Microstructure and yield strength of UDIMET 720LI alloyed with Co-16.9 Wt Pct Ti

We proposed a new method for developing Ni-base turbine disc alloy for application at temperatures above 700 °C by mixing a Ni-base superalloy U720LI with a two-phase alloy Co-16.9 wt pct Ti in various contents. The microstructure and phase stability of the alloys were analyzed using an optical microscope, a scanning electron microscope, energy-dispersive spectroscopy, and an X-ray diffractometer. The yield strength was studied by compression tests at temperatures ranging from 25 °C to 1200 °C. The results show that all the alloys had a dendritic structure. Ni₃Ti (η) phase was formed in the interdendritic region in the alloys with the addition of Co-16.9 wt pct Ti, and its volume fraction increased with the increase in the addition of Co-16.9 wt pct Ti. The results of exposure at 750 °C show that the addition of Co-16.9 wt pct Ti to U720LI had a great effect on suppressing the formation of σ phase due to the reduced Cr content in the γ matrix. Compared to U720LI, the alloys with the addition of Co-16.9 wt pct Ti possessed higher yield strength. The solid-solution strengthening of γ and γ′ and higher volume fraction of γ′ were assumed to cause this strength increase.     

On the computational power of insertion-deletion systems

Gene insertion and deletion are basic phenomena found in DNA processing or RNA editing in molecular biology. The genetic mechanism and development based on these evolutionary transformations have been formulated as a formal system with two operations of insertion and deletion, called insertion-deletion systems (Kari and Thierrin, 1996; Kari et al., 1997).We investigate the generative power of insertion-deletion systems (InsDel systems), and show that the family INS ¹ ₁ DEL ¹ ₁ is equal to the family of recursively enumerable languages. This gives a positive answer to an open problem posed in Kari et al. (1997) where it was conjectured contrary. This revised version was published online in June 2006 with corrections to the Cover Date.     

Role of ERAB/L-3-hydroxyacyl-coenzyme A dehydrogenase type II activity in Abeta-induced cytotoxicity

Endoplasmic reticulum-associated amyloid beta-peptide (Abeta)-binding protein (ERAB)/L-3-hydroxyacyl-CoA dehydrogenase type II (HADH II) is expressed at high levels in Alzheimer's disease (AD)-affected brain, binds Abeta, and contributes to Abeta-induced cytotoxicity. Purified recombinant ERAB/HADH II catalyzed the NADH-dependent reduction of S-acetoacetyl-CoA with a Km of approximately 68 microM and a Vmax of approximately 430 micromol/min/mg. The contribution of ERAB/HADH II enzymatic activity to Abeta-mediated cellular dysfunction was studied by site-directed mutagenesis in the catalytic domain (Y168G/K172G). Although COS cells cotransfected to overexpress wild-type ERAB/HADH II and variant beta-amyloid precursor protein (betaAPP(V717G)) showed DNA fragmentation, cotransfection with Y168G/K172G-altered ERAB and betaAPP(V717G) was without effect. We thus asked whether the enzyme might recognize alcohol substrates of which the aldehyde products could be cytotoxic; ERAB/HADH II catalyzed oxidation of a variety of simple alcohols (C2-C10) to their respective aldehydes in the presence of NAD+ and NAD-dependent oxidation of 17beta-estradiol. Addition of micromolar levels of synthetic Abeta(1-40) to purified ERAB/HADH II inhibited, in parallel, reduction of S-acetoacetyl-CoA (Ki approximately 1.6 microM), as well as oxidation of 17beta-estradiol (Ki approximately 3.2 microM) and (-)-2-octanol (Ki approximately 2.6 microM). Because micromolar levels of Abeta were required to inhibit ERAB/HADH II activity, whereas Abeta binding to ERAB/HADH II occurred at much lower concentrations (Km approximately 40-70 nM), the latter more closely simulating Abeta levels within cells, Abeta perturbation of ERAB/HADH II was likely to result from mechanisms other than the direct modulation of enzymatic activity. Cells cotransfected to overexpress ERAB/HADH II and betaAPP(V717G) generated malondialdehyde-protein and 4-hydroxynonenal-protein epitopes, which were detectable only at the lowest levels in cells overexpressing either ERAB/HADH II or betaAPP(V717G) alone. Generation of such toxic aldehydes was not observed in cells contransfected to overexpress Y168G/K172G-altered ERAB and betaAPP(V717G). We conclude that the generalized alcohol dehydrogenase activity of ERAB/HADH II is central to the cytotoxicity observed in an Abeta-rich environment.     

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.     

Functional and Structural Insights into Human PPARα/δ/γ Subtype Selectivity of Bezafibrate,Fenofibric Acid,and Pemafibrate

Among the agonists against three peroxisome proliferator-activated receptor (PPAR) subtypes, those against PPARα (fibrates) and PPARγ (glitazones) are currently used to treat dyslipidemia and type 2 diabetes, respectively, whereas PPARδ agonists are expected to be the next-generation metabolic disease drug. In addition, some dual/pan PPAR agonists are currently being investigated via clinical trials as one of the first curative drugs against nonalcoholic fatty liver disease (NAFLD). Because PPARα/δ/γ share considerable amino acid identity and three-dimensional structures, especially in ligand-binding domains (LBDs), clinically approved fibrates, such as bezafibrate, fenofibric acid, and pemafibrate, could also act on PPARδ/γ when used as anti-NAFLD drugs. Therefore, this study examined their PPARα/δ/γ selectivity using three independent assays—a dual luciferase-based GAL4 transactivation assay for COS-7 cells, time-resolved fluorescence resonance energy transfer-based coactivator recruitment assay, and circular dichroism spectroscopy-based thermostability assay. Although the efficacy and efficiency highly varied between agonists, assay types, and PPAR subtypes, the three fibrates, except fenofibric acid that did not affect PPARδ-mediated transactivation and coactivator recruitment, activated all PPAR subtypes in those assays. Furthermore, we aimed to obtain cocrystal structures of PPARδ/γ-LBD and the three fibrates via X-ray diffraction and versatile crystallization methods, which we recently used to obtain 34 structures of PPARα-LBD cocrystallized with 17 ligands, including the fibrates. We herein reveal five novel high-resolution structures of PPARδ/γ–bezafibrate, PPARγ–fenofibric acid, and PPARδ/γ–pemafibrate, thereby providing the molecular basis for their application beyond dyslipidemia treatment.     

Correction and evaluation of the effect due to parasitic motion on primary accelerometer calibration

Primary accelerometer calibration is carried out under the assumption that a vibration exciter gives a rectilinear motion to an accelerometer to be calibrated. However practical vibration given by the vibration exciter includes parasitic motion such as transverse, rocking, and bending motion. Such parasitic motion would give two serious effects on primary calibration results, transverse motion effect and vibration distribution effect. Transverse motion effect is caused by an inner product of the vectors of both transverse motion and transverse sensitivity. On the other hand, the vibration distribution effect is caused by relative motion between a sensing point of accelerometer and a spot sensed by the interferometer. As these effects have close interaction between parasitic motion and measuring instruments, it would be very difficult to evaluate them by measuring independently each component.     

Queuing Scheme for Improved Downlink Throughput on WLANs

A transmission queuing scheme is described that increases downlink throughput on wireless local area networks (WLANs) while also increasing the total throughput. When the amount of uplink traffic increases on a WLAN, the carrier sense multiple access with collision avoidance (CSMA/CA) protocol, which is the prescribed scheme for IEEE 802.11 WLAN channel access, may substantially reduce the rate of downlink data frame transmission. This results in severe throughput degradation for mobile stations with downlink traffic. The proposed scheme comprises a transmission control function based on consecutive transmission, as described in the IEEE 802.11e standard, and a dynamic queue prioritization algorithm. Simulation results demonstrate that the proposed scheme increases the maximum total throughput for uplink and downlink traffic by 17% compared with the conventional distributed coordination function (DCF) scheme and that it reduces the difference between uplink and downlink throughput. In an environment where transmission errors occur, the difference in throughput is reduced by about 50% compared with the conventional schemes.     

30-GHz bandwidth 1.55-/spl mu/m strain-compensated InGaAlAs-InGaAsP MQW laser

High-speed 1.55 /spl mu/m laser diodes with a 3-dB modulation bandwidths of 30 GHz were fabricated by using short-cavity mushroom structures with undoped, strain-compensated InGaAlAs-InGaAsP twenty-quantum-well active regions. The bandwidths were achieved at low bias current of 100 mA. The laser exhibited a high differential gain of 1.54/spl times/10/sup -15/ cm/sup 2/ and a small K factor of 0.135 ns. These results were achieved by using an In/sub 0.386/Ga/sub 0.465/AlAs barrier with 0.83% tensile strain to reduce the thermal emission time of holes from wells and hence the hole transport time.     

Subharmonic synchronous and hybrid mode-locking of a monolithic DBR laser operating at millimeter-wave frequencies

A detailed comparison of subharmonic synchronous and subharmonic hybrid mode-locking of a monolithic distributed Bragg reflector (DBR) laser operating at 33 GHz is presented. Optical injection at the 20th subharmonic frequency (1.65 GHz) has produced a locking range of 10 MHz with negligible amplitude modulation. In comparison, electrical injection at the 4th subharmonic frequency (5.83 GHz) has shown higher levels of amplitude modulation and a narrower locking range (4 MHz). While subharmonic hybrid mode-locking remains a simple and cost effective solution for the generation of low timing jitter high-repetition rate optical pulse trains, subharmonic synchronous mode-locking shows superior performance with regard to reduced amplitude modulation and larger locking range.