• Title/Summary/Keyword: coupled responses

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Navigating the Landscape of Intestinal Regeneration: A Spotlight on Quiescence Regulation and Fetal Reprogramming

  • Su-Jeong Oh;Yoojin Seo;Hyung-Sik Kim
    • International Journal of Stem Cells
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    • v.17 no.3
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    • pp.213-223
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    • 2024
  • Tissue-specific adult stem cells are pivotal in maintaining tissue homeostasis, especially in the rapidly renewing intestinal epithelium. At the heart of this process are leucine-rich repeat-containing G protein-coupled receptor 5-expressing crypt base columnar cells (CBCs) that differentiate into various intestinal epithelial cells. However, while these CBCs are vital for tissue turnover, they are vulnerable to cytotoxic agents. Recent advances indicate that alternative stem cell sources drive the epithelial regeneration post-injury. Techniques like lineage tracing and single-cell RNA sequencing, combined with in vitro organoid systems, highlight the remarkable cellular adaptability of the intestinal epithelium during repair. These regenerative responses are mediated by the reactivation of conserved stem cells, predominantly quiescent stem cells and revival stem cells. With focus on these cells, this review unpacks underlying mechanisms governing intestinal regeneration and explores their potential clinical applications.

Development of screening systems for modulators on phospholipase-mediated signal transduction

  • Lee, Young-Han-;Min, Do-Sik;Kim, Jae-Ho-;Suh, Pann-Ghill;Ryu, Sung-Ho
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.186-186
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    • 1994
  • Many agonists have been known to activate the hydrolysis of membrane phospholipids through the bindings with corresponding receptors on the various cells. Diacylglycerol and inositol 1,4,5-trisphosphate(IP3) generated by the action of phosphoinositide-specific phospholipase C (PI-PLC) are well known second messengers for the activation of protein kinase C and the mobilization of Ca2+ in many cells. Three types of PI-PLC isozyme (${\alpha}$,${\gamma}$, and $\delta$) and several subtrpes for each type have been identified from mammalian sources by purification of enzymes and cloning of their cDNAs. Each type PI-PLC isozyme is coupled to different receptors and mediators, for example, ${\beta}$-types are coupled to the seven-transmembrane-receptors via Gq family of G-proteins and ${\beta}$-types directly to the receptor tyrosine kinases. Specific modulators for the signaling pathway through each type of PI-PLC should be very useful as potential potential candidates for lend substances in developing novel drugs. To establish the sensitive and convenient screening systems for searching modulators on PI-PLC mediated signaling, two kinds of approaches have been tried. (1) Establishment of in vitro assay condition for each type of PI-PLC isozyme: Overexpression by using vaccinia virus and purification of each isozyme was carried out for the preparation of large amounts of enaymes. Optimum and sensitive assay condition for the measurements of PI-ELC activities were established. (2) Development of the cell lines in which each type of PI-PLC is permanently overexpressed: A fibroblast cell line (3T3${\gamma}$1-7) in which PI-PLC-${\gamma}$1 was overexpressed by using pZip-neo expression vector was developed and used for the measurement of PDGF-induced IP3 formation. The responses for IP3 formed in 3T3${\gamma}$1-7 cells by the treatment of PDGF is 8 times more sensitive than those in control cells. 3T3${\gamma}$l-7 cell is useful for the screening of the inhibitors on the PDGF-induced cellular responses from large number of samples in a small volume(50 ${\mu}$l) and short time(5-15 min). Using these systems, we screened hundreds of herb-extracts for the inhibition of PDGF-induced IP3 formation and selected several extracts that showed the inhibition as the candidates for isolation and characterization of active substances. The determination of the acting point of selected extracts or fractions in the PDGF signaling pathway has been analyzing.

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The Effects of Sloshing on the Responses of an LNG Carrier Moored in a Side-by-side Configuration with an Offshore Plant (해양플랜트에 병렬 계류된 LNG 운반선의 거동에 슬로싱이 미치는 영향)

  • Lee, Seung-Jae
    • Journal of Ocean Engineering and Technology
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    • v.24 no.5
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    • pp.16-21
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    • 2010
  • During the loading/offloading operation of a liquefied natural gas carrier (LNGC) that is moored in a side-by-side configuration with an offshore plant, sloshing that occurs due to the partially filled LNG tank and the interactive effect between the two floating bodies are important factors that affect safety and operability. Therefore, a time-domain software program, called CHARM3D, was developed to consider the interactions between sloshing and the motion of a floating body, as well as the interactions between multiple bodies using the potential-viscous hybrid method. For the simulation of a floating body in the time domain, hydrodynamic coefficients and wave forces were calculated in the frequency domain using the 3D radiation/diffraction panel program based on potential theory. The calculated values were used for the simulation of a floating body in the time domain by convolution integrals. The liquid sloshing in the inner tanks is solved by the 3D-FDM Navier-Stokes solver that includes the consideration of free-surface non-linearity through the SURF scheme. The computed sloshing forces and moments were fed into the time integration of the ship's motion, and the updated motion was, in turn, used as the excitation force for liquid sloshing, which is repeated for the ensuing time steps. For comparison, a sloshing motion coupled analysis program based on linear potential theory in the frequency domain was developed. The computer programs that were developed were applied to the side-by-side offloading operation between the offshore plant and the LNGC. The frequency-domain results reproduced the coupling effects qualitatively, but, in general, the peaks were over-predicted compared to experimental and time-domain results. The interactive effects between the sloshing liquid and the motion of the vessel can be intensified further in the case of multiple floating bodies.

Induction of a systemic IgG and secretory IgA responses in mice by peroral immunization with uropathogenic Escherichia coli adhesin protein coupled to cholera toxin A2B subunits

  • Lee, Yong-Hwa;Kim, Byung-Oh;Rhee, Dong-Kwon;Pyo, Suh-Kneung
    • Biomolecules & Therapeutics
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    • v.11 no.3
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    • pp.157-162
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    • 2003
  • The generation of secretory IgA antibodies(Abs) for specific immune protection of mucosal surfaces depends on stimulation of the mucosal immune system, but this is not effectively achieved by parenteral or even oral administration of most soluble antigens. Thus, to produce a possible vaccine antigen against urinary tract infections, the uropathogenic E. coli (UPEC) adhesin was genetically coupled to the ctxa2b gene and cloned into a pMAL-p2E expression vector. The chimeric construction of pMALfimHIctxa2b was then transformed into E. coli K-12 TB1 and its nucleotide sequence was verified. The chimeric protein was then purified by applying the affinity chromatography. The purified chimeric protein was confirmed by SDS-PAGE and western blotting using antibodies to the maltose binding protein (MBP) or the cholera toxin subunit B (CTXB), plus the N-terminal amino acid sequence was analyzed. The orderly-assembled chimeric protein was confirmed by a modified $G_{M1}$-ganglioside ELISA using antibodies to adhesin. The results indicate that the purified chimeric protein was an Adhesin/CTXA2B protein containing UPEC adhesin and the $G_{M1}$-ganglioside binding activity of CTXB. This study also demonstrate that peroral administration of this chimeric immunogen in mice elicited high level of secretory IgA and serum IgG Abs to the UPEC adhesin. The results suggest that the genetically linked CTXA2B acts as a useful mucosal adjuvant, and that the adhesin/CTXA2B chimeric protein might be a potential antigen for oral immunization against UPEC.

Analysis of High-Speed Pulse Propagation on Arbitrarily Interconnected Transmission Lines by an Efficient Node Discretization Technique (효율적인 노드분할법을 통한 임의 결선된 전송선로상의 고속 펄스 전송 해석)

  • 전상재;박의준
    • Journal of the Institute of Electronics Engineers of Korea TC
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    • v.40 no.1
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    • pp.37-46
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    • 2003
  • The transient responses on arbitrarily interconnected digital transmission lines are analyzed by an efficient node discretization technique. Since the proposed node discretization technique offers an efficient means to discretize transmission lines, the transient waveform at any position on the arbitrarily interconnected lines is easily predicted. Dispersive microstrip multiconductor transmission lines arbitrarily connected are analized for generality. The derivation of frequency-dependent equivalent circuit elements of coupled transmission lines have been carried out by the spectral domain approach(SDA). The effects of variations of excited pulse width on the crosstalks of the high-speed microstrip coupled-lines are also investigated. It has been well known that the crosstalk spike level is monotonously increased when the coupling length and effective permittivity of substrate are increased. In this paper, it is found that the variations of crosstalk level are not further monotonous as shortening the exciting pulse width toward several picosecond. The results are verified by the generalized S-parameter technique.

RNA-Seq Transcriptome Analysis of the Cutlass Fish Reveals Photoreceptors Gene Expression in Peripheral Tissues (RNA-Seq transcriptome 분석을 통한 갈치 광수용체 유전자 탐색 및 mRNA 조직발현)

  • Hyeon, Ji-Yeon;Kim, Mun-Kwan;Lim, Bong-Soo;Byun, Jun-Hwan;Moon, Ji-Sung;Kang, Hyeong-Cheol;Hur, Sung-Pyo;Oh, Seong-Rip
    • Ocean and Polar Research
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    • v.39 no.2
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    • pp.149-158
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    • 2017
  • The opsin family of light sensitive proteins family makes up are the universal photoreceptor molecules of all visual systems in the vertebrates including teleosts. They can change their conformation from a resting state to a signaling state upon light absorption, which activates the G-protein coupled receptor, thereby resulting in a signaling cascade that produces physiological responses. However, this species is poorly characterized at molecular level due to little sequence information available in public databases. We have investigated the opsin family of nocturnal cutlass fish using the whole transcriptome sequencing method. The opsin genes were cloned and its expression in the tissues and organs were examined by qPCR. We cloned 6 opsin genes (RRH, Opn4, Rh1, Rh2, VA-opsin, and Opn3) in retina and brain tissue. It contained the seven presumed transmembrane domains that are characteristic of the G-protein-coupled receptor family. However, short wavelength sensitive pigment (SWS) and long wavelength sensitive pigment (LWS) were not detected in this study. The mRNA expression of the 6 photoreceptor genes were detected in retina and peripheral tissue. Our studies will lead to further investigation of the photic entrainment mechanism at molecular and cellular levels in cutlass fish and can be used in comparative studies of other fishes.

Phosphatidylinositol 3-kinase functionally compartmentalizes the concurrent $G_s$ signaling during $\beta_2$-adrenergic stimulation

  • Jo, Su-Hyun
    • Proceedings of the Korean Biophysical Society Conference
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    • 2003.06a
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    • pp.29-29
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    • 2003
  • Compartmentation of intracellular signaling pathways serves as an important mechanism conferring the specificity of G protein-coupled receptor (GPCR) signaling. In the heart, stimulation of $\beta$$_2$-adrenoceptor ($\beta$$_2$-AR), a prototypical GPCR, activates a tightly localized protein kinase A (PKA) signaling, which regulates substrates at cell surface membranes, bypassing cytosolic target proteins (eg, phospholamban). Although a concurrent activation of $\beta$$_2$-AR-coupled $G_{i}$ proteins has been implicated in the functional compartmentation of PKA signaling, the exact mechanism underlying the restriction of the $\beta$$_2$-AR-PKA pathway remains unclear. In the present study, we demonstrate that phosphatidylinositol 3-kinase (PI3K) plays an essential role in confining the $\beta$$_2$-AR-PKA signaling. Inhibition of PI3K with LY294002 or wortmannin enables $\beta$$_2$-AR-PKA signaling to reach intracellular substrates, as manifested by a robust increase in phosphorylation of phospholamban, and markedly enhances the receptor-mediated positive contractile and relaxant responses in cardiac myocytes. These potentiating effects of PI3K inhibitors are not accompanied by an increase in $\beta$$_2$-AR-induced cAMP formation. Blocking $G_{i}$ or $G_{$\square$$\square$}$ signaling with pertussis toxin or $\beta$ARK-ct, a peptide inhibitor of $G_{$\square$$\square$}$, completely prevents the potentiating effects induced by PI3K inhibition, indicating that the pathway responsible for the functional compartmentation of $\beta$$_2$-AR-PKA siglaling sequentially involves $G_{i}$, $G_{$\square$$\square$}$, and PI3K. Thus, PI3K constitutes a key downstream event of $\beta$$_2$-AR- $G_{i}$ signaling, which confines and negates the concurrent $\beta$$_2$-AR/Gs-mediated PKA signaling.gnaling.

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Retrofitting of a weaker building by coupling it to an adjacent stronger building using MR dampers

  • Abdeddaim, Mahdi;Ounis, Abdelhafid;Shrimali, Mahendra K.;Datta, Tushar K.
    • Structural Engineering and Mechanics
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    • v.62 no.2
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    • pp.197-208
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    • 2017
  • Among various retrofitting strategies, use of semi-active control for retrofitting a building structure has gained momentum in recent years. One of the techniques for such retrofitting is to connect a weaker building to an adjacent stronger building by semi-active devices, so that performances of a weaker building are significantly improved for seismic forces. In this paper, a ten storey weaker building is connected to an adjacent stronger building using magneto-rheological (MR) dampers, for primarily improving the performance of the weaker building in terms of displacement, drift and base shear. For this, a fuzzy logic controller is specifically developed by fuzzyfying the responses of the coupled system. The performance of the control strategy is compared with the passive-on and passive-off controls. Pounding Mitigation between the two buildings is also investigated using all three control strategies. The results show that there exists a fundamental frequency ratio between the two buildings for which maximum control of the weaker building response takes place with no penalty on the stronger building. There exists also a fundamental frequency ratio where control of the weaker building response is achieved at the expense of the amplification of the stronger building. However, coupling strategy always improves the possibility of pounding mitigation.

Pavement condition assessment through jointly estimated road roughness and vehicle parameters

  • Shereena, O.A.;Rao, B.N.
    • Structural Monitoring and Maintenance
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    • v.6 no.4
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    • pp.317-346
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    • 2019
  • Performance assessment of pavements proves useful, in terms of handling the ride quality, controlling the travel time of vehicles and adequate maintenance of pavements. Roughness profiles provide a good measure of the deteriorating condition of the pavement. For the accurate estimates of pavement roughness from dynamic vehicle responses, vehicle parameters should be known accurately. Information on vehicle parameters is uncertain, due to the wear and tear over time. Hence, condition monitoring of pavement requires the identification of pavement roughness along with vehicle parameters. The present study proposes a scheme which estimates the roughness profile of the pavement with the use of accurate estimates of vehicle parameters computed in parallel. Pavement model used in this study is a two-layer Euler-Bernoulli beam resting on a nonlinear Pasternak foundation. The asphalt topping of the pavement in the top layer is modeled as viscoelastic, and the base course bottom layer is modeled as elastic. The viscoelastic response of the top layer is modeled with the help of the Burgers model. The vehicle model considered in this study is a half car model, fitted with accelerometers at specified points. The identification of the coupled system of vehicle-pavement interaction employs a coupled scheme of an unbiased minimum variance estimator and an optimization scheme. The partitioning of observed noisy quantities to be used in the two schemes is investigated in detail before the analysis. The unbiased minimum variance estimator (MVE) make use of a linear state-space formulation including roughness, to overcome the linearization difficulties as in conventional nonlinear filters. MVE gives estimates for the unknown input and fed into the optimization scheme to yield estimates of vehicle parameters. The issue of ill-posedness of the problem is dealt with by introducing a regularization equivalent term in the objective function, specifically where a large number of parameters are to be estimated. Effect of different objective functions is also studied. The outcome of this research is an overall measure of pavement condition.

Experimental Study on Interaction of Side-by-Side Moored Vessels (병렬계류 선박의 동유체력 상호간섭에 관한 실험연구)

  • Kim, Jin-Ha;Hong, Sa-Young;Cho, Seok-Gyo;Choi, Yoon-Rak;Song, Myong-Jae;Kim, Duk-Su
    • Proceedings of the Korea Committee for Ocean Resources and Engineering Conference
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    • 2003.05a
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    • pp.208-213
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    • 2003
  • Recently, Side-by-side mooring system of LNG FPSO and shuttle tanker is one of hot issues in offshore floating body dynamics, which requires accurate analysis of hydrodynamic interactions between side by side moored LNG FPSO and shuttle tanker than tandem moored vessels. This paper aims to investigate basic interaction characteristics of side-by-side moored multiple vessels both numerically and experimentally. A higher-order boundary element method combined with generalized nwde approach will be applied to analysis of motion and drift force of side by side moored multiple-body. Model tests were carried out for the same multiple floating bodies in regular and irregular waves. Motion responses and drift forces of vessels for two mooring situation(coupled & uncoupled) were compared with those of calculations. Discussions will be highlighted on applicability of numerical method to prediction of sophisticated multi-body interaction problem of which motion behavior is very important to analysis of mooring dynamics of deep sea floating bodies.

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