• 제목/요약/키워드: off-target effect

검색결과 60건 처리시간 0.021초

Rationally designed siRNAs without miRNA-like off-target repression

  • Seok, Heeyoung;Jang, Eun-Sook;Chi, Sung Wook
    • BMB Reports
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    • 제49권3호
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    • pp.135-136
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    • 2016
  • Small interfering RNAs (siRNAs) have been developed to intentionally repress a specific gene expression by directing RNA-induced silencing complex (RISC), mimicking the endogenous gene silencer, microRNAs (miRNAs). Although siRNA is designed to be perfectly complementary to an intended target mRNA, it also suppresses hundreds of off-targets by the way that miRNAs recognize targets. Until now, there is no efficient way to avoid such off-target repression, although the mode of miRNA-like interaction has been proposed. Rationally based on the model called "transitional nucleation" which pre-requires base-pairs from position 2 to the pivot (position 6) with targets, we developed a simple chemical modification which completely eliminates miRNA-like off-target repression (0%), achieved by substituting a nucleotide in pivot with abasic spacers (dSpacer or C3 spacer), which potentially destabilize the transitional nucleation. Furthermore, by alleviating steric hindrance in the complex with Argonaute (Ago), abasic pivot substitution also preserves near-perfect on-target activity (∼80-100%). Abasic pivot substitution offers a general means of harnessing target specificity of siRNAs to experimental and clinical applications where misleading and deleterious phenotypes from off-target repression must be considered.

Corporate Capital Structure Adjustments: Evidence from Vietnam Stock Exchange Market

  • NGUYEN, Cuong Thanh;BUI, Cuong Manh;PHAM, Tuan Dinh
    • The Journal of Asian Finance, Economics and Business
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    • 제6권3호
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    • pp.41-53
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    • 2019
  • Building a target capital structure is one of the most important decisions in corporate financial management. The purpose of this article is to identify the determinants of capital structure and adjustment mechanism toward the target leverage. The partial adjustment model was applied on a sample of 306 non-financial companies listed on Vietnam stock exchange market during the period of 2008-2017. By the fixed effect model estimation method, the research results have discovered the factors of growth opportunities, firm size, tangible fixed assets and firm's unique characteristics have a positive effect on the target capital structure of enterprises. Besides, profitability and dividend payment have a negative effect on the target capital structure of enterprises. Accordingly, the research results show that the average adjustment speed toward target leverage of the firms is 90.03%. Research results also demonstrate firms have higher or lower debt ratio than the target debt ratio, capital surplus or capital deficit also have an impact on the adjustment rate toward the target capital structure. The research results are consistent with the Dynamic Trade-off Theory. From this result, this article has provided policy implications for non-financial companies listed on Vietnam's stock market in building a reasonable target capital structure according to operating timeline to maximize enterprise value.

Effect of Target Angle and Thickness on the Heel Effect and X-ray Intensity Characteristics for 70 kV X-ray Tube Target

  • Kim, Gyehong;Lee, Rena
    • 한국의학물리학회지:의학물리
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    • 제27권4호
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    • pp.272-276
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    • 2016
  • To investigate the optimum x-ray tube design for the dental radiology, factors affecting x-ray beam characteristics such as tungsten target thickness and anode angle were evaluated. Another goal of the study was to addresses the anode heel effect and off-axis spectra for different target angles. MCNPX has been utilized to simulate the diagnostic x-ray tube with the aim of predicting optimum target angle and angular distribution of x-ray intensity around the x-ray target. For simulation of x-ray spectra, MCNPX was run in photon and electron using default values for PHYS:P and PHYS:E cards to enable full electron and photon transport. The x-ray tube consists of an evacuated 1 mm alumina envelope containing a tungsten anode embedded in a copper part. The envelope is encased in lead shield with an opening window. MCNPX simulations were run for x-ray tube potentials of 70 kV. A monoenergetic electron source at the distance of 2 cm from the anode surface was considered. The electron beam diameter was 0.3 mm striking on the focal spot. In this work, the optimum thickness of tungsten target was $3{\mu}m$ for the 70 kV electron potential. To determine the angle with the highest photon intensity per initial electron striking on the target, the x-ray intensity per initial electron was calculated for different tungsten target angles. The optimum anode angle based only on x-ray beam flatness was 35 degree. It should be mentioned that there is a considerable trade-off between anode angle which determines the focal spot size and geometric penumbra. The optimized thickness of a target material was calculated to maximize the x-ray intensity produced from a tungsten target materials for a 70 keV electron energy. Our results also showed that the anode angle has an influencing effect on heel effect and beam intensity across the beam.

No excessive mutations in transcription activator-like effector nuclease-mediated α-1,3-galactosyltransferase knockout Yucatan miniature pigs

  • Choi, Kimyung;Shim, Joohyun;Ko, Nayoung;Park, Joonghoon
    • Asian-Australasian Journal of Animal Sciences
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    • 제33권2호
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    • pp.360-372
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    • 2020
  • Objective: Specific genomic sites can be recognized and permanently modified by genome editing. The discovery of endonucleases has advanced genome editing in pigs, attenuating xenograft rejection and cross-species disease transmission. However, off-target mutagenesis caused by these nucleases is a major barrier to putative clinical applications. Furthermore, off-target mutagenesis by genome editing has not yet been addressed in pigs. Methods: Here, we generated genetically inheritable α-1,3-galactosyltransferase (GGTA1) knockout Yucatan miniature pigs by combining transcription activator-like effector nuclease (TALEN) and nuclear transfer. For precise estimation of genomic mutations induced by TALEN in GGTA1 knockout pigs, we obtained the whole-genome sequence of the donor cells for use as an internal control genome. Results: In-depth whole-genome sequencing analysis demonstrated that TALEN-mediated GGTA1 knockout pigs had a comparable mutation rate to homologous recombination-treated pigs and wild-type strain controls. RNA sequencing analysis associated with genomic mutations revealed that TALEN-induced off-target mutations had no discernable effect on RNA transcript abundance. Conclusion: Therefore, TALEN appears to be a precise and safe tool for generating genomeedited pigs, and the TALEN-mediated GGTA1 knockout Yucatan miniature pigs produced in this study can serve as a safe and effective organ and tissue resource for clinical applications.

LPI 레이더에 대한 원격지원 재머의 주엽 재밍 효과 (Jamming Effect of Stand-Off Jammer to Main Lobe of LPI Radar)

  • 임중수;채규수
    • 융합정보논문지
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    • 제10권3호
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    • pp.16-21
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    • 2020
  • 본 논문은 저 측엽 안테나를 사용하는 LPI(Low Probability Interceptor)레이다를 재밍하는 원격지원 재머의 특성에 대하여 기술한다. LPI 레이다는 재밍 영향을 줄이기 위해서 송수신 안테나의 측엽을 감소시킨다. 레이다는 재머가 표적과 같은 위치에 있는 자체보호 재머에 대해서는 재밍 효과를 쉽게 예측할 수 있으나, 표적과 다른 위치에서 재밍하는 원격지원 재머에 대해서는 재밍 효과를 예측하기가 어렵다. 본 논문에서는 LPI 레이다의 측엽을 재밍하는 원격지원 재머의 재밍 효과를 신호재밍비(SJR)와 재밍 유효 한계거리를 사용하여 분석하였다. 또한 안테나의 측엽이 -30dB 이하인 경우에는 재밍 효과가 미약하여, 안테나 주엽에 대한 원격지원 재밍 방법을 제안하고 재밍 효과를 분석하였다. 본 연구는 항공기용 원격지원 재머 설계 및 운용에 유용하게 사용될 것으로 판단된다.

태권도와 합기도의 돌려차기시 타격 높이가 지면반력에 미치는 영향 (Effect of Target Height on Ground reaction force factors during Taekwondo and Hapkido Dollyuchagi Motion)

  • 양창수
    • 한국운동역학회지
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    • 제12권1호
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    • pp.193-204
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    • 2002
  • The purpose of this study was to investigate the effect of martial art type and target height on the ground reaction force factors during Dollyuchagi motion. Data were collected using force plate. Five Taekwondo players and five Hapkido players were tested during Dollyuchagi motion to three different target heights(0.8, 1.2, 1.6 m). After analysis of kinetics using force plate data, maximum vertical ground reaction force was 1.62~2.44 BW, and impulse was $0.66\sim1.01 BW{\cdot}s$. Even though there was no difference for maximum ground reaction forces and impulse between Hapkido and Taekwondo, as target height was higher, impulse increased. Anterior-posterior and vertical ground reaction forces at kicking foot take-off were greater with target height, although there was no difference for medio-lateral force with target height. At impact there was significant difference for anterior-posterior ground reaction force between Hapkido and Taekwondo players. Taekwondo players' force (range, -0.23~-0.26 BW) was greater than Hapkido players's force (range, -0.08~-0.14 BW).

EFFECT OF PLASTICIZERS ON THE PROPERTIES OF COSMETIC MASK USING POLYVINYL ALCOHOL(PVA) AS A FILM FORMER

  • Park, J.H.;Kyong, K.Y.;Kwak, T.J.;Yoon, M.S.;Kang, S.H.
    • 대한화장품학회지
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    • 제25권4호
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    • pp.51-55
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    • 1999
  • Cosmetic mask is one of the traditional cosmetic product and is used to keep skin healthy and beautiful through moisturizing effect, cleansing effect and acceleration effect on microcirculation. There are several types of cosmetic mask such as peel-off type, tissue-off type, wash-off type and cotton sheet type immersed in cosmetic water. It is important for cosmetic formulators to develop an adequate type of cosmetic mask that meets the needs of the target consumers because each type of cosmetic mask has benefits and problems in its usage and efficacy. Polyvinyl alcohol (PVA) is widely used as an active ingredient of peel-off type cosmetic mask and the physical property of the PVA film changes with the usage of other ingredients. We studied the change of physical properties of the film containing PVA by formulating peel-off type cosmetic mask with the variation of humectants. Methylguceth-20 and glycereth-26 reduce the interaction between skin surface and PVA film without serious weakening of tensile strength and they can alleviate irritation. Glycerin, urea and betaine help PVA film soften and they also have excellent efficacy as humectants.

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EFFECT OF PLASTICIZERS ON THE PROPERTIES OF COSMETIC MASK USING POLYVINYL ALCOHOL (PVA) AS A FILM FORMER

  • Park, J.H.;K.Y.Kyong;Kwak, T.J.;Yoon, M.S.;Kang, S.H.
    • 대한화장품학회:학술대회논문집
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    • 대한화장품학회 1999년도 IFSCC . ASCS 학술대회 발표 논문
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    • pp.51-55
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    • 1999
  • Cosmetic mask is one of the traditional cosmetic product and is used to keep skin healthy and beautiful through moisturizing effect, cleansing effect and acceleration effect on microcirculation. There are several types of cosmetic mask such as peel-off type, tissue-off type, wash-off type and cotton sheet type immersed in cosmetic water. It is important for cosmetic formulators to develop an adequate type of cosmetic mask that meets the needs of the target consumers because each type of cosmetic mask has benefits and problems in its usage and efficacy. Polyvinyl alcohol (PVA) is widely used as an active ingredient of peel-off type cosmetic mask and the physical property of the PVA film changes with the usage of other ingredients. We studied the change of physical properties of the film containing PVA by formulating peel-off type cosmetic mask with the variation of humectants. Methylguceth-20 and glycereth-26 reduce the interaction between skin surface and PVA film without serious weakening of tensile strength and they can alleviate irritation. Glycerin, urea and betaine help PVA film soften and they also have excellent efficacy as humectants.

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Myostatin gene knockout mediated by Cas9-D10A nickase in chicken DF1 cells without off-target effect

  • Lee, Jeong Hyo;Kim, Si Won;Park, Tae Sub
    • Asian-Australasian Journal of Animal Sciences
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    • 제30권5호
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    • pp.743-748
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    • 2017
  • Objective: Based on rapid advancement of genetic modification techniques, genomic editing is expected to become the most efficient tool for improvement of economic traits in livestock as well as poultry. In this study, we examined and verified the nickase of mutated CRISPR-associated protein 9 (Cas9) to modulate the specific target gene in chicken DF1 cells. Methods: Chicken myostatin which inhibits muscle cell growth and differentiation during myogenesis was targeted to be deleted and mutated by the Cas9-D10A nickase. After co-transfection of the nickase expression vector with green fluorescent gene (GFP) gene and targeted multiplex guide RNAs (gRNAs), the GFP-positive cells were sorted out by fluorescence-activated cell sorting procedure. Results: Through the genotyping analysis of the knockout cells, the mutant induction efficiency was 100% in the targeted site. Number of the deleted nucleotides ranged from 2 to 39 nucleotide deletion. There was no phenotypic difference between regular cells and knockout cells. However, myostatin protein was not apparently detected in the knockout cells by Western blotting. Additionally, six off-target sites were predicted and analyzed but any non-specific mutation in the off-target sites was not observed. Conclusion: The knockout technical platform with the nickase and multiplex gRNAs can be efficiently and stablely applied to functional genomics study in poultry and finally adapted to generate the knockout poultry for agribio industry.

헬리데크 구조물의 피로해석 (Fatigue analysis of helideck structures)

  • 전상익;오심관;노지선;김봉재;장기복
    • 대한조선학회 특별논문집
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    • 대한조선학회 2015년도 특별논문집
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    • pp.63-68
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    • 2015
  • This paper presents fatigue analysis of helideck structures located in FPSO. After FPSO is moved to the target position where production of resource is performed, FPSO stays at the target position and performs production of resource, storage and off-loading during the design life. Helideck structure is located in FPSO essentially for the movement of personnel and life rescue at emergency situations by using helicopters. Because inertial load induced by FPSO motion and landing and taking-off load of helicopter occur at helideck structures cyclically, helideck structures should be designed to withstand fatigue loads. Therefore, The fatigue assessment of helideck structures should be performed with fatigue loads. Effect of stress concentration due to misalignment between welded plates is considered in fatigue assessment additionally.

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