• 제목/요약/키워드: critical evidence

검색결과 640건 처리시간 0.03초

기후변화와 개체의 생활사 (Climate Change and Individual Life History)

  • 이후승
    • Ocean and Polar Research
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    • 제34권3호
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    • pp.275-286
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    • 2012
  • Over the last 20 years there have been more than 3000 peer-reviewed papers relating to climate change and biodiversity published, and still the numbers are increasing. However, most studies focused on the impacts of climate change at population or community levels, and the results invariably reveal that there has been, or will be, a negative effect on the structure and pattern of biodiversity. Moreover, the climate change models and statistical analyses used to test the impacts are only newly developed, and the analyses or predictions can often be misled. In this review, I ask why an individual's life history is considered in the study how climate change affects biodiversity, and what ecological factors are impacted by climate change. Using evidence from a range of species, I demonstrate that diverse life history traits, such as early growth rate, migration/foraging behaviour and lifespan, can be shifted by climate change at individual level. Particularly I discuss that the optimal decision under unknown circumstance (climate change) would be the reduction of the ecological fitness at individual level, and hence, a shift in the balance of the ecosystem could be affected without having a critical impact on any one species. To conclude, I summarize the links between climate changes, ecological decision in life history, the revised consequence at individual level, and discuss how the finely-balanced relationship affects biodiversity and population structure.

Pre-clinical QT Risk Assessment in Pharmaceutical Companies - Issues of Current QT Risk Assessment -

  • Takasuna, Kiyoshi; Katsuyoshi, Chiba;Manabe, Sunao
    • Biomolecules & Therapeutics
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    • 제17권1호
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    • pp.1-11
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    • 2009
  • Since the Committee for Proprietary Medicinal Products (CPMP) of the European Union issued in 1997 a "points to consider" document for the assessment of the potential for QT interval prolongation by non-cardiovascular agents to predict drug-induced torsades de pointes (TdP), the QT liability has become the critical safety issue in the development of pharmaceuticals. As TdP is usually linked to delayed cardiac repolarization, international guideline (ICH S7B) has advocated the standard repolarization assays such as in vitro IKr (hERG current) and in vivo QT interval, or in vitro APD (as a follow up) as the best biomarkers for predicting the TdP risk. However, the recent increasing evidence suggests that the currently used above biomarkers and/or assays are not fully predictive for TdP, but also does not address potential new druginduced TdP due to the selective disruption of hERG protein trafficking to the cell membrane or VT and/or VF with QT shortening. There is, therefore, an urgent need for other surrogate markers or assays that can predict the proarrhythmic potential of drug candidate. In this review, we provide an ideal pre-clinical strategy to predict the potentials of QT liability and lethal arrhythmia of the drug candidates with recent issues in this field in mind, not at the expense of discarding therapeutically innovative drugs.

The Role of Internal and Network Constraints on Alliance Ambidexterity Decisions in Technology Intensive Industries

  • Vlas, Radu;Vlas, Cristina
    • Asia pacific journal of information systems
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    • 제26권2호
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    • pp.299-321
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    • 2016
  • Previous studies on strategic alliance formation have largely overlooked the effects that organizations' routine development can have on the relationship between organizations' network position and their alliance ambidexterity strategy. This study extends ambidexterity research by adding internal and network perspectives and examining their cumulative effects on alliance ambidexterity. We first acknowledge the interplay between organizations' internal knowledge exploration/exploitation strategies and organizations' alliance ambidexterity and determine that organizations with a high level of internal knowledge breadth are more likely to make focused alliance decisions. Second, our analysis of 145 US-based information technology organizations with an active alliance behavior reveals that having well-formed routines as a result of previous collaborations strengthens the tendency of brokerage organizations to follow alliances that focus on either exploration or exploitation. Although most alliance studies have commonly argued in favor of an ambidextrous approach, this study provides critical evidence that both internal knowledge exploration/exploitation strategies and development of routines constrain organizations' alliance formation decisions, guiding them towards a more focused approach.

Involvement of RUNX and BRD Family Members in Restriction Point

  • Lee, Jung-Won;Park, Tae-Geun;Bae, Suk-Chul
    • Molecules and Cells
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    • 제42권12호
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    • pp.836-839
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    • 2019
  • A tumor is an abnormal mass of tissue that arises when cells divide more than they should or do not die when they should. The cellular decision regarding whether to undergo division or death is made at the restriction (R)-point. Consistent with this, an increasingly large body of evidence indicates that deregulation of the R-point decision-making machinery accompanies the formation of most tumors. Although the R-point decision is literally a matter of life and death for the cell, and thus critical for the health of the organism, it remains unclear how a cell chooses its own fate. Recent work demonstrated that the R-point constitutes a novel oncogene surveillance mechanism operated by R-point-associated complexes of which RUNX3 and BRD2 are the core factors (Rpa-RX3 complexes). Here, we show that not only RUNX3 and BRD2, but also other members of the RUNX and BRD families (RUNX1, RUNX2, BRD3, and BRD4), are involved in R-point regulation.

Autophagy in Ischemic Livers: A Critical Role of Sirtuin 1/Mitofusin 2 Axis in Autophagy Induction

  • Chun, Sung Kook;Go, Kristina;Yang, Ming-Jim;Zendejas, Ivan;Behrns, Kevin E.;Kim, Jae-Sung
    • Toxicological Research
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    • 제32권1호
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    • pp.35-46
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    • 2016
  • No-flow ischemia occurs during cardiac arrest, hemorrhagic shock, liver resection and transplantation. Recovery of blood flow and normal physiological pH, however, irreversibly injures the liver and other tissues. Although the liver has the powerful machinery for mitochondrial quality control, a process called mitophagy, mitochondrial dysfunction and subsequent cell death occur after reperfusion. Growing evidence indicates that reperfusion impairs mitophagy, leading to mitochondrial dysfunction, defective oxidative phosphorylation, accumulation of toxic metabolites, energy loss and ultimately cell death. The importance of acetylation/deacetylation cycle in the mitochondria and mitophagy has recently gained attention. Emerging data suggest that sirtuins, enzymes deacetylating a variety of target proteins in cellular metabolism, survival and longevity, may also act as an autophagy modulator. This review highlights recent advances of our understanding of a mechanistic correlation between sirtuin 1, mitophagy and ischemic liver injury.

Purification and Characterization of Anticoagulant Protein from Ark Shell, Scapharca broughtonii

  • Jung, Won-Kyo;Park, Pyo-Jam;Kim, Se-Kwon
    • 한국어업기술학회:학술대회논문집
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    • 한국어업기술학회 2000년도 춘계수산관련학회 공동학술대회발표요지집
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    • pp.90-91
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    • 2000
  • The physiological systems that control blood fluidity are both complex and elegant. Blood must remain fluid within the vasculature and yet clot quickly when exposed to nonendothelial surfaces at sites of vascular injury. There are two principle mechanisms to control a delicate balance in higher organisms (Davie & Ratnoff, 1964). Present evidence suggests that the intrinsic pathway play an important role in the growth and maintenance of fibrin formation in the coagulation cascade while a second overlapping mechanism, called the extrinsic pathway, is critical in the initiation of fibrin formation. Coagulation factors is in two mechanisms, and in order to clot blood, they are activated by a cooperation with $Ca^{2+}$, phospholipid and vitamin K etc. For example, the human placental anticoagulant protein (PAP of PAP- I), which is a $Ca^{2+}$ -dependent phospholipid binding protein (Funakoshi et al., 1987) inhibited the activity of factor Xa, so that it prolonged fibrin formation. We wondered whether any other protein was involved in regulation of the coagulant system as an anticoagulant protein from natural organisms. Natural agents would have not harmful side-effects in comparision with chemically synthesized materials such as warfarin, aspirin, phenindione, etc.. But anticoagulant agents from natural, especially marine organisms have hardly been researched except for polysaccharides from marine algae. (omitted)

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국내의 e-Business 모델 분류 및 실태 분석 (An Analysis on the Classification and the Real Status of e-Business Model in Korea)

  • 허영호;주희엽;권혁인
    • Journal of Information Technology Applications and Management
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    • 제10권1호
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    • pp.1-17
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    • 2003
  • As the increase of internal users, there are many enterprises and organizations that regard the internal as the great ■marketing superhighway■. But the entrance of too many e-Business enterprises and shopping sites makes them to compete each other Consequently many sites are created and disappeared in the cyberspace. Although fascination and speculation surrounds the impact of the e-Business on business models via benefit-based concept, there is little evidence underlying all this speculation. This article provides on such data set. It reports on critical Issues that e-Business enterprises found salient as they browsed through e-Business model infrastructure on the world wide web, internet-based. We gathered domestic e-Business enterprise's kinds of business model during 2000∼2002 via KMAC's (Korea Management Association Consultants) K-WPI and K-WPC. We classified e-Business models as shopping mall, auction, community. value-chain, collaboration, information brokerage, advertising, Internet service, marketing that we had identified from the existing literature on business models. This study translated these models to the e-Business model context and explored their relative salience. The results suggest that e-Business manager need to think more about how they perform on the issues known to affect decision making for designing e-Business models. We offer advice for enhancing the effectiveness of business models.

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Comprehensive Vibration Assessment Program for Yonggwang Nuclear Power Plant Unit 4

  • Huinam Rhee;Hwang, Jong-Keun;Kim, Tae-Hyung;Kim, Jung-Kyu;Song, Heuy-Gap;Kim, Beom-Shig
    • 한국원자력학회:학술대회논문집
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    • 한국원자력학회 1995년도 추계학술발표회논문집(2)
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    • pp.1001-1007
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    • 1995
  • A Comprehensive Vibration Assessment Program (CVAP) has been performed for Yonggwang Nuclear Power Plant Unit 4 (YGN 4) in order to verify the structural integrity of the reactor internals for flow induced vibrations prior to commercial operation. The theoretical evidence for the structural integrity of the reactor internals and the basis for measurement and inspection are provided by the analysis. Flow induced hydraulic loads and reactor internals vibration response data were measured during pre-core hot functional testing in YGN 4 site. Also, the critical areas in the reactor internals were inspected visually to check any existence of structural abnormality before and after the pre-core hot functional testing. Then, the measured data have been analyzed and compared with the predicted data by analysis. The measured stresses are less than the predicted values and the allowable limits. It is concluded that the vibration response of the reactor internals due to the flow induced vibration under normal operation is acceptable for long term operation.

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OPERATOR BEHAVIORS OBSERVED IN FOLLOWING EMERGENCY OPERATING PROCEDURE UNDER A SIMULATED EMERGENCY

  • Choi, Sun-Yeong;Park, Jin-Kyun
    • Nuclear Engineering and Technology
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    • 제44권4호
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    • pp.379-386
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    • 2012
  • A symptom-based procedure with a critical safety function monitoring system has been established to reduce the operator's diagnosis and cognitive burden since the Three-Mile Island (TMI) accident. However, it has been reported that a symptom-based procedure also requires an operator's cognitive efforts to cope with off-normal events. This can be caused by mismatches between a static model, an emergency operating procedure (EOP), and a dynamic process, the nature of an ongoing situation. The purpose of this study is to share the evidence of mismatches that may result in an excessive cognitive burden in conducting EOPs. For this purpose, we analyzed simulated emergency operation records and observed some operator behaviors during the EOP operation: continuous steps, improper description, parameter check at a fixed time, decision by information previously obtained, execution complexity, operation by the operator's knowledge, notes and cautions, and a foldout page. Since observations in this study are comparable to the results of an existing study, it is expected that the operational behaviors observed in this study are generic features of operators who have to cope with a dynamic situation using a static procedure.

PPARγ Physiology and Pathology in Gastrointestinal Epithelial Cells

  • Thompson, E. Aubrey
    • Molecules and Cells
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    • 제24권2호
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    • pp.167-176
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    • 2007
  • Peroxisome proliferator-activated receptor-gamma ($PPAR{\gamma}$) is expressed at very high levels in the gastrointestinal epithelium. Many of the functions of $PPAR{\gamma}$ in gastrointestinal epithelial cells have been elucidated in recent years, and a pattern is emerging which suggests that this receptor plays an important role in gastrointestinal physiology. There is also strong evidence that $PPAR{\gamma}$ is a colon cancer suppressor in pre-clinical rodent models of sporadic colon cancer, and there is considerable interest in exploitation of $PPAR{\gamma}$ agonists as prophylactic or chemopreventive agents in colon cancer. Studies in mice and in human colon cancer cell lines suggest several mechanisms that might account for the tumor suppressive effects of $PPAR{\gamma}$ agonists, although it is not in all cases clear whether these effects are altogether mediated by $PPAR{\gamma}$. Conversely, several reports suggest that $PPAR{\gamma}$ agonists may promote colon cancer under certain circumstances. This possibility warrants considerable attention since several million individuals with type II diabetes are currently taking $PPAR{\gamma}$ agonists. This review will focus on recent data related to four critical questions: what is the physiological function of $PPAR{\gamma}$ in gastrointestinal epithelial cells; how does $PPAR{\gamma}$ suppress colon carcinogenesis; is $PPAR{\gamma}$ a tumor promoter; and what is the future of $PPAR{\gamma}$ in colon cancer prevention?