Design, Synthesis, and SAR Studies of Novel Scaffolds for Drug Discovery

Ngoc Pham, Tuan-Anh Kangwon National Univ 2013 국내박사

SECTION 1 Design, Synthesis, and Anti-inflammatory Activity of Novel Unnatural C-S-C and C-NH-C Linked Biflavones Biflavonoids are polyphenolic molecules which belong to flavonoid family and consist of a dimer of flavonoids linked to each other by either a C?C or a C?O?C covalent bond. Many different chemical structures of biflavonoids have been isolated from plants and found to possess interesting biological properties. Ochnaflavone, a naturally occurring biflavonoid mainly found in the medicinal plant Lonicera japonica Thunb. (Caprifoliaceae), strongly exhibit anti-inflammatory activity through multiple mechanisms. Furthermore, several synthetic approaches yielded a series of C-C and C-O-C linked biflavonoids with anti-inflammatory potential. Therefore, biflavonoids might provide a basis for novel anti-inflammatory drugs. As a part of continuing structural elaboration and searching more potent anti-inflammatory agents, a series of unnatural C-S-C and C-NH-C linked biflavones were designed, synthesized and evaluated their anti-inflammatory activities. By using transition metal-catalyzed cross-coupling reactions, a series of unnatural C-S-C and C-NH-C linked biflavones including 4 analogues of ochnaflavone and 17 basic biflavones possessing a different array of flavone-flavone linkage were generated successfully. The initial anti-inflammatory activities of ochnaflavone analogues showed promising results relate to iNOS-mediated NO production inhibition. Especially, penta-O-methyl C-S-C linked ochnaflavone analogue (BFO-1) possesses a dual strong inhibitory activities against COX-2-mediated PEG2 and iNOS-mediated NO production. To date, BFO-1 is the only synthetic biflavone having a dual promising PGE2 and NO inhibitory activities. This novel scaffolds might provide a basis for further SAR studies. Keywords: unnatural biflavone, ochnaflavone, anti-inflammatory activity, C-S-C linkage, C-NH-C linkage, cross-coupling reaction. SECTION 2 Novel Scaffolds With Potent GPR119 Agonistic Activity: Design, Synthesis, and SAR Study GPR119 is a G-protein-coupled receptor predominantly express on pancreatic beta cells and intestinal enteroendocrine cells. GPR119 can be actived by lysophosphatidylcholine (LPC), oleoylethanolamine (OEA), N-oleoyldopamin (OLDA), ovalnil and OEA most probably represents the endogenous ligand. GPR119 agonist stimulates glucose-dependent insulin secretion in vitro and lowers an elevated blood glucose level in vivo. Furthermore, they have been demonstrated to stimulate the release of the incretin (GLP-1 and GIP). Therefore, GPR119 agonist has emerged as a promising target for the treatment of type 2 diabetes and obesity by improving glucose homoeostasis while concurrently slowing gastric emptying, reducing food intake and promoting weight loss. To date, several candidates have been entered clinical trials for treatment of type 2 diabetes. Diverse fused aromatic heterocycle scaffolds were found in the precedent literatures and patents of GPR119 agonists. As a congener of bicyclic heterocycle scaffolds, we were interested in quinazoline and purine heterocycle since they have emerged as promising scaffolds in medicinal chemistry and drug development. We have synthesized and characterized a series of novel 2,4-disubstituted quinazolines. We found that the analogues bearing (2-fluoro-4-methylsulfonyl)phenylamino and azabicyclic amine groups with N-Boc (12a, 12c and 12g) exhibited better EC50 values than that of OEA even though they appeared to be partial agonists. Recently, a SAR study with purine scaffold to discover more potent GPR119 agonists is under progress. A series of purine analogues possessing (2-fluoro-4-methylsulfonyl)phenylamino group and aza(bi)cyclic alcohol or aza(bi)cyclic amine groups were generated. Their human GPR119 agonistic activities will be shown in a near future. Keywords: GPR119 agonist, type 2 diabetes, quinazoline, purine, azabicyclic amine, azabicyclic alcohol

Observation of thermal transport and spin-orbit torque using magneto-optical Kerr effect

Pham, Ngoc Luu Ly Sungkyunkwan University 2022 국내석사

Magneto-optical Kerr effect (MOKE) is a powerful measurement that can be used to study both spin dynamics and heat conduction. In this study, we present time-resolved magneto-optical Kerr effect (TR-MOKE) measurement using a pump-probe technique to investigate the thermal characterization of various materials. A substrate/ferromagnetic metal (FM) structure is prepared, where FM acts as a transducer to detect the thermal transport in substrates of silicon, sapphire, and highly ordered pyrolytic graphite. In addition, we introduce the polar MOKE to understand the current-induced spin-orbit torques (SOTs) mechanism in magnetic heterostructures. By analyzing polar MOKE responses, we extract damping-like components and determine composition dependence spin Hall angle for heavy metal alloys/ferromagnetic samples.

Selective Encryption Scheme for Vector Map Data in DCT Domain using Shape Components

Pham Ngoc Giao 부경대학교 대학원 2014 국내석사

Recently years, vector map has developed, used in many domains, and in most cases vector map data contains confidential information which must be kept away from unauthorized users. Moreover, the producing process of a vector map is considerably complex and the maintenance of a digital map requires substantial monetary and human resources. In addition, widespread of vector map applications, and the rapid development of vector map contents, a large volume of valuable vector map dataset has been distributed illegally. Therefore the problem focuses on how to protect the vector map data for multimedia applications, storage and transmission. At this point, security techniques for vector map focusing on secure network, copyright and data encryption have been studied. This paper presents the selective encryption scheme in DCT domain for vector map security for multimedia applications, storage, transmission and distribution to authorized users. In proposed scheme, polylines and polygons in vector map are targets of selective encryption. Vector map is separated to select polylines and polygons, and then they are randomized vertices by random algorithms before changing them in DCT domain. Here, I present two ways to perform selective encryption in DCT domain. First way, polylines/polygons are classified into groups and then 1D-DCT. Second way, I arrange all coordinates of vertices of polylines/polygons into a two dimensional array and then 2D-DCT. In DCT domain, I select DC values of polylines/polygons to encrypt by random algorithm and cryptography. Experimental results verified that proposed algorithm is effectively and security. Maps are changed whole after encryption process, and unauthorized users cannot access to copy or use them. Encrypted maps do not alter the size of file and it does not have loss accuracy. The error between original map and decrypted map is approximate zero.

Optimal Control for Delay-Sensitive Traffic in Wireless Networks : Optimal Control for Delay-Sensitive Traffic in Wireless Networks

Ngoc-Thai Pham 인제대학교 2012 국내박사

Abstract Since real-timetraffichasbecomeadominanttrafficonthefutureInternet,delay performance mustbeconsideredasakeyfeatureindesignsforwirelessnetworks. This thesistacklesseveralcontrolproblemsfordelay-sensitivetrafficusingop- timal controlprinciples.First,weconsiderdelay-constrainedcontrolpolicies for insingle-hopwirelessnetworks.Theresultingpolicyisaschedulingpol- icywithdelayguarantees.Foracross-layerdesignthatinvolvesbothflowcontrol and scheduling,theresultingpolicyisaflowcontrolandschedulingpolicythat guarantees delayconstraintsandachievesutilityperformancewithin O(1=V ) of the optimality.Second,weextendtheproblemintooptimalcontrolofadelay- constrained trafficinmulti-hopwirelessnetworkswithflowcontrolandschedul- ing policy.Ourthesisdevelopsaschedulingandflowcontrolalgorithmwhich guarantees delayconstraintsandachievesnearoptimalityofutility.Finally,we consider thecooperationbetweenbasestationandrelaystationstoincreasesys- tem throughputintime-slottedrelayingwirelessnetworks,suchasdynamictime divisionmultipleaccesssystems.Wefocusonthroughput-optimalscheduling policies forthecooperativerelayingatthenetworklayerlevel.

Novel Materials For Solar Energy Conversion

Pham Ngoc Duy 금오공과대학교 대학원 2015 국내석사

Three objectives were formulated for this thesis. The first objective focuses on galvanic displacement of Gallium Arsenide (GaAs) surface. Such method is a simple and low-cost method to deposit metal nanoparticles and films. The second objective focuses on direct solar to hydrogen production by monolithic III-V triple junction integrated with low-cost catalyst. The third objective focuses on fabrication process of hybrid inorganic-organic perovskite solar cell. On the galvanic displacement of metal nanoparticles and films onto single-crystalline GaAs (100) substrates, a simple and cost-effective method to fabricate highly controlled metal/semiconductor interface is reported. A time-resolved surface analysis of Au/GaAs system was conducted and microscopic mechanism of galvanic displacement was elucidated in detail. Quantitative temporal XPS measurements of the Au/GaAs interface showed that, initially, fast Au growth was slowed down as deposition process proceeded. This was attributed to growing oxide layer blocking hole conduction and causing quenching of the deposition process. Addition of various inorganic acids, which function as oxide etchants, was found to enhance deposition rates by effectively removing surface oxide, with HF the most effective. Various precious metals, such as Pt and Ag, could be deposited onto GaAs through galvanic displacement, which demonstrates the versatility of the method.

Production of optically pure lactic acid by lactobacillus sp.

Pham, Ngoc Tu University of Ulsan 2015 국내박사

Gonadal Sex Differentiation of Hatchery-Reared Longtooth Grouper (Epinephelus bruneus)

Pham, Ngoc Sao 제주대학교 대학원 2010 국내석사

This study was investigated the gonad development of the longtooth grouper (Epinephelus bruneus) from 1 to 365 days after hatching (DAH). Fertilized eggs were obtained from Marine and Environmental Research Institute, Cheju National University. Fish were sampled for histological analyses every five days from 1 to 50 DAH and then randomly until 365 DAH. The migrating primordial germ cells were first appeared in the area on the dorsal side of the intestine at 10 to 15 days after hatching (DAH). A diameter of the primordial germ cells ranged from 11.7 to 25.2 ㎛² at 10 and 15 DAH. The primordial gonad (PG) was first observed in 20 to 30 DAH larvae containing only somatic cell. The gonocytes were first observed at 45 DAH. At 50 DAH, the primordial gonad containing germ cells was surrounded by somatic cells and gonad remained undifferentiated. The initial ovarian cavity which was indicated by the presence of two elongated aggregations of somatic cells in the gonad at 60 DAH and then increased in size at 90 DAH. The ovarian cavity was formed at 110 DAH with large space. The oogonia were first observed in the edge of ovarian cavity of gonad at 140 DAH with average size was 13.3 ± 2.0 ㎛ in diameter. Primary-growth stage oocytes were observed in different lobules along of ovarian cavity at 270 DAH. The size of there primary-growth stage oocytes was 12.5 ± 4.7 ㎛ in diameter. The present observations indicates that ovarian differentiation associated with gonadal morphological begins at approximately 60 DAH and the gonads differentiate directly into ovaries in all experimental fish. 17α-methyltestosterone dose tested in this study could not induced masculinization of Longtooth grouper during gonadogenesis. The most effective period for sex reversal using androgen hormone treatment in Longtooth grouper (E. bruneus) could be at 50 DAH before formation of ovarian cavity.

3D printing security algorithms based on geometric features

Pham, Ngoc Giao Pukyong National University 2018 국내박사

With the development of 3D printing technology, 3D printing has recently been applied to many areas of life including education, healthcare, aerospace, automotive, industrial design and so on. Due to the fact that the benefit of 3D printing is great, 3D printing models are often copied, shared and used several times without charging any copyright fee from the original providers. Besides, user can download 3D weapon models from the Internet and easily print them out without any restriction from the production managers or share them unlimitedly. Moreover, 3D printing models are also attacked by hackers and distributed without agreement from the original providers. Furthermore, certain special models and anti-3D weapon models in 3D printing must be protected against unauthorized users. Therefore, the original providers desire a watermarking algorithm to protect the copyright of 3D printing. In addition, an anti-3D weapon model detection algorithm for safe 3D printing is also necessary to restrict the printing of dangerous 3D weapon in 3D printing industry. Finally, in order to prevent attacks, illegal copying and to ensure that all access is authorized, 3D printing models should be encrypted before being transmitted and stored. This thesis proposes and presents three algorithms which will respond to the copyright protection of 3D printing, safe 3D printing and 3D printing model encryption. First algorithm is a watermarking method for 3D printing based on the Menger curvature of facet and the K-mean clustering to protect the copyright of 3D printing. Second algorithm is an anti-3D weapon model detection algorithm for safe 3D printing based on the D2 shape distribution and improved convolutional neural networks. This algorithm detects anti-3D weapon model to prevent the printing of them when they are used as the input of 3D printing. Third algorithm is a novel perceptual encryption algorithm for 3D printing models for secure storage and transmission. This algorithm is based on encrypting the features of the interpolated spline curve of degree 2 in 3D space to obtain the encrypted 3D printing model. Experimental results showed that the proposed algorithms are responsive to the various formats of 3D printing models. The proposed watermarking for 3D printing is invisible, robust to geometric transformations. And the accuracy of the proposed watermarking is higher than the conventional works and previous proposed methods for 3D printing. Anti-3D weapon model detection algorithm provides a better solution for safe 3D printing than the matching methods. Finally, the results of the perceptual encryption process is more superior to the results of the previous methods. The proposed algorithm also provides a better method and more security than previous methods. 3D 프린팅 기술의 발전과 함께 3D 프린팅은 최근 교육, 의료, 우주 항공, 자동차, 산업 디자인 등 다양한 삶의 영역에 적용되고 있다. 하지만 이런 3D 프린팅의 이점에도 불구하고 원 저작자에게 저작권료를 청구하지 않고 무단으로 3D 프린팅 모델을 여러 번 복사 및 공유, 사용하는 문제가 발생하고 있다. 최근에는 인터넷에서 3D 무기 모델을 다운로드하여 제작, 관리자의 제한 없이 쉽게 프린팅하거나 무제한 유통하는 사건이 발생하고 있으며, 원 공급자 및 관리자의 동의 없이 해커들이 불법적으로 3D 프린팅 모델을 취득, 배포하는 문제 역시 빈번하게 발생하고 있다. 특히 3D 프린팅의 특정, 특수 모델 및 무기 모델을 프린팅하는 경우, 범죄에 악용되는 등 심각한 피해를 초래할 수 있으므로 반드시 권한이 없는 사용자로부터 보호되어져야 한다. 이와 같은 문제점을 해결하기 위해서는 원저작자의 3D 프린팅 모델 저작권을 보호하고 불법 3D 프린팅 사용자들이 위험한 3D 무기를 제작하지 못 하도록 워터마킹 알고리즘과 3D 무기 모델을 탐지하는 알고리즘이 필요하고 해킹이나 불법 복사를 방지하여 3D 프린팅의 도면을 안전하게 사용할 수 있도록 하는 암호화 알고리즘 등이 필요하다. 본 논문에서는 저작권을 보호하고 안전한 3D 프린팅 활용을 위해 3 가지 보안 알고리즘을 제안한다. 첫 번째는 3D 프린팅의 저작권을 보호하기 위한 Menger 곡면의 곡률과 K-mean 클러스터링을 기반으로 하는 워터마킹 알고리즘이고 두 번째는 D2 모양 분포에 기반한 안전한 3D 프린팅을 위한 안티 3D 무기 모델 검출 알고리즘과 향상된 CNN 기법이다. 본 기법은 3D 무기 모델을 감지하여 불법 제작을 방지한다. 세 번째는 3D 프린팅 모델의 안전한 저장 및 전송을 위한 새로운 지각 암호화 알고리즘으로, 본 알고리즘은 3D 공간에서 2차수의 보간 스플라인 곡선의 피쳐를 암호화하여 암호화 된 3D 프린팅 모델을 얻는다. 본 논문에서 실시한 실험 결과를 통해 제안된 알고리즘이 다양항 형식의 3D 프린팅 모델에 적용 가능함을 확인 하였으며, 3D 프린팅에 적용된 워터마킹이 비가시성을 만족하면서 기하학적 공격에도 강하고 모델의 정밀도 역시 기존 기법들에 비해 높은 것을 확인하였다. 그리고 본 논문에서 제안한 안티 3D 무기 모델 검출 알고리즘이 기존 매칭 기법에 비해 성능이 뛰어난 것 역시 확인하였다. 마지막으로 제안한 지각적 암호화 기법의 결과 역시 기존 기법에 비해 더 강한 보안을 제공하는 것을 확인할 수 있었다. 이를 통해 본 논문에서 제안하는 3D 프린팅 보안 알고리즘이 뛰어난 보안성으로 3D 프린팅 활용 분야에 널리 적용될 수 있을 것으로 예상된다.

A SIMO DC-DC buck converter using output voltage-related charge control scheme

Pham Ngoc Son 중앙대학교 대학원 2015 국내석사

Low cross-regulation, high-efficiency SIMO DC-DC converters using charge control

Pham, Ngoc Son Chung-Ang University 2019 국내박사

Recently, the complexity of portable devices increases rapidly due to the reduction in technology scale. Therefore, single-inductor multiple-output (SIMO) DC-DC converters become indispensable power management units in such systems. This dissertation introduces two architectures for SIMO DC-DC buck converter. The first idea focuses on reducing the cross regulation effect between output channels. The proposed output-voltage-aware charge control (OVACC) calculates the energy required by all the outputs to produce the exact amount of energy from the input. Thank to this balance of energy, the cross regulation in measurement is relative small – around 0.035mV/mA. The maximum power efficiency is 86%. The second idea concentrates on simplifying the complexity of the control block, at the same time, it produces small cross regulations and maintains a high efficiency for a wide load range. The proposed hybrid comparator-charge control can simplify the control block by utilizing comparators for most of the outputs. The low cross regulation is achieved by using a freewheeling switch. However, the on-time duration of the freewheeling switch will disappear in steady state. Frequency hopping with energy maintaining scheme is introduced to obtain high power efficiency for a wide load range. Simulation results show that the converter produces a 60mV cross regulation at any load change. Maximum power efficiency is 92%, and a high power efficiency is maintained over the load power ranged from 50mW to 660mW. The both converters were implemented in 0.18 1P6M CMOS process. And both of them can operate in both continuous-conduction-mode (CCM) and discontinuous-conduction-mode (DCM) which is suitable for wide load-range applications. 최근 휴대기기의 복잡성은 소형 설계 기술의 발달로 인하여 급격히 증가한다. 따라서 이러한 복잡성을 가진 기기에 전력을 공급하기 위해 SIMO(Single Inductor Multiple Output)구조의 DC-DC 변환기를 필요로 한다. 본 논문에서는 Buck type SIMO DC-DC 변환기를 구성하는 방법을 소개한다. 첫번째 방법은 출력 재널간의 Cross-regulation을 줄이는 방법에 중점을 두었다. 제안된 OVACC(output-voltage-aware charge control)방법은 모든 출력에 필요한 에너지를 정확히 계산, 그 총량을 입력으로부터 공급할 수 있도록 하는 방법이다. 이러한 입출력 간의 에너지량 계산은 Cross-regulation(약 0.035mV)을 줄이는데 매우 효과적이다. 이렇게 제안된 구조의 최대 전력변환효율은 86%이다. 두번째 방법은 제어부의 복잡성을 개선하는 것에 중점을 두면서 작은 crossregulation과 넓은 공급 전압 변화 범위를 가진다. 이렇게 제안하는 방법(hybrid comparator-charge control)은 대부분의 출력에 비교기를 사용하여 제어부를 단순화하였다. 그리고 작은 crossregulation은 freewheeling switch를 통하여 보장하는 방법을 사용하였다. 그러나 제안하는 방법에서는 Freewheeling switch는 안정상태에서는 사용되지 않고 각 부하들의 전력사용량이 변화할때만 사용된다. 또한 이번 제안하는 방식에서는 넓은 부하 범위에서 높은 전력 효율을 얻기 위해 에너지 유지 방식을 사용하는 주파수 호핑을 도입하였다. 이러한 방법을 통하여 시뮬레이션 한 결과 컨버터가 만들어내는 cross-regulation은 최대 60mV이내이고 전력 변환 효율을 92%, 부하전력 사용량은 50mW ~ 660mW범위로 설계되었다. 본 논문에서 제안한 두가지 컨버터는 모두 0.18 1P6M CMOS 공정으로 구현되었다. 또한 모두 CCM/DCM 모드에서 동작하도록 설계되었고 이는 부하 전력사용량의 범위를 넓게 한다.