Conditional BDNF release under pathological conditions improves Huntington's disease pathology by delaying neuronal dysfunction

Background Brain-Derived Neurotrophic Factor (BDNF) is the main candidate for neuroprotective therapy for Huntington's disease (HD), but its conditional administration is one of its most challenging problems. Results Here we used transgenic mice that over-express BDNF under the control of the Glial Fibrillary Acidic Protein (GFAP) promoter (pGFAP-BDNF mice) to test whether up-regulation and release of BDNF, dependent on astrogliosis, could be protective in HD. Thus, we cross-mated pGFAP-BDNF mice with R6/2 mice to generate a double-mutant mouse with mutant huntingtin protein and with a conditional over-expression of BDNF, only under pathological conditions. In these R6/2:pGFAP-BDNF animals, the decrease in striatal BDNF levels induced by mutant huntingtin was prevented in comparison to R6/2 animals at 12 weeks of age. The recovery of the neurotrophin levels in R6/2:pGFAP-BDNF mice correlated with an improvement in several motor coordination tasks and with a significant delay in anxiety and clasping alterations. Therefore, we next examined a possible improvement in cortico-striatal connectivity in R62:pGFAP-BDNF mice. Interestingly, we found that the over-expression of BDNF prevented the decrease of cortico-striatal presynaptic (VGLUT1) and postsynaptic (PSD-95) markers in the R6/2:pGFAP-BDNF striatum. Electrophysiological studies also showed that basal synaptic transmission and synaptic fatigue both improved in R6/2:pGAP-BDNF mice. Conclusions These results indicate that the conditional administration of BDNF under the GFAP promoter could become a therapeutic strategy for HD due to its positive effects on synaptic plasticity.

Analysis of leakage properties and guiding conditions of rib antiresonant reflecting optical waveguides

Power leakage properties and guiding conditions of rib antiresonant reflecting optical waveguides (rib-ARROW) have been theoretically and experimentally studied as a function of wavelength and polarization of the light for different geometrical and optical parameters that characterize the rib-ARROW structure. Obtained results show that rib-ARROWs can only be fabricated with low losses in a wavelength range when determined rib configurations are adopted. Furthermore, these waveguides exhibit a polarization sensitivity that largely depends on the core-substrate refractive index difference. Together with the experimental results, theoretical calculations from different modeling methods are also presented and discussed.

On-line event detection by recursive dynamic principal component analysis and gas sensor arrays under drift conditions

Leakage detection is an important issue in many chemical sensing applications. Leakage detection hy thresholds suffers from important drawbacks when sensors have serious drifts or they are affected by cross-sensitivities. Here we present an adaptive method based in a Dynamic Principal Component Analysis that models the relationships between the sensors in the may. In normal conditions a certain variance distribution characterizes sensor signals. However, in the presence of a new source of variance the PCA decomposition changes drastically. In order to prevent the influence of sensor drifts the model is adaptive and it is calculated in a recursive manner with minimum computational effort. The behavior of this technique is studied with synthetic signals and with real signals arising by oil vapor leakages in an air compressor. Results clearly demonstrate the efficiency of the proposed method.

Asymptotic analysis of the Gunn effect with realistic boundary conditions

A general asymptotic analysis of the Gunn effect in n-type GaAs under general boundary conditions for metal-semiconductor contacts is presented. Depending on the parameter values in the boundary condition of the injecting contact, different types of waves mediate the Gunn effect. The periodic current oscillation typical of the Gunn effect may be caused by moving charge-monopole accumulation or depletion layers, or by low- or high-field charge-dipole solitary waves. A new instability caused by multiple shedding of (low-field) dipole waves is found. In all cases the shape of the current oscillation is described in detail: we show the direct relationship between its major features (maxima, minima, plateaus, etc.) and several critical currents (which depend on the values of the contact parameters). Our results open the possibility of measuring contact parameters from the analysis of the shape of the current oscillation.

Stationary states and phase diagram for a model of the Gunn effect under realistic boundary conditions

A general formulation of boundary conditions for semiconductor-metal contacts follows from a phenomenological procedure sketched here. The resulting boundary conditions, which incorporate only physically well-defined parameters, are used to study the classical unipolar drift-diffusion model for the Gunn effect. The analysis of its stationary solutions reveals the presence of bistability and hysteresis for a certain range of contact parameters. Several types of Gunn effect are predicted to occur in the model, when no stable stationary solution exists, depending on the value of the parameters of the injecting contact appearing in the boundary condition. In this way, the critical role played by contacts in the Gunn effect is clearly established.

Gauge group and reality conditions in Ashtekar's complex formulation of canonical gravity

We discuss reality conditions and the relation between spacetime diffeomorphisms and gauge transformations in Ashtekars complex formulation of general relativity. We produce a general theoretical framework for the stabilization algorithm for the reality conditions, which is different from Diracs method of stabilization of constraints. We solve the problem of the projectability of the diffeomorphism transformations from configuration-velocity space to phase space, linking them to the reality conditions. We construct the complete set of canonical generators of the gauge group in the phase space which includes all the gauge variables. This result proves that the canonical formalism has all the gauge structure of the Lagrangian theory, including the time diffeomorphisms.

Decay of unstable states in the presence of colored noise and random initial conditions. I. Theory of nonlinear relaxation times

The general theory of nonlinear relaxation times is developed for the case of Gaussian colored noise. General expressions are obtained and applied to the study of the characteristic decay time of unstable states in different situations, including white and colored noise, with emphasis on the distributed initial conditions. Universal effects of the coupling between colored noise and random initial conditions are predicted.

Decay of unstable states in the presence of colored noise and random initial conditions. II. Analog experiments and digital simulations

The decay of an unstable state under the influence of external colored noise has been studied by means of analog experiments and digital simulations. For both fixed and random initial conditions, the time evolution of the second moment ¿x2(t)¿ of the system variable was determined and then used to evaluate the nonlinear relaxation time. The results obtained are found to be in excellent agreement with the theoretical predictions of the immediately preceding paper [Casademunt, Jiménez-Aquino, and Sancho, Phys. Rev. A 40, 5905 (1989)].

Absorbing boundary conditions for inertial processos

A recent paper by J. Heinrichs [Phys. Rev. E 48, 2397 (1993)] presents analytic expressions for the first-passage times and the survival probability for a particle moving in a field of random correlated forces. We believe that the analysis there is flawed due to an improper use of boundary conditions. We compare that result, in the white noise limit, with the known exact expression of the mean exit time.