Abstract. The Kobe earthquake struck at the edge of the densely populated Osaka-Kyoto corridor in southwest Japan. We investigate how the earthquake transferred stress to nearby faults, altering their proximity to failure and thus changing earthquake probabilities. We find that relative to the pre-Kobe seismicity, Kobe aftershocks were concentrated in regions of calculated Coulomb stress increase and less common in regions of stress decrease. We quantify this relationship by forming the spatial correlation between the seismicity rate change and the Coulomb stress change. The correlation is significant for stress changes greater than 0.2-1.0 bars (0.02-0.1 MPa), and the nonlinear dependence of seismicity rate change on stress change is compatible with a state-and rate-dependent formulation for earthquake occurrence. We extend this analysis to future mainshocks by resolving the stress changes on major faults within 100 km of Kobe and calculating the change in probability caused by these stress changes. Transient effects of the stress changes are incorporated by the state-dependent constitutive relation, which amplifies the permanent stress changes during the aftershock period. Earthquake probability framed in this manner is highly timedependent, much more so than is assumed in current practice. Because the probabilities depend on several poorly known parameters of the major faults, we estimate uncertainties of the probabilities by Monte Carlo simulation. This enables us to include uncertainties on the elapsed time since the last earthquake, the repeat time and its variability, and the period of aftershock decay. We estimate that a calculated 3-bar (0.3-MPa) stress increase on the eastern section of the Arima-Takatsuki Tectonic Line (ATTL) near Kyoto causes fivefold increase in the 30-year probability of a subsequent large earthquake near Kyoto; a 2-bar (0.2-MPa) stress decrease on the western section of the ATTL results in a reduction in probability by a factor of 140 to 2000. The probability of a M•,, = 6.9 earthquake within 50 km of Osaka during 1997-2007 is estimated to have risen from 5-6% before the Kobe earthquake to 7-11% afterward; during 1997-2027, it is estimated to have risen from 14-16% before Kobe to 16-22%.

[1] A swarm earthquake sequence is often assumed to be triggered by fluid flow within a brittle fault damage zone, which is assumed to be highly permeable. However, there is little seismological evidence of the relation between the fluid flow within the fault damage zone and the occurrence of swarm earthquakes. Here, we precisely determine the hypocenters and focal mechanisms of swarm earthquakes that occurred in the caldera of Hakone volcano, central Japan, using data from a dense seismic network. We demonstrate that the swarm earthquakes are concentrated on four thin plane-like zones, each of which has a thickness of approximately 100 m. One of the nodal planes of the focal mechanisms agrees with the planar hypocenter distribution. The swarm earthquakes that occurred during the initial stage of the activity exhibited a migration of hypocenters that appears to be represented by the diffusion equation. Based on the spatiotemporal distribution of the earthquakes, the hydraulic diffusivity is estimated to be approximately 0.5-1.0 m 2 /s. The observations imply that swarm earthquakes were triggered by the diffusion of highly pressured fluid within the fault damage zone. A burst-like occurrence of the swarm earthquakes is also observed in the later stage. These swarm earthquakes are thought to have been triggered primarily by local stress changes caused by the preceding activity. The complicated spatiotemporal pattern is thought to have been caused by the effect of the fluid flow within the high-permeability damage zones as well as the stress perturbations generated by the swarm earthquakes themselves.Citation: Yukutake, Y., H. Ito, R. Honda, M. Harada, T. Tanada, and A. Yoshida (2011), Fluid-induced swarm earthquake sequence revealed by precisely determined hypocenters and focal mechanisms in the 2009 activity at Hakone volcano, Japan,

Formalin-fixed, paraffin-embedded (FFPE) tissues used for pathological diagnosis are valuable for studying cancer genomics. In particular, laser-capture microdissection of target cells determined by histopathology combined with FFPE tissue section immunohistochemistry (IHC) enables precise analysis by next-generation sequencing (NGS) of the genetic events occurring in cancer. The result is a new strategy for a pathological tool for cancer diagnosis: ‘microgenomics’. To more conveniently and precisely perform microgenomics, we revealed by systematic analysis the following three details regarding FFPE DNA compared with paired frozen tissue DNA. 1) The best quality of FFPE DNA is obtained by tissue fixation with 10% neutral buffered formalin for 1 day and heat treatment of tissue lysates at 95°C for 30 minutes. 2) IHC staining of FFPE tissues decreases the quantity and quality of FFPE DNA to one-fourth, and antigen retrieval (at 120°C for 15 minutes, pH 6.0) is the major reason for this decrease. 3) FFPE DNA prepared as described herein is sufficient for NGS. For non-mutated tissue specimens, no artifactual mutation occurs during FFPE preparation, as shown by precise comparison of NGS of FFPE DNA and paired frozen tissue DNA followed by validation. These results demonstrate that even FFPE tissues used for routine clinical diagnosis can be utilized to obtain reliable NGS data if appropriate conditions of fixation and validation are applied.

The Pendred syndrome gene encodes a 780-amino acid putative transmembrane protein (pendrin) that is expressed in the apical membrane of thyroid follicular cells. Although pendrin was shown to transport iodide and chloride using Xenopus laevis oocytes and Sf9 insect cells, there is no report using mammalian cells to study its role in thyroid function. We show here, using COS-7 cells and Chinese hamster ovary cells transfected with expression vectors encoding sodium iodide symporter or human Pendred syndrome gene cDNA and by comparison with studies using rat thyroid FRTL-5 cells, that pendrin is an iodide-specific transporter in mammalian cells and is responsible for iodide efflux in the thyroid.

We performed an electrophysiological study to investigate ion transport of pendrin and thereby understand the pathogenesis of Pendred syndrome. Using pendrin-transfected COS-7 cells, we could show that pendrin transports both iodide and chloride measured as voltage-dependent inward and outward membrane currents. Chloride in the culture medium, [Cl-]o, was efficiently exchanged with cytoplasmic iodide, [I-]i, under physiological concentrations, indicating that pendrin is important for chloride uptake and iodide efflux. Although exchange of iodide in the medium, [I-]o, with cytoplasmic chloride, [Cl-]i, was observed, a significantly high concentration of iodide (10 mm) was required. In addition, either iodide or chloride was required on both sides of the cell membrane for the anion exchange activity of pendrin, indicating that iodide and chloride activate the exchange activity of pendrin while they are transported. The present study further supports that pendrin is responsible for the iodide efflux in thyroid cells where intracellular iodide concentration is high and that the general function of pendrin in other tissues is to transport chloride through exchange with other anions.