Laboratoire d'Énergétique Moléculaire et Macroscopique, Combustion

A thermal light-emitting source, such as a black body or the incandescent filament of a light bulb, is often presented as a typical example of an incoherent source and is in marked contrast to a laser. Whereas a laser is highly monochromatic and very directional, a thermal source has a broad spectrum and is usually quasi-isotropic. However, as is the case with many systems, different behaviour can be expected on a microscopic scale. It has been shown recently that the field emitted by a thermal source made of a polar material is enhanced by more than four orders of magnitude and is partially coherent at a distance of the order of 10 to 100nm. Here we demonstrate that by introducing a periodic microstructure into such a polar material (SiC) a thermal infrared source can be fabricated that is coherent over large distances (many wavelengths) and radiates in well defined directions. Narrow angular emission lobes similar to antenna lobes are observed and the emission spectra of the source depends on the observation angle--the so-called Wolf effect. The origin of the coherent emission lies in the diffraction of surface-phonon polaritons by the grating.

A subgrid scale model for large eddy simulations of turbulent premixed combustion is developed and validated. The approach is based on the concept of artificially thickened flames, keeping constant the laminar flame speed sl0. This thickening is simply achieved by decreasing the pre-exponential factor of the chemical Arrhenius law whereas the molecular diffusion is enhanced. When the flame is thickened, the combustion–turbulence interaction is affected and must be modeled. This point is investigated here using direct numerical simulations of flame–vortex interactions and an efficiency function E is introduced to incorporate thickening effects in the subgrid scale model. The input parameters in E are related to the subgrid scale turbulence (velocity and length scales). An efficient approach, based on similarity assumptions, is developed to extract these quantities from the resolved velocity field. A specific operator is developed to exclude the dilatational part of the velocity field from the estimation of turbulent fluctuations. The combustion model is then implemented in a compressible parallel finite volume–element solver able to handle hybrid grids to simulate a lateral injections combustor (LIC). Results are in agreement with the available experimental data.

Although the concept of energy starvation in the failing heart was proposed decades ago, still very little is known about the origin of energetic failure. Recent advances in molecular biology have started to elucidate the transcriptional events governing mitochondrial biogenesis. In particular, a great step was taken with the discovery that peroxisome proliferator-activated receptor gamma co-activator (PGC-1alpha) is the master regulator of mitochondrial biogenesis. The molecular mechanisms underlying the downregulation of PGC-1alpha and the consequent decrease in mitochondrial function in heart failure are, however, still poorly understood. Indeed, the main pathways involved in mitochondrial biogenesis are thought to be up- rather than down-regulated in pathological hypertrophy and heart failure. The current review summarizes recent advances in this field and is restricted to the heart when cardiac data are available.

The platinum derivative cis-diamminedichloroplatinum(II), best known as cisplatin, is currently employed for the clinical management of patients affected by testicular, ovarian, head and neck, colorectal, bladder and lung cancers. For a long time, the antineoplastic effects of cisplatin have been fully ascribed to its ability to generate unrepairable DNA lesions, hence inducing either a permanent proliferative arrest known as cellular senescence or the mitochondrial pathway of apoptosis. Accumulating evidence now suggests that the cytostatic and cytotoxic activity of cisplatin involves both a nuclear and a cytoplasmic component. Despite the unresolved issues regarding its mechanism of action, the administration of cisplatin is generally associated with high rates of clinical responses. However, in the vast majority of cases, malignant cells exposed to cisplatin activate a multipronged adaptive response that renders them less susceptible to the antiproliferative and cytotoxic effects of the drug, and eventually resume proliferation. Thus, a large fraction of cisplatin-treated patients is destined to experience therapeutic failure and tumor recurrence. Throughout the last four decades great efforts have been devoted to the characterization of the molecular mechanisms whereby neoplastic cells progressively lose their sensitivity to cisplatin. The advent of high-content and high-throughput screening technologies has accelerated the discovery of cell-intrinsic and cell-extrinsic pathways that may be targeted to prevent or reverse cisplatin resistance in cancer patients. Still, the multifactorial and redundant nature of this phenomenon poses a significant barrier against the identification of effective chemosensitization strategies. Here, we discuss recent systems biology studies aimed at deconvoluting the complex circuitries that underpin cisplatin resistance, and how their findings might drive the development of rational approaches to tackle this clinically relevant problem.

About one third of patients with various malignant diseases were found to have extractable amounts of DNA in their plasma whereas no DNA could be detected in normal controls. Using the test established by one of us (M.B.), which is based on decreased strand stability of cancer cell DNA, we have found that several plasma DNA originate from cancer cells.

We adapt tools of transformation optics, governed by a (elliptic) wave equation, to thermodynamics, governed by the (parabolic) heat equation. We apply this new concept to an invibility cloak in order to thermally protect a region (a dead core) and to a concentrator to focus heat flux in a small region. We finally propose a multilayered cloak consisting of 20 homogeneous concentric layers with a piecewise constant isotropic diffusivity working over a finite time interval (homogenization approach).

Multidrug-resistant strain Acinetobacter baumannii BM4454 was isolated from a patient with a urinary tract infection. The adeB gene, which encodes a resistance-nodulation-cell division (RND) protein, was detected in this strain by PCR with two degenerate oligodeoxynucleotides. Insertional inactivation of adeB in BM4454, which generated BM4454-1, showed that the corresponding protein was responsible for aminoglycoside resistance and was involved in the level of susceptibility to other drugs including fluoroquinolones, tetracyclines, chloramphenicol, erythromycin, trimethoprim, and ethidium bromide. Study of ethidium bromide accumulation in BM4454 and BM4454-1, in the presence or in the absence of carbonyl cyanide m-chlorophenylhydrazone, demonstrated that AdeB was responsible for the decrease in intracellular ethidium bromide levels in a proton motive force-dependent manner. The adeB gene was part of a cluster that included adeA and adeC which encodes proteins homologous to membrane fusion and outer membrane proteins of RND-type three-component efflux systems, respectively. The products of two upstream open reading frames encoding a putative two-component regulatory system might be involved in the regulation of expression of the adeABC gene cluster.

Combustion instability is investigated in the case of a multiple inlet combustor with dump. It is shown that low-frequency instabilities are acoustically coupled and occur at the eigenfrequencies of the system. Using spark-schlieren and a special phase-average imaging of the C 2 -radical emission, the fluid-mechanical processes involved in a vortex-driven mode of instability are investigated. The phase-average images provide maps of the local non-steady heat release. From the data collected on the combustor the processes of vortex shedding, growth, interactions and burning are described. The phases between the pressure, velocity and heat-release fluctuations are determined. The implications of the global Rayleigh criterion are verified and a mechanism for low-frequency vortex-driven instabilities is proposed.

Analysis of combustion instabilities relies in most cases on linear analysis but most observations of these processes are carried out in the nonlinear regime where the system oscillates at a limit cycle. The objective of this paper is to deal with these two manifestations of combustion instabilities in a unified framework. The flame is recognized as the main nonlinear element in the system and its response to perturbations is characterized in terms of generalized transfer functions which assume that the gain and phase depend on the amplitude level of the input. This ‘describing function’ framework implies that the fundamental frequency is predominant and that the higher harmonics generated in the nonlinear element are weak because the higher frequencies are filtered out by the other components of the system. Based on this idea, a methodology is proposed to investigate the nonlinear stability of burners by associating the flame describing function with a frequency-domain analysis of the burner acoustics. These elements yield a nonlinear dispersion relation which can be solved, yielding growth rates and eigenfrequencies, which depend on the amplitude level of perturbations impinging on the flame. This method is used to investigate the regimes of oscillation of a well-controlled experiment. The system includes a resonant upstream manifold formed by a duct having a continuously adjustable length and a combustion region comprising a large number of flames stabilized on a multipoint injection system. The growth rates and eigenfrequencies are determined for a wide range of duct lengths. For certain values of this parameter we find a positive growth rate for vanishingly small amplitude levels, indicating that the system is linearly unstable. The growth rate then changes as the amplitude is increased and eventually vanishes for a finite amplitude, indicating the existence of a limit cycle. For other values of the length, the growth rate is initially negative, becomes positive for a finite amplitude and drops to zero for a higher value. This indicates that the system is linearly stable but nonlinearly unstable. Using calculated growth rates it is possible to predict amplitudes of oscillation when the system operates on a limit cycle. Mode switching and instability triggering may also be anticipated by comparing the growth rate curves. Theoretical results are found to be in excellent agreement with measurements, indicating that the flame describing function (FDF) methodology constitutes a suitable framework for nonlinear instability analysis.

The higher second-harmonic efficiency, in powder, of a new organic molecular crystal N-(4-nitrophenyl)-(L)-prolinol (NPP) is reported. Electronic polarizability of NPP molecules relates to that of other para-nitroaniline-like structures such as that of previously reported N-(2,4-dinitrophenyl) methyl alaninate (MAP), and the increase in crystalline nonlinear efficiency by one order of magnitude above the latter is ascribed to an ‘‘optimized’’ crystalline structure rather than to minor changes of the molecular hyperpolarizability. The simultaneous chiral and hydrogen-bonding character of the prolinol electron-donating group leads to a quasioptimal angle, with respect to quadratic phase-matched nonlinear interactions, between the molecular transition dipole moments and the twofold axis of the monoclinic P21 crystal structure. Based on a simple oriented gas description of the quasiplanar structure of the crystal, two possible mutually exclusive second-harmonic phase-matched configurations are evidenced and shown to promote the optimized nonlinear tensor coefficient.

Gut microbiota composition influences the clinical benefit of immune checkpoints in patients with advanced cancer but mechanisms underlying this relationship remain unclear. Molecular mechanism whereby gut microbiota influences immune responses is mainly assigned to gut microbial metabolites. Short-chain fatty acids (SCFA) are produced in large amounts in the colon through bacterial fermentation of dietary fiber. We evaluate in mice and in patients treated with anti-CTLA-4 blocking mAbs whether SCFA levels is related to clinical outcome. High blood butyrate and propionate levels are associated with resistance to CTLA-4 blockade and higher proportion of Treg cells. In mice, butyrate restrains anti-CTLA-4-induced up-regulation of CD80/CD86 on dendritic cells and ICOS on T cells, accumulation of tumor-specific T cells and memory T cells. In patients, high blood butyrate levels moderate ipilimumab-induced accumulation of memory and ICOS + CD4 + T cells and IL-2 impregnation. Altogether, these results suggest that SCFA limits anti-CTLA-4 activity.

This paper presents formulation of computationally efficient models of photoionization produced by non-thermal gas discharges in air based on three-group Eddington and improved Eddington (SP3) approximations to the radiative transfer equation, and on effective representation of the classic integral model for photoionization in air developed by Zheleznyak et al (1982) by a set of three Helmholtz differential equations. The reported formulations represent extensions of ideas advanced recently by Ségur et al (2006) and Luque et al (2007), and allow fast and accurate solution of photoionization problems at different air pressures for the range 0.1< pO2 R< 150 Torr cm , where pO2 is the partial pressure of molecular oxygen in air in units of Torr ( pO2=150 Torr at atmospheric pressure) and R in cm is an effective geometrical size of the physical system of interest. The presented formulations can be extended to other gases and gas mixtures subject to availability of related emission, absorption and photoionization coefficients. The validity of the developed models is demonstrated by performing direct comparisons of the results from these models and results obtained from the classic integral model. Specific validation comparisons are presented for a set of artificial sources of photoionizing radiation with different Gaussian dimensions, and for a realistic problem involving development of a double-headed streamer at ground pressure. The reported results demonstrate the importance of accurate definition of the boundary conditions for the photoionization production rate for the solution of second order partial differential equations involved in the Eddington, SP3 and the Helmholtz formulations. The specific algorithms derived from the classic photoionization model of Zheleznyak et al (1982), allowing accurate calculations of boundary conditions for differential equations involved in all three new models described in this paper, are presented. It is noted that the accurate formulation of boundary conditions represents an important task needed for a successful extension of the proposed formulations to two- and three-dimensional physical systems with obstacles of complex geometry (i.e. electrodes, dust particles, aerosols, etc), which are opaque for the photoionizing UV photons.

We propose in this article an unambiguous definition of the local density of electromagnetic states (LDOS) in a vacuum near an interface in equilibrium at temperature T. We show that the LDOS depends only on the electric-field Green function of the system but does not reduce in general to the trace of its imaginary part, as often is used in the literature. We illustrate this result by a study of the LDOS variations with the distance to an interface and point out deviations from the standard definition. We show nevertheless that this definition remains correct at frequencies close to the material resonances such as surface polaritons. We also study the feasibility of detecting such a LDOS with apertureless scanning near-field optical microscope (SNOM) techniques. We first show that a thermal near-field emission spectrum above a sample should be detectable and that this measurement could give access to the electromagnetic LDOS. It is further shown that the apertureless SNOM is the optical analog of the scanning tunneling microscope, which is known to detect the electronic LDOS. We also discuss some recent SNOM experiments aimed at detecting the electromagnetic LDOS.

The AdeABC pump of Acinetobacter baumannii BM4454, which confers resistance to various antibiotic classes including aminoglycosides, is composed of the AdeA, AdeB, and AdeC proteins; AdeB is a member of the RND superfamily. The adeA, adeB, and adeC genes are contiguous and adjacent to adeS and adeR, which are transcribed in the opposite direction and which specify proteins homologous to sensors and regulators of two-component systems, respectively (S. Magnet, P. Courvalin, and T. Lambert, Antimicrob. Agents Chemother. 45:3375-3380, 2001). Analysis by Northern hybridization indicated that the three genes were cotranscribed, although mRNAs corresponding to adeAB and adeC were also present. Cotranscription of the two regulatory genes was demonstrated by reverse transcription-PCR. Inactivation of adeS led to aminoglycoside susceptibility. Transcripts corresponding to adeAB were not detected in susceptible A. baumannii CIP 70-10 but were present in spontaneous gentamicin-resistant mutants obtained in vitro. Analysis of these mutants revealed the substitutions Thr153-->Met in AdeS downstream from the putative His-149 site of autophosphorylation, which is presumably responsible for the loss of phosphorylase activity by the sensor, and Pro116-->Leu in AdeR at the first residue of the alpha(5) helix of the receiver domain, which is involved in interactions that control the output domain of response regulators. These mutations led to constitutive expression of the pump and, thus, to antibiotic resistance. These data indicate that the AdeABC pump is cryptic in wild A. baumannii due to stringent control by the AdeRS two-component system.

The structure of premixed turbulent flames is a problem of fundamental interest in combustion theory. Possible flame geometries have been imagined and diagrams indicating the corresponding regimes of combustion have been constructed on the basis of essentially intuitive and dimensional considerations. A new approach to this problem is described in the present paper. An extended definition of flamelet regimes based on the existence of a continuous active (not quenched) flame front separating fresh gases and burnt products is first introduced. Direct numerical simulations of flame/vortex interactions using the full Navier–Stokes equations and a simplified chemistry model are then performed to predict flame quenching by isolated vortices. The formulation includes non-unity Lewis number, non-constant viscosity and heat losses so that the effect of stretch, curvature, transient dynamics and viscous dissipation can be accounted for. As a result, flame quenching by vortices (which is one of the key processes in premixed turbulent combustion) may be computed accurately. The effects of curvature and viscous dissipation on flame/vortex interactions may also be characterized by the same simulations. The influence of non-unity Lewis number and of thermo-diffusive processes in turbulent premixed combustion is discussed by comparing flame responses for two values of the Lewis number ( Le = 0.8 and 1.2). An elementary (‘spectral’) diagram giving the response of one flame to a vortex pair is constructed. This spectral diagram is then used, along with certain assumptions, to establish a turbulent combustion diagram similar to those proposed by Borghi (1985) or Williams (1985). Results show that flame fronts are much more resistant to quenching by vortices than expected from the classical theories. A cut-off scale and a quenching scale are also obtained and compared with the characteristic scales proposed by Peters (1986). Results show that strain is not the only important parameters determining flame/vortex interaction. Heat losses, curvature, viscous dissipation and transient dynamics have significant effects, especially for small scales and they strongly influence the boundaries of the combustion regimes. It is found, for example, that the Klimov–Williams criterion which is generally advocated to limit the flamelet region, underestimates the size of this region by more than an order of magnitude.

Thirteen human bifidobacterial strains were tested for their abilities to adhere to human enterocyte-like Caco-2 cells in culture. The adhering strains were also tested for binding to the mucus produced by the human mucus-secreting HT29-MTX cell line in culture. A high level of calcium-independent adherence was observed for Bifidobacterium breve 4, for Bifidobacterium infantis 1, and for three fresh human isolates from adults. As observed by scanning electron microscopy, adhesion occurs to the apical brush border of the enterocytic Caco-2 cells and to the mucus secreted by the HT29-MTX mucus-secreting cells. The bacteria interacted with the well-defined apical microvilli of Caco-2 cells without cell damage. The adhesion to Caco-2 cells of bifidobacteria did not require calcium and was mediated by a proteinaceous adhesion-promoting factor which was present both in the bacterial whole cells and in the spent supernatant of bifidobacterium culture. This adhesion-promoting factor appeared species specific, as are the adhesion-promoting factors of lactobacilli. We investigated the inhibitory effect of adhering human bifidobacterial strains against intestinal cell monolayer colonization by a variety of diarrheagenic bacteria. B. breve 4, B. infantis 1, and fresh human isolates were shown to inhibit cell association of enterotoxigenic, enteropathogenic, diffusely adhering Escherichia coli and Salmonella typhimurium strains to enterocytic Caco-2 cells in a concentration-dependent manner. Moreover, B. breve 4 and B. infantis 1 strains inhibited, dose dependently, Caco-2 cell invasion by enteropathogenic E. coli, Yersinia pseudotuberculosis, and S. typhimurium strains.

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Malignant breast tissue contains a rare population of multi-potent cells with the capacity to self-renew; these cells are known as cancer stem-like cells (CSCs) or tumor-initiating cells. Primitive mammary CSCs/progenitor cells can be propagated in culture as floating spherical colonies termed 'mammospheres'. We show here that the expression of the autophagy protein Beclin 1 is higher in mammospheres established from human breast cancers or breast cancer cell lines (MCF-7 and BT474) than in the parental adherent cells. As a result, autophagic flux is more robust in mammospheres. We observed that basal and starvation-induced autophagy flux is also higher in aldehyde dehydrogenase 1-positive (ALDH1(+)) population derived from mammospheres than in the bulk population. Beclin 1 is critical for CSC maintenance and tumor development in nude mice, whereas its expression limits the development of tumors not enriched with breast CSCs/progenitor cells. We found that decreased survival in autophagy-deficient cells (MCF-7 Atg7 knockdown cells) during detachment does not contribute to an ultimate deficiency in mammosphere formation. This study demonstrates that a prosurvival autophagic pathway is critical for CSC maintenance, and that Beclin 1 plays a dual role in tumor development.

We report a quantitative model of a near-field thermophotovoltaic (TPV) device consisting in a thermal source located in the near field of a TPV cell. The enhanced radiative transfer at short distance leads to an increase of the photogeneration current. We analyze quantitatively other potential near-field effects, in particular, on the dark current. We also study the influence of the modification of the spectrum of the sources in the near field, comparing the case of a tungsten source with the case of a quasimonochromatic source. Our model leads to a quantitative evaluation of the near-field TPV device output electric power and efficiency.

A large body of evidence suggests that an increase in the brain beta-amyloid (Abeta) burden contributes to the etiology of Alzheimer's disease (AD). Much is now known about the intracellular processes regulating the production of Abeta, however, less is known regarding its secretion from cells. We now report that p-glycoprotein (p-gp), an ATP-binding cassette (ABC) transporter, is an Abeta efflux pump. Pharmacological blockade of p-gp rapidly decrease extracellular levels of Abeta secretion. In vitro binding studies showed that addition of synthetic human Abeta1-40 and Abeta1-42 peptides to hamster mdr1-enriched vesicles labeled with the fluorophore MIANS resulted in saturable quenching, suggesting that both peptides interact directly with the transporter. Finally, we were able to directly measure transport of Abeta peptides across the plasma membranes of p-gp enriched vesicles, and showed that this phenomenon was both ATP- and p-gp-dependent. Taken together, our study suggests a novel mechanism of Abeta detachment from cellular membranes, and represents an obvious route towards identification of such a mechanism in the brain.