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1.
Cancer J ; 30(3): 210-217, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38753756

RESUMEN

ABSTRACT: Fibroblast activation protein inhibitor positron emission tomography (PET) has gained interest for its ability to demonstrate uptake in a diverse range of tumors. Its molecular target, fibroblast activation protein, is expressed in cancer-associated fibroblasts, a major cell type in tumor microenvironment that surrounds various types of cancers. Although existing literature on FAPI PET is largely from single-center studies and case reports, initial findings show promise for some cancer types demonstrating improved imaging when compared with the widely used 18F-fludeoxyglucose PET for oncologic imaging. As we expand our knowledge of the utility of FAPI PET, accurate understanding of noncancerous uptake seen on FAPI PET is crucial for accurate evaluation. In this review, we summarize potential diagnostic and therapeutic applications of radiolabeled FAP inhibitors in oncological and nononcological disease processes.


Asunto(s)
Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/diagnóstico , Neoplasias/metabolismo , Tomografía de Emisión de Positrones/métodos , Endopeptidasas , Gelatinasas/antagonistas & inhibidores , Gelatinasas/metabolismo , Microambiente Tumoral/efectos de los fármacos , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/metabolismo , Radiofármacos , Serina Endopeptidasas/metabolismo , Animales , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/efectos de los fármacos
2.
Cognition ; 246: 105759, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38430752

RESUMEN

A key issue in recent visual word recognition literature is whether text rotation disrupts the early stages of orthographic processing. Previous research found no masked repetition priming effect when primes were rotated ≥90° in alphabetic languages. The present study investigated the impact of text rotation using logographic (two-character Japanese kanji) words. In Experiment 1, we conducted a masked repetition priming lexical decision experiment with upright and 180° rotated primes. The rotated primes produced a significant priming effect, although the effect was smaller than the upright primes. In Experiment 2, we further examined the effectiveness of 180° rotated primes in two different conditions: the whole words were rotated vs. each constituent character was rotated at their own positions. Both prime types produced significant priming effects of similar magnitudes. These findings suggest that orthographic processing is more robust against text rotation in logographic languages than in alphabetic languages.


Asunto(s)
Reconocimiento Visual de Modelos , Lectura , Humanos , Rotación , Japón , Lenguaje , Memoria Implícita , Enmascaramiento Perceptual
3.
J Exp Psychol Learn Mem Cogn ; 49(11): 1823-1843, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37053424

RESUMEN

Previous masked translation priming studies, especially those with different-script bilinguals, have shown that cognates provide more priming than noncognates, a difference attributed to cognates' phonological similarity. In our experiments employing a word naming task, we examined this issue for Chinese-Japanese bilinguals in a slightly different way, using same-script cognates as primes and targets. In Experiment 1, significant cognate priming effects were observed. The sizes of the priming effects were, however, statistically not different for phonologically similar (e.g., /xin4lai4/-/shiNrai/) and dissimilar cognate pairs (e.g., /bao3zheng4/- /hoshoR/), suggesting no impact of phonological similarity. In Experiment 2, using exclusively Chinese stimuli, we demonstrated a significant homophone priming effect using two-character logographic primes and targets, indicating that phonological priming is possible for two-character Chinese targets. However, priming only emerged for pairs that had the same tone pattern (e.g., /shou3wei4/-/shou3wei4/), suggesting that a match in lexical tone is crucial for observing phonologically based priming in that situation. Therefore, Experiment 3 involved phonologically similar Chinese-Japanese cognate pairs in which the similarity of their suprasegmental phonological features (i.e., lexical tone and pitch-accent information) was varied. Priming effects were statistically not different for tone/accent similar pairs (e.g., /guan1xin1/-/kaNsiN/) and dissimilar pairs (e.g., /man3zu2/-/maNzoku/). Our results indicate that phonological facilitation is not involved in producing cognate priming effects for Chinese-Japanese bilinguals. Possible explanations, based on underlying representations of logographic cognates, are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Asunto(s)
Multilingüismo , Humanos , Lingüística
4.
J Radiat Res ; 64(2): 203-209, 2023 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-36610718

RESUMEN

After the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, individual exposure doses to residents have been assessed by many municipalities, governments and research institutes. Various methods including measurements with personal dosimeters and simulations have been used for this evaluation depending on purposes, but the information of assessments and methods has not been systematically organized. A comprehensive review of the knowledge and experiences of individual exposure doses assessments accumulated so far and understanding the characteristics of the assessment methods will be very useful for radiation protection and risk communication, following to governmental policy planning. We reviewed the efforts made by the Japanese government and research institutes to assess radiation doses to residents after the FDNPS accident in Part 1. On the other hand, each method of assessing individual exposure doses includes uncertainties and points to be considered for the appropriate assessment. These knowledge and experiences are important for the assessment implementation and applying the assessment results to the governmental policy planning, and are summarized in Part 2 of this article.


Asunto(s)
Accidente Nuclear de Fukushima , Monitoreo de Radiación , Protección Radiológica , Japón , Dosímetros de Radiación , Plantas de Energía Nuclear , Dosis de Radiación
5.
J Radiat Res ; 64(1): 2-10, 2023 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-36503957

RESUMEN

The evacuation order areas established due to the accident at the Tokyo Electric Power Company Holdings' (TEPCO) Fukushima Daiichi Nuclear Power Plant (FDNPP) have been reorganized according to the decrease in ambient dose rates and the decontamination progress. The Japanese government decided to decontaminate the difficult-to-return areas and lift the evacuation order by 2030. This radiation protection strategy can be optimized by examining emergency exposure situations to date and the existing exposure after the accident. This article reviews the methods that can determine the individual radiation doses of residents who should return to their homes when the evacuation order is lifted in the specific reconstruction reproduction base area and the difficult-to-return areas outside this base area and summarizes the points to be considered when implementing these methods. In Part 1 of this article, we review the efforts made by the Japanese government and research institutes to assess radiation doses to residents after the FDNPP accident.


Asunto(s)
Accidente Nuclear de Fukushima , Monitoreo de Radiación , Dosis de Radiación , Japón , Plantas de Energía Nuclear , Gobierno , Políticas
6.
Front Psychol ; 13: 742965, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35967661

RESUMEN

For native (L1) English readers, masked presentations of past-tense verb primes (e.g., fell and looked) produce faster lexical decision latencies to their present-tense targets (e.g., FALL and LOOK) than orthographically related (e.g., fill and loose) or unrelated (e.g., master and bank) primes. This facilitation observed with morphologically related prime-target pairs (morphological priming) is generally taken as evidence for strong connections based on morphological relationships in the L1 lexicon. It is unclear, however, if similar, morphologically based, connections develop in non-native (L2) lexicons. Several earlier studies with L2 English readers have reported mixed results. The present experiments examine whether past-tense verb primes (both regular and irregular verbs) significantly facilitate target lexical decisions for Japanese-English bilinguals beyond any facilitation provided by prime-target orthographic similarity. Overall, past-tense verb primes facilitated lexical decisions to their present-tense targets relative to both orthographically related and unrelated primes. Replicating previous masked priming experiments with L2 readers, orthographically related primes also facilitated target recognition relative to unrelated primes, confirming that orthographic similarity facilitates L2 target recognition. The additional facilitation from past-tense verb primes beyond that provided by orthographic primes suggests that, in the L2 English lexicon, connections based on morphological relationships develop in a way that is similar to how they develop in the L1 English lexicon even though the connections and processing of lower level, lexical/orthographic information may differ. Further analyses involving L2 proficiency revealed that as L2 proficiency increased, orthographic facilitation was reduced, indicating that there is a decrease in the fuzziness in orthographic representations in the L2 lexicon with increased proficiency.

7.
ACS Med Chem Lett ; 13(2): 211-217, 2022 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-35178177

RESUMEN

Screening for small-molecule modulators targeting a particular receptor is frequently based on measurement of K d, i.e., the binding constant between the receptor and the compound of interest. However, K d values also reflect binding at receptor protein sites other than the modulatory site. We designed derivatives of retinoid X receptor (RXR) antagonist CBTF-EE (1) with modifications that altered their conformational flexibility. Compounds 6a,b and 7a,b showed quite similar K d values, but 7a,b exhibited 10-fold higher K i values than those of 6a,b. Further, 6a,b showed potent RXR-antagonistic activity, while 7a,b were inactive. These results suggest that increased conformational flexibility promotes binding at nontarget receptor sites. In this situation, conventional determination of K d is less effective for screening purposes than the determination of K i using a ligand that binds specifically to the site regulating transcriptional activity. Thus, the use of K i values for orthosteric ligands may increase the hit rate in screening active regulatory molecules.

8.
AJR Am J Roentgenol ; 217(1): 186-197, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34010036

RESUMEN

OBJECTIVE. Tumefactive demyelination mimics primary brain neoplasms on imaging, often necessitating brain biopsy. This article reviews the literature for the clinical and radiologic findings of tumefactive demyelination in various disease processes to facilitate identification of tumefactive demyelination on imaging. CONCLUSION. Both clinical and radiologic findings must be integrated to distinguish tumefactive demyelinating lesions from similarly appearing lesions on imaging. Further research on the immunopathogenesis of tumefactive demyelination and associated conditions will elucidate their interrelationship.

9.
Mem Cognit ; 49(1): 148-162, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32839892

RESUMEN

Norris, Kinoshita and colleagues (Kinoshita & Norris, Journal of Experimental Psychology: Learning, Memory, and Cognition, 35(1), 1-18, 2009; Journal of Experimental Psychology: General, 137(3), 434-455, 2010; Norris & Kinoshita, Quarterly Journal of Experimental Psychology, 63(1), 194-204, 2008) have suggested that the masked priming same-different task (SDT) is an excellent tool for studying the orthographic coding process because, in most circumstances, performance in that task is driven entirely by orthographic codes. More specifically, although evidence of phonological influences (i.e., phonological priming effects in the SDT) have been reported, Kinoshita, Gayed, and Norris (Journal of Experimental Psychology: Human Perception and Performance, 44(11), 1661-1671, 2018) have claimed that phonological priming does not arise in the SDT when the prime and target are written in the same script and the targets are words, the most typical experimental situation. Indeed, it does appear that no-one has yet reported phonological priming effects in such situations. The question of whether it is possible to observe phonological priming in such situations was more fully examined in the present experiments. Experiment 1 involved a masked priming SDT using Japanese Kanji script in which the primes and targets were homophonic but shared no characters. Experiment 2 was a parallel experiment using Chinese stimuli. In both experiments, phonological priming effects were observed for both one- and two-character words. These experiments indicate that, although the priming effects in masked priming SDTs undoubtedly have a strong orthographic basis, phonological codes also play a role even when the prime and (word) target are written in the same script.


Asunto(s)
Actividad Motora , Humanos , Enmascaramiento Perceptual , Fonética , Tiempo de Reacción , Lectura , Escritura
10.
Mem Cognit ; 49(3): 600-612, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33021727

RESUMEN

In attempting to understand mental processes, it is important to use a task that appropriately reflects the underlying processes being investigated. Recently, Verdonschot and Kinoshita (Memory & Cognition, 46, 410-425, 2018) proposed that a variant of the Stroop task-the "phonological Stroop task"-might be a suitable tool for investigating speech production. The major advantage of this task is that the task is apparently not affected by the orthographic properties of the stimuli, unlike other, commonly used, tasks (e.g., associative-cuing and word-reading tasks). The viability of this proposal was examined in the present experiments by manipulating the script types of Japanese distractors. For Romaji distractors (e.g., "kushi"), color-naming responses were faster when the initial phoneme was shared between the color name and the distractor than when the initial phonemes were different, thereby showing a phoneme-based phonological Stroop effect (Experiment 1). In contrast, no such effect was observed when the same distractors were presented in Katakana (e.g., "くし"), replicating Verdonschot and Kinoshita's original results (Experiment 2). A phoneme-based effect was again found when the Katakana distractors used in Verdonschot and Kinoshita's original study were transcribed and presented in Romaji (Experiment 3). Because the observation of a phonemic effect directly depended on the orthographic properties of the distractor stimuli, we conclude that the phonological Stroop task is also susceptible to orthographic influences.


Asunto(s)
Lectura , Habla , Comprensión , Humanos , Japón , Test de Stroop
11.
J Med Chem ; 64(1): 861-870, 2021 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-33378197

RESUMEN

Retinoid X receptor (RXR) modulators (rexinoids) are considered to have therapeutic potential for multiple diseases, such as Alzheimer's disease and Parkinson's disease. To overcome various disadvantages of prior screening methods, we previously developed an RXR binding assay using a fluorescent RXR ligand, CU-6PMN (4). However, this ligand binds not only at the ligand-binding domain (LBD) but also at the dimer-dimer interface of hRXRα. Here, we present a new fluorescent RXR antagonist 6-[N-ethyl-N-(5-isobutoxy-4-isopropyl-2-(11-oxo-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinoline-10-carboxamido)phenyl)amino]nicotinic acid (NEt-C343, 7), which emits strong fluorescence only when bound to the RXR-LBD. It allows us to perform a rapid, simple, and nonhazardous binding assay that does not require bound/free separation and uses a standard plate reader. The obtained Ki values of known compounds were correlated with the Ki values obtained using the standard [3H]9cis-retinoic acid assay. This assay should be useful for drug discovery as well as for research on endocrine disruptors, functional foods, and natural products.


Asunto(s)
Niacina/química , Receptores X Retinoide/antagonistas & inhibidores , Sitios de Unión , Humanos , Cinética , Ligandos , Simulación del Acoplamiento Molecular , Niacina/metabolismo , Niacina/farmacología , Unión Proteica , Receptores X Retinoide/genética , Receptores X Retinoide/metabolismo , Espectrometría de Fluorescencia , Activación Transcripcional/efectos de los fármacos
12.
J Exp Psychol Learn Mem Cogn ; 46(8): 1570-1589, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32150436

RESUMEN

In a masked priming word-naming task, a facilitation due to the initial-segmental sound overlap for 2-character kanji prime-target pairs was affected by certain orthographic properties (Yoshihara, Nakayama, Verdonschot, & Hino, 2017). That is, the facilitation that was due to the initial mora overlap occurred only when the mora was the whole pronunciation of their initial kanji characters (i.e., match pairs; e.g., /ka-se.ki/- /ka-rjo.ku/). When the shared initial mora was only a part of the kanji characters' readings, however, there was no facilitation (i.e., mismatch pairs; e.g., /ha.tu-a.N/- /ha.ku-bu.tu/). In the present study, we used a masked priming picture-naming task to investigate whether the previous results were relevant only when the orthography of targets is visually presented. In Experiment 1, the main findings of our word-naming task were fully replicated in a picture-naming task. In Experiments 2 and 3, the absence of facilitation for the mismatch pairs were confirmed with a new set of stimuli. On the other hand, a significant facilitation was observed for the match pairs that shared the 2 initial morae (in Experiment 4), which was again consistent with the results of our word-naming study. These results suggest that the orthographic properties constrain the phonological expression of masked priming for kanji words across 2 tasks that are likely to differ in how phonology is retrieved. Specifically, we propose that orthography of a word is activated online and constrains the phonological encoding processes in these tasks. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Asunto(s)
Reconocimiento Visual de Modelos/fisiología , Enmascaramiento Perceptual/fisiología , Psicolingüística , Lectura , Habla/fisiología , Adulto , Femenino , Humanos , Masculino , Adulto Joven
13.
J Exp Psychol Hum Percept Perform ; 44(8): 1168-1185, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29683717

RESUMEN

The present research examined whether a lexical competition process operates when different-script bilinguals process L2 words. In masked priming lexical decision experiments (67 ms prime duration), word neighbor primes facilitated target identification for Japanese-English bilinguals (Experiment 1) although the same primes produced inhibitory effects for L1 English readers (Experiment 2). Subsequent experiments confirmed that the facilitory priming effects are reliable (Experiment 4), and are not due to bilinguals' inability to process masked L2 primes to the lexical level (Experiments 3 and 4) or bilinguals relying on sublexical activation from neighbor primes in responding to upper-case English targets (Experiment 5). Some evidence of lexical competition was observed, however, with clearly visible primes (Experiment 6, using a 175 ms prime duration). These results suggest that different-script bilinguals deal with orthographic similarity in L2 words differently from L1 readers. The authors discuss ways in which the L2 lexicon of different-script bilinguals may be different. (PsycINFO Database Record


Asunto(s)
Multilingüismo , Reconocimiento Visual de Modelos/fisiología , Enmascaramiento Perceptual/fisiología , Psicolingüística , Lectura , Adulto , Humanos , Adulto Joven
14.
J Exp Psychol Learn Mem Cogn ; 44(8): 1317-1324, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29389191

RESUMEN

The present experiment provides an investigation of a promising new tool, the masked priming same-different task, for investigating the orthographic coding process. Orthographic coding is the process of establishing a mental representation of the letters and letter order in the word being read which is then used by readers to access higher-level (e.g., semantic) information about that word. Prior research (e.g., Norris & Kinoshita, 2008) had suggested that performance in this task may be based entirely on orthographic codes. As reported by Lupker, Nakayama, and Perea (2015a), however, in at least some circumstances, phonological codes also play a role. Specifically, even though their 2 languages are completely different orthographically, Lupker et al.'s Japanese-English bilinguals showed priming in this task when masked L1 primes were phonologically similar to L2 targets. An obvious follow-up question is whether Lupker et al.'s effect might have resulted from a strategy that was adopted by their bilinguals to aid in processing of, and memory for, the somewhat unfamiliar L2 targets. In the present experiment, Japanese readers responded to (Japanese) Kanji targets with phonologically identical primes (on "related" trials) being presented in a completely different but highly familiar Japanese script, Hiragana. Once again, significant priming effects were observed, indicating that, although performance in the masked priming same-different task may be mainly based on orthographic codes, phonological codes can play a role even when the stimuli being matched are familiar words from a reader's L1. (PsycINFO Database Record


Asunto(s)
Multilingüismo , Fonética , Lectura , Memoria Implícita , Humanos , Reconocimiento Visual de Modelos , Enmascaramiento Perceptual
15.
J Exp Psychol Hum Percept Perform ; 43(7): 1303-1328, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28301184

RESUMEN

Using the masked priming paradigm, we examined which phonological unit is used when naming Kanji compounds. Although the phonological unit in the Japanese language has been suggested to be the mora, Experiment 1 found no priming for mora-related Kanji prime-target pairs. In Experiment 2, significant priming was only found when Kanji pairs shared the whole sound of their initial Kanji characters. Nevertheless, when the same Kanji pairs used in Experiment 2 were transcribed into Kana, significant mora priming was observed in Experiment 3. In Experiment 4, matching the syllable structure and pitch-accent of the initial Kanji characters did not lead to mora priming, ruling out potential alternative explanations for the earlier absence of the effect. A significant mora priming effect was observed, however, when the shared initial mora constituted the whole sound of their initial Kanji characters in Experiments 5. Lastly, these results were replicated in Experiment 6. Overall, these results indicate that the phonological unit involved when naming Kanji compounds is not the mora but the whole sound of each Kanji character. We discuss how different phonological units may be involved when processing Kanji and Kana words as well as the implications for theories dealing with language production processes. (PsycINFO Database Record


Asunto(s)
Reconocimiento Visual de Modelos/fisiología , Enmascaramiento Perceptual/fisiología , Psicolingüística , Lectura , Memoria Implícita/fisiología , Habla/fisiología , Adulto , Humanos , Japón , Fonética , Adulto Joven
16.
J Exp Psychol Learn Mem Cogn ; 43(7): 1140-1146, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28114782

RESUMEN

Models of written word recognition in languages using the Roman alphabet assume that a word's visual form is quickly mapped onto abstract units. This proposal is consistent with the finding that masked priming effects are of similar magnitude from lowercase, uppercase, and alternating-case primes (e.g., beard-BEARD, BEARD-BEARD, and BeArD-BEARD). We examined whether this claim can be readily generalized to the 2 syllabaries of Japanese Kana (Hiragana and Katakana). The specific rationale was that if the visual form of Kana words is lost early in the lexical access process, alternating-script repetition primes should be as effective as same-script repetition primes at activating a target word. Results showed that alternating-script repetition primes were less effective at activating lexical representations of Katakana words than same-script repetition primes-indeed, they were no more effective than partial primes that contained only the Katakana characters from the alternating-script primes. Thus, the idiosyncrasies of each writing system do appear to shape the pathways to lexical access. (PsycINFO Database Record


Asunto(s)
Lenguaje , Reconocimiento Visual de Modelos/fisiología , Lectura , Vocabulario , Escritura , Pueblo Asiatico , Femenino , Humanos , Masculino , Estimulación Luminosa , Estudiantes , Universidades
17.
Front Psychol ; 7: 175, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26941669

RESUMEN

Recent research has revealed that the way phonology is constructed during word production differs across languages. Dutch and English native speakers are suggested to incrementally insert phonemes into a metrical frame, whereas Mandarin Chinese speakers use syllables and Japanese speakers use a unit called the mora (often a CV cluster such as "ka" or "ki"). The present study is concerned with the question how bilinguals construct phonology in their L2 when the phonological unit size differs from the unit in their L1. Japanese-English bilinguals of varying proficiency read aloud English words preceded by masked primes that overlapped in just the onset (e.g., bark-BENCH) or the onset plus vowel corresponding to the mora-sized unit (e.g., bell-BENCH). Low-proficient Japanese-English bilinguals showed CV priming but did not show onset priming, indicating that they use their L1 phonological unit when reading L2 English words. In contrast, high-proficient Japanese-English bilinguals showed significant onset priming. The size of the onset priming effect was correlated with the length of time spent in English-speaking countries, which suggests that extensive exposure to L2 phonology may play a key role in the emergence of a language-specific phonological unit in L2 word production.

18.
J Exp Psychol Hum Percept Perform ; 41(5): 1281-99, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26076173

RESUMEN

Norris and colleagues (Kinoshita & Norris, 2009; Norris & Kinoshita, 2008; Norris, Kinoshita, & van Casteren, 2010) have suggested that priming effects in the masked prime same-different task are based solely on prelexical orthographic codes. This suggestion was evaluated by examining phonological priming in that task using Japanese-English bilinguals. Targets and reference words were English words with the primes written in Katakana script, a syllabic script that is orthographically quite different from the Roman letter script used in writing English. Phonological priming was observed both when the primes were Japanese cognate translation equivalents of the English target/reference words (Experiment 1) and when the primes were phonologically similar Katakana nonwords (Experiment 2), with the former effects being substantially larger than the noncognate translation priming effects reported by Lupker, Perea, and Nakayama (2015). These results indicate that the same-different task is influenced by phonological information. One implication is that, due to the fact that phonology and orthography are inevitably confounded in Roman letter languages, previously reported priming effects in those languages may have been at least partly due to phonological, rather than orthographic, similarity. The potential extent of this problem, the nature of the matching process in the same-different task, and the implications for using this task as a means of investigating the orthographic code in reading are discussed.


Asunto(s)
Multilingüismo , Reconocimiento Visual de Modelos/fisiología , Psicolingüística/métodos , Desempeño Psicomotor/fisiología , Lectura , Memoria Implícita/fisiología , Adulto , Humanos , Pruebas Neuropsicológicas/normas , Fonética , Adulto Joven
19.
J Med Chem ; 58(2): 912-26, 2015 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-25486327

RESUMEN

We previously reported RXR partial agonist CBt-PMN (1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-1H-benzotriazole-5-carboxylic acid: 5, EC50 = 143 nM, Emax = 75%), which showed a potent glucose-lowering effect without causing serious adverse effects. However, it remains important to elucidate the structural requirements for RXR efficacy and the glucose-lowering effect because RXR-permissive heterodimers such as PPAR/RXR or LXR/RXR are reported to be activated differently depending upon the chemical structure of RXR agonists. In this work, we show that an RXR partial agonist, NEt-4IB (6-[ethyl-(4-isobutoxy-3-isopropylphenyl)amino]pyridine-3-carboxylic acid: 8b, EC50 = 169 nM, Emax = 55%), can be obtained simply by repositioning the side chains (interchanging the isobutoxy and isopropoxy groups) at the hydrophobic moiety of the RXR full agonist NEt-3IB (6-[ethyl-(3-isobutoxy-4-isopropylphenyl)amino]pyridine-3-carboxylic acid: 7b, EC50 = 19 nM). NEt-4IB (8b) showed antitype 2 diabetes activity without the above side effects upon repeated oral administration to mice at 10 mg/kg/day, similarly to 5.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/síntesis química , Receptores X Retinoide/agonistas , Animales , Células COS , Chlorocebus aethiops , Femenino , Hipoglucemiantes/farmacología , Hipoglucemiantes/toxicidad , Masculino , Ratones , Ratones Endogámicos ICR , Ratas , Ratas Sprague-Dawley
20.
J Exp Psychol Hum Percept Perform ; 40(2): 813-40, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24364705

RESUMEN

In the masked priming paradigm, when a word target is primed by a higher frequency neighbor (e.g., blue-BLUR), lexical decision latencies are slower than when the same word is primed by an unrelated word of equivalent frequency (e.g., care-BLUR). This inhibitory neighbor priming effect (e.g., Davis & Lupker, 2006; Segui & Grainger, 1990) is taken as evidence for the lexical competition process that is an important component of localist activation-based models of visual word recognition (Davis, 2003; Grainger & Jacobs, 1996; McClelland & Rumelhart, 1981). The present research looked for evidence of an inhibitory neighbor priming effect using words written in Japanese Kanji, a logographic, nonalphabetic script. In 4 experiments (Experiments 1A, 1B, 3A, and 3B), inhibitory neighbor priming effects were observed for low-frequency targets primed by higher frequency Kanji word neighbors ([symbol in text]). In contrast, there was a significant facilitation effect when targets were primed by Kanji nonword neighbors ([symbols in text]; Experiments 2 and 3). Significant facilitation was also observed when targets were primed by single constituent Kanji characters ([symbols in text]; Experiment 4). Taken together, these results suggest that lexical competition plays a role in the recognition of Kanji words, just as it does for words in alphabetic languages. However, in Kanji, and likely in other logographic languages, the effect of lexical competition appears to be counteracted by facilitory morphological priming due to the repetition of a morphological unit in the prime and target (i.e., in Kanji, each character represents a morpheme).


Asunto(s)
Inhibición Psicológica , Reconocimiento Visual de Modelos/fisiología , Enmascaramiento Perceptual/fisiología , Lectura , Memoria Implícita/fisiología , Adulto , Humanos , Adulto Joven
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