. When the voltage oscillation frequency is equal to the mode frequency difference, the modes exchange energy periodically and faster than their free energy decay rate. This flexible method can potentially be useful for rapid state control and transfer between modes, and is an important step toward parametric spin sensing experiments with membrane resonators.

Noninvasive observation of skeletal muscle contraction using near-infrared time-resolved reflectance and diffusing-wave spectroscopy.

We introduce a method for noninvasively measuring muscle contraction in vivo, based on near-infrared diffusing-wave spectroscopy (DWS). The method exploits the information about time-dependent shear motions within the contracting muscle that are contained in the temporal autocorrelation function g(1)(τ,t) of the multiply scattered light field measured as a function of lag time, τ, and time after stimulus, t. The analysis of g(1)(τ,t) measured on the human M. biceps brachii during repetitive electrical stimulation, using optical properties measured with time-resolved reflectance spectroscopy, shows that the tissue dynamics giving rise to the speckle fluctuations can be described by a combination of diffusion and shearing. The evolution of the tissue Cauchy strain e(t) shows a strong correlation with the force, indicating that a significant part of the shear observed with DWS is due to muscle contraction. The evolution of the DWS decay time shows quantitative differences between the M. biceps brachii and the M. gastrocnemius, suggesting that DWS allows to discriminate contraction of fast- and slow-twitch muscle fibers.

Scraping and stapling of end-grafted DNA chains by a bioadhesive spreading vesicle to reveal chain internal friction and topological complexity.

Stained end-grafted DNA molecules about 20 µm long are scraped away and stretched out by the spreading front of a bioadhesive vesicle. Tethered biotin ligands bind the vesicle bilayer to a streptavidin substrate, stapling the DNAs into frozen confinement paths. Image analysis of the stapled DNA gives access, within optical resolution, to the local stretching values of individual DNA molecules swept by the spreading front, and provides evidence of self-entanglements.

Processing of emotional words measured simultaneously with steady-state visually evoked potentials and near-infrared diffusing-wave spectroscopy.

BACKGROUND: Emotional stimuli are preferentially processed compared to neutral ones. Measuring the magnetic resonance blood-oxygen level dependent (BOLD) response or EEG event-related potentials, this has also been demonstrated for emotional versus neutral words. However, it is currently unclear whether emotion effects in word processing can also be detected with other measures such as EEG steady-state visual evoked potentials (SSVEPs) or optical brain imaging techniques. In the present study, we simultaneously performed SSVEP measurements and near-infrared diffusing-wave spectroscopy (DWS), a new optical technique for the non-invasive measurement of brain function, to measure brain responses to neutral, pleasant, and unpleasant nouns flickering at a frequency of 7.5 Hz. RESULTS: The power of the SSVEP signal was significantly modulated by the words' emotional content at occipital electrodes, showing reduced SSVEP power during stimulation with pleasant compared to neutral nouns. By contrast, the DWS signal measured over the visual cortex showed significant differences between stimulation with flickering words and baseline periods, but no modulation in response to the words' emotional significance. CONCLUSIONS: This study is the first investigation of brain responses to emotional words using simultaneous measurements of SSVEPs and DWS. Emotional modulation of word processing was detected with EEG SSVEPs, but not by DWS. SSVEP power for emotional, specifically pleasant, compared to neutral words was reduced, which contrasts with previous results obtained when presenting emotional pictures. This appears to reflect processing differences between symbolic and pictorial emotional stimuli. While pictures prompt sustained perceptual processing, decoding the significance of emotional words requires more internal associative processing. Reasons for an absence of emotion effects in the DWS signal are discussed.

Diffusing-wave spectroscopy with dynamic contrast variation: disentangling the effects of blood flow and extravascular tissue shearing on signals from deep tissue.

We investigate the effects of blood flow and extravascular tissue shearing on diffusing-wave spectroscopy (DWS) signals from deep tissue, using an ex vivo porcine kidney model perfused artificially at controlled arterial pressure and flow. Temporal autocorrelation functions g((1))(τ) of the multiply scattered light field show a decay which is described by diffusion for constant flow, with a diffusion coefficient scaling linearly with volume flow rate. Replacing blood by a non-scattering fluid reveals a flow-independent background dynamics of the extravascular tissue. For a sinusoidally driven perfusion, field autocorrelation functions g((1))(τ, t') depend on the phase t' within the pulsation cycle and are approximately described by diffusion. The effective diffusion coefficient D(eff)(t') is modulated at the driving frequency in the presence of blood, showing coupling with flow rate; in the absence of blood, D(eff)(t') is modulated at twice the driving frequency, indicating shearing of extravascular tissue as the origin of the DWS signal. For both constant and pulsatile flow the contribution of extravascular tissue shearing to the DWS signal is small.

Force-induced unfolding of human telomeric G-quadruplex: a steered molecular dynamics simulation study.

We study the unfolding of a parallel G-quadruplex from human telomeric DNA by mechanical stretching using steered molecular dynamics (MD) simulation. We find that the force curves and unfolding processes strongly depend on the pulling sites. With pulling sites located on the sugar-phosphate backbone, the force-extension curve shows a single peak and the unfolding proceeds sequentially. Pulling sites located on the terminal nucleobases lead to a force-extension curve with two peaks and the unfolding is more cooperative. Simulations of the refolding of partially unfolded quadruplexes show very different behavior for the two different pulling modalities. In particular, starting from an unfolded state prepared by nucleobase pulling leads to a long-lived intermediate state whose existence is also corroborated by the free energy profile computed with the Jarzynski equation. Based on this observation, we propose a novel folding pathway for parallel G-quadruplexes with the human telomere sequence.

Spreading of bio-adhesive vesicles on DNA carpets.

Cell-adhesion events involve often the formation of a contact region between phospholipid membranes decorated with a variety of bio-macromolecular species. We mimic here such hairy bio-adhesive contact zones by spreading phospholipid vesicles onto surfaces carpeted with end-grafted λ-phage DNA. Our study reveals that the spreading front acts as a scraper that strongly stretches the DNA molecules, and that the multiple bonds created during vesicle spreading effectively staple the stretched chains in the gap between the membrane and the substrate. The scraping and stapling mechanisms revealed here for the long DNA molecules are expected to also play a role in actual bio-adhesion events of cell walls and tissues.

Activity of the human visual cortex measured non-invasively by diffusing-wave spectroscopy.

Activity of the human visual cortex, elicited by steady-state flickering at 8Hz, is non-invasively probed by multi-speckle diffusingwave spectroscopy (DWS). Parallel detection of the intensity fluctuations of statistically equivalent, but independent speckles allows to resolve stimulation-induced changes in the field autocorrelation of multiply scattered light of less than 2%. In a group of 9 healthy subjects we find a faster decay of the field autocorrelation function during the stimulation periods for data measured with a long-distance probe (30mm source-receiver distance) at 2 positions over the occipital cortex (t-test: t(8) = -2.672, p = 0.028 < 0.05 for position 1, t(8) = -2.874, p = 0.021 < 0.05 for position 2). In contrast, no statistically significant change is seen when a short-distance probe (16mm source-receiver distance) is used (t-test: t(8) = -2.043, p = 0.075 > 0.05 for position 1, t(8) = -2.146, p = 0.064 > 0.05 for position 2). The enhanced dynamics observed with DWS is positively correlated with the functional increase of blood volume in the visual cortex, while the heartbeat rate is not affected by stimulation. Our results indicate that the DWS signal from the visual cortex is governed by the regional cerebral blood flow velocity.

Pulsation-resolved deep tissue dynamics measured with diffusing-wave spectroscopy.

We present a technique for measuring transient microscopic dynamics within deep tissue with sub-second temporal resolution, using diffusing-wave spectroscopy with gated single-photon avalanche photodiodes (APDs) combined with standard ungated multi-tau correlators. Using the temporal autocorrelation function of a reference signal allows to correct the temporal intensity autocorrelation function of the sample signal for the distortions induced by the non-constant average photon count rate. We apply this technique to pulsation-synchronized measurements of tissue dynamics in humans. Measurements on the forearm show no dependence on the pulsation phase. In contrast, the decay rate of the DWS signal measured on the wrist over the radial artery shows a pulsation-induced modulation of 60-90% consistent with pulsatile variations of arterial erythrocyte flow velocity. This might make time-resolved DWS interesting as a sensitive and fast method for investigating deep tissue perfusion, e.g. in intensive care.

Diffusing-wave spectroscopy from head-like tissue phantoms: influence of a non-scattering layer.

We investigate the influence of a non-scattering layer on the temporal field autocorrelation function of multiple scattered light from a multilayer turbid medium such as the human head. Data from Monte Carlo simulations show very good agreement with the predictions of the correlation-diffusion equation with boundary conditions taking into account non-diffusive light transport within the non-scattering layer. Field autocorrelation functions measured at the surface of a multilayer phantom including a non-scattering layer agree well with theory and simulations when the source-receiver distance is significantly larger than the depth and the thickness of the non-scattering layer. Our results show that for source-receiver distances large enough to probe the dynamics in the human cortex, the cortical diffusion coefficient obtained by analyzing field autocorrelation functions neglecting the presence of the non-scattering cerebrospinal fluid layer is underestimated by about~$40\,\%$ in situations representative of the human head.

Noninvasive detection of functional brain activity with near-infrared diffusing-wave spectroscopy.

We use near-infrared dynamic multiple scattering of light [diffusing-wave spectroscopy (DWS)] to detect the activation of the somato-motor cortex in 11 right-handed volunteers performing a finger opposition task separately with their right and left hands. Temporal autocorrelation functions g(1)(r,tau) of the scattered light field are measured during 100-s periods of motor task alternating with 100-s resting baseline periods. From an analysis of the experimental data with an analytical theory for g(1)(r,tau) from a three-layer geometry with optical and dynamical heterogeneity representing scalp, skull, and cortex, we obtain quantitative estimates of the diffusion coefficient in cortical regions. Consistent with earlier results, the measured cortical diffusion coefficient is found to be increased during the motor task, with a strong contralateral and a weaker ipsilateral increase consistent with the known brain hemispheric asymmetry for right-handed subjects. Our results support the interpretation of the increase of the cortical diffusion coefficient during finger opposition being due to the functional increase in cortical blood flow rate related to vasodilation.