Magnetoencephalography

This is a practical book on MEG that covers a wide range of topics. The book begins with a series of reviews on the use of MEG for clinical applications, the study of cognitive functions in various diseases, and one chapter focusing specifically on studies of memory with MEG. There are sections with chapters that describe source localization issues, the use of beamformers and dipole source methods, as well as phase-based analyses, and a step-by-step guide to using dipoles for epilepsy spike analyses. The book ends with a section describing new innovations in MEG systems, namely an on-line real-time MEG data acquisition system, novel applications for MEG research, and a proposal for a helium re-circulation system. With such breadth of topics, there will be a chapter that is of interest to every MEG researcher or clinician

Laser-induced forward transfer (LIFT) of water soluble polyvinyl alcohol (PVA) polymers for use as support material for 3D-printed structures

The additive microfabrication method of laser-induced forward transfer (LIFT) permits the creation of functional microstructures with feature sizes down to below a micrometre [1]. Compared to other additive manufacturing techniques, LIFT can be used to deposit a broad range of materials in a contactless fashion. LIFT features the possibility of building out of plane features, but is currently limited to 2D or 2½D structures [2–4]. That is because printing of 3D structures requires sophisticated printing strategies, such as mechanical support structures and post-processing, as the material to be printed is in the liquid phase. Therefore, we propose the use of water-soluble materials as a support (and sacrificial) material, which can be easily removed after printing, by submerging the printed structure in water, without exposing the sample to more aggressive solvents or sintering treatments. Here, we present studies on LIFT printing of polyvinyl alcohol (PVA) polymer thin films via a picosecond pulsed laser source. Glass carriers are coated with a solution of PVA (donor) and brought into proximity to a receiver substrate (glass, silicon) once dried. Focussing of a laser pulse with a beam radius of 2 µm at the interface of carrier and donor leads to the ejection of a small volume of PVA that is being deposited on a receiver substrate. The effect of laser pulse fluence , donor film thickness and receiver material on the morphology (shape and size) of the deposits are studied. Adhesion of the deposits on the receiver is verified via deposition on various receiver materials and via a tape test. The solubility of PVA after laser irradiation is confirmed via dissolution in de-ionised water. In our study, the feasibility of the concept of printing PVA with the help of LIFT is demonstrated. The transfer process maintains the ability of water solubility of the deposits allowing the use as support material in LIFT printing of complex 3D structures. Future studies will investigate the compatibility (i.e. adhesion) of PVA with relevant donor materials, such as metals and functional polymers. References: [1] A. Piqué and P. Serra (2018) Laser Printing of Functional Materials. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA. [2] R. C. Y. Auyeung, H. Kim, A. J. Birnbaum, M. Zalalutdinov, S. A. Mathews, and A. Piqué (2009) Laser decal transfer of freestanding microcantilevers and microbridges, Appl. Phys. A, vol. 97, no. 3, pp. 513–519. [3] C. W. Visser, R. Pohl, C. Sun, G.-W. Römer, B. Huis in ‘t Veld, and D. Lohse (2015) Toward 3D Printing of Pure Metals by Laser-Induced Forward Transfer, Adv. Mater., vol. 27, no. 27, pp. 4087–4092. [4] J. Luo et al. (2017) Printing Functional 3D Microdevices by Laser-Induced Forward Transfer, Small, vol. 13, no. 9, p. 1602553

고출력 양성자 입사기에서 저에너지 빔 수송 향상에 관한 연구

학위논문(박사) -- 서울대학교대학원 : 공과대학 에너지시스템공학부, 2021.8. 김동환.A proton injector is the key element of a high current beam and high-performance fast neutron sources for basic science and future energy resources. The proton injector in the study transports a high-current and low-energy proton beam with minimum loss and makes the beam parameters matched to a subsequent accelerator such as radio-frequency quadrupole. A high-current proton beam contains strong space charge effect and non-linear electric field, increasing beam size and emittance during transport. To reduce the beam size, solenoid focusing lens is used, which rather causes spherical aberration and another emittance growth. In addition, the presence of such an electromagnetic element gives rise to alignment error. Solenoid magnet makes it difficult to control a position of beam centroid since it has characteristics of rotating and coupling the beam in the transverse plane. This study has established a proton injector test stand and introduced novel techniques to improve the low energy beam transport in a high-intensity proton injector. Proton injector test stand includes transverse beam profile monitor, which is composed of a scintillation screen and a CCD camera, to measure the position, size, and emittance of the beam. Two key factors for improving low-energy beam transport are low beam emittance and a fast and accurate beam tuning method. For this purpose, a residual gas molecule analysis method and an artificial neural network (ANN) model are introduced. As a first result, low beam emittance was measured by preventing beam emittance from growing through an inert gas injection technique based on numerical analysis on steady-state pressure in high vacuum condition. A space charge potential increases beam emittance, not preserving the intrinsic emittance at the beam extraction region. One of the natural processes to cancel space charge force is that proton beam collides with residual gases mainly composed of hydrogen molecules flowing out of ion source and air molecules, causing some ionization. It is a self-neutralization that the generated electrons are trapped in the space charge potential of the beam. It is known to be more effective as the number of residual gas molecules in the transport pipe increases and the heavier inert gas molecules are involved since they generally have larger collisional cross-section. Suppression of emittance growth is achieved and beam emittance is decreased up to 23% through the residual gas injection. Artificial neural network (ANN) model can greatly reduce time and increase accuracy in low energy beam tuning. There are unknowns such as alignment errors that are difficult to measure between elements involved in the beam transport process, such as beam extraction, focusing, and deflection. To correct for these errors, steering magnets control the beam centroid in the transverse plane. In order to optimize the beam transport, it is necessary to observe the change of beam centroid and size for various magnet settings. Multi-layer perceptron model is utilized to interpret this nonlinear relationship and to control the beam properly based on the measured data. Extensive beam dynamics simulations are performed to verify the efficient training and the practicality of the predictive model. The output results of calculating the beam size and beam position at a specific location are obtained according to various sources of errors and unknowns that may occur in the LEBT. It is confirmed that the predictive model with high accuracy can be derived from sufficient measurement data, and it is applied to actual beam diagnosis and beam control experiments. The ANN model developed in this study shows more accurate prediction at a speed 49 times faster than the existing scan method. This study contributed to the suppression of the beam emittance growth and the development of a fast and accurate beam transport control technique in high intensity proton injector. This can be applied to the evaluation and improvement of beam emittance in beamlines under various conditions by increasing the utility of beam diagnostic data. In addition, there is a possibility to greatly improve beam tuning efficiency to higher energy sections and beamlines that have more control variables and are more complex than low-energy beam transport systems. Ultimately, the study can be developed as a base technology for autonomous operation of accelerator with minimum human intervention.고출력 양성자 가속기는 잘 정립된 기술과 연속 운전성을 기반으로 하여 고성능 고속 중성자원 개발에 주로 응용된다. 그 중에서 양성자 입사기는 높은 전류의 빔을 얻기 위한 중요한 기반이다. 이 장치는 이온원에서 형성된 초기 빔을 최소한의 손실로 수송하고, 고주파 사중극과 같은 후속 가속관이 요구하는 입력 빔 파라미터를 정합시키는 역할을 수행한다. 고전류 빔은 비선형적인 전기장 성분을 포함하여 강한 공간 전하 효과를 일으키기 때문에, 수송 과정에서 빔 크기와 에미턴스가 상승하는 문제가 있다. 빔 크기를 줄이기 위해 솔레노이드 집속 렌즈를 이용하는데, 이는 오히려 구면 수차를 일으키며 에미턴스를 보존시키지 못한다. 그리고 전자석과 같은 빔 수송 요소는 수송관의 정렬 오차를 일으킨다. 특히, 솔레노이드 전자석은 빔을 횡방향으로 회전시키는 특성이 있기 때문에 정렬 오차와 더불어 빔 중심 위치 제어를 더욱 어렵게 만든다. 이 연구는 고출력 양성자 입사기의 저에너지 빔 수송 성능 향상을 위한 기법 개발을 목표로 하고, 입사기 시험 시설을 구축한다. 성능 개선을 실험적으로 확인하기 위해 섬광판과 CCD 카메라를 이용한 빔 프로파일 모니터를 주요 진단 장치로 이용한다. 저에너지 빔 수송 성능의 핵심 요소 두 가지는 낮은 빔 에미턴스와 빠르고 정확한 빔 튜닝 방법이다. 이를 위해 잔류 분자 해석 방법과 기계 학습 기법을 각각 도입한다. 첫 번째 결과로, 잔류 분자 해석을 기반으로 한 비활성 기체 주입 기법을 통해 빔 에미턴스 성장을 막아 낮은 빔 에미턴스를 측정한다. 고전류 빔의 높은 공간 전하 포텐셜은 빔이 진행함에 따라 빔 에미턴스를 상승시키는 문제가 있다. 이를 상쇄시키는 자연스러운 과정 중 하나는, 양성자 입사기의 경우 수소 이온원에서 흘러나온 수소 분자와, 미량으로 유입되어 평형을 이루고 있는 공기 분자가 양성자 빔과 충돌하면서 일부 이온화가 진행되고, 발생된 전자가 빔의 공간 전하 퍼텐셜을 상쇄시키는 자기 중성화(self-neutralization)이다. 빔라인의 잔류 기체 분자의 밀도가 일정 수준일 때, 빔 손실 효과에 대비해 최적의 에미턴스 상승 억제 효과를 낼 수 있음을 실험적으로 확인한다. 3차원 잔류 분자 거동 해석을 통해 빔 수송관에서 수소 분자와 공기 분자의 부분 압력을 낮추고, 비활성 기체 분자의 부분 압력을 높이는 시나리오의 효과를 계산해보고, 실험에서 크립톤 가스 1.2 sccm 주입 시 최대 약 23%의 빔 에미턴스 개선 효과를 얻었다. 두 번째 결과로, 기계 학습 기법 중 인공 신경망 모형을 기반으로 빔 튜닝의 속도와 정확도를 개선하였다. 빔 인출, 집속, 그리고 편향과 같이 빔 수송 과정에 관여되는 요소들 사이에는 측정하기 어려운 정렬 오차 등의 미지수들이 존재한다. 이 오차를 보상해주기 위해 편향 전자석을 사용한다. 이 과정에서 빔 수송을 최적화하기 위해서 여러 전자석 설정 값에 대해 측정되는 빔의 변화 규칙을 관찰하고 그 자료들을 활용할 필요가 있다. 이러한 비선형적인 관계를 측정 자료를 기반으로 해석하기 위해 다층 퍼셉트론 모형을 이용한다. 먼저 예측 모형을 효율적으로 훈련시키고 그 실용성을 대해 검증하기 위해 빔 동역학 기반의 계산을 수행한다. 저에너지 빔 수송계에서 일어날 수 있는 여러 가지 오차 요인과 미지수들의 변화에 따라 특정 위치에서의 빔 크기와 빔 위치를 계산한 결과를 얻는다. 이를 바탕으로 충분한 측정 자료로부터 정확도가 높은 예측 모형을 도출할 수 있음을 확인하고, 실제 빔 진단과 빔 제어 실험에 적용한다. 본 연구에서 개발한 인공신경망 모형은 전자석 값을 일정 간격으로 건너뛰어 설정하며 빔 위치 변화를 측정하는 기존의 스캔 방법에 비해 49 배 이상 빠른 속도로 더 정확한 빔 튜닝 성능을 보인다. 본 연구는 고출력 양성자 입사기의 중요 성능 요소인 빔 에미턴스의 성장 억제와, 빠르고 정확한 빔 수송 제어 기법 개발에 기여하였다. 이것은 가속기 빔 동역학 연구에 빔진단 자료의 활용성을 높여 다양한 조건의 빔라인에서 빔 에미턴스 평가와 향상에 적용시킬 수 있다. 그리고 저에너지 빔 수송 계통보다 제어 변수가 더 많고 복잡한 고에너지 가속단과 빔라인에 확장 적용함으로써 빔 튜닝 효율성을 크게 개선할 가능성이 있다. 궁극적으로는 운전자의 개입을 최소화하는 가속기 자율 운전의 기반 기술로 발전시킬 수 있다.Chapter 1. Introduction 1 1.1. High Intensity Proton Injector 1 1.2. Applications of High Intensity Proton Injector 4 1.3. Previous Work and Research Motivation 11 1.4. Contribution and Scope of the Study 14 Chapter 2. Theoretical Background 18 2.1. Ion Source for High-Intensity Proton Injector 18 2.2. Beam Formation and Extraction 24 2.3. Beam Parameters and Beam Dynamics 27 2.4. Low Energy Beam Transport and Beam Matching 32 2.5. Beam Diagnostics for the Low Energy Beam 36 2.6. Machine Learning and its Application in Accelerator Control 40 Chapter 3. Experimental Setup of Proton Injector Test Stand 46 3.1. Microwave Ion Source and Beam Extraction System 46 3.2. Low Energy Beam Transport System 59 3.3. Low Energy Beam Diagnostics 69 Chapter 4. Beam Emittance Measurement and Mitigation of Emittance Growth 74 4.1. Space Charge Effect and Self-Neutralization 74 4.2. Numerical Analysis on Residual Gas Molecules 78 4.3. Transverse Beam Emittance Measurement with Solenoid Scan Method 85 4.4. Mitigation of Emittance Growth by Enhanced Self-Neutralization 92 Chapter 5. Tuning of the Beam Parameters by Artificial Neural Network Model 97 5.1. Beam Dynamics Simulations: Training Data Preparation 97 5.2. Artificial Neural Network Model for the Fast Beam tuning 101 5.3. Experimental Validation and Application on Beam Control Experiment 109 Chapter 6. Conclusion and Future Work 116 6.1. Conclusive Summary of the Study 116 6.2. Recommendations for Future Work 119 Bibliography 121 Abstract in Korean 129박

The effects of macrophage-stimulating protein and gamma synuclein on the development of brainstem motor systems

Disorders of motility are among the most common and debilitating neurological ailments. In most cases, treatment of these conditions is at best palliative. This is mainly due to the apparent inability of central neurons to regenerate after a given noxious event. In the past, embryos have proven to be valuable objects to study the mechanisms of growth and death in nerve cells since both are physiological events in the developing nervous system. The discovery and study of an ever-growing list of molecules that are involved in these events has significantly furthered our understanding of the conditions that have to be met for individual nerve cell populations to develop into functional structures. It also has the potential to contribute significantly to the establishment of more targeted and efficient therapeutic strategies.Here, the effects of macrophage-stimulating protein (MSP) and 7- synuclein on two systems in the developing brainstem involved in controlling movement have been studied: a) the cranial motoneurons and b) the dopaminergic neurons of the substantia nigra and the ventral tegmental area. MSP exerts a variety of biological actions on many cell types, but has no known functions in the brain. To investigate whether MSP is also capable of acting as a neurotrophic factor, hypoglossal motoneurons were purified from the embryonic chicken hindbrain because these neurons are known to express the MSP receptor tyrosine kinase RON. The study shows that MSP promotes the in vitro survival of these neurons during the period of naturally occurring neuronal cell death and enhances the growth of neurites from these neurons. Furthermore, MSP mRNA was detected in the developing tongue which is the XXI target tissue for hypoglossal neurons. These studies demonstrate that MSP is a neurotrophic factor for a distinct population of developing motoneurons.γ-synuclein is a recently discovered member of the synuclein family. Another member of this family, a-synuclein has been implicated in the pathogenesis of Parkinson's disease. However, little is known about the function of γ-synuclein and it has not yet been directly implicated in the genesis of neurodegenerative conditions. Here, brainstems of transgenic mice lacking γ-synuclein have been analysed by means of immunohistochemical and histological techniques. The data obtained shows that γ-synuclein is expressed in the murine substantia nigra and in most cranial motor nuclei and that the localization of the protein undergoes a shift during development from a cytosomal to an axonal and synaptic localization. Mice lacking γ-synuclein have a deficit of neurons in these structures. In the context of recent studies which have revealed in vivo and in vitro interactions between the synucleins, this data suggests that a fine balance between α- and γ-synuclein seems critical to prevent the demise of certain neurons during the period of naturally occurring neuronal cell death. It also indicates that γ-synuclein may play a role in the pathogenesis of Parkinson's diseas

Doctor of Philosophy

dissertationOptical methods are well-established in the fields of neuroscience, medical imaging, and diagnostics, etc. Optogenetics, for example, enables molecular specificity in optical neural stimulation and recording and has been named the "Method of the Year 2010" by Nature Methods. A novel microdevice was designed, fabricated, developed, and tested to facilitate three-dimensional (3D) deep-tissue light penetration with the capacity to accommodate spatiotemporal modulation of one or more wavelengths to advance a broad range of applications for optical neural interfaces. A 3D optrode array consisting of optically transparent "needles" can penetrate >1 mm directly into tissue, thereby creating multiple independent paths for light propagation that avoid attenuation due to tissue absorption and scattering, providing a high level of selectivity and comprehensive access to tissue not available in current interfaces. Arrays were developed based upon silicon and glass. The silicon optrode array is based upon the well-established Utah electrode array architectures and is suitable for near-infrared (NIR) applications; glass optrodes are appropriate waveguides for both visible and NIR wavelengths. Arrays were bulk-micromachined with high-aspect ratio, a process that has not been reported to be applied to glass previously. In addition to device fabrication, extensive laboratory testing was performed with various optical sources to determine loss mechanisms and emitted beam profiles in tissue across the relevant wavelength ranges, with particular focus on performance metrics for optogenetic and infrared neural stimulation applications. Optrode arrays were determined to be amenable to integration with typical neural stimulation and imaging light delivery mechanisms such as optical fibers and microscopes. Glass optrodes were able to transmit light at ~90% efficiency through depths many times greater than the tissue attenuation length, with negligible light in-coupling loss. Si optrodes were determined to be only ~40% efficient with losses mostly from high index contrast, tip backreflection, and taper radiation. The in-coupling technique and optrode geometry may be modified to produce illumination volumes appropriate for various experimental paradigms. While the focus of this work is on optical neural stimulation, optrode array devices have application in basic neuroscience research, highly selective photodynamic therapy, and deep tissue imaging for diagnostics and therapy