Term Structure of Interest Rates under Recursive Preferences in Continuous Time ( Revised in February 2008, subsequently published in "Asia-Pacific Financial Markets", Vol.15-3,4, 273-305. )

This paper proposes a testable continuous-time term-structure model with recursive utility to investigate structural relationships between the real economy and the term structure of real and nominal interest rates. In a representative-agent model with recursive utility and mean-reverting expectations on real output growth and inflation, this paper shows that, if (1) real short-term interest rates are high during economic booms and (2) the agent is comparatively risk-averse (less risk-averse) relative to time-separable utility, then a real yield curve slopes down (slopes up, respectively). Additionally, for the comparatively risk-averse agent, if (3) expected inflation is negatively correlated with the real output and its expected growth, then a nominal yield curve can slope up, regardless of the slope of the real yield curve.

Present and Future Therapies for Alzheimer’s Disease

Alzheimer’s disease (AD) is an incurable, progressive neurodegenerative disorder and the most common type of dementia. Although four kinds of drugs are currently available for AD, these are symptomatic treatments and do not halt disease progression. Therefore, there is an urgent need for development of curative drugs for AD. Amyloid plaques are the main disease hallmark observed in AD brains. As amyloid-β (Aβ) is a major constituent of amyloid plaques, Aβ has been supposed to be pathogenic for AD (amyloid hypothesis). Thus, current, mainstream AD drug development is based around this hypothesis. In particular, both active and passive immunotherapies are aggressively employed. However, most clinical trials based on this hypothesis, including immunotherapies, failed to improve cognitive impairment in AD. Therefore, it is likely that AD onset is caused by factors besides Aβ. We have previously demonstrated that the intracellular domain of amyloid precursor protein (AICD) induces dynamic changes in gene expression and neuron-specific apoptosis, probably related to AD pathogenesis. Therefore, AICD may be a favorable target for AD therapies. In this chapter, current trials for AD therapies, especially immunotherapies targeting Aβ, are summarized. In addition, therapies targeting tau, another possible pathogenic molecule, are also described. Furthermore, we discuss the possibility of AICD as a novel therapeutic target for AD

γ-Secretase-Regulated Mechanisms Similar to Notch Signaling May Play a Role in Signaling Events, Including APP Signaling, Which Leads to Alzheimer's Disease

Although gamma-secretase was first identified as a protease that cleaves amyloid precursor protein (APP) within the transmembrane domain, thus producing A beta peptides that are thought to be pathogenic in Alzheimer's disease (AD), its physiological functions have not been fully elucidated. In the canonical Notch signaling pathway, intramembrane cleavage by gamma-secretase serves to release an intracellular domain of Notch that shows activity in the nucleus through binding to transcription factors. Many type 1 transmembrane proteins, including Notch, Delta, and APP, have recently been shown to be substrates for gamma-secretase, and their intracellular domains are released from the cell membrane following cleavage by gamma-secretase. The common enzyme gamma-secretase modulates proteolysis and the turnover of possible signaling molecules, which has led to the attractive hypothesis that mechanisms similar to Notch signaling contribute widely to proteolysis-regulated signaling pathways. APP is also likely to have a signaling mechanism, although the physiological functions of APP have not been elucidated. Indeed, we have shown that the intracellular domain of APP alters gene expression and induces neuron-specific apoptosis. These results suggest that APP signaling responds to the onset of AD. Here, we review the possibility of gamma-secretase-regulated signaling, including APP signaling, which leads to AD.ArticleCELLULAR AND MOLECULAR NEUROBIOLOGY. 31(6):887-900 (2011)journal articl

24- and 120-chanell transmultiplexers built with new digital signal processing LSI\u27s

金沢大学大学院自然科学研究科情報システム金沢大学工学部Two new digital transmultiplexers intended for commerical use have been developed. One transmultiplexer performs a bilateral conversion between two 12-channel FDM group signals and a 24-channel PCM carrier signal. The other mutually connects two 60-channel FDM supergroup signals and five 24-channel or four 30-channel PCM signals. Both exploit a block processing digital SSB-FDM multiplex/demultiplex scheme employing a cascade of an FFT processor and a set of complex coefficient digital filters. They have been built using newly developed high-level DSP LSI chips. Algorithmic considerations, developed LSI architecture, and equipment configuration are described as well as digital processor design details and measured performance

Ochratoxin A, citrinin and deoxynivalenol decrease claudin-2 expression in mouse rectum CMT93-II cells.

Intestinal epithelial cells are the first targets of ingested mycotoxins, such as ochratoxin A, citrinin and deoxynivalenol. It has been reported that paracellular permeability regulated by tight junctions is modulated by several mycotoxins by reducing the expression of specific claudins and integral membrane proteins in cell-cell contacts, accompanied by increase in phosphorylation of mitogen-activated protein kinases, including extracellular signal-related kinase (ERK) 1/2, p38 and c-Jun NH2-terminal protein kinase. Claudin-2 is expressed in the deep crypt cells, but not in the villus/surface cells in vivo. While Caco-2, T84 and IPEC-J2 cells, which are widely used intestinal epithelial cell lines to assess the influence of mycotoxins, do not express claudin-2, CMT93-II cells express claudin-2. We previously reported that inhibition of the ERK pathway reduced claudin-2 levels in cell-cell contacts in CMT93-II cells. In this study, we examined whether ochratoxin A, citrinin and deoxynivalenol affect claudin-2 expression and ERK1/2 phosphorylation in CMT93-II cells. We found that all mycotoxins reduced claudin-2 expression in cell-cell contacts, with reduction (by citrinin and deoxynivalenol) or no change (by ochratoxin A) in phosphorylated ERK1/2. All mycotoxins increased transepithelial electrical resistance, but did not affect flux of fluorescein. While ochratoxin A and citrinin are known to be nephrotoxic, only deoxynivalenol reduced claudin-2 expression in MDCK II cells derived from the renal tubule. These results suggest that claudin-2 expression is regulated not only by the ERK pathway, but also by other pathways in an organ-specific manner.福岡歯科大学2017年