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        Development of Magnetic Bearing System for a New Third‐Generation Blood Pump

        Lee, Jung Joo,Ahn, Chi Bum,Choi, Jaesoon,Park, Jun Woo,Song, Seung‐,Joon,Sun, Kyung Blackwell Publishing Inc 2011 Artificial Organs Vol.35 No.11

        <P><B>Abstract</B></P><P>A magnetic bearing system is a crucial component in a third‐generation blood pump, particularly when we consider aspects such as system durability and blood compatibility. Many factors such as efficiency, occupying volume, hemodynamic stability in the flow path, mechanical stability, and stiffness need to be considered for the use of a magnetic bearing system in a third‐generation blood pump, and a number of studies have been conducted to develop novel magnetic bearing design for better handling of these factors. In this study, we developed and evaluated a new magnetic bearing system having a motor for a new third‐generation blood pump. This magnetic bearing system consists of a magnetic levitation compartment and a brushless direct current (BLDC) motor compartment. The active‐control degree of freedom is one; this control is used for controlling the levitation in the axial direction. The levitation in the radial direction has a passive magnetic levitation structure. In order to improve the system efficiency, we separated the magnetic circuit for axial levitation by using a magnetic circuit for motor drive. Each magnetic circuit in the bearing system was designed to have a minimum gap by placing mechanical parts, such as the impeller blades, outside the circuit. A custom‐designed noncontact gap sensor was used for minimizing the system volume. We fabricated an experimental prototype of the proposed magnetic bearing system and evaluated its performance by a control system using the Matlab xPC Target system. The noncontact gap sensor was an eddy current gap sensor with an outer diameter of 2.38 mm, thickness of 0.88 mm, and resolution of 5 µm. The BLDC motor compartment was designed to have an outer diameter of 20 mm, length of 28.75 mm, and power of 4.5 W. It exhibited a torque of 8.6 mNm at 5000 rpm. The entire bearing system, including the motor and the sensor, had an outer diameter of 22 mm and a length of 97 mm. The prototype exhibited sufficient levitation performance in the stop state and the rotation state with a gap of 0.2 mm between the rotor and the stator. The system had a steady position error of 0.01 µm in the stop state and a position error of 0.02 µm at a rotational speed of 5000 rpm; the current consumption rates were 0.15 A and 0.17 A in the stop state and the rotation state, respectively. In summary, we developed and evaluated a unique magnetic bearing system with an integrated motor. We believe that our design will be an important basis for the further development of the design of an entire third‐generation blood pump system.</P>

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        Optimal Pressure Regulation of the Pneumatic Ventricular Assist Device With Bellows-Type Driver

        Lee, Jung Joo,Kim, Bum Soo,Choi, Jaesoon,Choi, Hyuk,Ahn, Chi Bum,Nam, Kyoung Won,Jeong, Gi Seok,Lim, Choon Hak,Son, Ho Sung,Sun, Kyung Blackwell Publishing Inc 2009 Artificial Organs Vol.33 No.8

        <P>Abstract</P><P>The bellows-type pneumatic ventricular assist device (VAD) generates pneumatic pressure with compression of bellows instead of using an air compressor. This VAD driver has a small volume that is suitable for portable devices. However, improper pneumatic pressure setup can not only cause a lack of adequate flow generation, but also cause durability problems. In this study, a pneumatic pressure regulation system for optimal operation of the bellows-type VAD has been developed. The optimal pneumatic pressure conditions according to various afterload conditions aiming for optimal flow rates were investigated, and an afterload estimation algorithm was developed. The developed regulation system, which consists of a pressure sensor and a two-way solenoid valve, estimates the current afterload and regulates the pneumatic pressure to the optimal point for the current afterload condition. Experiments were performed in a mock circulation system. The afterload estimation algorithm showed sufficient performance with the standard deviation of error, 8.8 mm Hg. The flow rate could be stably regulated with a developed system under various afterload conditions. The shortcoming of a bellows-type VAD could be handled with this simple pressure regulation system.</P>

      • A Mutation in <i>PMP2</i> Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy

        Hong, Young Bin,Joo, Jaesoon,Hyun, Young Se,Kwak, Geon,Choi, Yu-Ri,Yeo, Ha Kyung,Jwa, Dong Hwan,Kim, Eun Ja,Mo, Won Min,Nam, Soo Hyun,Kim, Sung Min,Yoo, Jeong Hyun,Koo, Heasoo,Park, Hwan Tae,Chung, Ki Public Library of Science 2016 PLoS genetics Vol.12 No.2

        <▼1><P>Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of peripheral neuropathies with diverse genetic causes. In this study, we identified p.I43N mutation in <I>PMP2</I> from a family exhibiting autosomal dominant demyelinating CMT neuropathy by whole exome sequencing and characterized the clinical features. The age at onset was the first to second decades and muscle atrophy started in the distal portion of the leg. Predominant fatty replacement in the anterior and lateral compartment was similar to that in CMT1A caused by <I>PMP22</I> duplication. Sural nerve biopsy showed onion bulbs and degenerating fibers with various myelin abnormalities. The relevance of <I>PMP2</I> mutation as a genetic cause of dominant CMT1 was assessed using transgenic mouse models. Transgenic mice expressing wild type or mutant (p.I43N) <I>PMP2</I> exhibited abnormal motor function. Electrophysiological data revealed that both mice had reduced motor nerve conduction velocities (MNCV). Electron microscopy revealed that demyelinating fibers and internodal lengths were shortened in both transgenic mice. These data imply that overexpression of wild type as well as mutant <I>PMP2</I> also causes the CMT1 phenotype, which has been documented in the <I>PMP22</I>. This report might expand the genetic and clinical features of CMT and a further mechanism study will enhance our understanding of <I>PMP2</I>-associated peripheral neuropathy.</P></▼1><▼2><P><B>Author Summary</B></P><P>Isolation of causative mutation is still challenging in genetic diseases with a variety of genetic causes. We discovered a mutation in a novel gene from a family exhibiting a peripheral neuropathy by virtue of next-generation sequencing. Although the family shows characteristic clinical features of hereditary motor and sensory neuropathy, we could not find a mutation from well-known genes. To demonstrate the clinical relevance of the novel gene, we generated transgenic mice, which carry the patients’ mutation within their chromosome. The transgenic mice exhibited the same phenotype as the patients including peripheral neuropathic symptoms and reduced locomotor function. We also observed the affected peripheral nervous system through electron microscopy. It seems that the expression of the mutant protein impairs the myelin of peripheral nervous system. These data might expand the genetic, clinical, and pathophysiological features of the peripheral neuropathy and a further investigation will enhance our understanding of disease in the peripheral nervous system.</P></▼2>

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        Sodium Alginate Hydrogel‐Based Bioprinting Using a Novel Multinozzle Bioprinting System

        Song, Seung‐,Joon,Choi, Jaesoon,Park, Yong‐,Doo,Hong, Soyoung,Lee, Jung Joo,Ahn, Chi Bum,Choi, Hyuk,Sun, Kyung Blackwell Publishing Inc 2011 Artificial Organs Vol.35 No.11

        <P><B>Abstract</B></P><P>Bioprinting is a technology for constructing bioartificial tissue or organs of complex three‐dimensional (3‐D) structure with high‐precision spatial shape forming ability in larger scale than conventional tissue engineering methods and simultaneous multiple components composition ability. It utilizes computer‐controlled 3‐D printer mechanism or solid free‐form fabrication technologies. In this study, sodium alginate hydrogel that can be utilized for large‐dimension tissue fabrication with its fast gelation property was studied regarding material‐specific printing technique and printing parameters using a multinozzle bioprinting system developed by the authors. A sodium alginate solution was prepared with a concentration of 1% (wt/vol), and 1% CaCl<SUB>2</SUB> solution was used as cross‐linker for the gelation. The two materials were loaded in each of two nozzles in the multinozzle bioprinting system that has a total of four nozzles of which the injection speed can be independently controlled. A 3‐D alginate structure was fabricated through layer‐by‐layer printing. Each layer was formed through two phases of printing, the first phase with the sodium alginate solution and the second phase with the calcium chloride solution, in identical printing pattern and speed condition. The target patterns were lattice shaped with 2‐mm spacing and two different line widths. The nozzle moving speed was 6.67 mm/s, and the injection head speed was 10 µm/s. For the two different line widths, two injection needles with inner diameters of 260 and 410 µm were used. The number of layers accumulated was five in this experiment. By varying the nozzle moving speed and the injection speed, various pattern widths could be achieved. The feasibility of sodium alginate hydrogel free‐form formation by alternate printing of alginate solution and sodium chloride solution was confirmed in the developed multinozzle bioprinting system.</P>

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        Overexpression of mutant HSP27 causes axonal neuropathy in mice

        Lee, Jinho,Jung, Sung-Chul,Joo, Jaesoon,Choi, Yu-Ri,Moon, Hyo Won,Kwak, Geon,Yeo, Ha Kyung,Lee, Ji-Su,Ahn, Hye-Jee,Jung, Namhee,Hwang, Sunhee,Rheey, Jingeun,Woo, So-Youn,Kim, Ji Yon,Hong, Young Bin,Ch BioMed Central 2015 JOURNAL OF BIOMEDICAL SCIENCE -BASEL- Vol.22 No.1

        <P><B>Background</B></P><P>Mutations in heat shock 27 kDa protein 1 (HSP27 or HSPB1) cause distal hereditary motor neuropathy (dHMN) or Charcot-Marie-Tooth disease type 2 F (CMT2F) according to unknown factors. Mutant HSP27 proteins affect axonal transport by reducing acetylated tubulin.</P><P><B>Results</B></P><P>We generated a transgenic mouse model overexpressing HSP27-S135F mutant protein driven by Cytomegalovirus (CMV) immediate early promoter. The mouse phenotype was similar to dHMN patients in that they exhibit motor neuropathy. To determine the phenotypic aberration of transgenic mice, behavior test, magnetic resonance imaging (MRI), electrophysiological study, and pathology were performed. Rotarod test showed that founder mice exhibited lowered motor performance. MRI also revealed marked fatty infiltration in the anterior and posterior compartments at calf level. Electrophysiologically, compound muscle action potential (CMAP) but not motor nerve conduction velocity (MNCV) was reduced in the transgenic mice. Toluidine staining with semi-thin section of sciatic nerve showed the ratio of large myelinated axon fiber was reduced, which might cause reduced locomotion in the transgenic mice. Electron microscopy also revealed abundant aberrant myelination. Immunohistochemically, neuronal dysfunctions included elevated level of phosphorylated neurofilament and reduced level of acetylated tubulin in the sural nerve of transgenic mice. There was no additional phenotype besides motor neuronal defects.</P><P><B>Conclusions</B></P><P>Overexpression of HSP27-S135F protein causes peripheral neuropathy. The mouse model can be applied to future development of therapeutic strategies for dHMN or CMT2F.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1186/s12929-015-0154-y) contains supplementary material, which is available to authorized users.</P>

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        A Three‐Dimensional Bioprinting System for Use With a Hydrogel‐Based Biomaterial and Printing Parameter Characterization

        Song, Seung‐,Joon,Choi, Jaesoon,Park, Yong‐,Doo,Lee, Jung‐,Joo,Hong, So Young,Sun, Kyung Blackwell Publishing Inc 2010 Artificial Organs Vol.34 No.11

        <P><B>Abstract</B></P><P>Bioprinting is an emerging technology for constructing tissue or bioartificial organs with complex three‐dimensional (3D) structures. It provides high‐precision spatial shape forming ability on a larger scale than conventional tissue engineering methods, and simultaneous multiple components composition ability. Bioprinting utilizes a computer‐controlled 3D printer mechanism for 3D biological structure construction. To implement minimal pattern width in a hydrogel‐based bioprinting system, a study on printing characteristics was performed by varying printer control parameters. The experimental results showed that printing pattern width depends on associated printer control parameters such as printing flow rate, nozzle diameter, and nozzle velocity. The system under development showed acceptable feasibility of potential use for accurate printing pattern implementation in tissue engineering applications and is another example of novel techniques for regenerative medicine based on computer‐aided biofabrication system.</P>

      • Association of <i>Interferon Gamma</i> Polymorphism with Ossification of the Posterior Longitudinal Ligament in the Korean Population

        Kim, Ki Tack,Kim, Dong Hwan,Chung, Jun-Young,Lee, Soojeong,Joo, Jaesoon,Nah, Seong-Su,Song, Ho-Yeon,Kim, Hak-Jae Informa Healthcare 2012 Immunological investigations Vol.41 No.8

        <P>In this study, we investigated whether genetic polymorphisms of the interferon gamma (<I>IFNG)</I> gene were associated with the susceptibility of ossification of the posterior longitudinal ligament (OPLL) in the Korean population. To observe the association between the <I>IFNG</I> gene and the susceptibility of OPLL, we genotyped 135 OPLL patients and 222 control subjects for a single nucleotide polymorphism (SNP, rs2430561) and a microsatellite (CA<SUB>n</SUB> repeats, rs3138557) located in the first intron of the <I>IFNG</I> gene, using the direct sequencing and gene scan method. The numbers of microsatellites (CA<SUB>13</SUB> and CA<SUB>15</SUB>) were significantly changed in the OPLL patients. A combined analysis of the genotype of rs2430561 and the number of microsatellites revealed that the OPLL was associated with frequencies of CA<SUB>13</SUB>-AA, CA<SUB>15</SUB>-AA and CA<SUB>15</SUB>-AT. Our results suggest that the <I>IFNG</I> gene may be one of the factors determining the OPLL in the Korean population. However, larger collaborative and biological studies are needed to confirm these results.</P>

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        A Durability Study of a Paracorporeal Pulsatile Electro‐Mechanical Pneumatic Biventricular Assist Device

        Choi, Hyuk,Lee, Heung‐,Man,Nam, Kyoung Won,Choi, Jaesoon,Lee, Jung‐,Joo,Kim, Ho Chul,Song, Seung Joon,Ahn, Chi Bum,Son, Ho Sung,Lim, Choon Hak,Son, Kuk Hui,Park, Yong Doo,Jeong, Gi Seok,Su Blackwell Publishing Inc 2011 Artificial Organs Vol.35 No.6

        <P><B>Abstract</B></P><P>In 2002, the paracorporeal pulsatile electro‐mechanical pneumatic ventricular assist device (VAD) began to be developed by the Korea Artificial Organ Center at Korea University under a Health & Medical Technology Research and Development program which finished in 2008. In vitro durability testing was conducted on the paracorporeal pulsatile pneumatic VAD to determine device durability and to evaluate device failures. The 1‐ and 2‐year reliability of the paracorporeal pulsatile pneumatic VAD was shown to be 91.2% and 54.9%, respectively, with an 80% confidence level. Failure modes were analyzed using fault tree analysis, with customized software continuously acquiring data during the test period. After this period, 21 in vivo animal tests were done, with 14 cases of left atrium to left ventricle (LV) inflow cannulation (36Fr)/outflow grafting to descending aorta, and seven cases of apex cannulation of LV to descending aorta (12 mm). The longest postoperative day (182 days) in Korea was recently recorded in in vivo animal testing (bovine, 90 kg, male, 3.5–4.0 L/min flow rate, and 55 bpm).</P>

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