International Stock Market Efficiency: A Non-Bayesian Time-Varying Model Approach

This paper develops a non-Bayesian methodology to analyze the time-varying structure of international linkages and market efficiency in G7 countries. We consider a non-Bayesian time-varying vector autoregressive (TV-VAR) model, and apply it to estimate the joint degree of market efficiency in the sense of Fama (1970, 1991). Our empirical results provide a new perspective that the international linkages and market efficiency change over time and that their behaviors correspond well to historical events of the international financial system.Comment: 21 pages, 2 tables, 6 figure

Stress acts cumulatively to precipitate Alzheimer’s disease-like tau pathology and cognitive deficits

Stressful life experiences are likely tiological factors in sporadic forms of Alzheimer’s disease (AD). Many AD patients hypersecrete glucocorticoids (GCs), and their GC levels correlate with the rate of cognitive impairment and extent of neuronal atrophy. Severity of cognitive deficits in AD correlates strongly with levels of perphosphorylated forms of the cytoskeletal protein TAU, an essential mediator of the actions of amyloid Beta (ABeta ), another molecule with a key pathogenic role in AD. Our objective was to investigate the sequential interrelationships between these various pathogenic elements, in particular with respect to the mechanisms through which stress might precipitate cognitive decline. We thus examined whether stress, through the mediation of GCs, influences TAU hyperphosphorylation, a critical and early event in the cascade of processes leading to AD pathology. Results from healthy, wild-type, middle-aged rats show that chronic stress and GC induce abnormal hyperphosphorylation of TAU in the hippocampus and prefrontal cortex (PFC), with contemporaneous impairments of hippocampus- and PFC-dependent behaviors. Exogenous GC potentiated the ability of centrally infused ABeta to induce hyperphosphorylation of TAU epitopes associated with AD and cytoplasmic accumulation of TAU, while previous exposure to stress aggravated the biochemical and behavioral effects of GC in ABeta-infused animals. Thus, lifetime stress/GC exposure may have a cumulative impact on the onset and progress of AD pathology, with TAU hyperphosphorylation serving to transduce the negative effects of stress and GC on cognition.Marie Curie Training FellowshipsEU CRESCENDO Consortium contract FP6-018652University College, London.Max Planck Society and European Union (EU) German-Portuguese Luso-Alemas Program and the EU CRESCENDO Consortium (Contract FP6-018652).German-Portuguese Luso-Alemas Progra

Ferromagnetism and giant magnetoresistance in the rare earth fullerides Eu6-xSrxC60

We have studied crystal structure, magnetism and electric transport properties of a europium fulleride Eu6C60 and its Sr-substituted compounds, Eu6-xSrxC60. They have a bcc structure, which is an isostructure of other M6C60 (M represents an alkali atom or an alkaline earth atom). Magnetic measurements revealed that magnetic moment is ascribed to the divalent europium atom with S = 7/2 spin, and a ferromagnetic transition was observed at TC = 10 - 14 K. In Eu6C60, we also confirm the ferromagnetic transition by heat capacity measurement. The striking feature in Eu6-xSrxC60} is very large negative magnetoresistance at low temperature; the resistivity ratio \rho(H = 9 T)/\rho(H = 0 T) reaches almost 10^{-3} at 1 K in Eu6C60. Such large magnetoresistance is the manifestation of a strong pi-f interaction between conduction carriers on C60 and 4f electrons of Eu.Comment: 5 pages, 4 figure

Pronounced and unavoidable impacts of low-end global warming on northern high-latitude land ecosystems

Arctic ecosystems are particularly vulnerable to climate change because of Arctic amplification. Here, we assessed the climatic impacts of low-end, 1.5 °C, and 2.0 °C global temperature increases above pre-industrial levels, on the warming of terrestrial ecosystems in northern high latitudes (NHL, above 60 °N including pan-Arctic tundra and boreal forests) under the framework of the Inter-Sectoral Impact Model Intercomparison Project phase 2b protocol. We analyzed the simulated changes of net primary productivity, vegetation biomass, and soil carbon stocks of eight ecosystem models that were forced by the projections of four global climate models and two atmospheric greenhouse gas pathways (RCP2.6 and RCP6.0). Our results showed that considerable impacts on ecosystem carbon budgets, particularly primary productivity and vegetation biomass, are very likely to occur in the NHL areas. The models agreed on increases in primary productivity and biomass accumulation, despite considerable inter-model and inter-scenario differences in the magnitudes of the responses. The inter-model variability highlighted the inadequacies of the present models, which fail to consider important components such as permafrost and wildfire. The simulated impacts were attributable primarily to the rapid temperature increases in the NHL and the greater sensitivity of northern vegetation to warming, which contrasted with the less pronounced responses of soil carbon stocks. The simulated increases of vegetation biomass by 30–60 Pg C in this century have implications for climate policy such as the Paris Agreement. Comparison between the results at two warming levels showed the effectiveness of emission reductions in ameliorating the impacts and revealed unavoidable impacts for which adaptation options are urgently needed in the NHL ecosystems

Simple incentives and group dependence for successful payments for ecosystem services programs: evidence from an experimental game in rural Lao PDR

In this paper, we use a new game-based tool to evaluate the immediate and longer-term behavioral change potential of three different payment for environmental services (PES) delivery mechanisms: direct payments for individual performance, direct payments for group performance and insurance. Results from four rural shifting-cultivation dependent communities in Lao PDR suggest that easily understood group-oriented incentives yield the greatest immediate resource-use reduction and experience less free-riding. Group-based incentives may succeed because they motivate participants to communicate about strategies and coordinate their actions and are perceived as fair. No incentive had a lasting effect after it ceased, but neither did any crowd out the participants’ baseline behavior. Temporary reductions in resource dependence may provide a buffer for development of new livelihoods and longer-term change. Games like the one developed here can help policymakers appropriately target environmental incentive programs to local contexts and teach program participants how incentive schemes work

AR and MA representation of partial autocorrelation functions, with applications

We prove a representation of the partial autocorrelation function (PACF), or the Verblunsky coefficients, of a stationary process in terms of the AR and MA coefficients. We apply it to show the asymptotic behaviour of the PACF. We also propose a new definition of short and long memory in terms of the PACF.Comment: Published in Probability Theory and Related Field

Impact of functional studies on exome sequence variant interpretation in early-onset cardiac conduction system diseases

Aims The genetic cause of cardiac conduction system disease (CCSD) has not been fully elucidated. Whole-exome sequencing (WES) can detect various genetic variants; however, the identification of pathogenic variants remains a challenge. We aimed to identify pathogenic or likely pathogenic variants in CCSD patients by using WES and 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines as well as evaluating the usefulness of functional studies for determining them. Methods and Results We performed WES of 23 probands diagnosed with early-onset (<65 years) CCSD and analyzed 117 genes linked to arrhythmogenic diseases or cardiomyopathies. We focused on rare variants (minor allele frequency < 0.1%) that were absent from population databases. Five probands had protein truncating variants in EMD and LMNA which were classified as “pathogenic” by 2015 ACMG standards and guidelines. To evaluate the functional changes brought about by these variants, we generated a knock-out zebrafish with CRISPR-mediated insertions or deletions of the EMD or LMNA homologs in zebrafish. The mean heart rate and conduction velocities in the CRISPR/Cas9-injected embryos and F2 generation embryos with homozygous deletions were significantly decreased. Twenty-one variants of uncertain significance were identified in 11 probands. Cellular electrophysiological study and in vivo zebrafish cardiac assay showed that 2 variants in KCNH2 and SCN5A, 4 variants in SCN10A, and 1 variant in MYH6 damaged each gene, which resulted in the change of the clinical significance of them from “Uncertain significance” to “Likely pathogenic” in 6 probands. Conclusions Of 23 CCSD probands, we successfully identified pathogenic or likely pathogenic variants in 11 probands (48%). Functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants in patients with CCSD. SCN10A may be one of the major genes responsible for CCSD. Translational Perspective Whole-exome sequencing (WES) may be helpful in determining the causes of cardiac conduction system disease (CCSD), however, the identification of pathogenic variants remains a challenge. We performed WES of 23 probands diagnosed with early-onset CCSD, and identified 12 pathogenic or likely pathogenic variants in 11 of these probands (48%) according to the 2015 ACMG standards and guidelines. In this context, functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants, and SCN10A may be one of the major development factors in CCSD

Phosphodiesterase III inhibitor promotes drainage of cerebrovascular β-amyloid

The predominant action of cilostazol on Aβ metabolism is likely to facilitate Aβ clearance due to the sustained cerebrovascular function in vivo. Our findings mechanistically demonstrate that cilostazol is a promising therapeutic approach for AD and CAA

Altered Host Immunity, Human T Lymphotropic Virus Type I Replication, and Risk of Adult T-Cell Leukemia/Lymphoma: A Prospective Analysis from the ATL Cohort Consortium

Background: Adult T-cell leukemia/lymphoma (ATL) is a rare and often fatal outcome of infection with human T-lymphotropic virus type I (HTLV-I). Altered host immunity in HTLV-I carriers has been postulated as a risk factor for ATL, but is not well understood. Methods: We prospectively examined well-validated serologic markers of HTLV-I pathogenesis and host immunity in 53 incident ATL cases and 150 carefully matched asymptomatic HTLV-I carriers from eight population-based studies in Japan, Jamaica, the United States and Brazil. We used multivariable conditional logistic regression, conditioned on the matching factors (cohort/race, age, sex, and sample collection year), to evaluate the biomarkers’ associations with ATL in all subjects and by years (≤5, >5) from blood draw to ATL diagnosis. Results: In the pooled population, above-median soluble interleukin-2-receptor-alpha levels (sIL2R, v. ≤ median; odds ratio (OR), 95% confidence interval (CI)=4.08, 1.47-11.29) and anti-Tax seropositivity (anti-Tax; OR, 95% CI=2.97, 1.15-7.67), which indicate T cell activation and HTLV-I replication, respectively, were independently associated with an increased ATL risk. Above-median total immunoglobulin E levels (v. ≤ median; OR, 95% CI=0.45, 0.19-1.06), which indicate type 2 (B cell) activation, predicted a lower ATL risk. The sIL2R and anti-Tax associations with ATL were stronger in samples collected ≤5 years pre-diagnosis. Conclusions: The biomarker profile predictive of ATL risk suggests a role for heightened T cell activation and HTLV-I replication and diminished type 2 immunity in the etiology of ATL in HTLV-I carriers. Translation of these findings to clinical risk prediction or early ATL detection requires further investigation. Acknowledgements: This abstract is presented on behalf of the ATL Cohort Consortium