Measuring the Intertemporal Elasticity of Substitution for Consumption: Some Evidence from Japan

The purpose of this paper is to present improved estimates of the intertemporal elasticity of substitution (IES) for Japan assuming a constant relative risk aversion (CRRA) utility function. The estimates of the IES we obtain range from 0.2 to 0.5 when we use quarterly consumption data and the Continuous Updating Estimator (CUE). We find that the IES is weakly identified when we employ the two-step GMM estimator, while the CUE can identify the IES. Moreover, we also find that using consumption data of different frequencies leads to quite different estimates of the IES.Intertemporal Elasticity of Substitution, Relative Risk Aversion, Generalized Method of Moments, Continuous Updating Estimator, Weak Identification

Accretion Geometry of the Low-Mass X-ray Binary Aquila X-1 in the Soft and Hard States

The neutron-star Low-Mass X-ray Binary Aquila X-1 was observed seven times in total with the Suzaku X-ray observatory from September 28 to October 30 in 2007, in the decaying phase of an outburst. In order to constrain the flux-dependent accretion geometry of this source over wider energy bands than employed in most of previous works, the present study utilized two out of the seven data sets. The 0.8-31 keV spectrum on September 28, taken with the XIS and HXD-PIN for an exposure of 13.8 ks, shows an absorbed 0.8-31 keV flux of $3.6\times 10^{-9}$ erg s$^{-1}$ cm$^{-2}$, together with typical characteristics of the soft state of this type of objects. The spectrum was successfully explained by an optically-thick disk emission plus a Comptonized blackbody component. Although these results are in general agreement with previous studies, the significance of a hard tail recently reported using the same data was inconclusive in our analysis. The spectrum acquired on October 9 for an exposure of 19.7 ks was detected over a 0.8-100 keV band with the XIS, HXD-PIN, and HXD-GSO, at an absorbed flux of $8.5\times 10^{-10}$ erg s$^{-1}$ cm$^{-2}$ (in 0.8-100 keV). It shows characteristics of the hard state, and was successfully explained by the same two continuum components but with rather different parameters including much stronger thermal Comptonization, of which the seed photon source was identified with blackbody emission from the neutron-star surface. As a result, the accretion flow in the hard state is inferred to take a form of an optically-thick and geometrically-thin disk down to a radius of $21\pm 4$ km from the neutron star, and then turn into an optically-thin nearly-spherical hot flow.Comment: PASJ in publish. 12 pages including 16 figure

Longitudinal observation of insulin secretory ability before and after the onset of immune checkpoint inhibitor-induced diabetes mellitus: A report of two cases

Immune checkpoint inhibitor-induced diabetes mellitus is a rare immune-related adverse event. This report illustrates clinical data and insulin secretory ability before and after the onset of immune checkpoint inhibitor-induced diabetes

Prevalence of gastroesophageal reflux disorder in arrhythmic patients and adjunctive effects of proton pump inhibitors on comorbid atrial fibrillation

Background: Although the coexistence of atrial fibrillation (AF) and gastroesophageal reflux disorder (GERD) has been reported, the prevalence of GERD in arrhythmic patients remains unknown. This study aimed to investigate the relationship between GERD and several kinds of arrhythmia, and the therapeutic effects of proton pump inhibitors (PPI) on AF.Methods: In Study 1, patients with various kinds of arrhythmia (n=147) including AF (n=98) were administered a GERD-specific questionnaire (F-scale). In Study 2, patients with AF and GERD (n=27) responded to an AF-specific questionnaire (AFQLQ) before and after the additive PPI therapy to explore the effects of PPI on comorbid AF. In Study 3, device memory was assessed as it is related to PPI administration in pacemaker patients with GERD and AF (n=5) to study the effects of PPI on device-documented AF.Results: Left atrial (LA) size and F-scale scores in AF patients were the largest among the arrhythmic patients in Study 1. Logistic regression analysis showed no independent determinants of GERD. F-scale scores and AFQLQ scores showed temporal and partial correlations and significant improvement after starting PPI in Study 2. However, device interrogation confirmed limited AF improvement by starting PPI in Study 3.Conclusions: GERD is prevalent in AF patients. LA size is not an independent determinant of GERD. Symptoms of AF were improved, whereas device-documented paroxysms of AF were not ameliorated by PPI administration. A large-scale prospective study is required to conclude the efficacy of PPI on the comorbid AF

The grid-dose-spreading algorithm for dose distribution calculation in heavy charged particle radiotherapy

A new variant of the pencil-beam (PB) algorithm for dose distribution calculation for radiotherapy with protons and heavier ions, the grid-dose spreading (GDS) algorithm, is proposed. The GDS algorithm is intrinsically faster than conventional PB algorithms due to approximations in convolution integral, where physical calculations are decoupled from simple grid-to-grid energy transfer. It was effortlessly implemented to a carbon-ion radiotherapy treatment planning system to enable realistic beam blurring in the field, which was absent with the broad-beam (BB) algorithm. For a typical prostate treatment, the slowing factor of the GDS algorithm relative to the BB algorithm was 1.4, which is a great improvement over the conventional PB algorithms with a typical slowing factor of several tens. The GDS algorithm is mathematically equivalent to the PB algorithm for horizontal and vertical coplanar beams commonly used in carbon-ion radiotherapy while dose deformation within the size of the pristine spread occurs for angled beams, which was within 3 mm for a single proton pencil beam of $30^\circ$ incidence, and needs to be assessed against the clinical requirements and tolerances in practical situations.Comment: 7 pages, 3 figure

Neuroprotective response after photodynamic therapy: Role of vascular endothelial growth factor

Background: Anti-vascular endothelial growth factor (VEGF) drugs and/or photodynamic therapy (PDT) constitute current treatments targeting pathological vascular tissues in tumors and age-related macular degeneration. Concern that PDT might induce VEGF and exacerbate the disease has led us to current practice of using anti-VEGF drugs with PDT simultaneously. However, the underlying molecular mechanisms of these therapies are not well understood. Methods: We assessed VEGF levels after PDT of normal mouse retinal tissue, using a laser duration that did not cause obvious tissue damage. To determine the role of PDT-induced VEGF and its downstream signaling, we intravitreally injected a VEGF inhibitor, VEGFR1 Fc, or a PI3K/Akt inhibitor, LY294002, immediately after PDT. Then, histological and biochemical changes of the retinal tissue were analyzed by immunohistochemistry and immunoblot analyses, respectively. Results: At both the mRNA and protein levels, VEGF was upregulated immediately and transiently after PDT. VEGF suppression after PDT resulted in apoptotic destruction of the photoreceptor cell layer in only the irradiated area during PDT. Under these conditions, activation of the anti-apoptotic molecule Akt was suppressed in the irradiated area, and levels of the pro-apoptotic protein BAX were increased. Intravitreal injection of a PI3K/Akt inhibitor immediately after PDT increased BAX levels and photoreceptor cell apoptosis. Conclusion: Cytotoxic stress caused by PDT, at levels that do not cause overt tissue damage, induces VEGF and activates Akt to rescue the neural tissue, suppressing BAX. Thus, the immediate and transient induction of VEGF after PDT is neuroprotective

Elimination of MYCN-Amplified Neuroblastoma Cells by Telomerase-Targeted Oncolytic Virus via MYCN Suppression

Neuroblastoma (NB) is a primary malignant tumor of the peripheral sympathetic nervous system. High-risk NB is characterized by MYCN amplification and human telomerase reverse transcriptase (hTERT) rearrangement, contributing to hTERT activation and a poor outcome. For targeting hTERT-activated tumors, we developed two oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in which the hTERT promoter drives expression of the viral E1 gene for tumor-specific virus replication. In this study, we demonstrate the therapeutic potential of the hTERT-driven oncolytic adenoviruses OBP-301 and OBP-702 using four human MYCN-amplified NB cell lines (IMR-32, CHP-134, NB-1, LA-N-5) exhibiting high hTERT expression. OBP-301 and OBP-702 exhibited a strong antitumor effect in association with autophagy in NB cells. Virus-mediated activation of E2F1 protein suppressed MYCN expression. OBP-301 and OBP-702 significantly suppressed the growth of subcutaneous CHP-134 tumors. Thus, these hTERT-driven oncolytic adenoviruses are promising antitumor agents for eliminating MYCN-amplified NB cells via E2F1-mediated suppression of MYCN protein

Reversion-inducing cysteine-rich protein with Kazal motifs interferes with epidermal growth factor receptor signaling

金沢大学がん研究所The reversion-inducing cysteine-rich protein with Kazal motifs (RECK) gene had been isolated as an antagonist to RAS signaling; however, the mechanism of its action is not clear. In this study, the effect of loss of RECK function was assessed in various ways and cell systems. Successive cell cultivation of mouse embryonic fibroblasts (MEFs) according to 3T3 protocol revealed that the germline knockout of RECK confers accelerated cell proliferation and early escape from cellular senescence associated with downregulation of p19 Arf, Trp53 and p21Cdkn1a. In contrast, short hairpin RNA-mediated depletion of RECK induced irreversible growth arrest along with several features of the Arf, Trp53 and Cdkn1a-dependent cellular senescence. Within 2 days of RECK depletion, we observed a transient increase in protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) phosphorylation associated with an upregulated expression of cyclin D1, p19Arf, Trp53, p21Cdkn1a and Sprouty 2. On further cultivation, RAS, AKT and ERK activities were then downregulated to a level lower than control, indicating that RECK depletion leads to a negative feedback to RAS signaling and subsequent cellular senescence. In addition, we observed that epidermal growth factor receptor (EGFR) activity was transiently upregulated by RECK depletion in MEFs, and continuously downregulated by RECK overexpression in colon cancer cells. These findings indicate that RECK is a novel modulator of EGFR signaling. © 2011 Macmillan Publishers Limited All rights reserved