Observation of the Brownian motion of a small probe interacting with its environment provides one of the main strategies for characterizing soft matter. Essentially, two counteracting forces govern the motion of the Brownian particle. First, the particle is driven by rapid collisions with the surrounding solvent molecules, referred to as thermal noise. Second, the friction between the particle and the viscous solvent damps its motion. Conventionally, the thermal force is assumed to be random and characterized by a Gaussian white noise spectrum. The friction is assumed to be given by the Stokes drag, suggesting that motion is overdamped at long times in particle tracking experiments, when inertia becomes negligible. However, as the particle receives momentum from the fluctuating fluid molecules, it also displaces the fluid in its immediate vicinity. The entrained fluid acts back on the particle and gives rise to long-range correlations. This hydrodynamic 'memory' translates to thermal forces, which have a coloured, that is, non-white, noise spectrum. One hundred years after Perrin's pioneering experiments on Brownian motion, direct experimental observation of this colour is still elusive. Here we measure the spectrum of thermal noise by confining the Brownian fluctuations of a microsphere in a strong optical trap. We show that hydrodynamic correlations result in a resonant peak in the power spectral density of the sphere's positional fluctuations, in strong contrast to overdamped systems. Furthermore, we demonstrate different strategies to achieve peak amplification. By analogy with microcantilever-based sensors, our results reveal that the particle-fluid-trap system can be considered a nanomechanical resonator in which the intrinsic hydrodynamic backflow enhances resonance. Therefore, instead of being treated as a disturbance, details in thermal noise could be exploited for the development of new types of sensor and particle-based assay in lab-on-a-chip applications.

The equilibrium dynamics of a spherical particle immersed in a complex Maxwell fluid is analyzed in terms of velocity autocorrelation function (VACF), mean-square displacement (MSD), and power spectral density (PSD). We elucidate the role of hydrodynamic memory and its interplay with medium viscoelasticity for a free and a harmonically confined particle. The elastic response at high frequencies introduces oscillations in the VACF, which are found to be strongly damped by the coupling to the fluid. We show that in all Maxwell fluids hydrodynamic memory eventually leads to a power-law decay in the VACF as is already known for Newtonian fluids. The MSD displays asymptotically an intermediate plateau reflecting the elastic restoring forces of the medium. In the frequency domain, the PSD exhibits at high frequencies a step due to the trapping, whereas the low-frequency decay reflects the viscoelastic relaxation. Our results suggest that high-frequency microrheology is well-suited to infer the elastic modulus, which is sensitive over a wide range of Maxwell times.

Calcineurin-inhibitor therapy can lead to renal dysfunction in heart transplantation patients. The novel immunosuppressive (IS) drug sirolmus (Srl) lacks nephrotoxic effects; however, proteinuria associated with Srl has been reported following renal transplantation. In cardiac transplantation, the incidence of proteinuria associated with Srl is unknown. In this study, long-term cardiac transplant patients were switched from cyclosporine to Srl-based IS. Concomitant IS consisted of mycophenolate mofetil ± steroids. Proteinuria increased significantly from a median of 0.13 g/day (range 0-5.7) preswitch to 0.23 g/day (0-9.88) at 24 months postswitch (p = 0.0024). Before the switch, 11.5% of patients had high-grade proteinuria (>1.0 g/day); this increased to 22.9% postswitch (p = 0.006). ACE inhibitor and angiotensin-releasing blocker (ARB) therapy reduced proteinuria development. Patients without proteinuria had increased renal function (median 42.5 vs. 64.1, p = 0.25), whereas patients who developed high-grade proteinuria showed decreased renal function at the end of follow-up (median 39.6 vs. 29.2, p = 0.125). Thus, proteinuria may develop in cardiac transplant patients after switch to Srl, which may have an adverse effect on renal function in these patients. Srl should be used with ACEi/ARB therapy and patients monitored for proteinuria and increased renal dysfunction.

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Charging mechanisms of trapped, element-selectively excited free SiO2 nanoparticles by soft x rays are reported. The absolute charge state of the particles is measured and the electron emission probability is derived. Changes in electron emission processes as a function of photon energy and particle charge are obtained from the charging current. This allows us to distinguish contributions from primary photoelectrons, Auger electrons, and secondary electrons. Processes leading to no change in charge state after absorption of x-ray photons are identified. O 1s-excited SiO2 particles of low charge state indicate that the charging current follows the inner-shell absorption. In contrast, highly charged SiO2 nanoparticles are efficiently charged by resonant Auger processes, whereas direct photoemission and normal Auger processes do not contribute to changes in particle charge. These results are discussed in terms of an electrostatic model.

We have developed an in situ method to calibrate optical tweezers experiments and simultaneously measure the size of the trapped particle or the viscosity of the surrounding fluid. The positional fluctuations of the trapped particle are recorded with a high-bandwidth photodetector. We compute the mean-square displacement, as well as the velocity autocorrelation function of the sphere, and compare it to the theory of Brownian motion including hydrodynamic memory effects. A careful measurement and analysis of the time scales characterizing the dynamics of the harmonically bound sphere fluctuating in a viscous medium directly yields all relevant parameters. Finally, we test the method for different optical trap strengths, with different bead sizes and in different fluids, and we find excellent agreement with the values provided by the manufacturers. The proposed approach overcomes the most commonly encountered limitations in precision when analyzing the power spectrum of position fluctuations in the region around the corner frequency. These low frequencies are usually prone to errors due to drift, limitations in the detection, and trap linearity as well as short acquisition times resulting in poor statistics. Furthermore, the strategy can be generalized to Brownian motion in more complex environments, provided the adequate theories are available.

elution with 5 mM sodium phosphate buffer on a phosphate-containing Dowex 1-X2 column. The free trisaccharide 3, whose interglycosidic linkages were confirmed by i H-NMR spectroscopy,"] was thereby obtained directly on a 50-pmol scale (yield: 31 mg, 52%).

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