Mono-PEGylates of exenatide in branched and dimeric structures can improve in vivo stability and hypoglycemic bioactivity

Exenatide, a synthetic version of exendin-4, is a glucagon-like peptide-1 receptor agonist (GLP-1RA) used for treating diabetes, but its relatively short half-life is a major disadvantage. In this study, we attempted residue-specific mono-PEGylation to the middle of the amino acid backbone to extend its in vivo half-life. Exenatide was point-mutated from Lys to Cys at the 12th residue to yield a variant (K12C), and PEG-maleimide of varying molecular weights (MW) (5, 10, 20, 40 kD) was site-specifically conjugated to yield a mono-PEGylate with branched T-shape molecular structure. In another approach, we conjugated a bis-maleimide PEG (10 kD) to the middle of two K12Cs to yield an H-shape homodimer PEGylate In vitro bioactivity assays indicated that: (1) PEGylates conjugated with higher MW PEG lead to stronger receptor binding, (2) the branched form was superior to the linear configuration in the binding, and (3) both T-shape and H-shape mono-PEGylates demonstrated better potency than the native exenatide, evidenced by lower EC50. Db/db mouse experiments to evaluate in vivo hypoglycemic activity indicated that: (1) all mono-PEGylates resulted in improved glucose tolerance compared to the native exenatide, (2) the homodimer PEGylate demonstrated much stronger hypoglycemic activity, especially during the initial period, and (3) the H-shape and T-shape mono-PEGylates (40 kD) maintained hypoglycemia for up to ca. 168 and 140 h, representing approximately 12- and 14-fold increase, respectively, compared with the native exenatide. Our findings suggest that the exenatide mono-PEGylates in unclassical molecular structures can improve in vivo pharmacokinetics properties.This work was supported by a National Research Foundation (NRF) of Korea grant funded by the Korean government (MSIP) (No.2014R1A2A2A03004266)

Far-Field Polarization Measurement of PQR Laser and AOTF Realization

Maste

지역 동향] 울산지역의 인적자원개발 현황과 과제

울산지역 인적자원개발 현황 울산RHRD센터 소개 울산지역 시범사업 소개 기타 지역 특화사업 울산지역 인적자원개발의 과

「롤즈」의 社會 正義論에 나타난 平等主義의 含義에 관한 硏究 : 差等의 原理를 中心으로

학위논문(석사)--서울대학교 대학원 :국민윤리교육과,1999.Maste

A Study on Improvement Plan of Maritime Traffic Safety Audit Report Based on Text-Mining Analysis

Maritime traffic safety Audit is a kind of consultation process that secures the safety of ship passage and prepares a plan to reduce maritime accidents for various stakeholder in a wide range of areas due to the nature of maritime traffic. The result of this process, the maritime traffic safety audit report, is composed of a vast amount of text and is the most essential part of the maritime traffic safety audit system. Traditionally, text analysis methods include a method that the researcher directly reads and analyzes, and a text data approach that regards text as quantitative data and utilizes statistical techniques. The text mining method is one of the text data approaches, an effective method for quantitatively analyzing a large amount of unstructured data such as a maritime traffic safety audit report. In this study, the maritime traffic safety audit report was analyzed through the method. As a result of the analysis, issues such as the distribution of the roles of the central administrative agency and the local administrative agency, and improvement of standards for port design were derived. Since it may have an effect, it was suggested to improve the maritime traffic safety audit report by confirming that neutral words should be used as much as possible. As a result of the analysis, pending issues such as the distribution of the roles of the central administrative agency and the local administrative agency, and improvement of port design standards were derived. And according to the sentiment analysis result, a lot of positive words were used in general, but since this can have a direct/indirect effect on the evaluation of the maritime traffic safety audit report, it was suggested that neutral words should be used to improve the maritime traffic safety audit report.1. 서 론 1 1.1 연구의 배경 및 목적 1 1.2 연구의 내용 및 방법 3 2. 해상교통안전진단서의 구성 4 2.1 해상교통안전진단의 개요 4 2.2 해상교통안전진단서의 구성 6 2.3 주요 해상교통안전진단 사례 조사 8 2.4 해상교통안전진단의 한계 13 3. 텍스트 마이닝 기법 16 3.1 텍스트 마이닝 개념 16 3.2 텍스트 마이닝 과정 17 3.3 텍스트 마이닝 기법을 활용한 선행연구 조사 27 4. 해상교통안전진단서 분석 29 4.1 데이터의 수집과 분석방법 29 4.2 텍스트 마이닝 분석 35 5. 결 론 68 참고문헌 70 국문초록 74Maste

Accurate Positioning of the Moving Vehicle Using RFID

Telematics is regarded as the technology to enhance and make everyday-driving experience more comfortable and safer. An essential part of the telematics is navigation and it is based on GPS combined with map-matching and/or MEMS DR as the choice of positioning technology. However, GPS cannot supply position information continuously in case of poor visibility of satellites. In this paper, we research into techniques of RFID which may be regarded as a portion of USN sensor node in order to measure accurate position information of vehicles regardless of environment condition. RFID tag recognition is tested to verify feasibility of accurate positioning according to the speed of vehicle. We also propose characteristics of the USN sensor node and data format for positioning.ETR

Atomic-Scale Chemical Analysis for Understanding the Role of Dopant (Al, Ti, Zr) on the Structure Properties of Nickel-Rich Cathode for Lithium-Ion Batteries

1

Atomic-Scale Chemical Analysis for Understanding the Role of Dopant (Al, Zr) on the Structure Properties of Nickel-Rich Cathode for Lithium-Ion Batteries

1