198,838 research outputs found
A 43.4μW photoplethysmogram-based heart-rate sensor using heart-beat-locked loop
No full textPhotoplethysmogram (PPG) sensors have gained great popularity in recent years as they can easily obtain heart rate (HR) in wearable devices such as smart watches and smart rings. However, one of the biggest problems for PPG sensors is their large power consumption, as wearable devices are highly limited in its battery capacity. The power consumption of a PPG sensor is typically dominated by the LED driver, which requires several to a few tens of mA of current. Thus, many previous works are aimed at reducing the LED driver power [1-5]. The most widely used method is duty-cycling the LED by using a train of discrete pulses instead of always turning on the LED [1-4]. As a PPG signal has low bandwidth, the duty-cycle ratio of the LED can be as low as 1%. Another low-power method is compressive sampling, which exploits the sparse nature of PPG signals [5]. Although it can reduce the effective duty-cycle ratio down to 0.0125%, a critical problem is that a large power consumption is required in reconstructing the compressive-sampled signal. In this work, we present an ultra-low-power PPG sensor with a heartbeat-locked loop (HBLL) that turns on the LED only during the PPG peaks and thus achieves an effective duty cycle of 0.0175%. We also reduce the power consumption of the analog front-end (AFE) by using the HBLL, which is in contrast to previous works where AFE power is not duty-cycled. A prototype implemented in 0.18μm CMOS demonstrates 43.4μW of total power consumption with less than 2.1bpm error in heart rate
Jang, Seok Hun
No full text학위논문(석사)--아주대학교 일반대학원 :의학과,2008. 2척수소뇌성운동실조증 제7형(SCA7) 또는 상염색체우성 소뇌성운동실조증 제II형(ADCA II)은 주로 소뇌와 망막의 이상기능과 퇴행에 의한 소뇌성 운동실조와 실명을 임상적 특징으로 하는 상염색체 우성의 진행성 신경퇴행질환이다. SCA7의 유병률은 전세계적으로 인구 약 1,000,000명 당 1-4명이다. SCA7은 Ataxin-7 단백질을 코드하는 ATXN7 유전자 내의 불안정한 CAG 반복서열의 확장으로 유발된다. 정상 ATXN7 대립유전자에서 CAG 반복서열의 수는 4-35개이다. 돌연변이 대립유전자의 CAG 확장범위는 36에서 460개이며, 이러한 CAG 반복서열 수는 질병발병의 나이와 반비례를 보인다. 하지만 28-35개의 CAG를 갖는 중간형 대립유전자는 자식세대로 넘어가면서 CAG 반복서열이 확장되면서 돌연변이 대립유전자로 전환될 수 있다. Ataxin-7은 많은 CNS, 비 CNS 조직들에서 관찰되나 질병을 일으키는 증상들은 단지 몇 가지 신경계 세포(예를 들어 조롱박세포와 원뿔 및 막대 세포)에 국한된다. Ataxin-7의 기능은 완전히 밝혀지지 못하였으나 최근 들어 히스톤 아세틸전이효소의 활성을 갖는 전사 공동활성자복합체(TFTC 또는 STAGA)의 구성요소로 추정되고 있다.
현재까지도 SCA7을 포함한 폴리글루타민(poly Q) 질환에 효과적인 치료법은 개발되지 못하였다. 돌연변이 대립유전자 발현의 억제는 SCA7의 근본적인 치료법이 될 수 있다. 최근 들어 이중가닥의 RNA(dsRNA)로 유도되는 RNA 간섭(RNA interference, RNAi)을 이용한 방법이 표적으로 하는 유전자의 발현을 억제하는 데에 매우 유용한 방법으로 대두되고 있다. 이러한 새로운 방법은 DNA 염기서열 특이적 유전자 억제를 위한 유일한 도구가 되며 폴리글루타민 질환과 같은 기능획득성(gain of function) 질환들에 있어서 부작용이 가장 적은 잠재적인 치료법이 될 수 있다.
이 연구에서 SCA7의 치료를 위해 돌연변이 ATXN7 대립유전자 특이적 또는 비특이적인 두 종류의 RNAi 시스템을 구축하고자 하였다. 돌연변이 대립유전자 특이적 RNAi 시스템을 제작하기위하여 ATXN7 유전자 내에 기존에 알려진 두 단일염기변이(SNP)를 이용하였다. 그 중 한 SNP(G 또는 A)는 엑손 12(ORF에 존재)에 위치하며 다른 한 SNP(G 또는 A)는 엑손 13(3‘-UTR에 존재)에 위치한다. 이들 두 SNP의 빈도를 한국인 SCA7 환자에서 밝히기 위해, 16명의 SCA7 환자들로부터 두 유형의 SNP의 빈도수를 분석하였다. 엑손 12의 A가 84%, G가 16%이었으며, 엑손 13의 경우는 반대로 G가 84%, A가 16%로 존재하였다. 이형접합률은 31.3%로서 나타났으며, 이것은 돌연변이 단백질 선별적 억제 치료가 가능한 수치이다. 최초 두 SNP 유형을 조합할 경우 보다 높은 이형접합률을 확보해 돌연변이 대립유전자 특이적 발현억제 RNAi에 보다 많은 환자의 적용이 가능하리라 판단하였다. 하지만 SNP 분석결과 엑손 12의 G와 엑손 13의 A가 서로 연관되어 있는 것으로 나타나 실제로 그 가능성은 높지 않은 것으로 밝혀졌다. 엑손 12의 G/A SNP를 이용하고자 A와 G를 타깃으로 하는 각각의 short hairpin RNA(shRNA) 발현 construct를 제작하였다. HeLa 세포에서 이들 두 RNAi construct RNAi-A와 RNAi-G는 SNP를 인지하는 대립유전자 특이적 방식으로 돌연변이 Ataxin-7(55Q)의 발현을 각각 약 80%, 50%까지 억제하였다. 또한 이러한 RNAi 적용시, 세포자멸사 유도제인 staurosporine(STS)에 의해 유도된 SK-N-SH(신경모세포종 세포주)의 세포자멸사의 진행이 억제되는 것을 일부 확인하였다. 다음으로, ATXN7 돌연변이 대립유전자 비특이적인 shRNA construct를 제작하였다. 이 중 하나가 Ataxin-7의 발현을 약 80%까지 감소시켰다. 상기의 두 가지 시스템으로 제작한 shRNA는 HeLa 세포에서 돌연변이 Ataxin-7(55Q)의 과발현에 의하여 형성된 핵포함체(응집)를 눈에 띄게 감소시켰다. 이러한 결과로부터 유추해 볼 때, 대립유전자 특이적 및 비특이적 돌연변이 Ataxin-7의 발현억제를 위한 두 RNAi 시스템을 조합하여 사용한다면, 추가적인 상승효과를 가져와 SCA7의 새로운 치료법으로서 큰 효과가 기대된다.― 국문요약 ― = i
그림 차례 = vi
표 차례 = vii
I. 서론 = 1
II 재료 및 방법 = 13
A. 주요 실험재료 = 13
B. SCA7에 대한 분자유전학적 분석 = 13
1. 조직별 CAG 반복서열 수 분석 = 13
2. ATXN7의 두 SNP 타입 분석 = 14
C. Ataxin-7 발현 벡터 제작 = 16
1. PCR 프라이머 디자인 = 16
2. RNA 추출 및 cDNA 합성 = 16
3. ATXN7 유전자 클로닝 = 18
4. Ataxin-7 발현 벡터 제작 = 19
D. shRNA 발현 벡터 제작 = 20
1. PCR 프라이머 디자인 = 20
2. 인간의 U6 프로모터 클로닝 = 21
3. shRNA 발현 벡터 제작 = 21
E. 세포배양, 진핵형질전환, 약물처리 = 22
F. Western blotting = 26
G. 공초점현미경 관찰 = 27
III. 결과 = 28
A. 주요 SCA 유형별 유병률 분석 = 28
B. SCA7 환자 조직별 CAG 반복서열 수 분석 = 28
C. ATXN7 유전자의 두 SNP 타입 분석 = 32
D. Ataxin-7과 shRNA 발현 벡터 제작 = 36
E. 돌연변이 대립유전자 비선별적 RNAi의 효과 확인 = 36
F. 돌연변이 대립유전자 선별적 RNAi의 효과 확인 = 39
G. 공초점현미경을 통한 RNAi의 효과 확인 = 39
H. 돌연변이 대립유전자 선별적 RNAi 적용 후 세포자멸사 확인 = 42
IV. 고찰 = 44
V. 결론 = 50
참고문헌 = 51
― ABSTRACT ― = 58MasterSpinocerebellar ataxia type 7 (SCA7), autosomal dominant cerebellar ataxia type II (ADCA II), is a progressive autosomal dominant neurodegenerative disorder characterized clinically by cerebellar ataxia and blindness resulting from dysfunction and degeneration mainly of the cerebellum and retina. The prevalence of SCA7 is about 1-4 in 1,000,000 worldwide. SCA7 is caused by expansion of an unstable trinucleotide CAG repeat in ATXN7 gene which encodes Ataxin-7 protein. Normal ATXN7 alleles contain 4-35 CAG repeats. Expansion of CAG repeat in the mutant allele ranges from 36 to 460, with repeat length inversely correlated to the age of disease onset. However intermediate size alleles (having 28-35 CAG repeats) can be converted into mutational expanded alleles in offspring. Ataxin-7 exists in many CNS and non-CNS tissues but pathological symptoms are confined to a few types of neuronal cells (e.g. mainly Purkinje and cone-rod cells). The function of Ataxin-7 is not fully understood but currently supposed a subunit of a transcriptional coactivator complex (called TFTC or STAGA) that has histone acetyltransferase activity.
So far effective treatmentsof polyglutamine diseases containing SCA7 have not yet been developed. Inhibition of mutated allele expression provides a direct approach to SCA7 therapy. More recently, gene silencing through RNA interference (RNAi) by double-stranded RNA (dsRNA) has emerged as a powerful method to inhibit expression of targeted gene. This new method provides a unique tool for sequence-specific gene suppression and may hold great promise for a potential therapy of gain-of-function diseases like polyglutamine diseases with a minimal side effect.
In this study, we aimed establishing two RNAi systems for treatment of SCA7, a mutant allele-specific and a mutant allele-nonspecific system. For mutant allele-specific RNAi system, we used two known single nucleotide polymorphisms (SNPs) in the ATXN7 gene, a G/A SNP in the exon 12 (ORF region) and a G/A SNP in the exon 13 (3'-UTR region). At first, we have analyzed frequencies of two SNP types in the 16 Korean SCA7 patients. We found that in the exon 12 SNP A was 84% and SNP G was 16%, and in the exon 13 SNP G was 84% and SNP A was 16%. And heterozygosity is 31.3% in both of them. These all data are different from that of Japanese and Chinese. We first had assumed that combination of these two SNP typeswould be beneficialfor RNAi treatment of SCA7. But this assumption is not correct because two SNP types (G in the exon 12 and A in the exon 13) were related. To use the G/A SNP in the exon 12, we have engineered two short hairpin RNA (shRNA) expressing vector constructs targeting SNP A and G.. They suppressed the expression of mutant Ataxin-7 (55Q) with allele-specific manner by approximately 80% and 50%, respectively, in HeLa cells, indicating that theRNAi system for SNP A is more efficient than G.. Also we partially found that staurosporine-induced apoptotic progress decreased by this RNAi system in SK-N-SH (neuroblastoma cell line) cells. We have also engineered four shRNA constructs targeting ATXN directly by mutant allele-nonspecific manner. One of them decreased the expression of whole Ataxin-7 by approximately 80%. Furthermore, these two effective shRNAs significantly decreased the nuclear inclusion body (aggregation) generated by over-expression of YFP-Ataxin-7 (55Q) in HeLa cells. Our results suggest that a combination of two shRNA systems for allele-specific and non-specific silencing of mutant Ataxin-7 may produce an additive effect on a new RNAi-based therapy for SCA7
산소가 제거된 수화학환경에서 저합금강의 저주기 피로거동
No full text학위논문(석사) - 한국과학기술원 : 원자력및양자공학과, 2008.2, [ xi, 63 p. ]After low cycle fatigue tests of SA508 Gr.1a low alloy steel in 310\degC deoxygenated water, the fatigue surface and the sectioned area of specimens were observed to understand the effect of the cyclic strain rate on the environmentally assisted cracking behaviors. From the fatigue crack morphologies of the specimen tested at a strain rate of 0.008 %/s, unclear ductile striations and blunt crack tip were observed. So, metal dissolution could be the main cracking mechanism of the material at the strain rate. On the other hand, on the fatigue surface of the specimen tested at strain rates of 0.04 and 0.4 %/s, the brittle cracks and the flat facets, which are the evidence of the hydrogen induced cracking, were observed. Also, the tendency of linkage between the main crack and micro-cracks was observed on the sectioned area. Therefore, the main cracking mechanism at the strain rates of 0.04 and 0.4 %/s could be the hydrogen induced cracking. Additionally, the evidence of the dissolved MnS inclusions was observed on the fatigue surface from energy dispersive x-ray spectrometer analyses. So, despite of the low sulfur content of the test material, the sulfides seem to contribute to environmentally assisted cracking of SA508 Gr.1a low alloy steel in 310\degC deoxygenated water. Additionally, our experimental fatigue life data of SA508 Gr.1a low alloy steel (heat A) showed a consistent difference with statistical model produced in argon national laboratory. So, additional low cycle fatigue tests of other heat SA508 Gr.1a (heat B) and SA508 Gr.3 low alloy steels were performed to investigate the effect of material variability on fatigue behaviors of low alloy steels in 310\degC deoxygenated water. In results, the fatigue lives of three low alloy steels were increased following order; SA508 Gr.1a low alloy steel - heat A, SA508 Gr.3 low alloy steel, and SA508 Gr.1a low alloy steel - heat B. From microstructure observation, the fatigue surface of SA508 Gr.1a low alloy ...한국과학기술원 : 원자력및양자공학과
Convex Programming Approach of Robust Powered Descent Guidance through Dynamic Tube MPC
No full textThis paper presents robust powered descent guidance(PDG) algorithm based on dynamic tube model predictive
control(MPC). Employing the dynamic tube MPC as a baseline guidance methodology, the modeling error
and disturbances are explicitly considered in the MPC problem and the robust control invariant tube geometry is
simultaneously optimized along with the original powered descent guidance states. Furthermore, the proposed
robust PDG problem is transformed into convex optimization framework through sequential convex programming(
SCP) algorithm which is suitable form for real-time application. In the end, numerical experiments are
carried out to validate the performance and robustness of the proposed PDG algorithm
Feasibility assessment of the alumina-forming duplex stainless steels as accident tolerant fuel cladding materials for light water reactors
No full textPreviously, the Fe-based alumina-forming duplex stainless steels (ADSSs) were developed for the application of accident tolerant fuel (ATF) cladding materials for light water reactors (LWRs). The on-going research activities focusing on the feasibility assessment of ADSS alloys for ATF cladding are summarized. A long-term corrosion behavior in simulated LWR environment and short-term corrosion resistance in steam environment at temperature range of 800 degrees C to 1200 degrees C were performed, and the results showed excellent corrosion resistance of ADSS alloys. The tensile properties of ADSS alloys were evaluated at room temperature to 550 degrees C, which showed much higher strength compared with other Fe-based alloys. After accelerated thermal aging at 425 degrees C for 1000 hours, strength of ADSS alloys was increased and the elongation was decreased. However, the elongation of aged ADSS alloys was still greater than 15% because of the presence of ductile austenite phase. Meanwhile, because of the neutron absorption by Ni, Cr, and Fe, the use of ADSS alloys as ATF cladding would have detrimental effects on the fuel cycle length. Nonetheless, it was assessed that the neutronics penalty could be readily overcome by adopting thinner fuel cladding and slightly higher fuel enrichment. Finally, the fabrication of thin-walled tube was introduced. Overall, it has been shown that ADSS alloys could be considered as candidate alloys as ATF cladding materials.
Canadian multiculturalism policy and ethnicity
No full textThesis(Master) --KDI School:Master of Public Policy,2002masterpublishedby Jung Ae Jang
Designing zero-dimensional dimer-type all-inorganic perovskites for ultra-fast switching memory
No full textHalide perovskite has been applied for resistive switching memory devices, but there are challenges remained to achieve practical application. By using high-throughput screening based on first-principles calculations, the authors discover that lead-free dimer-Cs3Sb2I9 meets the requirements, which exhibits switching speed of 20 ns
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