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Biomedical subjects

B Perrin

Publications and source records attributed to B Perrin.

At least 19 recordsLinked to original sources

Subterahertz phonon dynamics in acoustic nanocavities.

We report a direct determination of the dynamic behavior of confined acoustic phonons in nanocavities by picosecond acoustics. We provide the broadband, high resolution transmission amplitude curve in the subterahertz range, and we give evidence of resonant transmission peaks in three successive stop bands, in quantitative agreement with acoustic simulations. We furthermore demonstrate transit times in the nanosecond range at the cavity peaks reflecting the strong confinement of resonant phonons within the cavity layer. On the other hand, picosecond transit times are measured in the stop band, shorter than in any of the constituting materials, a tunneling effect well known both in photonic crystals and in macroscopic phononic systems.

Journal Article↗

Individual and collective vibrational modes of nanostructures studied by picosecond ultrasonics.

We report on picosecond ultrasonic measurements obtained on aluminum and platinum nanostructures with variable dot size and lateral periodicity which realized a 2D phononic crystal. Performing investigations at different resolution scales, we have identified individual modes of vibration depending on the dot size, and mode of vibration strongly correlated with the bi-dimensional organization. The platinum dots sputtered on an aluminum layer have shown a behavior of isolated oscillators without any coupling between neighbor elements in this phononic crystal. The frequency of such normal modes, extracted from time resolved measurements are in good agreement with 3D finite element simulations. In contrast, with aluminum dot systems where the coupling is more efficient we observe a complex spectrum of vibrational modes related to the band structure induced by the bi-dimensional patterning.

Algorithms↗

Generation and detection of incoherent phonons in picosecond ultrasonics.

In picosecond ultrasonics experiments the absorption of a femtosecond laser pulse in a thin metallic transducer is used to generate very short acoustic pulses. These pulses are made of coherent longitudinal waves with a frequency spectrum that can reach 100-200 GHz. The laser pulse absorption gives rise to a heating of the film of a few Kelvin within a typical time of 1 ps. Later on, the heat goes in the substrate through an interface thermal resistance and is diffused by thermal conduction. At very low temperature and in pure crystals the thermal phonons emitted by the heated metallic film can propagate ballistically over large distances and produce a so-called heat pulse. We report on the experimental evidence of the coexistence of the coherent acoustic pulse and the incoherent heat pulse generated and detected by laser ultrasonics.

Journal Article↗

Simulations of the active transport of a neutral solute based on a kinase-channel-phosphatase topology.

Simulations of coupled interactions involving two opposite enzymatic reactions, solute diffusions, and electrostatic interactions between membrane charges and charged solutes were conducted under a fixed kinase-channel-phosphatase (KCP) topology oriented from the outside to the inside of a porous membrane structure. Depending on the kinase and phosphatase locations, we recently demonstrated that an active transport of a phosphorylated substrate may occur via the opposite topology, that is, a PCK topology. The present analysis demonstrates that, under a KCP membrane topology, which also behaves as a specific ATP-dependent transporter, the active transport of a neutral substrate may occur. This analogous active transport appears to be dependent on the phosphatase location and on the membrane surface potentials. A broad analysis of the role played by the main parameters taken into account in the model was conducted in order to define precisely the physico-chemical conditions and the membrane topology needed for the highest active transports within the shortest time.

Biological Transport, Active↗

Isoform specific function of calpain 2 in regulating membrane protrusion.

Previous studies have demonstrated a role for calpains in cell migration through their capacity to regulate focal adhesion dynamics and rear retraction. In this study, we provide evidence that calpains also modulate membrane protrusion activity in fibroblasts. We find that an immortalized Capn4(-/-) fibroblast line displays an altered morphology, characterized by numerous thin membrane projections and increased transient membrane activity. Furthermore, we show that protrusion kinetics of lamellipodia at the leading edge are improperly regulated in Capn4(-/-) cells, leading to impaired net forward lamellipodial extension. To address the isoform specific functions of calpain 1 and calpain 2 during cell protrusion, we stably introduced small interfering RNAs (siRNAs) targeting each isoform into a fibroblast cell line. Despite a loss in calpain 1 activity, calpain 1 knockdown cells show normal morphology and membrane protrusion dynamics. However, cells in which calpain 2 is knocked down are characterized by a protrusive morphology, increased transient membrane activity and altered protrusion kinetics, similar to the Capn4(-/-) fibroblasts. Additionally, we find that calpain 2, but not calpain 1, is required for proteolysis of the cytoskeletal and focal adhesion proteins FAK, paxillin, spectrin, and talin. Together, our findings support a novel role for calpain 2 in limiting membrane protrusions and in regulating lamellipodial dynamics at the leading edge of migrating cells.

Animals↗

ATP-dependent active transport simulations based on a phosphatase-channel-kinase membrane structure.

Simulations of coupled interactions involving enzymatic reaction diffusion and electrostatic interactions were conducted under a fixed phosphatase-channel-kinase (PCK) topology oriented from the outside to the inside of a charged membrane structure. Depending on the phosphatase and kinase locations, we recently demonstrated that active transport of a phosphorylated substrate may occur via this PCK topology. The present analysis demonstrates that, if in addition to this topology, a phosphatase activity (P(1)) is also present on the inner side of the membrane, but outside the unstirred layer surrounding the inner membrane surface, then active transport of the corresponding unphosphorylated substrate may also occur. Therefore, this PCK membrane topology, which behaves as a specific ATP-dependent transporter, appears as a general topology permitting; first, on its own the active transport of a phosphorylated substrate; second, when associated with a phosphatase acting in the bulk of the receiver compartment, the active transport of the corresponding unphosphorylated substrate, that is, in most cases, the transport of an uncharged substrate. The general mathematical model given permits the active transport of a phosphorylated substrate to be analyzed (in the absence of P(1)), the active transport of an unphosphorylated substrate (in the presence of P(1)), whatever the charge distributions on both sides of the membrane surface and whatever the positions of the membrane-bound phosphatase and the membrane-bound kinase. This general model also takes into account the consumption of ATP occurring into the receiver compartment during the time course of these transport phenomena. A broad analysis of the role played by the main parameters taken into account in the model was conducted to precisely define the physicochemical conditions and the membrane topology needed for the highest active transports within the shortest time.

Adenosine Triphosphate↗

Key roles of enzyme positions and membrane surface potentials in the properties of biomimetic membranes.

The coupling of diffusion, reaction, and electrostatic interactions existing in the microenvironment of permeable and charged bi-enzymatic membranes has led to the concept of biomimetic membranes. These membranes permit the active and specific transport of small hydrophilic molecules against their concentration gradients, at constant temperature and pressure. This study shows that such membranes behave in totally different ways, depending both on the relative position of the two enzymes, either within or outside the ionic double layer, and on the membrane surface potentials.

Biomimetic Materials↗

Formulation of a coupled mechanism between solute diffusion, phosphatase-kinase reactions and membrane potentials for the primary active transport of phosphorylated substrates through biological membranes.

Coupled interrelations occurring between a phosphatase/kinase reaction sequence acting in unstirred layers and on both sides of a charged biomembrane pore structure are presented as a plausible kinetic model for the primary active transport of phosphorylated molecules. Simulations conducted at the cell level and with credible numerical values demonstrate that the enzymes positions strongly regulate the membrane permeability for the transported substrate. Depending on both the enzymes positions (more or less far from the membrane) and the membrane charges, the membrane may appear either impervious, either permeable or able to actively transport a phosphorylated substrate. Globally all happens as if, in function of the enzymes positions, a permanent pore may be regulated, changing from a more closed to a more open conformation.

Animals↗

Anisotropic nonlinear elastic properties of an icosahedral quasicrystal

We show that the nonlinear behavior of transverse acoustic waves can reveal the anisotropic structure of an icosahedral quasicrystal, at the macroscopic level. We report experiments performed in i-Al-Pd-Mn. We observe that a primary transverse acoustic wave can generate a second harmonic transverse acoustic wave. We also observe a specific relation between the polarization directions of those waves. These observations are manifestations on a macroscopic scale of the long-range order in quasicrystals.

Journal Article↗

Investigation of dose homogeneity in paediatric anthropomorphic phantoms for a simple total body irradiation technique.

The technique for treating total body irradiation patients used at the centre involves no compensation for the inhomogeneity of patient shape. Dose is prescribed to the lung, and monitor units are derived from standard data depending on the external dimensions of the patient at nipple level. Dose measurements were made during standard treatments on three paediatric anthropomorphic phantoms representing children of 5, 10 and 15 years of age. The results confirmed that the measured dose to the lung was within 4% of the prescribed dose, and dose homogeneity was within +/- 5%, excluding the neck, where the higher measured doses were still within tissue tolerance.

Child↗

Effect of factor Xa inhibitors on the platelet-derived microparticles procoagulant activity in vitro and in vivo in rats.

The aim of this study was to investigate the effect of factor Xa inhibitors on the prothrombinase activity of platelet-derived microparticles in vitro and in vivo. The factor Xa inhibitors studied were DX9065A (a direct factor Xa inhibitor) and Sanorg34006 (an antithrombin (AT)-mediated factor Xa inhibitor). Microparticles formed from the platelet surface following activation were isolated by size exclusion gel chromatography. After purification, their presence was detected by their procoagulant activity and by flow cytometry. Our results show that factor Xa and/or factor Va were present at the surface of the platelet-derived microparticles. Prothrombinase formed on the microparticles was inhibited by factor Xa inhibitors at IC50 values of 0.45+/-0.05 and 0.045+/-0.005 microM for DX9065A and AT-Sanorg34006 respectively. In an experiment aimed at determining the kinetics of microparticles formation we demonstrated that thrombin traces were sufficient to induce the formation of a significant quantity of microparticles. Both factor Xa inhibitors delayed the formation of microparticles by delaying thrombin generation. The thrombogenic effect of the microparticles were studied in vivo in a modified arterio-venous shunt model in the rat. In this model, the increase in the thrombus weigh due to microparticles or phospholipids did not differ significantly (33% and 23% respectively). In these conditions, prothrombinase activity seemed to play a lesser role in the thrombogenic effect than phospholipids. Nevertheless, factor Xa inhibitors were efficient and inhibited thrombus formation in a dose-dependent manner. These results demonstrate that platelet-derived microparticles display a potent prothrombotic effect in vivo and show that factor Xa inhibitors are potent antithrombotic compounds when thrombosis was induced by microparticles.

Animals↗

Follow up of workers previously exposed to silver solder containing cadmium.

OBJECTIVES: To study longitudinal biological monitoring data on urinary and blood cadmium collected in a small cohort of nine workers who had been brazing for several years with solders containing cadmium. METHODS: Cadmium was measured by neutron activation analysis in livers and kidneys, and estimates of renal function were carried out in 1983 and 1995. During the intervening period exposure to cadmium was dramatically reduced by local exhaust ventilation control and substitution of the solder containing cadmium. RESULTS: From urinary protein measurements there was evidence within the group of increasing renal tubular damage over the 12 year period, even though exposure to cadmium was dramatically reduced over this period and almost eliminated by 1995. There was no evidence from serum creatinine of decreasing glomerular filtration rate, and the renal tubular handling of calcium, phosphate, or urate had not worsened significantly. Blood and urinary cadmium concentrations reduced significantly over the 12 year period but were still substantial in 1995. Blood cadmium concentrations tended to reflect cadmium body burden in 1995 when exposure had been low for several years, and decreased most significantly during 1983-90. By contrast urinary cadmium concentrations only decreased significantly from about 1990 onwards. Urinary cadmium was not significantly correlated with liver or kidney cadmium concentration in either 1983 or 1995. This may be due to the level of tubular dysfunction in the cohort. Calculated cumulative excretion of cadmium over the 12 year period was substantially greater than the loss of cadmium measured in livers and kidneys and the derived loss in body burden. Reasons for this are discussed. It is possible that in cohorts, where renal damage is apparent, urinary concentrations reflect a substantial component of current exposure rather than stored body losses. CONCLUSIONS: The data reinforce the concept that blood cadmium concentrations may not always reflect recent exposure, but may reflect body burden derived from historical exposure depending on the degree of current exposure; and that the decline in urinary and blood cadmium measurements after removal from, or reduction in, exposure will be slow and depend on the historical body burden.

Adult↗

A European inter-laboratory trial to evaluate the reliability of serological diagnosis of bovine herpesvirus 1 infections.

The detection of cattle latently infected with bovine herpesvirus 1 (BHV1) is of importance in control programs and in international trade activities. Therefore, tests to detect specific antibodies in serum must be highly sensitive. To evaluate the reliability of serological diagnosis of BHV1 infections in Europe, seventeen laboratories in 15 European countries were asked to determine BHV1-specific antibodies in a panel of bovine serum samples using the serological tests available in their laboratory. Laboratory tests included virus neutralisation tests (1, 2 and 24 h), indirect immunofluorescence tests and ELISAs. The serum panel consisted of 12 duplicate lyophilised samples which were randomly coded from 1 to 24 and included negative, weak- and strong-positive samples as well as international reference sera. Virus neutralisation tests and ELISAs showed a high specificity. All participants using neutralisation tests (n = 13) scored the negative samples correctly. Twenty three of 25 ELISAs showed 100% specificity. A serum sample obtained at day 7 after infection was scored as negative by all tests except one home-made blocking ELISA. Samples obtained at day 9 and at day 11 after infection were scored as positive by approximately half and by all tests, respectively. To score the weak-positive European reference standard (EU2) correctly, 24 h neutralisation tests (positive by 8 of 9 laboratories) and home-made blocking ELISAs (positive by 5 of 6 laboratories) were the most reliable. The results indicate that standardisation is urgently needed to ensure that BHV1-infected animals with low antibody titres are recognised.

Animals↗