Yap1-mediated Flr1 expression reveals crosstalk between oxidative stress signaling and caffeine resistance in Saccharomyces cerevisiae.

Caffeine, a methylxanthine derivative, affects various physiological conditions such as cell growth, proliferation, and energy metabolism. A genome-wide screening for genes required for caffeine resistance in Schizosaccharomyces pombe revealed several candidates, including Pap1 and downstream target genes involved in caffeine efflux. We found that Yap1, a budding yeast AP-1 homolog required for oxidative stress response, has a caffeine tolerance function. Although the Yap1 mutant is not sensitive to caffeine, overexpression of Yap1 renders cells resistant to high concentrations of caffeine. Caffeine sensitivity of mutants lacking two multidrug transporters, Pdr5 or Snq2, is completely recovered by Yap1 overexpression. Among Yap1-dependent target genes, FLR1, a fluconazole-resistant gene, is necessary but not sufficient for caffeine tolerance. Low concentrations of hydrogen peroxide induce Yap1 activation, which restores cell viability against caffeine toxicity. Intriguingly, oxidative stress-mediated cellular adaptation to caffeine toxicity requires Yap1, but not Flr1. Moreover, caffeine is involved in reduction of intracellular reactive oxygen species (ROS), as well as mutation rate and Rad52 foci formation. Altogether, we identified novel reciprocal crosstalk between ROS signaling and caffeine resistance.

Electrochemiluminescence Systems for the Detection of Biomarkers: Strategical and Technological Advances.

Electrochemiluminescence (ECL)-based sensing systems rely on light emissions from luminophores, which are generated by high-energy electron transfer reactions between electrogenerated species on an electrode. ECL systems have been widely used in the detection and monitoring of diverse, disease-related biomarkers due to their high selectivity and fast response times, as well as their spatial and temporal control of luminance, high controllability, and a wide detection range. This review focuses on the recent strategic and technological advances in ECL-based biomarker detection systems. We introduce several sensing systems for medical applications that are classified according to the reactions that drive ECL signal emissions. We also provide recent examples of sensing strategies and technologies based on factors that enhance sensitivity and multiplexing abilities as well as simplify sensing procedures. This review also discusses the potential strategies and technologies for the development of ECL systems with an enhanced detection ability.

Lack of superoxide dismutase in a rad51 mutant exacerbates genomic instability and oxidative stress-mediated cytotoxicity in Saccharomyces cerevisiae.

A genetic analysis of synthetic lethal interactions in yeast revealed that the mutation of SOD1, encoding an antioxidant enzyme that scavenges superoxide anion radical, impaired the growth of a set of mutants defective in homologous recombination (HR) pathway. Hence, SOD1 inhibition has been proposed as a promising approach for the selective killing of HR-deficient cancer cells. However, we show that the deletion of RAD51 and SOD1 is not synthetic lethal but displays considerably slow growth and synergistic sensitivity to both reactive oxygen species (ROS)- and DNA double-strand break (DSB)-generating drugs in the budding yeast Saccharomyces cerevisiae. The function of Sod1 in regard to Rad51 is dependent on Ccs1, a copper chaperone for Sod1. Sod1 deficiency aggravates genomic instability in conjunction with the absence of Rad51 by inducing DSBs and an elevated mutation frequency. Inversely, lack of Rad51 causes a Sod1 deficiency-derived increase of intracellular ROS levels. Taken together, our results indicate that there is a significant and specific crosstalk between two major cellular damage response pathways, ROS signaling and DSB repair, for cell survival.

Automotive Frequency Modulated Continuous Wave Radar Interference Reduction Using Per-Vehicle Chirp Sequences.

Recently, many automobiles adopt radar sensors to support advanced driver assistance system (ADAS) functions. As the number of vehicles with radar systems increases the probability of radar signal interference and the accompanying ghost target problems become serious. In this paper, we propose a novel algorithm where we deploy per-vehicle chirp sequence in a frequency modulated continuous wave (FMCW) radar to mitigate the vehicle-to-vehicle radar interference. We devise a chirp sequence set so that the slope of each vehicle's chirp sequence does not overlap within the set. By assigning one of the chirp sequences to each vehicle, we mitigate the interference from the radar signals transmitted by the neighboring vehicles. We confirm the performance of the proposed method stochastically by computer simulation. The simulation results show that the detection and false alarm performance is improved significantly by the proposed method.

Gender differences in pharmacokinetics and tissue distribution of 3 perfluoroalkyl and polyfluoroalkyl substances in rats.

The aim of this study was to confirm and investigate the gender differences in pharmacokinetic (PK) characteristics and tissue distribution of 3 perfluoroalkyl and polyfluoroalkyl substances (PFASs) consisted of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS) in both male and female rats. For this study, a simultaneous determination method of the 3 PFASs in rat plasma and tissues was developed and validated using a UPLC-MS/MS system. The PK parameters after a single oral or intravenous administration of the 3 PFASs in both rats were calculated using WinNonlin® software. The mean half-life of the 3 PFASs in female and male rats was in the range of 0.15-0.19 and 1.6-1.8 days for PFOA, 23.5-24.8 and 26.4-28.7 days for PFOS, and 0.9-1.7 and 20.7-26.9 days for PFHxS, respectively. The 3 PFASs were highly distributed in the liver and kidney. These results suggest that there are gender differences in the PKs for PFOA and PFHxS in rats, whereas the PFOS represented no significant gender differences except the Kp value of liver. The validated simultaneous determination method of the 3 PFASs was also within the accepted criteria of the international guidance.

Immediate effects of Kinesio Taping on the movement of the hyoid bone and epiglottis during swallowing by stroke patients with dysphagia.

[Purpose] The purpose of this study was to identify the effects of Kinesio Taping (KT) on the swallowing function of stroke patients. [Subjects and Methods] Twenty-two stroke patients were randomly assigned to two groups; an experimental group which received KT, and a control group which received no taping intervention. Two-dimensional kinematic analysis was used to determine the displacement of the hyoid bone and the angular variation of the epiglottis using human anatomy-based coordinates. The functional dysphagia scale (FDS) was determined by a videofluoroscopic study (VFSS). [Results] The experimental group presented statistically significant improvements in kinematic changes of the vertical excursion of the hyoid bone and epiglottal rotation. [Conclusion] Clinical use of KT for dysphagia patients should be considered as a treatment approach. In future research, more subjects and more diverse patterns should be studied to accumulate further evidence.

Immediate effects of kinesio taping on fixed postural alignment and foot balance in stroke patients.

[Purpose] The main aim of this study was to identify the short-term effects of Kinesio taping (KT) on the static body alignment and overall balance function presented by the coordinate and foot balance in stroke patients. [Subjects and Methods] Thirty-eight stroke subjects were randomly allocated into the study groups. The kinematic analysis measured deviation or changes from standard body alignment and foot pressure by the human anatomy-based coordinates were examined using the Shisei Innovation System PA200 ver.9.0. [Results] The glabellas on the front view, larynx on the front view, rt. greater tubercle of the humerus (vertical changes), lt. greater tubercle of the humerus (vertical changes), posterior superior iliac spine, and greater trochanter (horizontal changes) showed statistically significant decreases, indicating dislocation from the axis center, after taping. [Conclusion] The clinical use of KT for stroke patients who have asymmetrical and imbalanced body posture could be an optimal therapeutic approach. Since more evidence based practices are needed, future studies should include large numbers of subjects and examine diverse KT application patterns.

Optimization of the autocorrelation weighting function for the time-domain calculation of spectral centroids.

Spectral centroid from the backscattered ultrasound provides important information about the attenuation properties of soft tissues and Doppler effects of blood flows. Because the spectral centroid is originally determined from the power spectrum of backscattered ultrasound signals in the frequency domain, it is natural to calculate it after converting time-domain signals into spectral domain signals, using the fast Fourier transform (FFT). Recent research, however, derived the time-domain equations for calculating the spectral centroid using a Parseval's theorem, to avoid the calculation of the Fourier transform. The work only presented the final result, which showed that the computational time of the proposed time-domain method was 4.4 times faster than that of the original FFT-based method, whereas the average estimation error was negligible. In this paper, we present the optimal design of the autocorrelation weighting function, which is used for the timedomain spectral centroid estimation process, to reduce the computational time significantly. We also carry out a comprehensive analysis of the computational complexities of the FFTbased and time-domain methods with respect to the length of ultrasound signal segments. The simulation results using numerical phantoms show that, with the optimized autocorrelation weighting function, we only need approximately 3% of the full set of data points. In addition to that, because the proposed optimization technique requires a fixed number of data points to calculate the spectral centroid, the execution time is constant as the length of the data segment increases, whereas the execution time of the conventional FFT-based method is increased. Analysis of the computational complexities between the proposed method and the conventional FFT-based method presents O(N) and O(Nlog2N), respectively.

Time-domain calculation of spectral centroid from backscattered ultrasound signals.

Spectral centroid estimation from backscattered ultrasound RF signals is the preliminary step for quantitative ultrasound analysis in many medical applications. The traditional approach of estimating the spectral centroid in the frequency domain takes a long time because discrete Fourier transform (DFT) processing for each RF segment is required. To avoid this, we propose time-domain methods to estimate the spectral centroid in this paper. First, we derive the continuous-time-domain equations for the spectral centroid estimation using Parseval's theorem and Hilbert transform theory. Then, we extend the method to the discrete-time domain to ease the implementation while maintaining the same accuracy as the calculation in the frequency domain. From the result, we observe that it is not practical to apply the discrete-time equations directly, because a high sampling rate is needed to approximate the time derivative in the discrete-time domain. Therefore, we also derive the feasible version of the discrete-time equations using a circular autocorrelation function, which has no constraints on the sampling rate for real RF signals acquired from pulse-echo ultrasound systems. Simulation results using numerical phantoms show that the time-domain calculation is approximately 4.4 times faster on average than the frequency-domain method when the software's built-in functions were used. The average estimation error compared with that of the frequency-domain method using DFT is less than 0.2% for the entire propagation depths. The proposed time-domain approach to estimate the spectral centroid can be easily implemented in real-time ultrasound systems.

A novel power spectrum calculation method using phase-compensation and weighted averaging for the estimation of ultrasound attenuation.

An estimation of ultrasound attenuation in soft tissues is critical in the quantitative ultrasound analysis since it is not only related to the estimations of other ultrasound parameters, such as speed of sound, integrated scatterers, or scatterer size, but also provides pathological information of the scanned tissue. However, estimation performances of ultrasound attenuation are intimately tied to the accurate extraction of spectral information from the backscattered radiofrequency (RF) signals. In this paper, we propose two novel techniques for calculating a block power spectrum from the backscattered ultrasound signals. These are based on the phase-compensation of each RF segment using the normalized cross-correlation to minimize estimation errors due to phase variations, and the weighted averaging technique to maximize the signal-to-noise ratio (SNR). The simulation results with uniform numerical phantoms demonstrate that the proposed method estimates local attenuation coefficients within 1.57% of the actual values while the conventional methods estimate those within 2.96%. The proposed method is especially effective when we deal with the signal reflected from the deeper depth where the SNR level is lower or when the gated window contains a small number of signal samples. Experimental results, performed at 5MHz, were obtained with a one-dimensional 128 elements array, using the tissue-mimicking phantoms also show that the proposed method provides better estimation results (within 3.04% of the actual value) with smaller estimation variances compared to the conventional methods (within 5.93%) for all cases considered.