No abstract

Different from the conventional phased array, frequency diverse array (FDA) can provide electronic beam scanning without phase shifters and its beam steering is rangeangle-dependent. Nevertheless, reported studies on FDA are most in continuous waveforms and the corresponding beampattern is time-variant, which increases difficulty in controlling the mainbeam direction and complexity of signal processing. To alleviate this problem, a pulsed-FDA is proposed with an aim to generate quasi-static beampattern in this paper. The corresponding constraint is derived together with the method to control the mainbeam direction. Moreover, the range-angle-dependent characteristics of the quasi-static transmit/receive beampattern are addressed considering the radar applications. Besides, rangeangle-dependent beampattern significantly enhances the flexibility of beam scanning and its signal processing. Simulation results are in good agreement with the theoretical analysis.Index Terms-Pulsed frequency diverse array, quasistatic beampattern, range-angle-dependent beamforming, transmit/receive beamforming.

J. Neurochem. (2012) 121, 263–276. Abstract Insulin offers trophic support through receptors expressed widely on peripheral neurons. In this work, we studied whether peripheral sensory neurons demonstrate resistance to its trophic properties, a property relevant during type 2 diabetes mellitus or following supraphysiological therapy. Insulin receptors were not only localized to neuronal membranes and cytoplasm but also had a unique, previously unrecognized localization to neuronal nuclei. We confirmed that nanomolar doses increased neurite outgrowth of adult sensory neurons, but in response to micromolar doses of insulin, even following a brief 2‐h exposure, survival and outgrowth of neurites were blunted. Neurons exposed to picomolar insulin concentrations in their media for 5 days had resistance to the impact of later nanomolar doses of insulin. Using a stripe assay seeded with insulin, neurites were more likely to reject higher doses of insulin. Insulin down‐regulated mRNAs of the insulin receptor β subunit and up‐regulated levels of GSK‐3β, both potential mechanisms of insulin resistance, while down‐regulating the protein expression of pAkt and pGSK‐3β. Overall, these studies identify neuronal nuclear targeting of insulin and evidence for insulin‐induced resistance to its trophic properties. The findings have implications for the understanding of the actions of insulin in the treatment of diabetes and neurological disorders.

By comparing mRNA profiles in cultured fibroblasts from patients affected with lysosomal storage diseases, we identified differentially expressed genes common to these conditions. These studies, confirmed by biochemical experiments, demonstrated that lysosomal storage is associated with downregulation of ubiquitin C-terminal hydrolase, UCH-L1 in the cells of eight different lysosomal disorders, as well as in the brain of a mouse model of Sandhoff disease. Induction of lysosomal storage by the cysteine protease inhibitor E-64 also reduced UCH-L1 mRNA, protein level and activity. All cells exhibiting lysosomal storage contained ubiquitinated protein aggregates and showed reduced levels of free ubiquitin and decreased proteasome activity. The caspase-mediated apoptosis in E-64-treated fibroblasts was reversed by transfection with a UCH-L1 plasmid, and increased after downregulation of UCH-L1 by siRNA, suggesting that UCH-L1 deficiency and impairment of the ubiquitin-dependent protein degradation pathway can contribute to the increased cell death observed in many lysosomal storage disorders.

No abstract