Radiation-induced immune responses: mechanisms and therapeutic perspectives

정회빈,복서연,홍범주,Hyung-Seok Choi,안지완 대한혈액학회 2016 Blood Research Vol.51 No.3

Recent advancement in the radiotherapy technology has allowed conformal delivery of high doses of ionizing radiation precisely to the tumors while sparing large volume of the normal tissues, which have led to better clinical responses. Despite this technological advancement many advanced tumors often recur and they do so within the previously irradiated regions. How could tumors recur after receiving such high ablative doses of radiation? In this review, we outlined how radiation can elicit anti-tumor responses by introducing some of the cytokines that can be induced by ionizing radiation. We then dis-cuss how tumor hypoxia, a major limiting factor responsible for failure of radiotherapy, may also negatively impact the anti-tumor responses. In addition, we highlight how there may be other populations of immune cells including regulatory T cells (Tregs), mye-loid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) that can be recruited to tumors interfering with the anti-tumor immunity. Finally, the impact of irradiation on tumor hypoxia and the immune responses according to different radio-therapy regimen is also delineated. It is indeed an exciting time to see that radiotherapy is being combined with immunotherapy in the clinic and we hope that this review can add an excitement to the field.

Tumor hypoxia and reoxygenation: the yin and yang for radiotherapy

홍범주,김정우,정회빈,복서연,김영은,안지완 대한방사선종양학회 2016 Radiation Oncology Journal Vol.34 No.4

Tumor hypoxia, a common feature occurring in nearly all human solid tumors is a major contributing factor for failures of anticancer therapies. Because ionizing radiation depends heavily on the presence of molecular oxygen to produce cytotoxic effect, the negative impact of tumor hypoxia had long been recognized. In this review, we will highlight some of the past attempts to overcome tumor hypoxia including hypoxic radiosensitizers and hypoxia-selective cytotoxin. Although they were (still are) a very clever idea, they lacked clinical efficacy largely because of ‘reoxygenation’ phenomenon occurring in the conventional low dose hyperfractionation radiotherapy prevented proper activation of these compounds. Recent meta-analysis and imaging studies do however indicate that there may be a significant clinical benefit in lowering the locoregional failures by using these compounds. Latest technological advancement in radiotherapy has allowed to deliver high doses of radiation conformally to the tumor volume. Although this technology has brought superb clinical responses for many types of cancer, recent modeling studies have predicted that tumor hypoxia is even more serious because ‘reoxygenation’ is low thereby leaving a large portion of hypoxic tumor cells behind. Wouldn’t it be then reasonable to combine hypoxic radiosensitizers and/or hypoxia-selective cytotoxin with the latest radiotherapy? We will provide some preclinical and clinical evidence to support this idea hoping to revamp an enthusiasm for hypoxic radiosensitizers or hypoxia-selective cytotoxins as an adjunct therapy for radiotherapy.

The Extracellular Signal-Regulated Kinase Mitogen- Activated Protein Kinase Pathway in Osteoblasts

Matthew B. Greenblatt,Jae-Hyuck Shim,복서연,Jung-Min Kim 대한골대사학회 2022 대한골대사학회지 Vol.29 No.1

Extracellular signal-regulated kinases (ERKs) are evolutionarily ancient signal transduc- ers of the mitogen-activated protein kinase (MAPK) family that have long been linked to the regulation of osteoblast differentiation and bone formation. Here, we review the physiological functions, biochemistry, upstream activators, and downstream substrates of the ERK pathway. ERK is activated in skeletal progenitors and regulates osteoblast dif- ferentiation and skeletal mineralization, with ERK serving as a key regulator of Runt-re- lated transcription factor 2, a critical transcription factor for osteoblast differentiation. However, new evidence highlights context-dependent changes in ERK MAPK pathway wiring and function, indicating a broader set of physiological roles associated with changes in ERK pathway components or substrates. Consistent with this importance, several human skeletal dysplasias are associated with dysregulation of the ERK MAPK pathway, including neurofibromatosis type 1 and Noonan syndrome. The continually broadening array of drugs targeting the ERK pathway for the treatment of cancer and other disorders makes it increasingly important to understand how interference with this pathway impacts bone metabolism, highlighting the importance of mouse studies to model the role of the ERK MAPK pathway in bone formation.

Enhancement of antitumor effect of radiotherapy via combination with Au@SiO2 nanoparticles targeted to tumor-associated macrophages

Mi Sun Kim,Jae Sang Lee,Jung-Eun Kim,Jae-Won Kim,복서연,KiChangKeum,Won-Gun Koh,Woong Sub Koom 한국공업화학회 2020 Journal of Industrial and Engineering Chemistry Vol.84 No.-

Tumor-associated macrophages (TAMs) exhibit the M2 phenotype and serve as critical tumor-promotingimmune cells in the tumor microenvironment. As TAMs are an important target, we examined the effectof gold nanoparticles (AuNPs) with radiotherapy (RT) on M2 TAMs in tumors. We synthesized CD163antibody-conjugated, silica-coated AuNPs (CD163-GNPs) that were specifically recognized by M2 TAMs. Bone marrow-derived macrophages and Raw 264.7 macrophages were polarized into M1 and M2phenotypes. The effect of CD163-GNPs combined with RT was evaluated in a CT26 syngeneic mousemodel (BALB/c mice). Immunostaining,flow cytometry, microscopic analyses, enzyme-linkedimmunosorbent assay, quantitative real-time polymerase chain reaction (qRT-PCR), and tumor growthdelay assay were performed following irradiation combined with CD163-GNP treatment. We observedselective phagocytosis of CD163-GNPs by Raw 264.7 macrophages following M1/M2 polarization. Immunostaining analyses revealed higher numbers of CD163-GNPs taken up by M2 macrophages thanM0 or M1 type. CD163-GNPs combined with RT significantly reduced tumor growth in the CT26syngeneic mouse model. Macrophages subjected to the combination treatment showed increasedexpression of M1 markers. The depletion of M2 TAMs in tumors upon combination treatment withCD163-GNPs enhances the efficiency of RT.

모바일 애플리케이션을 통한 만성 요통의 관리 경험 연구: 인지행동치료와 재활운동의 복합적 적용 사례를 중심으로

박서라(Seora Park),이설희(Seolhee Lee),전하연(Hayeon Jeon),진예원(Yewon Jin),박재현(Jaehyeon Park),최치현(Chihyun Choi),임하진(Hajin Lim),박선영(Sunyoung Park),이준환(Joonhwan Lee) 한국HCI학회 2024 한국HCI학회 학술대회 Vol.2024 No.1

만성 요통은 단일 치료 방식을 넘어선 인지적, 신체적 영역을 아우르는 통합적 관리 방식을 필요로 한다. 따라서 본 연구는 만성 요통을 경험하는 성인 24 명을 대상으로 4 주 동안 인지행동치료와 재활운동을 함께 제공하는 모바일 애플리케이션에 대한 사용자 경험 연구를 진행했다. 이를 통해 수집된 정량적, 정성적 데이터의 분석 결과, 신체적 활동에 대한 참여자의 두려움이 줄고 지속적인 통증 관리에 대한 자신감과 신뢰도가 증가하였다. 하지만, 인지행동치료나 재활운동의 구체적인 일상 적용 부분에 대한 일부 제안점이 도출되었다. 더불어 사용자의 개인적, 사회적 맥락에 있어 고려해야 할 사용자 경험 요소들이 발견되었다. 본 연구는 향후 만성 요통을 다층적으로 관리하기 위한 모바일 시스템의 설계에 대한 함의점을 제공하였다는 의의를 갖는다.

의인화된 인공지능 스피커 디자인 제안 :인간 중심 인터페이스를 중심으로

박서현(Seo Hyeon Park),이하리(Ha Ri Lee),김숙연(Sook Yeon Kim) 한국HCI학회 2022 한국HCI학회 학술대회 Vol.2022 No.2

인공지능 스피커 시장은 70 억달러 이상의 가치를 가지고 있으며, 향후 지속적으로 성장할 것으로 예상된다. 하지만 상시 주변의 소리를 듣고 있음에도 작동 상태에 대한 올바른 기표를 제공하고 있지 않아 사용자는 개인정보침해에 대해 인지하기 어렵다는 문제가 꾸준히 발생되고 있다. 본 연구는 인공지능 기술 발전에 발 맞추어 인간적 속성을 가진 인공지능 스피커를 통해 사용자의 정서적 교류와 친밀감 향상을 목적으로 한다. 의인화 요소와 다양한 사용자 인터페이스에 관한 선행 연구를 진행하였고, 그중 비언어적 의사소통에 대한 이해를 바탕으로 디자인 제안을 하였다. 첫째, 의인화 요소 중 시각적으로 단순한 움직임을 표현할 수 있는 숨쉬는 모습을 제공한다. 둘째, 사용자의 동작을 학습하고 이해하여 인간 중심의 동작 인터페이스를 제공한다. 일상에서 사용하는 동작을 시각적으로 활용한다면 사용자와 인공지능 스피커는 원활한 인터랙션을 구성할 수 있을 것이다.

Functional Microbial Pigments Isolated from Chryseobacterium and Deinococcus species for Bio-paint Application

박서아,안수연,최권영 한국생물공학회 2020 Biotechnology and Bioprocess Engineering Vol.25 No.3

In this study, bioproduction and application of a microbial pigment from Chryseobacterium and Deinococcus species screened from soil were investigated. The pigments extracted from both cell cultures were identified as a flexirubin (FL)- and deinoxanthin-type (DX). The isolated pigments showed a mass value of 618.48 and 584.41 m/z by LC/MS, respectively. Flask production of the crude FL pigment in complex medium yielded 0.443 ± 0.047 g/L, while crude DX production was less than 20 mg/L. Similar to previously identified FL and DX pigments, both have unsaturated long-chain alkyl-substituted phenol and cyclohexanone units and showed excellent radical scavenging capacities of 0.6 and 3.2 mg/mL IC50 values, respectively. In order to utilize the pigments for functional painting materials, both pigments were mixed with casein paint to prepare FL bio-paint and DX bio-paint, respectively. Interestingly, yellow-colored FL bio-paint and red-colored DX bio-paint showed an outstanding coloration and coating performance onto glass plate. Furthermore, it was confirmed that the produced DX bio-paint had a unique crystal structure when analyzed by SEM.

자연채광 및 에너지 복합성능 최적화 프로세스를 통한 체육관 천창 통합설계

이병연(Lee, Byungyun),박서우(Park, Seowoo) 대한건축학회 2022 대한건축학회논문집 Vol.38 No.10

This study aimed to analyze multi-purpose optimized design alternatives for sports halls to minimize total energy consumption, maximize daylight quantity, minimize glare probability and develop meta-models to predict energy and daylight performance during the early design stage. The automatic optimization tool of Modefrontier integrated with the rhino-grasshopper model was developed and simulated with the energy plus and radiance engine. Three optimization phases were conducted, and the variable ranges and optimization algorithms were selected for each phases aim. In the first and second phases, the optimized cases were selected in the Pareto surfaces and compared to analyze the influence of glare prevention on the best-performing cases. Lastly, the meta-model was developed and presented to predict energy and daylight performance with a variation of the three most sensitive variables to predict the performance without energy simulation by architects and all participants. The rooftop daylighting model with cone-type lightwell was selected for the analysis with four geometric variables and two material variables for parametric design development. The results revealed that the window-floor-ratio was a dominant variable for all energy, useful daylight index, and daylight glare probability followed by tilting height and lightwell height. The window-floor ratio in the Pareto-optimized cases ranged between 11 and 21 percent in the first optimization without the glare-free objective; the range was reduced to between 8.5 and 14 percent. The range of lightwell height shrunk between 360 and 480 mm to between 240 and 360 in relieving glare. The developed response surface model with restricted window-floor ratio of 9.5-13 percent is expected to provide relevant information for future decision-making purposes.

Bio-indigo Production using Wild-type Acinetobacter sp. and Indole-3-acetate Monooxygenase (iacA) Expressed in Escherichia coli

안수연,박서아,Pradeep Kumar,최권영 한국생물공학회 2023 Biotechnology and Bioprocess Engineering Vol.28 No.2

This study reports the identification of a novel bio-indigo-producing bacterium from soil sources. Bluecolored colonies were first screened and isolated from a screening plate containing M9 minimal medium and 1.0mM indole. The blue colony was selected among various colonies and identified as an Acinetobacter species. The purified blue dye exhibited a distinct spectral feature of λmax at 490 nm. The structure of the dye was then analyzed. Thinlayer chromatography separation and liquid chromatography/ mass spectrometry analysis confirmed that the blue dye was indigo (with Rf and m/z values of 0.8 and 263.4, respectively). Wild-type Acinetobacter sp. could produce bio-indigo up to 1.018 ± 0.013 mg/L in an M9 minimal medium supplemented with 1.0 mM indole. Next, the genes involved in the production of indigo were investigated using sequence analysis and by comparing them with those in related Acinetobacter species. The indole-3-acetate monooxygenase-encoding gene iacA was found to be responsible for indigo synthesis from indole. The iacA gene was then amplified and expressed in Escherichia coli BL21(DE3), and the recombinant E. coli strain could produce bio-indigo at levels up to 0.291 ± 0.027 g/L over 24 h. Indigo production was highly dependent on indole substrate feeding. These findings may facilitate the industrial bioprocess of bio-indigo production.

GPT-4를 활용한 인간과 인공지능의 한국어 사용 양상 비교 연구

박서윤,김한샘,강예지,강조은,김유진,이재원,정가연,최규리 국어국문학회 2024 국어국문학 Vol.0 No.206

본 논문은 인간과 인공지능 모델이 생성한 텍스트 간 차이점을 밝히고자 에세이를 중심으로 형태론적, 통사론적, 사회언어학적 특징 등 언어학적 층위에 따라 연구하였다. 고등학교 1학년〜3학년 학생들이 작성한 에세이를 인간 생성 에세이 데이터셋으로 사용하였으며, 인공지능 모델 생성 데이터로는 GPT-4가 생성한 에세이를 사용하였다. 형태론적 층위 분석을 위해 품사 빈도와 어휘 다양도, 어휘 밀도 그리고 어휘 정교도를 사용하였으며, 카이 제곱 검정, 윌콕슨의 부호-서열 검정 등을 활용하여 인간과 GPT-4의 어휘 사용 양상 간 차이의 유의미성을 검정하였다. 검정 결과 품사 빈도, 어휘 다양도, 어휘 밀도에서는 유의 확률(p-value)이 모두 0.05 이하로 나타나 실제로 어휘 사용 양상에 통계적으로 유의미한 차이가 있음을 확인할 수 있었다. 어휘 정교도에서는 인간과 GPT-4 간 통계적으로 유의미한 차이가 드러나지 않았다. 통사론적 층위 분석은 문장 기초 특성과 의존 구문 분석 결과를 바탕으로 진행하였으며, 분석 결과 인간이 GPT-4보다 각 특성별로 편차와 분포가 넓은 양상을 보여 다양한 문장을 사용하여 에세이를 작성하고 있음을 확인할 수 있었다. 한편 구문 분석을 수행한 결과, 인간이 생성한 문장에는 VP와 AP가 상대적으로 빈번하게 등장하였고 GPT-4 생성 문장의 경우 NP와 수식 관련 성분이 자주 등장하였다. 언어 사용자 시각에서의 주체별 언어적 특징 분석을 위해 성별어 분석을 진행한 결과, GPT-4는 성별별 기호어, 혐오어, 그리고 성별 공통 혐오어를 거의 사용하지 않고 성별 공통 기호어는 자주 사용하는 경향을 보였다. 이에 따라 GPT-4는 성별 편향 혹은 혐오 표현에 대해 회피하도록 학습되었음을 확인하였다. 감성 분석의 경우에는 GPT-4가 생성한 에세이가 인간의 에세이보다 긍정의 극성을 가지는 비중이 높아, 학습 데이터 구성 시 부정적인 감성이 드러나는 데이터를 필터링하였거나 생성 시에 극성에 대한 조정이 가해졌을 가능성이 있음이 드러났다. This paper aims to enlighten the differences between texts which were generated by human and AI model, focusing on ‘essays’. We analyzed Korean usage patterns according to linguistic layers such as morphological, syntactic, and sociolinguistic features. In an aspect of dataset, we used essays written by high school students in the 1st to 3rd grades as ‘human-generated essays’, and essays generated by GPT-4 as data for ‘GPT-4 generated essays’. For morphological feature analysis, we used part-of- speech tag frequency, Type Token Ratio (TTR), lexical density, and lexical sophistication. We found that human and GPT-4 have different patterns of Part-Of-Speech by using statistical analysis. Also we observed that there are differences between human and GPT-4 in lexical features except lexical sophistication. The syntactic analysis was based on basic sentence characteristics and dependency parsing. The results showed that humans’ sentences have a wider range of deviations and distributions for each sentence characteristic than GPT-4s’, which indicates that humans write a variety of sentences than AI model. On the other hand, the dependency parsing showed that ‘VP’ and ‘AP’ appeared relatively frequently in human- generated sentences, while ‘NP’ and modifier(MOD) appeared frequently in GPT-4-generated sentences. To examine the linguistic features in the sight of language users, we analyzed gender-biased words, and found that GPT-4 rarely used gender-specific preferred words, gender-aversive words, and gender-common aversive words but frequently used gender-common preferred words. This suggests that GPT-4 has been pre-trained to avoid gender-biased or hate speech. In the case of sentiment analysis, GPT-4s showed more positive emotions than humans, and this also revealed that as same as gender bias results, GPT-4 has been pre-trained to generate positive sentences that negative sentences.