Monthly Variations of Microphytobenthos Pigments and Photo-Physiological Characteristics in the Middle Intertidal Zone of Geunso Bay, West Coast of Korea

In this study, the surveys were carried out from October 2016 to October 2017 along the tidal flat of Geunso Bay, Taean Peninsula of the western edge of Korea. The sampling trips were carried out for a total of 16 times, once or twice a month. In order to investigate the monthly variation of the microphytobenthos (MPB) biomass and community composition, microphytobenthic pigments on the surface of the sediment were analyzed by HPLC (High performance liquid chromatography). The total chlorophyll a (TChl a) concentrations have used as an indicator of MPB biomasses in the upper 1 cm sediment layer ranged from 40.4 to 218.9 mg m-2 throughout the sampling period. TChl a concentrations showed the maximum level on 24th of February and remained high throughout March after which it started to declined. The biomass of MPB showed high values in winter and low values in summer. The monthly variations of pheophorbide a concentrations suggested that the low grazing intensity of the predator in the winter may have partly attributed to the MPB winter blooming. As a result of monthly variations of the MPB community composition using the major marker pigments, the concentrations of fucoxanthin, the marker pigment of benthic diatoms, were the highest throughout the year. The concentrations of most of the marker pigments except for chlorophyll b (chlorophytes) and peridinin (dinoflagellates) increased in winter. However, the concentrations of fucoxanthin increased to the highest, and therefore, the relative ratios of the major marker pigments other than fucoxanthin to the TChl a decreased during this period. The vertical distribution of chlorophyll a and oxygen concentrations in the sediments using a fluorometer and an oxygen micro-optode chlorophyll a concentrations decreased with oxygen concentrations with increasing depth of the sediment layers. Moreover, this tendency became more apparent in winter. The chlorophyll a was uniformly vertical down to 12 mm from May to July, but the oxygen concentration distribution in May decreased sharply below 1 mm. The increase in pheophorbide a concentration observed at this time is likely to be caused by increased oxygen consumption of zoobenthic grazing activities. This could be presumed that MPB cells are transported downward by bioturbation of zoobenthos. Measuring chlorophyll fluorescence via Diving PAM (Pulse amplitude modulated fluorometer) at every hour was perform in order to investigate the vertical migration and photo-physiological characteristics of MPB. The steady-state fluorescence in ambient light (F＇) increased as time passes during the daytime emersion periods, which suggests that MPB moves upward to the surface of the sediments. The light utilization efficiency of PSⅡ (ΔF/Fm＇) and the relative electron transport rate (rETR) was negatively and positively correlated to irradiance. |본 연구에서는 태안반도 근소만 갯벌에서 저서미세조류(MPB)의 현존량, 군집조성에 대해 알아보기 위하여 2016년 10월부터 2017년 10월까지 월 1~2회씩 총 16회에 걸쳐 갯벌 표층에 분포하는 저서미세조류 색소를 HPLC (High performance liquid chromatography)를 이용 분석하였다. 갯벌 표층 1 cm 깊이에 분포하는 저서미세조류의 광합성 색소 중 현존량의 지표로 사용되는 총 chlorophyll a (TChl a) 농도는 연중 40.4~218.9 mg m-2 의 범위를 보였다. TChl a 농도는 2월 24일에 최대값이 나타났고 3월에도 높은 값을 보인 뒤 이후 감소하였다. 저서미세조류의 현존량은 동계에 높고 하계에 낮은 값을 나타냈다. Pheophorbide a 농도의 월별 변동을 통해 동계에 상위포식자의 낮은 포식압이 저서미세조류 동계번성에 일부 기여한 것으로 사료된다. 또한 주요지시색소를 이용한 저서미세조류 군집조성의 분석한 결과 저서규조류의 지시색소인 fucoxanthin의 농도가 연중 가장 높게 나타났다. Chlorophyll b(녹조류), peridinin(와편모조류)을 제외한 대부분의 지시색소의 농도는 동계에 증가하였으나, fucoxanthin의 농도 증가율이 가장 높아 fucoxanthin을 제외한 TChl a에 대한 주요지시색소의 상대비는 동계에 감소하는 경향이 있었다. 형광광도계와 산소미세전극을 이용하여 측정한 퇴적물 내 chlorophyll a와 산소 농도의 연직분포 특성은 퇴적층 표면에서 깊이가 깊어질수록 chlorophyll a와 산소 농도가 함께 감소하는 경향을 보였고, 동계로 갈수록 이런 경향이 더욱 뚜렷하게 나타났다. 하지만 5~7월의 chlorophyll a 농도는 다른 기간에 비해 12 mm까지 연직으로 유사하게 나타났으나, 5월의 산소 농도 분포는 1 mm이하에서 급격하게 감소하였다. 같은 시기에 pheophorbide a 농도가 증가하는 것으로 보아 저서동물의 포식활동에 의한 산소 소비량이 증가하였을 가능성이 있으며, 저서동물의 생물교란에 의해 저서미세조류의 세포가 아래로 옮겨진 것으로 추측된다. Diving PAM (Pulse amplitude modulated fluorometer)으로 엽록소 형광을 시간별로 측정하여 저서미세조류의 수직 이동과 광생리적 특성에 대해 조사하였다. 낮 동안 간조 시 시간이 지남에 따라 자연광 조건에서의 평형 상태 형광 발생량(F＇)은 증가하여, 저서미세조류가 퇴적물 표면으로 수직 상승을 하는 것으로 추정된다. 제 2 광계의 유효양자수율(ΔF/Fm＇)과 상대 최대 전자전달율(rETR)은 일사량에 따라 각각 양의 상관관계와 음의 상관관계를 보였다.List of Tables ⅳ List of Figures ⅴ Abstract ⅶ 1. Introduction 1.1 Avoidance strategies to reduce the light stress of MPB and necessity of research 1 1.2 Advantages of pigments analysis using HPLC and preceding studies 1 1.3 Advantages of PAM measurement 2 1.4 Aims of this study 3 2. Materials and Methods 2.1 Sampling sites 4 2.2 Photosynthetic pigments analysis 6 2.3 Chlorophyll fluorescence measurement 10 2.4 Oxygen concentration measurement 12 3. Results 3.1 Temporal variation in pigment concentrations 13 3.2 Temporal variation in fluorescence parameters 21 3.3 Distribution of oxygen concentration in sediments 25 4. Discussion 4.1 Monthly variations of MPB biomass 26 4.2 The community composition of MPB 29 4.3 Monthly Chl a vertical distribution 29 4.4 Daily vertical movement of MPB 32 4.5 Temporal variation of photo-physiological characteristics of MPB 32 5. Conclusions 34 Acknowledgements 35 References 36Maste

탄성파 토모그래피를 이용한 3 차원 지각 속도 구조 산출 및 유효 매질 이론을 적용한 암석의 비등방적 탄성 특성 모델링

학위논문(박사)--서울대학교 대학원 :자연과학대학 지구환경과학부,2020. 2. 김영희.탄성파 토모그래피는 탄성파 속도 구조를 영상화하여 지구 내부 구조에 대한 지식을 향상시킬 수 있는 기법이다. 암석 물리 이론에 따르면 균열종횡비가 작은 얇은 균열들이 존재하는 경우 다공성이 증가함에 따라 Vp/Vs 가 증가하는 반면에, 균열종횡비가 큰 두꺼운 균열들은 Vp/Vs 를 감소시킨다. 본 학위논문에서는 탄성파 토모그래피로 산출한 Juan de Fuca Ridge 의 Endeavour segment 지역 상부 해양 지각의 3차원 속도 구조와 함께 속도 구조 해석을 위해 적용한 이론적 방법인 차등 유효 매질 이론 (differential effective medium theory; DEM)을 제시한다. 탄성파 속도 구조 산출을 위해서, Endeavour segment 의 상부 해양 지각을 전파하여 기록된 P 파와 S파의 굴절파를 복합역산 기법을 이용하여 분석하였다. P파 주행시간만을 이용해서 토모그래피를 수행한 이전 연구에서 탄성파 비등방성이 축상에서는 높지만 축에서5 – 10 km 정도 멀어질수록 감소하는 것으로 나타났으며 이는 열수 순환과 관련된 광물 석출에 의한 균열 막힘때문이라고 보고하였다. Endeavour segment 에서의 굴절파 복합역산 결과, 해령 축에서는Vp/Vs 가 낮고 축에서 5 – 10 km 떨어진 지점에서는 Vp/Vs가 높아진다. 이러한 결과에 DEM 결과를 적용하면, 얇은 균열에 대한 두꺼운 균열의 존재 비율이 해령 축상에서부터 멀어질수록 감소하는 것을 지시한다. 해령 축 하부에서는 두꺼운 균열이 열수 순환의 상승 파트에 필요한 장기간의 유체 도관 역할을 하는 것으로 보이며, 해령 축 측면에서는 열수 순환의 하강 파트에서 일어나는 광물 석출로 인해 두꺼운 균열이 점진적으로 막히고 얇은 균열의 비율이 증가하여 투수성이 감소하는 것으로 보인다. DEM 은 유효 매질 이론 (effective medium theory; EMT) 중 하나로 암석의 탄성파 속도 및 비등방성을 모델링하는 데 이용된다. 본 학위논문에서는 GassDem (Gassmann Differential effective medium) 이라고 명명된 매틀랩 (MATLAB) 프로그램을 제시하고 몇 가지 모델링 예시를 사용자들이 실습할 수 있도록 설명한다. 이 소프트웨어는 DEM 뿐만 아니라 Gassmann (1951) 이 제안한 다공성-탄성 관계 이론을 바탕으로 암석 미세구조 데이터를 토대로 탄성파의 비등방성을 모델링한다. DEM 은 두 가지 구성 성분인 배경 암석과 포함물로 이루어진 합성물에 대해서 모델링한다. 다공성, 균열의 기하학적 구조, 균열 내의 유체 종류와 같은 암석 미세구조를 포함물의 특성으로 고려하여 모델링에 포함시킬 수 있다. Gassmann의 다공성-탄성 관계 이론을 DEM 과 결합하여 유체-포화상태의 암석에 대한 탄성 특성을 계산할 수 있고, 감쇄 또한 산출할 수 있다. 암석의 탄성 특성을 예측하는 방법과 관련하여 자가-부합적 근사법 (self-consistent approximation; SCA) 또한 많이 사용되고 있는 EMT 중 하나이다. SCA는 다결정 암석과 같이 복수의 구성성분으로 이루어진 합성체에 대한 모델링에 사용된다. 본 학위논문에서는 SCA 모델링을 위한MATLAB 소프트웨어 AnisEulerSC (Anisotropy from Euler angles using self-consistent approximation) 를 제시하고 몇 가지 예시에 대해 설명한다. SCA 기법으로 구성 광물의 부피비, 각 광물의 격자 선호 방향, 단결정 탄성력 상수를 이용하여 암석의 비등방적 탄성 특성을 예측할 수 있다. 또한, 모양 선호 방향과 같은 특성도 SCA 모델링에서는 고려할 수 있다. 여러가지 SCA 모델링 예시들은 단 2% 의 균열 다공성만으로도 탄성파 비등방성이 변화할 수 있으며, 이러한 속도 변화 및 비등방성의 정도는 균열 모양과 정렬 방향에 좌우된다는 것을 보여준다. DEM 과 SCA 가 단순 평균 기법들보다 복잡한 방법이긴 하지만, 본 학위논문에서 제시한 두 개의MATLAB 프로그램인 GassDem과 AnisEulerSC 는 각각 DEM 과 SCA 모델링을 할 때 손쉽게 사용할 수 있는 툴을 제공함으로써 지각과 맨틀의 암석의 탄성 특성을 모델링 하여 탄성파 속도 구조를 해석할 때에 유용하게 활용될 수 있다.Seismic tomography enhances knowledge of the Earths internal structure by imaging the seismic velocity structures. The interpretation of seismic velocities is based on the rock sample data from experimental measurements and the prediction of seismic properties from theoretical methods. A number of drilling programs have provided rock samples and in-situ data at depths in the continental and oceanic crust. However, the discrepancy in seismic velocities between rock sample data and seismic observation has been reported. As a result, the prediction of seismic properties based on theoretical approaches has been emphasized to understand what controls the seismic velocities in the crust and mantle. Rock physics theory has been used to interpret Poissons anomaly observed in the young oceanic crust, because it predicts that the distribution and aspect ratios of cracks have strong effects on Poissons ratio. In addition, it is emphasized that knowledge of both P and S wave velocities is useful to infer the characteristic and distribution of cracks. This dissertation presents the seismic tomographic results of three-dimensional velocity structure of the upper oceanic crust at the Endeavour segment of the Juan de Fuca Ridge and the interpretation of seismic velocities using the effective medium theory. For seismic velocity structure at the Endeavour segment, P and S waves refracted in the upper oceanic crust are analyzed using a joint inversion of P and S traveltimes collected from a seismic refraction experiment. Since the Endeavour segment is one of the most active and long-lived hydrothermal areas of the mid-ocean ridges, the fluid pathways for hydrothermal circulation may be well established. However, the permeability structure beneath this long-term venting system is not well known. To understand the active hydrothermal circulation beneath the Endeavour segment, P and S wave velocities are three-dimensionally imaged using seismic tomography and porosity and crack density are estimated applying the differential effective medium (DEM) theory to the observed seismic velocities. Based on the predicted models, low Vp/Vs on-axis and high Vp/Vs off-axis over 5 – 10 km at the Endeavour segment indicate that the proportion of thick versus thin cracks decreases from the ridge axis to the flanks. The dominant presence of thick cracks on the ridge axis may provide long-term conduits for upflow in hydrothermal circulation. The increased proportion of thin cracks on the ridge flanks indicates that the permeability decreases by progressive clogging of thick cracks due to mineral precipitation in the downflow zone of hydrothermal circulation. DEM is one of the effective medium theory (EMT) for modeling the seismic velocity and anisotropy of rocks. In this dissertation, a MATLAB program of GassDem (Gassmann Differential effective medium) and a description for users to replicate the examples are presented. This software can be used to model the anisotropic seismic properties from rock microstructure based on the DEM and Gassmanns (1951) poroelastic relationship. DEM models a two-phase composite that consists of a background medium and inclusions. The rock microstructures, such as porosity, crack geometry, and fluid type in the cracks, are taken into account to be inclusion properties in the DEM modeling. Since the Gassmanns poroelastic relationship combined with DEM calculates the elastic stiffness for fluid-saturated rocks, the attenuation can be also estimated. The self-consistent (SC) approximation is also one of the most popularized methods of EMT. The SC approximation has been used for multi-phase composites such as polycrystalline rocks. In this dissertation, a MATLAB-based software of AnisEulerSC (Anisotropy from Euler angles using self-consistent approximation) and descriptions of several examples are presented. In this method, the shape preferred orientation can be taken into account, because the shape and distribution of components are parameterized in the formulation of SC modeling. Several examples show that only 2% crack porosity is enough to change the seismic anisotropy, although seismic velocities and their degree of anisotropy depend on the shape and orientation of cracks. The main objective of this dissertation is to present that the seismic velocities of the crust and mantle imaged using the seismic tomography can be interpreted based on the predicted seismic properties from the effective medium theory such as DEM and SC methods. Although DEM and SC methods are more complex than the simple averaging methods, two MATLAB-based programs of GassDem and AnisEulerSC provide easy tools for predicting the elastic properties of crustal and mantle rocks based on the DEM and SC methods.Chapter 1. Introduction 1 References 7 Chapter 2. Upper crustal Vp/Vs ratios at the Endeavour segment, Juan de Fuca Ridge, from joint inversion of P and S travel times: Implications for hydrothermal circulation 12 Abstract 12 2.1. Introduction 13 2.2. Geologic Setting 16 2.3. Data and Methods 19 2.3.1. ETOMO Experiment 19 2.3.2. Sg Travel Time Dataset 20 2.3.3. Tomographic Method 23 2.3.4. Differential Effective Medium theory 27 2.4. Tomographic Analysis 32 2.4.1. Starting Model and Vp/Vs Coupling 32 2.4.2. Tomographic Resolution 33 2.4.3. Tomographic Results 35 2.5. Discussion 42 2.5.1. Comparison with an Earlier 1-D Inversion Model 42 2.5.2. Lateral Heterogeneity of Vp/Vs Ratios and Cracks 43 2.5.3. Across-axis Model of Crack Distribution within Layer 2B 44 2.5.4. Crack Geometry and Seafloor Spreading, Hydrothermal Circulation and Tectonics 47 2.5.5. Evolution of Crack Distributions and Hydrothermal Circulation 50 2.6. Conclusions 52 Appendix 53 2A-1. Supporting Information 53 2A-2. Additional Figures 58 References 66 Chapter 3. GassDem: A MATLAB program for modeling the anisotropic seismic properties of porous medium using differential effective medium theory and Gassmanns poroelastic relationship 79 Abstract 79 3.1. Introduction 80 3.2. Microstructure and seismic properties 81 3.2.1. Pressure and seismic velocity 81 3.2.2. Effect of crack alignment on seismic anisotropy 82 3.2.3. Prediction of seismic properties for in-situ state 83 3.3. Modeling schemes 84 3.3.1. Eshelbys (1957) solution 84 3.3.2. Self-consistent (SC) scheme 85 3.3.3. Differential effective medium (DEM) theory 86 3.3.4. Gassmanns (1951) poroelastic relationship 88 3.3.5. Attenuation 89 3.4. Examples 89 3.4.1. Background medium 90 3.4.2. Inclusion 90 3.4.3. GassDem GUI 91 3.4.4. DEM results 95 3.5. Discussion 98 3.5.1. Improvements in computing for GassDem 98 3.5.2. Kelvin tensor notation 100 3.5.3. Tensor Greens function Fourier integral 101 3.6. Summary 106 Appendix 106 3A-1. User manual for GassDem GUI 106 References 116 Chapter 4. AnisEulerSC: A MATLAB program combined with MTEX for modeling the anisotropic seismic properties of a polycrystalline aggregate with microcracks using self-consistent approximation 123 Abstract 123 4.1. Introduction 123 4.2. Theories 126 4.2.1. Simple averages for effective elastic properties of polycrystals 126 4.2.2. Self-consistent (SC) approximation 128 4.2.3. Christoffel equation 130 4.3. AnisEulerSC 130 4.4. Examples 134 4.4.1. Single-crystal elastic stiffness tensor 135 4.4.1.1. Crystal reference frame 135 4.4.1.2. Crystal orientations 136 4.4.2. Anisotropic properties of polycrystalline materials 138 4.4.2.1. SC modeling for a polyphase aggregate 138 4.4.2.2. SC modeling for cracked materials 147 4.5. Discussion 153 4.5.1. Comparison of SC aggregates with simple averages 153 4.5.2. Effect of grain shape on anisotropic elastic properties of aggregates 158 4.5.3. Effect of cracks on the anisotropic properties of a polyphase aggregate 160 4.5.4. Combination of SC approximation and various methods 161 4.6. Conclusions 163 Appendix 164 4A-1. User Guide for AnisEulerSC 164 References 190 Chapter 5. Application of effective medium theory to the crustal and upper mantle structure of the Rainbow area, Mid-Atlantic Ridge 198 5.1. Motivation 198 5.2. Seismic tomographic results beneath the Rainbow massif 203 5.3. Effect of serpentinization on seismic wave velocity and anisotropy 205 5.4. Modeling for ultramafic rocks at the Rainbow massif 209 References 210 Appendix. Publication list 213 5A-1. Journal Articles 213 5A-2. Conference Abstracts 213 요약 (국문초록) 218Docto

Presence of mEGFR ctDNA predicts a poor clinical outcome in lung adenocarcinoma

BACKGROUND: Circulating tumor DNA (ctDNA) is a biomarker for the selection of target agents in various malignancies. In this study, we examined the effect of ctDNA presence on the response to EGFR-tyrosine kinase inhibitor (TKI) and on the prognosis in lung adenocarcinoma. METHODS: ctDNA of EGFR-TKI sensitizing mutations (mEGFR), L858R substitution and Exon 19 deletion (E19d) mutation, was evaluated using droplet digital PCR (ddPCR) in 81 patients with lung adenocarcinoma which harbored mEGFR in the corresponding tumor tissues. RESULTS: The study recruited lung cancer patients at various stages, and the sensitivity, specificity, and area under the curve (AUC) of mEGFR ctDNA detection by ddPCR were 40.0%, 88.5%, and 0.68, respectively. It showed higher sensitivity (75.0% vs. 10.0%) and AUC (0.83 vs. 0.49) in the advanced stages of lung adenocarcinoma compared with the early stages and the number of metastases and the fractional abundance of mEGFR ctDNA showed a strong correlation (σ = 0.516; P < 0.001, Spearman correlation test). There was a significantly shorter progression-free survival and duration of disease control by EGFR-TKIs in the ctDNA-positive group than the negative group (14.0 vs. 41.0 months, P = 0.02 and 12.0 vs. 23.0 months, P = 0.02, log-rank test, respectively). There was a trend for overall survival time to be shorter in patients with mEGFR ctDNA than for patients without mEGFR ctDNA (35.6 vs. 67.1 months, P = 0.06, log-rank test). CONCLUSIONS: These data showed that mEGFR ctDNA detection using ddPCR is useful in the advanced stages and its presence predicted distant metastasis and poor clinical outcome in lung adenocarcinoma.ope

루쉰은 왜 허구적 글쓰기를 그만두었는가? : 「복을 비는 제사」 그리고 서사와 공감의 실패

루쉰이 소위 환등기 사건 이후 의학 공부를 포기하고 문학의 길로 접어든 것은 잘 알려진 사실이다. 그러한 선택을 내린 이유에 대해, 루쉰은 『납함(吶喊)』 서문에서 스스로 다음과 같이 말하고 있다. 우리들의 첫 번째 중요한 일은 그들[중국인]의 정신을 고치는 데 있다. 당시 나는 정신을 고치는 데 있어 최선으로 당연히 문예를 들어야 한다고 여겼다.(루쉰, 2008: 12) 아무런 동정심도 느끼지 못한 채 일본군에게 처형당하는 동포의 모습을 그저 구경삼아 지켜보던 무감각한 중국인들에게 루쉰이 깊은 실망감을 느꼈음을 생각해 볼 때, 정신을 고치는 것은 아마도 감성(aect)의 차원에서 상상의 공동체로서의 국가를 건설하는 것을 의미할 것이며, 만약 이러한 가정이 옳다면, 문학, 특히 허구적 장르로서의 소설은 베네딕트 앤더슨이 『상상의 공동체』에서 주장했듯이 근대적 민족 건설에 있어 가장 효과적인 수단 가운데 하나일지도 모른다

Diagnostic value of the combined use of radial probe endobronchial ultrasound and transbronchial biopsy in lung cancer

Background: Although the use of radial endobronchial ultrasound (R-EBUS) with a guide sheath has shown improved diagnostic capability in peripheral pulmonary lesions, its utility is still low due to variable performance. To overcome its limitation, we evaluated the feasibility and efficacy of R-EBUS combined with transbronchial biopsy (TBB) under fluoroscopic guidance. Methods: We retrospectively reviewed medical records of 74 patients with non-small cell lung cancer (NSCLC) who underwent R-EBUS combined with TBB or TBB alone as a diagnostic technique. Subjects were grouped according to the diagnostic modality used (R-EBUS combined with TBB vs. TBB alone). Each group was matched for age, sex, and location of the biopsy. The chi-square test and paired t-test were used to compare characteristics and identify factors that affected the diagnostic yield. Results: The mean age of the study cohort was 67.4 ± 12.8 years, with 21 (56.8%) men and 16 (43.2%) women in each group. The lesion size was significantly smaller in the R-EBUS group (23.6 vs. 33.9, P < 0.001). The diagnostic yield with the combined use of R-EBUS and TBB (27/37, 72.9%) was significantly higher than that with standard TBB alone (22/37, 59.4%). Lung lesions with a positive bronchus sign were associated with a higher diagnostic yield (odds ratio = 3.52 [1.17-10.62]; P = 0.025). Conclusions: The combination of R-EBUS with TBB resulted in a higher diagnostic yield than either technique alone. Thus, the addition of R-EBUS biopsy would be helpful to improve the diagnostic yield of TBB. Key points: SIGNIFICANT FINDINGS OF THE STUDY: The combination of R-EBUS with TBB under fluoroscopic guidance improved the diagnostic yield of PPLs compared to TBB alone. A tissue diagnosis was more likely in pulmonary lesions with the air-bronchus sign. What this study adds: The use of R-EBUS could help improve the low diagnostic yield of TBB under fluoroscopic guidance without increasing the incidence of complications.ope

A national survey of lung cancer specialists' views on low-dose CT screening for lung cancer in Korea

Lung cancer specialists play an important role in designing and implementing lung cancer screening. We aimed to describe their 1) attitudes toward low-dose lung computed tomography (LDCT) screening, 2) current practices and experiences of LDCT screening and 3) attitudes and opinions towards national lung cancer screening program (NLCSP). We conducted a national web-based survey of pulmonologists, thoracic surgeons, medical oncologists, and radiological oncologists who are members of Korean Association for Lung Cancer (N = 183). Almost all respondents agreed that LDCT screening increases early detection (100%), improves survival (95.1%), and gives a good smoking cessation counseling opportunity (88.6%). Most were concerned about its high false positive results (79.8%) and the subsequent negative effects. Less than half were concerned about radiation hazard (37.2%). Overall, most (89.1%) believed that the benefits outweigh the risks and harms. Most (79.2%) stated that they proactively recommend LDCT screening to those who are eligible for the current guidelines, but the screening propensity varied considerably. The majority (77.6%) agreed with the idea of NLCSP and its beneficial effect, but had concerns about the quality control of CT devices (74.9%), quality assurance of radiologic interpretation (63.3%), poor access to LDCT (56.3%), and difficulties in selecting eligible population using self-report history (66.7%). Most (79.2%) thought that program need to be funded by a specialized fund rather than by the National Health Insurance. The opinions on the level of copayment for screening varied. Our findings would be an important source for health policy decision when considering for NLCSP in Korea.ope

Specificity of surround interaction for global motion directionality in awake monkey V1

학위논문 (석사)-- 서울대학교 대학원 : 심리학과, 2014. 2. 이춘길.Neurons of the primary visual cortex (V1) process visual information presented within the classical receptive field (cRF), and this local information is thought to be integrated with that outside the cRF to recover global visual features in later stages. However, it has been known that even in the V1, neuronal activity is modulated by stimuli outside the cRF. In line with this, it was reported that V1 neurons are modulated by temporal interval of spatiotemporal stimulus sequence extending beyond the cRF (Kim et al., 2012), suggesting that V1 neurons participate in processing stimulus motion extending beyond the cRF – global motion. In the current study, we tested the hypothesis that V1 neurons have directional preference for global motion extending beyond the cRF, and that this is based on fine-tuned surround interaction. Specifically, we measured global directional preference with a sequence of two focal stationary Gabor stimulithe preceding one (S1) presented outside the cRF and the following one (S2) presented inside the cRF with a stimulus onset asynchrony (SOA) of 50 or 100ms. The S1 stimulus appeared at either flanking sides of the cRF before the S2, thus making two directions of stimulus sequence. And this was compared with local directional preference that we measured with a Gabor stimulus confined within the cRF that drifted along two directions orthogonal to preferred orientation. Although the S1 alone did not evoke spiking responses, the response to the S2 was significantly modulated by the S1, consistent with the previous study (Kim et al., 2012). The magnitude of modulation was asymmetrical between the two sequence directions, indicating that the cells showed a direction preference for apparent motion consisting of S1 and S2 that extended beyond the cRF. There was a significant positive relationship between global and local directional preferences, suggesting that V1 neurons tend to prefer the global motion direction that matched with their local directional preference. This positive correlation was significant for SOA of 50ms, but not for 100ms. These results suggest that V1 neurons participate in processing global motion based on surround interaction that is fine tuned for spatial and temporal relations between center and surround stimuli.1. Introduction -------------------------------------------------------------------------------------1 2. Method -------------------------------------------------------------------------------------------5 2.1. Subjects ------------------------------------------------------------------------------------5 2.1.1. Surgical procedures -----------------------------------------------------------------5 2.1.2. Behavioral training: Fixation and saccade tasks --------------------------------6 2.1.3. Craniotomy and dura cleaning ----------------------------------------------------7 2.2. Experiment environment ----------------------------------------------------------------8 2.2.1. Computer system --------------------------------------------------------------------8 2.2.2. Stimuli ---------------------------------------------------------------------------------9 2.3. Measuring eye signal --------------------------------------------------------------------11 2.4. Measuring neural signal -----------------------------------------------------------------12 2.4.1. Electrophysiological procedures --------------------------------------------------12 2.4.2. Extracting Spikes -------------------------------------------------------------------13 2.4.3. Sorting Spikes -----------------------------------------------------------------------14 2.4.4. Confirming the single-unit classification ----------------------------------------16 2.4.5. Spike density function --------------------------------------------------------------17 2.4.6. Eliminating outliers -----------------------------------------------------------------18 2.5. Methods of data analysis ----------------------------------------------------------------23 2.5.1. Direction selectivity ----------------------------------------------------------------23 2.6. Experiment procedures ------------------------------------------------------------------25 2.6.1. Receptive field mapping -----------------------------------------------------------25 2.6.2. Main experiment --------------------------------------------------------------------27 3. Result ---------------------------------------------------------------------------------------------30 3.1. Data summary -----------------------------------------------------------------------------30 3.2. Classification of simple and complex cell ---------------------------------------------34 3.2.1. Criterion of Simple and complex cells ---------------------------------------------34 3.2.2. Response pattern to different spatial and temporal frequencies ----------------36 3.3. Local and global directionalities --------------------------------------------------------39 3.3.1. Representative cell implying positive relationship ------------------------------39 3.3.2. Representative cell showing the effect of surround is differed by the SOAs--44 3.3.3. Correlation analysis ------------------------------------------------------------------46 3.4. Surround modulation index -------------------------------------------------------------49 3.5. Speed of local and global motion -------------------------------------------------------50 3.6. Local directionality index measuring by F1 component -----------------------------52 3.7. Eccentricities and cortical distances of surround stimuli ----------------------------53 4. Discussion ----------------------------------------------------------------------------------------57 4.1. Global directionality ---------------------------------------------------------------------57 4.2. Sequential stimuli as a global motion stimulus ---------------------------------------58 4.3. Analysis period for calculating the mean response ----------------------------------59 4.4. Low proportion of simple cell & directional cell ------------------------------------59 4.5. Implications for motion processing ----------------------------------------------------60 References -------------------------------------------------------------------------------------------62 Abstract in Korean ---------------------------------------------------------------------------------68Maste

Different mutational characteristics of the subsets of EGFR-tyrosine kinase inhibitor sensitizing mutation-positive lung adenocarcinoma

BACKGROUND: A subset of lung adenocarcinoma with EGFR-tyrosine kinase inhibitor sensitizing mutations (mEGFR) is common in non-smokers and women, suggesting that mutational stressors other than smoking are involved. METHODS: Targeted sequencing using a custom panel containing 70 cancer-related genes were performed from 73 cases of lung adenocarcinoma with mEGFR (study cohort). In parallel, publicly available data of 47 TCGA-LUAD cases with mEGFR (LUAD cohort) were extracted from the GDC data portal and analyzed by non-negative matrix factorization using the Maftools package. RESULTS: In the study cohort, the C > A transversions accounted for 12.9% of all single nucleotide variations (SNVs), comprising the second smallest proportion among SNVs. The E19del-subgroup had a significantly lower mutational burden with significantly higher Ti/Tv ratio than the SNV-subgroup, which includes cases with L858R and other EGFR-TKI sensitizing SNVs. (P = 0.0326 and 0.0002, respectively, Mann-Whitney U test). In the LUAD cohort, the mutational burden was substantially lower than in other TCGA cancer cohorts, and the frequency of C > A transversions was 30.3%, occupying the second frequency. The E19del-subgroup had a lower mutational burden overall and a higher Ti/Tv ratio than the SNV-subgroup (P = 0.0497 and P = 0.0055, respectively, Mann-Whitney U test). Smoking-related signature 4 was observed only in the L858R-subgroup, while ignature 30 and 5 was observed in both groups. CONCLUSIONS: Lung adenocarcinoma with mEGFR(+) has a lower mutational burden and does not show a characteristic mutation pattern influenced by smoking. E19del and L858R, which are representative subtypes of mEGFR(+) lung adenocarcinoma, differ in terms of mutational spectrum, as the E19del-subgroup has a lower mutation burden and a higher Ti/Tv ratio than the SNV-subgroup. These findings could help explain the differences in the responses to EGFR-TKIs and in the clinical courses between the two lung adenocarcinoma subgroups.ope

A phase II, multicenter study of lazertinib as consolidation therapy in patients with locally advanced, unresectable, EGFR mutation-positive non-small cell lung cancer (stage III) who have not progressed following definitive, platinum-based, chemoradiation therapy (PLATINUM trial)

Introduction: The PACIFIC study demonstrated that durvalumab consolidation therapy significantly improved progression-free survival (PFS) and overall survival (OS) in patients with unresectable stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CCRT). However, there was no clinical benefit in both PFS and OS in epidermal growth factor receptor (EGFR) mutation-positive patient groups in a post hoc exploratory analysis. Moreover, the clinical effects of immune checkpoint inhibitors (ICIs) in EGFR mutation-positive stage IV NSCLC were demonstrated to be poor. Personalized treatment according to the mutation status is also required in stage III NSCLC. Lazertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), is newly developed and approved for use in Korea. Methods: This prospective, open, single-arm, multicenter, phase II clinical trial aims to evaluate the efficacy and safety of lazertinib as a consolidative therapy after CCRT treatment in unresectable, EGFR mutation-positive NSCLC stage III patients. The primary endpoint of this study is PFS, and the secondary endpoints are OS, objective response rate (ORR), duration of response (DoR), time to death or distant metastasis (TTDM), and safety profiles. Discussion: Our study may extend the indications for third-generation EGFR-TKIs to treat patients with stage III NSCLC. Moreover, using this drug to treat stage III NSCLC would emphasize the value of mutation analysis and personalized medicine. Trial registration: ClinicalTrials.gov NCT05338619.ope

Real-World Study of Osimertinib in Korean Patients with Epidermal Growth Factor Receptor T790M Mutation-Positive Non-Small Cell Lung Cancer

Purpose: Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation-positive non-small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea. Materials and methods: Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints. Results: A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects. Conclusion: Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation-positive in Korean patients with no new safety signals.ope