• Title/Summary/Keyword: Current derivative

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Modulation of $Ca^{2+}-Activated$ Potassium Channels by cGMP-Dependent Signal Transduction Mechanism in Cerebral Arterial Smooth Muscle Cell of the Rabbit

  • Han, Jin;Kim, Na-Ri;Lee, Kwang-Bok;Kim, Eui-Yong
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.6
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    • pp.445-453
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    • 2000
  • The present investigation tested the hypothesis that the activation of protein kinase G (PKG) leads to a phosphorylation of $Ca^{2+}-activated$ potassium channel $(K_{Ca}\;channel)$ and is involved in the activation of $K_{Ca}$ channel activity in cerebral arterial smooth muscle cells of the rabbit. Single-channel currents were recorded in cell-attached and inside-out patch configurations of patch-clamp techniques. Both molsidomine derivative 3-morpholinosydnonimine-N-ethylcarbamide $(SIN-1,\;50\;{\mu}M)$ and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate $(8-pCPT-cGMP,\;100\;{\mu}M),$ a membrane-permeable analogue of cGMP, increased the $K_{Ca}$ channel activity in the cell-attached patch configuration, and the effect was removed upon washout of the drugs. In inside-out patches, single-channel current amplitude was not changed by SIN-1 and 8-pCPT-cGMP. Application of ATP $(100\;{\mu}M),$ cGMP $(100\;{\mu}M),$ ATP+cGMP $(100\;{\mu}M\;each),$ PKG $(5\;U/{\mu}l),$ ATP $(100\;{\mu}M)+PKG\;(5\;U/{\mu}l),$ or cGMP $(100\;{\mu}M)+PKG\;(5\;U/{\mu}l)$ did not increase the channel activity. ATP $(100\;{\mu}M)+cGMP\;(100\;{\mu}M)+PKG\;(5\;U/{\mu}l)$ added directly to the intracellular phase of inside-out patches increased the channel activity with no changes in the conductance. The heat-inactivated PKG had no effect on the channel activity, and the effect of PKG was inhibited by 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate, Rp-isomer $(Rp-pCPT-cGMP,\;100\;{\mu}M),$ a potent inhibitor of PKG or protein phosphatase 2A (PP2A, 1 U/ml). In the presence of okadaic acid (OA, 5 nM), PP2A had no effect on the channel activity. The $K_{Ca}$ channel activity spontaneously decayed to the control level upon washout of ATP, cGMP and PKG, and this was prevented by OA (5 nM) in the medium. These results suggest that the PKG-mediated phosphorylations of $K_{Ca}$ channels, or some associated proteins in the membrane patch increase the activity of the $K_{Ca}$ channel, and the activation may be associated with the vasodilating action.

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A Role for the Carbohydrate Portion of Ginsenoside Rg3 in Na+ Channel Inhibition

  • Kim, Jong-Hoon;Hong, Yoon-Hee;Lee, Jun-Ho;Kim, Dong-Hyun;Nam, Ghilsoo;Jeong, Sang Min;Lee, Byung-Hwan;Lee, Sang-Mok;Nah, Seung-Yeol
    • Molecules and Cells
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    • v.19 no.1
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    • pp.137-142
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    • 2005
  • We showed recently that ginsenosides inhibit the activity of various types of ion channel. Here we have investigated the role of the carbohydrate component of ginsenoside $Rg_3$ in the inhibition of $Na^+$ channels. The channels were expressed in Xenopus oocytes by injecting cRNAs encoding rat brain Nav1.2 ${\alpha}$ and ${\beta}1$ subunits, and analyzed by the two-electrode voltage clamp technique. Treatment with $Rg_3$ reversibly inhibited the inward $Na^+$ peak current ($I_{Na}$) with an $IC_{50}$ of $32.2{\pm}4.5{\mu}M$, and the inhibition was voltage-dependent. To examine the role of the sugar moiety, we prepared a straight chain form of the second glucose and a conjugate of this glucose with 3-(4-hydroxyphenyl) propionic acid hydrazide (HPPH). Neither derivative inhibited $I_{Na}$. Treatment with the carbohydrate portion of ginsenoside $Rg_3$, sophorose [${\beta}-D-glucopyranosyl$ ($1{\rightarrow}2$)-${\beta}-glucopyranoside$], or the aglycone (protopanaxadiol), on their own or in combination had no effect on $I_{Na}$. These observations indicate that the carbohydrate portion of ginsenoside $Rg_3$ plays an important role in its effect on the $Na^+$ channel.

An Examination of Knowledge Sourcing Strategies Effects on Corporate Performance in Small Enterprises (소규모 기업에 있어서 지식소싱 전략이 기업성과에 미치는 영향 고찰)

  • Choi, Byoung-Gu
    • Asia pacific journal of information systems
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    • v.18 no.4
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    • pp.57-81
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    • 2008
  • Knowledge is an essential strategic weapon for sustaining competitive advantage and is the key determinant for organizational growth. When knowledge is shared and disseminated throughout the organization, it increases an organization's value by providing the ability to respond to new and unusual situations. The growing importance of knowledge as a critical resource has forced executives to pay attention to their organizational knowledge. Organizations are increasingly undertaking knowledge management initiatives and making significant investments. Knowledge sourcing is considered as the first important step in effective knowledge management. Most firms continue to make an effort to realize the benefits of knowledge management by using various knowledge sources effectively. Appropriate knowledge sourcing strategies enable organizations to create, acquire, and access knowledge in a timely manner by reducing search and transfer costs, which result in better firm performance. In response, the knowledge management literature has devoted substantial attention to the analysis of knowledge sourcing strategies. Many studies have categorized knowledge sourcing strategies into intemal- and external-oriented. Internal-oriented sourcing strategy attempts to increase firm performance by integrating knowledge within the boundary of the firm. On the contrary, external-oriented strategy attempts to bring knowledge in from outside sources via either acquisition or imitation, and then to transfer that knowledge across to the organization. However, the extant literature on knowledge sourcing strategies focuses primarily on large organizations. Although many studies have clearly highlighted major differences between large and small firms and the need to adopt different strategies for different firm sizes, scant attention has been given to analyzing how knowledge sourcing strategies affect firm performance in small firms and what are the differences between small and large firms in the patterns of knowledge sourcing strategies adoption. This study attempts to advance the current literature by examining the impact of knowledge sourcing strategies on small firm performance from a holistic perspective. By drawing on knowledge based theory from organization science and complementarity theory from the economics literature, this paper is motivated by the following questions: (1) what are the adoption patterns of different knowledge sourcing strategies in small firms (i,e., what sourcing strategies should be adopted and which sourcing strategies work well together in small firms)?; and (2) what are the performance implications of these adoption patterns? In order to answer the questions, this study developed three hypotheses. First hypothesis based on knowledge based theory is that internal-oriented knowledge sourcing is positively associated with small firm performance. Second hypothesis developed on the basis of knowledge based theory is that external-oriented knowledge sourcing is positively associated with small firm performance. The third one based on complementarity theory is that pursuing both internal- and external-oriented knowledge sourcing simultaneously is negatively or less positively associated with small firm performance. As a sampling frame, 700 firms were identified from the Annual Corporation Report in Korea. Survey questionnaires were mailed to owners or executives who were most erudite about the firm s knowledge sourcing strategies and performance. A total of 188 companies replied, yielding a response rate of 26.8%. Due to incomplete data, 12 responses were eliminated, leaving 176 responses for the final analysis. Since all independent variables were measured using continuous variables, supermodularity function was used to test the hypotheses based on the cross partial derivative of payoff function. The results indicated no significant impact of internal-oriented sourcing strategies while positive impact of external-oriented sourcing strategy on small firm performance. This intriguing result could be explained on the basis of various resource and capital constraints of small firms. Small firms typically have restricted financial and human resources. They do not have enough assets to always develop knowledge internally. Another possible explanation is competency traps or core rigidities. Building up a knowledge base based on internal knowledge creates core competences, but at the same time, excessive internal focused knowledge exploration leads to behaviors blind to other knowledge. Interestingly, this study found that Internal- and external-oriented knowledge sourcing strategies had a substitutive relationship, which was inconsistent with previous studies that suggested complementary relationship between them. This result might be explained using organizational identification theory. Internal organizational members may perceive external knowledge as a threat, and tend to ignore knowledge from external sources because they prefer to maintain their own knowledge, legitimacy, and homogeneous attitudes. Therefore, integrating knowledge from internal and external sources might not be effective, resulting in failure of improvements of firm performance. Another possible explanation is small firms resource and capital constraints and lack of management expertise and absorptive capacity. Although the integration of different knowledge sources is critical, high levels of knowledge sourcing in many areas are quite expensive and so are often unrealistic for small enterprises. This study provides several implications for research as well as practice. First this study extends the existing knowledge by examining the substitutability (and complementarity) of knowledge sourcing strategies. Most prior studies have tended to investigate the independent effects of these strategies on performance without considering their combined impacts. Furthermore, this study tests complementarity based on the productivity approach that has been considered as a definitive test method for complementarity. Second, this study sheds new light on knowledge management research by identifying the relationship between knowledge sourcing strategies and small firm performance. Most current literature has insisted complementary relationship between knowledge sourcing strategies on the basis of data from large firms. Contrary to the conventional wisdom, this study identifies substitutive relationship between knowledge sourcing strategies using data from small firms. Third, implications for practice highlight that managers of small firms should focus on knowledge sourcing from external-oriented strategies. Moreover, adoption of both sourcing strategies simultaneousiy impedes small firm performance.

2020 Dietary Reference Intakes for Koreans: riboflavin (2020 한국인 영양소 섭취기준: 리보플라빈)

  • Lee, Jung Eun;Cho, Jin Ah;Kim, Ki Nam
    • Journal of Nutrition and Health
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    • v.55 no.3
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    • pp.321-329
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    • 2022
  • Riboflavin and its derivatives, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), are key components of mitochondrial energy metabolism and oxidation-reduction reactions. Proposed dietary reference intakes for Koreans (KDRIs), that is, estimated average requirements (EARs), for riboflavin, based on current knowledge of riboflavin and riboflavin derivative levels, and glutathione reductase activity, are 1.3 mg/d for men aged 19-64 years and 1.0 mg/d for women aged 19-64 years. By applying a coefficient of variance of 10%, reference nutrient intakes (RNIs) were set at 1.5 mg/d for men aged 19-64 years and 1.2 mg/d for women aged 19-64 years. Likewise, EARs and RNIs of riboflavin intake were proposed for all age groups and women in specific life stages such as pregnancy. Mean adult riboflavin intake for adults aged ≥ 19 years was 1.69 mg/d in Korea National Health and Nutrition Examination Survey (KNHANES) 2020, which was 124.9% of EAR according to the 2020 KDRIs. In the 2015-2017 KNHANES study, the mean riboflavin intake from foods and supplements was 2.79 mg/d for all age groups, and 32.7% of individuals consumed less riboflavin than EAR according to the 2020 KDRIs. For those that used supplements, mean intakes were 1.50 mg/d for riboflavin from foods, 10.26 mg/d from supplements, and 11.76 mg/d from food and supplements, and 5.5% of individuals consumed less riboflavin than EAR. Although the upper limit of riboflavin has not been established, the merits of increasing supplement use warrant further consideration. Also, additional epidemiologic and intervention studies are required to explore the role of riboflavin in the etiology of chronic diseases.