Mechanisms Responsible for the Trophic Effect of Beta-Adrenoceptors on the I-to Current Density in Type 1 Diabetic Rat Cardiomyocytes

Background/Aims: In diabetic ventricular myocytes, transient outward potassium current (I-to) amplitude is severely reduced because of the impaired catecholamine release that characterizes diabetic autonomic neuropathy. Sympathetic nervous system exhibits a trophic effect on I-to since incubation of myocytes with noradrenaline restores current amplitude via beta-adrenoceptor (beta AR) stimulation. Here, we investigate the intracellular signalling pathway though which incubation of diabetic cardiomyocytes with the beta AR agonist isoproterenol recovers I-to amplitude to normal values. Methods: Experiments were performed in ventricular myocytes isolated from streptozotocin-diabetic rats. I-to current was recorded by using the patch-clamp technique. Kv4 channel expression was determined by immunofluorescence. Protein-protein interaction was determined by coimmunoprecipitation. Results: Stimulation of beta AR activates first a G alpha s protein, adenylyl cyclase and Protein Kinase A. PKA-phosphorylated receptor then switches to the G alpha i protein. This leads to the activation of the beta AR-Kinase-1 and further receptor phosphorylation and arrestin dependent internalization. The internalized receptor-arrestin complex recruits and activates cSrc and the MAPK cascade, where Ras, c-Raf1 and finally ERK1/2 mediate the increase in Kv4.2 and Kv4.3 protein abundance in the plasma membrane. Conclusion: beta(2)AR stimulation activates a G alpha s and G alpha i protein dependent pathway where the ERK1/2 modulates the Ito current amplitude and the density of the Kv4.2 and Kv4.2 channels in the plasma membrane upon sympathetic stimulation in diabetic heart.

Increase in the density of resting microglia precedes neuritic plaque formation and microglial activation in a transgenic model of Alzheimer's disease

The formation of cerebral senile plaques composed of amyloid beta peptide (A beta) is a fundamental feature of Alzheimer's disease (AD). Glial cells and more specifically microglia become reactive in the presence of A beta. In a triple transgenic model of AD (3 x Tg-AD), we found a significant increase in activated microglia at 12 (by 111%) and 18 (by 88%) months of age when compared with non-transgenic (non-Tg) controls. This microglial activation correlated with A beta plaque formation, and the activation in microglia was closely associated with A beta plaques and smaller A beta deposits. We also found a significant increase in the area density of resting microglia in 3 x Tg-AD animals both at plaque-free stage (at 9 months by 105%) and after the development of A plaques (at 12 months by 54% and at 18 months by 131%). Our results show for the first time that the increase in the density of resting microglia precedes both plaque formation and activation of microglia by extracellular A beta accumulation. We suggest that AD pathology triggers a complex microglial reaction: at the initial stages of the disease the number of resting microglia increases, as if in preparation for the ensuing activation in an attempt to fight the extracellular A beta load that is characteristic of the terminal stages of the disease. Cell Death and Disease (2010) 1, e1; doi:10.1038/cddis.2009.2; published online 14 January 2010

The diagnostics of density distribution for inhomogeneous dense DT plasmas using fast protons

The density distribution of inhomogeneous dense deuterium-tritium plasmas in laser fusion is revealed by the energy loss of fast protons going through the plasma. In our simulation of a plasma density diagnostics, the fast protons used for the diagnostics may be generated in the laser-plasma interaction. Dividing a two-dimensional area into grids and knowing the initial and final energies of the protons, we can obtain a large linear and ill-posed equation set. for the densities of all grids, which is solved with the Tikhonov regularization method. We find that the accuracy of the set plan with four proton sources is better than those of the set plans with less than four proton sources. Also we have done the density reconstruction especially. for four proton sources with and without assuming circularly symmetrical density distribution, and find that the accuracy is better for the reconstruction assuming circular symmetry. The error is about 9% when no noise is added to the final energy for the reconstruction of four proton sources assuming circular symmetry. The accuracies for different random noises to final proton energies with four proton sources are also calculated.

Time-resolved investigation of low-density plasma channels produced by a kilohertz femtosecond laser in air

By employing pump-probe back longitudinal diffractometry, the electron density and decay dynamics of a weak plasma channel created by a 1-KHz fs laser in air has been investigated. With ultrashort laser pulses of 50 fs and low energy of 0.6 mJ, we observe weak plasma channels with a length similar to 2 cm in air. An analytical reconstruction method of electron density has been analyzed, which is sensitive to the phase shift and channel size. The electron density in the weak plasma channel is extracted to be about 4x10(16) cm(-3). The diameters of the plasma channel and the filament are about 50 and 150 mu m, respectively, and the measurable electron density can be extended to less than 10(15) cm(-3). Moreover, a different time-frequency technique called linearly chirped longitudinal diffractometry is proposed to time-resolved investigate ultrafast ionization dynamics of laser-irradiated gas, laser interaction with cluster beam, etc.

Formalization of concept-relatedness using ontologies: conceptual density

370 p.

Bilingual Dictionary Drafting. The Example of German-Basque, a Medium-density Language Pair

Edited by Andrea Abel, Chiara Vettori, Natascia Ralli.

Influence of target thickness on the generation of high-density ion bunches by ultrashort circularly polarized laser pulses

Ion acceleration by ultrashort circularly polarized laser pulse in a solid-density target is investigated using two-dimensional particle-in-cell simulation. The ions are accelerated and compressed by the continuously extending space-charge field created by the evacuation and compression of the target electrons by the laser light pressure. For a sufficiently thin target, the accelerated and compressed ions can reach and exit from the rear surface as a high-density high-energy ion bunch. The peak ion energy depends on the target thickness and reaches maximum when the compressed ion layer can just reach the rear target surface. The compressed ion layer exhibits lateral striation which can be suppressed by using a sharp-rising laser pulse. (c) 2008 American Institute of Physics.

Direct acceleration of solid-density plasma bunch by ultraintense laser

The interaction of a petawatt laser with a small solid-density plasma bunch is studied by particle-in-cell simulation. It is shown that when irradiated by a laser of intensity >10(21) W/cm(2), a dense plasma bunch of micrometer size can be efficiently accelerated. The kinetic energy of the ions in the high-density region of the plasma bunch can exceed ten MeV at a density in the 10(23)-cm(-3) level. Having a flux density orders of magnitude higher than that of the traditional charged-particle pulses, the laser-accelerated plasma bunch can have a wide range of applications. In particular, such a dense energetic plasma bunch impinging on the compressed fuel in inertial fusion can significantly enhance the nuclear-reaction cross section and is thus a promising alternative for fast ignition.

Optimum hot electron production with low-density foams for laser fusion by fast ignition

We propose a foam cone-in-shell target design aiming at optimum hot electron production for the fast ignition. A thin low-density foam is proposed to cover the inner tip of a gold cone inserted in a fuel shell. An intense laser is then focused on the foam to generate hot electrons for the fast ignition. Element experiments demonstrate increased laser energy coupling efficiency into hot electrons without increasing the electron temperature and beam divergence with foam coated targets in comparison with solid targets. This may enhance the laser energy deposition in the compressed fuel plasma.

The deep ocean density structure at the Last Glacial Maximum : What was it and why?

The search for reliable proxies of past deep ocean temperature and salinity has proved difficult, thereby limiting our ability to understand the coupling of ocean circulation and climate over glacial-interglacial timescales. Previous inferences of deep ocean temperature and salinity from sediment pore fluid oxygen isotopes and chlorinity indicate that the deep ocean density structure at the Last Glacial Maximum (LGM, approximately 20,000 years BP) was set by salinity, and that the density contrast between northern and southern sourced deep waters was markedly greater than in the modern ocean. High density stratification could help explain the marked contrast in carbon isotope distribution recorded in the LGM ocean relative to that we observe today, but what made the ocean's density structure so different at the LGM? How did it evolve from one state to another? Further, given the sparsity of the LGM temperature and salinity data set, what else can we learn by increasing the spatial density of proxy records?

We investigate the cause and feasibility of a highly and salinity stratified deep ocean at the LGM and we work to increase the amount of information we can glean about the past ocean from pore fluid profiles of oxygen isotopes and chloride. Using a coupled ocean--sea ice--ice shelf cavity model we test whether the deep ocean density structure at the LGM can be explained by ice--ocean interactions over the Antarctic continental shelves, and show that a large contribution of the LGM salinity stratification can be explained through lower ocean temperature. In order to extract the maximum information from pore fluid profiles of oxygen isotopes and chloride we evaluate several inverse methods for ill-posed problems and their ability to recover bottom water histories from sediment pore fluid profiles. We demonstrate that Bayesian Markov Chain Monte Carlo parameter estimation techniques enable us to robustly recover the full solution space of bottom water histories, not only at the LGM, but through the most recent deglaciation and the Holocene up to the present. Finally, we evaluate a non-destructive pore fluid sampling technique, Rhizon samplers, in comparison to traditional squeezing methods and show that despite their promise, Rhizons are unlikely to be a good sampling tool for pore fluid measurements of oxygen isotopes and chloride.

Short-pulse laser absorption in very steep plasma density gradients

An analytical fluid model for resonance absorption during the oblique incidence by femtosecond laser pulses on a small-scale-length density plasma [k(0)L is an element of(0.1,10)] is proposed. The physics of resonance absorption is analyzed more clearly as we separate the electric field into an electromagnetic part and an electrostatic part. It is found that the characteristics of the physical quantities (fractional absorption, optimum angle, etc.) in a small-scale-length plasma are quite different from the predictions of classical theory. Absorption processes are generally dependent on the density scale length. For shorter scale length or higher laser intensity, vacuum heating tends to be dominant. It is shown that the electrons being pulled out and then returned to the plasma at the interface layer by the wave field can lead to a phenomenon like wave breaking. This can lead to heating of the plasma at the expanse of the wave energy. It is found that the optimum angle is independent of the laser intensity while the absorption rate increases with the laser intensity, and the absorption rate can reach as high as 25%. (c) 2006 American Institute of Physics.