Mutations of the transforming growth factor-beta type II receptor gene are strongly related to sporadic proximal colon carcinomas with microsatellite instability

BACKGROUND: Mutations of the transforming growth factor-beta type II receptor gene (TGF-beta RII) have been found in several replication error-positive sporadic colorectal carcinomas and hereditary nonpolyposis colorectal carcinoma cell lines. The aim of this study was to clarify the role of TGF-beta RII in sporadic colorectal carcinogenesis. METHODS: The authors screened for mutations at simple repeated sequences in the TGF-beta RII gene by polymerase chain reaction-single strand conformation polymorphism. They also examined genomic instability, using five microsatellite DNA markers in 69 sporadic colorectal carcinomas. When the carcinomas exhibited the TGF-beta RII mutations, the authors screened further for mutations in two DNA mismatch repair genes, hMSH2 and hMLH1. RESULTS: Seven of the 69 cancers (10%) showed one or two A deletions in TGF-beta RII and resultant frameshift mutations in nucleotide positions 709-718 containing a (A) 10 repeated sequence; but none of these appeared in the corresponding normal DNA, indicating a somatic mutation. All of the seven cancers were located in the proximal colon; there were none in the distal colon (P < 0.01). On the other hand, 22 of the 69 carcinomas (32%) showed the replication error-positive phenotype. The frequency of replication errors in proximal colon carcinomas was higher than that in distal colon carcinomas (P < 0.05). All 7 cancers with TGF-beta RII mutations showed replication errors. One of them revealed a nonsense mutation at codon 413, and 1 revealed a loss of heterozygosity in hMSH2. CONCLUSIONS: These data indicate that mutations of TGF-beta RII are strongly related to proximal colon carcinomas with microsatellite instability and that the mechanism of carcinogenesis in some proximal colon carcinomas is similar to that in hereditary nonpolyposis colorectal carcinoma.     

Turbulence generated by a wind tunnel of multi-fan type in uniformly active and quasi-grid modes

In an attempt to simulate atmospheric turbulence at high-Reynolds numbers, an innovative wind tunnel of “multi-fan type” is developed. The airflow is driven by an array of fans (9 columns × 11 rows), each of which is independently controlled by a computer. A driving mode (“uniformly active mode”) is applied, which has been typically used for turbulence modeling using a smaller wind tunnel. Another mode with grid-like distributed fans that are driven steadily (“quasi-grid mode”) is introduced and found to produce turbulence characteristics similar to the conventional grid turbulence. Comparison of turbulence characteristics of the two modes reveals the turbulence structure of the uniformly active mode.     

Pulmonary arterial impedance analysis by the use of the oscillated assist flow

Pulmonary arterial impedance is an important and interesting characteristic that can be used to evaluate the physiological properties of the pulmonary vessel. However, power spectrum analysis of the pulmonary artery pressure and flow pattern have suggested that peak power in the relatively high frequency range (> 10 Hz) is significantly low; thus, we cannot analyze the vessel properties in the high frequency range. In this study, we used the newly developed vibrating flow pump (VFP), which can generate oscillated blood flow with a relatively high frequency (10-50 Hz) for right heart bypass, to evaluate the pulmonary arterial impedance pattern in the high frequency range. Acute animal experiments of the right heart bypass from the right atrium to the pulmonary artery using 6 healthy adult goats were performed. The flow pattern and pressure of the pulmonary artery, electrocardiograms (ECGs), and arterial and right atrial pressures were continuously monitored during the experiments. Spectral analysis of the hemodynamic parameters using the fast Fourier transform (FFT) method was performed to evaluate the spectral properties. The coherence function, transfer function, and phase patterns were calculated to analyze the impedance pattern in the relatively high frequency area. Previously, various investigators had tried to analyze the impedance patterns of the pulmonary artery; however, they could not analyze the impedance patterns over 10 Hz because the spectral patterns of the pulmonary flow do not have high power at high frequencies. These physiological analyses may be useful in designing the optimal pulmonary circulation.     

Study of point defects in CuGaSe2 single crystals by means of electron paramagnetic resonance and photoluminescence

Point defects in CuGaSe₂ single crystals as vacancies V_Se, V_Cu and defect pair (2V_Cu⁻+Ga_Cu²⁺) have been studied by means of electron paramagnetic resonance (EPR) and low-temperature photoluminescence (PL). EPR hyperfine structure has been found at temperatures as low as 1.45–45 K and the temperature dependence of EPR line is discussed. Photo-EPR spectrum reveals optically active behavior of intrinsic point defects in CuGaSe₂ crystals. Three bands of PL emission show different origins and two low-energy bands at 1.55 and 1.58 eV have been found to be steady despite H₂-, O₂- and Se₂-annealings. The experimental data added with electric characterization in accordance with the used annealings and together with a defect physics model allow consideration of the point defect ensemble in CuGaSe₂ in more detail.     

Optimal number of uses for an intermittently-used system

This paper studies an intermittently-used system which fails by continuous deterioration with age or by discrete deterioration with use. The system is replaced before failure at number N of uses. The optimal number N^* to minimize the expected cost rate is discussed for three particular cases. The case where the system deteriorates with both operating time and use time is considered.     

Modeling resistive switching materials and devices across scales

Resistance switching devices based on electrochemical processes have attractive significant attention in the field of nanoelectronics due to the possibility of switching in nanosecond timescales, miniaturization to tens of nanometer and multi-bit storage. Their deceptively simple structures (metal-insulator-metal stack) hide a set of complex, coupled, processes that govern their operation, from electrochemical reactions at interfaces, diffusion and aggregation of ionic species, to electron and hole trapping and Joule heating. A combination of experiments and modeling efforts are contributing to a fundamental understanding of these devices, and progress towards a predictive understanding of their operation is opening the possibility for the rational optimization. In this paper we review recent progress in modeling resistive switching devices at multiple scales; we briefly describe simulation tools appropriate at each scale and the key insight that has been derived from them. Starting with ab initio electronic structure simulations that provide an understanding of the mechanisms of operation of valence change devices pointing to the importance of the aggregation of oxygen vacancies in resistance switching and how dopants affect performance. At slightly larger scales we describe reactive molecular dynamics simulations of the operation of electrochemical metallization cells. Here the dynamical simulations provide an atomic picture of the mechanisms behind the electrochemical formation and stabilization of conductive metallic filaments that provide a low-resistance path for electronic conduction. Kinetic Monte Carlo simulations are one step higher in the multiscale ladder and enable larger scale simulations and longer times, enabling, for example, the study of variability in switching speed and resistance. Finally, we discuss physics-based simulations that accurately capture subtleties of device behavior and that can be incorporated in circuit simulations.