191 research outputs found

    Belief inference for hierarchical hidden states in spatial navigation

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    Uncertainty abounds in the real world, and in environments with multiple layers of unobservable hidden states, decision-making requires resolving uncertainties based on mutual inference. Focusing on a spatial navigation problem, we develop a Tiger maze task that involved simultaneously inferring the local hidden state and the global hidden state from probabilistically uncertain observation. We adopt a Bayesian computational approach by proposing a hierarchical inference model. Applying this to human task behaviour, alongside functional magnetic resonance brain imaging, allows us to separate the neural correlates associated with reinforcement and reassessment of belief in hidden states. The imaging results also suggest that different layers of uncertainty differentially involve the basal ganglia and dorsomedial prefrontal cortex, and that the regions responsible are organised along the rostral axis of these areas according to the type of inference and the level of abstraction of the hidden state, i.e. higher-order state inference involves more anterior parts

    Adsorption of Urinary Proteins on the Conventionally Used Urine Collection Tubes: Possible Effects on Urinary Proteome Analysis and Prevention of the Adsorption by Polymer Coating

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    One possible factor determining recovery of trace amount of protein biomarker candidates during proteome analyses could be adsorption on urine tubes. This issue, however, has not been well addressed so far. Recently, a new technical device of surface coating by poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate (BMA)) (poly(MPC-co-BMA)) has been developed mainly to prevent the adsorption of plasma proteins. We assessed whether conventionally used urine tubes adsorb trace amount of urinary proteins and, if any, whether the surface coating by poly(MPC-co-BMA) can minimize the adsorption. Proteinuric urine samples were kept in poly(MPC-co-BMA)-coated and noncoated urine tubes for 15 min and possibly adsorbed proteins and/or peptides onto urine tubes were analyzed by SDS-PAGE, 2-DE, and the MALDI-TOF MS. It was found that a number of proteins and/or peptides adsorb on the conventionally used urine tubes and that surface coating by poly(MPC-co-BMA) can minimize the adsorption without any significant effects on routine urinalysis test results. Although it remains to be clarified to what extent the protein adsorption can modify the results of urinary proteome analyses, one has to consider this possible adsorption of urinary proteins when searching for trace amounts of protein biomarkers in urine

    Synthesis of carbon nanotubes by microwave heating: Influence of diameter of catalytic Ni nanoparticles on diameter of CNTs

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    We rapidly synthesized multi walled carbon nanotubes (MWCNTs) by calcination of granulated polystyrene with nickel nanoparticles having different average diameter (D-Ni = 10, 20, 50 or 90 nm) under nitrogen gas at a certain temperature and time (700 degrees C, 15 min or 800 degrees C, 10 min), using a domestic microwave oven in order to systematically investigate the influence of the diameter of nickel nanoparticles on the diameter of MWCNTs. The MWCNTs synthesized here were characterized by a transmission electron microscope, a Raman spectrophotometer and a wide angle X-ray diffractometer. We found that for the calcination condition of (800 degrees C, 10 min), a relationship between the outer diameter of the resulted carbon nanotubes (D-CNT) and the diameter of catalytic nickel nanoparticles (D-Ni) can be described as a linear function, D-CNT = 1.01D(Ni) + 14.79 nm with the correlation coefficient R = 0.99, and that for the calcination condition of 700 degrees C, 15 min, D-CNT = 1.12D(Ni) + 7.80 nm with R = 0.95. Thus, we revealed that when the diameter of the catalytic nickel nanoparticles (D-Ni) increases by 1 nm, the outer diameter of the obtained MWCNTs (D-CNT) increases by about 1 nm.ArticleJOURNAL OF MATERIALS CHEMISTRY A. 2(8):2773-2780 (2014)journal articl

    Molecular Evolutionary Analyses of the RNA-Dependent RNA Polymerase Region in Norovirus Genogroup II

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    Noroviruses are the leading cause of viral gastroenteritis in humans across the world. RNA-dependent RNA polymerase (RdRp) plays a critical role in the replication of the viral genome. Although there have been some reports on a limited number of genotypes with respect to the norovirus evolution of the RdRp region, no comprehensive molecular evolution examination of the norovirus GII genotype has yet been undertaken. Therefore, we conducted an evolutionary analysis of the 25 genotypes of the norovirus GII RdRp region (full-length), collected globally using different bioinformatics technologies. The time-scaled phylogenetic tree, generated using the Bayesian Markov Chain Monte Carlo (MCMC) method, indicated that the common ancestor of GII diverged from GIV around 1443 CE [95% highest posterior density (HPD), 1336–1542]. The GII RdRp region emerged around 1731 CE (95% HPD, 1703–1757), forming three lineages. The evolutionary rate of the RdRp region of the norovirus GII strains was estimated at over 10−3 substitutions/site/year. The evolutionary rates were significantly distinct in each genotype. The composition of the phylogenetic distances differed among the strains for each genotype. Furthermore, we mapped the negative selection sites on the RdRp protein and many of these were predicted in the GII.P4 RdRp proteins. The phylodynamics of GII.P4, GII.P12, GII.P16, and GII.Pe showed that their effective population sizes increased during the period from 2003 to 2014. Our results cumulatively suggest that the RdRp region of the norovirus GII rapidly and uniquely evolved with a high divergence similar to that of the norovirus VP1 gene

    Inhibition of EP4 Signaling Attenuates Aortic Aneurysm Formation

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    BACKGROUND: Aortic aneurysm is a common but life-threatening disease among the elderly, for which no effective medical therapy is currently available. Activation of prostaglandin E(2) (PGE(2)) is known to increase the expression of matrix metalloproteinase (MMP) and the release of inflammatory cytokines, and may thus exacerbate abdominal aortic aneurysm (AAA) formation. We hypothesized that selective blocking of PGE(2), in particular, EP4 prostanoid receptor signaling, would attenuate the development of AAA. METHODS AND FINDINGS: Immunohistochemical analysis of human AAA tissues demonstrated that EP4 expression was greater in AAA areas than that in non-diseased areas. Interestingly, EP4 expression was proportional to the degree of elastic fiber degradation. In cultured human aortic smooth muscle cells (ASMCs), PGE(2) stimulation increased EP4 protein expression (1.4 ± 0.08-fold), and EP4 stimulation with ONO-AE1-329 increased MMP-2 activity and interleukin-6 (IL-6) production (1.4 ± 0.03- and 1.7 ± 0.14-fold, respectively, P<0.05). Accordingly, we examined the effect of EP4 inhibition in an ApoE(-/-) mouse model of AAA infused with angiotensin II. Oral administration of ONO-AE3-208 (0.01-0.5 mg/kg/day), an EP4 antagonist, for 4 weeks significantly decreased the formation of AAA (45-87% reduction, P<0.05). Similarly, EP4(+/-)/ApoE(-/-) mice exhibited significantly less AAA formation than EP4(+/+)/ApoE(-/-) mice (76% reduction, P<0.01). AAA formation induced by periaortic CaCl(2) application was also reduced in EP4(+/-) mice compared with wild-type mice (73% reduction, P<0.001). Furthermore, in human AAA tissue organ cultures containing SMCs and macrophages, doses of the EP4 antagonist at 10-100 nM decreased MMP-2 activation and IL-6 production (0.6 ± 0.06- and 0.7 ± 0.06-fold, respectively, P<0.05) without increasing MMP-9 activity or MCP-1 secretion. Thus, either pharmacological or genetic EP4 inhibition attenuated AAA formation in multiple mouse and human models by lowering MMP activity and cytokine release. CONCLUSION: An EP4 antagonist that prevents the activation of MMP and thereby inhibits the degradation of aortic elastic fiber may serve as a new strategy for medical treatment of AAA

    Telephone triage service use is associated with better outcomes among patients with cerebrovascular diseases: a propensity score analysis using population-based data

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    IntroductionThe telephone triage service is an emergency medical system through which citizens consult telephone triage nurses regarding illness, and the nurses determine the urgency and need for an ambulance. Despite being introduced in several countries, its impact on emergency patients has not been reported. We aimed to determine the effect of the telephone triage service on the outcomes of hospitalized patients diagnosed with cerebrovascular disease upon arrival after being transported by an ambulance.MethodsThis retrospective study included patients with cerebrovascular disease who were transported by ambulance between January 2016 and December 2019. The primary outcome was discharge to home by day 21 of hospitalization. A total of 344 patients who used the telephone triage service were propensity score-matched to 344 patients who directly called for an ambulance.ResultsTelephone triage service use was associated with discharge to home by hospital day 21 (crude odd ratio: 1.8; 95% confidence interval: 1.3–2.4) and was not significantly associated with survival on hospital day 21 in multivariate regression analysis.ConclusionThe prognoses of cerebral infarction, intracerebral hemorrhage, and subarachnoid hemorrhage depend on the time from symptom onset to treatment. Telephone triage services may allow patients to receive treatment more rapidly than traditional ambulance requests, resulting in improved patient outcomes. The findings of this study suggest that the use of telephone triage services is associated with improved outcomes in patients with cerebrovascular disease and indicate that the costs for medical expenses and disability may be greatly reduced in an aging society
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