16 results on '"Kim, Ilsoo"'
Search Results
2. A Microscopic Capacitor Model of Voltage Coupling in Membrane Proteins: Gating Charge Fluctuations in Ci-VSD.
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Kim, Ilsoo and Warshel, Arieh
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MICROSCOPES , *ELECTRIC charge , *CAPACITORS , *ELECTRIC potential , *MEMBRANE proteins , *VOLTAGE-sensitive dyes - Abstract
The voltage sensitivity of membrane proteins is reflected in the response of the voltage sensing domains (VSDs) to the changes in membrane potential. This response is implicated in the displacement of positively charged residues, associated with the conformational changes of VSDs. The displaced charges generate nonlinear (i.e., voltage-dependent) capacitance current called the gating current (and its corresponding gating charge), which is a key experimental quantity that characterizes voltage activation in VSMP. However, the relevant theoretical/computational approaches, aimed to correlate the structural information on VSMP to electrophysiological measurements, have been rather limited, posing a broad challenge in computer simulations of VSMP. Concomitant with the development of our coarse-graining (CG) model of voltage coupling, we apply our theoretical framework for the treatments of voltage effects in membrane proteins to modeling the VSMP activation, taking the VSDs (Ci-VSD) derived from the Ciona intestinalis voltage sensitive phosphatase (Ci-VSP) as a model system. Our CG model reproduces the observed gating charge of Ci-VSD activation in several different perspectives. In particular, a new closed-form expression of the gating charge is evaluated in both nonequilibrium and equilibrium ways, while considering the fluctuation-dissipation relation that connects a nonequilibrium measurement of the gating charge to an equilibrium measurement of charge fluctuations (i.e., the voltage-independent linear component of membrane capacitance). In turn, the expression uncovers a novel link that connects an equilibrium measurement of the voltage-independent linear capacitance to a nonequilibrium measurement of the voltage-dependent nonlinear capacitance (whose integral over voltage is equal to the gating charge). In addition, our CG model yields capacitor-like voltage dependent free energy parabolas, resulting in the free energy difference and the free energy barrier for the Ci-VSD activation at "zero" (depolarization) membrane potential. Significantly, the resultant voltage dependent energetics enables a direct evaluation of capacitance-voltage relationship (C-V curve) as well as charge-voltage relationship (Q-V curve) that is in a good agreement with the observed measurement of Ci-VSD voltage activation. Importantly, an extension of our kinetic/thermodynamic model of voltage dependent activation in VSMP allows for novel derivations of voltage-dependent rate constants, whose parameters are expressed by the intrinsic properties of VSMP. These novel closed-form expressions offer a physicochemical foundation for the semiempirical Eyring-type voltage dependent rate equations that have been the cornerstone for the phenomenological (kinetic) descriptions of gating and membrane currents in the mechanistic study of ion channels and transporters. Our extended theoretical framework developed in the present study has potential implications on the roles played by gating charge fluctuations for the spike generations in nerve cells within the framework of the Hodgkin-Huxley-type model. [ABSTRACT FROM AUTHOR]
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- 2016
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3. Equilibrium fluctuation relations for voltage coupling in membrane proteins.
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Kim, Ilsoo and Warshel, Arieh
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MEMBRANE proteins , *CONFORMATIONAL analysis , *CHARGE exchange , *FREE energy (Thermodynamics) , *COUPLING reactions (Chemistry) , *ION channels , *MEMBRANE potential - Abstract
A general theoretical framework is developed to account for the effects of an external potential on the energetics of membrane proteins. The framework is based on the free energy relation between two (forward/backward) probability densities, which was recently generalized to non-equilibrium processes, culminating in the work-fluctuation theorem. Starting from the probability densities of the conformational states along the "voltage coupling" reaction coordinate, we investigate several interconnected free energy relations between these two conformational states, considering voltage activation of ion channels. The free energy difference between the two conformational states at zero (depolarization) membrane potential (i.e., known as the chemical component of free energy change in ion channels) is shown to be equivalent to the free energy difference between the two “equilibrium” (resting and activated) conformational states along the one-dimensional voltage couplin reaction coordinate. Furthermore, the requirement that the application of linear response approximation to the free energy functionals of voltage coupling should satisfy the general free energy relations, yields a novel closed-form expression for the gating charge in terms of other basic properties of ion channels. This connection is familiar in statistical mechanics, known as the equilibrium fluctuation-response relation. The theory is illustrated by considering the coupling of a unit charge to the external voltage in the two sites near the surface of membrane, representing the activated and resting states. This is done using a coarse-graining (CG) model of membrane proteins, which includes the membrane, the electrolytes and the electrodes. The CG model yields Marcus-type voltage dependent free energy parabolas for the response of the electrostatic environment (electrolytes etc.) to the transition from the initial to the final configuratinal states, leading to equilibrium free energy difference and free energy barrier that follow the trend of the equilibrium fluctuation relation and the Marcus theory of electron transfer. These energetics also allow for a direct estimation of the voltage dependence of channel activation (Q-V curve), offering a quantitative rationale for a correlation between the voltage dependence parabolas and the Q-V curve, upon site-directed mutagenesis or drug binding. Taken together, by introducing the voltage coupling as the energy gap reaction coordinate, our framework brings new perspectives to the thermodynamic models of voltage activation in voltage-sensitive membrane proteins, offering an a framework for a better understating of the structure-function correlations of voltage gating in ion channels as well as electrogenic phenomena in ion pumps and transporters. Significantly, this formulation also provides a powerful bridge between the CG model of voltage coupling and the conventional macroscopic treatments. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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4. A novel variant of dehydrodolichol diphosphate synthase (DHDDS) mutation with adult-onset progressive myoclonus ataxia.
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Kim, Jinhee, Kim, Ilsoo, and Koh, Seong-Beom
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ATAXIA , *MYOCLONUS , *EPILEPSY , *DIAGNOSIS of epilepsy , *GENETIC mutation , *TRANSFERASES , *AGE factors in disease - Abstract
We report a novel variant of DHDDS mutation in a patient with progressive adult-onset myoclonus ataxia. The mutation in our patient was different from previous reports of denovo mutations in DHDDS in 6 patients who showed tremor-like myoclonus and generalized epilepsy. [ABSTRACT FROM AUTHOR]
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- 2021
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5. Bacterial Recognition of Silicon Nanowire Arrays.
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Jeong, Hoon Eui, Kim, Ilsoo, Karam, Pierre, Choi, Heon-Jin, and Yang, Peidong
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SILICON nanowires , *MOLECULAR recognition , *NANOSTRUCTURES , *CRYSTAL structure , *BACTERIAL growth , *SHEWANELLA oneidensis - Abstract
Understanding how living cells interactwith nanostructures isintegral to a better understanding of the fundamental principles ofbiology and the development of next-generation biomedical/bioenergydevices. Recent studies have demonstrated that mammalian cells canrecognize nanoscale topographies and respond to these structures.From this perspective, there is a growing recognition that nanostructures,along with their specific physicochemical properties, can also beused to regulate the responses and motions of bacterial cells. Here,by utilizing a well-defined silicon nanowire array platform and single-cellimaging, we present direct evidence that Shewanella oneidensisMR-1 can recognize nanoscale structures and that their swimmingpatterns and initial attachment locations are strongly influencedby the presence of nanowires on a surface. Analyses of bacterial trajectoriesrevealed that MR-1 cells exhibited a confined diffusion mode in thepresence of nanowires and showed preferential attachment to the nanowires,whereas a superdiffusion mode was observed in the absence of nanowires.These results demonstrate that nanoscale topography can affect bacterialmovement and attachment and play an important role during the earlystages of biofilm formation. [ABSTRACT FROM AUTHOR]
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- 2013
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6. Mechanism of potassium-channel selectivity revealed by Na+ and Li+ binding sites within the KcsA pore.
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Thompson, Ameer N., Kim, Ilsoo, Panosian, Timothy D., Iverson, Tina M., Allen, Toby W., and Nimigean, Crina M.
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POTASSIUM channels , *SODIUM channels , *PROTEINS , *MOLECULAR dynamics , *ION channels , *ELECTROPHYSIOLOGY , *X-ray crystallography - Abstract
Potassium channels allow K+ ions to diffuse through their pores while preventing smaller Na+ ions from permeating. Discrimination between these similar, abundant ions enables these proteins to control electrical and chemical activity in all organisms. Selection occurs at the narrow selectivity filter containing structurally identified K+ binding sites. Selectivity is thought to arise because smaller ions such as Na+ do not bind to these K+ sites in a thermodynamically favorable way. Using the model K+ channel KcsA, we examined how intracellular Na+ and Li+ interact with the pore and the permeant ions using electrophysiology, molecular dynamics simulations and X-ray crystallography. Our results suggest that these small cations have a separate binding site within the K+ selectivity filter. We propose that selective permeation from the intracellular side primarily results from a large energy barrier blocking filter entry for Na+ and Li+ in the presence of K+, not from a difference of binding affinity between ions. [ABSTRACT FROM AUTHOR]
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- 2009
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7. Interfacial reaction-dominated full oxidation of 5 nm diameter silicon nanowires.
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Kim, Ilsoo, Park, Tae-Eon, Lee, Ki-Young, Ha, Ryong, Kim, Byung-Hyun, Chung, Yong-Chae, Lee, Kwang-Ryeol, and Choi, Heon-Jin
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SILICON nanowires , *CHEMICAL vapor deposition , *NANOSTRUCTURED materials , *OXIDATION , *SEMICONDUCTOR doping - Abstract
While almost all Si nanostructures, including Si nanowires (SiNWs), Si nanocrystals, and Si nanotrench-like structures on a supra- or sub-10 nm scale exhibit self-limiting oxidative behavior, herein we report full oxidation of SiNWs 5 nm in diameter. We investigated the oxidative behavior of SiNWs with diameters of 5 nm and compared our findings with those for SiNWs with diameters of 30 nm. Single-crystalline SiNWs 5 and 30 nm in diameter were grown by a chemical vapor deposition (CVD) process using Ti as a catalyst. The SiNWs were then oxidized at 600-1000 °C for 30 min to 240 min in O2. The thicknesses of the resulting oxide layers were determined by transmission electron microscopy (TEM). As expected, the SiNWs 30 nm in underwent self-limiting oxidation that was parabolic in nature. However, under the same conditions, the SiNWs 5 nm in diameter underwent full oxidation that was linear in nature. Atomic-scale molecular dynamic simulations revealed that the compressive stress in the oxide layer, which is generated owing to the increase in the volume of the oxide formed, decreased in the case of the SiNWs 5 nm in diameter. It is likely that this decrease in the compressive stress results in a lowering of the energy barrier for the diffusion of oxygen into the oxide layer, leading to the full oxidation of the SiNWs 5 nm in diameter. It is also responsible for the oxidation in the case of SiNWs 5 nm in diameter being interfacial reaction-dominated as opposed to the diffusion dominated-oxidation typical for SiNWs. [ABSTRACT FROM AUTHOR]
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- 2012
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8. Bennett's acceptance ratio and histogram analysis methods enhanced by umbrella sampling along a reaction coordinate in configurational space.
- Author
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Kim, Ilsoo and Allen, Toby W.
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PERTURBATION theory , *FORCE & energy , *ESTIMATION theory , *HARMONIC oscillators , *BROWNIAN motion , *ELECTROSTATICS , *ION channels - Abstract
Free energy perturbation, a method for computing the free energy difference between two states, is often combined with non-Boltzmann biased sampling techniques in order to accelerate the convergence of free energy calculations. Here we present a new extension of the Bennett acceptance ratio (BAR) method by combining it with umbrella sampling (US) along a reaction coordinate in configurational space. In this approach, which we call Bennett acceptance ratio with umbrella sampling (BAR-US), the conditional histogram of energy difference (a mapping of the 3N-dimensional configurational space via a reaction coordinate onto 1D energy difference space) is weighted for marginalization with the associated population density along a reaction coordinate computed by US. This procedure produces marginal histograms of energy difference, from forward and backward simulations, with higher overlap in energy difference space, rendering free energy difference estimations using BAR statistically more reliable. In addition to BAR-US, two histogram analysis methods, termed Bennett overlapping histograms with US (BOH-US) and Bennett-Hummer (linear) least square with US (BHLS-US), are employed as consistency and convergence checks for free energy difference estimation by BAR-US. The proposed methods (BAR-US, BOH-US, and BHLS-US) are applied to a 1-dimensional asymmetric model potential, as has been used previously to test free energy calculations from non-equilibrium processes. We then consider the more stringent test of a 1-dimensional strongly (but linearly) shifted harmonic oscillator, which exhibits no overlap between two states when sampled using unbiased Brownian dynamics. We find that the efficiency of the proposed methods is enhanced over the original Bennett's methods (BAR, BOH, and BHLS) through fast uniform sampling of energy difference space via US in configurational space. We apply the proposed methods to the calculation of the electrostatic contribution to the absolute solvation free energy (excess chemical potential) of water. We then address the controversial issue of ion selectivity in the K+ ion channel, KcsA. We have calculated the relative binding affinity of K+ over Na+ within a binding site of the KcsA channel for which different, though adjacent, K+ and Na+ configurations exist, ideally suited to these US-enhanced methods. Our studies demonstrate that the significant improvements in free energy calculations obtained using the proposed methods can have serious consequences for elucidating biological mechanisms and for the interpretation of experimental data. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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9. Magnetic anisotropy in vertically aligned diluted magnetic Mn:Ge semiconductor nanowires.
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Kim, Ungkil, Park, Tae-Eon, Kim, Ilsoo, Seong, Han-Kyu, Kim, Myeong-Ha, Chang, Joonyeon, Park, Jae-Gwan, and Choi, Heon-Jin
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ANISOTROPY , *DILUTED magnetic semiconductors , *NANOWIRES , *MANGANESE , *GERMANIUM - Abstract
Semiconductors doped with magnetic ion, the so-called diluted magnetic semiconductors, are promising candidates for spintronics. Herein, we report on magnetic anisotropy in Mn:Ge diluted magnetic semiconductor nanowires. We grew single crystal Mn:Ge nanowires vertically on a Ge substrate and found the anisotropy in ratios of orbital to spin magnetic moments in the angle-dependent x-ray magnetic circular dichroism measurements. Our further characterization indicates that this anisotropy comes from the unique characteristics of nanowires, i.e., very high aspect ratio in their shape and tensile stress along the longitudinal direction, which confine the spins along the longitudinal direction and make an easy axis in that direction. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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10. A prospective multi-centre study of susceptibility map-weighted MRI for the diagnosis of neurodegenerative parkinsonism.
- Author
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Sung, Young Hee, Kim, Joong-Seok, Yoo, Sang-Won, Shin, Na-Young, Nam, Yoonho, Ahn, Tae-Beom, Yoo, Dallah, Lee, Kyung Mi, Kim, Hyug-Gi, Koh, Seong-Beom, Kim, Jinhee, Kim, Ilsoo, Kwon, Do-Young, Lee, Younghen, Kim, Chulhan, Chung, Sun Ju, Jo, Sungyang, Lee, Seung Hyun, Kim, Sang Joon, and Kim, Minjae
- Abstract
Objectives: This study aimed to compare susceptibility map-weighted imaging (SMwI) using various MRI machines (three vendors) with N-3-fluoropropyl-2-β-carbomethoxy-3-β-(4-iodophe nyl)nortropane (18F-FP-CIT) PET in the diagnosis of neurodegenerative parkinsonism in a multi-centre setting. Methods: We prospectively recruited 257 subjects, including 157 patients with neurodegenerative parkinsonism, 54 patients with non-neurodegenerative parkinsonism, and 46 healthy subjects from 10 hospitals between November 2019 and October 2020. All participants underwent both SMwI and 18F-FP-CIT PET. SMwI was interpreted by two independent reviewers for the presence or absence of abnormalities in nigrosome 1, and discrepancies were resolved by consensus. 18F-FP-CIT PET was used as the reference standard. Inter-observer agreement was tested using Cohen's kappa coefficient. McNemar's test was used to test the agreement between the interpretations of SMwI and 18F-FP-CIT PET per participant and substantia nigra (SN). Results: The inter-observer agreement was 0.924 and 0.942 per SN and participant, respectively. The diagnostic sensitivity of SMwI was 97.9% and 99.4% per SN and participant, respectively; its specificity was 95.9% and 95.2%, respectively, and its accuracy was 97.1% and 97.7%, respectively. There was no significant difference between the results of SMwI and 18F-FP-CIT PET (p > 0.05, for both SN and participant). Conclusions: This study demonstrated that the high diagnostic performance of SMwI was maintained in a multi-centre setting with various MRI scanners, suggesting the generalisability of SMwI for determining nigrostriatal degeneration in patients with parkinsonism. Key Points: • Susceptibility map-weighted imaging helps clinicians to predict nigrostriatal degeneration. • The protocol for susceptibility map-weighted imaging can be standardised across MRI vendors. • Susceptibility map-weighted imaging showed diagnostic performance comparable to that of dopamine transporter PET in a multi-centre setting with various MRI scanners. [ABSTRACT FROM AUTHOR]
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- 2022
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11. Effect of surface roughness on thermal conductivity of VLS-grown rough SiGe nanowires.
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Kim, Hyoungjoon, Park, Yong-Hee, Kim, Ilsoo, Kim, Jungwon, Choi, Heon-Jin, and Kim, Woochul
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SURFACE roughness , *THERMAL conductivity , *CRYSTAL growth , *SILICON alloys , *NANOWIRES , *SEMICONDUCTOR etching , *SCATTERING (Physics) , *SIMULATION methods & models - Abstract
The recent demonstration of thermal conductivity of rough electrolessly etched Si nanowire (Hochbaum et al., Nature, 451:163, ) attracted a lot of interest, because it could not be explained by the existing theory; thermal conductivity of rough Si nanowires falls below the boundary scattering of the thermal conductivity. However, nanoscale pores presented in the nanowires (Hochbaum et al., Nano Letters, 9:3550-3554, ) hinder one to be fully convinced that the surface roughness solely made a contribution to the significant reduction in thermal conductivity. In this study, we synthesized vapor-liquid-solid (VLS) grown rough SiGe nanowire and measured and theoretically simulated thermal conductivity of the nanowire. The thermal conductivity of rough SiGe nanowire is an order of magnitude lower than that of bulk SiGe and around a factor of four times lower than that of smooth SiGe nanowire. This significant reduction could be explained by the fact that the surface roughness scatters medium-wavelength phonons, whereas the long-wavelength phonons are scattered by phonon boundary scattering, and the short-wavelength phonons are scattered by alloy scattering. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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12. Self-catalytic growth of silicon nanowires on stainless steel
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Kim, Myoung-Ha, Park, Yong-Hee, Kim, Ilsoo, Park, Tae-Eon, Sung, Yun-Mo, and Choi, Heon-Jin
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NANOWIRES , *SILICON , *AUTOCATALYSIS , *CRYSTAL growth , *STAINLESS steel , *HYDROGEN , *SEMICONDUCTORS , *TRANSPORT theory - Abstract
Abstract: Silicon nanowires were grown on a stainless steel substrate using a vapor–liquid–solid mechanism in self-catalytic mode. The multi-component Fe–Cr–Ni–Mn–Si catalyst that was formed from the substrate leads the growth of single-crystal Si nanowires with lengths of several micrometers and diameters ranging from 100 to 150nm. A systematic investigation of the processing parameters revealed that the hydrogen flow rate is critical to the growth of the nanowires. At a high flow rate that exceeds 1000sccm, the substrate is embrittled by H2, and liquid droplets, which lead the growth of nanowires by the vapor–liquid–solid mechanism, are formed on the substrate. Electrical transport measurements indicated that the nanowires grown with the multi-component catalyst have electrical properties comparable to those grown by a single-component Ti catalyst. [Copyright &y& Elsevier]
- Published
- 2010
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13. Coupled thermo–electrical analysis of highly scaled GaN micro-LEDs with meshed hybrid conductors.
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Shin, Yuseop, Bae, Junho, Lim, Jinho, Jeon, Dasom, Kim, Ilsoo, Jung, Taeil, Han, Myungsoo, and Lee, Seunghyun
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PIXEL density measurement , *GALLIUM nitride , *QUANTUM efficiency , *MIXED reality , *LIQUID crystals , *ELECTRICAL conductors - Abstract
Display technology with ultrafine pixels for near-eye application is a rapidly growing field due to the recent emergence of augmented/mixed reality. With the constant demand for high energy efficiency, long lifetime, and high luminosity, micro-LED displays based on compound semiconductors are promising candidates for such applications. However, miniaturizing LEDs results in significant drawbacks in terms of their quantum efficiency, current injection efficiency, and heat extraction. With relatively low device resistance compared to that of liquid crystals or organic LEDs, micro-LEDs are also more susceptible to the effects of parasitic resistance. In this study, gallium nitride based micro-LED displays with very small pixels (5 μm pixel, 10 μm pitch) are fabricated to study the thermal–electrical effect of meshed hybrid conductors on the optical emission efficiency. In situ thermographic imaging with I–V measurement confirms a significant trade-off among heat transfer, electrical conductivity, and light extraction efficiency. An increase of 37.9% in the emission efficiency (2540 pixels per inch, 5 μm pixels, 1 mm2 display, at 49.2 °C) is achieved by optimizing the thermal and electrical conduction paths. This study experimentally confirms the importance of thermal management and multi-physics analysis in designing ultra-small-pixel micro-LEDs with high energy efficiency. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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14. Social capital and career growth.
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Kang, Dae-seok, Gold, Jeff, Kim, Jeongeun, and Kim, Ilsoo
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SOCIAL capital , *CAREER development , *JOB security , *BRAIN drain , *SOCIAL influence - Abstract
Purpose: The purpose of this paper is to examine the instrumental use of social capital regarding career growth within an organization, focusing on the mediating role of perceived competence mobilization and the moderating role of two situational variables: perceived external prestige and job insecurity climate. Design/methodology/approach: Relationships among the constructs are predicted based on relevant literature, and are tested using survey results from 324 employees working in 14 leading corporations in Korea. Findings: Results show that social capital positively influenced, via perceived competence mobilization, each of two career growth dimensions (i.e. the personal efforts to develop a career and the experience of being rewarded by the organization). In contrast, moderated path analysis indicated that perceptions of external prestige and job insecurity climate failed to moderate the indirect effect of social capital on career growth. Practical implications: In light of the instrumental use of social capital and the ensuring mechanism of competence mobilization, a detailed understanding of this effect on career growth cannot only neutralize the fears of brain drain, but is also helpful in providing possibilities for building new career development strategies. Originality/value: Although social capital has become an influential concept in social sciences, little evidence has been presented on the above relationship, particularly from the perspective of careerist orientation. This may be the first research examining how and when the influence of social capital becomes instrumental with respect to career attainment within an organization. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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15. Thermal conductivity of VLS-grown rough Si nanowires with various surface roughnesses and diameters.
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Park, Yong-Hee, Kim, Jungwon, Kim, Hyoungjoon, Kim, Ilsoo, Lee, Ki-Young, Seo, Dongjea, Choi, Heon-Jin, and Kim, Woochul
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THERMAL conductivity , *NANOSILICON , *CRYSTAL growth , *NANOWIRES , *SURFACE roughness , *INORGANIC synthesis , *MANGANESE catalysts , *PHONON scattering , *THERMOELECTRIC apparatus & appliances - Abstract
In this paper, we synthesize VLS-grown rough Si nanowires using Mn as a catalyst with various surface roughnesses and diameters and measured their thermal conductivities. We grew the nanowires by a combination vapor-liquid-solid and vapor-solid mechanism for longitudinal and radial growth, respectively. The surface roughness was controlled from smooth up to about 37 nm by the radial growth. Our measurements showed that the thermal conductivity of rough surface Si nanowires is significantly lower than that of smooth surface nanowires and decreased with increasing surface roughness even though the diameter of the smooth nanowire was lower than that of the rough nanowires. Considering both nanowires were grown via the same growth mechanism, these outcomes clearly demonstrate that the rough surface induces phonon scattering and reduces thermal conductivity with this nanoscale-hole-free nanowires. Control of roughness induced phonon scattering in Si nanowires holds promise for novel thermoelectric devices with high figures of merit. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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16. Milk Fat Globule-EGF Factor 8 Contributes to Progression of Hepatocellular Carcinoma.
- Author
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Ko, Duck Sung, Kim, Su Hyun, Park, Ji Young, Lee, Gyunggyu, Kim, Hyo Jin, Kim, Gyeongmin, Chi, Kyun You, Kim, Ilsoo, Lee, Jinseok, Won, Kyu-Yeoun, Han, Jiyou, Son, Jeongsang, Woo, Dong-Hun, Han, Choongseong, and Kim, Jong-Hoon
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ANIMAL experimentation , *ANTIGENS , *CELL lines , *CELL motility , *CELLULAR signal transduction , *GENE expression , *HEPATOCELLULAR carcinoma , *MICE , *MILK proteins , *T-test (Statistics) , *XENOGRAFTS , *IN vitro studies , *IN vivo studies - Abstract
Milk fat globule-EGF factor 8 (MFG-E8) is an anti-inflammatory glycoprotein that mediates a wide spectrum of pathophysiological processes. MFG-E8 has been studied as a key regulator of cancer cell invasion, migration, and proliferation in different tissues and organs. However, potential roles of MFG-E8 in the growth and progression of liver cancer have not been investigated to date. Here, we analyzed 33 human hepatocellular carcinoma (HCC) samples and found that levels of MFG-E8 expression were significantly higher in HCC cells than in normal liver tissues. In addition, our in vitro gain-of-function study in three different HCC cell lines revealed that overexpression of MFG-E8 promoted the proliferation and migration of HCC cells, as determined by RT-qPCR, MTT assays, and wound healing analyses. Conversely, an MFG-E8 loss-of function study showed that proliferation capacity was significantly reduced by MFG-E8 knockdown in HCC cells. Additionally, MFG-E8 activity-neutralizing antibodies profoundly inhibited both migration and proliferation of HCC cells, attenuating their tumorigenic properties. These reductions in migration and proliferation were rescued by treatment of HCC cells with recombinant MFG-E8 protein. Furthermore, an in vivo HCC xenograft study showed that the number of proliferating HCC cells and tumor volume/weight were all significantly increased by MFG-E8 overexpression, compared to control mice. These results clearly show that MFG-E8 plays an important role in HCC progression and may provide a basis for future mechanistic studies and new strategies for the treatment of liver cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
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