A hERG mutation E1039X produced a synergistic lesion on I _Ks together with KCNQ1-R174C mutation in a LQTS family with three compound mutations

Congenital long QT syndrome (LQTS) caused by compound mutations is usually associated with more severe clinical phenotypes. We identified a LQTS family harboring three compound mutations in different genes (KCNQ1-R174C, hERG-E1039X and SCN5A-E428K). KCNQ1-R174C, hERG-E1039X and SCN5A-E428K mutations and/or relevant wild-type (WT) cDNAs were respectively expressed in mammalian cells. IKs-like, IKr-like, INa-like currents and the functional interaction between KCNQ1-R174C and hERG-E1039X channels were studied using patch-clamp and immunocytochemistry techniques. (1) Expression of KCNQ1-R174C alone showed no IKs. Co-expression of KCNQ1-WT + KCNQ1-R174C caused a loss-of-function in IKs and blunted the activation of IKs in response to isoproterenol. (2) Expression of hERG-E1039X alone and co-expression of hERG-WT + hERG-E1039X negatively shifted inactivation curves and decelerated the recovery time from inactivation. (3) Expression of SCN5A-E428K increased peak INa, but had no effect on late INa. (4) IKs and IKr interact, and hERG-E1039X caused a loss-of-function in IKs. (5) Immunocytochemical studies indicated that KCNQ1-R174C is trafficking defective and hERG-E1039X is defective in biosynthesis/degradation, but the abnormities were rescued by co-expression with WT. Thus, KCNQ1-R174C and hERG-E1039X disrupted IKs and IKr functions, respectively. The synergistic lesion, caused by KCNQ1-R174C and hERG-E1039X in IKs, is very likely why patients showed more severe phenotypes in the compound mutation case

Simple Prediction Method for Rubber Adhesive Friction by the Combining Friction Test and FE Analysis

In the design and development of rubber products, it is important to evaluate the contact load dependency of the friction coefficient. In particular, since the pressure distribution varies depending on the dimensions of sliding bodies and the pattern of the contact surface, a simplified and accurate evaluation method that can take these influences into account is desired. In this study, we proposed a prediction method for the adhesive friction between rubber specimens of arbitrary shapes with arbitrary roughness and a smooth hard surface, by combining the: (1) friction theory considering the influence of roughness; (2) basic friction test; and (3) finite element analysis. Further, we verified the effectiveness of the proposed method by comparing the predicted results with the measurement results of friction between a hemispherical PDMS specimen and a PMMA flat plate and between a PDMS block specimen with a grooved surface and a flat prism. Results show that the prediction accuracy of the contact load dependency of the friction coefficient is reasonably good

Infrared Hollow Optical Fiber Probe for Localized Carbon Dioxide Measurement in Respiratory Tracts

A real-time gas monitoring system based on optical absorption spectroscopy is proposed for localized carbon dioxide (CO2) measurement in respiratory tracts. In this system, a small gas cell is attached to the end of a hollow optical fiber that delivers mid-infrared light with small transmission loss. The diameters of the fiber and the gas cell are smaller than 1.2 mm so that the probe can be inserted into a working channel of common bronchoscopes. The dimensions of the gas cell are designed based on absorption spectra of CO2 standard gases in the 4.2 μm wavelength region, which are measured using a Fourier-transform infrared spectrometer. A miniature gas cell that is comprised of a stainless-steel tube with slots for gas inlet and a micro-mirror is fabricated. A compact probing system with a quantum cascade laser (QCL) light source is built using a gas cell with a hollow optical fiber for monitoring CO2 concentration. Experimental results using human breaths show the feasibility of the system for in-situ measurement of localized CO2 concentration in human airways

Aerated Irrigation and Pruning Residue Biochar on N2O Emission, Yield and Ion Uptake of Komatsuna

After irrigation in intensive vegetable cultivation, the soil is filled with water leading to reduced oxygen content of the soil air which will affect vegetable growth and soil N2O emission. In this study, the effect of aerated irrigation and residue biochar on soil N2O emission, yield, and ion uptake of komatsuna grown in Andosol was explored. The experiment included four treatments; control (tap water irrigation), aerated water irrigation, pruning residue biochar with tap water irrigation, and a combination of aerated irrigation and biochar. The results showed that aerated irrigation had no effect on plant growth, but it also increased N2O emission by 12.3% for several days after planting. Plant ion uptake was not affected by aerated irrigation. Biochar amendment increased shoot dry weight and significantly reduced soil N2O emission by 27.9% compared with the control. Plant uptake of N and K also increased with biochar. This study showed that pruning residue biochar has the potential to mitigate N2O emission while increasing vegetable growth and plant nutrient uptake. However, the study soil, Andosol, already has high soil porosity with low bulk density. Thus, further injection of air through irrigation showed no effect on plant growth but increased N2O emission, hence soil aeration was not a limiting factor in Andosol

範囲探索可能な構造化オーバレイにてOverlap ID-Spaceを用いた安定的な負荷分散手法

Structured overlay networks that support range queries cannot hash data IDs for load balancing, in order to preserve the total order on the IDs. Since data and queries are not equally distributed on the ID-space without hashing in range-based overlay networks, uneven loads are imposed on the overlay nodes. Existing load balancing techniques for range-based overlay networks distribute the loads by using data reallocation or node migration, which makes the networks very unstable due to heavy data reallocation or frequent churn.This paper proposes a novel scheme that distributes, fairly, the loads without node migration and with little data reallocation, by sharing some ID-space regions between neighboring nodes. Our “overlapping” ID-space management scheme derives the optimal overlap based on kernel density estimations; the query loads based on the statistical theory are used to calculate the best overlap regions. This calculation is executed in a distributed manner with no central coordinator. We conduct thorough computer simulations, and show that our scheme alleviates the worst node load by 20-90 % against existing techniques without node migration and with least data reallocation

A rare KCNE1 polymorphism, D85N, as a genetic modifier of long QT syndrome

AbstractBackgroundThe gene KCNE1 encodes the β-subunit of cardiac voltage-gated K+ channels and causes long QT syndrome (LQTS). LQTS is characterized by the prolongation of QT interval and lethal arrhythmias such as torsade de pointes (TdP). A KCNE1 polymorphism, D85N, has been shown to modify the phenotype of LQTS through a loss-of-function effect on both KCNQ1 and KCNH2 channels when co-expressed and reconstituted in a heterologous expression system.MethodsA screening for the D85N polymorphism was performed in 355 LQTS families with mutations in KCNQ1, KCNH2, or SCN5A. Among the probands who had a heterozygous status with the polymorphism, we focused on a family with a KCNH2 mutation (E58K), a N-terminal missense mutation, and examined the clinical significance of this polymorphism. We also conducted biophysical assays to analyze the effect of the polymorphism in mammalian cells.ResultsIn 355 probands, we found 14 probands (3.9%) who had a heterozygous compound status with the D85N polymorphism. In the family with a KCNE1-D85N polymorphism and a KCNH2-E58K mutation, the proband and her daughter carried both the KCNH2 mutation and the KCNE1-D85N polymorphism. They experienced repetitive syncope and TdP. Two sons of the proband had either KCNH2-E58K mutation or KCNE1-D85N, but were asymptomatic. Biophysical assays of KCNE1-D85N with KCNH2-E58K variants produced a larger reduction in the reconstituted IKr currents compared to co-expression with wild-type KCNE1.ConclusionsThe KCNE1-D85N polymorphism modified the clinical features of LQTS patients