Optical timing distribution system with femtosecond stability

Stable timing distribution is a key technology for the many fields that use timing signals for synchronization. The frequency of the timing signal depends on the field and multiple timing signals are sometimes required. In our DWDM‐based timing distribution system, phase deviation is detected by high‐speed round‐trip signal (10 GHz signal is used as this control signal). Fiber stretchers are controlled so as to minimize the phase deviation of the control signal. Multiple signals and the control signal are densely multiplexed and transmitted through the same stretchers. Therefore, the transmission of all signals is stabilized. This configuration provides a flexible platform for distributing various RF or microwave signals. As an example of arbitrary timing signals, a 1 GHz signal is transmitted over a length‐stabilized 400‐m fiber for more than 1 day. The recorded propagation time fluctuations are 10.4 and 2.8 fs rms for the 1 and 10 GHz signals, respectively. The Allan deviations are 2.7 × 10⁻¹⁹ (1 GHz) and 6.0 × 10⁻²⁰ (10 GHz) for the averaging time of 10⁵ s. © 2012 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.     

Dimethyl Fumarate Induces Apoptosis via Inhibition of NF-κB and Enhances the Effect of Paclitaxel and Adriamycin in Human TNBC Cells

Triple-negative breast cancer (TNBC) has the poorest prognosis of all breast cancer subtypes. Recently, the activation of NF-κB, which is involved in the growth and survival of malignant tumors, has been demonstrated in TNBC, suggesting that NF-κB may serve as a new therapeutic target. In the present study, we examined whether dimethyl fumarate (DMF), an NF-κB inhibitor, induces apoptosis in TNBC cells and enhances the apoptosis-inducing effect of paclitaxel and adriamycin. Cell survival was analyzed by the trypan blue assay and apoptosis assay. Protein detection was examined by immunoblotting. The activation of NF-κB p65 was correlated with poor prognosis in patients with TNBC. DMF induced apoptosis in MDA-MB-231 and BT-549 cells at concentrations that were non-cytotoxic to the normal mammary cell line MCF-10A. Furthermore, DMF inhibited NF-κB nuclear translocation and Survivin, XIAP, Bcl-xL, and Bcl-2 expression in MDA-MB-231 and BT-549 cells. Moreover, DMF enhanced the apoptosis-inducing effect of paclitaxel and adriamycin in MDA-MB-231 cells. These findings suggest that DMF may be an effective therapeutic agent for the treatment of TNBC, in which NF-κB is constitutively active. DMF may also be useful as an adjuvant therapy to conventional anticancer drugs.     

Observation Site Atmospheric Phase Fluctuations Observed by Three-Element VLBI

The beacon signals from a geostationary satellite were observed using three-element very long baseline interferometry (VLBI), and the phase fluctuations along the baselines between three sites were obtained. The atmospheric phase fluctuations at each observation site were derived from the baseline phase fluctuation data. The fluctuations were classified into three time-interval regions based on the dependence of the Allan standard deviation of the fluctuations on the time interval. In the region where the interval was less than a few seconds and in the one where it was greater than one hundred seconds, the curve of the Allan standard deviation was steep and showed the property of white phase noise. In the region between these two regions, the dependence of the Allan standard deviation on the time interval was weak. The magnitude of the Allan standard deviations for the three observation sites showed time variations in the region where the time interval was longer than a few seconds. Comparison with the weather conditions suggested that the time variations of the Allan standard deviation reflected atmospheric instability above the sites.     

In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([189, 191Pt]cisplatin) Emitting Auger Electrons

Due to their short-range (2–500 nm), Auger electrons (Auger e⁻) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger e⁻, it remains challenging to maximize the interaction between Auger e⁻ and DNA. To assess the DNA-damaging effect of Auger e⁻ released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [^{189, 191}Pt]cisplatin and evaluated both its in vitro properties and DNA-damaging effect. Cellular uptake, intracellular distribution, and DNA binding were investigated, and DNA double-strand breaks (DSBs) were evaluated by immunofluorescence staining of γH2AX and gel electrophoresis of plasmid DNA. Approximately 20% of intracellular radio-Pt was in a nucleus, and about 2% of intra-nucleus radio-Pt bound to DNA, although uptake of n.c.a. radio-cisplatin was low (0.6% incubated dose after 25-h incubation), resulting in the frequency of cells with γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by the release of Auger e⁻ very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger e⁻.     

Simple Time and Frequency Dissemination Method Using Optical Fiber Network

This paper describes a simple and cost-effective method of frequency dissemination. In current digital communication networks, node clocks are hierarchically synchronized to the atomic master clock through fiber links. This synchronized network is used as an intermediate link for remote calibration services like the global positioning system common-view method. A prototype reference signal generator has been developed for recovering the communication clock signal and synthesizing a 10-MHz signal from it. The generator output frequency at the client site can be traced to coordinated universal time (UTC) National Metrology Institute of Japan (NMIJ) with some uncertainty, depending on the stability of the node clocks and the distance from the master clock. The stability performance of the generated reference signal has been tested at Okinawa-the farthest prefecture from Tokyo, where the master clock is located (baseline distance of 1500 km). The primary rate (1.544 MHz) for telecommunication services was chosen for the 10-MHz signal generation in the experiment. A sinusoidal phase fluctuation within a one-day period is dominantly observed. This fluctuation is mainly caused by fiber expansion and contraction due to normal daily temperature changes. It degrades the stability (Allan deviation) to the level of 5 X 10^-13 (t = 40 000 s, which is almost half a day). However, the major part of the phase fluctuation can be canceled by averaging a full day's data. In this case, the Allan deviation becomes 1 X 10^-13, which is obtained at Okinawa over ten consecutive days of measurement. The worst average frequency offset relative to UTC (NMIJ) (one-day averaging) is -6.3 X 10^-13. The results indicate that this method promises to be suitable for most applications, providing an uncertainty of less than 1 X 10^-12 at an averaging time of one day.     

Structural Development of Salicylanilide-Based SPAK Inhibitors as Candidate Antihypertensive Agents

Hypertension is an important target for drug discovery. We have focused on the with-no-lysine kinase (WNK)-oxidative stress-responsive 1 (OSR1) and STE20/SPS1-related proline-alanine-rich protein kinase (SPAK)-NaCl cotransporter (NCC) signal cascade as a potential target, and we previously developed a screening system for inhibitors of WNK-OSR1/SPAK-NCC signaling. Herein we used this system to examine the structure-activity relationship (SAR) of salicylanilide derivatives as SPAK kinase inhibitors. Structural design and development based on our previous hit compound, aryloxybenzanilide derivative 2 , and the veterinary anthelmintic closantel ( 3 ) led to the discovery of compound 10 a as a potent SPAK inhibitor with reduced toxicity. Compound 10 a decreased the phosphorylation level of NCC in mouse kidney in vivo, and appears to be a promising lead compound for a new class of antihypertensive drugs.     

Nursing skills for monitoring patients

This paper analyses the constraints used to define the elements of mixing matrices employed in deterministic models of the transmission dynamics of sexually transmitted infections. These matrices define the degree to which the choice of sexual partners in a population is assortative (like with like) or dissassortative (like with unlike) in populatiions stratified by sexual activity (i.e. the number of different sexual partners per unit of time). An expanded set of constraints is described which defines patterns of mixing on the assortative to disassortative spectrum in populations of finite size. The relevance of these new constraints to past work in this area is assessed. Keywords: mixing matrices     

Emergence of [GAR+] cells in yeast from sake brewing affects the fermentation properties

In the traditional (kimoto) method of sake (Japanese rice wine) brewing, Saccharomyces cerevisiae yeast cells are exposed to lactate, which is produced by lactic acid bacteria in the seed mash. Lactate promotes the appearance of glucose-repression-resistant [GAR⁺] cells. Herein, we compared the resistance to glucose repression among kimoto, industrial, and laboratory yeast strains. We observed that the frequencies of the spontaneous emergence of [GAR⁺] cells among the kimoto strains were higher than those among the industrial and laboratory strains. The fermentation ability of a kimoto yeast (strain U44) was lower than that of an industrial strain (K701), as [GAR⁺] cells generally showed slower ethanol production. The addition of lactate decreased the fermentation abilities of the K701 strain by increasing the number of [GAR⁺] cells, but it did not affect those of the U44 strain. These results suggest that lactate controlled fermentation by promoting the appearance of [GAR⁺] cells in the industrial sake strains but not in the kimoto strains.