Wideband digital phase comparator for high current shunts

A wideband phase comparator for precise measurements of phase difference of high current shunts has been developed at INRIM. The two-input digital phase detector is realized with a precision wideband digitizer connected through a pair of symmetric active guarded transformers to the outputs of the shunts under comparison. Data are first acquired asynchronously, and then transferred from on-board memory to host memory. Because of the large amount of data collected the filtering process and the analysis algorithms are performed outside the acquisition routine. Most of the systematic errors can be compensated by a proper inversion procedure. The system is suitable for comparing shunts in a wide range of currents, from several hundred of milliampere up to 100 A, and frequencies ranging between 500 Hz and 100 kHz. Expanded uncertainty (k=2) less than 0.05 mrad, for frequency up to 100 kHz, is obtained in the measurement of the phase difference of a group of 10 A shunts, provided by some European NMIs, using a digitizer with sampling frequency up to 1 MHz. An enhanced version of the phase comparator employs a new digital phase detector with higher sampling frequency and vertical resolution. This permits to decrease the contribution to the uncertainty budget of the phase detector of a factor two from 20 kHz to 100 kHz. Theories and experiments show that the phase difference between two high precision wideband digitizers, coupled as phase detector, depends on multiple factors derived from both analog and digital imprint of each sampling system.Comment: 20 pages, 9 figure

Disease-Aging Network Reveals Significant Roles of Aging Genes in Connecting Genetic Diseases

One of the challenging problems in biology and medicine is exploring the underlying mechanisms of genetic diseases. Recent studies suggest that the relationship between genetic diseases and the aging process is important in understanding the molecular mechanisms of complex diseases. Although some intricate associations have been investigated for a long time, the studies are still in their early stages. In this paper, we construct a human disease-aging network to study the relationship among aging genes and genetic disease genes. Specifically, we integrate human protein-protein interactions (PPIs), disease-gene associations, aging-gene associations, and physiological system–based genetic disease classification information in a single graph-theoretic framework and find that (1) human disease genes are much closer to aging genes than expected by chance; and (2) diseases can be categorized into two types according to their relationships with aging. Type I diseases have their genes significantly close to aging genes, while type II diseases do not. Furthermore, we examine the topological characters of the disease-aging network from a systems perspective. Theoretical results reveal that the genes of type I diseases are in a central position of a PPI network while type II are not; (3) more importantly, we define an asymmetric closeness based on the PPI network to describe relationships between diseases, and find that aging genes make a significant contribution to associations among diseases, especially among type I diseases. In conclusion, the network-based study provides not only evidence for the intricate relationship between the aging process and genetic diseases, but also biological implications for prying into the nature of human diseases

A genetic analysis of nitric oxide-mediated signaling during chronological aging in the yeast

In mammals, NO•, a signaling molecule is implicated in the regulation of vasodilation, neurotransmission and immune response. It is believed that NO• is a signaling molecule also in unicellular organism like yeast and may be involved in the regulation of apoptosis and sporulation. It has been reported that NO• is produced during chronological aging (CA) leading to an increase of the superoxide level, which in turn mediates apoptosis. Since this conclusion was based on indirect measurements of NO• by the Griess reaction, the role of NO• signaling during CA in the yeast remains uncertain. We investigated this issue more precisely using different genetic and biochemical methodologies. We used cells lacking the factors influencing nitrosative stress response like flavohemoglobin metabolizing NO•, S-nitrosoglutathione reductase metabolizing S-nitrosoglutathione and the transcription factor Fzf1p mediating NO• response. We measured the standard parameters describing CA and found an elevation in the superoxide level, percentage of death cells, the level of TUNEL positive cells and a decrease in proliferating potential. These observations showed no significant differences between wild type cells and the disruptants except for a small elevation of the superoxide level in the Δsfa1 mutant. The intracellular NO• level and flavohemoglobin expression decreased rather than increased during CA. Products of general nitrogen metabolism and protein tyrosine nitration were slightly decreased during CA, the magnitude of changes showing no differences between the wild type and the mutant yeast. Altogether, our data indicate that apoptosis during yeast CA is mediated by superoxide signaling rather than NO• signaling