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BACKGROUND: The Fukushima Daiichi Nuclear Power Plant accident (2011) released large amounts of radioactive substances into the environment and generated highly radioactive debris. Post-accident countermeasures are currently in the phase of fuel debris removal, which requires the analysis of radioactive contaminants in the environment and fuel. The spectra of solely ß-emitting nuclides, such as 90Sr, overlap; thus, an effective method for nuclide separation is desired. Since conventional methods for high-dose sample analysis pose substantial exposure risks and generate large amounts of secondary radioactive waste, faster procedures allowing for decreased radiation emission are highly desirable. RESULTS: In this study, we developed a 90Sr2+ quantitation technique based on liquid scintillation counting (LSC)-coupled capillary transient isotachophoresis (ctITP), along with two-point detection and relying on the rapid concentration, separation, and fractionation of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-complexed 90Sr2+ in a single run. The applicability of our method for the analysis of real-world samples was verified by conducting addition-recovery experiments using a seawater reference material and radioactive liquid waste obtained from the radioactive waste treatment facility at the Japan Atomic Energy Agency. The recovery determined by LSC was 95-113%, indicating successful quantitative analysis. 90Sr recovery was determined to be 90.1% from a contaminated water sample obtained from the Fukushima Daiichi Nuclear Power Plant, which was analyzed using the standard addition of 90Sr. The sensitivity (detection limit = 0.016 Bq) of the proposed method on a radioactivity basis was equal to or higher than that of the conventional method using ion exchange-LSC (0.012-0.07 Bq). SIGNIFICANCE AND NOVELTY: Our method allows for the handling of high-dose radioactive samples at the microliter level and is substantially faster than conventional ion exchange protocols, whereas ctITP has not been used for practical applications due to inaccurate collection and lack of a suitable chemical system. The concentration-separation-fractionation protocol in ctITP is successful due to the existence of a rare inert Sr2+ complex and precise fractionation. This study establishes a pathway toward safer and more practical analysis of radionuclides.
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Visual perception is closely related to body movements and action, and it is known that processing visual stimuli is facilitated at the hand or at the hand-movement goal. Such facilitation suggests that there may be an attentional process associated with the hands or hand movements. To investigate the underlying mechanisms of visual attention at a hand-movement goal, we conducted two experiments to examine whether attention at the hand-movement goal is a process independent from endogenous attention. Endogenous attention is attention that is intentionally focused on a location, feature, or object. We controlled the hand-movement goal and endogenous attention separately to investigate the spatial profiles of the two types of attention. A visual target was presented either at the goal of hand movement (same condition) or at its opposite side (opposite condition) while steady-state visual-evoked potential (SSVEP) was used to estimate the spatial distributions of the facilitation effect from the 2 types of attention around the hand-movement goal and around the visual target through EEG. We estimated the spatial profile of attentional modulation for the hand-movement goal by taking the difference in SSVEP amplitude between conditions with and without hand movement, thereby obtaining the effect of visual endogenous attention alone. The results showed a peak at the hand-movement goal, independent of the location of the visual target where participants intentionally focused their attention (endogenous attention). We also found differences in the spatial extent of attentional modulation. Spatial tuning was narrow around the hand-movement goal (i.e., attentional facilitation only at the goal location) but was broadly tuned around the focus of endogenous attention (i.e., attentional facilitation spreading over adjacent stimulus locations), which was obtained from the condition without hand movement. These results suggest the existence of two separate mechanisms, one underlying the attention at the hand-movement goal and another underlying endogenous attention.
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Objetivos , Percepção Visual , Humanos , Percepção Visual/fisiologia , Mãos/fisiologia , Potenciais Evocados Visuais , Movimento/fisiologia , EletroencefalografiaRESUMO
Local interactions between unlike molecules (1-2) in solution are commonly measured with spectroscopy and used to estimate local composition. Herein, a viscosity model based on preferential solvation (PS) theory is developed for aqueous and nonaqueous binary liquid mixtures containing a dipolar aprotic solvent that provides local composition considering the hydration or solvation shell around complex (1-2) molecules. Spectral-derived and viscosity-derived local composition distributions showed similar trends with bulk composition, and their correspondence is attributed to characteristics of the hydration or solvation shell. Viscosity-derived local compositions were consistent with literature molecular simulations, whereas spectral-derived local composition distributions contained artifacts. The PS viscosity model is also applicable to nonpolar-polar mixtures for which self-association occurs, and it can be used to estimate solvent mixture dipolarity/polarizability. Since the PS viscosity model only requires bulk viscosity, it may provide a means to estimate microviscosity or the solvent environment around biomolecules.
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After the serious nuclear accident at the Fukushima Daiichi Nuclear Power Plant caused by the Great East Japan Earthquake in 2011, the development of feasible, safe, and highly sensitive analytical methods (in terms of low levels of radiation exposure and radioactive waste generation) for radioactive samples, especially actinide (An) ions, represents an important challenge. Here we propose a methodology for selecting appropriate emissive probes for An ions with very low consumption and emission of radioactivity by capillary electrophoresis-laser-induced fluorescence detection (CE-LIF), using a small chemical library of probes with eight different chelating moieties. It was found that the emissive probe L1, which possesses the tetradentate chelating moiety 1,10-phenanthroline-2,9-dicarboxylic acid (PDA), was suitable for detecting uranyl ions. The detection limit for the uranyl-L1 complex using CE-LIF combined with dynamic ternary complexation and on-capillary concentration techniques was determined to be 2.9â¯×â¯10-12â¯M (0.7â¯ppt). No interference from the large excess of matrix metal ions was observed. This method was successfully applied to real radioactive liquid samples collected from nuclear facilities, including the Fukushima Daiichi Nuclear Power Plant. This strategy not only permitted the development of a safe and rapid analytical method but also provided insight into the coordination chemistry of An ion complexes. Specifically, the PDA structure provided substantial kinetic inertness to its uranyl complex; the formation of a ternary complex between uranyl-L1 and carbonate was revealed; and unusual interactions were observed between the π-electron systems of uranyl and the phenanthroline ring, which stabilized the uranyl-PDA interaction.
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An 82-year-old male was admitted due to mild chest discomfort. Enhanced computed tomography showed a large bronchial artery aneurysm(BAA) of 26×27 mm at the left hilus. To avoid the rupture of BAA, coil embolization alone was performed. There has been no enlargement of BAA for these 4 years. In general, coil embolization only should be indicated in a patient with BAA with a stalk because of thoracic endovascular aortic repair (TEVAR) being off-label and low cost performance. TEVAR would be considered as a last resort only in case of enlarging BAA even after coil embolization.
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Aneurisma/terapia , Artérias Brônquicas , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Idoso de 80 Anos ou mais , Aneurisma Roto/prevenção & controle , Artérias Brônquicas/diagnóstico por imagem , Humanos , Masculino , Resultado do TratamentoRESUMO
A 32-year-old Japanese woman was admitted to our hospital for the diagnosis and treatment of multiple liver tumors. She had been receiving 125 mg testosterone enanthate every 2 weeks following female-to-male gender identity disorder (GID) diagnosis at 20 years of age. Ultrasonography, computed tomography, and magnetic resonance imaging showed 11 hepatic nodular tumors with a maximum diameter of 28 mm. Liver tumors with hepatocellular adenoma (HCA) were diagnosed with needle biopsy. Segmentectomy of the left lateral lobe including two lesions, subsegmentectomy of S6 including two lesions, enucleation of each tumor in S5 and S7, and open surgical radiofrequency ablation for each tumor in S4 and S7 were performed. Immunohistochemical specimens showed that the tumor cells were diffusely and strongly positive for glutamine synthetase and that the nuclei were ectopically positive for ß-catenin. Thus, the tumors were diagnosed as ß-catenin-activated HCA (b-HCA). Transcatheter arterial chemoembolization plus subsequent radiofrequency ablation was performed for the 3 residual lesions in S4 and S8. Although testosterone enanthate was being continued for GID, no recurrence was observed until at least 22 months after the intensive treatments. HCA development in such patients receiving testosterone should be closely monitored using image inspection.
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Androgênios/efeitos adversos , Carcinoma Hepatocelular/induzido quimicamente , Identidade de Gênero , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Primárias Múltiplas/induzido quimicamente , Testosterona/análogos & derivados , Adulto , Carcinoma Hepatocelular/classificação , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/cirurgia , Feminino , Humanos , Neoplasias Hepáticas/classificação , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirurgia , Neoplasias Primárias Múltiplas/classificação , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/cirurgia , Testosterona/efeitos adversosRESUMO
A 40-year-old man was transferred to our hospital following an isolated horse kick injury to the anterior chest wall. The case showed bi-fascicular block, severe tricuspid valve regurgitation due to ruptured chordae tendineae of the anterior leaflet, moderate mitral valve regurgitation due to prolapse of mitral anterior leaflet, and hypokinetic motion of the inferior septal wall. Both tricuspid and mitral insufficiency were completely repaired by a surgical operation. Fortunately, these injuries were not fatal in this case, but the comprehensive assessment of cardiac damage and careful observation are important for managing patients with cardiac injury.
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Bloqueio de Ramo/etiologia , Cordas Tendinosas/lesões , Traumatismos Cardíacos/etiologia , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Tricúspide/etiologia , Adulto , Animais , Bloqueio de Ramo/diagnóstico , Bloqueio de Ramo/cirurgia , Traumatismos Cardíacos/diagnóstico , Traumatismos Cardíacos/terapia , Cavalos , Humanos , Masculino , Insuficiência da Valva Mitral/diagnóstico , Insuficiência da Valva Mitral/cirurgia , Insuficiência da Valva Tricúspide/diagnóstico , Insuficiência da Valva Tricúspide/cirurgiaRESUMO
Aqueous mixtures of dipolar aprotic solvents (acetonitrile, γ-valerolactone, γ-butyrolactone, tetrahydrofuran, 1,4-dioxane, acetone, pyridine, N-methyl-2-pyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, and dimethyl sulfoxide) show synergism in microscopic polarity and extrema in macroscopic viscosity (η) and molar excess enthalpy (HE) in water-rich compositions that correlate with solvent functional group electrostatic basicity (ß2H). Microscopic polarities of aqueous solvent mixtures were estimated by measuring the spectral shift (λmax) of 4-nitroaniline with UV-vis spectroscopy at 25 °C. Dynamic viscosities (η) and densities were measured for eight aqueous dipolar aprotic mixtures over the full range of compositions at (25 to 45) °C. The λmax, η, and HE values of the aqueous mixtures showed a linear trend with increasing electrostatic basicity of the solvent functional groups that is attributed to the size and strength of the hydration shell of water. Density functional theory (DFT) calculations were performed for 1:3 complexes (solvent: (H2O)3) and it was found that aqueous mixtures with high basicity have high binding energies and short hydrogen bonding distances implying that the size and strength of the hydration shell of water is proportional to functional group basicity. Consideration of functional group basicity of dipolar aprotic solvents allows one to relate synergism in microscopic polarity to extrema in macroscopic properties for a wide range of aqueous dipolar aprotic solvent mixtures.
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BACKGROUND: Polymethoxyflavone (PMF) is one of bioactive compounds in Citrus Unshiu and included mainly in the peels rather than the fruits, seeds and leaves. HYPOTHESIS/PURPOSE: Supercritical CO2 extraction is one candidate for selective extraction of polymethoxyflavone and in this study, supercritical CO2 extraction with/without ethanol entrainer from Citrus Unshiu peels was examined at a temperature of 333K and a pressure of 30MPa. METHODS: CRE (cyclic AMP response element)-mediated transcriptional assay was examined by using the extracts from supercritical fluid extraction. RESULTS: The results showed that extracts including nobiletin increased with increasing ethanol concentration in supercritical CO2 and the elapsed extraction time. Extracts at ethanol concentration of 5 mol% showed high CRE-mediated transcription activity. This can be caused by activity of the extract including nobiletin in addition to the other methoxylated flavonoid species such as tangeretin. Extracts at ethanol concentration of 50% showed the highest CRE-mediated transcription activity, which can be attributed to flavonoid glycoside such as hesperidin. From our investigations, flavonoid glycoside can be one of promoters of CRE-mediated transcription activity.
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Citrus/química , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Flavonas/análise , Flavonas/farmacologia , Frutas/química , Extratos Vegetais/farmacologia , Japão , Extratos Vegetais/análiseRESUMO
OBJECTIVE: To assess the usefulness of C-arm cone beam computed tomography (CBCT) combined with ultrasound for the treatment of hepatocellular carcinoma (HCC) by radiofrequency ablation (RFA). METHODS: Patients underwent RFA following transcatheter arterial chemoembolization (TACE) or RFA alone under ultrasound or CBCT guidance combined with ultrasound-based techniques. They were divided into 2 groups based on the use (C group) and nonuse (NC group) of CBCT guidance. The technical success of RFA and local tumor progression after the first RFA session were evaluated by dynamic contrast-enhanced imaging methods. Between-group differences were assessed retrospectively. RESULTS: We enrolled 198 patients with 260 HCC nodules. The complete ablation rates were 63.0 and 89.4% in the NC and C groups, respectively. In log-rank testing, local tumor progression occurred significantly more often in the NC group when RFA was used without TACE, in males when des-gamma-carboxy prothrombin was ≥29 mAU/mL, and when the diameter of a nodule was ≥18 mm. On Cox proportional-hazards regression analysis, the NC group, RFA alone without TACE, and male gender were significant independent variables. CONCLUSION: TACE followed by RFA under CBCT and ultrasound guidance improves the reliability of ablation of target HCC nodules, reduces the need for additional treatment sessions, and prevents local tumor progression.
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Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Estudos de Coortes , Terapia Combinada , Tomografia Computadorizada de Feixe Cônico/métodos , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
A flow-type cell was developed for measuring Compton scattering spectra of heat-sensitive aqueous solution. Compton scattering spectra of water and ethanol were measured in the region from ambient conditions to 623 K and 20 MPa. Compton profiles derived from measurement with the flow-type cell were comparable with those in the literature. Results obtained from the flow-type cell showed that delocalization of electronic charge density of water and ethanol at high temperatures occurred. Delocalization of the electronic charge density of ethanol was greater than that of water at high temperature, which is consistent with the prior works that use proton NMR chemical shifts to describe hydrogen bonding.
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Espectroscopia de Ressonância Magnética/métodos , Modelos Teóricos , Pressão , Difração de Raios X/métodosRESUMO
Kamlet-Taft solvatochromic parameters (polarity, basicity, acidity) of hydrogen bond donor (HBD)/acceptor (HBA) mixed-solvent systems, water (H2O)-γ-valerolactone (GVL), methanol (MeOH)-GVL, ethanol (EtOH)-GVL, H2O-γ-butyrolactone (GBL), MeOH-GBL, and EtOH-GBL, were measured over their entire composition region at 25 °C using UV-vis spectroscopy. Basicity of H2O-GVL and H2O-GBL systems exhibited positive deviation from ideality and synergism in the Kamlet-Taft basicity values. The cybotactic region around each indicator in the mixed-solvent systems was analyzed with the preferential solvation model. Both H2O-GVL and H2O-GBL mixed-solvent systems were found to be completely saturated with mutual complex molecules and to have higher basicity than pure water because water prefers to interact with GVL or GBL molecules rather than with itself. Formation of H2O-GVL and H2O-GBL complex molecules via specific hydrogen bond donor-acceptor interactions were confirmed by infrared spectroscopy. In MeOH-GVL or MeOH-GBL mixed-solvent systems, MeOH molecules prefer self-interaction over that with GVL or GBL so that synergistic basicity was not observed. Synergistic basicity and basicity increase for various functional groups of ten mixed-solvent (water-HBA solvent) systems can be quantitatively explained by considering electrostatic basicity and a ratio of the partial excess HBA solvent basicity with the HBA solvent molar volume that correlate linearly with the preferential solvation model complex molecular parameter (f12/1). Analysis of the cybotactic region of indicators in aqueous mixtures with the preferential solvation model allows one to estimate the trends of mixed-solvent basicity.
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Hydrogen bond donor/acceptor mixed-solvent systems for solutes that exhibit strong specific interactions are not readily characterized with methods that depend on solvatochromic parameters. In this work, the reaction of two monomers, 4,4'-oxidianiline (ODA) and pyromellitic dianhydride (PMDA), to form the common engineering plastic precursor, poly(amic acid) (PAA), are studied for the tetrahydrofuran (THF) mixed-solvent systems (THF-methanol, THF-ethanol, THF-water) with spectroscopy. Solute-centric (SC) KamletTaft solvatochromic (K-T) parameters for the solvent environment around the monomer are determined using a proposed model that incorporates spectroscopically determined local composition (X(L)) around the ODA monomer and the preferential solvation model. For the example reaction to occur under homogeneous conditions, mixed-solvent conditions need have HBA-rich local compositions (0.30 < X(HBA)(L) < 0.83), high solute-centric basicity (ß(SC) > 0.60), high solute-centric polarity, (π(SC)* > 0.63), and low solute-centric acidity (α(SC) < 0.63). The method developed allows characterization of mixed-solvent effects and can be readily extended to other systems that have strong specific interactions.
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Imidas/química , Modelos Químicos , Solventes/químicaRESUMO
UNLABELLED: The aim of study was to analyze the outcome of aggressive, early surgical intervention to active infective endocarditis (IE) complicated by acute congestive heart failure, uncontrollable infection and large, mobile vegetation and to evaluate the validity of current therapeutic strategy on it's long-term outcome. PATIENTS AND METHODS: We retrospectively investigated surgical outcome of 51 patients who underwent surgical intervention to eradicate intra-cardiac infection and to reconstruct subsequent structural destruction due to active IE performed between 2002 and 2013. Patient's mean age was 56 ± 17 (14~83) years and 36 males, 2 prior cardiac surgery-performed and 2 hemodialysis-dependent renal failure patients were included. All patients were followed on long-term basis. Mean follow up duration was 61 ± 46 (1~164) months. We classified patients into 2 groups according to urgency of surgical intervention:early surgical (ES) group who underwent surgery within 2 weeks from diagnosis of IE and conservative surgical (CS) group who underwent after 2 weeks more from the diagnosis. RESULTS: Two patients died during hospitalization due to low cardiac output syndrome (LOS) for ischemic myopathy after old myocardial infarction and postoperative ischemic colitis (preoperative hemodialysis-dependent patient). Two cerebral infarctions and 1 hemorrhagic transformation of cerebral infarction occurred postoperatively. There was no mediastinal infection and recurrent intracardiac infection postoperatively. On long-term follow up, cumulative survival was 90/79/68% in 1/5/10 years. on ES group and 100/89/79% in 1/5/10 years. on CS group, respectively. Freedom from cardiac death were 100/100/100% in 1/5/10 years. on ES group and 100/100/100% in 1/5/10 years. on CS group, respectively. There were 1 cardiac death(125 months after operation) and 8 non-cardiac deaths on long-term survival. CONCLUSION: Early surgical strategy for active infective endocarditis to prevent IE-related preoperative adverse complications seems to be acceptable.
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Endocardite Bacteriana/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/cirurgia , Reoperação , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Photoautotrophic fatty acid production of a highly CO2 -tolerant green alga Chlorococcum littorale in the presence of inorganic carbon at 295 K and light intensity of 170 µmol-photon m(-2) s(-1) was investigated. CO2 concentration in the bubbling gas was adjusted by mixing pure gas components of CO2 and N2 to avoid photorespiration and ß-oxidation of fatty acids under O2 surrounding conditions. Maximum content of total fatty acid showed pH-dependence after nitrate depletion of the culture media and increased with the corresponding inorganic carbon ratio. Namely, [HCO3 (-) ]/([CO2 ]+n[ CO32-]) ratio in the culture media was found to be a controlling factor for photoautotrophic fatty acid production after the nitrate limitation. At a CO2 concentration of 5% (vol/vol) and a pH of 6.7, the fatty acid content was 47.8 wt % (dry basis) at its maximum that is comparable with land plant seed oils.
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Biocombustíveis , Dióxido de Carbono/metabolismo , Clorófitas/metabolismo , Ácidos Graxos/metabolismo , Microalgas/metabolismo , Concentração de Íons de HidrogênioRESUMO
A highly CO2-tolerant green alga, Chlorococcum littorale, was investigated at temperatures ranging from 8 to 28 °C, light intensities from 30 to 170 µmol m-2 s-1, a constant CO2 concentration of 5% (v/v) and atmospheric pressure. The experimental results showed that a specific growth rate µ, defined in terms of cell growth rate under a logarithmic growth phase, increased with temperature up to the maximum value (ca. 22 °C), while the µ decreased at higher temperatures. These promotion and inhibition of the cell growth rate were expressed by both a multiple linear regression and a mathematical model taking account of the Arrhenius activation/deactivation energies. Light intensity affected on the cell growth was independently treated in the mathematical model. The proposed growth model agreed well with the experimental data to within 6.6 %, which provides good correlation for both temperature and light intensity effects on the microalgal cell growth.
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A 28-year-old man was referred to our hospital with a giant right atrial diverticulum. The mass of the right atrial diverticulum compressed the right atrium and right ventricle, and thrombus formation was suspected. The diverticulum was surgically excised and the patient remained asymptomatic a year later.
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Divertículo/complicações , Aneurisma Cardíaco/complicações , Átrios do Coração/fisiopatologia , Ventrículos do Coração/fisiopatologia , Trombose/etiologia , Adulto , Procedimentos Cirúrgicos Cardíacos/métodos , Átrios do Coração/cirurgia , Ventrículos do Coração/cirurgia , Humanos , Masculino , Esternotomia/métodos , Resultado do TratamentoRESUMO
Our brain often needs to estimate unknown variables from imperfect information. Our knowledge about the statistical distributions of quantities in our environment (called priors) and currently available information from sensory inputs (called likelihood) are the basis of all Bayesian models of perception and action. While we know that priors are learned, most studies of prior-likelihood integration simply assume that subjects know about the likelihood. However, as the quality of sensory inputs change over time, we also need to learn about new likelihoods. Here, we show that human subjects readily learn the distribution of visual cues (likelihood function) in a way that can be predicted by models of statistically optimal learning. Using a likelihood that depended on color context, we found that a learned likelihood generalized to new priors. Thus, we conclude that subjects learn about likelihood.
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Retroalimentação Sensorial/fisiologia , Aprendizagem/fisiologia , Desempenho Psicomotor/fisiologia , Adulto , Teorema de Bayes , Feminino , Humanos , Funções Verossimilhança , Masculino , Destreza Motora/fisiologia , Adulto JovemRESUMO
A simple and rapid method with low radiation exposure risk was developed for the determination of neodymium in spent nuclear fuel by capillary electrophoresis with laser-induced fluorescence detection using a fluorescent probe having a macrocyclic hexadentate polyaminocarboxylate structure. The concentration of Nd(III) in a spent nuclear fuel sample was determined with no interference from various matrix elements, including lanthanides and uranium (at a 200-fold excess), with 92 ± 3% recovery. This is due to high resolution based on establishing a ternary complex equilibrium during migration in which the hydroxyl ion plays an auxiliary role (log K(Ln-L-OH) = 3.9-5.3).