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Imaging Neuroreceptors in the Living Human Brain

  • Wagner Jr Henry N.;Dannals Robert F.;Frost J. James;Wong Dean F.;Ravert Hayden T.;Wilson Alan A.;Links Jonathan M.;Burns H. Donald;Kuhar Michael J.;Snyder Solomon H.
    • The Korean Journal of Nuclear Medicine
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    • v.18 no.2
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    • pp.17-23
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    • 1984
  • For nearly a century it has been known that chemical activity accompanies mental activity, but only recently has it been possible to begin to examine its exact nature. Positron-emitting radioactive tracers have made it possible to study the chemistry of the human mind in health and disease, using chiefly cyclotron-produced radionuclides, carbon-11, fluorine-18 and oxygen-15. It is now well established that measurable increases in regional cerebral blood flow, glucose and oxygen metabolism accompany the mental functions of perception, cognition, emotion and motion. On May 25, 1983 the first imaging of a neuroreceptor in the human brain was accomplished with carbon-11 methyl spiperone, a ligand that binds preferentially to dopamine-2 receptors, 80% of which are located in the caudate nucleus and putamen. Quantitative imaging of serotonin-2, opiate, benzodiazapine and muscarinic cholinergic receptors has subsequently been accomplished. In studies of normal men and women, it has been found that dopamine and serotonin receptor activity decreases dramatically with age, such a decrease being more pronounced in men than in women and greater in the case of dopamine receptors than serotonin-2 receptors. Preliminary studies in patients with neuropsychiatric disorders suggests that dopamine-2 receptor activity is diminished in the caudate nucleus of patients with Huntington's disease. Positron tomography permits quantitative assay of picomolar quantities of neuro-receptors within the living human brain. Studies of patients with Parkinson's disease, Alzheimer's disease, depression, anxiety, schizophrenia, acute and chronic pain states and drug addiction are now in progress. The growth of any scientific field is based on a paradigm or set of ideas that the community of scientists accepts. The unifying principle of nuclear medicine is the tracer principle applied to the study of human disease. Nineteen hundred and sixty-three was a landmark year in which technetium-99m and the Anger camera combined to move the field from its latent stage into a second stage characterized by exponential growth within the framework of the paradigm. The third stage, characterized by gradually declining growth, began in 1973. Faced with competing advances, such as computed tomography and ultrasonography, proponents and participants in the field of nuclear medicine began to search for greener pastures or to pursue narrow sub-specialties. Research became characterized by refinements of existing techniques. In 1983 nuclear medicine experienced what could be a profound change. A new paradigm was born when it was demonstrated that, despite their extremely low chemical concentrations, in the picomolar range, it was possible to image and quantify the distribution of receptors in the human body. Thus, nuclear medicine was able to move beyond physiology into biochemistry and pharmacology. Fundamental to the science of pharmacology is the concept that many drugs and endogenous substances, such as neurotransmitters, react with specific macromolecules that mediate their pharmacologic actions. Such receptors are usually identified in the study of excised tissues, cells or cell membranes, or in autoradiographic studies in animals. The first imaging and quantification of a neuroreceptor in a living human being was performed on May 25, 1983 and reported in the September 23, 1983 issue of SCIENCE. The study involved the development and use of carbon-11 N-methyl spiperone (NMSP), a drug with a high affinity for dopamine receptors. Since then, studies of dopamine and serotonin receptors have been carried out in over 100 normal persons or patients with various neuropsychiatric disorders. Exactly one year later, the first imaging of opitate receptors in a living human being was performed [1].

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EST Profiling for Seed-hair Characteristic and Development of EST-SSR and SNP Markers in Carrot (당근 종모 형질 관련 EST profiling과 이를 이용한 EST-SSR 및 SNP 마커 개발)

  • Oh, Gyu-Dong;Hwang, Eun-Mi;Shim, Eun-Jo;Jeon, Sang-Jin;Park, Young-Doo
    • Horticultural Science & Technology
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    • v.28 no.6
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    • pp.1025-1038
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    • 2010
  • Carrot ($Daucus$ $carota$ L. var. $sativa$) is one of the most widely used crops in the world. Moreover it is an important crop because of its high content of ${\beta}$-carotene, well-known as the precursor of vitamin A carotenoid. However, seed-hair which is generated in epidermal cell of seeds inhibits absorption and germination. For that reason, carrot seeds are commercialized after mechanical hair removal process. To overcome such cumbersome weaknesses, new breeding program for developing hairless-seed carrot cultivar has been needed. Therefore, in this study, cDNA libraries from seeds of short-hair seed phenotype CT-ATR615 OP 666-13line and hairy seed CT-ATR615 OP-CK1-9 line were constructed and expression patterns related to generation of seed-hair were analyzed by comparison of EST sequences. Differential EST sequence results between two lines were classified into FunCat functional categories based on the results of BlastX search. Higher expression quantities belonging to metabolic category were shown on short-hair seed line than hairy-seed one. Differential expression quantities between those two lines in the protein folding and stabilization, subcellular localization categories were supposed to contribute variously on the generation of seed-hair. We confirmed 50 and 59 SSR sites, and 2 SNP sites by analyzing EST sequences in two lines; thereafter, we designed SNP and SSR primer sets from these EST sequence information as a molecular marker. These markers are thought to be used in research of molecular markers for classification of carrot family and related to various traits, as well as seed-hair characteristic.

Isolation and characterization of sigH from Corynebacterium glutamicum (Corynebacterium glutamicum의 sigH 유전자의 분리 및 기능분석)

  • Kim Tae-Hyun;Kim Hyung-Joon;Park Joon-Sung;Kim Younhee;Lee Heung-Shick
    • Korean Journal of Microbiology
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    • v.41 no.2
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    • pp.99-104
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    • 2005
  • Corynebacterial clones which exert regulatory effects on the expression of the glyoxylate bypass genes were isolated using a reporter plasmid carrying the enteric lacZ fused to the aceB promoter of Corynebacterium glutamicum. Some clones carried common fragments as turned out by DNA mapping technique. Subcloning analysis followed by the measurement of $\beta-galactosidase$ activity in Escherichia coli identified the region responsible for the aceB-repressing activity. Sequence analysis of the DNA fragment identified two independent ORFs of ORF1 and ORF2. Among them, ORF2 was turned out to be responsible for the aceB-repressing activity. ORF1 encoded a 23,216 Da protein composed of 206 amino acids. Sequence similarity search indicated that the ORF may encode a ECF-type $\sigma$ factor and designated sigH. To identify the function of sigH, C. glutamicum sigH mutant was constructed by gene disruption technique and the sigH mutant showed growth retardation as compared to the wild type strain. In addition, the mutant strain showed sensitivity to oxidative-stress generating agent plumbagin. This result imply that sigH is probably involved in the stress response occurring during normal cell growth.

Antioxidant and Anti-inflammatory Activities of Functional Plant Materials (항산화 및 면역 활성 증강을 위한 생약재의 탐색)

  • Lee, Soo-Jung;Shin, Jung-Hye;Lee, Hye-Jin;Tak, Hyun-Min;Kang, Min-Jung;Sung, Nak-Ju
    • Journal of Life Science
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    • v.23 no.7
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    • pp.869-878
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    • 2013
  • Eleven functional plant materials were identified via a literature search, and their antioxidant capacity and inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells were tested. Yields from hot water extracts of the materials were the highest (52.10%) in Lycii fructus, and the yields from Phellinus linteus were the lowest (5.7%). The yields of another were 14.50-42.47%. Total phenol and flavonoids contents were the highest in P. linteus. The $EC_{50}$ values for DPPH and ABTS radical scavenging activities were lower than $100{\mu}g/ml$ for Salvia miltiorrhiza, whereas the values for P. linteus, Scutellaria baicalensis, and Paeonia lactiflora were $100-200{\mu}g/ml$. The $EC_{50}$ value for the superoxide anion radical scavenging activity of all the extracts was higher than $300{\mu}g/ml$. P. linteus for the reducing power was shown the highest activity. $Fe^{2+}$ chelating activity was the highest in the Morus alba extract. In an MTT assay, the cell viability of the RAW264.7 LPS-exposed cells was above 80% in extracts of $50{\mu}g/ml$ and above 77% in extracts of $100{\mu}g/ml$ in all the plant materials except Acanthopanax sessiliflorum. NO production in the RAW264.7 LPS-exposed cells showed a 12-fold increase compared to the control. The NO production level of all the extracts was $6.86-26.18{\mu}M$. Notably, $100{\mu}g/ml$ of S. baicalensis extract showed a remarkable decrease in NO production (72%) compared with the control. The potent antioxidant and anti-inflammatory activities of S.baicalensis, P. linteus, S. miltiorrhiza, M. alba, and P. lactiflora suggest that they are potential candidates as functional materials.

Potential Antitumor $\alpha$-Methylene-$\gamma$-butyrolactone-Bearing Nucleic Acid Base. 3. Synthesis of $5^1$-Methyl-$5^1$-[(6-substituted-9H-purin-9-yl)methyl]-$2^1$-oxo-$3^1$-methylenetetrahydrofurans

  • Kim, Jack-C.;Kim, Si-Hwan;Kim, Ji-A;Choi, Soon-Kyu;Park, Won-Woo
    • Archives of Pharmacal Research
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    • v.21 no.4
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    • pp.458-464
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    • 1998
  • Search for a new $\alpha$-methylene-$\gamma$-butyrolactone-bearing 6-substituted purine as a potental antitumor agent has led to synthesize seven, hitherto unreported, $5^1$-Methyl-$5^1$-[(6-substituted-9H-purin-9-yl)methyl]-$2^1$-oxo-$3^1$- methylenetetrahydrofurans (H, Cl, l, $CH_3$, $NH_2$, SH, >C=O) (6a-g). These include $5^1$-Methyl-$5^1$-[(9H-purin-9-yl)methyll-$2^1$-oxo-$3^1$ -methylenetetrahydrofurans (6a), $5^1$-Methyl-$5^1$-[(6-chloro-9H-purin-9-yl)methyl]-$2^1$-oxo-$3^1$-methylenetetrahydr ofurans (6b), $5^1$-Methyl-$5^1$-[(6-chloro-9H-purin-9-yl) methyl]-$2^1$-oxo-$3^1$-methylenetetrahydrofurans (6c), $5^1$-Methyl-$5^1$-[(6-methyl-9H-purin-9-yl) methyl]-$2^1$-oxo-$3^1$-methylenetetrahydrofurans (6d), $5^1$-Methyl-$5^1$-[(9H-adenin-9-yl)methyll-$2^1$-oxo-$3^1$-methylenetetrahydrofurans (6e), $5^1$-Methyl-$5^1$-[(6-mercapto-9H-purin-9-yl) methyl]-$2^1$-oxo-$3^1$-methylenetetrahydrofurans (6f) and $5^1$-Methyl-$5^1$-[(9H-hypoxanthin-9-yl)methyll-$2^1$-oxo-$3^1$-methylenetetrahydrof urans (6g) which were made by the Reformatsky-type reaction of ethyl $\alpha$-(bromomethyl) acrylate with the corresponding (6-substituted-9H-purin-9-yl)-2-propanone intermediates (5a-g). These ketone intermediates 5a-g, 1-(9H-purin-9-yl)-2-propanone (5a), 1-(6-chloro-9H-purin-9-yl)-2-propanone (5b), 1-(6-iodo-9H-purin-9-yi)-2-propanone (5c), 1-(6-methyl-9H-purin-9-yl)-2-propanone (5d), 1-(9H-adenin-9-yl)-2-propanone (Se), 1-(6-mercapto-9H-purin-9-yl)-2-propanone (5f), and 1-(9H-hypoxanthin-9-yl)-2-propanone (5g) were directly obtained by the alkylation of the 6-substituted purine bases with the chloroacetone in the presence of $K_2$$CO_3$ (or NaH) under DMF (or DMSO). The preliminary in vitro cytotoxcity assay for the synthetic .alpha.-methylene-y-butyro-lactone compounds (6a-g) were determined against three cell lines (PM-3A, P-388, and K-562) and showed the moderate antitumor activity ($IC_50$ ranged from 1.4 to 4.3 $\mu\textrm{g}$/ml) with the compound $5^1$-methyl-$5^1$ -[(9H-hypoxanthin-9-yl)methyl]-$2^1$-oxo-$3^1$-methylenetetrahydrofuran (6g) showing the least antitumor activity.

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How Enduring Product Involvement and Perceived Risk Affect Consumers' Online Merchant Selection Process: The 'Required Trust Level' Perspective (지속적 관여도 및 인지된 위험이 소비자의 온라인 상인선택 프로세스에 미치는 영향에 관한 연구: 요구신뢰 수준 개념을 중심으로)

  • Hong, Il-Yoo B.;Lee, Jung-Min;Cho, Hwi-Hyung
    • Asia pacific journal of information systems
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    • v.22 no.1
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    • pp.29-52
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    • 2012
  • Consumers differ in the way they make a purchase. An audio mania would willingly make a bold, yet serious, decision to buy a top-of-the-line home theater system, while he is not interested in replacing his two-decade-old shabby car. On the contrary, an automobile enthusiast wouldn't mind spending forty thousand dollars to buy a new Jaguar convertible, yet cares little about his junky component system. It is product involvement that helps us explain such differences among individuals in the purchase style. Product involvement refers to the extent to which a product is perceived to be important to a consumer (Zaichkowsky, 2001). Product involvement is an important factor that strongly influences consumer's purchase decision-making process, and thus has been of prime interest to consumer behavior researchers. Furthermore, researchers found that involvement is closely related to perceived risk (Dholakia, 2001). While abundant research exists addressing how product involvement relates to overall perceived risk, little attention has been paid to the relationship between involvement and different types of perceived risk in an electronic commerce setting. Given that perceived risk can be a substantial barrier to the online purchase (Jarvenpaa, 2000), research addressing such an issue will offer useful implications on what specific types of perceived risk an online firm should focus on mitigating if it is to increase sales to a fullest potential. Meanwhile, past research has focused on such consumer responses as information search and dissemination as a consequence of involvement, neglecting other behavioral responses like online merchant selection. For one example, will a consumer seriously considering the purchase of a pricey Guzzi bag perceive a great degree of risk associated with online buying and therefore choose to buy it from a digital storefront rather than from an online marketplace to mitigate risk? Will a consumer require greater trust on the part of the online merchant when the perceived risk of online buying is rather high? We intend to find answers to these research questions through an empirical study. This paper explores the impact of enduring product involvement and perceived risks on required trust level, and further on online merchant choice. For the purpose of the research, five types or components of perceived risk are taken into consideration, including financial, performance, delivery, psychological, and social risks. A research model has been built around the constructs under consideration, and 12 hypotheses have been developed based on the research model to examine the relationships between enduring involvement and five components of perceived risk, between five components of perceived risk and required trust level, between enduring involvement and required trust level, and finally between required trust level and preference toward an e-tailer. To attain our research objectives, we conducted an empirical analysis consisting of two phases of data collection: a pilot test and main survey. The pilot test was conducted using 25 college students to ensure that the questionnaire items are clear and straightforward. Then the main survey was conducted using 295 college students at a major university for nine days between December 13, 2010 and December 21, 2010. The measures employed to test the model included eight constructs: (1) enduring involvement, (2) financial risk, (3) performance risk, (4) delivery risk, (5) psychological risk, (6) social risk, (7) required trust level, (8) preference toward an e-tailer. The statistical package, SPSS 17.0, was used to test the internal consistency among the items within the individual measures. Based on the Cronbach's ${\alpha}$ coefficients of the individual measure, the reliability of all the variables is supported. Meanwhile, the Amos 18.0 package was employed to perform a confirmatory factor analysis designed to assess the unidimensionality of the measures. The goodness of fit for the measurement model was satisfied. Unidimensionality was tested using convergent, discriminant, and nomological validity. The statistical evidences proved that the three types of validity were all satisfied. Now the structured equation modeling technique was used to analyze the individual paths along the relationships among the research constructs. The results indicated that enduring involvement has significant positive relationships with all the five components of perceived risk, while only performance risk is significantly related to trust level required by consumers for purchase. It can be inferred from the findings that product performance problems are mostly likely to occur when a merchant behaves in an opportunistic manner. Positive relationships were also found between involvement and required trust level and between required trust level and online merchant choice. Enduring involvement is concerned with the pleasure a consumer derives from a product class and/or with the desire for knowledge for the product class, and thus is likely to motivate the consumer to look for ways of mitigating perceived risk by requiring a higher level of trust on the part of the online merchant. Likewise, a consumer requiring a high level of trust on the merchant will choose a digital storefront rather than an e-marketplace, since a digital storefront is believed to be trustworthier than an e-marketplace, as it fulfills orders by itself rather than acting as an intermediary. The findings of the present research provide both academic and practical implications. The first academic implication is that enduring product involvement is a strong motivator of consumer responses, especially the selection of a merchant, in the context of electronic shopping. Secondly, academicians are advised to pay attention to the finding that an individual component or type of perceived risk can be used as an important research construct, since it would allow one to pinpoint the specific types of risk that are influenced by antecedents or that influence consequents. Meanwhile, our research provides implications useful for online merchants (both online storefronts and e-marketplaces). Merchants may develop strategies to attract consumers by managing perceived performance risk involved in purchase decisions, since it was found to have significant positive relationship with the level of trust required by a consumer on the part of the merchant. One way to manage performance risk would be to thoroughly examine the product before shipping to ensure that it has no deficiencies or flaws. Secondly, digital storefronts are advised to focus on symbolic goods (e.g., cars, cell phones, fashion outfits, and handbags) in which consumers are relatively more involved than others, whereas e- marketplaces should put their emphasis on non-symbolic goods (e.g., drinks, books, MP3 players, and bike accessories).

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