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OBJECTIVES: To determine prognostic factors for the Health Assessment Questionnaire-Disability Index (HAQ-DI) progression in patients with rheumatoid arthritis (RA) in clinical practice. METHODS: We evaluated 388 biological disease-modifying anti-rheumatic drug (bDMARD)-naïve Japanese patients with RA with moderate to high disease activity at study entry after being treated with conventional synthetic DMARDs. These patients were treated according to a treat-to-target (T2T) strategy for one year. The Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) and the HAQ-DI were assessed every three months. We also evaluated joint destruction using a modified total Sharp score at baseline and at one year. HAQ-DI progression was defined as the yearly progression of HAQ-DI >0.1. We performed a multiple logistic regression analysis to explore the factors predicting HAQ-DI progression at one year. RESULTS: HAQ-DI progression was observed in 18% of the patients. The multiple logistic regression analysis revealed the independent variables associated with HAQ-DI progression were: DAS28-ESR >5.1 at baseline (odds ratio [OR] 0.31, 95% con dence interval [CI] 0.13-0.74, p=0.0083); HAQ-DI score at baseline <0.5 (OR 2.27, 95% CI 1.22-4.26, p=0.0102); and achievement of low disease activity at 12 weeks (OR 0.42, 95% CI 0.21-0.82, p=0.0112). CONCLUSIONS: Our data suggest that maintaining clinical improvement according to T2T and initiating the treatment at an early stage are important for functional improvement after one year and that patients with low baseline HAQ scores have a higher risk of HAQ disability progression.
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Antirreumáticos , Artrite Reumatoide , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Avaliação da Deficiência , Progressão da Doença , Humanos , Japão/epidemiologia , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
Dysphagia occurs in 11% to 93% of patients following tracheostomy. Despite its benefits, the tracheostomy often co-exists with dysphagia given its anatomical location, the shared pathway of the respiratory and alimentary systems, and the medical complexities necessitating the need for the artificial airway. When tracheostomy weaning commences, it is often debated whether the methods used facilitate swallowing recovery. We conducted a systematic review to determine whether tracheostomy modifications alter swallowing physiology in adults. We searched eight electronic databases, nine grey literature repositories and conducted handsearching. We included studies that reported on oropharyngeal dysphagia as identified by instrumentation in adults with a tracheostomy. We accepted case series (n > 10), prospective or retrospective observational studies, and randomized control trials. We excluded patients with head and neck cancer and/or neurodegenerative disease. Two independent and blinded reviewers rated abstracts and articles for study inclusion. Data abstraction and risk of bias assessment was conducted on included studies. Discrepancies were resolved by consensus. A total of 7079 citations were identified, of which, 639 articles were reviewed, with ten articles meeting our inclusion criteria. The studies were heterogeneous in study design, patient population, and outcome measures. For these reasons, we presented our findings descriptively. All studies were limited by bias risk. This study highlights the limitations of the evidence and therefore the inability to conclude whether tracheostomy modifications alter swallowing physiology.
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Transtornos de Deglutição , Doenças Neurodegenerativas , Adulto , Deglutição , Transtornos de Deglutição/etiologia , Humanos , Estudos Prospectivos , Estudos Retrospectivos , TraqueostomiaRESUMO
We discussed the electron impact dissociation behavior of the organosilicon molecules with methyl groups, based on the fragment pattern and molecular-orbital calculation of the bond dissociation energies for the molecules. From the calculation of bond dissociation energy of the organosilicon molecules, methyl groups, which bonded directly to the silicon atom, were found to have the weakest. Regarding the fragment patterns of the reactants investigated by a quadrupole mass spectrometer, the hexamethyldisiloxane was harder to dissociate than the trimethylmethoxysilane due to the strong Si-O bonding force, which also affected the dissociation in the plasma. From the above considerations, dissociation reactions by electron impact could be partly identified.
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Compostos Orgânicos/química , Gases em Plasma , Silício/química , ElétronsRESUMO
Arc discharge in solution, generated by applying a high voltage of unipolar pulsed dc to electrodes of Ag and Pt, was used as a method to form Ag/Pt bimetallic nanocomposites via electrode erosion by the effects of the electric arc at the cathode (Ag rod) and the sputtering at the anode (Pt rod). Ag/Pt bimetallic nanocomposites were formed as colloidal particles dispersed in solution via the reduction of hydrogen radicals generated during discharge without the addition of chemical precursor or reducing agent. At a discharge time of 30 s, the fine bimetallic nanoparticles with a mean particle size of approximately 5 nm were observed by transmission electron microscopy (TEM). With increasing discharge time, the bimetallic nanoparticle size tended to increase by forming an agglomeration. The presence of the relatively small amount of Pt dispersed in the Ag matrix could be observed by the analytical mapping mode of energy-dispersive x-ray spectroscopy and high-resolution TEM. This demonstrated that the synthesized particle was in the form of a nanocomposite. No contamination of other chemical substances was detected by x-ray photoelectron spectroscopy. Hence, solution plasma could be a clean and simple process to effectively synthesize Ag/Pt bimetallic nanocomposites and it is expected to be widely applicable in the preparation of several types of nanoparticle.
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Nanopartículas Metálicas/química , Nanocompostos/química , Nanotecnologia/métodos , Gases em Plasma/química , Platina/química , Prata/química , Condutividade Elétrica , Eletrodos , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Espectroscopia Fotoeletrônica , Espectrometria por Raios X , TemperaturaRESUMO
SiO2-added MgF2 nanoparticle coatings with various surface roughness properties were formed on fused silica-glass substrates from autoclaved sols prepared at 100-180 °C. To give it hydrophobicity, we treated the samples with fluoro-alkyl silane (FAS) vapor to form self-assembled monolayers on the nanoparticle coating and we examined the wettability of the samples. The samples preserved good transparency even after the FAS treatment. The wettability examination revealed that higher autoclave temperatures produced a larger average MgF2 nanoparticle particle size, a larger surface roughness, and a higher contact angle and the roll-off angle.
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Microstructural characteristics of gold nanoparticles (Au NPs) fabricated by solution plasma processing (SPP) in reverse micelle solutions have been studied by high-resolution transmission electron microscopy (HRTEM). The synthesized Au NPs, with an average size of 6.3 ± 1.4 nm, have different crystal characteristics; fcc single-crystalline particles, multiply twinned particles (MTPs), and incomplete MTPs (single-nanotwinned fcc configuration). The crystal structure characteristics of the Au NPs synthesized by the SPP method were analyzed and compared with similar-size Au NPs obtained by the conventional chemical reduction synthesis (CRS) method. The TEM analysis results show that the Au NPs synthesized by the CRS method have shapes and crystal structures similar to those nanoparticles obtained by the SPP method. However, from the detailed HRTEM analysis, the relative number of the Au MTPs and incomplete MTPs to the total number of the Au NPs synthesized by the SPP method was observed to be around 94%, whereas the relative number of these kinds of crystal structures fabricated by the CRS method was about 63%. It is most likely that the enhanced formation of the Au MTPs is due to the fact that the SPP method generates highly reaction-activated species under low environmental temperature conditions.
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A micropatterned superhydrophobic/superhydrophilic surface was successfully fabricated by plasma CVD and VUV irradiation. Physicochemical properties of the superhydrophobic, superhydrophilic, and superhydrophobic/superhydrophilic surfaces were investigated. The roughness structures on the superhydrophilic surface remained intact compared to those of the superhydrophobic surface. The micropatterned superhydrophobic/superhydrophilic surface was used as a scaffold of cell culture. On the micropatterned surface, the cells attached to the superhydrophilic regions in a highly selective manner, forming circular microarrays of the cells corresponding to the pattern. On the micropatterned surface with pattern distances of 200 microm between superhydrophilic regions, the cells adhered on the superhydrophilic regions and partly extended to the neighboring cells. In contrast, when the pattern distances between the superhydrophilic regions were more than 400 microm, the cells did not extend to the neighboring cells. Cell adhesion behaviors on superhydrophobic and superhydrophilic surfaces were also examined. The cells adhered and proliferated on both superhydrophobic and superhydrophilic surfaces. However, on the superhydrophobic surface, constant contact to facilitate cell division and proliferation was required. On the other hand, the cells easily adhered and proliferated on the superhydrophilic surface immediately after seeding. These differences in cell adhesion behavior induced site-selective cell adhesion on the superhydrophilic regions. Furthermore, protein adsorption behavior that plays an important role in cell adhesion on flat hydrophobic and hydrophilic surface was also examined. The amounts of the protein adsorption on the flat hydrophilic surface were much greater than those on the flat hydrophobic surface.
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Adesão Celular , Células 3T3 , Animais , Camundongos , Microscopia Eletrônica de Varredura , Análise Espectral/métodos , Propriedades de Superfície , Raios XRESUMO
We report a case of systemic lupus erythematosus (SLE) with Jaccoud's arthropathy, presenting atlantoaxial subluxation and multiple joint hypermobility. Radiological studies showed degenerative changes, but no destructive changes like rheumatoid arthritis (RA) were observed. Since these are rare complications of SLE, the coexistence of these complications suggests that they have a common pathogenesis. Generalized laxity of connective tissues may be a novel syndrome in SLE.
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Doenças do Tecido Conjuntivo/complicações , Instabilidade Articular/complicações , Lúpus Eritematoso Sistêmico/complicações , Adulto , Doenças do Tecido Conjuntivo/diagnóstico por imagem , Doenças do Tecido Conjuntivo/patologia , Feminino , Articulação da Mão/diagnóstico por imagem , Articulação da Mão/patologia , Humanos , Deformidades Articulares Adquiridas/complicações , Deformidades Articulares Adquiridas/diagnóstico por imagem , Instabilidade Articular/diagnóstico por imagem , Instabilidade Articular/patologia , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/patologia , Radiografia , SíndromeRESUMO
Wet specimens are notoriously difficult to image in scanning electron microscopes (SEM) owing to evaporation from the required vacuum of the specimen chamber. Traditionally, this issue has been addressed by increasing the specimen chamber pressure. Unfortunately, observation under high specimen chamber pressure cannot prevent the initial evaporation effects. The wet cover method, where the original surface water is retained (and, therefore, considered wet), provides a way to introduce and subsequently image specimens that are sensitive to evaporation within a SEM, while preventing evaporation-related damage, and to observe interesting specimen-water interactions.
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Microscopia Eletrônica de Varredura/métodos , Manejo de Espécimes/métodos , Água , Manejo de Espécimes/instrumentação , VácuoRESUMO
We report a simple room-temperature synthesis route for increasing the reactivity of a TiO2 photocatalyst using a solution plasma process (SPP). Hydrogen radicals generated from the SPP chamber interact with the TiO2 photocatalyst feedstock, transforming its crystalline phase and introducing oxygen vacancy defects. In this work, we examined a pure anatase TiO2 as a model feedstock because of its photocatalytic attributes and well-characterized properties. After the SPP treatment, the pure anatase crystalline phase was transformed to an anatase/brookite heterocrystalline phase with oxygen vacancies. Furthermore, the SPP treatment promoted the absorption of both UV and visible light by TiO2. As a result, TiO2 treated by the SPP for 3 h showed a high gaseous photocatalytic performance (91.1%) for acetaldehyde degradation to CO2 compared with the activity of untreated TiO2 (51%). The SPP-treated TiO2 was also more active than nitrogen-doped TiO2 driven by visible light (66%). The overall photocatalytic performance was related to the SPP treatment time. The SPP technique could be used to enhance the activity of readily available feedstocks with a short processing time. These results demonstrate the potential of this method for modifying narrow-band gap metal oxides, metal sulfides, and polymer composite-based catalyst materials. The modifications of these materials are not limited to photocatalysts and could be used in a wide range of energy and environment-based applications.
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Hydrophobic gold nanorods were fabricated from hydrophilic gold nanorods coated with hexadecyltrimethylammonium bromide by treating with mercaptopropyltrimethoxysilane (MPS) and subsequently octadecyltrimethoxysilane (ODS). The fabrication of the hydrophobic shell went through the process of (1) binding MPS onto the nanorods, (2) hydrolysis of methoxysilanes, and (3) immobilization of ODS by dehydration condensation. The 2- or 3-D ordered structures of hydrophobic nanorods were self-assembled by the evaporation of solvent on a substrate. The aspects of 2-D assemblies were dependent on the concentration of the nanorods, as was seen in transmission electron microscopic images. At a low concentration, the nanorods assembled parallel to the substrate, whereas they stood on the substrate at a high concentration. On the other hand, in a solid of the gold nanorods, the formation of the 3-D assembly was confirmed by small-angle X-ray scattering. The assembly consisted of hexagonal arrays of the gold nanorods and their lamellar accumulation.
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Ouro/química , Nanotubos/química , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica de Transmissão , Modelos Químicos , Compostos de Organossilício/química , Silanos/química , Compostos de Sulfidrila/químicaRESUMO
In this study, we applied an ultra-water-repellent film to cell culture. We cultured cells in droplets on the film and fabricated cell aggregates. Furthermore, we allocated cells on micropatterned surfaces consisting of ultra-water-repellent regions and cell culture-treated regions. The results show that the material is useful for cell culture.
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Técnicas de Cultura de Células/métodos , Engenharia Tecidual/métodos , Água/química , Animais , Linhagem Celular , Humanos , Camundongos , Propriedades de SuperfícieRESUMO
OBJECTIVES: To determine prognostic factors of clinically relevant radiographic progression (CRRP) in patients with rheumatoid arthritis (RA) achieving remission or low disease activity (LDA) in clinical practice. METHODS: Using data from a nationwide, multicenter, prospective study in Japan, we evaluated 198 biological disease-modifying antirheumatic drug (bDMARD)-naïve RA patients who were in remission or had LDA at study entry after being treated with conventional synthetic DMARDs (csDMARDs). CRRP was defined as the yearly progression of modified total Sharp score (mTSS) >3.0 U. We performed a multiple logistic regression analysis to explore the factors to predict CRRP at 1 year. We used receiver operating characteristic (ROC) curve to estimate the performance of relevant variables for predicting CRRP. RESULTS: The mean Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) was 2.32 ± 0.58 at study entry. During the 1-year observation, remission or LDA persisted in 72% of the patients. CRRP was observed in 7.6% of the patients. The multiple logistic regression analysis revealed that the independent variables to predict the development of CRRP were: anti-citrullinated peptide antibodies (ACPA) positivity at baseline (OR = 15.2, 95%CI 2.64-299), time-integrated DAS28-ESR during the 1 year post-baseline (7.85-unit increase, OR = 1.83, 95%CI 1.03-3.45), and the mTSS at baseline (13-unit increase, OR = 1.22, 95%CI 1.06-1.42). CONCLUSIONS: ACPA positivity was the strongest independent predictor of CRRP in patients with RA in remission or LDA. Physicians should recognize ACPA as a poor-prognosis factor regarding the radiographic outcome of RA, even among patients showing a clinically favorable response to DMARDs.
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Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Fragmentos de Peptídeos/imunologia , Idoso , Artrite Reumatoide/tratamento farmacológico , Biomarcadores , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fragmentos de Peptídeos/antagonistas & inibidores , Prognóstico , Curva ROC , Radiografia , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Biomimetic materials processing (BMMP) is defined as the design and synthesis of new functional materials by refining knowledge and understanding of related biological products, structures, functions, and processes. By using BMMP, we can make a new nanotechnology, which is named "biomimetic nanotechnology." This is based on lessons from nature, becomes important for industries from the viewpoint of its applications, and closely relates to "converging technologies." The concept and applications of this biomimetic nanotechnology are described in this article.
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Materiais Biomiméticos , Biomimética/métodos , Comunicação Interdisciplinar , Nanotecnologia/métodos , Animais , Técnicas de Cultura de Células , HumanosRESUMO
To determine prognostic factors of clinically relevant radiographic progression (CRRP) in patients with rheumatoid arthritis (RA) in clinical practice.We performed a multicenter prospective study in Japan of biological disease-modifying antirheumatic drug (bDMARD)-naive RA patients with moderate to high disease activity treated with conventional synthetic DMARDs (csDMARDs) at study entry. We longitudinally observed 408 patients for 1 year and assessed disease activity every 3 months. CRRP was defined as yearly progression of modified total Sharp score (mTSS)â>â3.0âU. We also divided the cohort into 2 groups based on disease duration (<3 vs ≥3 years) and performed a subgroup analysis.CRRP was found in 10.3% of the patients. A multiple logistic regression analysis revealed that the independent variables to predict the development of CRRP were: CRP at baseline (0.30âmg/dL increase, 95% confidence interval [CI] 1.01-1.11), time-integrated Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) during the 1 year postbaseline (12.4-unit increase, 95%CI 1.17-2.59), RA typical erosion at baseline (95%CI 1.56-21.1), and the introduction of bDMARDs (95%CI 0.06-0.38). The subgroup analysis revealed that time-integrated DAS28-ESR is not a predictor whereas the introduction of bDMARDs is a significant protective factor for CRRP in RA patients with disease duration <3 years.We identified factors that could be used to predict the development of CRRP in RA patients treated with DMARDs. These variables appear to be different based on the RA patients' disease durations.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Idoso , Artrite Reumatoide/imunologia , Autoanticorpos/sangue , Sedimentação Sanguínea , Proteína C-Reativa/análise , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Japão , Articulações/diagnóstico por imagem , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , RiscoRESUMO
Nanoprobe chemistry offers a promising approach for the construction of nanostructures consisting of organic molecules by employing the tip of a scanning probe microscope. In a previous report, we demonstrated that a nitroso-terminated surface on an organosilane self-assembled monolayer could be converted into an amino-terminated surface by applying such a nanoprobe electrochemical technique. This paper reports on surface-potential reversibility originating from a reversible chemical reaction between amino and nitroso groups. In addition, we demonstrate surface-potential memory based on this chemical reversibility. Amino-terminated SAMs were prepared from p-aminophenyl-trimethoxysilane through chemical vapor deposition. Surface potentials were acquired by Kelvin force microscopy. When scanning probe lithography was conducted with a gold tip at positive-bias voltages, the surface potential of the scanned area shifted dramatically in the negative direction. Scanning with negative-bias voltages led to positive shift in the surface potential of the scanned area. The surface potential could be recovered even after multiple scannings with positive and negative applied bias voltages. On the basis of this discovery, we also succeeded in demonstrating surface-potential memory via our nanoprobe electrochemical technique.
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Alkyl groups of n-octadecyltrimethoxysilane (ODS) in a self-assembled monolayer on a silicon substrate were oxidized to carboxyl groups by partial irradiation of vacuum ultra-violet light under the photomask, producing a COOH/ODS line pattern. After active esterification of carboxyl groups, two kinds of amine-terminated dendrimers, poly(propyleneimine) and poly(amido amine) (PAMAM) dendrimers, were immobilized on a COOH line through amide-bond so that photolithographic dendrimer/ODS pattern was finally fabricated. Preparation was certified by atomic force microscopy (AFM) and surface-enhanced infrared absorption spectroscopy at transmission mode. Adsorption of linear macromolecules was examined on PAMAM dendrimer/ODS pattern. After adsorption of poly-L-glutamic acid (PGA) at a pH below alpha-helix--random coil transition, rod-shape texture was observed only on the dendrimer line in an AFM image. This texture is an aggregate of alpha-helical PGA. Sodium hyaluronate and DNA were also adsorbed selectively on the dendrimer line, keeping the line profile, although characteristic textures were not observed.
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Compostos de Organossilício/química , Adsorção , Aminas/química , Materiais Biocompatíveis/química , DNA/química , Dendrímeros , Eletroquímica , Ácido Hialurônico/química , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Substâncias Macromoleculares/química , Microscopia de Força Atômica , Conformação de Ácido Nucleico , Poliaminas/química , Ácido Poliglutâmico/química , Polímeros/química , Silício/química , Espectrofotometria , Propriedades de Superfície , Raios UltravioletaRESUMO
Organosilane self-assembled monolayers (SAMs) have been applied to resist materials for nanolithography based on scanning probe microscopy. An organosilane SAM was prepared on Si substrates from a precursor, that is octadecyltrimethoxysilane. Using an atomic force microscope with a conductive probe, current was injected from the probe into the SAM-covered Si substrate so that the SAM was locally degraded at the probe-contacting point. Nanoscale patterns drawn on the SAM was clearly imaged by lateral force microscopy. The patterning could be conducted in air while, in vacuum at the order of 10(-6) Torr, no detectable patterns were fabricated. The presence of adsorbed water at the probe/sample junction was confirmed to be crucial for the patterning of the SAM/Si. Its mechanism was, thus, ascribed to electrochemical reactions of both the SAM and Si with adsorbed water.
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Surface potentials of Si substrates covered with a organosilane self-assembled monolayers (SAMs) were measured with reference to the substrate uncovered with the SAM using Kelvin probe force microscopy. Based on a photolithographic technique, the reference surface was prepared in a micrometer scale on each of the samples. SAMs were prepared from n-octadecyltrimethoxysilane [ODS: CH3(CH2)17Si(OCH3)3], 3,3,3-trifluoropropyltrimethoxysilane [FAS3: CF3(CH2)2Si(OCH3)3], heptadecafluoro-1,1,2,2-tetahydro-decyl-1-trimethoxysilane [FAS17: CF3(CF2)7(CH2)2Si(OCH3)3] or n-(6-aminohexyl) aminopropyltrimethoxysilane [AHAPS: H2N(CH2)6NH(CH2)3Si(OCH3)3) by chemical vapor deposition. Potentials of the surfaces covered with ODS-, FAS3- and FAS17-SAMs became more negative than the uncovered Si substrate, while the surface covered with AHAPS-SAM showed a more positive surface potential than the reference. The potential contrasts of these SAMs to the reference were -25, -170, -225 and +50 mV for ODS-, FAS3-, FAS17- and AHAPS-SAMs, respectively. These results almost agreed with potentials expected from the dipole moments of the corresponding precursor molecules estimated by ab initio molecular orbital calculation, except for FAS3-SAM. Despite FAS3 molecule having a larger dipole moment than FAS17 molecule, the surface potential contrast of FAS3-SAM was smaller than that of FAS17-SAM, since surface coverage of FAS3-SAM was relatively incomplete compared with the other SAMs.
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In adult readers, letters, and words are rapidly identified within visual networks to allow for efficient reading abilities. Neuroimaging studies of orthography have mostly used words and letter strings that recruit many hierarchical levels in reading. Understanding how single letters are processed could provide further insight into orthographic processing. The present study investigated orthographic processing using single letters and pseudoletters when adults were encouraged to pay attention to or away from orthographic features. We measured evoked potentials (EPs) to single letters and pseudoletters from adults while they performed an orthographic-discrimination task (letters vs. pseudoletters), a color-discrimination task (red vs. blue), and a target-detection task (respond to #1 and #2). Larger and later peaking N1 responses (~170 ms) and larger P2 responses (~250 ms) occurred to pseudoletters as compared to letters. This reflected greater visual processing for pseudoletters. Dipole analyses localized this effect to bilateral fusiform and inferior temporal cortices. Moreover, this letter-pseudoletter difference was not modulated by task and thus indicates that directing attention to or away from orthographic features did not affect early visual processing of single letters or pseudoletters within extrastriate regions. Paying attention to orthography or color as compared to disregarding the stimuli (target-detection task) elicited selection negativities at about 175 ms, which were followed by a classical N2-P3 complex. This indicated that the tasks sufficiently drew participant's attention to and away from the stimuli. Together these findings revealed that visual processing of single letters and pseudoletters, in adults, appeared to be sensory-contingent and independent of paying attention to stimulus features (e.g., orthography or color).