Transverse spin forces and non-equilibrium particle dynamics in a circularly polarized vacuum optical trap.

We provide a vivid demonstration of the mechanical effect of transverse spin momentum in an optical beam in free space. This component of the Poynting momentum was previously thought to be virtual, and unmeasurable. Here, its effect is revealed in the inertial motion of a probe particle in a circularly polarized Gaussian trap, in vacuum. Transverse spin forces combine with thermal fluctuations to induce a striking range of non-equilibrium phenomena. With increasing beam power we observe (i) growing departures from energy equipartition, (ii) the formation of coherent, thermally excited orbits and, ultimately, (iii) the ejection of the particle from the trap. As well as corroborating existing measurements of spin momentum, our results reveal its dynamic effect. We show how the under-damped motion of probe particles in structured light fields can expose the nature and morphology of optical momentum flows, and provide a testbed for elementary non-equilibrium statistical mechanics.

PCAF ubiquitin ligase activity inhibits Hedgehog/Gli1 signaling in p53-dependent response to genotoxic stress.

The Hedgehog (Hh) signaling regulates tissue development, and its aberrant activation is a leading cause of malignancies, including medulloblastoma (Mb). Hh-dependent tumorigenesis often occurs in synergy with other mechanisms, such as loss of p53, the master regulator of the DNA damage response. To date, little is known about mechanisms connecting DNA-damaging events to morphogen-dependent processes. Here, we show that genotoxic stress triggers a cascade of signals, culminating with inhibition of the activity of Gli1, the final transcriptional effector of Hh signaling. This inhibition is dependent on the p53-mediated elevation of the acetyltransferase p300/CBP-associated factor (PCAF). Notably, we identify PCAF as a novel E3 ubiquitin ligase of Gli1. Indeed PCAF, but not a mutant with a deletion of its ubiquitination domain, represses Hh signaling in response to DNA damage by promoting Gli1 ubiquitination and its proteasome-dependent degradation. Restoring Gli1 levels rescues the growth arrest and apoptosis effect triggered by genotoxic drugs. Consistently, DNA-damaging agents fail to inhibit Gli1 activity in the absence of either p53 or PCAF. Finally, Mb samples from p53-null mice display low levels of PCAF and upregulation of Gli1 in vivo, suggesting PCAF as potential therapeutic target in Hh-dependent tumors. Together, our data define a mechanism of inactivation of a morphogenic signaling in response to genotoxic stress and unveil a p53/PCAF/Gli1 circuitry centered on PCAF that limits Gli1-enhanced mitogenic and prosurvival response.

Static and dynamic behavior of two optically bound microparticles in a standing wave.

It is generally accepted that the interaction between particles mediated by the scattered light (called optical binding) is very weak. Therefore, the optical binding is usually neglected in a multi-particle trapping in distinct optical traps. Here we show that even the presence of only two dielectric particles confined in the standing wave leads to their significantly different behavior comparing to the case of a single trapped particle. We obtained persuading coincidence between our experimental records and the results of the deterministic and stochastic theoretical simulations based on the coupled dipole method.

Experimental and theoretical determination of optical binding forces.

We present an experimental and theoretical study of long distance optical binding effects acting upon micro-particles placed in a standing wave optical field. In particular we present for the first time quantitatively the binding forces between individual particles for varying inter-particle separations, polarizations and incident angles of the binding beam. Our quantitative experimental data and numerical simulations show that these effects are essentially enhanced due to the presence of a reflective surface in a sample chamber. They also reveal conditions to form stable optically bound clusters of two and three particles in this geometry. We also show that the inter-particle separation in the formed clusters can be controlled by altering the angle of the beam incident upon the sample plane. This demonstrates new perspectives for the generation and control of optically bound soft matter and may be useful to understand various inter-particle effects in the presence of reflective surfaces.

Septic and technical complications of central venous catheterization. A prospective study of 200 consecutive patients.

The results of central venous catheterization for total parenteral nutrition were prospectively evaluated in 200 consecutive patients. All catheters were fabricated of polyurethane tubing inserted by the Seldinger technique. Two hundred sixty-three lines were inserted in 200 patients for a total of 4103 days. Major complications occurred in 2.3% patients. Twenty-four per cent of catheters were associated with suspected sepsis; of these, 52% were removed directly and 48% were changed over a guidewire. The total catheter sepsis rate was 5.7%. The incidence of sepsis correlated with the number of attempts to insert the line and with positive skin cultures. These data indicate that: use of the Seldinger technique to insert nonthrombogenic flexible catheters results in lower technical morbidity; the incidence of established infection is much lower than the incidence of suspected sepsis; guidewire change may be performed without risk to the patient or interruption of therapy; sepsis rates can be decreased by reducing the number of attempts to catheterize the subclavian vein; and sepsis rates correlate with positive skin cultures at the insertion site.