Pharmacological And Genetic Reversal Of Age-Dependent Cognitive Deficits Attributable To Decreased Presenilin Function

Alzheimer\u27s disease (AD) is the leading cause of cognitive loss and neurodegeneration in the developed world. Although its genetic and environmental causes are not generally known, familial forms of the disease (FAD) are attributable to mutations in a single copy of the Presenilin (PS) and amyloid precursor protein genes. The dominant inheritance pattern of FAD indicates that it may be attributable to gain or change of function mutations. Studies of FAD-linked forms of presenilin (psn) in model organisms, however, indicate that they are loss of function, leading to the possibility that a reduction in PS activity might contribute to FAD and that proper psn levels are important for maintaining normal cognition throughout life. To explore this issue further, we have tested the effect of reducing psn activity during aging in Drosophila melanogaster males. We have found that flies in which the dosage of psn function is reduced by 50% display age-onset impairments in learning and memory. Treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium during the aging process prevented the onset of these deficits, and treatment of aged flies reversed the age-dependent deficits. Genetic reduction of Drosophila metabotropic glutamate receptor (DmGluRA), the inositol trisphosphate receptor (InsP(3)R), or inositol polyphosphate 1-phosphatase also prevented these age-onset cognitive deficits. These findings suggest that reduced psn activity may contribute to the age-onset cognitive loss observed with FAD. They also indicate that enhanced mGluR signaling and calcium release regulated by InsP(3)R as underlying causes of the age-dependent cognitive phenotypes observed when psn activity is reduced

Effects of Vacancies on Properties of Relaxor Ferroelectrics: a First-Principles Study

A first-principles-based model is developed to investigate the influence of lead vacancies on the properties of relaxor ferroelectric Pb(Sc1/2Nb1/2)O3 (PSN). Lead vacancies generate large, inhomogeneous, electric fields that reduce barriers between energy minima for different polarization directions. This naturally explains why relaxors with significant lead vacancy concentrations have broadened dielectric peaks at lower temperatures, and why lead vacancies smear properties in the neighborhood of the ferroelectric transition in PSN. We also reconsider the conventional wisdom that lead vacancies reduce the magnitude of dielectric response.Comment: 11 pages, 1 figur

Prodsimplicial-Neighborly Polytopes

Simultaneously generalizing both neighborly and neighborly cubical polytopes, we introduce PSN polytopes: their k-skeleton is combinatorially equivalent to that of a product of r simplices. We construct PSN polytopes by three different methods, the most versatile of which is an extension of Sanyal and Ziegler's "projecting deformed products" construction to products of arbitrary simple polytopes. For general r and k, the lowest dimension we achieve is 2k+r+1. Using topological obstructions similar to those introduced by Sanyal to bound the number of vertices of Minkowski sums, we show that this dimension is minimal if we additionally require that the PSN polytope is obtained as a projection of a polytope that is combinatorially equivalent to the product of r simplices, when the dimensions of these simplices are all large compared to k.Comment: 28 pages, 9 figures; minor correction

A fully digital power supply noise thermometer

Power Supply Noise (PSN) is one of the main concerns in scaled technology circuits, both if performance reliability must be assured and if power supply is to be dynamically reduced for dissipation regulation. In this paper we propose a new system for digitally sensing Power Supply and Ground levels that can be both transferred to the output for verification purposes and used by a control block within the circuit under test (CUT) for the activation of power aware policies. The sensor system shows very low overhead in terms of power and area, and works at the nominal CUT frequency. It allows to change on-site the Power Supply and Ground ranges to be sensed and, after a fine tuning, can be arranged for a process variation aware measures. This sensor is fully digital and standard cell based and can be used for every type of architecture on a systematic basis for PSN measure as scan chains are for fault verification. It thus represents a change of paradigm in the way in which PSN measure systems are thought nowaday

Context Information Based Initial Cell Search for Millimeter Wave 5G Cellular Networks

Millimeter wave (mmWave) communication is envisioned as a cornerstone to fulfill the data rate requirements for fifth generation (5G) cellular networks. In mmWave communication, beamforming is considered as a key technology to combat the high path-loss, and unlike in conventional microwave communication, beamforming may be necessary even during initial access/cell search. Among the proposed beamforming schemes for initial cell search, analog beamforming is a power efficient approach but suffers from its inherent search delay during initial access. In this work, we argue that analog beamforming can still be a viable choice when context information about mmWave base stations (BS) is available at the mobile station (MS). We then study how the performance of analog beamforming degrades in case of angular errors in the available context information. Finally, we present an analog beamforming receiver architecture that uses multiple arrays of Phase Shifters and a single RF chain to combat the effect of angular errors, showing that it can achieve the same performance as hybrid beamforming