Biallelic Deletion of Pxdn in Mice Leads to Anophthalmia and Severe Eye Malformation

Peroxidasin (PXDN) is a unique peroxidase containing extracellular matrix motifs and stabilizes collagen IV networks by forming sulfilimine crosslinks. PXDN gene knockout in Caenorhabditis elegans (C. elegans) and Drosophila results in the demise at the embryonic and larval stages. PXDN mutations lead to severe eye disorders, including microphthalmia, cataract, glaucoma, and anterior segment dysgenesis in humans and mice. To investigate how PXDN loss of function affects organ development, we generated Pxdn knockout mice by deletion of exon 1 and its 5' upstream sequences of the Pxdn gene using the CRISPR/Cas9 system. Loss of both PXDN expression and collagen IV sulfilimine cross-links was detected only in the homozygous mice, which showed completely or almost closed eyelids with small eyes, having no apparent external morphological defects in other organs. In histological analysis of eye tissues, the homozygous mice had extreme defects in eye development, including no eyeballs or drastically disorganized eye structures, whereas the heterozygous mice showed normal eye structure. Visual function tests also revealed no obvious functional abnormalities in the eyes between heterozygous mice and wild-type mice. Thus, these results suggest that PXDN activity is essential in eye development, and also indicate that a single allele of Pxdn gene is sufficient for eye-structure formation and normal visual function.ope

Association of Metabolomic Change and Treatment Response in Patients with Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the major cause of chronic liver disease, yet cost-effective and non-invasive diagnostic tools to monitor the severity of the disease are lacking. We aimed to investigate the metabolomic changes in NAFLD associated with therapeutic responses. It was conducted in 63 patients with NAFLD who received either ezetimibe plus rosuvastatin or rosuvastatin monotherapy. The treatment response was determined by MRI performed at baseline and week 24. The metabolites were measured at baseline and week 12. In the combination group, a relative decrease in xanthine was associated with a good response to liver fat decrease, while a relative increase in choline was associated with a good response to liver stiffness. In the monotherapy group, the relative decreases in triglyceride (TG) 20:5_36:2, TG 18:1_38:6, acetylcarnitine (C2), fatty acid (FA) 18:2, FA 18:1, and docosahexaenoic acid were associated with a decrease in liver fat, while hexosylceramide (d18:2/16:0) and hippuric acid were associated with a decrease in liver stiffness. Models using the metabolite changes showed an AUC of >0.75 in receiver operating curve analysis for predicting an improvement in liver fat and stiffness. This approach revealed the physiological impact of drugs, suggesting the mechanism underlying the development of this disease.ope

항공기용 구조물로 쓰이는 유리섬유 에폭시 수지 프리프레그의 경화 특성에 관한 연구

학위논문(석사)--서울대학교 대학원 :화학공학과,1995.Maste

CPTPP 암호화 조항의 발전에 관한 연구 : WTO와 디지털무역협정에 주는 함의를 중심으로

학위논문(석사) -- 서울대학교대학원 : 국제대학원 국제학과(국제통상전공), 2024. 2. 안덕근.This thesis explores the evolving relationship between encryption technologies, regulatory frameworks, and global trade, with a specific focus on the Information and Communication Technology (ICT) sector. Motivated by the increasing autonomy of the 'Encryption Provision' within digital trade agreements, as first introduced in the Technical Barriers to Trade (TBT) Annex of the Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP), the research aims to uncover meaningful implications for both the World Trade Organization (WTO) and the expanding landscape of digital trade agreements. The study begins with a thorough historical examination in Chapter 2, tracing the trajectory of encryption technology and its ramifications for international trade. Chapters 3 and 4 narrow the focus to the genesis of the encryption provision, utilizing Specific Trade Concerns (STC) databases and scrutinizing China's encryption-related regulations. This analysis reveals substantial trade barriers embedded in mandatory domestic encryption usage and joint cooperation, shedding light on the contextual basis for introducing encryption provisions, particularly in mitigating market entry barriers for ICT products. Chapter 4 conducts a comparative analysis of encryption provisions across various agreements, including the CPTPP, U.S.-Mexico-Canada Agreement (USMCA), and the UK-Singapore Digital Economy Agreement (UKSDEA). This comparative exploration seeks to extract valuable insights for devising strategies to address encryption-related challenges in future agreements. Chapter 5, building upon the comparative analysis, emphasizes the crucial role of the WTO's TBT regime in the digital trade realm. Specific recommendations for enhancement, particularly in addressing STC and TBT mechanisms, are presented, advocating for the reinforcement of encryption provisions in future digital domain agreements. Furthermore, the chapter extends its contribution by providing insights to guide the formulation of future digital trade agreements. In its entirety, this research not only traces the evolutionary path of encryption provisions but also delves into the prospective trajectory of trade agreements. By dissecting the intricate dynamics of encryption technologies within the global trade landscape, this study contributes a unique and forward-looking perspective to the discourse on the intersection of encryption, regulations, and international trade in the digital age.본 연구는 정보통신기술(ICT) 제품을 중심으로 암호화 기술, 규제 프레임워크 및 글로벌 무역 간의 유기적인 관계를 연구한다. CPTPP의 TBT 부속서에 최초로 등장한 암호화 조항이 최근 확산되고 있는 디지털무역협정에서 독자적인 조항으로 채택되는 추세에 착안하여, 이로부터 WTO와 디지털무역협정에 주는 함의를 도출하고자 한다. 제2장은 암호화 기술의 역사와 이 기술이 국제 무역에 미치는 영향을 조명하여 논문의 전반적인 이해를 돕기 위한 맥락을 제시한다. 제3장과 4장은 특정무역현안(STC) 데이터 베이스를 통해 암호화 조항의 출현 배경을 살펴본다. 가장 빈번히 STC 제기 대상으로 지목된 중국의 암호화 관련 규제 분석을 통해 자국 암호화 의무 사용 및 공동 협력 요건이 주요 무역장벽으로 작용하는 것을 확인하고, 이를 바탕으로 ICT 제품의 시장 진입 장벽을 해결하기 위해 설계된 암호화 조항의 도입 배경을 명확히 하였다. 제4장에서는 각기 다른 협정내에 자리잡은 암호화 조항을 비교 분석하여 시사점을 도출하고자 한다. 특히 영국-싱가포르 디지털 경제 협정(UKSDEA)을 포함한 엄선된 4개의 디지털무역협정의 비교 분석과 함께 CPTPP와 미국-멕시코-캐나다 협정(USMCA) 간의 암호화 조항의 차이를 면밀히 분석하여 향후 협정에서 암호화 관련 과제를 해결하기 위한 통상 환경을 수립하는 데 필요한 시사점을 도출한다. 비교 분석 결과를 기반으로 제5장에서는 디지털 무역과에서 WTO의 무역기술장벽(TBT) 체제의 중요성을 강조하며, 특정무역현안을 비롯한 TBT 체제의 개선과 관련된 구체적인 제언을 제시한다. 또한, 향후 디지털 관련 협정에서 암호화 조항의 중추적인 요소를 역설하며 해당 조항 개선의 필요성을 주장한다. 본 연구는 암호화 조항의 발전 과정 뿐만 아니라 미래의 디지털무역협정의 방향성을 탐색하고, 기존 다자무역체제 개선을 연구한다는 점에서 차별성과 의의를 지닌다.Chapter I. Introduction 1 1.1. Study Background 1 1.2. Purpose of Research 3 Chapter II. Encryption 5 2.1. Evolution of Encryption Technology 5 2.2. Encryption and International Trade 8 Chapter III. Chinas Encryption Regulations 15 3.1. Overview of Chinas Encryption Regulations 15 3.1.1. The STC database 15 3.1.2. The State Cryptography Administration 19 3.1.3. Administrative Measures for Commercial Encryption, Regulations for the Administration of Commercial Encryption . 20 3.1.4. WAPI 21 3.1.5. Regulation on the Management of Import and Export of Encryption Products (2004, 2017) . 22 3.1.6. Cybersecurity Law 23 3.1.7. Encryption Law . 24 3.1.8. MLPS 26 3.2. STC raised on Chinas Encryption Regulations 28 3.2.1. WAPI (ID 103) 29 3.2.2 Regulations on Commercial Encryption Products, MLPS (ID 294) 30 3.2.3. Cybersecurity Law (ID 526) 32 3.2.4. Encryption Law (ID 534) . 34 Chapter IV. Encryption Provisions 37 4.1. Encryption Provisions within Mega-FTAs 37 4.1.1. TBT Annex within CPTPP and USMCA 37 4.1.2. A Comparative Analysis of CPTPP and USMCA 42 4.2. Encryption Provisions within Digital Trade Agreements 47 4.2.1. DEPA, USJDTA, ASDEA, and UKSDEA 47 4.2.2. A Comparative Analysis of Digital Trade Agreements 49 Chapter V. Implications on Digital Trade Agreements and the WTO 56 5.1. Implications on Digital Trade Agreements 56 5.2. Implications on the WTO 61 Chapter VI. Conclusion 64 6.1. Conclusion 64 Bibliography 67 Abstract in Korean 71석

On the Relationship between Viscosity and Dielectric Loss Factor of a Thermoset Resin

본 연구에서는 열경화성 수지의 경화반응 중의 점도변화를 rheometrics mechanical spectroscopy (RMS)로 측정하였고, dielectric analyzer (DEA)의 결과와 비교하였다. 승온조건에서 수지의 점도는 온도가 올라감에 따라 감소하다가 경화가 진행되면서 급격히 증가하는 전형적인 열경화성 수지의 점도 변화 거동을 보이는 것을 확인하였다. 유전율 손실인자(ε")는 온도가 증가하면서 이온의 모빌리티가 중가함에 따라 커지다가 경화가 진행됨에 따라 서서히 감소하였다. 일반적으로 ε"은 점도에 반비례한다는 것이 알려져 있고, 이러한 관계는 경화가 진행되면 성립하지 않음을 관찰하였다. 본 연구에서는 80℃ 부근에 존재하는 열경화성 수지의 물리적 상변화를 중심으로 ε"과 점도사이의 관계가 변하는 것을 확인하였고, 따라서 물리적 상변화 과정은 이온의 전기전도도의 변화에 의해 결정된다는 것을 알았다. ; The change of complex viscosity measured by rheometrics mechanical spectroscopy (RMS) was compared with dielectric loss factor (ε") change measured by dielectric analyzer (DEA) in a curing reaction of a thermosetting resin. Complex viscosity of the resin initially decreased with increasing temperature and then increased rapidly due to the curing reaction within the resin. ε" initially increased with increasing temperature due to the increase of ionic mobility within the resin and then decreased slowly as the curing reaction progressed. It is generally known that there is a reciprocal relationship between complex viscosity and ionic conductivity or ε", and that this relationship is valid up to the onset of the curing reaction. In present study, it is, however, found that this reciprocal relationship between ε" and complex viscosity is changed at the phase transition around 80℃, which leads to imply that the physical phase transition of the resin before curing is due to the change in ionic conductivity

A Study on Curing Process of Epoxy/Glass Fiber Prepregs

본 연구에서는 항공기용 구조물로 많이 사용되는 에폭시/유리섬유 프리프레그의 경화 반응을 시차 주사 열량계 (differential scanning calorimetry (DSC)) 및 유전율 측정법 (dielectric analysis (DEA))을 사용하여 등온 및 가온 조건에서 살펴보았다. 프리프레그의 등온 경화 반응에 대한 실험 결과는 자촉매 (autocatalysis) 반응식으로 잘 표현됨을 알았다. 또한 실제 복합재료 가공 공정과 유사한 조건을 만들기 위하여 부분 경화 (fractional cure) 실험을 통하여 얻은 결과를 등온 실험에서 얻어진 경화 모델식의 예측과 비교하였다. 등온 조건에서 DEA 및 DSC 실험 결과로부터 정성적인 Time-Temperature-Transformation (TTT) 경화 곡선 (cure diagram)을 얻을 수 있었다. 등온 실험에서 얻어진 모델식의 가온 조건에서의 적용 가능성을 확인하기 위하여 초기 경화도 (α0)와 가온 비율 (heating rate)에 따른 영향을 가온 DSC 및 DEA 실험을 통하여 분석하였다. 가온 DSC 실험 결과 초기 경화도 (α0)가 0에서 0.46까지는 등온 실험에서 얻저진 경화식의 예측 결과보다 실제 경화 피이크가 높은 온도에서 나타남을 확인하였으며, 초기 경화도가 0.46 이상인 경우는 등온 경화 모델식의 예측과 일치된 실험 결과를 얻었다. 가온 조건 하의 DEA 실험 결과 경화 반응 이전에 80℃ 부근에서 물리적 전이 현상이 존재하는 것이 관찰되었고, 이러한 전이는 초기 경화도가 0.46 이상이 되면 사라짐을 관찰하였다. 따라서 고온에서 등온 DSC 실험을 하여 구한 모델식은 이러한 경화 온도 이전의 저온 영역에서의 전이를 고려할 수 없었기 때문에, 가온 실험 조건에서는 초기 경화도가 작을 때에 실험으로부터 구한 경화 곡선이 등온 모델식의 예측보다 느리게 나타나며, 초기 경화도가 약 0.4 이상이 되면 등온 모델식과 잘 맞는다는 것을 알 수 있었다. ; The curing behavior of epoxy/glass fiber prepregs, widely used for aeronautic structural materials, has been investigated under isothermal and dynamic conditions using a differential scanning calorimetry (DSC) and a dielectric analyser (DEA). The isothermal curing reactions for the prepregs were found to be well-expressed by the autocatalytic kinetics. The fractional cure experiments, which are closely related to the practical composite processing, were also performed and compared with results from the isothermal cure reaction. The experimental results obtained from DEA and DSC under isothermal condition allowed us to construct a qualitative Time-Temperature-Transformation cure diagram (TTT cure diagram). In order to test the possibility that the kinetic expression for the isothermal cure reaction can be applied to dynamic cure condition, the effect of initial degree of cure (α0) and heating rate on the dynamic curing behavior has been studied using DSC as well as DEA. Dynamic DSC experiments show that the experimentally determined temperature at cure peak is higher than that for the cure peak predicted from the isothermal cure kinetics when α0 ranges between zero and 0.46. When α0 is larger than 0.46 the experimentally determined dynamic cure exotherm is in good agreement with that predicted from the isothermal cure kinetics. From the DEA experiments under dynamic cure condition we observed that there was a physical phase transition around 80℃ before curing reaction and the physical transition at the low temperature was not considered in the isothermal kinetics obtained at high cure temperatures, causing the deviation from the model predictions. When α0 was larger than about 0.4 the physical transition around 80℃ disappeared which could, in turn, explain the good agreement between experiment and model predictions

Characterization of Composite Cure Behaviors Using The Dielectric Analysis (DEA) Technique

DEA(Dielectric Analyzer)를 사용하여 유리섬유/에폭시수지 복합재료의 경화반응을 등온 및 승온 조건 하에서 시험하였으며 기존의 열분석 및 유동특성 시험결과와 비교검토하였다. DEA의 등온시험 결과 일정한 시간대에서 Loss Tangent(Tan δ)의 Peak를 관창할 수 있었으며 이 현상은 수지의 Vitrification에 기인하는 것으로 판단된다. DEA의 승온시험에서는 저주파수 영역에서 3개의 Tan δ의 Peak가 나타났으며 점도측정 결과와 비교하면 각각의 Peak는 최저점도, 급격한 점도증가, 유리전이 지점과 일치한다는 것을 알 수 있었다. 정량적으로는 반응이 일어나기 이전의 수지점도를 DEA의 Loss Factor(ε")로부터 측정할 수 있었다. 또한 후경화반응에서 나타나는 미세한 반응변화,, 초기 경화반응에 따른 기계적 물성 변화, 높은 점도에서의 기계적 물성 변화 등 기존의 열분석 및 유동특성 분석장비로 측정이 제한되어 있는 현상들을 DEA를 이용하여 정성적으로 분석할 수 있었다. ; Cure behaviors of the glass fiber/epoxy(GF/Ep) prepreg were characterized using the dielectric analysis(DEA1 under both isothermal and dynamic cure conditions, and their results were compared with those measured by conventional thermal and rheological analysis techniques. In isothermal DEA experiments, the loss tangent(Tan δ) exhibited a peak at specific times which increased with decreasing frequencies. Comparing with the Differential Scanning Calorimetry (DSC) results, this phenomenon was likely to be attributed to vitrification of the resin matrix. On the other hand, the dynamic DEA thermograms exhibited three peaks in Tan δ at low frequencies corresponding to minimum viscosity, gelation/vitrification, and glass transition of the cured matrix, respectively. Quantitatively, the DEA loss factor(ε") was also found to be inversely proportional to the viscosity of the uncured resin matrix. In addition, the slight changes in mechanical and physicochemical properties occurring in the entire cycle of the curing process, which might be difficult to detect with conventional thermal and rheological analysis techniques, could be measured using the dielectric analysis method

The Effect of Blocking Layer Thickness on Dielectric Properties during the Curing of Epoxy/Glass Fiber Prepregs as Measured by a Remote Single Surface Sensor

본 연구에서는 항공기용 구조물로 쓰이는 에폭시/유기섬유로 구성된 프리프레그의 경화반응을 평판형 센서와 분리형 단평면 센서를 이용한 유전율 측정법을 통하여 등온조건에서 살펴보았다. 평판형 센서를 이용하여 측정한 결과 100 ℃의 등온 조건에서 일반적으로 경화반응이 종료된 것으로 판단되는 시간 이후에도 미세한 반응이 진행되고 있는 것을 알 수 있었다. 분리형 센서를 이용한 경우에는 차폐막 효과에 의해 유전율 상수와 손실 인자 등이 평판형 센서의 결과와 다른 형태를 보였고, 주파수를 낮출수록 이 영향은 크게 나타났나. 차폐막의 두께를 보정하여 평판형 센서의 결과와 비교함으로써 분리형 센서의 전기장이 미치는 범위가 센서 표면에서 약 1 mm 정도가 된다는 것을 알 수 있었고, 분리형 센서의 위와 아래에 각기 적층한 프리프레그의 두께를 달리하였을 때 측정되는 유전물성으로부터 이를 확인할 수 있었다. 또한 측정되는 유전물성은 분리형 센서의 아랫부분에 적층된 프리프레그의 두께에는 영향을 받지 않는다는 것을 알 수 있었다. ; Curing reaction of epoxy/glass fiber prepregs has been investigated under isothermal condition using dielectric analysis with both parallel plate electrode sensors and remote single surface sensors. Minute changes In dielectric properties eden after the end of curins reaction determined by other methods were detected with DEA carrying parallel plate sensors. Dielectric properties obtained with remote single surface sensors were generally different from those with parallel plate sensors due to blocking layer effect. which was observed to be more significant as applied frequency was lowered. Upon Correction due to blocking layer thickness, it was shown that the electric field of remote single surface sensor reached to about 1 mm above the sensor surface and it was confirmed by the results of dielectric properties measured with remote sensors inserted to different places across the prepreg thickness We also found that prepreg thickness beneath the sensor had no effect on the measured dielectric properties of the prepreg.본 연구는 1994년도 한국과학재단의 국제공동연구과제(94-KOSEF-NSF Joint Research Project)로 수행되었으며 이에 감사드립니다

Pax3 function is required specifically for inner ear structures with melanogenic fates

Pax3 mutations result in malformed inner ears in Splotch mutant mice and hearing loss in humans with Waardenburg’s syndrome type I. In the inner ear, Pax3 is thought to be involved mainly in the development of neural crest. However, recent studies have shown that Pax3-expressing cells contribute extensively to multiple inner ear structures, some of which were considered to be derived from the otic epithelium. To examine the specific functions of Pax3 during inner ear development, fate mapping of Pax3 lineage was performed in the presence or absence of functional Pax3 proteins using Pax3Cre knock-in mice bred to Rosa26 reporter (R26R) line. β-gal-positive cells were widely distributed in Pax3Cre/+; R26R inner ears at embryonic day (E) 15.5, including the endolymphatic duct, common crus, cristae, maculae, cochleovestibular ganglion, and stria vascularis. In the absence of Pax3 in Pax3Cre/Cre; R26R inner ears, β-gal-positive cells disappeared from regions with melanocytes such as the stria vascularis of the cochlea and dark cells in the vestibule. Consistently, the expression of Dct, a melanoblast marker, was also absent in the mutant inner ears. However, when examined at E11.5, β-gal positive cells were present in Pax3Cre/Cre mutant otocysts, whereas Dct expression was absent, suggesting that Pax3 lineage with a melanogenic fate migrated to the inner ear, yet failed to differentiate and survive without Pax3 function. Gross inner ear morphology was generally normal in Pax3Cre/Cre mutants, unless neural tube defects extended to the cranial region. Taken together, these results suggest that despite the extensive contribution of Pax3-expressing cells to multiple inner ear tissues, Pax3 function is required specifically for inner ear components with melanogenic fates.ope