Alfv\'en-dynamo balance and magnetic excess in MHD turbulence

3D Magnetohydrodynamic (MHD) turbulent flows with initially magnetic and kinetic energies at equipartition spontaneously develop a magnetic excess (or residual energy), as well in numerical simulations and in the solar wind. Closure equations obtained in 1983 describe the residual spectrum as being produced by a dynamo source proportional to the total energy spectrum, balanced by a linear Alfv\'en damping term. A good agreement was found in 2005 with incompressible simulations; however, recent solar wind measurements disagree with these results. The previous dynamo-Alfv\'en theory is generalized to a family of models, leading to simple relations between residual and total energy spectra. We want to assess these models in detail against MHD simulations and solar wind data. The family of models is tested against compressible decaying MHD simulations with low Mach number, low cross-helicity, zero mean magnetic field, without or with expansion terms (EBM or expanding box model). A single dynamo-Alfv\'en model is found to describe correctly both solar wind scalings and compressible simulations without or with expansion. It is equivalent to the 1983-2005 closure equation but with critical balance of nonlinear turnover and linear Alfv\'en times, while the dynamo source term remains unchanged. The discrepancy with previous incompressible simulations is elucidated. The model predicts a linear relation between the spectral slopes of total and residual energies $m_R = -1/2 + 3/2 m_T$. Examining the solar wind data as in \cite{2013ApJ...770..125C}, our relation is found to be valid whatever the cross-helicity, even better so at high cross-helicity, with the total energy slope varying from $1.7$ to $1.55$.Comment: 7 pages, 7 figures, accepted for publication in A&

Unsaturated fatty acid regulation of cytochrome P450 expression via a CAR-dependent pathway.

The liver is responsible for key metabolic functions, including control of normal homoeostasis in response to diet and xenobiotic metabolism/detoxification. We have shown previously that inactivation of the hepatic cytochrome P450 system through conditional deletion of POR (P450 oxidoreductase) induces hepatic steatosis, liver growth and P450 expression. We have exploited a new conditional model of POR deletion to investigate the mechanism underlying these changes. We demonstrate that P450 induction, liver growth and hepatic triacylglycerol (triglyceride) homoeostasis are intimately linked and provide evidence that the observed phenotypes result from hepatic accumulation of unsaturated fatty acids, which mediate these phenotypes by activation of the nuclear receptor CAR (constitutive androstane receptor) and, to a lesser degree, PXR (pregnane X receptor). To our knowledge this is the first direct evidence that P450s play a major role in controlling unsaturated fatty acid homoeostasis via CAR. The regulation of P450s involved in xenobiotic metabolism by this mechanism has potentially significant implications for individual responses to drugs and environmental chemicals

Three-dimensional Iroshnikov-Kraichnan turbulence in a mean magnetic field

Forced, weak MHD turbulence with guide field is shown to adopt different regimes, depending on the magnetic excess of the large forced scales. When the magnetic excess is large enough, the classical perpendicular cascade with $5/3$ scaling is obtained, while when equipartition is imposed, an isotropic $3/2$ scaling appears in all directions with respect to the mean field (\cite{2010PhRvE..82b6406G} or GM10). We show here that the $3/2$ scaling of the GM10 regime is not ruled by a small-scale cross-helicity cascade, and propose that it is a 3D extension of a perpendicular weak Iroshnikov-Kraichnan (IK) cascade. We analyze in detail the structure functions in real space and show that they closely follow the critical balance relation both in the local frame and the global frame: we show that there is no contradiction between this and the isotropic $3/2$ scaling of the spectra. We propose a scenario explaining the spectral structure of the GM10 regime, that starts with a perpendicular weak IK cascade and extends to 3D by using quasi-resonant couplings. The quasi-resonance condition happens to reduce the energy flux in the same way as is done in the weak perpendicular cascade, so leading to a $3/2$ scaling in all directions. We discuss the possible applications of these findings to solar wind turbulence.Comment: Major re-write of manuscrip

Anisotropy of third-order structure functions in MHD turbulence

The measure of the third-order structure function, Y, is employed in the solar wind to compute the cascade rate of turbulence. In the absence of a mean field B0=0, Y is expected to be isotropic (radial) and independent of the direction of increments, so its measure yields directly the cascade rate. For turbulence with mean field, as in the solar wind, Y is expected to become more two dimensional (2D), that is, to have larger perpendicular components, loosing the above simple symmetry. To get the cascade rate one should compute the flux of Y, which is not feasible with single-spacecraft data, thus measurements rely upon assumptions about the unknown symmetry. We use direct numerical simulations (DNS) of magneto-hydrodynamic (MHD) turbulence to characterize the anisotropy of Y. We find that for strong guide field B0=5 the degree of two-dimensionalization depends on the relative importance of shear and pseudo polarizations (the two components of an Alfv\'en mode in incompressible MHD). The anisotropy also shows up in the inertial range. The more Y is 2D, the more the inertial range extent differs along parallel and perpendicular directions. We finally test the two methods employed in observations and find that the so-obtained cascade rate may depend on the angle between B0 and the direction of increments. Both methods yield a vanishing cascade rate along the parallel direction, contrary to observations, suggesting a weaker anisotropy of solar wind turbulence compared to our DNS. This could be due to a weaker mean field and/or to solar wind expansion.Comment: Some text editing and typos corrected, 13 pages, 6 figures, to be published in Ap

Aortic volume determines global end-diastolic volume measured by transpulmonary thermodilution

BACKGROUND: Global end-diastolic volume (GEDV) measured by transpulmonary thermodilution is regarded as indicator of cardiac preload. A bolus of cold saline injected in a central vein travels through the heart and lung, but also the aorta until detection in a femoral artery. While it is well accepted that injection in the inferior vena cava results in higher values, the impact of the aortic volume on GEDV is unknown. In this study, we hypothesized that a larger aortic volume directly translates to a numerically higher GEDV measurement. METHODS: We retrospectively analyzed data from 88 critically ill patients with thermodilution monitoring and who did require a contrast-enhanced thoraco-abdominal computed tomography scan. Aortic volumes derived from imaging were compared with GEDV measurements in temporal proximity. RESULTS: Median aortic volume was 194 ml (interquartile range 147 to 249 ml). Per milliliter increase of the aortic volume, we found a GEDV increase by 3.0 ml (95% CI 2.0 to 4.1 ml, p < 0.001). In case a femoral central venous line was used for saline bolus injection, GEDV raised additionally by 2.1 ml (95% CI 0.5 to 3.7 ml, p = 0.01) per ml volume of the vena cava inferior. Aortic volume explained 59.3% of the variance of thermodilution-derived GEDV. When aortic volume was included in multivariate regression, GEDV variance was unaffected by sex, age, body height, and weight. CONCLUSIONS: Our results suggest that the aortic volume is a substantial confounding variable for GEDV measurements performed with transpulmonary thermodilution. As the aorta is anatomically located after the heart, GEDV should not be considered to reflect cardiac preload. Guiding volume management by raw or indexed reference ranges of GEDV may be misleading

Cytochrome P450 CYP1B1 interacts with 8-<i>methoxypsoralen</i> (8-MOP) and influences psoralen-Ultraviolet A (PUVA) sensitivity

Background: There are unpredictable inter-individual differences in sensitivity to psoralen-UVA (PUVA) photochemotherapy, used to treat skin diseases including psoriasis. Psoralens are metabolised by cytochrome P450 enzymes (P450), and we hypothesised that variability in cutaneous P450 expression may influence PUVA sensitivity. We previously showed that P450 CYP1B1 was abundantly expressed in human skin and regulated by PUVA, and described marked inter-individual differences in cutaneous CYP1B1 expression.Objectives: We investigated whether CYP1B1 made a significant contribution to 8-methoxypsoralen (8-MOP) metabolism, and whether individuality in CYP1B1 activity influenced PUVA sensitivity.Methods: We used E. coli membranes co-expressing various P450s and cytochrome P450 reductase (CPR) to study 8-MOP metabolism and cytotoxicity assays in CYP1B1-expressing mammalian cells to assess PUVA sensitivity.Results: We showed that P450s CYP1A1, CYP1A2, CYP1B1, CYP2A6 and CYP2E1 influence 8-MOP metabolism. As CYP1B1 is the most abundant P450 in human skin, we further demonstrated that: (i) CYP1B1 interacts with 8-MOP (ii) metabolism of the CYP1B1 substrates 7-ethoxyresorufin and 17-b-estradiol showed concentration-dependent inhibition by 8-MOP and (iii) inhibition of 7-ethoxyresorufin metabolism by 8-MOP was influenced by CYP1B1 genotype. The influence of CYP1B1 on PUVA cytotoxicity was further investigated in a Chinese hamster ovary cell line, stably expressing CYP1B1 and CPR, which was more sensitive to PUVA than control cells, suggesting that CYP1B1 metabolises 8-MOP to a more phototoxicmetabolite(s).Conclusion: Our data therefore suggest that CYP1B1 significantly contributes to cutaneous 8-MOP metabolism, and that individuality in CYP1B1 expression may influence PUVA sensitivity

Rapid prototyping of reflectors for vehicle lighting using laser activated remote phosphor

Bright white light sources are of significant importance for automotive front lighting systems. Todays upper class vehicles mainly use HID or LED as light source. As a further step in this development laser diode based systems offer high luminance, efficiency and allow the realization of new styling concepts and new dynamic lighting functions. These white laser diode systems can either be realized by mixing different spectral sources or by combining diodes with specific phosphors. Based on the approach of generating light using a laser and remote phosphor, lighting modules are manufactured. Four blue laser diodes (450 nm) are used to activate a phosphor coating and thus to achieve white light. A segmented paraboloid reflector generates the desired light distribution for an additional car headlamp. We use high speed milling and selective laser melting to build the reflector system for this lighting module. We compare the spectral reflection grade of these materials. Furthermore the generated modules are analyzed regarding their efficiency and light distribution. The use of Rapid Prototyping technologies allows an early validation of the chosen concept and is supposed to reduce cost and time in the product development process significantly. Therefor we discuss costs and times of the applied manufacturing technologies

HDAC inhibitors increase NRF2-signaling in tumour cells and blunt the efficacy of co-adminstered cytotoxic agents

The NRF2 signalling cascade provides a primary response against electrophilic chemicals and oxidative stress. The activation of NRF2-signaling is anticipated to have adverse clinical consequences; NRF2 is activated in a number of cancers and, additionally, its pharmacological activation by one compound can reduce the toxicity or efficiency of a second agent administered concomitantly. In this work, we have analysed systematically the ability of 152 research, pre-clinical or clinically used drugs to induce an NRF2 response using the MCF7-AREc32 NRF2 reporter. Ten percent of the tested drugs induced an NRF2 response. The NRF2 activators were not restricted to classical cytotoxic alkylating agents but also included a number of emerging anticancer drugs, including an IGF1-R inhibitor (NVP-AEW541), a PIM-1 kinase inhibitor (Pim1 inhibitor 2), a PLK1 inhibitor (BI 2536) and most strikingly seven of nine tested HDAC inhibitors. These findings were further confirmed by demonstrating NRF2-dependent induction of endogenous AKR genes, biomarkers of NRF2 activity. The ability of HDAC inhibitors to stimulate NRF2-signalling did not diminish their own potency as antitumour agents. However, when used to pre-treat cells, they did reduce the efficacy of acrolein. Taken together, our data suggest that the ability of drugs to stimulate NRF2 activity is common and should be investigated as part of the drug-development process