Publications by authors named "Hyungwoo Lee"

80 Publications

Cooperative evolution of polar distortion and nonpolar rotation of oxygen octahedra in oxide heterostructures.

Sci Adv 2021 Apr 21;7(17). Epub 2021 Apr 21.

Department of Energy Science, Sungkyunkwan University, Suwon 16419, Republic of Korea.

Polarity discontinuity across LaAlO/SrTiO (LAO/STO) heterostructures induces electronic reconstruction involving the formation of two-dimensional electron gas (2DEG) and structural distortions characterized by antiferrodistortive (AFD) rotation and ferroelectric (FE) distortion. We show that AFD and FE modes are cooperatively coupled in LAO/STO (111) heterostructures; they coexist below the critical thickness () and disappear simultaneously above with the formation of 2DEG. Electron energy-loss spectroscopy and density functional theory (DFT) calculations provide direct evidence of oxygen vacancy () formation at the LAO (111) surface, which acts as the source of 2DEG. Tracing the AFD rotation and FE distortion of LAO reveals that their evolution is strongly correlated with distribution. The present study demonstrates that AFD and FE modes in oxide heterostructures emerge as a consequence of interplay between misfit strain and polar field, and further that their combination can be tuned to competitive or cooperative coupling by changing the interface orientation.
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http://dx.doi.org/10.1126/sciadv.abe9053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059930PMC
April 2021

Automated Quantification of Vitreous Hyperreflective Foci and Vitreous Haze Using Optical Coherence Tomography in Uveitis Patients.

Retina 2021 Apr 12. Epub 2021 Apr 12.

Department of Ophthalmology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Republic of Korea.

Purpose: Development of an automated method to quantify the count of vitreous hyperreflective foci (vHF) and intensity of vitreous haze in uveitis patients by optical coherence tomography (OCT).

Methods: A method based on deep learning to automatically segment the vHF, vitreous and retinal pigment epithelium (RPE) in OCT was developed using 1,058 scans from 88 OCT volumes of 33 patients with intermediate, posterior or panuveitis. Based on segmented images, the vHF count and the relative intensity of vitreous to RPE (VIT/RPE-relative intensity) was quantified. Dice coefficient and intraclass correlation coefficient (ICC) were calculated between ground truth and the trained network.

Results: The segmented area of vHF, vitreous and RPE by the deep learning-based model showed good agreement with the clinicians' results, yielding a Dice coefficient of 0.69, 0.99, and 0.88, respectively. The ICC of the vHF count and the VIT/RPE-relative intensity per scan was 0.99 and 1.00, respectively. In eyes of test set, changes in vHF and VIT/RPE-relative intensity during treatment did not show similar patterns.

Conclusions: Automated segmentation of the vHF, vitreous and RPE in OCT images of uveitis patients was accomplished by a deep learning approach. The vHF count and VIT/RPE-relative intensity could be quantified with high reliability.
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http://dx.doi.org/10.1097/IAE.0000000000003190DOI Listing
April 2021

Association between Exposure to Ambient Air Pollution and Age-Related Cataract: A Nationwide Population-Based Retrospective Cohort Study.

Int J Environ Res Public Health 2020 12 10;17(24). Epub 2020 Dec 10.

Department of Preventive Medicine, Konkuk University School of Medicine, Seoul 05030, Korea.

This study aimed to investigate the association between ambient air pollutants and cataracts in the general population aged 50 years or older using data from the Korean National Insurance Service-National Sample Cohort. Cataract patients were defined as those diagnosed by a physician and having undergone cataract surgery. After matching the average concentrations of PM, PM, NO, CO, SO, and O in residential areas, the association between quartile level of air pollutants and incidence of cataract was analyzed using a multivariate Cox-proportional hazard risk model. Among the 115,728 participants, 16,814 (14.5%) were newly diagnosed with cataract and underwent related surgery between 1 January 2004, and 31 December 2015. Exposure to PM, NO, and SO was positively associated with cataract incidence, while O was negatively associated. The adjusted hazard ratio (HR) with 95% confidence interval was 1.069 (1.025-1.115) in PM and 1.080 (1.030-1.133) in NO. However, the association between cataract and the quartile of PM measured during one year in 2015 was not clear. The HR of female participants aged 65 or older was significantly increased according to quartile of air pollutants. We identified exposure to PM, NO, SO, and O associated with cataract development in Korean adults aged ≥ 50 years. This information may be helpful for policymaking to control air pollution as a risk factor for eye health.
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http://dx.doi.org/10.3390/ijerph17249231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763970PMC
December 2020

Engineered spin-orbit interactions in LaAlO/SrTiO-based 1D serpentine electron waveguides.

Sci Adv 2020 Nov 25;6(48). Epub 2020 Nov 25.

Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, PA 15260, USA.

The quest to understand, design, and synthesize new forms of quantum matter guides much of contemporary research in condensed matter physics. One-dimensional (1D) electronic systems form the basis for some of the most interesting and exotic phases of quantum matter. Here, we describe a family of quasi-1D nanostructures, based on LaAlO/SrTiO electron waveguides, in which a sinusoidal transverse spatial modulation is imposed. These devices display unique dispersive features in the subband spectra, namely, a sizeable shift (∼7 T) in the spin-dependent subband minima, and fractional conductance plateaus. The first property can be understood as an engineered spin-orbit interaction associated with the periodic acceleration of electrons as they undulate through the nanowire (ballistically), while the second property signifies the presence of enhanced electron-electron scattering in this system. The ability to engineer these interactions in quantum wires contributes to the tool set of a 1D solid-state quantum simulation platform.
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http://dx.doi.org/10.1126/sciadv.aba6337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688326PMC
November 2020

Long-Term Non Anesthetic Preclinical Study Available Extra-Cranial Brain Activator (ECBA) System for the Future Minimally Invasive Human Neuro Modulation.

IEEE Trans Biomed Circuits Syst 2020 12 31;14(6):1393-1406. Epub 2020 Dec 31.

In recent years, electroceuticals have been spotlighted as an emerging treatment for various severe chronic brain diseases, owing to their intrinsic advantage of electrical interaction with the brain, which is the most electrically active organ. However, the majority of research has verified only the short-term efficacy through acute studies in laboratory tests owing to the lack of a reliable miniaturized platform for long-term animal studies. The construction of a sufficient integrated system for such a platform is extremely difficult because it requires multi-disciplinary work using state-of-the-art technologies in a wide range of fields. In this study, we propose a complete system of an implantable platform for long-term preclinical brain studies. Our proposed system, the extra-cranial brain activator (ECBA), consists of a titanium-packaged implantable module and a helmet-type base station that powers the module wirelessly. The ECBA can also be controlled by a remote handheld device. Using the ECBA, we performed a long-term non-anesthetic study with multiple canine subjects, and the resulting PET-CT scans demonstrated remarkable enhancement in brain activity relating to memory and sensory skills. Furthermore, the histological analysis and high-temperature aging test confirmed the reliability of the system for up to 31 months. Hence, the proposed ECBA system is expected to lead a new paradigm of human neuromodulation studies in the near future.
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http://dx.doi.org/10.1109/TBCAS.2020.3034444DOI Listing
December 2020

Characterization of microvascular tortuosity in retinal vein occlusion utilizing optical coherence tomography angiography.

Sci Rep 2020 10 20;10(1):17788. Epub 2020 Oct 20.

Department of Ophthalmology, Konkuk University School of Medicine, Konkuk University Medical Center, 120-1 Neungdong-ro, Gwangjin-gu, Seoul, 05030, Republic of Korea.

We investigated the characteristics of microvessel tortuosity in branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) and their associations with visual outcomes using optical coherence tomography angiography (OCTA). Thirty-four BRVO and 21 CRVO patients and 31 healthy subjects were included. From OCTA, the branch number (BN), mean branch length (BL), mean Euclidean length (EL), vessel density (VD) and vessel tortuosity (VT) were quantified. In BRVO eyes, compared with that in the controls, the affected area of the deep capillary plexus (DCP) showed a decreased BN and VD, an increased BL, and unchanged VT. The nonaffected area of the DCP showed decreases in BN, VD and VT. The affected area of the superficial capillary plexus (SCP) showed higher VT. In CRVO eyes, the DCP showed a lower BN, VD and VT, while the SCP showed a lower BN and greater BL and EL. Improved visual acuity (VA) after 1 year in BRVO eyes was associated with decreases in BN, BL, VD and VT in the affected area in the DCP and lower VT in the nonaffected area of the SCP; in CRVO eyes, improved VA was associated with a higher BL and EL in the DCP. VT, BL, and EL may be new microvascular markers associated with changes in VA in BRVO and CRVO.
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http://dx.doi.org/10.1038/s41598-020-74871-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576190PMC
October 2020

Large-Scale Assembly of Peptide-Based Hierarchical Nanostructures and Their Antiferroelectric Properties.

Small 2020 11 20;16(45):e2003986. Epub 2020 Oct 20.

Department of Nanotechnology and Advanced Materials Engineering, Hybrid Materials Research Center (HMC), Sejong University, Seoul, 05006, Republic of Korea.

An effective strategy is developed to create peptide-based hierarchical nanostructures through the meniscus-driven self-assembly in a large area and fabricate antiferroelectric devices based on these nanostructures for the first time. The diphenylalanine hierarchical nanostructures (FF-HNs) are self-assembled by vertically pulling a substrate from a diphenylalanine (FF) solution dissolved in a miscible solvent under precisely controlled conditions. Owing to the unique structural properties of FF nanostructures, including high crystallinity and α-helix structures, FF-HNs possess a net electrical dipole moment, which can be switched in an external electric field. The mass production of antiferroelectric devices based on FF-HNs can be successfully achieved by means of this biomimetic assembly technique. The devices show an evident antiferroelectric to ferroelectric transition under dark conditions, while the ferroelectricity is found to be tunable by light. Notably, it is discovered that the modulation of antiferroelectric behaviors of FF-HNs under glutaraldehyde exposure is due to the FF molecules that are transformed into cyclophenylalanine by glutaraldehyde. This work provides a stepping stone toward the mass production of self-assembled hierarchical nanostructures based on biomolecules as well as the mass fabrication of electronic devices based on biomolecular nanostructures for practical applications.
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http://dx.doi.org/10.1002/smll.202003986DOI Listing
November 2020

Long-term Non-Anesthetic Preclinical Study Available Extra-Cranial Brain Activator (ECBA) System for the Future Minimally-Invasive Human Neuro-Modulation.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:5184-5187

Long-term preclinical study available extracranial brain activator (ECBA) system, ECBAv2, is proposed for the non-anesthetic canine models. The titanium-packaged module shows enhanced durability, even after a year of implantation in the scalp. In addition, the wearable helmet type base station provides a stable experimental environment without anesthesia. In this work, HFS stimulation is induced to six canine models for 30 minutes every day over 4 weeks (10Hz, 40Hz and no stimulation for each pair of subjects). Pre- and post-HFS stimulation PET-CT image shows remarkable increases of glucose metabolism in the temporal and parietal lobes. Moreover, both the 40-Hz and 10-Hz groups shows noticeable increase and the former group has more increments than the latter. Our results establish that HFS stimulation definitely worked as facilitating brain activity which may affect memory and sensory skills, respectively.
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http://dx.doi.org/10.1109/EMBC44109.2020.9176408DOI Listing
July 2020

A 10 nV/rt Hz noise level 32-channel neural impedance sensing ASIC for local activation imaging on nerve section.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:4012-4015

A 10 nV/rt Hz noise level 32-channel neural impedance sensing ASIC is presented for the application of local activation imaging in nerve section. It is increasingly known that the monitoring and control of nerve signals can improve physical and mental health. Major nerves, such as the vagus nerve and the sciatic nerve, consist of a bundle of fascicles. Therefore, to accurately control a particular application without any side effects, we need to know exactly which fascicle was activated. The only way to find locally activated fascicle is to use electrical impedance tomography (EIT). The ASIC to be introduced is designed for neural EIT applications. A neural impedance sensing ASIC was implemented using CMOS 180-nm process technology. The integrated input referred noise was calculated to be 0.46 μVrms (noise floor 10.3 nVrms/rt Hz) in the measured noise spectrum. At an input of 80 mV, the squared correlation coefficient for linear regression was 0.99998. The amplification gain uniformity of 32 channels was in the range of + 0.23% and - 0.29%. Using the resistor phantom, the simplest model of nerve, it was verified that a single readout channel could detect a signal-to- noise ratio of 75.6 dB or more. Through the reservoir phantom, real-time EIT images were reconstructed at a rate of 8.3 frames per second. The developed ASIC has been applied to in vivo experiments with rat sciatic nerves, and signal processing is currently underway to obtain activated nerve cross-sectional images. The developed ASIC was also applied to in-vivo experiments with rat sciatic nerves, and signal processing is currently underway to obtain locally activated nerve cross-sectional images.
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http://dx.doi.org/10.1109/EMBC44109.2020.9176708DOI Listing
July 2020

Diabetic macular edema with pachychoroid features.

BMC Ophthalmol 2020 Oct 2;20(1):392. Epub 2020 Oct 2.

Department of Ophthalmology, Konkuk University School of Medicine, Konkuk University Medical Center, 120-1 Neungdong-ro, Gwangjin-gu, Seoul, 05030, Republic of Korea.

Background: To investigate the clinical features of diabetic macular edema (DME) in eyes with pachychoroid phenotypes using multimodal retinal imaging.

Methods: We retrospectively reviewed 210 eyes from 210 DME patients and analyzed the clinical and imaging parameters, including visual acuity, central macular thickness (CMT), subfoveal choroidal thickness (SFCT) and neural retina layer thickness (NRT). The DME eyes were divided into two groups: group 1 (80 eyes with submacular detachment [SMD]) and group 2 (130 eyes without SMD). The clinical and imaging parameters of 285 eyes from 285 diabetic patients without DME were collected as a control group.

Results: DME eyes with pachychoroid phenotypes were more frequent in group 1 than in group 2 (53 eyes [66.25%] and 53 eyes [40.77%], respectively, P < 0.001). Pachychoroid phenotypes were identified in 108 (37.90%) of the control eyes. CMT and NRT were greater in group 1 than in group 2. In group 1, 37 eyes had SMD combined with focal edema, and 43 eyes had SMD combined with diffuse-type edema. No significant difference in pachychoroid phenotypes was found between the focal and diffuse types (26 [70.27%] and 27 [62.79%], respectively, P = 0.481). In group 2, 70 eyes had focal-type edema, and 60 eyes had diffuse-type edema. No significant difference in the frequency of pachychoroid phenotypes was found (32 [45.71%] and 21 [35.00%], respectively, P = 0.215). Interestingly, among the 70 eyes with focal edema in group 2, 13 (40.6%) and 5 (13.2%) eyes with and without pachychoroid phenotypes showed no definite microaneurysms, respectively.

Conclusion: SMD and focal edema without definite microaneurysms may be clinical manifestations of DME with pachychoroid phenotypes and possibly related to choroidal circulation disturbance in DME.
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http://dx.doi.org/10.1186/s12886-020-01663-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532553PMC
October 2020

Gate-Tunable Optical Nonlinearities and Extinction in Graphene/LaAlO/SrTiO Nanostructures.

Nano Lett 2020 Oct 1;20(10):6966-6973. Epub 2020 Sep 1.

Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.

We explore the ultrafast optical response of graphene subjected to intense (∼10 V/cm) local (∼10 nm) electric fields. Nanoscale gating of graphene is achieved using a voltage-biased, SrTiO-based conductive nanowire junction "written" directly under the graphene and isolated from it by an insulating ultrathin (<2 nm) LaAlO barrier. Upon illumination with ultrafast visible-to-near-infrared (VIS-NIR) light pulses, the local field from the nanojunction creates a strong gate-tunable second-order nonlinearity in the graphene and produces a substantial difference-frequency (DFG) and sum-frequency generation (SFG) response detected by the nanojunction. Spectrally sharp, gate-tunable extinction features (>99.9%) are observed in the VIS-NIR and SFG spectral ranges, in parameter regimes that are positively correlated with the enhanced nonlinear response. The observed graphene-light interaction and nonlinear response are of fundamental interest and open the way for future exploitation in graphene-based optical devices such as phase shifters, modulators, and nanoscale THz sources.
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http://dx.doi.org/10.1021/acs.nanolett.0c01379DOI Listing
October 2020

POST-TREATMENT PREDICTION OF OPTICAL COHERENCE TOMOGRAPHY USING A CONDITIONAL GENERATIVE ADVERSARIAL NETWORK IN AGE-RELATED MACULAR DEGENERATION.

Retina 2021 Mar;41(3):572-580

Department of Ophthalmology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Republic of Korea.

Purpose: To develop a deep learning model to generate posttreatment optical coherence tomography (OCT) images of neovascular age-related macular degeneration.

Methods: Two hundred ninety-eight patients with neovascular age-related macular degeneration were included. The conditional generative adversarial network was trained using 15,183 augmented paired OCT B-scan images obtained from 723 scans of 241 patients at baseline and 1 month after 3 loading doses of an anti-vascular endothelial growth factor treatment. The network was also trained using baseline fluorescein angiography (FA) or indocyanine green angiography (ICGA) images together with baseline OCT images. A test set of 150 images of 50 eyes was used to evaluate its ability to predict the presence of intraretinal fluid, subretinal fluid, PED, and subretinal hyperreflective material. Posttreatment OCT images were compared with images generated from baseline OCT with or without FA and indocyanine green angiography images.

Results: The predicted images inferred from baseline OCT images achieved an acceptable accuracy, specificity, and negative predictive value for four lesions (range: 77.0-91.9, 94.1-95.1, and 54.7-96.5%, respectively). The addition of both FA and indocyanine green angiography images improved the accuracy, specificity, and negative predictive value (range: 80.7-96.3, 97.3-99.0, and 59.0-98.3%, respectively).

Conclusion: A conditional generative adversarial network is able to generate posttreatment OCT images from baseline OCT, FA, and indocyanine green angiography images.
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http://dx.doi.org/10.1097/IAE.0000000000002898DOI Listing
March 2021

Fabrication and evaluation of activated carbon-Pt microparticle based glutamate biosensor.

J Electroanal Chem (Lausanne) 2020 Jun 17;866. Epub 2020 Apr 17.

Weldon School of Biomedical Engineering, Birck Nanotechnology Center, Center for Implantable Device, Purdue University, West Lafayette, IN, USA.

As one of the most abundant neurotransmitters in the brain and the spinal cord, glutamate plays many important roles in the nervous system. Precise information about the level of glutamate in the extracellular space of living brain tissue may provide new insights on fundamental understanding of the role of glutamate in neurological disorders as well as neurophysiological phenomena. Electrochemical sensor has emerged as a promising solution that can satisfy the requirement for highly reliable and continuous monitoring method with good spatiotemporal resolution for characterization of extracellular glutamate concentration. Recently, we published a method to create a simple printable glutamate biosensor using platinum nanoparticles. In this work, we introduce an even simpler and lower cost conductive polymer composite using commercially available activated carbon with platinum microparticles to easily fabricate highly sensitive glutamate biosensor using direct ink writing method. The fabricated biosensors are functionality superior than previously reported with the sensitivity of 5.73 ± 0.078 nA μM mm, detection limit of 0.03 μM, response time less than or equal to 1 s, and a linear range from 1 μM up to 925 μM. In this study, we utilize astrocyte cell culture to demonstrate our biosensor's ability to monitor glutamate uptake process. We also demonstrate direct measurement of glutamate release from optogenetic stimulation in mouse primary visual cortex (V1) brain slices.
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http://dx.doi.org/10.1016/j.jelechem.2020.114136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266303PMC
June 2020

Pascal conductance series in ballistic one-dimensional LaAlO/SrTiO channels.

Science 2020 02;367(6479):769-772

Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, PA 15260, USA.

One-dimensional electronic systems can support exotic collective phases because of the enhanced role of electron correlations. We describe the experimental observation of a series of quantized conductance steps within strongly interacting electron waveguides formed at the lanthanum aluminate-strontium titanate (LaAlO/SrTiO) interface. The waveguide conductance follows a characteristic sequence within Pascal's triangle: (1, 3, 6, 10, 15, …) ⋅ , where is the electron charge and is the Planck constant. This behavior is consistent with the existence of a family of degenerate quantum liquids formed from bound states of = 2, 3, 4, … electrons. Our experimental setup could provide a setting for solid-state analogs of a wide range of composite fermionic phases.
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http://dx.doi.org/10.1126/science.aat6467DOI Listing
February 2020

Heterogeneous integration of single-crystalline complex-oxide membranes.

Nature 2020 02 5;578(7793):75-81. Epub 2020 Feb 5.

Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

Complex-oxide materials exhibit a vast range of functional properties desirable for next-generation electronic, spintronic, magnetoelectric, neuromorphic, and energy conversion storage devices. Their physical functionalities can be coupled by stacking layers of such materials to create heterostructures and can be further boosted by applying strain. The predominant method for heterogeneous integration and application of strain has been through heteroepitaxy, which drastically limits the possible material combinations and the ability to integrate complex oxides with mature semiconductor technologies. Moreover, key physical properties of complex-oxide thin films, such as piezoelectricity and magnetostriction, are severely reduced by the substrate clamping effect. Here we demonstrate a universal mechanical exfoliation method of producing freestanding single-crystalline membranes made from a wide range of complex-oxide materials including perovskite, spinel and garnet crystal structures with varying crystallographic orientations. In addition, we create artificial heterostructures and hybridize their physical properties by directly stacking such freestanding membranes with different crystal structures and orientations, which is not possible using conventional methods. Our results establish a platform for stacking and coupling three-dimensional structures, akin to two-dimensional material-based heterostructures, for enhancing device functionalities.
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http://dx.doi.org/10.1038/s41586-020-1939-zDOI Listing
February 2020

A minimally invasive wirelessly powered brain stimulation system for treating neurological disorders.

Annu Int Conf IEEE Eng Med Biol Soc 2019 Jul;2019:6141-6144

A novel minimally invasive wirelessly powered medical device, a magnetic induction extra-cranial brain stimulation (MI-ECBS) system is implemented for treating neurological disorders, Alzheimer's disease (AD) and Epilepsy. The proposed system provides 2 different types of clinically significant stimulation waveforms for the therapy. For high frequency stimulation (HFS), we used 1mA, 10Hz, rectangular, charge balanced (0.5msec pulse width) pulses for 3sec with 21sec rest (total 600 pulses). Subsequently, under same configuration, a low frequency stimulation (LFS; 1Hz, 600 pulses) protocol was applied to canine-animal models. As a result, complementary neuro-modulation, facilitation and an inhibition are successfully demonstrated with an EEG power spectrum monitoring and the stimulation delivery efficacy is enhanced to 39.57x comparing to conventional transcutaneous direct current stimulation (tDCS).
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http://dx.doi.org/10.1109/EMBC.2019.8857038DOI Listing
July 2019

Association of imaging factors derived from convolutional neural network with visual outcomes in age-related macular degeneration and polypoidal choroidal vasculopathy.

Sci Rep 2019 12 27;9(1):19857. Epub 2019 Dec 27.

Department of Ophthalmology, Konkuk University School of Medicine, Konkuk University Medical Center, Seoul, Republic of Korea.

We investigated the association of visual outcome in typical neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) with or without pachychoroid with lesion areas on optical coherence tomography (OCT) quantified by convolutional neural network (CNN) analysis. Treatment-naïve 132 nAMD and 45 PCV eyes treated with ranibizumab or aflibercept for at least 12 months were retrospectively reviewed. Significant factors, including intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED) and subretinal hyperreflective material (SHRM) area quantified by CNN at baseline and 12 months, were analyzed by logistic regression analyses for 3-line visual gain or maintenance of 20/30 Snellen vision. Visual gain at the final visit in nAMD was associated with a smaller SHRM at baseline (OR 0.167, P = 0.03), greater decrease in SRF and SHRM from baseline to month 12 (OR 1.564, P = 0.02; OR 12.877, P = 0.01, respectively). Visual gain in nAMD without pachychoroid was associated with a greater decrease in SRF and SHRM (OR 1.574, P = 0.03, OR 1.775, P = 0.04). No association was found in nAMD with pachychoroid and any type of PCV. Greater decrease in SRF and SHRM from baseline to month 12 was associated with favorable visual outcomes in nAMD without pachychoroid but not in nAMD with pachychoroid and PCV.
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http://dx.doi.org/10.1038/s41598-019-56420-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934705PMC
December 2019

ASSOCIATION OF TREATMENT RESPONSE WITH QUANTITATIVE CHANGES IN CHOROIDAL NEOVASCULARIZATION AND CHOROIDAL VESSEL IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

Retina 2020 Sep;40(9):1704-1718

Department of Ophthalmology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Republic of Korea.

Purpose: To evaluate the association between treatment response and quantitative morphological changes in choroidal neovascularization and outer choroidal vessels using optical coherence tomography angiography (OCTA) and en face OCT in neovascular age-related macular degeneration (nAMD).

Methods: We retrospectively analyzed 75 eyes of typical nAMD patients and 53 polypoidal choroidal vasculopathy eyes of 124 patients with OCTA performed at least 6 months after initial antivascular endothelial growth factor treatment. Quantitative parameters, including vessel area, vessel diameter, branch vessel length, fractal dimension, and lacunarity were analyzed based on en face images of the choroidal neovascularization and choroidal vessel in Haller's layer. Parameters associated with loss of logarithm of the minimum angle of resolution visual acuity with the basis of 0.3 and the treatment interval (good vs. poor responder based on 12 weeks) were analyzed. Analyses were conducted for "before OCTA" (initial visit to OCTA) and "after OCTA" (OCTA to 6 months post-OCTA).

Results: In typical nAMD, visual acuity loss before OCTA was associated with a higher SD of choroidal neovascularization diameter and lower choroidal fractal dimension. Visual acuity loss after OCTA in typical nAMD was associated with higher lacunarity of the choroid. Poor responders before OCTA were not associated with any factor. Poor responders after OCTA were associated with a lower SD of outer choroidal vessel diameter in typical nAMD. In polypoidal choroidal vasculopathy, no factor was associated with clinical outcomes in either period.

Conclusion: Quantitative analyses of choroidal neovascularization on OCTA and choroidal vessels on en face OCT provide information about treatment response, including changes in visual acuity and treatment interval, in nAMD.
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http://dx.doi.org/10.1097/IAE.0000000000002678DOI Listing
September 2020

Electroluminescent soft elastomer actuators with adjustable luminance and strain.

Soft Matter 2019 Oct 2;15(40):7996-8000. Epub 2019 Oct 2.

Department of Mechanical Engineering, Korea University, Seoul 02841, Republic of Korea.

We demonstrate a multifunctional soft actuator that exhibits both electroluminescence (EL) and soft actuation with a strain of 85% and a maximum luminance of 300 cd m, superior to previous devices with individual functions. This was possible by combining several strategies such as the development of highly conductive, transparent, and stretchable electrodes, incorporation of high-k nanoparticles to increase the electric field applied to the EL particles, and application of AC + DC composite signals to simplify the device structure. We expect this research to contribute to the development of new soft devices that can further enhance human-machine interactions in color displaying actuator applications.
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http://dx.doi.org/10.1039/c9sm01122fDOI Listing
October 2019

Large and Reconfigurable Infrared Photothermoelectric Effect at Oxide Interfaces.

Nano Lett 2019 10 23;19(10):7149-7154. Epub 2019 Sep 23.

Department of Physics and Astronomy , West Virginia University , Morgantown , West Virginia 26506 , United States.

To maximize the photovoltaic efficiency, it is highly desirable to enable the electricity conversion from low energy photons and to extract the excessive energy from hot carriers. Here we report a large photovoltage generation at the LaAlO/SrTiO interfaces from infrared photons with energies far below the oxide bandgaps. This effect is a result of the photoexcitation of hot carriers in metasurface electrical contacts and the subsequent thermoelectric charge separations by the interfacial two-dimensional electron gas (2DEG). Reaching a room-temperature responsivity of 4.4 V/W, such light-to-charge conversion can be spatially controlled and reconfigured through the patterning of 2DEG using conducting atomic force microscope. Compatible for broadband applications, our results demonstrate a new path toward efficient and programmable light sensing using oxide-based low-dimensional electron systems.
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http://dx.doi.org/10.1021/acs.nanolett.9b02712DOI Listing
October 2019

Development of wirelessly-powered, extracranial brain activator (ECBA) in a large animal model for the future non-invasive human neuromodulation.

Sci Rep 2019 07 29;9(1):10906. Epub 2019 Jul 29.

Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

As transcranial electrical stimulation (tES) is an emerging and promising technique for neuromodulation, we developed a novel device; wirelessly-powered, extracranial brain activator (ECBA), which is mounted subcutaneously, and its neuromodulation effect was investigated. The oscillatory changes in electrocorticography (EcoG) were analyzed from two types of stimulation. Two weeks prior to the recording experiment, we underwent surgery for implantation of subdural strips and ECBA module over centroparietal regions of anesthetized beagles. Low-frequency stimulation (LFS) and subsequent high-frequency stimulation (HFS) protocols (600 pulses respectively) were applied. Then, the power changes before and after each stimulation in five different bands were compared. A significantly larger voltage difference with subcutaneous than transcutaneous stimulation measured at EcoG channels indicated a substantial current attenuation between the skin and skull. Compared with the baseline, all subjects showed consistently decreased delta power and increased gamma power after HFS. LFS also induced a similar, but opposite, pattern of power change in four beagles. The results from this study indicate that LFS and HFS with our novel ECBA can consistently and effectively modulate neural activity of the cortex, inducing neural inhibition and facilitation functions, respectively. Future studies are necessary to further ensuring a consistent efficacy and long-term safety.
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http://dx.doi.org/10.1038/s41598-019-47383-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662771PMC
July 2019

Corrigendum to Facile fabrication of flexible glutamate biosensor using direct writing of platinum nanoparticle-based nanocomposite ink.

Biosens Bioelectron 2019 09 17;141:111429. Epub 2019 Jun 17.

Weldon School of Biomedical Engineering, Birck Nanotechnology Center, Center for Implantable Device, Purdue University, West Lafayette, IN, USA. Electronic address:

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http://dx.doi.org/10.1016/j.bios.2019.111429DOI Listing
September 2019

Facile fabrication of flexible glutamate biosensor using direct writing of platinum nanoparticle-based nanocomposite ink.

Biosens Bioelectron 2019 Apr 31;131:257-266. Epub 2019 Jan 31.

Weldon School of Biomedical Engineering, Birck Nanotechnology Center, Center for Implantable Device, Purdue University, West Lafayette, IN, USA. Electronic address:

Glutamate excitotoxicity is a pathology in which excessive glutamate can cause neuronal damage and degeneration. It has also been linked to secondary injury mechanisms in traumatic spinal cord injury. Conventional bioanalytical techniques used to characterize glutamate levels in vivo, such as microdialysis, have low spatiotemporal resolution, which has impeded our understanding of this dynamic event. In this study, we present an amperometric biosensor fabricated using a simple direct ink writing technique for the purpose of in vivo glutamate monitoring. The biosensor is fabricated by immobilizing glutamate oxidase on nanocomposite electrodes made of platinum nanoparticles, multi-walled carbon nanotubes, and a conductive polymer on a flexible substrate. The sensor is designed to measure extracellular dynamics of glutamate and other potential biomarkers during a traumatic spinal cord injury event. Here we demonstrate good sensitivity and selectivity of these rapidly prototyped implantable biosensors that can be inserted into a spinal cord and measure extracellular glutamate concentration. We show that our biosensors exhibit good flexibility, linear range, repeatability, and stability that are suitable for future in vivo evaluation.
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http://dx.doi.org/10.1016/j.bios.2019.01.051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261495PMC
April 2019

Over 100-THz bandwidth selective difference frequency generation at LaAlO/SrTiO nanojunctions.

Light Sci Appl 2019 27;8:24. Epub 2019 Feb 27.

1Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, PA 15260 USA.

The ability to combine continuously tunable narrow-band terahertz (THz) generation that can access both the far-infrared and mid-infrared regimes with nanometer-scale spatial resolution is highly promising for identifying underlying light-matter interactions and realizing selective control of rotational or vibrational resonances in nanoparticles or molecules. Here, we report selective difference frequency generation with over 100 THz bandwidth via femtosecond optical pulse shaping. The THz emission is generated at nanoscale junctions at the interface of LaAlO/SrTiO (LAO/STO) that is defined by conductive atomic force microscope lithography, with the potential to perform THz spectroscopy on individual nanoparticles or molecules. Numerical simulation of the time-domain signal facilitates the identification of components that contribute to the THz generation. This ultra-wide-bandwidth tunable nanoscale coherent THz source transforms the LAO/STO interface into a promising platform for integrated lab-on-chip optoelectronic devices with various functionalities.
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http://dx.doi.org/10.1038/s41377-019-0135-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393436PMC
February 2019

Probing vacancy behavior across complex oxide heterointerfaces.

Sci Adv 2019 Feb 22;5(2):eaau8467. Epub 2019 Feb 22.

Department of Mechanical and Industrial Engineering, University of Massachusetts-Amherst, Amherst, MA 01003, USA.

Oxygen vacancies ( ) play a critical role as defects in complex oxides in establishing functionality in systems including memristors, all-oxide electronics, and electrochemical cells that comprise metal-insulator-metal or complex oxide heterostructure configurations. Improving oxide-oxide interfaces necessitates a direct, spatial understanding of vacancy distributions that define electrochemically active regions. We show vacancies deplete over micrometer-level distances in Nb-doped SrTiO (Nb:SrTiO) substrates due to deposition and post-annealing processes. We convert the surface potential across a strontium titanate/yttria-stabilized zirconia (STO/YSZ) heterostructured film to spatial (<100 nm) vacancy profiles within STO using ( = 500°C) in situ scanning probes and semiconductor analysis. Oxygen scavenging occurring during pulsed laser deposition reduces Nb:STO substantially, which partially reoxidizes in an oxygen-rich environment upon cooling. These results (i) introduce the means to spatially resolve quantitative vacancy distributions across oxide films and (ii) indicate the mechanisms by which oxide thin films enhance and then deplete vacancies within the underlying substrate.
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http://dx.doi.org/10.1126/sciadv.aau8467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386560PMC
February 2019

Three-dimensional analysis of morphologic changes and visual outcomes in diabetic macular edema.

Jpn J Ophthalmol 2019 May 19;63(3):234-242. Epub 2019 Feb 19.

Department of Ophthalmology, Konkuk University School of Medicine, Konkuk University Medical Center, 120-1 Neungdong-ro, Gwangjin-gu, Seoul, 05030, Republic of Korea.

Purpose: To investigate the association of retinal fluid volume with the visual and anatomic outcomes of patients with diabetic macular edema (DME) after treatment with bevacizumab.

Study Design: Retrospective observational study.

Methods: We retrospectively analyzed 65 eyes of 58 DME patients treated with bevacizumab. The volumes of the inner intraretinal fluid (IRF) in the inner nuclear layer (INL), outer IRF in the outer plexiform layer (OPL)/outer nuclear layer (ONL), and subretinal fluid (SRF) were calculated. The correlations between the baseline fluid volumes and best-corrected visual acuity (BCVA), area of disorganization of the retinal inner layers (DRIL), disrupted external limiting membrane (ELM), and disrupted ellipsoid zone (EZ) at 12 months after treatment were assessed.

Results: The baseline volume of the inner IRF correlated with poor BCVA at the final visit (r = 0.52, P < .001) whereas the baseline volume of the outer IRF and SRF volume did not show a significant correlation with BCVA at the final visit (P = .07 and P = .61, respectively). The improvement in BCVA correlated with the reduction in the baseline volume of the inner IRF and outer IRF (r = 0.25, P = .04 and r = 0.36, P = .003), but not with the SRF volume (P = .59). The baseline volume of the inner IRF correlated positively with the area of DRIL and the disrupted ELM at the final visit (r = 0.56, P < .001 and r = 0.25, P = .04, respectively). Such relationship remained in each quadrant of the macula (P < .005 for all quadrants).

Conclusion: The baseline volume of the inner IRF correlated with a poor visual outcome, an increased DRIL area, and a more disrupted ELM area in patients with DME after treatment with bevacizumab.
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http://dx.doi.org/10.1007/s10384-019-00657-8DOI Listing
May 2019

Author Response: Hyperreflective Intraretinal Foci as an OCT Biomarker of Retinal Inflammation in Diabetic Macular Edema.

Invest Ophthalmol Vis Sci 2018 11;59(13):5367

Department of Ophthalmology, Konkuk University School of Medicine, Konkuk University Medical Center, Seoul, Republic of Korea.

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http://dx.doi.org/10.1167/iovs.18-25825DOI Listing
November 2018

An Energy Efficient Programmable Neuro-Mimicking Stimulator IC for Implantable Electroceutical Systems.

Annu Int Conf IEEE Eng Med Biol Soc 2018 Jul;2018:4174-4177

Energy efficient programmable neuro-mimicking stimulator is designed for implantable electroceutical systems (IES). To provide clinically-proved stimulation waveforms, a complex waveform programmer (CWP) is proposed. It makes a number of pulses, trains and clusters in a time sequence with the separate dead-time slots. Due to CWP, the single period of one therapy can be up to 24 hours. Moreover, V decision-loop is applied to guarantee more than 90% of energy efficiency. It finds contact impedance, Z, to make sure V has the only tight margin for driving I. In addition, the novel stimulation method based on the silicon neuron cell (SNC) is proposed to mimic behaviors of a real-neuron cell. Due to the SNC artificial neuron model, the proposed stimulator can mimic 4 different types of neural spikes with 10uW power consumption.
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http://dx.doi.org/10.1109/EMBC.2018.8513285DOI Listing
July 2018

Changes in Stromal and Luminal Areas of the Choroid in Pachychoroid Diseases: Insights Into the Pathophysiology of Pachychoroid Diseases.

Invest Ophthalmol Vis Sci 2018 10;59(12):4896-4908

Department of Ophthalmology, Konkuk University School of Medicine, Konkuk University Medical Center, Seoul, Republic of Korea.

Purpose: To evaluate and compare changes in choroidal vascular and stromal areas in patients with three major pachychoroid diseases for better insight into the pathophysiology of these diseases.

Methods: Eighty-six eyes of 86 patients (50 men and 36 women; mean age, 49.1 years) were evaluated, including 21 patients with chronic central serous chorioretinopathy (CSC), 14 with pachychoroid pigment epitheliopathy (PPE), 19 with pachychoroid neovasculopathy (PNV), 14 with myopic choroidal neovascularization (mCNV), and 18 controls. Multimodal retinal imaging, including enhanced-depth imaging optical coherence tomography (EDI-OCT), was performed. Each EDI-OCT image was binarized with ImageJ software, and luminal (dark pixels) and stromal (light pixels) areas were calculated (3000 μm wide in the subfoveal choroid centered on the fovea).

Results: The subfoveal choroidal thickness (SFCT) was greater in the three pachychoroid groups than in the control group (430.01 vs. 282.61 μm, P < 0.001). There was no significant difference in SFCT among the three pachychoroid groups. The luminal-to-total choroidal ratio (L/C) was highest (ANOVA, P = 0.001) and the stromal-to-total choroidal ratio (S/C) lowest in the CSC group (ANOVA, P = 0.001). Interestingly, stromal area changes were not correlated with SFCT in the CSC and PNV groups, in contrast to the good correlation between luminal area changes and SFCT in these groups.

Conclusions: The eyes of CSC patients had significantly smaller choroidal stromal areas than those of controls or of PPE, PNV, or mCNV patients. The differences in choroidal stromal area, L/C, and S/C in different pachychoroid diseases may reflect different predominant pathogenic processes.
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http://dx.doi.org/10.1167/iovs.18-25018DOI Listing
October 2018