Autologous tumor cell vaccination plus infusion of GM-CSF by a programmable pump in the treatment of recurrent malignant gliomas

International audienceWe report on the safety and feasibility of autologous tumor cell vaccination combined with infusion of granulocyte-macrophage colony-stimulating factor by a programmable pump in the treatment of recurrent malignant gliomas. The programmable pump is a promising tool used to infuse cytokines subcutaneously for vaccination. Our trial enrolled nine patients who had undergone surgery, radiation and had been successfully weaned off steroids. Unfortunately, only five patients completed the protocol and were monitored for side effects, local reactions, delayed-type hypersensitivity (DTH) responses and survival. The treatment was well tolerated. Two patients developed DTH reactions after vaccination and three patients had an unusually long survival without any other treatment. Despite the few patients treated, the results of this trial are encouraging. This study also highlights the specific difficulties encountered in vaccination programs for the treatment of glioma

Practical application and clinical impact of the WHO histopathological criteria on bone marrow biopsy for the diagnosis of essential thrombocythemia versus prefibrotic primary myelofibrosis

Aims: To evaluate the feasibility of the histopathological diagnosis of prefibrotic–early primary myelofibrosis (PM) as described in the World Health Organization (WHO) classification and to evaluate the clinical implications of prefibrotic–early PM in a series of patients previously diagnosed as having essential thrombocythemia (ET) according to the Polycythemia Vera Study Group criteria. Methods and results: WHO criteria were applied to bone marrow biopsy specimens by two pathologists who then reclassified 127 cases as 102 ET (80.3%), 18 prefibrotic–early PM (14.2%) and seven fibrotic PM (5.5%). In 45 cases (35%), the final diagnosis was only reached by consensus. The megakaryocytic criteria that best discriminated between ET and prefibrotic–early PM were an increased nucleo–cytoplasmic ratio, presence of cloudlike nuclei, hyperchromatic-dysplastic nuclei, paratrabecular megakaryocytes and tight clusters. A histological score discriminated between ET (score ≤3) and PM (score ≥6), but 21 cases showed an intermediate ambiguous score. No significant differences were observed at diagnosis and at follow-up (median time 93 months) for thrombosis, major haemorrhage, laboratory data, transformation into overt myeloid metaplasia and survival. Conclusions: The distinction between ET and prefibrotic–early PM is impaired by subjectivity in pathological practice and is of questionable clinical relevance, at least when considering individual patients

Characterization of integrated optics components for the second generation of VLTI instruments

Two of the three instruments proposed to ESO for the second generation instrumentation of the VLTI would use integrated optics for beam combination. Several design are studied, including co-axial and multi-axial recombination. An extensive quantity of combiners are therefore under test in our laboratories. We will present the various components, and the method used to validate and compare the different combiners. Finally, we will discuss the performances and their implication for both VSI and Gravity VLTI instruments.Comment: SPIE Astronomical Instrumentation 2008 in Marseille, France -- Equation (7) update

Fundamental limitations for quantum and nano thermodynamics

The relationship between thermodynamics and statistical physics is valid in the thermodynamic limit - when the number of particles becomes very large. Here, we study thermodynamics in the opposite regime - at both the nano scale, and when quantum effects become important. Applying results from quantum information theory we construct a theory of thermodynamics in these limits. We derive general criteria for thermodynamical state transformations, and as special cases, find two free energies: one that quantifies the deterministically extractable work from a small system in contact with a heat bath, and the other that quantifies the reverse process. We find that there are fundamental limitations on work extraction from nonequilibrium states, owing to finite size effects and quantum coherences. This implies that thermodynamical transitions are generically irreversible at this scale. As one application of these methods, we analyse the efficiency of small heat engines and find that they are irreversible during the adiabatic stages of the cycle.Comment: Final, published versio

Depinning of kinks in a Josephson-junction ratchet array

We have measured the depinning of trapped kinks in a ratchet potential using a fabricated circular array of Josephson junctions. Our ratchet system consists of a parallel array of junctions with alternating cell inductances and junctions areas. We have compared this ratchet array with other circular arrays. We find experimentally and numerically that the depinning current depends on the direction of the applied current in our ratchet ring. We also find other properties of the depinning current versus applied field, such as a long period and a lack of reflection symmetry, which we can explain analytically.Comment: to be published in PR

Reducing vortex density in superconductors using the ratchet effect

A serious obstacle that impedes the application of low and high temperature superconductor (SC) devices is the presence of trapped flux. Flux lines or vortices are induced by fields as small as the Earth's magnetic field. Once present, vortices dissipate energy and generate internal noise, limiting the operation of numerous superconducting devices. Methods used to overcome this difficulty include the pinning of vortices by the incorporation of impurities and defects, the construction of flux dams, slots and holes and magnetic shields which block the penetration of new flux lines in the bulk of the SC or reduce the magnetic field in the immediate vicinity of the superconducting device. Naturally, the most desirable would be to remove the vortices from the bulk of the SC. There is no known phenomenon, however, that could form the basis for such a process. Here we show that the application of an ac current to a SC that is patterned with an asymmetric pinning potential can induce vortex motion whose direction is determined only by the asymmetry of the pattern. The mechanism responsible for this phenomenon is the so called ratchet effect, and its working principle applies to both low and high temperature SCs. As a first step here we demonstrate that with an appropriate choice of the pinning potential the ratchet effect can be used to remove vortices from low temperature SCs in the parameter range required for various applications.Comment: 7 pages, 4 figures, Nature (in press

Ferrofluids as thermal ratchets

Colloidal suspensions of ferromagnetic nano-particles, so-called ferrofluids, are shown to be suitable systems to demonstrate and investigate thermal ratchet behavior: By rectifying thermal fluctuations, angular momentum is transferred to a resting ferrofluid from an oscillating magnetic field without net rotating component. Via viscous coupling the noise driven rotation of the microscopic ferromagnetic grains is transmitted to the carrier liquid to yield a macroscopic torque. For a simple setup we analyze the rotation of the ferrofluid theoretically and show that the results are compatible with the outcome of a simple demonstration experiment.Comment: 4 pages, 3 figures, corrected version, improved figures, to be published in Phys. Rev. Let

Enhanced diffusion due to active swimmers at a solid surface

We consider two systems of active swimmers moving close to a solid surface, one being a living population of wild-type \textit{E. coli} and the other being an assembly of self-propelled Au-Pt rods. In both situations, we have identified two different types of motion at the surface and evaluated the fraction of the population that displayed ballistic trajectories (active swimmers) with respect to those showing random-like behavior. We studied the effect of this complex swimming activity on the diffusivity of passive tracers also present at the surface. We found that the tracer diffusivity is enhanced with respect to standard Brownian motion and increases linearly with the activity of the fluid, defined as the product of the fraction of active swimmers and their mean velocity. This result can be understood in terms of series of elementary encounters between the active swimmers and the tracers.Comment: 4 pages, 2 figures in color, Physical Review Letters (in production

Fluctuating-friction molecular motors

We show that the correlated stochastic fluctuation of the friction coefficient can give rise to long-range directional motion of a particle undergoing Brownian random walk in a constant periodic energy potential landscape. The occurrence of this motion requires the presence of two additional independent bodies interacting with the particle via friction and via the energy potential, respectively, which can move relative to each other. Such three-body system generalizes the classical Brownian ratchet mechanism, which requires only two interacting bodies. In particular, we describe a simple two-level model of fluctuating-friction molecular motor that can be solved analytically. In our previous work [M.K., L.M and D.P. 2000 J. Nonlinear Opt. Phys. Mater. vol. 9, 157] this model has been first applied to understanding the fundamental mechanism of the photoinduced reorientation of dye-doped liquid crystals. Applications of the same idea to other fields such as molecular biology and nanotechnology can however be envisioned. As an example, in this paper we work out a model of the actomyosin system based on the fluctuating-friction mechanism.Comment: to be published in J. Physics Condensed Matter (http://www.iop.org/Journals/JPhysCM