Genomics is providing targets faster than we can validate them and combinatorial chemistry is providing new chemical entities faster than we can screen them. Historically, the drug discovery cascade has been established as a sequential process initiated with a potency screening against a selected biological target. In this sequential process, pharmacokinetics was often regarded as a low-throughput activity. Typically, limited pharmacokinetics studies would be conducted prior to acceptance of a compound for safety evaluation and, as a result, compounds often failed to reach a clinical testing due to unfavorable pharmacokinetic characteristics. A new paradigm in drug discovery has emerged in which the entire sample collection is rapidly screened using robotized high-throughput assays at the outset of the program. Higher-throughput pharmacokinetics (HTPK) is being achieved through introduction of new techniques, including automation for sample preparation and new experimental approaches. A number of in vitro and in vivo methods are being developed for the HTPK. In vitro studies, in which many cell lines are used to screen absorption and metabolism, are generally faster than in vivo screening, and, in this sense, in vitro screening is often considered as a real HTPK. Despite the elegance of the in vitro models, however, in vivo screenings are always essential for the final confirmation. Among these in vivo methods, cassette dosing technique, is believed the methods that is applicable in the screening of pharmacokinetics of many compounds at a time. The widespread use of liquid chromatography (LC) interfaced to mass spectrometry (MS) or tandem mass spectrometry (MS/MS) allowed the feasibility of the cassette dosing technique. Another approach to increase the throughput of in vivo screening of pharmacokinetics is to reduce the number of sample analysis. Two common approaches are used for this purpose. First, samples from identical study designs but that contain different drug candidate can be pooled to produce single set of samples, thus, reducing sample to be analyzed. Second, for a single test compound, serial plasma samples can be pooled to produce a single composite sample for analysis. In this review, we validated the issue whether the second method can be applied to practical screening of in vivo pharmacokinetics using data from seven of our previous bioequivalence studies. For a given drug, equally spaced serial plasma samples were pooled to achieve a 'Pooled Concentration' for the drug. An area under the plasma drug concentration-time curve (AUC) was then calculated theoretically using the pooled concentration and the predicted AUC value was statistically compared with the traditionally calculated AUC value. The comparison revealed that the sample pooling method generated reasonably accurate AUC values when compared with those obtained by the traditional approach. It is especially noteworthy that the accuracy was obtained by the analysis of only one sample instead of analyses of a number of samples that necessitates a significant man-power and time. Thus, we propose the sample pooling method as an alternative to in vivo pharmacokinetic approach in the selection potential lead(s) from combinatorial libraries.
CHO Deuk Moon;PYEUN Jae Hyeung;BYUN Dae Seok;KIM Chang Yang
Korean Journal of Fisheries and Aquatic Sciences
/
v.16
no.3
/
pp.216-224
/
1983
This work was undertaken to obtain some characteristics of proteolytic enzyme of marine gastropods such as sea hare, Aplysia kurodai, top shell, Turbo cornutus, and abalone, Haliotis discus hannai. An influence of pH, temperature and some chemicals on proteolytic activity of the crude enzyme extracted from digestive tract of the samples was taken into account and the stability of the enzyme during the storage at low temperature was also discussed. In comparison of the activities of the crude enzyme from the samples to the optimum conditions, it was characterized that abalone has twice or the more times higher activities than the other two species of the gastropoda in the acid and weak acid region, while, in the alkaline region, sea hare has six or the more times higher acitivities than the other two species. The proteolytic activity was facilitated by $Mn^{2+}$, some reducing agents, EDTA and DTT, and inhibited by $Hg^{2+}$ and SDS, but the other chemicals were not significantly affected to the activity. The low temperature storage of the enzymes of sea hare and top shell at $0^{\circ}C\;or\;-20^{\circ}C$ was not affected to the enzymic activity under the optimum pH condition except in the alkaline region. On the other hand, the low temperature storage was brought about no significant effect on the activity of the enzymes extracted from abalone under the optimum condition of the weak acid region, but apparently influenced to the activity under the optimum condition of the acid and alkaline region.
In this study, the effect of probiotic supplementation on growth performance, blood metabolites, and meat quality of Hanwoo steer was investigated. A total of 32 Hanwoo steers (15-17 months, average body weight $462{\pm}37.9kg$) were randomly allotted to 4 dietary treatments (0, 0.5, 1.0, and 1.5% mixed probiotics), with four Hanwoo steers per pen (two replicates per treatments), and reared for 12 months. There were no differences among treatments in growth performance of Hanwoo steer (P>0.05); however, feed intake decreased linearly with increasing levels of mixed probiotics. Growth hormone and Blood Urea Nitrogen (BUN) levels responded linearly with increasing levels of dietary mixed probiotics (P<0.05), but not insulin and blood glucose did not. In particular, total cholesterol was significantly lower for the 1% mixed probiotic treatment in comparison with that of the other treatments (P<0.05). The pH, Thiobarbituric Acid Reactive Substances (TBARS), cooking loss, and meat color were influenced by increasing levels of mixed probiotics (P<0.05), but the carcass characteristics and shear force were not. Regarding sensory evaluation, the addition of mixed probiotics resulted in significant difference in meat color, tenderness, aroma, off-flavor, juiciness, and marbling score, but not in overall acceptability. In addition, fatty acid profiles indicated no differences between control and mixed probiotic treatments. In conclusion, mixed probiotic treatment at 1% levels can enhance consumer preferences possibly by reducing cholesterol and TBARS.
The influence of phenolsulfunate concentrations on electroplating characteristics and electrochemical behaviors was investigated with a viewpoint of electrolyte aging using the circulation cell and potentiostate And comparison of tinplate coating appearance such as glossiness and Image clarify has been also studied with varying of phenolsulfonic acid (PSA) solutions. As the aging of electrolyte proceeded, the limiting current density was moved to a lower current density region by the limitation of mass transfer, and higher phenolsulfunate concentrations resulted in the narrower optimum current density range and deterioration of coating surface of tinplates. The difference of the limiting current density was not remarkable with increasing electrolyte temperature. Thus the electrolyte aging was attributed to the limitation of thermally-activated process such as mass transfer of reducible ions. It has also been considered that the accumulation of phenolsulfonate suppressed normal electrotinning reaction by reducing the mobility of stannous ions, taking into account of the smaller effect of electrolyte aging. Experiments showed similar polarization behavior between the electrolyte of high phenolsufonate solution and the aged one, which comes to conclude that the accumulation of phenolsulfonate is one of the major causes of electrolyte aging.
Hydrological factors, especially the spatial distribution of interpretation on precipitation is often topic of interest in studying of water resource. The popular methods such as Thiessen method, inverse distance method, and isohyetal method are limited in calculating the spatial continuity and geographical characteristics. This study was intended to overcome those limitations with improved method that will yield higher accuracy. The monthly and yearly precipitation data were produced and compared with the observed daily precipitation to find correlation between them. They were then used as secondary variables in Co-kriging method, and the result was compared with the outcome of existing methods like inverse distance method and kriging method. The comparison of the data showed that the daily precipitation had high correlation with corresponding year's average monthly amounts of precipitation and the observed average monthly amounts of precipitation. Then the result from the application of these data for a Co-kriging method confirmed increased accuracy in the modeling of spatial distribution of precipitation, thus indirectly reducing inconsistency of the spatial distribution of hydrological factors other than precipitation.
Immature apple fruits of cultivars Fuji and Miller were completely resistant to Macrophoma sp. until 10 July. When inoculated on 31 July, apples became susceptible to this fungus, irrespective of cultivar. This fungus grew better on Fuji than Miller. Lesion enlargement on apple at $25^{\circ}C$ was remarkably pronounced relative to $20^{\circ}C$. In both cultivars, the amount of total soluble carbohydrates or reducing sugars in apple fruit flesh was gradually increased as apples became mature. The healthy apples of cultivar Fuji had a higher amount of carbohydrates than those of Miller. The infected apples contained more soluble carbohydrates in comparison to the healthy ones. In healthy apples, there were no consistent differences between Fuji and Miller in amount of total soluble amino acids. With increasing age of apples, the amount of soluble amino acids declined in the fruit flesh of both cultivars. Levels of carbohydrates and amino acids in apple fruits were discussed in association with the immature fruit resistance to Macrophoma sp.
Bearings are essential for reducing vibration and wear, in order to achieve high durability and increase longevity. White metal treatment of tilting pads via centrifugal casting method has the possibility of increasing durability. However, this manufacturing method has drawbacks such as long processing time, high defect rate, and harmful health effects. Laser cladding deposition technique is a powerful method that can address these issues by decreasing the processing time and providing good adhesion. In this study, we suggest optimum conditions for laser cladding deposition that can be used in industrial applications. We deposited a soft white metal layer on SCM440 that is primarily used in shafts to minimize wear of bearing pads. During the laser deposition process, we controlled factors such as laser power, powder feed rate, and laser head speed to determine the optimum conditions. In addition, we measured the hardness using micro Vickers, and performed field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction, and friction tests to investigate the mechanical properties and surface characteristics for different parameters. Based on the experimental results, we suggest that laser power, powder feed rate, and laser head speed of 1.3 kW, 2.5 rpm, and 10 mm/s, respectively, constitute the optimum conditions for producing white metals using laser cladding.
Journal of the Korea institute for structural maintenance and inspection
/
v.22
no.1
/
pp.167-175
/
2018
This research deals, The characteristics of mechanics and behavior of the tube structural systems, It has been investigated and considered conventional theory and case models, It has shown the suitability, The best location, And optimal shape of the unit module system, Considered variables materials of stiffness increase and decrease in hybrid tube structural systems this study carried out adapting analysis of statistical concepts. In a concrete way, This study exams the effect of reducing horizontal displacement and the shear lag phenomenon, Also, The purpose of this study is to utilize the basic data on the design and study of future high-rise hybrid structural system using this research. As a result, The framed- tube structural system does not effectively cope with horizontal behavior of high-rise buildings, The results of using varying material tested resistance factors and lateral loads in hybrid tube structural system, When each material is compared Bracing material is identified as a key factor in lateral behavior. In a ratio of material quantity framed-tube structural system, The level of sensitivity affecting the horizontal displacement is greater then the beam's column, In case of braced tube structural system, Braced appeared to be most sensitive in comparison of material quantity ratio in columns and beams.
Byeong Hyeon Yun;Ji Hae Jun;Il-Sheob Shin;Hyun Ran Kim;Kang Hee Cho;Jae Hoon Jeong;Se Hee Kim;Sang-Yun Cho;Sewon Oh
Korean Journal of Plant Resources
/
v.37
no.1
/
pp.62-70
/
2024
Fruit thinning rate and characteristics were investigated for three years on seven promising pear (Pyrus pyrifolia Nakai) cultivars, which were treated by lime-sulfur as an eco-chemical thinning substance. Lime-sulfur was treated twice at the second and third days after full bloom by cultivar. Most of pear cultivars were significantly thinned by lime-sulfur compounds. Especially 'Whangkeumbae', 'Supergold' and 'Hanareum' exhibited high flower thinning rates, 41.5%, 40.1% and 39.9%, respectively. As weather conditions at the lime-sulfur treatment, insolation and cloud amount were correlated with flower thinning rate but not significant (r = 0.49 and r = -0.45, respectively). These results suggest that lime-sulfur is suitable for reducing labor force for flower thinning of Korean pears but flower thinning effects of lime-sulfur can vary depending on other factors such as environmental conditions. This information will provide useful data for low labor force cultivation of Korean pear cultivars.
Three-dimensional (3-D) optimally-interpolated sea surface temperature (SST) field was produced by using AQUA/AMSR-E satellite data, and its limitations were described by comparing the temporal average of sea surface temperatures. The 3-D OI (Optimum Interpolation) SST showed a small error of less than $0.05^{\circ}C$ in the central North Pacific, but yielded large errors of greater than $0.4^{\circ}C$ at the coastal area where the satellite microwave data were not available. OI SST composite around pixels with no observation due to heavy rainfall or cloudy pixels had estimation errors of $0.1-0.15^{\circ}C$. Comparison with temporal means showed a tendency that overall OI SSTs were underestimated around heavy cloudy pixels and smoothed out by reducing the magnitude of SST fronts. In the low-latitude areas near the equator, OI SST field produced discontinuity, originated from the window size for the OI procedure. This was mainly caused by differences in the spatial scale of oceanic features. Infernal Rossby deformation radius, as a measure of spatial stale, showed dominant latitudinal variations with O(1) difference in the North Pacific. This study suggests that OI SST methodology should consider latitudinally-varying size of window and the characteristics of spatial scales of oceanic phenomena with substantial dependency on latitude and vertical structure of density.
본 웹사이트에 게시된 이메일 주소가 전자우편 수집 프로그램이나
그 밖의 기술적 장치를 이용하여 무단으로 수집되는 것을 거부하며,
이를 위반시 정보통신망법에 의해 형사 처벌됨을 유념하시기 바랍니다.
[게시일 2004년 10월 1일]
이용약관
제 1 장 총칙
제 1 조 (목적)
이 이용약관은 KoreaScience 홈페이지(이하 “당 사이트”)에서 제공하는 인터넷 서비스(이하 '서비스')의 가입조건 및 이용에 관한 제반 사항과 기타 필요한 사항을 구체적으로 규정함을 목적으로 합니다.
제 2 조 (용어의 정의)
① "이용자"라 함은 당 사이트에 접속하여 이 약관에 따라 당 사이트가 제공하는 서비스를 받는 회원 및 비회원을
말합니다.
② "회원"이라 함은 서비스를 이용하기 위하여 당 사이트에 개인정보를 제공하여 아이디(ID)와 비밀번호를 부여
받은 자를 말합니다.
③ "회원 아이디(ID)"라 함은 회원의 식별 및 서비스 이용을 위하여 자신이 선정한 문자 및 숫자의 조합을
말합니다.
④ "비밀번호(패스워드)"라 함은 회원이 자신의 비밀보호를 위하여 선정한 문자 및 숫자의 조합을 말합니다.
제 3 조 (이용약관의 효력 및 변경)
① 이 약관은 당 사이트에 게시하거나 기타의 방법으로 회원에게 공지함으로써 효력이 발생합니다.
② 당 사이트는 이 약관을 개정할 경우에 적용일자 및 개정사유를 명시하여 현행 약관과 함께 당 사이트의
초기화면에 그 적용일자 7일 이전부터 적용일자 전일까지 공지합니다. 다만, 회원에게 불리하게 약관내용을
변경하는 경우에는 최소한 30일 이상의 사전 유예기간을 두고 공지합니다. 이 경우 당 사이트는 개정 전
내용과 개정 후 내용을 명확하게 비교하여 이용자가 알기 쉽도록 표시합니다.
제 4 조(약관 외 준칙)
① 이 약관은 당 사이트가 제공하는 서비스에 관한 이용안내와 함께 적용됩니다.
② 이 약관에 명시되지 아니한 사항은 관계법령의 규정이 적용됩니다.
제 2 장 이용계약의 체결
제 5 조 (이용계약의 성립 등)
① 이용계약은 이용고객이 당 사이트가 정한 약관에 「동의합니다」를 선택하고, 당 사이트가 정한
온라인신청양식을 작성하여 서비스 이용을 신청한 후, 당 사이트가 이를 승낙함으로써 성립합니다.
② 제1항의 승낙은 당 사이트가 제공하는 과학기술정보검색, 맞춤정보, 서지정보 등 다른 서비스의 이용승낙을
포함합니다.
제 6 조 (회원가입)
서비스를 이용하고자 하는 고객은 당 사이트에서 정한 회원가입양식에 개인정보를 기재하여 가입을 하여야 합니다.
제 7 조 (개인정보의 보호 및 사용)
당 사이트는 관계법령이 정하는 바에 따라 회원 등록정보를 포함한 회원의 개인정보를 보호하기 위해 노력합니다. 회원 개인정보의 보호 및 사용에 대해서는 관련법령 및 당 사이트의 개인정보 보호정책이 적용됩니다.
제 8 조 (이용 신청의 승낙과 제한)
① 당 사이트는 제6조의 규정에 의한 이용신청고객에 대하여 서비스 이용을 승낙합니다.
② 당 사이트는 아래사항에 해당하는 경우에 대해서 승낙하지 아니 합니다.
- 이용계약 신청서의 내용을 허위로 기재한 경우
- 기타 규정한 제반사항을 위반하며 신청하는 경우
제 9 조 (회원 ID 부여 및 변경 등)
① 당 사이트는 이용고객에 대하여 약관에 정하는 바에 따라 자신이 선정한 회원 ID를 부여합니다.
② 회원 ID는 원칙적으로 변경이 불가하며 부득이한 사유로 인하여 변경 하고자 하는 경우에는 해당 ID를
해지하고 재가입해야 합니다.
③ 기타 회원 개인정보 관리 및 변경 등에 관한 사항은 서비스별 안내에 정하는 바에 의합니다.
제 3 장 계약 당사자의 의무
제 10 조 (KISTI의 의무)
① 당 사이트는 이용고객이 희망한 서비스 제공 개시일에 특별한 사정이 없는 한 서비스를 이용할 수 있도록
하여야 합니다.
② 당 사이트는 개인정보 보호를 위해 보안시스템을 구축하며 개인정보 보호정책을 공시하고 준수합니다.
③ 당 사이트는 회원으로부터 제기되는 의견이나 불만이 정당하다고 객관적으로 인정될 경우에는 적절한 절차를
거쳐 즉시 처리하여야 합니다. 다만, 즉시 처리가 곤란한 경우는 회원에게 그 사유와 처리일정을 통보하여야
합니다.
제 11 조 (회원의 의무)
① 이용자는 회원가입 신청 또는 회원정보 변경 시 실명으로 모든 사항을 사실에 근거하여 작성하여야 하며,
허위 또는 타인의 정보를 등록할 경우 일체의 권리를 주장할 수 없습니다.
② 당 사이트가 관계법령 및 개인정보 보호정책에 의거하여 그 책임을 지는 경우를 제외하고 회원에게 부여된
ID의 비밀번호 관리소홀, 부정사용에 의하여 발생하는 모든 결과에 대한 책임은 회원에게 있습니다.
③ 회원은 당 사이트 및 제 3자의 지적 재산권을 침해해서는 안 됩니다.
제 4 장 서비스의 이용
제 12 조 (서비스 이용 시간)
① 서비스 이용은 당 사이트의 업무상 또는 기술상 특별한 지장이 없는 한 연중무휴, 1일 24시간 운영을
원칙으로 합니다. 단, 당 사이트는 시스템 정기점검, 증설 및 교체를 위해 당 사이트가 정한 날이나 시간에
서비스를 일시 중단할 수 있으며, 예정되어 있는 작업으로 인한 서비스 일시중단은 당 사이트 홈페이지를
통해 사전에 공지합니다.
② 당 사이트는 서비스를 특정범위로 분할하여 각 범위별로 이용가능시간을 별도로 지정할 수 있습니다. 다만
이 경우 그 내용을 공지합니다.
제 13 조 (홈페이지 저작권)
① NDSL에서 제공하는 모든 저작물의 저작권은 원저작자에게 있으며, KISTI는 복제/배포/전송권을 확보하고
있습니다.
② NDSL에서 제공하는 콘텐츠를 상업적 및 기타 영리목적으로 복제/배포/전송할 경우 사전에 KISTI의 허락을
받아야 합니다.
③ NDSL에서 제공하는 콘텐츠를 보도, 비평, 교육, 연구 등을 위하여 정당한 범위 안에서 공정한 관행에
합치되게 인용할 수 있습니다.
④ NDSL에서 제공하는 콘텐츠를 무단 복제, 전송, 배포 기타 저작권법에 위반되는 방법으로 이용할 경우
저작권법 제136조에 따라 5년 이하의 징역 또는 5천만 원 이하의 벌금에 처해질 수 있습니다.
제 14 조 (유료서비스)
① 당 사이트 및 협력기관이 정한 유료서비스(원문복사 등)는 별도로 정해진 바에 따르며, 변경사항은 시행 전에
당 사이트 홈페이지를 통하여 회원에게 공지합니다.
② 유료서비스를 이용하려는 회원은 정해진 요금체계에 따라 요금을 납부해야 합니다.
제 5 장 계약 해지 및 이용 제한
제 15 조 (계약 해지)
회원이 이용계약을 해지하고자 하는 때에는 [가입해지] 메뉴를 이용해 직접 해지해야 합니다.
제 16 조 (서비스 이용제한)
① 당 사이트는 회원이 서비스 이용내용에 있어서 본 약관 제 11조 내용을 위반하거나, 다음 각 호에 해당하는
경우 서비스 이용을 제한할 수 있습니다.
- 2년 이상 서비스를 이용한 적이 없는 경우
- 기타 정상적인 서비스 운영에 방해가 될 경우
② 상기 이용제한 규정에 따라 서비스를 이용하는 회원에게 서비스 이용에 대하여 별도 공지 없이 서비스 이용의
일시정지, 이용계약 해지 할 수 있습니다.
제 17 조 (전자우편주소 수집 금지)
회원은 전자우편주소 추출기 등을 이용하여 전자우편주소를 수집 또는 제3자에게 제공할 수 없습니다.
제 6 장 손해배상 및 기타사항
제 18 조 (손해배상)
당 사이트는 무료로 제공되는 서비스와 관련하여 회원에게 어떠한 손해가 발생하더라도 당 사이트가 고의 또는 과실로 인한 손해발생을 제외하고는 이에 대하여 책임을 부담하지 아니합니다.
제 19 조 (관할 법원)
서비스 이용으로 발생한 분쟁에 대해 소송이 제기되는 경우 민사 소송법상의 관할 법원에 제기합니다.
[부 칙]
1. (시행일) 이 약관은 2016년 9월 5일부터 적용되며, 종전 약관은 본 약관으로 대체되며, 개정된 약관의 적용일 이전 가입자도 개정된 약관의 적용을 받습니다.