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Metal amorphous nanocomposite (MANC) alloys are an emerging class of soft magnetic materials showing promise for a range of inductive components targeted for higher power density and higher efficiency power conversion applications including inductors, transformers, and rotating electrical machinery. Magnetization reversal mechanisms within these alloys are typically determined by composition optimization as well as controlled annealing treatments to generate a nanocomposite structure composed of nanocrystals embedded in an amorphous precursor. Here we demonstrate the concept of spatially varying the permeability within a given component for optimization of performance by using the strain annealing process. The concept is realized experimentally through the smoothing of the flux profile from the inner to outer core radius achieved by a monotonic variation in tension during the strain annealing process. Great potential exists for an extension of this concept to a wide range of other power magnetic components and more complex spatially varying permeability profiles through advances in strain annealing techniques and controls.

It has been established that mutations in Drosophila Polo cause abnormalities in mitosis 1 . In human cells, maximal Plk activity is reached in the M phase of the cell cycle, and the function of Plk is therefore considered to be required for mitotic cellular events such as spindle formation, chromosome segregation and cytokinesis. Microinjection of anti-Plk antibody into living cells has been found to induce a mitotic abnormality that contributes to the generation of aneuploidy 2 , and this is an important finding in relation to tumour development. Indeed, previous studies have shown that the level of expression of a mitotic checkpoint gene, hsMAD2 , is reduced 3 and that another checkpoint gene, BUB1 , is mutated in certain human cancer cells 4 .

Bcl-x(L), an anti-apoptotic Bcl-2 family member protein, contributes to the resistance against chemotherapies such as tubulin-binder treatment in many human tumors. Although Bcl-x(L) is phosphorylated after tubulin-binder treatment, the role of the phosphorylation and its responsible kinase(s) are poorly understood. Here, we identified Plk1 (polo-like kinase 1) as a Bcl-x(L) kinase. Same location of Bcl-x(L) and Plk1 was revealed by immunocytochemical analyses at M-phase in situ. Plk1 phosphorylates Bcl-x(L) in vitro, and we identified Plk1 phosphorylation sites in Bcl-x(L). When all of these phosphorylation sites were substituted to alanines, the anti-apoptotic activity of the Bcl-x(L) mutant against the apoptosis induced by pironetin, but not against ultraviolet-induced apoptosis, was increased. These observations suggest that Plk1 is a regulator of Bcl-x(L) phosphorylation and controls the anti-apoptotic activity of Bcl-x(L) during pironetin-induced apoptosis.

[Bcl-x.sub.L], an anti-apoptotic Bcl-2 family member protein, contributes to the resistance against chemotherapies such as tubulin-binder treatment in many human tumors. Although [Bcl-x.sub.L] is phosphorylated after tubulin-binder treatment, the role of the phosphorylation and its responsible kinase(s) are poorly understood. Here, we identified Plk1 (polo-like kinase 1) as a [Bcl-x.sub.L] kinase. Same location of [Bcl-x.sub.L] and Plk1 was revealed by immunocytochemical analyses at M-phase in situ. Plk1 phosphorylates [Bcl-x.sub.L] in vitro, and we identified Plk1 phosphorylation sites in [Bcl-x.sub.L]. When all of these phosphorylation sites were substituted to alanines, the anti-apoptotic activity of the [Bcl-x.sub.L] mutant against the apoptosis induced by pironetin, but not against ultraviolet-induced apoptosis, was increased. These observations suggest that Plk1 is a regulator of [Bcl-x.sub.L] phosphorylation and controls the anti-apoptotic activity of [Bcl-x.sub.L] during pironetin-induced apoptosis.

Cancer cells require the ability to degrade the extracellular matrix (ECM) in order to turn into invasive and metastatic cancer cells. Many proteases and glycosidases are essential in the process of dissolving the components of the ECM. An endo‐β‐D‐glucuronidase, heparanase, is capable of specifically degrading one of the ECM components, heparan sulfate, and this activity is associated with the metastatic potential of tumor cells. Since heparanase mRNA is overexpressed in many human tumors (e.g., hepatomas, head and neck tumors, and esophageal carcinomas), the mechanisms regulating the activity of heparanase should be clarified; considering the possible role of heparanase in cancer, the development of heparanase inhibitors would appear to be advantageous. This review will focus on recent findings that have contributed to the characterization of heparanase and to the elucidation of the transcriptional regulation of heparanase mRNA expression, as well as the development of heparanase inhibitors.

The anti‐apoptotic protein, Bcl‐2 was phosphorylated at the Ser‐87 residue in normal human blood cells, while it was not phosphorylated in tumor cells. We identified protein phosphatase 2A (PP2A) as a Bcl‐2‐associated phosphatase that is responsible for dephosphorylation of Bcl‐2 in tumor cell lines. Treatment of the tumor cells with a PP2A inhibitor resulted in the appearance of Bcl‐2 phosphorylation at Ser‐87. This observation suggests that Bcl‐2 is constitutively phosphorylated, but is immediately dephosphorylated by PP2A in tumors. Phosphorylation of Bcl‐2 protein at the Ser‐87 residue resulted in a reduction in anti‐apoptotic function in human tumor cell lines. Thus, not only the expression level, but also the dephosphorylation status may have important implications for the oncogenic activity of Bcl‐2.

Bcl-x L , an anti-apoptotic Bcl-2 family member protein, contributes to the resistance against chemotherapies such as tubulin-binder treatment in many human tumors. Although Bcl-x L is phosphorylated after tubulin-binder treatment, the role of the phosphorylation and its responsible kinase(s) are poorly understood. Here, we identified Plk1 (polo-like kinase 1) as a Bcl-x L kinase. Same location of Bcl-x L and Plk1 was revealed by immunocytochemical analyses at M-phase in situ . Plk1 phosphorylates Bcl-x L in vitro , and we identified Plk1 phosphorylation sites in Bcl-x L . When all of these phosphorylation sites were substituted to alanines, the anti-apoptotic activity of the Bcl-x L mutant against the apoptosis induced by pironetin, but not against ultraviolet-induced apoptosis, was increased. These observations suggest that Plk1 is a regulator of Bcl-x L phosphorylation and controls the anti-apoptotic activity of Bcl-x L during pironetin-induced apoptosis.

Bcl-x sub(L), an anti-apoptotic Bcl-2 family member protein, contributes to the resistance against chemotherapies such as tubulin-binder treatment in many human tumors. Although Bcl-x sub(L) is phosphorylated after tubulin-binder treatment, the role of the phosphorylation and its responsible kinase(s) are poorly understood. Here, we identified Plk1 (polo-like kinase 1) as a Bcl- x sub(L) kinase. Same location of Bcl-x sub(L) and Plk1 was revealed by immunocytochemical analyses at M-phase in situ. Plk1 phosphorylates Bcl- x sub(L) in vitro, and we identified Plk1 phosphorylation sites in Bcl- x sub(L). When all of these phosphorylation sites were substituted to alanines, the anti-apoptotic activity of the Bcl-x sub(L) mutant against the apoptosis induced by pironetin, but not against ultraviolet-induced apoptosis, was increased. These observations suggest that Plk1 is a regulator of Bcl-x sub(L) phosphorylation and controls the anti-apoptotic activity of Bcl-x sub(L) during pironetin-induced apoptosis.

It is well known that human leukemia cells, such as HL‐60 and U937 are sensitive to antitumor drugs, but human normal lung fibroblasts, such as WI‐38 cells are resistant to the drugs. However, the mechanisms of the different responses to apoptosis in these cell lines remain unclear. We report here that an increase of Fas and Fas ligand (FasL) expression was required for antitumor druginduced apoptosis in WI‐38 and baby hamster kidney (BHK) cells, but not in HL‐60 cells. Then, we used BHK cells transfected with the bcl‐2 gene to investigate the involvement of complex formation of Bcl‐2 and calcineurin. Calcineurin was imported to the nucleus in response to the drug treatment. Overexpression of Bcl‐2 and cyclosporin A treatment inhibited the nuclear import and FasL expression, and as a result, both inhibited apoptosis. Although a caspase inhibitor, z‐Asp‐CH2‐DCB, suppressed the drug‐induced apoptosis, it failed to inhibit the drug‐induced expression of Fas and FasL. These findings suggest that initially the Fas/FasL system is activated by calcineurindependent transcription followed by activation of the downstream caspase cascade resulting in antitumor drug‐induced apoptosis in BHK cells, but not in HL‐60 cells. Furthermore, Bcl‐2 inhibits the nuclear import of calcineurin and suppresses calcineurin‐mediated FasL expression during antitumor drug‐induced apoptosis.