Asset Prices and Monetary Policy

How should central banks take into account movements in asset prices in the conduct of monetary policy? We provide an analysis to address this issue using a dynamic stochastic general equilibrium model incorporating both price rigidities and financial market imperfections. Our findings are twofold. First, in the presence of these two sources of distortion in the economy, central banks face a policy trade-off between stabilizing inflation and the output gap. With this trade-off, central banks could strike a better balance between both objectives if they took variables other than inflation, such as asset prices, into consideration. Second, these benefits decrease when central banks rely on limited information about the underlying sources of asset price movements and cannot judge which part of the observed asset price movements reflects inefficiencies in the economy.Asset prices; Monetary policy; Financial frictions; Policy trade-offs

Asset Prices and Monetary Policy

How should central banks take into account movements in asset prices in the conduct of monetary policy? We provide an analysis to address this issue using a dynamic stochastic general equilibrium model incorporating both price rigidities and financial market imperfections. Our findings are twofold. First, in the presence of these two sources of distortion in the economy, central banks face a policy tradeoff between stabilizing inflation and the output gap. With this tradeoff, central banks could strike a better balance between both objectives if they took variables other than inflation, such as asset prices, into consideration. Second, these benefits decrease when central banks rely on limited information about the underlying sources of asset price movements and cannot judge which part of the observed asset price movements reflects inefficiencies in the economy.asset prices, monetary policy, financial frictions, policy tradeoffs

The Effects of Oil Price Changes on the Industry-Level Production and Prices in the U.S. and Japan.

In this paper, we decompose oil price changes into their component parts following Kilian (2009) and estimate the dynamic effects of each component on industry-level production and prices in the U.S. and Japan using identified VAR models. The way oil price changes affect each industry depends on what kind of underlying shock drives oil price changes as well as on industry characteristics. Unexpected disruptions of oil supply act mainly as negative supply shocks for oil- intensive industries and act mainly as negative demand shocks for less oil- intensive industries. For most industries in the U.S., shocks to the global demand for all industrial commodities act mainly as positive demand shocks, and demand shocks that are specific to the global oil market act mainly as negative supply shocks. In Japan, the oil-specific demand shocks as well as the global demand shocks act mainly as positive demand shocks for many industries.Oil price, Identified VAR, Industry-level data, Japan

Monetary transmission mechanism: Heterogeneous information, inventories, and credit-market imperfections.

This thesis presents a theoretical investigation into the monetary transmission mechanism. In particular, I focus on heterogeneous information, inventories, and credit-market imperfections as factors that help to propagate monetary disturbances to the economy in a way that can explain plausibly the observed effects of monetary policy. First, I consider heterogeneous information among price-setters who can only observe the state of the economy through noisy private signals. I construct a model which incorporates the imperfect common knowledge into the Taylor-Calvo staggered price-setting model. The average price chosen in each period depends on the higher-order expectations about not only the current state of the economy but also the future states during the periods the prices will be fixed. The response of inflation to a monetary disturbance is delayed following a sluggish initial adjustment of prices and the response of output is amplified by the imperfection in common knowledge. These results are robust when a noisy public signal in addition to private signals is introduced. Secondly, I consider inventories by developing simple dynamic general equilibrium models which assume pre-determined prices and incorporate a production-smoothing motive and a sales-facilitating motive for holding inventories. Inventories serve as a source of real rigidities, that is, amplify the persistence of the real effects of monetary policy. Inventories respond pro-cyclically and prices are adjusted gradually to a nominal disturbance only if the sales-facilitating motive is relatively strong enough; otherwise inventories respond countercyclically and prices are adjusted excessively. I also consider the case where production as well as prices is pre-determined. Lastly, I consider credit-market imperfections by examining a model which incorporates asymmetric information between lenders and borrowers into a standard dynamic New Keynesian model. I calibrate the model using Japanese data and find that the large volatility of Japan's corporate investment can be explained by taking account of the credit-market imperfections. Based on this model, I simulate alternative monetary policy rules and evaluate their performances

The Effects of Oil Price Changes on the Industry-Level Production and Prices in the U.S. and Japan

In this paper, we decompose oil price changes into their component parts following Kilian (2009) and estimate the dynamic effects of each component on industry-level production and prices in the U.S. and Japan using identified VAR models. The way oil price changes affect each industry depends on what kind of underlying shock drives oil price changes as well as on industry characteristics. Unexpected disruptions of oil supply act mainly as negative supply shocks for oil-intensive industries and act mainly as negative demand shocks for less oil-intensive industries. For most industries in the U.S., shocks to the global demand for all industrial commodities act mainly as positive demand shocks, and demand shocks that are specific to the global oil market act mainly as negative supply shocks. In Japan, the oil-specific demand shocks as well as the global demand shocks act mainly as positive demand shocks for many industries.

ESSENCE-Q - dash; a first clinical validation study of a new screening questionnaire for young children with suspected neurodevelopmental problems in south Japan

Background: Early identification of autism spectrum disorder, intellectual developmental disorder, attention-deficit/hyperactivity disorder, and other neurodevelopmental disorders/problems is crucial, yet diagnosis is often delayed for years under the often misguided “wait-and-see” paradigm. The early symptomatic syndromes eliciting neurodevelopmental clinical examinations-questionnaire (ESSENCE-Q) is a brief (12-item) screening questionnaire developed specifically for the purpose of speeding up the identification process of a wide variety of neurodevelopmental problems. The aims were to 1) estimate the reliability of the ESSENCE-Q, 2) evaluate the clinical cutoff levels suggested by the author of the ESSENCE-Q, and 3) propose optimal cutoff levels based on receiver operating characteristic analysis. Methods: The ESSENCE-Q was used for 1 year by a psychiatrist in Kochi, Japan, assessing children under the age of 6 years referred for developmental problems. The children were also clinically assessed with regard to whether or not they met criteria for a developmental disorder (diagnosis positive and diagnosis negative groups). We contrasted the results of the ESSENCE-Q and those of clinical diagnostic assessments in 130 cases. Results: Cronbach’s alpha was 0.82, sensitivity was 0.94 (95% confidence interval [CI]: [0.88, 0.98]), and specificity 0.53 (95% CI: [0.28, 0.77]), which are reasonable psychometrics for a first-step screening tool. Based on receiver operating characteristic analysis, we recommended an optimal cutoff level of yes ≥2 or maybe/a little ≥3 on the ESSENCE-Q (0.87 (95% CI: [0.79, 0.92]) sensitivity and 0.77 (95% CI: [0.50, 0.93]) specificity). Conclusion and implication: The ESSENCE-Q can be a good instrument for use as a screening tool for aiding in the process of early identification of neurodevelopmental disorders in clinical settings. To establish the broader validity and reliability of the ESSENCE-Q, case–control studies and general population studies of children in different age groups are needed

ESSENCE-Q – a first clinical validation study of a new screening questionnaire for young children with suspected neurodevelopmental problems in south Japan

BACKGROUND: Early identification of autism spectrum disorder, intellectual developmental disorder, attention-deficit/hyperactivity disorder, and other neurodevelopmental disorders/problems is crucial, yet diagnosis is often delayed for years under the often misguided “wait-and-see” paradigm. The early symptomatic syndromes eliciting neurodevelopmental clinical examinations-questionnaire (ESSENCE-Q) is a brief (12-item) screening questionnaire developed specifically for the purpose of speeding up the identification process of a wide variety of neurodevelopmental problems. The aims were to 1) estimate the reliability of the ESSENCE-Q, 2) evaluate the clinical cutoff levels suggested by the author of the ESSENCE-Q, and 3) propose optimal cutoff levels based on receiver operating characteristic analysis. METHODS: The ESSENCE-Q was used for 1 year by a psychiatrist in Kochi, Japan, assessing children under the age of 6 years referred for developmental problems. The children were also clinically assessed with regard to whether or not they met criteria for a developmental disorder (diagnosis positive and diagnosis negative groups). We contrasted the results of the ESSENCE-Q and those of clinical diagnostic assessments in 130 cases. RESULTS: Cronbach’s alpha was 0.82, sensitivity was 0.94 (95% confidence interval [CI]: [0.88, 0.98]), and specificity 0.53 (95% CI: [0.28, 0.77]), which are reasonable psychometrics for a first-step screening tool. Based on receiver operating characteristic analysis, we recommended an optimal cutoff level of yes ≥2 or maybe/a little ≥3 on the ESSENCE-Q (0.87 (95% CI: [0.79, 0.92]) sensitivity and 0.77 (95% CI: [0.50, 0.93]) specificity). CONCLUSION AND IMPLICATION: The ESSENCE-Q can be a good instrument for use as a screening tool for aiding in the process of early identification of neurodevelopmental disorders in clinical settings. To establish the broader validity and reliability of the ESSENCE-Q, case–control studies and general population studies of children in different age groups are needed

SAK3 Administration Improves Spine Abnormalities and Cognitive Deficits in AppNL-G-F/NL-G-F Knock-in Mice by Increasing Proteasome Activity through CaMKII/Rpt6 Signaling

Alzheimer’s disease (AD) is the most common form of dementia and is characterized by neuropathological hallmarks consisting of accumulation of extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles (NFT). Recently, we have identified a new AD therapeutic candidate, ethyl-8′-methyl-2′,4-dioxo-2-(piperidin-1-yl)-2′H-spiro[cyclopentane-1,3′-imidazo [1,2-a] pyridin]-2-ene-3-carboxylate (SAK3), which ameliorates the AD-like pathology in AppNL-F/NL-F knock-in mice. However, the detailed mechanism underlying the therapeutic effects of SAK3 remains unclear. In this study, we found that SAK3 administration improved the reduced proteasome activity through the activation of CaMKII/Rpt6 signaling in AppNL-F/NL-F knock-in (NL-G-F) mice. Moreover, spine abnormalities observed in NL-G-F mice were significantly reversed by SAK3 administration. Along with this, cognitive impairments found in NL-G-F mice were markedly ameliorated by SAK3. In summary, our data suggest that SAK3 administration increases the activity of the proteasome via activation of the CaMKII/Rpt6 signaling pathway, contributing to improvements in spine abnormalities and cognitive deficits in NL-G-F mice. Overall, our findings suggest that SAK3 might be a new attractive drug candidate, representing a new mechanism for the treatment of AD pathology

Preliminary results of phase I trial of oral uracil/tegafur (UFT), leucovorin plus irinotecan and radiation therapy for patients with locally recurrent rectal cancer

BACKGROUND: Surgical attempts for locally recurrent rectal cancer often fail due to local re-recurrence and distant metastasis. Preoperative chemoradiation may enhance better local control and survival. The aim of this study was to assess the safety of oral uracil and tegafur (UFT) plus leucovorin (LV), and irinotecan combined with radiation and determine the maximum-tolerated dose (MTD) and dose limiting toxicity (DLT) of the triple drug regimen. PATIENTS AND METHODS: Patients with locally recurrent rectal cancer received escalating doses of irinotecan on days 1, 8, 15, and 22 (starting at 30 mg/m(2), with 10 mg increments between consecutive cohorts) and fixed doses of UFT (300 mg/m(2)) plus LV (75 mg/day) on days 3 to 7, 10 to 14, 17 to 21, and 24 to 28. Radiation was given 5 days per week totaling 40 to 50 Gy (2Gy/day). RESULTS: Six patients were treated at the starting dose, and 2 received the full scheduled chemoradiotherapy. The other 4 patients had grade 3 diarrhea and diarrhea was the DLT. One patient had partial response and he had subsequently radical surgical resection. Median progression free survival for local recurrence was 320 days. CONCLUSION: Irinotecan plus UFT/LV with concomitant radiotherapy in patients with locally recurrent rectal cancer was not feasible due to diarrhea in this setting. Modification of the treatment is needed

An α-synuclein decoy peptide prevents cytotoxic α-synuclein aggregation caused by fatty acid binding protein 3

α-synuclein (αSyn) is a protein known to form intracellular aggregates during the manifestation of Parkinson’s disease. Previously, it was shown that αSyn aggregation was strongly suppressed in the midbrain region of mice that did not possess the gene encoding the lipid transport protein fatty acid binding protein 3 (FABP3). An interaction between these two proteins was detected in vitro, suggesting that FABP3 may play a role in the aggregation and deposition of αSyn in neurons. In order to characterize the molecular mechanisms that underlie the interactions between FABP3 and αSyn that modulate the cellular accumulation of the latter, in this report, we used in vitro fluorescence assays combined with fluorescence microscopy, transmission electron microscopy, and quartz crystal microbalance assays to characterize in detail the process and consequences of FABP3-αSyn interaction. We demonstrated that binding of FABP3 to αSyn results in changes in the aggregation mechanism of the latter; specifically, a suppression of fibrillar forms of αSyn, and also the production of aggregates with an enhanced cytotoxicity toward mice neuro2A cells. Since this interaction involved the C-terminal sequence region of αSyn, we tested a peptide derived from this region of αSyn (αSynP130-140) as a decoy to prevent the FABP3-αSyn interaction. We observed that the peptide competitively inhibited binding of αSyn to FABP3 in vitro and in cultured cells. We propose that administration of αSynP130-140 might be used to prevent the accumulation of toxic FABP3-αSyn oligomers in cells, thereby preventing the progression of Parkinson’s disease