A robust feedforward hybrid active noise control system with online secondary‐path modelling

Abstract In this study, a robust feedforward hybrid active noise control (ANC) system with online secondary‐path modelling (SPM) is proposed that is capable of not only effectively suppressing the broadband and narrowband noise components but also tracking the secondary path (SP) variations. An finite impulse response online SPM subsystem as well as an efficient decoupling filter are included in the proposed feedforward hybrid ANC (HANC) system. The decoupling filter is a parallel‐form bandpass filter bank that consists of multiple bandpass filters that are derived from the second‐order infinite impulse response notch filters. It takes the residual noise as its input and separates the broadband component from the narrowband component, with the former used as not only a desired signal for the SPM but also as an error signal for updating the broadband sub‐controller, whereas the latter adapted simultaneously to scale the auxiliary white Gaussian noise and to update the narrowband sub‐controller. Extensive simulations are conducted with both the synthetic and real SPs as well as the synthetic and real noise signals that are generated by a large‐scale factory cutting machine (strand‐cutter) to demonstrate the advantages and effectiveness of the proposed feedforward HANC system. Comparisons are also demonstrated with the original HANC system as well as its directly extended version with an online SPM subsystem

tRNA Modifying Enzymes, NSUN2 and METTL1, Determine Sensitivity to 5-Fluorouracil in HeLa Cells

<div><p>Nonessential tRNA modifications by methyltransferases are evolutionarily conserved and have been reported to stabilize mature tRNA molecules and prevent rapid tRNA decay (RTD). The tRNA modifying enzymes, NSUN2 and METTL1, are mammalian orthologs of yeast Trm4 and Trm8, which are required for protecting tRNA against RTD. A simultaneous overexpression of NSUN2 and METTL1 is widely observed among human cancers suggesting that targeting of both proteins provides a novel powerful strategy for cancer chemotherapy. Here, we show that combined knockdown of NSUN2 and METTL1 in HeLa cells drastically potentiate sensitivity of cells to 5-fluorouracil (5-FU) whereas heat stress of cells revealed no effects. Since NSUN2 and METTL1 are phosphorylated by Aurora-B and Akt, respectively, and their tRNA modifying activities are suppressed by phosphorylation, overexpression of constitutively dephosphorylated forms of both methyltransferases is able to suppress 5-FU sensitivity. Thus, NSUN2 and METTL1 are implicated in 5-FU sensitivity in HeLa cells. Interfering with methylation of tRNAs might provide a promising rationale to improve 5-FU chemotherapy of cancer.</p></div

Red Indians

red aDuring Cabot's visit to the island he had intercourse with the Red Indians, who were dressed in skins, and painted with red ochre . . . .PRINTED ITEMW. J. KIRWIN DEC 1 5 1969JH 12/69Used I and SupUsed I and Sup3Not use

Degradation of tRNAs in HeLa cells treated with heat stress or 5-FU.

<p>(A) Northern blot analysis of tRNA(Val^AAC), tRNA(iMet), tRNA(eMet), and 5S rRNA. NSUN2 and METTL1 knockdown cells and control vector-transfected cells were treated with 37°C (control), 43°C (heat stress), or 5-FU (7.69 mM) for indicated time. Total RNA (20 µg) was loaded and blotted. (B) Degradation profile of tRNA(Val^AAC), tRNA(iMet), and tRNA(eMet) in NSUN2 and METTL1 knockdown cells (closed symbols) and control vector-transfected cells (open symbols). The cells were treated with 37°C (<i>circle</i>), 43°C (<i>triangle</i>), and 5-FU (<i>square</i>). 5S rRNA transcribed by RNA polymerase III was used as a control, and quantitative data were indicated.</p

Model for how loss of NSUN2- and METTL1-dependent tRNA(Val^AAC) modifications causes 5-FU-induced tRNA destabilization.

<p>(A) Synthetic interaction between <i>trm4</i> and <i>trm8</i> mutations in yeast. The temperature-sensitive phenotype of yeast <i>trm4</i>/<i>trm8</i> double mutant is due to rapid decay of hypomodified tRNA. A melted loop indicates destabilized tRNA. Although 5-FU-induced tRNA damage(s) that mediate tRNA destabilization remains to be fully determined, reduced pseudouridylation is the most likely cause of this. Only <i>trm8</i> mutant, but not <i>trm4</i> mutant, is sensitive to 5-FU. And so hypomodified tRNA caused by <i>trm4</i> and <i>trm8</i> mutations is probably hypersensitive to 5-FU (shown as a melted loop with question mark). (B) Cooperative effect between NSUN2 and METTL1 in HeLa cells. Hypomodified tRNA caused by double knockdown of NSUN2 and METTL1 is not heat-sensitive but is 5-FU-sensitive. A melted loop indicates destabilized tRNA.</p

Colony formation assay showing synergistic effects of NSUN2 and METTL1 double knock down and 5-FU-treatment.

<p>(A) Depiction of colonies formed after 5-FU treatment at various concentrations on Giemsa-stained dishes. (B) Dose-dependent cell survival in response to 5-FU in NSUN2 and METTL1 knockdown cells (<i>open triangle</i>), the parent cells (<i>closed circle</i>), and control vector-transfected cells (<i>open circle</i>) in colony formation assay. (C) Comparison of the average IC₅₀ values for 5-FU assessed by colony formation assay between NSUN2 and METTL1 knockdown cells and control vector-transfected cells. *Significant difference compared with control vector-transfected cells (<i>P</i><0.05).</p