No abstract

We study the asymptotic behaviour of tame harmonic bundles. First of all, we prove a local freeness of the prolongation by an increasing order. Then we obtain the polarized mixed twistor structure. As one of the applications, we obtain the norm estimate of holomorphic or flat sections by weight filtrations of the monodromies.As other application, we establish the correspondence of semisimple regular holonomic D-modules and polarizable pure imaginary pure twistor D-modules through a tame pure imaginary harmonic bundles, which is a conjecture of Sabbah. Then the regular holonomic version of Kashiwara's conjecture follows from the results of Sabbah and us.

Pancreatic adenocarcinoma is an aggressive human malignancy and is characterized by resistance to apoptosis. Recently, NADPH oxidase (Nox) 4-mediated generation of intracellular reactive oxygen species (ROS) was proposed to confer antiapoptotic activity and thus a growth advantage to pancreatic cancer cells. The signaling mechanism by which Nox4 transmits cell survival signals remains unclear. Here, we show that both a flavoprotein inhibitor, diphenylene iodonium (DPI), and small interfering RNAs designed to target Nox4 mRNA (siNox4R-NAs) inhibited superoxide production in PANC-1 pancreatic cancer cells, and depletion of ROS by DPI or siNox4RNAs induced apoptosis. Parallely, DPI treatment and siNox4RNA transfection blocked activation of the cell survival kinase AKT by attenuating phosphorylation of AKT. Furthermore, AKT phosphorylation of apoptosis signal-regulating kinase 1 (ASK1) on Ser-83 was reduced by DPI and siNox4RNAs. When ASK1Ser83Ala (an AKT phosphorylation-defective ASK1 mutant) was introduced into PANC-1 cells, this mutant alone induced apoptosis. But, addition of DPI or co-transfection of siNox4RNA had no additive effect, indicating that the mutant can substitute for these reagents in apoptosis induction. Taken together, these findings suggest that ROS generated by Nox4, at least in part, transmit cell survival signals through the AKT-ASK1 pathway in pancreatic cancer cells and their depletion leads to apoptosis.

Let X be a smooth projective complex variety with an ample line bundle L, and let D be a simple normal crossing divisor. We establish the Kobayashi-Hitchin correspondence between tame harmonic bundles on X − D and µL-stable parabolic λ-flat bundles with trivial characteristic numbers on (X, D). Especially, we obtain the quasiprojective version of the Corlette-Simpson correspondence between flat bundles and Higgs bundles.

We study the asymptotic behaviour of tame harmonic bundles. First of all, we prove a local freeness of the prolongation by an increasing order. Then we obtain the polarized mixed twistor structure. As one of the applications, we obtain the norm estimate of holomorphic or flat sections by weight filtrations of the monodromies.As other application, we establish the correspondence of semisimple regular holonomic D-modules and polarizable pure imaginary pure twistor D-modules through a tame pure imaginary harmonic bundles, which is a conjecture of Sabbah. Then the regular holonomic version of Kashiwara's conjecture follows from the results of Sabbah and us.