50 research outputs found
Experimental assessment of the speed of light perturbation in free-fall absolute gravimeters
Precision absolute gravity measurements are growing in importance, especially
in the context of the new definition of the kilogram. For the case of free-fall
absolute gravimeters with a Michelson-type interferometer tracking the position
of a free falling body, one of the effects that needs to be taken into account
is the speed of light perturbation due to the finite speed of propagation of
light. This effect has been extensively discussed in the past, and there is at
present a disagreement between different studies. In this work, we present the
analysis of new data and confirm the result expected from the theoretical
analysis applied nowadays in free-fall gravimeters. We also review the standard
derivations of this effect (by using phase shift or Doppler effect arguments)
and show their equivalence
Simultaneous determination of wave speed and arrival time of reflected waves using the pressure-velocity loop
This is the post print version of the article. The official published version can be found at the link below.In a previous paper we demonstrated that the linear portion of the pressureâvelocity loop (PU-loop) corresponding to early systole could be used to calculate the local wave speed. In this paper we extend this work to show that determination of the time at which the PU-loop first deviates from linearity provides a convenient way to determine the arrival time of reflected waves (Tr). We also present a new technique using the PU-loop that allows for the determination of wave speed and Tr simultaneously. We measured pressure and flow in elastic tubes of different diameters, where a strong reflection site existed at known distances away form the measurement site. We also measured pressure and flow in the ascending aorta of 11 anaesthetised dogs where a strong reflection site was produced through total arterial occlusion at four different sites. Wave speed was determined from the initial slope of the PU-loop and Tr was determined using a new algorithm that detects the sampling point at which the initial linear part of the PU-loop deviates from linearity. The results of the new technique for detecting Tr were comparable to those determined using the foot-to-foot and wave intensity analysis methods. In elastic tubes Tr detected using the new algorithm was almost identical to that detected using wave intensity analysis and foot-to-foot methods with a maximum difference of 2%. Tr detected using the PU-loop in vivo highly correlated with that detected using wave intensity analysis (r 2 = 0.83, P < 0.001). We conclude that the new technique described in this paper offers a convenient and objective method for detecting Tr, and allows for the dynamic determination of wave speed and Tr, simultaneously
Therapeutic efficacy of regulable GDNF expression for Huntington's and Parkinson's disease by a high-induction, background-free "GeneSwitch" vector.
Gene therapy is currently an irreversible approach, without possibilities to fine-tune or halt the expression of a therapeutic gene product. Especially when expressing neurotrophic factors to treat neurodegenerative disorders, options to regulate transgene expression levels might be beneficial. We thus developed an advanced single-genome inducible AAV vector for expression of GDNF, under control of the approved small molecule drug mifepristone. In the rat brain, GDNF expression can be induced over a wide range up to three hundred-fold over endogenous background, and completely returns to baseline within 3-4âŻweeks. When applied with appropriate serotype and titre, the vector is absolutely free of any non-induced background expression. In the BACHD model of Huntington's disease we demonstrate that the vector can be kept in a continuous ON-state for extended periods of time. In a model of Parkinson's disease we demonstrate that repeated short-term expression of GDNF restores motor capabilities in 6-OHDA-lesioned rats. We also report on sex-dependent pharmacodynamics of mifepristone in the rodent brain. Taken together, we show that wide-range and high-level induction, background-free, fully reversible and therapeutically active GDNF expression can be achieved under tight pharmacological control by this novel AAV - "Gene Switch" vector
Production of CXC and CC chemokines by human antigen-presenting cells in response to Lassa virus or closely related immunogenic viruses, and in cynomolgus monkeys with lassa fever.
International audienceThe pathogenesis of Lassa fever (LF), a hemorrhagic fever endemic to West Africa, remains unclear. We previously compared Lassa virus (LASV) with its genetically close, but nonpathogenic homolog Mopeia virus (MOPV) and demonstrated that the strong activation of antigen-presenting cells (APC), including type I IFN production, observed in response to MOPV probably plays a crucial role in controlling infection. We show here that human macrophages (MP) produce large amounts of CC and CXC chemokines in response to MOPV infection, whereas dendritic cells (DC) release only moderate amounts of CXC chemokines. However, in the presence of autologous T cells, DCs produced CC and CXC chemokines. Chemokines were produced in response to type I IFN synthesis, as the levels of both mediators were strongly correlated and the neutralization of type I IFN resulted in an inhibition of chemokine production. By contrast, LASV induced only low levels of CXCL-10 and CXCL-11 production. These differences in chemokine production may profoundly affect the generation of virus-specific T-cell responses and may therefore contribute to the difference of pathogenicity between these two viruses. In addition, a recombinant LASV (rLASV) harboring the NP-D389A/G392A mutations, which abolish the inhibition of type I IFN response by nucleoprotein (NP), induced the massive synthesis of CC and CXC chemokines in both DC and MP, confirming the crucial role of arenavirus NP in immunosuppression and pathogenicity. Finally, we confirmed, using PBMC samples and lymph nodes obtained from LASV-infected cynomolgus monkeys, that LF was associated with high levels of CXC chemokine mRNA synthesis, suggesting that the very early synthesis of these mediators may be correlated with a favourable outcome
Separation of arterial pressure waves into their forward and backward running components
A new separation technique has been developed to determine the forward and backward running arterial pressure wave components. It takes into account friction as well as nonlinear effects due to convective acceleration and to the pressure dependence of the arterial compliance. The new method is a combination of two methods treating friction and nonlinearities separately. The method requires the measurements of pressure and flow at one location as well as the knowledge of the area-pressure relationship. The validity of the method was tested by a simulation experiment in which the forward and backward waves were known a priori. It was shown that the new method is significantly more accurate in the predictions of the forward and backward waves when compared to the classical method assuming linearity and no dissipation. The new wave separation method was also applied to simulated aortic waves for (a) a healthy subject and (b) a subject with decreased compliance. Comparison with the classical linear method showed that neglecting nonlinearities leads to an overestimation of the forward and backward pressure wave amplitudes. The errors, however, were in the order of 5 to 10 percent. We concluded that, for most clinical purposes, the improvement using the nonlinear method is of the same magnitude as experimental errors, and thus the linear method would suffice
Forward and backward waves in the arterial system: nonlinear separation using Riemann invariants
A nonlinear method has been developed to separate arterial pressure and flow waves into their forward and backward running components. It takes into account nonlinearities arising from the area-pressure relationship as well as convective acceleration. The method is based on the treatment of the Riemann invariants and requires measurements of pressure, flow and diameter at one arterial location. The method has been successfully tested by means of a simulation experiment in which the forward and backward waves were known a priori. It was shown that the new method is significantly more accurate in the predictions of the forward and backward waves when compared to the classical linear method. The new wave separation method was then applied to simulated aortic waves for a) a healthy subject and b) a subject with decreased compliance. Comparison with the classical linear method showed that neglecting nonlinearities leads to an overestimation of the forward and backward pressure wave amplitudes of the order of 5 to 10%
Modeling of the wave transmission properties of large arteries using nonlinear elastic tubes
We propose a new, simple way of constructing elastic tubes which can be used to model the nonlinear elastic properties of large arteries. The tube models are constructed from a silicon elastomer (Sylgard 184, Dow Corning), which exhibits a nonlinear behavior with increased stiffness at high strains. Tests conducted on different tube models showed that, with the proper choice of geometric parameters, the elastic properties, in terms of area-pressure relation and compliance, can be similar to that of real arteries
Separation of Arterial Pressure Waves Into Their Forward and Backward Running Components
Method for determining distribution of reflection sites in the arterial system
We developed a new method to determine the location and importance of reflection sites in the arterial system. The method is based on the decomposition of the aortic pressure wave into its forward and backward components, and it provides the reflection profile of the arterial system as a wave reflection site amplitude versus distance from the heart. The reflection profile can be seen as the response of the arterial system to a pressure delta pulse where reflections upstream from the measurement location have been eliminated. The method was successfully tested on a simple model loaded with a pure resistor, a two-element windkessel, and a bifurcating tube system. It was then applied to the aortic pressure and flow signals measured in six mongrel dogs whose aorta was occluded at different levels. The profiles obtained from measurements at control showed two main reflection regions, one located in the vicinity (0.1-0.2 m) of the heart and the other located in the region of the iliac bifurcation. All occlusions, even the most distant one at the iliac bifurcation, could be identified in both amplitude (amount of reflections) and distance from the heart. The spatial resolution of the profiles was approximately 0.1 m as a result of the limited power spectrum contained in the arterial pulse, and the identification of reflection sites decreased rapidly with the distance