Coiled-coil structure-dependent interactions between polyQ proteins and Foxo lead to dendrite pathology and behavioral defects

Kwon, Min Jee,Han, Myeong Hoon,Bagley, Joshua A.,Hyeon, Do Young,Ko, Byung Su,Lee, Yun Mi,Cha, In Jun,Kim, Seung Yeol,Kim, Dong Young,Kim, Ho Min,Hwang, Daehee,Lee, Sung Bae,Jan, Yuh Nung National Academy of Sciences 2018 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.115 No.45

<P><B>Significance</B></P><P>It remains unclear how the structural properties of polyglutamine (polyQ) proteins, which underlie several neurodegenerative disorders, including Huntington’s disease and spinocerebellar ataxias (SCAs), translate into the toxicity of these proteins. Here, we demonstrate that coiled-coil structures in expanded polyQ regions of SCA type 3 (SCA3) proteins cause dendrite defects in <I>Drosophila</I> neurons, as well as behavioral abnormalities. Moreover, interactions of SCA3 with Foxo mediated by coiled-coil domains of these two proteins resulted in functional impairment of this transcription factor, whereas its overexpression significantly rescued the SCA3-induced defects. Our study expanded the current understanding of neuronal pathology mediated by polyQ proteins via the coiled-coil–mediated interactions. These results may have important implications in therapeutic strategies for polyQ protein-related diseases.</P><P>Neurodegenerative disorders, such as Huntington’s diseases and spinocerebellar ataxias (SCAs), are driven by proteins with expanded polyglutamine (polyQ) tracts. Recently, coiled-coil structures in polyQ regions of such proteins were shown to facilitate aggregate formation and ultimately lead to cell death. However, the molecular mechanism linking these structural domains to neuronal toxicity of polyQ proteins remains elusive. Here, we demonstrate that coiled-coil structures in the Q repeat region of SCA type 3 (SCA3) polyQ proteins confer protein toxicity in <I>Drosophila</I> neurons. To functionally characterize coiled-coil structures in the Q repeat regions, we generated three structural variants of SCA3 polyQ proteins: (<I>i</I>) MJDtr-76Q, containing both α-helical coiled-coil and β-sheet hairpin structures in the Q repeat region; (<I>ii</I>) MJDtr-70Q_cc0, possessing only α-helical coiled-coil structures due to the incorporation of β-sheet–breaking residues (Q-to-N or Q-to-E mutations); and (<I>iii</I>) MJDtr-70Q_pQp, with no secondary structure due to the introduced proline residues (Q-to-P mutations). Through comparative analysis of these variants, we found that coiled-coil structures facilitated nuclear localization of SCA3 polyQ proteins and induced dendrite defects in <I>Drosophila</I> dendritic arborization neurons. Furthermore, genetic and functional screening identified the transcription factor Foxo as a target of polyQ proteins, and coiled-coil–mediated interactions of Foxo and polyQ proteins in the nucleus resulted in the observed dendrite and behavioral defects in <I>Drosophila</I>. These results demonstrate that coiled-coil structures of polyQ proteins are crucial for their neuronal toxicity, which is conferred through coiled-coil to coiled-coil interactions with the nuclear targets of these proteins.</P>

Coil Gun Electromagnetic Launcher (EML) System with Multi-stage Electromagnetic Coils

Su-Jeong Lee,Ji-Hun Kim,Bong Sob Song,Jin Ho Kim 한국자기학회 2013 Journal of Magnetics Vol.18 No.4

An electromagnetic launcher (EML) system accelerates and launches a projectile by converting electric energy into kinetic energy. There are two types of EML systems under development: the rail gun and the coil gun. A railgun comprises a pair of parallel conducting rails, along which a sliding armature is accelerated by the electromagnetic effects of a current that flows down one rail, into the armature and then back along the other rail, but the high mechanical friction between the projectile and the rail can damage the projectile. A coil gun launches the projectile by the attractive magnetic force of the electromagnetic coil. A higher projectile muzzle velocity needs multiple stages of electromagnetic coils, which makes the coil gun EML system longer. As a result, the installation cost of a coil gun EML system is very high due to the large installation site needed for the EML. We present a coil gun EML system that has a new structure and arrangement for multiple electromagnetic coils to reduce the length of the system. A mathematical model of the proposed coil gun EML system is developed in order to calculate the magnetic field and forces, and to simulate the muzzle velocity of a projectile by driving and switching the electric current into multiple stages of electromagnetic coils. Using the proposed design, the length of the coil gun EML system is shortened by 31% compared with a conventional coil gun system while satisfying a target projectile muzzle velocity of over 100 m/s.

Four Stage Induction Coilgun System Design and Analytical Calculation of Electromagnetic Expansion Force on the Stator Coil in the System

Hui Min Kim,Yong Kyu Lee,Meung Geun Song 한국자기학회 2023 Journal of Magnetics Vol.28 No.3

The solenoid coil is one of the most important design component for electromagnetic induction type coil gun system. When the voltage and current are applied across the coil, a uniform magnetic field is generated inside the coil and that is proportional to the number of coil windings, and the high-density magnetic field generated by the coil can be converted to mechanical energy by applying the strong electromagnetic force to a ferromagnetic material. At this time, the interaction between the current and magnetic field of the solenoid coil generates a strong electromagnetic expansive force between each coil wire. In this paper, we introduced a four-stage induction coil gun as the launcher system using high voltage pulsed power source. Also, we proposed both the method and formula to calculate the electromagnetic expansion force acting on the multi-winding layer solenoid coil gun by using energy transfer equations. When the current flows a solenoid coil, the expansion force is generated in the radial direction of the coil. The mathematical calculation results were verified by simulated ones.

거리조절 가능한 두부 수신 코일의 유용성 평가

강인한,이호범,장지성,양선욱,서대건 대한자기공명기술학회 2019 대한자기공명기술학회지 Vol.29 No.2

Purpose:When inspecting MRI, A variety of efficient receiving coils are being developed as the importance of collecting high signal intensity by receiving coils gradually increases. This means that the receiving coil is made light and flexible, or that distance between the receiving coil and the human surface can be adjusted. Therefore, it is possible to collect high signals by keeping as close as possible to the examination areas of patients of various sizes of shapes. Thus, the purpose of this study was to compare the signal intensity with the distance between the receiving coil and the phantom by adjusting the distance control developed in consideration of the various patients and to find the actual clinical efficiency compared to the existing coil. Materials and Methods:In order to measure the signal intensity according to the distance variation between the receiving coil and the surface of inspection area, two cylindrical fluid phantom with same component and only different size were used. And the phantom images were acquired by increasing the distance between the receiving coil and the phantoms by 1cm from 0cm to 3cm. At this point, the ARC acceleration factor was applied up to 1-3 for each distance to measure the change in signal intensity according to the application of PI technique when the distance of the receiving coil and inspection area is varied. Standard T1 and T2 images were obtained using a 3.0T MRI and 48-channel head coil. Using acquired images, signal and noise data were obtained using subtraction methods according to the NEMA specification. And signal intensity of images was measured using the image evaluation program(Image J). The measured signal intensity was evaluated by comparing the variation in signal intensity with using one-way ANOVA and Duncan’s post hoc. Results:As a result, both in large and small phantoms, The closer the distance, the lower the AF of the PI technique, the greater the SNR and the farther the distance, the higher the AF, the lower the SNR in All phantoms. According to the ANOVA and Duncan’s post hoc test, there were no significant difference at 0cm, AF 1 which meant they showed almost identical signal intensities(p<0.05) in Large phantom but In Small phantoms, all groups had statistically significant differences from the maximum SNR. Conclusion:When using distance-controlled head-only coils, there was no statistical difference in the strength of the SNR when the distance was not increased within a certain distance without the use of PI techniques. Therefore, it is believed that MRI images with high quality SNRs can be obtained if the patient's physique is large or if the distance needs to be increased due to the use of medical devices. 목 적:자기공명영상 검사 시, 수신 코일에 의한 높은 신호강도 수집의 중요성이 점차 증대됨에 따라 다양하고 효율적인 수신 코일들이 개발되는 추세다. 즉, 수신 코일을 가볍고 유연하게 제작하거나 수신 코일과 인체 표면 간 거리조절이 가능하게 설계하여 다양한 크기나 모양을 가진 환자의 검사 부위에 최대한 밀착시켜 높은 신호를 수집할 수 있게 되었다. 따라서 본 연구에서는 다양한 환자를 고려하여 개발된 거리조절이 가능한 두부 수신 코일의 거리를 조절하여 수신 코일과 팬텀의 거리에 따른 신호강도를 비교하여 기존 코일과 비교해 실제 임상에서의 효율성을 알아보고자 하였다. 대상 및 방법:연구방법은, 수신 코일과 검사 부위 간 거리변화에 따른 신호강도를 측정하기 위해 성분은 같고 크기만 다른 2개의 원통형 팬텀을 사용하였으며, 수신 코일과 검사 부위 간 거리를 0cm부터 3cm까지 1cm씩 거리를 늘려 팬텀 영상을 획득하였다. 이때, 거리마다 ARC 가속 인자를 1-3까지 적용하여 수신 코일과 검사 부위의 거리변화 시, PI 기법 적용에 따른 신호 강도의 변화를 비교 측정하였다. 영상획득은 3.0T 초전도 자기공명영상장치와 48채널 Head Coil을 사용하여병렬 영상기법을 적용한 표준 T1, T2 강조 영상을 획득하였고, 획득한 영상으로 NEMA 규격에 따른 감산 방법을 사용하여 신호와 잡음 데이터를 얻어 영상평가프로그램을 이용하여 영상의 신호강도를 측정하였다. 측정된 신호강도는 일원배치분산 분석과 사후분석을 이용하여 신호강도의 변화에 유의한 차이가 있는지 비교 평가하였다. 결 과:연구결과, Large phantom과 Small phantom 모두 T2, T1 강조영상에서 거리가 가까울수록, PI 기법의 AF가 낮을수록 SNR이 증가했고 거리가 멀수록, AF가 높아질수록 SNR이 감소했다. 통계적 유의성을 알아보기 위해 일원배치분산분석과 Duncan의 사후분석을 시행한 결과 유의수준 0.05에 대한 부 집단 중 Large phantom에서는 AF 1일 때 1, 2cm에서 통계적으로 최대 SNR을 나타내는 0cm, AF 1과 유의한 차이가 없었다. 반면 Small phantom에서는 모든 그룹이최대 SNR과 통계적으로 유의한 차이가 있었다. 결 론:거리조절 두부 전용 코일을 사용할 경우 PI 기법을 사용하지 않는 일정 거리 내에서는 거리를 늘리지 않았을 때와 SNR의 강도에 통계적 차이가 없었다. 따라서 환자의 체격이 크거나 의료기구의 사용 등으로 거리를 증가시켜야 하는 경우 환자에게 불편함을 주지 않고 양질의 SNR을 가진 MRI 영상을 얻을 수 있을 것이라고 사료 된다.

소아에서의 Coil 색전술의 임상체험

유정진,이재영,천은정,허준,김연우,김호성,노정일,최정연,윤용수 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.5

A Review on the RF Coil Designs and Trends for Ultra High Field Magnetic Resonance Imaging

Jose Daniel Hernandez Chang,김경남 대한자기공명의과학회 2020 Investigative Magnetic Resonance Imaging Vol.24 No.3

In this article, we evaluated the performance of radiofrequency (RF) coils in terms of the signal-to-noise ratio (S/N) and homogeneity of magnetic resonance images when used for ultrahigh-frequency (UHF) 7T magnetic resonance imaging (MRI). Highquality MRI can be obtained when these two basic requirements are met. However, because of the dielectric effect, 7T magnetic resonance imaging still produces essentially a non-uniform magnetic flux (|B1|) density distribution. In general, heterogeneous and homogeneous RF coils may be designed using electromagnetic (EM) modeling. Heterogeneous coils, which are surface coils, are used in consideration of scalability in the |B1| region with a high S/N as multichannel loop coils rather than selecting a single loop. Loop coils are considered state of the art for their simplicity yet effective |B1|-field distribution and intensity. In addition, combining multiple loop coils allows phase arrays (PA). PA coils have gained great interest for use in receiving signals because of parallel imaging (PI) techniques, such as sensitivity encoding (SENSE) and generalized autocalibrating partial parallel acquisition (GRAPPA), which drastically reduce the acquisition time. With the introduction of a parallel transmit coil (pTx) system, a form of transceiver loop arrays has also been proposed. In this article, we discussed the applications and proposed designs of loop coils. RF homogeneous coils for volume imaging include Alderman-Grant resonators, birdcage coils, saddle coils, traveling wave coils, transmission line arrays, composite right-/left-handed arrays, and fusion coils. In this article, we also discussed the basic operation, design, and applications of these coils.

다단 코일건의 성능향상을 위한 솔레노이드 코일 및 캐패시터 설계

김선명,김진호 한국정밀공학회 2022 한국정밀공학회지 Vol.39 No.8

The purpose of this study was to design capacitors and a coil, which are components of an electric circuit, for improved performance of multi-stage electromagnetic coil guns. The electromagnetic force generated in the solenoid coil isdetermined by the magnitude of the current, supplied from the capacitor to the solenoid coil. Since the current flowing in the solenoid coil is not constant, the variability of electromagnetic force becomes larger. Design variables such as the capacitor capacity, coil winding, and firing distance are complicatedly related and determine the coil gun firing rate together. This study sets the number of turns of the solenoid coil, capacitor capacity, and firing distance as design variables for a five-stage coil gun. The electric circuit configuration of the coil gun with the highest velocity in each firing stage, was derived through the design of experiments. The coil gun’s finite element analysis model was constructed using ANSYS Maxwell, an electromagnetic analysis program, and implemented through a transient simulation to calculate the projectile’s velocity. Additionally, a prototype was manufactured based on the derived results to conduct launch experiments, and the experimental and simulation results were compared.

In Vitro Head-to-Head Comparison of Flow Reduction between Fibered and Non-Fibered Pushable Coils

Yoon Jong-Tae,Kwon Boseong,Choi Joon Ho,Hwang Sun Moon,Kim Mihyeon,Hwang Sungbin,Song Yunsun,Lee Deok Hee 대한신경중재치료의학회 2024 Neurointervention Vol.19 No.1

Purpose: To compare the embolization effects of a non-fibered pushable coil with a conventional fibered pushable coil in an <i>in vitro</i> bench-top experiment.Materials and Methods: A simplified vascular phantom with 4 channels (1 for the non-fibered coil, 1 for the fibered coil, and 2 for continuous circuit flow) was used. A single coil of the longest length was inserted to evaluate the effect of single-coil embolization, and 3 consecutive coils were inserted to assess the effect of multiple-coil embolization. Post-embolization angiography was performed to obtain flow variables (time to peak [TTP], relative peak intensity [rPI], and angiographic flow reduction score [AFRS]) from time density curves. The packing densities of the two coil types were calculated, and the AFRS of each channel was determined by dividing the TTP by the rPI.Results: When inserting a single coil, the conventional fibered coil demonstrated better flow reduction, as indicated by a higher AFRS (25.6 vs. 17.4, P=0.034). However, the non-fibered coil exhibited a significantly higher packing density (12.9 vs. 2.4, P=0.001). Similar trends were observed with multiple coils.Conclusion: The conventional fibered pushable coil showed better flow reduction efficiency, while the non-fibered pushable coil had a higher packing density, likely due to the flexibility of the coil loops. A better understanding of the distinct characteristics of different pushable coils can enhance the outcomes of various vascular embolization.

A Review on the RF Coil Designs and Trends for Ultra High Field Magnetic Resonance Imaging

Hernandez, Daniel,Kim, Kyoung-Nam Korean Society of Magnetic Resonance in Medicine 2020 Investigative Magnetic Resonance Imaging Vol.24 No.3

In this article, we evaluated the performance of radiofrequency (RF) coils in terms of the signal-to-noise ratio (S/N) and homogeneity of magnetic resonance images when used for ultrahigh-frequency (UHF) 7T magnetic resonance imaging (MRI). High-quality MRI can be obtained when these two basic requirements are met. However, because of the dielectric effect, 7T magnetic resonance imaging still produces essentially a non-uniform magnetic flux (|B₁|) density distribution. In general, heterogeneous and homogeneous RF coils may be designed using electromagnetic (EM) modeling. Heterogeneous coils, which are surface coils, are used in consideration of scalability in the |B₁| region with a high S/N as multichannel loop coils rather than selecting a single loop. Loop coils are considered state of the art for their simplicity yet effective |B₁|-field distribution and intensity. In addition, combining multiple loop coils allows phase arrays (PA). PA coils have gained great interest for use in receiving signals because of parallel imaging (PI) techniques, such as sensitivity encoding (SENSE) and generalized autocalibrating partial parallel acquisition (GRAPPA), which drastically reduce the acquisition time. With the introduction of a parallel transmit coil (pTx) system, a form of transceiver loop arrays has also been proposed. In this article, we discussed the applications and proposed designs of loop coils. RF homogeneous coils for volume imaging include Alderman-Grant resonators, birdcage coils, saddle coils, traveling wave coils, transmission line arrays, composite right-/left-handed arrays, and fusion coils. In this article, we also discussed the basic operation, design, and applications of these coils.

6채널 SENSE Cardiac Array 코일을 이용한 검사 시 코일의 위치 변화에 따른 신호강도

최관우(Kwan-Woo Choi),손순룡(Soon-Yong Son),유병규(Beong-Gyu Yoo) 한국방사선학회 2018 한국방사선학회 논문지 Vol.12 No.5

본 연구는 array 코일을 이용한 검사 시 코일의 위치변화에 따른 신호강도를 측정하여 영상의 신호강도가 급격히 저하되지 않는 기준 방향과 거리를 제시함으로써, 동일선상에 코일들이 위치하지 않았을 경우 신호강도가 저하되는 문제점을 개선해 보고자 하였다. 연구방법은 두 부분으로 나눠져 있는 array 코일에 multi-purpose MRI 팬텀을 위치시킨 다음 array 코일의 앞부분을 상, 하, 좌, 우 네 방향으로 중심에서 2 cm 씩 10 cm 까지 이동하며 영상을 획득한 후 신호강도를 측정하여 비교평가 하였다. 연구결과, T1, T2 강조 영상 모두 상 방향을 제외한 하 방향과 좌, 우 방향의 위치변화가 2 cm 이내인 경우 기준 신호강도인 중심의 신호강도와 유의한 차이가 없어 동일한 신호강도를 나타냄을 알 수 있었다. 결론적으로 array 코일을 이용한 검사 시 여러 가지 원인에 의해 동일선상에 코일들을 위치시킬 수 없을 경우 상 방향을 제외한 나머지 방향의 위치변화를 중심에서 2 cm 이내로 설정한다면 위치변화로 인해 신호강도가 저하되는 문제점을 개선할 수 있다. In this study, we measured signal intensities according to array coil position changes to provide reference data of coil directions and the distances as it deters image quality unless the coils are aligned properly. The multi-purpose MRI phantom was placed in body array coils, and it was moved to the top, bottom, left, and right directions by 2 cm from the center to 10 cm. After obtaining images, signal intensities were measured and compared. The results of this study were as follows: Except for the upward direction, the signal intensities of the reference signal was not significantly different from that of the reference signal intensity within 2cm in both T1 and T2-weighted images. In conclusion, in clinical circumstances which various challenges exist to align the coils exactly on the same lines, array coils should be positioned at least within 2 cm from the center except for the upward direction, on the same line to prevent the image qualities are lowered.