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LuminanceGAN: Controlling the brightness of generated images for various night conditions
No full textThere are diverse datasets available for training deep learning models utilized in autonomous driving. However, most of these datasets are composed of images obtained in day conditions, leading to a data imbalance issue when dealing with night condition images. Several day-to-night image translation models have been proposed to resolve the insufficiency of the night condition dataset, but these models often generate artifacts and cannot control the brightness of the generated image. In this study, we propose a LuminanceGAN, for controlling the brightness degree in night conditions to generate realistic night image outputs. The proposed novel Y-control loss converges the brightness degree of the output image to a specific luminance value. Furthermore, the implementation of the self-attention module effectively reduces artifacts in the generated images. Consequently, in qualitative comparisons, our model demonstrates superior performance in day-to-night image translation. Additionally, a quantitative evaluation was conducted using lane detection models, showing that our proposed method improves performance in night lane detection tasks. Moreover, the quality of the generated indoor dark images was assessed using an evaluation metric. It can be proven that our model generates images most similar to real dark images compared to other image translation models. © 2024 Elsevier B.V.FALSEsciescopu
Preclinical efficacy of IL13Rα2-targeting polypeptide-drug conjugate (Self-DepotTM OncoPDC) in glioblastoma and diffuse intrinsic pontine glioma
No full textGlioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG) are currently incurable cancers. Systemic chemotherapy shows limited efficacy because of the intact blood-brain barrier. Convection-enhanced delivery (CED) offers promise by concentrating high doses of chemotherapeutics directly within these tumors. However, drugs administered via CED often face challenges in confirming precise target delivery and are quickly cleared by increased interstitial fluid flow and drug efflux transporters. This highlights the urgent need for innovative drugs that demonstrate target specificity and prolonged retention capabilities. Intrinsically disordered polypeptides (IDPs), derived from tropoelastin, self-assemble into water-insoluble structures with extended retention properties triggered by body temperature. IL13Rα2, differentially amplified in U87MG GBM and SF8628 DIPG cells, serves as a target for therapeutic intervention. An IL13Rα2-targeting IDP (XM161) was developed by incorporating IL13Rα2 binding sequences into the IDP domains. XM161 demonstrated high selectivity in binding to IL13Rα2, with Kd values of 1,786 nM for IL13Rα1 and 12.8 nM for IL13Rα2. Conjugation of XM161 with SN38, a potent topoisomerase I inhibitor, resulted in XM161-SN38, which remained in a dissolved state up to 50°C but formed insoluble aggregates above 27°C in the presence of cerebrospinal fluid. XM161-SN38 exhibited strong cytotoxicity against U87MG and SF8628 cells, with IC50 values of 14.2 nM and 0.48 nM, respectively. Importantly, XM161-SN38 demonstrated efficacy in overcoming Temozolomide resistance in T98G GBM cells, with IC50 values of 3.35 nM compared to 10.87 nM for unconjugated SN38. In orthotopic xenograft models established in BALB/cSlc-nu/nu male mice using U87MG-Luc2 cells, three doses (3 x 0.95 μg SN38 equivalents) of XM161-SN38 delivered via CED were well tolerated and significantly extended median survival to over 65 days, providing a notable survival benefit compared to untreated controls (42 days) and Topotecan-treated group (42.5 days). These findings validate the feasibility and therapeutic potential of XM161-SN38 for GBM treatment. Ongoing studies are underway to investigate the safety and pharmacokinetics of XM161-SN38 in tumor-naive mouse brains
Characterization of lung epithelial cell plasticity and its implications for lung diseases by single-cell RNA sequencing
No full textEpithelial plasticity;scRNA-seq;COVID-19;Lung adenocarcinoma;Disease severityAbstract i
List of contents ii
List of figures iv
Ⅰ. Introduction 1
1.1 Definition of cell plasticity 1
1.2 Cell plasticity across diverse organs 1
1.3 Cell plasticity in tissue damage or disease conditions 3
IⅠ. Unraveling epithelial plasticity in response to SARS-CoV-2 Infection: Insights into variations
induced by viral variants and the underlying regulatory mechanisms through scRNA-seq analysis 8
2.1 Disease introduction 8
2.2 Results 11
2.2.1 scRNA-seq profiling unveils the transcriptomic landscape of SARS-CoV-2
infection in the mouse lung 11
2.2.2 Comparing virus infection patterns in the lung over time: Two SARS-CoV-2 strains
at single-cell resolution 12
2.2.3 Immune responses of the myeloid compartment to SARS-CoV-2 in the mouse lung
13
2.2.4 Immune responses of the lymphoid compartment to SARS-CoV-2 in the mouse
lung 15
2.2.5 Epithelial cell plasticity in the context of SARS-CoV-2 infection 18
2.2.6 Recovery of AT2 transdifferentiation from club cells in the Omicron BA.1 variant
infection model 19
2.2.7 Exploring cell-cell interactions to identify factors modulating lung epithelial cell
plasticity in SARS-CoV-2 infection response 21
2.3 Methods 22
2.4 Discussion 24
IIⅠ. scRNA-seq reveals cancer cell plasticity and differential regulation in the tumor
microenvironment in the Lung Adenocarcinoma across three histologic subtypes 27
3.1 Disease introduction 27
3.2 Results 29
3.2.1 Exploring single-cell transcriptomic landscapes across three distinct histological
subtypes of LUAD 29
3.2.2 Characterizing lymphocytes within the TME of LUAD through single-cell
transcriptomics across various histologic subtypes 30
3.2.3 Enrichment of exhausted CD8+ T cells in solid-type LUAD compared to other
histologic subtypes 31
3.2.4 Enrichment of immunosuppressive and tumor-promoting macrophage subtype
(Mac.SPP1.GPNMB) in solid-type LUAD 33
3.2.5 Dysregulation of cholesterol efflux metabolism in the immune system within the
TME of solid-type LUAD 34
3.2.6 Elevated Senescence-Associated Secretory Phenotype (SASP) signature in alveolar
macrophages of solid-type LUAD 35
3.2.7 Identification of inter-tumoral heterogeneity and diverse cancer cell plasticity
across distinct histologic subtypes of LUAD 35
3.2.8 The presence of a minor solid component induces intra-tumoral heterogeneity in
A/P patients through clonal evolution 38
3.2.9 Identification of cell-cell interaction patterns specific to histologic subtypes to
regulate the cellular plasticity of cancer cells in LUAD 39
3.2.10 Clinical significance 40
3.3 Methods 42
3.4 Discussion 44
IV. References 78
V. 요약문 84DoctordCollectio
이식형 장치를 이용한 운동 피질과 좌골 신경에서의 자기자극
No full textmagnetic stimulation;brain stimulation;peripheral nerve stimulation;epidural stimulation;implantable coil자기자극은 강한 세기의 전류 펄스에 의해 형성된 자기장을 활용하여 신경조직을 자극하는 기술이다. 이 기술은 전기적 절연층으로 둘러싸인 코일을 이용하여 전극과 조직 간의 직접적인 접촉 없이도 신경자극이 가능하기 때문에, 전극 표면에서의 생물학적 반응에 의한 자극성능 저하를 고려하지 않아도 되는 장점을 가지고 있다. 그러나 사용되는 코일의 크기가 사람의 반구를 덮을 만큼 크기 때문에, 의도치 않은 피질영역에도 자극이 가해질 수 있는 제약이 있다. 이러한 제약은 코일 크기를 축소함으로써 공간적 해상도를 높이는 방법으로 해결할 수 있지만, 이는 자극 세기의 감쇠와 높은 발열로 인한 조직 손상 가능성을 높일 수 있다는 문제를 동반한다. 따라서 국소적인 신경조직 영역의 자극을 달성하기 위해서는 소형 코일을 사용한 신경자극 여부와 더불어 열적 안전성을 평가하는 연구가 필요하다. 본 연구에서는 체내에 삽입 가능한 크기의 소형 코일을 활용한 국소적 자기자극 기술의 실현 가능성을 평가하였다. 첫 번째 장에서는 박막 형상의 코일을 이용한 피질에서의 자기자극 가능성을 살펴보았다. 선 폭, 두께, 및 층 수를 달리 한 박막형 코일들을 미세전자기계시스템 및 연성회로기판 공정으로 각각 제작한 뒤, 전기적 및 열적 특성들을 평가하였다. 이후, 박막형 코일들을 랫트의 우측 뒷다리에 해당하는 운동피질 위에 위치시킨 뒤 자기자극을 인가하였을 때 피질에서의 국소 장 전위 및 뒷다리에서의 복합운동유발전위의 변화를 관찰하였다. 그 결과, 박막형 코일을 이용한 자기자극으로는 주목할 만한 신경반응이 관찰되지 않았다. 이를 통해 박막형 구조는 낮은 유도 전기장 세기와 높은 발열로 인해 자기자극을 위한 삽입형 장치의 형상으로 활용하기에는 적합하지 않음을 실험적으로 확인하였다. 두 번째 장에서는, 박막형 코일 대신 솔레노이드 타입의 코일을 도입하여 좌골 신경에서 신경 반응을 이끌어내는 자기 자극의 타당성을 입증했다. 작은 코일은 페라이트 코어에 감겨 있어 낮은 전류 세기에도 강한 세기의 전기장을 유도할 수 있었다. 동물실험에 앞서 소형 코일을 이용하여 신경을 자극에 필요한 전기장 세기와 입력 전류 세기를 3차원 랫트 모델을 사용한 시뮬레이션으로 예측하였다. 시뮬레이션 결과를 바탕으로 해당 코일을 이용하여 랫트의 좌골신경에 자극 펄스를 인가하여 복합운동유발전위가 발생하는 것을 확인하였다. 세번째 장에서는, 좌골신경의 자극을 이끌어낸 코일을 좌측 운동피질의 경막 위에 완전히 삽입한 후, 경막외 자기자극을 통해 운동피질에서의 신경조절 효과를 연구하였다. 그 결과, 좌측 운동피질의 자극에 대응하는 우측 뒷다리의 운동유발전위가 크게 증가하는 효과를 확인하였다. 이는 기존의 피질을 손상시키지 않은 자기자극 연구들 중에서 가장 높은 공간해상도를 달성한 것이었다. 코일의 발열 또한 체내 삽입형 의료기기에 대한 가이드라인에서 규정한 온도보다 낮게 유지되도록 하였다. 종합적으로, 본 연구에서는 삽입 가능한 크기의 코일을 이용하여 국소영역의 신경조직을 자극하는 자기자극 기술의 실현가능성을 평가하였고, 좌골신경과 운동피질에서 자기자극의 효과를 성공적으로 확인하였다.|Magnetic stimulation is a technique that modulate neural responses by applying a magnetic field generated by strong current pulse. This technique allows for neural stimulation without direct contact between the electrode and the tissue due to the coil encapsulated with electrical insulation layer. This advantage eliminates concerns about the degradation in stimulation performance due to biological response, such as immune response on the electrode surface. However, the size of the coil used in magnetic stimulation is large enough to cover a hemisphere of a human brain, which introduces a limitation as it may inadvertently stimulate adjacent areas to the target region. While reducing the size of the coil can increase spatial resolution, it comes with the constraints: attenuation of the stimulation intensity, thermal tissue damaging due to high heat generation. Therefore, research evaluating the use of miniature coils for neural stimulation, along with assessing thermal safety, is necessary to achieve localized stimulation of neural tissue. In this study, the feasibility of focal magnetic stimulation using small-sized coils that can be implanted into the body was evaluated. In the first section (Chapter Ⅱ), the potential for cortical magnetic stimulation using thin film coils with different dimensional parameters was examined. These thin film coils were fabricated using microelectromechanical systems (MEMS) and flexible printed circuit board (FPCB) manufacturing processes. After evaluating their electrical and thermal characteristics, the thin film coils were positioned on the rat motor cortex corresponding to the right hind limb. Upon applying magnetic stimulation, no significant neural responses were observed. These results confirmed that thin film structures are not suitable for use as implantable devices for magnetic stimulation due to their low intensity of induced electric field and high heat generation. In the second section (Chapter Ⅲ), a solenoidal type of coil was employed instead of thin film coils to demonstrate the feasibility of eliciting neural responses in sciatic nerve. Small coils with a diameter of 3mm wound around a ferrite core were able to induce a strong electric field near the coil even at low intensity current pulse. Prior to in vivo experiments, the electric field intensity and input current were estimated using simulations with a 3D rat model. Based on the simulated results, compound muscular action potentials were successfully elicited in vivo in limb muscles by applying current pulses of a few amperes. Furthermore, it was ensured that the coil surface temperature remained within 2 ℃ defined by guidelines for implantable medical devices. In the third section (Chapter Ⅳ), the coil, eliciting responses in the sciatic nerve, was completely implanted epidurally on the left motor cortex to observe the neuromodulation effect of magnetic stimulation. The results showed a significant increase in motor evoked potentials in the right hind limb corresponding to the stimulation region using the coil. This achieved the highest spatial resolution among magnetic stimulation studies that did not damage the cortical tissues. The heat generation of the coil was also carefully managed to keep the temperature below the safety threshold of 2 ℃. Overall, this study evaluated the feasibility of magnetic stimulation using implantable coils for focal stimulation, and successfully confirmed the neuromodulation effects of magnetic stimulation for the sciatic nerve and motor cortex.Chapter I. Introduction 1
1. Background 2
2. Principle of Magnetic Stimulation 3
2.1 Induced electric field by magnetic stimulation 3
2.2 Magnetic stimulation in axon by using the passive cable model 5
2.3 Related studies for thresholds of magnetic stimulation 9
3. Recent Studies 11
4. Research Objective 12
5. References 14
Chapter II. Magnetic Stimulation Using Thin Film Type Planar Coils 17
1. Introduction 18
2. Methods 19
2.1 Simulation 19
2.2 Fabrication 20
2.3 Measurements 22
2.4 In vivo experiments 23
3. Results and Discussion 24
3.1 Simulation of induced electric field and heat generation 25
3.2 Thin film coils 26
3.3 Measurement of heat generation 28
3.4 MEP and LFP measurement 31
4. Conclusion 35
5. References 36
Chapter III. Magnetic Stimulation for Sciatic Nerve Using an Implantable Coil 38
1. Introduction 39
2. Materials and Methods 40
2.1 Selection of coil and power source 40
2.2 In silico experiment 43
2.3 In vivo experiment 45
2.4 Heat measurement 46
3. Results and Discussion 47
3.1 Estimated threshold current 47
3.2 Muscle response to magnetic stimulation 49
3.3 Temperature increase during stimulation 54
4. Conclusion 56
5. References 57
Chapter IV. Magnetic Stimulation for Motor Cortex Using an Implantable Coil 60
1. Introduction 61
2. Methods 62
2.1 Coil and pulse generator for MEP modulation 62
2.2 Heat measurement 64
2.3 Simulation of induced electric field 65
2.4 Coil implantation 65
2.5 Anesthesia during epidural magnetic stimulation 66
2.6 Subthreshold repetitive magnetic stimulation with QPS 66
2.7 MEP recording 66
2.8 Data analysis 67
3. Results 67
3.1 Heat measurement and maximum applicable current 67
3.2 Simulation of induced electric field 68
3.3 MEP measurement 69
3.4 Time course of MEP changes 71
4. Discussion 71
4.1 Coil implantation 71
4.2 MEP modulation 73
4.3 Thermal safety 74
5. Conclusion 75
6. References 75
Chapter V. Conclusion and Future Research 79
APPENDIX 83
요약문 87DoctordCollectio
Four-Wave Mixing Processes in a Photonic Molecule Reconfigured by Micro-Electro-Mechanical System(MEMS)
No full textSilicon photonics; Four-wave mixing; Photonic integrated circuit; Micro-electro-mechanical systems (MEMS); Coupled-resonator optical waveguide (CROW)Microring resonators intensify the four-wave mixing (FWM) process, a crucial nonlinear optical phenomenon, owing to their ability to enhance optical power significantly. Nonetheless, traditional resonators in integrated photonics typically encounter difficulties with accurately adjusting coupling intensities and phases. Addressing this, we introduce a pioneering, fully reconfigurable photonic molecule device, empowered by electrostatic micro-electro-mechanical systems (MEMS), which provides unparalleled control over both the coupling strength and resonant wavelengths of each microring for the first time.
This novel device, operated through low-power electrostatic MEMS, incorporates tunable directional couplers and phase shifters for each microring, exemplifying its utility as a photonic molecule and establishing its functionality as a coupled-resonator optical waveguide (CROW) filter. Our experimental analysis reveals that this extensive tunability shows the complex interaction between the two resonances of microrings, confirming its proficiency as a photonic molecule device and enabling FWM across all wavelengths. a seeded FWM has been successfully demonstrated with a conversion efficiency of -56 dB at a pump power of 7.3 dBm, underscoring the device's significant potential in enhancing optical applications.
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초소형 링 공진기는 강한 광학적 세기 증가 특성을 이용해 중요한 비선형 광학 현상인 네 파장 혼합 과정을 강화합니다. 그럼에도 불구하고, 광 직접 회로를 구성하는 기존의 공진기들은 결합 강도와 위상을 정확하게 조절하는 데 어려움이 있습니다. 이에 대응하여, 우리는 정전기력 기반의 마이크로미터 크기의 전기기계 시스템(멤스)을 이용해 각 초소형 링의 결합 강도와 공진 파장을 정밀하게 제어할 수 있는 완전히 재구성 가능한 광자 분자 장치를 처음으로 소개합니다.
이 새로운 장치는 각 초소형 링에 조절 가능한 방향성 결합기와 위상 변환기를 결합하여 설계되었습니다. 이 장치는 매우 낮은 전력을 소비하는 정전기력 멤스를 활용해 효율적으로 동작하며, 광자 분자로서의 유용성을 입증하고 결합된 광학 도파로 공진기(크로우) 필터로서의 기능을 확립합니다. 실험 분석을 통해 보여준 이 광범위한 조절성은 초소형 링의 두 공진 간의 복잡한 상호 작용을 설명할 수 있고, 광자 분자 장치로서의 능력을 확인하고 임의의 파장에 대해 네 파장 혼합 과정을 가능하게 합니다. 또한 펌프 출력 7.3 dBm에서 - 56 dB의 변환 효율을 달성한 네 파장 혼합 과정은 이 장치가 광학 분야에서 응용될 중대한 잠재력을 강조합니다.Ⅰ Introduction 1
Ⅱ Device architecture 4
2.1 Device concept 4
2.1.1 Tunable directional coupler 4
2.1.2 Tunable phase shifter 8
2.1.3 Electrostatic MEMS cantilever actuator 11
2.2 MEMS-based reconfigurable photonic molecule device 14
Ⅲ Results 15
3.1 Fabrication 16
3.2 Experimental setup 21
3.3 Fundamental characterization in MEMS-based CROW 22
3.3.1 Spectral response measurement 22
3.3.2 Mechanical response measurement 26
3.3.3 Electrical power consumption 28
3.4 Nonlinear application in MEMS-based photonic molecule 30
3.4.1 Spectral response measurement 30
3.4.2 Four-wave mixing process 32
Ⅳ Future work 35
Ⅴ Conclusion 37
References 38
요 약 문 41MasterdCollectio
Investigation on synaptic functions of leucine- rich repeat domain-containing adhesion molecules LRRTMs and Slitrks at hippocampal neural circuits
No full textLRRTMs;Slitrks;시냅스;해마;신경회로Introduction 1
1.1 Synapse & Synaptic adhesion molecules 1
1.2 Leucine-rich repeat-containing proteins 7
1.3 LRRTMs: extracellular binding family members for Neurexins 10
1.4 Slitrks: isoform-specific synaptic organizers at excitatory synapse and inhibitory synapse 12
1.5 Non-canonical functions of synaptic adhesion molecules 17
Materials and methods
2.1 Materials 20
2.1.1 Animals 20
2.1.2 Chemicals and Drugs 20
2.1.3 Recombinant DNA 21
2.1.4 Software 21
2.2 Methods 21
2.2.1 Electrophysiology 21
2.2.2 Expression vectors 24
2.2.3 Adeno-associated virus preparation 25
2.2.4 Virus titration 26
2.2.5 Statistical analysis 26
Results 27
3.1 LRRTM3 regulates the development of excitatory synapses at MEC-DG-CA3 synapses 27
3.1.1 LRRTM3 specifically regulates the development of excitatory synapses at MPP synapses. 27
3.1.2 LRRTM3 deficiency impairs long-term synaptic plasticity at Mf-CA3 synapses. 28
3.1.3 LRRTM3 regulates MEC-DG-CA3 synaptic homeostasis. 35
3.2 LRRTM4 regulates the development of excitatory synapses at LEC-DG synapses 42
3.2.1 LRRTM4 regulates spontaneous release at PP synapses. 42
3.2.2 LRRTM4 specifically regulates NMDAR-dependent EPSCs at LPP synapses. 46
3.2.3 LRRTM4 is not required for maintaining long-term synaptic plasticity at LPP synapses. 46
3.3 LRRTM2 is not required for regulating excitatory synaptic transmission in the DG 51
3.4 Synaptic functions of Slitrk1 and Slitrk2 in the hippocampal CA1 pyramidal neurons 55
3.4.1 Slitrk1 deficiency enhances spontaneous synaptic transmission and Slitrk2 deficiency reduces spontaneous synaptic transmission in CA1 pyramidal neurons. 55
3.4.2 Slitrk1 deficiency increases NMDAR-dependent eEPSCs at TA synapses, and Slitrk2 deficiency decreases both AMPAR-dependent eEPSCs and NMDAR-dependent eEPSCs at SC synapses. 59
3.4.3 Slitrk1 does not regulate asynchronous synaptic transmission at both SC and TA synapses, while Slitrk2 is crucial for regulating asynchronous synaptic transmission at SC synapses but not at TA synapses. 64
3.5 Synaptic functions of Slitrk1 and Slitrk2 in hippocampal DG granule neurons 69
3.5.1 Slitrk1 cKO or Slitrk2 cKO in the DG does not affect spontaneous synaptic transmission in DG granule neurons. 69
3.5.2 Slitrk2 regulates synchronous synaptic transmission at both MPP and LPP synapses, while Slitrk1 does not regulate synchronous synaptic transmission in DG granule neurons. 69
3.5.3 Slitrk1 regulates asynchronous synaptic transmission at MPP and LPP synapses, while Slitrk 2does not regulate asynchronous synaptic transmission at both PP synapses. 70
3.6 Significance of interactions with LAR-RPTPs for non-canonical synaptic functions of Slitrk 1 and Slitrk2. 82
3.6.1 LAR-RPTPs are indispensable binding partners of Slitrk2 for the regulation of synchronous synaptic transmission at SC synapses. 82
Discussion 85
References 90DoctordCollectio
Core-shell carbon@Ni2 (CO3 )(OH)2 particles as advanced cathode materials for hybrid supercapacitor: The key role of carbon for enhanced electrochemical properties
No full textThree-dimensional porous Ni2(CO3)(OH)2 compounds were grown on carbon nanopowder using a facile hydrothermal method for the production of core-shell carbon@Ni2(CO3)(OH)2 compounds. This work successfully overcame the shortcomings related to the low electrical conductivity and poor electrical stability caused by the presence of hollows in the Ni2(CO3)(OH)2 structure. The hollow spaces were filled with carbon powder, which acted as a seed material, yielding an ideal electrode material with a large specific surface area, high electrical conductivity, and good stability. A Ni2(CO3)(OH)2 electrode containing 50 mg of carbon powder could store more energy than a Ni2(CO3)(OH)2 electrode without carbon seed materials. The Ni2(CO3)(OH)2 electrode comprising 50 mg of carbon powder has a considerably high specific capacity (181.7 mAh g−1 at 3 A g−1) and excellent cycling stability (77.9 % capacity retention after 5000 cycles), which is 1.5 times higher than that of the Ni2(CO3)(OH)2 electrode without carbon powder. Moreover, an asymmetric supercapacitor using Ni2(CO3)(OH)2 containing 50 mg of carbon powder as the positive electrode and graphene as the negative electrode exhibits a high energy density of 34.2 Wh kg−1 and a power density of 176.1 W kg−1 at a current density of 2 A g−1. Using a combination of carbon and a Ni2(CO3)(OH)2 nanowire compound to increase the electrochemical property and specific surface area, respectively, a suitable synergistic effect can be obtained, which may pave the way for efficient electrode design for high-performance supercapacitors. © 2024 Elsevier LtdFALSEsciescopu