Non-irradiation-derived reactive oxygen species (ROS) and cancer: therapeutic implications

Owing to their chemical reactivity, radicals have cytocidal properties. Destruction of cells by irradiation-induced radical formation is one of the most frequent interventions in cancer therapy. An alternative to irradiation-induced radical formation is in principle drug-induced formation of radicals, and the formation of toxic metabolites by enzyme catalysed reactions. Although these developments are currently still in their infancy, they nevertheless deserve consideration. There are now numerous examples known of conventional anti-cancer drugs that may at least in part exert cytotoxicity by induction of radical formation. Some drugs, such as arsenic trioxide and 2-methoxy-estradiol, were shown to induce programmed cell death due to radical formation. Enzyme-catalysed radical formation has the advantage that cytotoxic products are produced continuously over an extended period of time in the vicinity of tumour cells. Up to now the enzymatic formation of toxic metabolites has nearly exclusively been investigated using bovine serum amine oxidase (BSAO), and spermine as substrate. The metabolites of this reaction, hydrogen peroxide and aldehydes are cytotoxic. The combination of BSAO and spermine is not only able to prevent tumour cell growth, but prevents also tumour growth, particularly well if the enzyme has been conjugated with a biocompatible gel. Since the tumour cells release substrates of BSAO, the administration of spermine is not required. Combination with cytotoxic drugs, and elevation of temperature improves the cytocidal effect of spermine metabolites. The fact that multidrug resistant cells are more sensitive to spermine metabolites than their wild type counterparts makes this new approach especially attractive, since the development of multidrug resistance is one of the major problems of conventional cancer therapy

Investigation of the magnetic properties of Si-gradient steel sheet by comparison with 6.5%Si steel sheet

In this study, we investigated the magnetic properties of Si-gradient steel sheet produced by CVD (chemical vapor deposition) siliconizing process, comparing with 6.5% Si steel sheet. The Si-gradient steel sheet having silicon concentration gradient in the thickness direction, has larger hysteresis loss and smaller eddy current loss than the 6.5% Si steel sheet. In such a loss configuration, the iron loss of the Si-gradient steel sheet becomes lower than that of the 6.5% Si steel sheet at high frequencies. The experiment suggests that tensile stress is formed at the surface layer and compressive stress is formed at the inner layer in the Si gradient steel sheet. The magnetic anisotropy is induced by the internal stress and it is considered to affect the magnetization behavior of the Si-gradient steel sheet. The small eddy current loss of Si-gradient steel sheet can be explained as an effect of magnetic flux concentration on the surface layer

Evaluation of MAX-DOAS aerosol retrievals by coincident observations using CRDS, lidar, and sky radiometer inTsukuba, Japan

Coincident aerosol observations of multi-axis differential optical absorption spectroscopy (MAX-DOAS), cavity ring-down spectroscopy (CRDS), lidar, and sky radiometer were conducted in Tsukuba, Japan, on 5–18 October 2010. MAX-DOAS aerosol retrieval (for aerosol extinction coefficient and aerosol optical depth at 476 nm) was evaluated from the viewpoint of the need for a correction factor for oxygen collision complexes (O₄ or O₂–O₂) absorption. The present study strongly supports this need, as systematic residuals at relatively high elevation angles (20 and 30°) were evident in MAX-DOAS profile retrievals conducted without the correction. However, adopting a single number for the correction factor (<i>f</i>_O₄ = 1.25) for all of the elevation angles led to systematic overestimation of near-surface aerosol extinction coefficients, as reported in the literature. To achieve agreement with all three observations, we limited the set of elevation angles to &le;10° and adopted an elevation-angle-dependent correction factor for practical profile retrievals with scattered light observations by a ground-based MAX-DOAS. With these modifications, we expect to minimize the possible effects of temperature-dependent O₄ absorption cross section and uncertainty in DOAS fit on an aerosol profile retrieval, although more efforts are encouraged to quantitatively identify a physical explanation for the need of a correction factor

A Dof-CLE circuit controls phloem organization

This study shows that Dof transcription factors in the phloem precursors not only induce formation of phloem, but also cause secretion of CLE peptides, which in turn inhibit phloem formation in neighbourhing cells by post-transcriptionally decreasing Dofs. The phloem consists of sieve elements (SEs) and companion cells (CCs). Here we show that Dof-class transcription factors preferentially expressed in the phloem (phloem-Dofs) are not only necessary and sufficient for SE and CC differentiation, but also induce negative regulators of phloem development, CLAVATA3/EMBRYO SURROUNDING REGION-RELATED25 (CLE25), CLE26 and CLE45 secretory peptides. CLEs were perceived by BARELY ANY MERISTEM (BAM)-class receptors and CLAVATA3 INSENSITIVE RECEPTOR KINASE (CIK) co-receptors, and post-transcriptionally decreased phloem-Dof proteins and repressed SE and CC formation. Multiple mutations in CLE-, BAM- or CIK-class genes caused ectopic formation of SEs and CCs, producing an SE/CC cluster at each phloem region. We propose that while phloem-Dofs induce phloem cell formation, they inhibit excess phloem cell formation by inducing CLEs. Normal-positioned SE and CC precursor cells appear to overcome the effect of CLEs by reinforcing the production of phloem-Dofs through a positive feedback transcriptional regulation