Activation status of integrated stress response pathways in neurones and astrocytes of HIV-associated neurocognitive disorders (HAND) cortex.

AIMS: Combined anti-retroviral therapy (cART) has led to a reduction in the incidence of HIV-associated dementia (HAD), a severe motor/cognitive disorder afflicting HIV(+) patients. However, the prevalence of subtler forms of neurocognitive dysfunction, which together with HAD are termed HIV-associated neurocognitive disorders (HAND), continues to escalate in the post-cART era. The microgliosis, astrogliosis, dendritic damage, and synaptic and neuronal loss observed in autopsy cases suggest an underlying neuroinflammatory process, due to the neurotoxic factors released by HIV-infected/activated macrophages/microglia in the brain, might underlie the pathogenesis of HAND in the post-cART era. These factors are known to induce the integrated stress response (ISR) in several neurodegenerative diseases; we have previously shown that BiP, an indicator of general ISR activation, is upregulated in cortical autopsy tissue from HIV-infected patients. The ISR is composed of three pathways, each with its own initiator protein: PERK, IRE1α and ATF6. METHODS: To further elucidate the specific ISR pathways activated in the central nervous system of HAND patients, we examined the protein levels of several ISR proteins, including ATF6, peIF2α and ATF4, in cortical tissue from HIV-infected patients. RESULTS: The ISR does not respond in an all-or-none fashion in HAND, but rather demonstrates a nuanced activation pattern. Specifically, our studies implicate the ATF6 pathway of the ISR as a more likely candidate than the PERK pathway for increases in BiP levels in astrocytes. CONCLUSION: These findings begin to characterize the nature of the ISR response in HAND and provide potential targets for therapeutic intervention in this disease.

Comments on "Silicon models of lateral inhibition" [with reply].

The commenters refer to the above mentioned paper by Wolpert and Micheli-Tzanakou (ibid. p.955-61, 1993), and point out the oversight of previous activity in circuit design. In their opinion the paper in question does not seem to represent a novel approach either in circuitry or computationally. In reply, the authors acknowledge their oversight of the conference papers cited by the commenters, but point out that they never suggested that a simple shunting lateral inhibitory (SLI) pair was a novel circuit, and the overall objective of their effort was simply to carry analysis of SLI to a higher dimension.

Volterra series analysis and synthesis of a neural network for velocity estimation.

The motion detection problem occurs frequently in many applications connected with computer vision. Researchers have studied motion detection based on naturally occurring biological circuits for over a century. In this paper, we propose and analyze a motion detection circuit which is based on nerve membrane conduction. It consists of two unidirectional neural networks connected in an opposing fashion. Volterra input-output (I-O) models are then derived for the network so that velocity estimation can be cast as a parameter estimation problem. The technique is demonstrated through simulation.

Controllable formation of nanoscale patterns on TiO2 by conductive-AFM nanolithography.

We report on the nanopatterning of double-bond-terminated silane (5-hexenyltrichlorosilane, HTCS) molecules on titania (TiO2) using conductive atomic force microscopy (AFM). The influences of tip electrostatic potential and scanning velocity, relative humidity and of the repeated application of voltage on the topographic height, width, and hydrophilic and hydrophobic contrast of the resultant patterns were investigated. Tip voltage and tip velocity ( v) were applied between -10 V

Heterogeneous animal group models and their group-level alignment dynamics: an equation-free approach.

We study coarse-grained (group-level) alignment dynamics of individual-based animal group models for heterogeneous populations consisting of informed (on preferred directions) and uninformed individuals. The orientation of each individual is characterized by an angle, whose dynamics are nonlinearly coupled with those of all the other individuals, with an explicit dependence on the difference between the individual's orientation and the instantaneous average direction. Choosing convenient coarse-grained variables (suggested by uncertainty quantification methods) that account for rapidly developing correlations during initial transients, we perform efficient computations of coarse-grained steady states and their bifurcation analysis. We circumvent the derivation of coarse-grained governing equations, following an equation-free computational approach.

Design of a dual-effect lens on lanthanum-modified lead zirconate titanate for continuous variation of focal length.

The design of a Fresnel lens with continuous focal length is proposed for use in optical processing. A convex lens is induced in lanthanum-modified lead zirconate titanate through the application of an electric-field profile supplied by the indium tin oxide electrodes that make up the zones of a Fresnel lens. The use of a numerical method based on fast Fourier transform algorithms was required to analyze accurately the induced field inside a Fresnel lens with an initial focal length of 0.4 m (at 470 nm) and 20 indium tin oxide electrodes. The effective focal location obtained by the combined mechanisms is derived. This design is expected to produce continuous variations of ~16% in focal length; the ability of previous designs to achieve focal length switching is maintained.

Simple analytical model of bias dependence of the photocurrent of metal-semiconductor-metal photodetectors.

The current-voltage (I-V) characteristics of metal-semiconductor-metal (MSM) photodetectors under various light intensities are examined. The current shows an initial increase followed by saturation and a subsequent sharp increase as bias increases. We propose a theoretical model for bias dependence in all regions of operation except for breakdown, based on drift collection of carriers in the depleted regions under the contacts and diffusion and recombination in the undepleted region. This is based on the solution of the diffusion equation in the undepleted area between the two contacts of the MSM structure. The solution is subject to boundary conditions on excess minority carriers at the cathode end and continuity of current at the anode end. The latter is written in terms of a parameter, denoted as effective diffusion length, which describes the collection efficiency of carriers at the anode. The closed-form solution thus derived corroborates with physical expectations in several limiting cases. To compare theory with experiment, we propose methods to extract parameters that are used to normalize the I-V curves and calculate depletion widths under different light intensities, from current- and capacitance-voltage measurements. A close match between experimental and theoretical results is observed, and possible breakdown mechanisms are discussed.