• Title/Summary/Keyword: Rate Limiting

Search Result 749, Processing Time 0.03 seconds

Metabolic Engineering of the Brassinosteroid Biosynthetic Pathways (Brassinosteroid의 대사공학)

  • Lee, Mi-Ock;Song, Ki-Hong;Lee, Hyun-Kyung;Jung, Ji-Yoon;Choe, Vit-Nary;Choe, Sung-Hwa
    • Proceedings of the Korean Society of Plant Biotechnology Conference
    • /
    • 2002.04b
    • /
    • pp.69-75
    • /
    • 2002
  • Sterols play two major roles in plants: a bulk component in biological membranes and precursors of plant steroid hormones. Physiological effects of plant steroids, brassinosteroids (BRs), include cell elongation, cell division, stress tolerance, and senescence acceleration. Arabidopsis mutants that carry genetic defects in BR biosynthesis or its signaling display characteristic phenotypes, such as short robust inflorescences, dark-green round leaves, and sterility. Currently there are more than 100 dwarf mutants representing 7 genetic loci in Arabidopsis. Mutants of 6 loci, dwf1/dim1/cbb1, cpd/dwf3, dwf4, dwf5, det2/dwf6, dwf7 are rescued by exogenous application of BRs, whereas bri1/dwf2 shares phenotypes with the above 6 loci but are resistant to BRs. These suggest that the 6 loci are defective in BR biosynthesis, and the one locus is in BR signaling. Biochemical analyses, such as intermediate feeding tests, examining the levels of endogenous BR, and molecular cloning of the genes revealed that dwf7, dwf5, and dwf1 are defective in the three consecutive steps of sterol biosynthesis, from episterol to campesterol via 5-dehydroepisterol. Similarly, det2/dwf6, dwf4, and cpd/dwf3 were Shown to be blocked in $D^4$ reduction, 22a-hydroxylation, and 23 a-hydroxylation, respectively. A signaling mutant bri1/dwf2 carries mutations in a Leucine-rich repeat receptor kinase. Interestingly, the bri1 mutant was shown to accumulate significant amount of BRs, suggesting that signaling and biosynthesis are dynamically coupled in Arabidopsis. Thus it is likely that transgenic plants over-expressing the rate-limiting step enzyme DWF4 as well as blocking its use by BRI1 could dramatically increase the biosynthetic yield of BRs. When applied industrially, BRs will boost new sector of plant biotechnology because of its potential use as a precursor of human steroid hormones, a novel lead compound for cholesterol-lowering effects, and a various application in plant protection.

  • PDF

Continual Reassessment Method in Phase I Clinical Trials for Leukemia Patients (백혈병환자 대상의 제1상임상시험 연속재평가방법)

  • Lee, Joo-Hyoung;Song, Hae-Hiang
    • Communications for Statistical Applications and Methods
    • /
    • v.18 no.5
    • /
    • pp.581-594
    • /
    • 2011
  • The traditional method of 3+3 standard design and model-based Bayesian continual reassessment method (CRM) are commonly used in Phase I clinical trials to identify the maximal tolerated dose(MTD) of a new drug. In this paper we review clinical examples of Phase I trials that were carried out in patients with refractory or relapsed leukemia and myelodysplastic syndrome. The recently proposed 3+1+1 design and rolling-6 design can shorten the trial duration, when a very slow accrual of patients with a simple 3+3 standard design may result in the untimely termination of trials. Too conservative approaches in determining the dose levels in Phase I clinical trials can leave clinical investigators unable to accurately determine the MTD. When determining future patient doses, the designs that use a time-to-event CRM can cooperate late toxicities by accounting for the proportion of the observation period of each enrolled patient. With the CRM design, simulations under different scenarios during the trial are important in detecting the under- or over-estimation of the initial estimate of the dose-limiting toxicity rate for each dose level. We present the advantages and drawbacks of the designs used in Phase I clinical trials for leukemia patients.

Ecological Studies on the Culture Bed and Production of Young Top Shell, Batillus cornutus in Cheju Island (제주도산 소라의 치패생산 및 서식생태에 관한 연구)

  • Pyen Choong Kyu;Youn Jeong Su
    • Journal of Aquaculture
    • /
    • v.3 no.1
    • /
    • pp.89-125
    • /
    • 1990
  • In order to improve top shell seed production techniques spawning and larvae rearing were done in rearing tanks. Growth of young top shell in the nursing ground were also investigated. For induced spawning, top shells were maintained in still water during night time. Then they were treated with ultra violet iradiated sea water after dried up in air for 60 minutes. Spawning rate were 10 to $39.77\%$. It was found that young top shells moved in the growing grounds from nursing grounds when they reached approximately 30-40mm in shell heignt. Among main food algae for top shell in the natural growing grounds, sea mustard were melted away during June. Therefore, presence of another food algae such as Ecklonia cava or Sargassum spp. seems to be the main limiting factor for survival of top shell during summer. The tolerance of top shells ranging from 30mm to 60mm to low density of seawater for were tested at the temperature between 29.5 and $31.4^{\circ}C$. Hundred percent mortality occoured in 20, 55 and 90 hours after first stocking at the specific gravity of 1.010, 1.015, and 1.020, respectively.

  • PDF

Earthquake-Resistant Design of Cantilever Retaining-Walls with Sloped Base (기초슬래브의 밑면이 경사진 캔티레바식 옹벽의 내진설계)

  • Kim, Hong Taek
    • KSCE Journal of Civil and Environmental Engineering Research
    • /
    • v.10 no.3
    • /
    • pp.87-98
    • /
    • 1990
  • The present Study dealt with the earthquake-resistant design of cantilever retaining walls supporting cohesionless soils. With design examples of three different types of cantilever retaining walls, the factors of safety against sliding were computed at various values of horizontal acceleration coefficient and compared with each other. The horizontal inertia effect due to the weights of concrete wall itself and a portion of backfill was taken into account in the analyses, and also Mononobe-Okabe pseudo-static solution method was modified to deal with various states different from limiting equilibrium state. From the analyses of safety against sliding, it was found that a cantilever retaining wall with sloped base was the most efficient type in earthquake resistant design. It was also found that by sloping the base, the width of the base slab could be reduced, resulting in the least volume of concrete, excavation and backfill as compared to the other types of walls. In the case of a cantilever retaining wall with sloped feel, the efficiency similar to that of a wall with sloped base could be expected under static loading as well as at relatively low level of earthquake loading. However, this efficiency became vanished with the increase of horizontal acceleration coefficient, since the rate of reduction in developed earth pressures on the heel became smaller. In addition, the design charts with different soil friction angles as well as with different earthquake resistant design criteria of safety factor against sliding were presented for the design of cantilever retaining walls sith sloped base.

  • PDF

Effects of Various Garlic (Allium sativum) Extracts on Cholesterol Synthesis in HepG2 Cells (다양한 마늘 추출물이 HepG2 세포에서 콜레스테롤 합성에 미치는 효과)

  • Jung, Suhan;Lee, Sang Hoon;Ko, Kwang Suk
    • Journal of the Korean Society of Food Science and Nutrition
    • /
    • v.44 no.12
    • /
    • pp.1779-1784
    • /
    • 2015
  • This study was performed to investigate the effects of various garlic extracts on cholesterol synthesis in HepG2 cells. Raw garlic, grilled garlic, and freeze dried garlic were subjected to cold water extraction, and extracts were incubated at room temperature for 1 min or 60 min. The extracts were treated to HepG2 cells for 4 h, and cholesterol synthesis and mRNA expression level of HMG-CoA reductase were investigated. The alliin contents were reduced when garlic was incubated at room temperature for 60 min. Raw garlic extracts showed lower intracellular cholesterol contents compared to that of the control group. However, raw garlic extracts incubated for 60 min showed no differences compared to the control group. Freeze-dried garlic extract showed minimum intracellular triglyceride and cholesterol contents. Relative mRNA expression level of HMG-CoA reductase, a rate-limiting enzyme of cholesterol synthesis, decreased in the garlic extracts. Compared with 60 min, garlic extracts incubated for 1 min showed a reduced level of HMG-CoA reductase mRNA expression. The freeze-dried garlic extract reduced mRNA expression level of HMG-CoA reductase in a dose-dependent manner in cells treated with 5% of 0.2, 0.5, 0.8, 1.0, and 1.5 mg/mL in medium, and the effect was maxed out at dose of 5% garlic extract at 1.0 mg/mL in medium.

The Effect of a Natural Zeolite (Clinoptilolite) on the Performance of Broiler Chickens and the Quality of Their Litter

  • Karamanlis, X.;Fortomaris, P.;Arsenos, G.;Dosis, I.;Papaioannou, D.;Batzios, C.;Kamarianos, A.
    • Asian-Australasian Journal of Animal Sciences
    • /
    • v.21 no.11
    • /
    • pp.1642-1650
    • /
    • 2008
  • The objective of this study was to assess the effect of clinoptilolite (a natural zeolite) on growth and performance of broilers as well as on the quality of their litter. A total of 5,200 one-day old broiler chickens (Cobb 500) were used in two consecutive rounds lasting 42 days each. The broilers were given free and continuous access to a nutritionally non-limiting diet (in meal form) that was either a basal diet (B) or a 'zeolite diet' (Z; the basal diet supplemented with clinoptilolite at a level of 2%). A $2{\times}2$ factorial design consisted of two feeding treatments (B and Z) and two bedding types, sawdust (S) and sawdust with zeolite (Sz, which was the result of adding $2kg\;zeolite/m^2$), was used. In each round the broilers were randomly assigned to one of four (n = 650), treatment groups: two fed on the basal diet (B) and had bedding of either sawdust (group BS) or sawdust and zeolite (group BSz) and two fed on the Z diet and had as bedding either sawdust (ZS) or sawdust and zeolite (ZSz). Average growth rates were significantly (p<0.05) different between broilers of different groups; broilers that were fed on the 'zeolite diet' (Z) and were placed either in a compartment with sawdust bedding or sawdust bedding and zeolite (ZS and ZSz) as well those that were fed on the basal diet in a compartment with sawdust bedding and zeolite (BSz) grew at a faster rate (p<0.05) compared with those of the control group (BS). The incorporation of NZ in broilers diets and in their bedding material decreased the organic content in litter samples throughout the experimental period. The lowest organic content was recorded in group ZSz where NZ was added in both feed and litter. Mean ammonia concentration (ppm) was significantly higher in group ZS in comparison to groups BSz and ZSz (27.00 vs. 20.55 and 21.71 respectively). The results of this study showed that the incorporation of the clinoptilolite both in feed and into the litter had a positive effect on broiler growth and also on the quality of their litter.

Association between Single Nucleotide Polymorphisms in the Dgat2 Gene and Beef Carcass and Quality Traits in Commercial Feedlot Steers

  • Li, J.;Xu, X.;Zhang, Q.;Wang, X.;Deng, G.;Fang, X.;Gao, X.;Ren, H.;Xu, S.
    • Asian-Australasian Journal of Animal Sciences
    • /
    • v.22 no.7
    • /
    • pp.943-954
    • /
    • 2009
  • Diacylglycerol acyltransferase (DGAT) is a key enzyme that catalyzes the final and rate-limiting step of triglyceride synthesis. Both DGAT1 and DGAT2 genes code proteins with DGAT activity. Studies have shown DGAT1 polymorphisms associate with intramuscular fat deposition in beef cattle, but fewer associations between DGAT2 and beef cattle economic traits have been reported. The objective of this study was to investigate single nucleotide polymorphism (SNP) in intron3 of bovine DGAT2 and evaluate the associations of that with carcass, meat quality, and fat yield traits. Test animals were 157 commercial feedlot steers belonging to 3 Chinese native breeds (22 for Luxi, 24 for Jinnan, and 23 for Qinchuan), 3 cross populations (20 for Charolais${\times}$Fuzhou, 18 for Limousin ${\times}$Luxi, and 17 for Simmental${\times}$Jinan) and 1 Taurus pure breed population (16 Angus steers). In the current study, 15 SNP were discovered in intron3 and exon4 of DGAT2 at positions 65, 128, 178, 210, 241, 255, 270, 312, 328, 334, 365, 366, 371, 415, and 437 (named as their positions in PCR amplified fragments). Only 7 of them (128, 178, 241, 270, 312, 328, and 371) were analyzed, because SNP in three groups (65-128-255, 178-210-365 and 241-334-366) were in complete linkage disequilibrium within the group, and SNP 415 was a deletion and 437 was a null mutation. Frequencies for rare alleles in the 3 native breed populations were higher than in the 3 cross populations for 178 (p = 0.04), 270 (p = 0.001), 312 (p = 0.03) and 371 (p = 0.002). A general linear model was used to evaluate the associations between either SNP genotypes or allele substitutions and the measured traits. Results showed that SNP 270 had a significant association with the fat yield associated with kidney, pelvic cavity, heart, intestine, and stomach (KPHISY). Animals with genotype CC and CT for 270 had less (CC: -7.71${\pm}$3.3 kg and CT: -5.34${\pm}$2.5 kg) KPHISY than animals with genotype TT (p = 0.02). Allele C for 270 was associated with an increase of -4.26${\pm}$1.52 kg KPHISY (p = 0.006) and $-0.92{\pm}0.45%$ of retail cuts weight percentage (NMP, Retail cuts weight/slaughter body weight) (p = 0.045); allele G for 312 was associated with an increase of -5.45${\pm}$2.41 kg KPHISY (p = 0.026). An initial conclusion was that associations do exist between DGAT2 gene and carcass fat traits. Because of the small sample size of this study, it is proposed that further effort is required to validate these findings in larger populations.

A Development of Automation system and a way to use Solar Energy System Efficiently in Greenhouse(2) - Study on improvement of growth and yield of a cucumber in soil heating - (시설원예 태양열 시스템의 효율적 이용과 자동화 장치개발(2) -지중가온에 의한 오이 생육 및 수량성 향상에 관한 연구-)

  • 김진현;오중열;구건효;김태욱
    • Journal of Bio-Environment Control
    • /
    • v.7 no.1
    • /
    • pp.25-33
    • /
    • 1998
  • Root zone temperature have influenced on protected cultivation in winter season. Especially root zone temperature is acted on limiting factor in crop cultivation. This study was conducted to obtain optimum temperature of root zone in Protected cultivation Root zone was warmed by heated water($28^{\circ}C$) flowing through the PPC pipe(${\phi}15$) buried depth 40 cm. And the flowing water was heated by solar system. Minimum air temperature during night time was set at $14^{\circ}C$ and maximum air temperature during day time was set at $28~30^{\circ}C$ the growing period of cucumber was from Nov. 6, 1996 to Jan. 30, 1997. The results are summarized as follows. 1. Average soil temperature at 15~20 cm depth was $22^{\circ}C$ at warming plots, $17~18^{\circ}C$ at non-warming plots 2. Early growth in leaf length, stem diameter, number of leaves and leaf area for 30 days after planting were accelerated by root zone warming. Especially, the grawing rate of soil warming plots was higher 27% in leaf length, 51% in leaf number, 150% in leaf area than non-warming Plots. Above-ground and underground part of warming plots was higher 117%, 56% than non-warming plots. 3. In total yield analysis, number of fruits were 614 in soil warming and 313 in non-warming plots. In the result, total yield of soil warming plots was increased with 196% than non-warming plots. 3. In total yield analysis. number of fruits were 614 in soil warming and 313 in non-warming plots. In the result. total yield of soil warming plots was increased with 196% than non-warming plots.

  • PDF

Analyses of Scenarios Based on a Leakage of Highly Compressed Air and Fire Anticipated in CAES (Compressed Air Energy Storage) Facility (압축공기에너지저장 시설에서 발생 가능한 압축공기 유출 및 화재 시나리오 분석)

  • Yoon, Yong-Kyun;Ju, Eun-Hye
    • Tunnel and Underground Space
    • /
    • v.25 no.6
    • /
    • pp.568-576
    • /
    • 2015
  • In this study, scenarios based on the leakage of highly compressed air and fire occurrence turned out to be high risks in an operation stage of CAES facility were constructed and estimated. By combining Bernoulli equation with momentum equation, an expression to calculate an impact force of a jet flow of compressed air was derived. An impact force was found to be proportional to the square of diameter of fracture and the pressure of compressed air. Four types of fire scenarios were composed to evaluate an effects that seasonal change and location of fire source have on the spread behavior of smoke. Smoke from the fire ignited in the vicinity of CAES opening descended more quickly below the limit line of breathing than one from the fire occurred 10 m away from CAES opening, which is expected to occur due to a propagation of wave front of smoke. It was shown that a rate of smoke spread of the winter fire is faster than one of the summer fire and smoke from the winter fire spreads farther than one of the summer fire, which are dependent on the direction of air flow into access opening. Evacuation simulation indicated that the required safe evacuation time(RSET) of the summer and winter fires are 262, 670 s each.

Metabolic Engineering of the Brassinosteroid Biosynthetic Pathways (Brassinosteroid의 대사공학)

  • Lee, Mi-Ock;Song, Ki-Hong;Lee, Hyun-Kyung;Jung, Ji-Yoon;Choe, Vit-Nary;Choe, Sung-Hwa
    • Journal of Plant Biotechnology
    • /
    • v.29 no.2
    • /
    • pp.139-144
    • /
    • 2002
  • Sterols play two major roles in plants: a bulk component in biological membranes and precursors of plant steroid hormones. Physiological effects of plant steroids, brassinosteroids (BRs), include cell elongation, cell division, stress tolerance, and senescence acceleration. Arabidopsis mutants that carry genetic defects in BR biosynthesis or its signaling display characteristic phenotypes, such as short robust inflorescences, dark-green round leaves, and sterility. Currently there are more than 100 dwarf mutants representing 7 genetic loci in Arabidopsis. Mutants of 6 loci, dwf1/dim1/cbb1, cpd/dwf3, dwf4, dwf5, det2/dwf6, dwf7 are rescued by exogenous application of BRs, whereas bri1/dwf2 shares phenotypes with the above 6 loci but are resistant to BRs. These suggest that the 6 loci are defective in BR biosynthesis, and the one locus is in BR signaling. Biochemical analyses, such as intermediate feeding tests, examining the levels of endogenous BR, and molecular cloning of the genes revealed that dwf7, dwf5, and dwf1 are defective in the three consecutive steps of sterol biosynthesis, from episterol to campesterol via 5-dehydroepisterol. Similarly, det2/dwf6, dwf4, and cpd /dwf3 were shown to be blocked in D$^4$reduction, 22a-hydroxylation, and 23 a-hydroxylation, respectively. A signaling mutant bril/dwf2 carries mutations in a Leucine-rich repeat receptor kinase. Interestingly, the bri1 mutant was shown to accumulate significant amount of BRs, suggesting that signaling and biosynthesis are dynamically coupled in Arabidopsis. Thus it is likely that transgenic plants over-expressing the rate-limiting step enzyme DWF4 as well as blocking its use by BRIl could dramatically increase the biosynthetic yield of BRs. When applied industrially, BRs will boost new sector of plant biotechnology because of its potential use as a precursor of human steroid hormones, a novel lead compound for cholesterol-lowering effects, and a various application in plant protection.