• 제목/요약/키워드: Critical Pathways

검색결과 268건 처리시간 0.024초

RNA Binding Protein-Mediated Post-Transcriptional Gene Regulation in Medulloblastoma

  • Bish, Rebecca;Vogel, Christine
    • Molecules and Cells
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    • 제37권5호
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    • pp.357-364
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    • 2014
  • Medulloblastoma, the most common malignant brain tumor in children, is a disease whose mechanisms are now beginning to be uncovered by high-throughput studies of somatic mutations, mRNA expression patterns, and epigenetic profiles of patient tumors. One emerging theme from studies that sequenced the tumor genomes of large cohorts of medulloblastoma patients is frequent mutation of RNA binding proteins. Proteins which bind multiple RNA targets can act as master regulators of gene expression at the post-transcriptional level to co-ordinate cellular processes and alter the phenotype of the cell. Identification of the target genes of RNA binding proteins may highlight essential pathways of medulloblastomagenesis that cannot be detected by study of transcriptomics alone. Furthermore, a subset of RNA binding proteins are attractive drug targets. For example, compounds that are under development as anti-viral targets due to their ability to inhibit RNA helicases could also be tested in novel approaches to medulloblastoma therapy by targeting key RNA binding proteins. In this review, we discuss a number of RNA binding proteins, including Musashi1 (MSI1), DEAD (Asp-Glu-Ala-Asp) box helicase 3 X-linked (DDX3X), DDX31, and cell division cycle and apoptosis regulator 1 (CCAR1), which play potentially critical roles in the growth and/or maintenance of medulloblastoma.

치과의원 외래환자 예약관리체계의 계량적 평가 (Quantitative Evaluation of Appointment System for Outpatients in Dental Clinic)

  • 이형주;장혜정
    • 한국병원경영학회지
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    • 제8권2호
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    • pp.49-69
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    • 2003
  • This study purported to evaluate the performance of the appointment system for outpatients in primary care dental clinic. The data of patients' time flow for 1,245 patients in Y Dental Clinic were collected for one month in 2002 and then analyzed. Specifically, the time periods of treatment and patients' waiting as well as rates of appointment and it's failure are estimated. The accuracy of expected treatment time period was also evaluated. The results showed that 72% of patients visited the clinic with appointments, and only 56% kept their appointments. The patient's waiting time period turned out to be 11 minutes in Y clinic. The expected treatment time period is turned out to be very important because they influence significantly on patient's waiting time period. Practically, the expected treatment time period should be overestimated about 9 minutes in general, and the characteristics of dentist, each patient's diagnosis and age need to be especially considered. Hospitals and clinics also need to make the systematic and detailed critical pathways for a variety of patient cases by analyzing the patients' treatment pattern. With the improved appointment systems, healthcare institutions will approach the goal of effective and efficient management of the institution and also satisfy their customers.

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다운스뷰파크 국제설계경기를 통해 본 조경설계의 새로운 전략 (New Strategies for Contemporary Landscape Design -Downsview Park International Design Competition and Its Implications-)

  • 배정한
    • 한국조경학회지
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    • 제29권6호
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    • pp.62-71
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    • 2002
  • How parks are to be made in the twenty-first century should certainly be different. This is the inevitable conclusion of the recent significant international design competition for Downsview Park in Toronto, 2000. The purpose of this critical study is to investigate new strategies for urban park design manifested in the proposals of that competition and to explore alternative ways of landscape design that could solve the recent crisis of urban parks. Tree City, the winning entry, and other final entries proclaim that city is park and park is city. In this sense, Downsview Park marks the end of traditional Olmstedian parks and the dichotomy between city(culture) and park(nature). Rem Koolhaas and Bruce Mau's Tree City will become the model for urban park design in the near future. There are three reasons for this. First, its design is a strategy rather than a form. We can interpret that Tree City is to be developed over time as directed by six strategies: grow the park, manufacture nature, 1000 pathways, sacrifice and save, curate culture, destination and dispersal. Second, it places faith in landscape as a revenue generator instead of a fiscal liability. Third, its implementation is possible with crude installation, requiring virtually no craft. Koolhaas and Mau intend for Downsview to be an environment that is never actually designed but is formed through natural succession, cultural action, and programmatical insertions. Rather than designed objects and formal solutions, their strategy is to allow the landscape to evolve with changing uses.

Osteoclast Activity and Osteoporosis

  • Kim, Hong-Hee
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 2001년도 춘계학술대회
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    • pp.103-112
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    • 2001
  • Bone homeostasis is maintained by a balance between activities of osteoblasts(bone forming cells) and osteoclasts (bone resorbing cells). The activities of these cells are closely regulated by multiple factors including hormones and cytokines. The cessation of estrogen at menopause disrupts the balanced regulation and is the main cause of osteoporosis in postmenopausal women. Recent molecular biological studies led to a discovery of tumor necrosis factor(TNF) and TNF receptor families genes that play critical roles in the regulation of osteoclast formation and function. RANKL (receptor activator of nuclear factor kappa B ligand; also called ODF, TRANCE, and OPGL) expressed on cells supporting osteoclast is essential for osteoclast differentiation, activation, and survival. RANK, the counter-receptor for RANKL, is expressed on progenitor and mature osteoclasts. The interaction between RANKL and RANK is requlated by a soluble decoy receptor OPG (osteoprotegerin). Gene knock out studies of these molecules showed profound effects on bone. These results prompted development of new strategies for treatment of bone diseases. Inhibition of osteoclast activity by blocking the RANKL-RANK interaction using OPG is being attempted. Research on the signaling pathways of RANK is also actively carried out. Screening natural products that inhibit the RANKL-RANK interaction or the activity of obteoclasts would be another effective means to a new drug target for bone resorbing diseases.

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Use of DNA-Specific Anthraquinone Dyes to Directly Reveal Cytoplasmic and Nuclear Boundaries in Live and Fixed Cells

  • Edward, Roy
    • Molecules and Cells
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    • 제27권4호
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    • pp.391-396
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    • 2009
  • Image-based, high-content screening assays demand solutions for image segmentation and cellular compartment encoding to track critical events - for example those reported by GFP fusions within mitosis, signalling pathways and protein translocations. To meet this need, a series of nuclear/cytoplasmic discriminating probes have been developed: DRAQ5$^{TM}$ and CyTRAK Orange$^{TM}$. These are spectrally compatible with GFP reporters offering new solutions in imaging and cytometry. At their most fundamental they provide a convenient fluorescent emission signature which is spectrally separated from the commonly used reporter proteins (e.g. eGFP, YFP, mRFP) and fluorescent tags such as Alexafluor 488, fluorescein and Cy2. Additionally, they do not excite in the UV and thus avoid the complications of compound UV-autofluorescence in drug discovery whilst limiting the impact of background sample autofluorescence. They provide a convenient means of stoichiometrically labelling cell nuclei in live cells without the aid of DMSO and can equally be used for fixed cells. Further developments have permitted the simultaneous and differential labelling of both nuclear and cytoplasmic compartments in live and fixed cells to clearly render the precise location of cell boundaries which may be beneficial for quantitative expression measurements, cell-cell interactions and most recently compound in vitro toxicology testing.

Insight into the pathogensis of polycystic ovarian syndrome

  • Jung, Yong Wook;Lee, Gun Ho;Han, You Jung;Cha, Dong Hyun
    • Journal of Genetic Medicine
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    • 제17권1호
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    • pp.1-10
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    • 2020
  • Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women, which is characterized by the oligo/anovulation, hyperandrogenism (HA) and polycystic ovarian morphology which are diagnostic criteria. PCOS has diverse clinical aspects in addition to those diagnostic criteria including increased risk for cardiovascular diseases, metabolic syndrome, dyslipidemia, type 2 diabetes and impaired fertility. Because of the heterogeneity of the disease, the pathogenesis of the disease has not been elucidated yet. Therefore, there is no cure for the endocrinopathy. HA and insulin resistance (IR) has been considered two major pillars of the pathogenesis of PCOS. Recent advances in animal studies revealed the critical role of neuroendocrine abnormalities in developing PCOS. Several pathways related to neuroendocrine origin have been investigated such as hypothalamus pituitary ovarian axis, hypothalamus pituitary adrenal axis and hypothalamus pituitary adipose axis. This review summarizes the current knowledge about the role of HA and IR in developing PCOS. In addition, we review the results of recent genome wide association studies for PCOS. This new perspective improves our understanding of the role of neuroendocrine origins in PCOS and suggest a novel potential therapeutic target for the treatment of PCOS.

스텐트와 풍선의 상호작용을 고려한 스텐트 팽창의 유한요소해석 (Finite Element Analysis of Stent Expansion Considering Stent-Balloon Interaction)

  • 오병기;조해용
    • 대한기계학회논문집A
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    • 제29권1호
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    • pp.156-162
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    • 2005
  • Stouts are frequently used throughout the human body, but the most critical areas are in coronary arteries. They open pathways in vessels and supply blood directly to the heart muscle. To simulate behavior of expansion for the coronary stent by balloon, the commercial finite element code LS-DYNA and ANSYS were used in the analysis. The explicit method is used to analyze the expansion of the stent and the implicit method is performed to simulate the springback that developed in a stent after the balloon pressure has been removed. Finally the experimental results for the expansion of the PS153 stents were compared with the FEM results. The springback was measured with the stents subjected to no external pressure to which stents are subjected in vivo. The simulated results were in good agreement with experimental results. Standard mechanical characteristics such as stress, plastic strains, and springback can be derived from the numerical results. These data can be used to determine maximum expansion diameter without fracture and expansion pressure considering elastic recoil.

Gastrulation : Current Concepts and Implications for Spinal Malformations

  • Thompson, Dominic Nolan Paul
    • Journal of Korean Neurosurgical Society
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    • 제64권3호
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    • pp.329-339
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    • 2021
  • It has been recognised for over a century that the events of gastrulation are fundamental in determining, not only the development of the neuraxis but the organisation of the entire primitive embryo. Until recently our understanding of gastrulation was based on detailed histological analysis in animal models and relatively rare human tissue preparations from aborted fetuses. Such studies resulted in a model of gastrulation that neurosurgeons have subsequently used as a means of trying to explain some of the congenital anomalies of caudal spinal cord and vertebral development that present in paediatric neurosurgical practice. Recent advances in developmental biology, in particular cellular biology and molecular genetics have offered new insights into very early development. Understanding the processes that underlie cellular interactions, gene expression and activation/inhibition of signalling pathways has changed the way embryologists view gastrulation and this has led to a shift in emphasis from the 'descriptive and morphological' to the 'mechanistic and functional'. Unfortunately, thus far it has proved difficult to translate this improved knowledge of normal development, typically derived from non-human models, into an understanding of the mechanisms underlying human malformations such as the spinal dysraphisms and anomalies of caudal development. A paediatric neurosurgeons perspective of current concepts in gastrulation is presented along with a critical review of the current hypotheses of human malformations that have been attributed to disorders of this stage of embryogenesis.

Circulating HOTAIR LncRNA Is Potentially Up-regulated in Coronary Artery Disease

  • Avazpour, Niloofar;Hajjari, Mohammadreza;Yazdankhah, Saeed;Sahni, Azita;Foroughmand, Ali Mohammad
    • Genomics & Informatics
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    • 제16권4호
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    • pp.25.1-25.5
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    • 2018
  • Coronary artery disease (CAD) is one of the leading causes of death and disability all around the world. Recent studies have revealed that aberrantly regulated long non-coding RNA (lncRNA) as one of the main classes of cellular transcript plays a key regulatory role in transcriptional and epigenetic pathways. Recent reports have demonstrated that circulating lncRNAs in the blood can be potential biomarkers for CAD. HOTAIR is one of the most cited lncRNAs with a critical role in the initiation and progression of the gene expression regulation. Recent research on the role of the HOTAIR in cardiovascular disease lays the basis for the development of new studies considering this lncRNA as a potential biomarker and therapeutic target in CAD. In this study, we aimed to compare the expression of HOTAIR lncRNA in the blood samples of patients with CAD and control samples. The expression level was examined by semi-quantitative reverse transcriptase polymerase chain reaction technique. Our data shows that expression of HOTAIR is up-regulated in blood samples of patients with CAD.

Anti-Inflammatory Role of TAM Family of Receptor Tyrosine Kinases Via Modulating Macrophage Function

  • Lee, Chang-Hee;Chun, Taehoon
    • Molecules and Cells
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    • 제42권1호
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    • pp.1-7
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    • 2019
  • Macrophage is an important innate immune cell that not only initiates inflammatory responses, but also functions in tissue repair and anti-inflammatory responses. Regulating macrophage activity is thus critical to maintain immune homeostasis. Tyro3, Axl, and Mer are integral membrane proteins that constitute TAM family of receptor tyrosine kinases (RTKs). Growing evidence indicates that TAM family receptors play an important role in anti-inflammatory responses through modulating the function of macrophages. First, macrophages can recognize apoptotic bodies through interaction between TAM family receptors expressed on macrophages and their ligands attached to apoptotic bodies. Without TAM signaling, macrophages cannot clear up apoptotic cells, leading to broad inflammation due to over-activation of immune cells. Second, TAM signaling can prevent chronic activation of macrophages by attenuating inflammatory pathways through particular pattern recognition receptors and cytokine receptors. Third, TAM signaling can induce autophagy which is an important mechanism to inhibit NLRP3 inflammasome activation in macrophages. Fourth, TAM signaling can inhibit polarization of M1 macrophages. In this review, we will focus on mechanisms involved in how TAM family of RTKs can modulate function of macrophage associated with anti-inflammatory responses described above. We will also discuss several human diseases related to TAM signaling and potential therapeutic strategies of targeting TAM signaling.