• Genomics & Informatics
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• v.6 no.4
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• pp.202-209
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• 2008

Biological pathways are known as collections of knowledge of certain biological processes. Although knowledge about a pathway is quite significant to further analysis, it covers only tiny portion of genes that exists. In this paper, we suggest a model to extend each individual pathway using a microarray expression data based on the known knowledge about the pathway. We take the Rosetta compendium dataset to extend pathways of Saccharomyces cerevisiae obtained from KEGG (Kyoto Encyclopedia of genes and genomes) database. Before applying our model, we verify the underlying assumption that microarray data reflect the interactive knowledge from pathway, and we evaluate our scoring system by introducing performance function. In the last step, we validate proposed candidates with the help of another type of biological information. We introduced a pathway extending model using its intrinsic structure and microarray expression data. The model provides the suitable candidate genes for each single biological pathway to extend it.

• Interdisciplinary Bio Central
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• v.3 no.1
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• pp.5.1-5.5
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• 2011

Introduction: Many signal transduction pathways mediate cell's behavior by regulating expression level of involved genes. Abnormal behavior indicates loss of regulatory potential of pathways, and this can be attributed to loss of expression regulation of downstream genes. Therefore, function of pathways should be assessed by activity of a pathway itself and relative activity between a pathway and downstream genes, simultaneously. Results and Discussion: In this study, we suggested a new method to assess pathway's function by introducing concept of 'responsiveness'. The responsiveness was defined as a relative activity between a pathway itself and its downstream genes. The expression level of a downstream gene as a function of an upstream pathway activation characterizes disease status. In this aspect, by using the responsiveness we predicted potential progress in cancer development. We applied our method to predict primary and metastatic status of melanoma cancer. The result shows that the responsiveness-based approach achieves better performance than using gene or pathway information alone. The mean of ROC scores in the responsiveness-based approach was 0.90 for GSE7553 data set, increased more than 40% compared to a gene-based method. Moreover, identifying the abnormal regulatory patterns between pathway and its downstream genes provided more biologically interpretable information compared to gene or pathway based approaches.

• Journal of Korean Neurosurgical Society
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• v.62 no.3
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• pp.272-287
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• 2019

The mechanistic target of rapamycin (mTOR) pathway coordinates the metabolic activity of eukaryotic cells through environmental signals, including nutrients, energy, growth factors, and oxygen. In the nervous system, the mTOR pathway regulates fundamental biological processes associated with neural development and neurodegeneration. Intriguingly, genes that constitute the mTOR pathway have been found to be germline and somatic mutation from patients with various epileptic disorders. Hyperactivation of the mTOR pathway due to said mutations has garnered increasing attention as culprits of these conditions : somatic mutations, in particular, in epileptic foci have recently been identified as a major genetic cause of intractable focal epilepsy, such as focal cortical dysplasia. Meanwhile, epilepsy models with aberrant activation of the mTOR pathway have helped elucidate the role of the mTOR pathway in epileptogenesis, and evidence from epilepsy models of human mutations recapitulating the features of epileptic patients has indicated that mTOR inhibitors may be of use in treating epilepsy associated with mutations in mTOR pathway genes. Here, we review recent advances in the molecular and genetic understanding of mTOR signaling in epileptic disorders. In particular, we focus on the development of and limitations to therapies targeting the mTOR pathway to treat epileptic seizures. We also discuss future perspectives on mTOR inhibition therapies and special diagnostic methods for intractable epilepsies caused by brain somatic mutations.

• Journal of the korean academy of Pediatric Dentistry
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• v.29 no.3
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• pp.337-344
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• 2002

Runx2, a Runt-related osteoblast-specific transcription factor, is essential for osteoblast differentiation and function. Runx2 was identified as a key regulator of osteoblast-specific gene expression through its binding to the OSE2 element present in these genes. However, little is known about the signaling mechanism regulating Runx2 activity. This study examines the role of protein kinase C (PKC) pathway and mitogen-activated protein kinase (MAPK) pathway in regulating Runx2 and bone marker genes (osteopontin; OP, osteocalcin; OC). Luciferase assay and Northern blot analysis suggested that the stimulation of PKC by PMA increased transcription activity of Runx2 and bone marker genes (OP and OC) and also increased expression of Runx2. The stimulation of MAPK by okadaic acid increased transcription activity of Runx2 and bone marker genes (OP and OC). Pretreatment with PD98059 (Erk pathway inhibitor) and SB203580 (P38 pathway inhibitor) prior to PMA treatment decreased PMA stimulated Runx2 activity. Together these results indicate that both PKC and MAPKs are involved in the regulation of Runx2 activity and also the stimulation of Runx2 transcriptional activity by the PKC pathway is through activation of MAPK pathway.

• Journal of Korean Academy of Nursing Administration
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• v.8 no.1
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• pp.85-95
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• 2002

The purpose of this study was to develope a critical pathway for the chemotherapy of non-small cell lung cancer patients and to identify its effects after implementation. Critical pathway was developed through 5 steps including content and clinical validity tests with collaborative efforts of nurses, clinicians, and other allied healthcare professionals with the aim of improving the quality of patient care, while minimizing cost to the patients. This paper was described an evaluation of the impact of a developed critical pathway on complication rate, length of stay, costs, the interval of treatment and patient satisfaction by nonequivalent control group posttest-only non-synchronized research design.Results were compared between the two groups of patients. There were no significant differences in demographic variables and the occurrence of bone marrow suppression between experimental group and control group(t=-0.01, p=0.992). There were statistically significant decreases in the average length of stay(t=-10.45, p=0.000), in the average cost(t=-2.988, p=0.004), and in the interval of treatment(t=-6.75, p=0.000) after implementation of the critical pathway compared to control group. Also, there was a statistically significant improvement of the patient satisfaction after implementation of the critical pathway compared to control group(t=4.57, p=0.000). This paper concludes that critical pathway in chemotherapy for lung cancer, implemented in the context of an general hospital, is the useful tool to shorten the hospital stay, reduce treatment costs, and improve the quality of life in cancer patients. Further study needs to be conducted to identify other clinical outcomes including job satisfaction, collaboration among health professionals and potential for use in education. Also, it is recommended that nurses should revise continuously the developed critical pathway through clinical implementation and maintain their role of patient advocacy through monitoring pathway compliance.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9791-9795
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• 2014

To study the gene expression change and possible signal pathway during androgen-dependent prostate cancer (ADPC) becoming androgen-independent prostate cancer (AIPC), an LNCaP cell model of AIPC was established using flutamide in combination with androgen-free environment inducement, and differential expression genes were screened by microarray. Then the biological process, molecular function and KEGG pathway of differential expression genes are analyzed by Molecule Annotation System (MAS). By comparison of 12,207 expression genes, 347 expression genes were acquired, of which 156 were up-ragulated and 191 down-regulated. After analyzing the biological process and molecule function of differential expression genes, these genes are found to play crucial roles in cell proliferation, differntiation, cell cycle control, protein metabolism and modification and other biological process, serve as signal molecules, enzymes, peptide hormones, cytokines, cytoskeletal proteins and adhesion molecules. The analysis of KEGG show that the relevant genes of AIPC transformation participate in glutathione metabolism, cell cycle, P53 signal pathway, cytochrome P450 metabolism, Hedgehog signal pathway, MAPK signal pathway, adipocytokines signal pathway, PPAR signal pathway, TGF-${\beta}$ signal pathway and JAK-STAT signal pathway. In conclusion, during the process of ADPC becoming AIPC, it is not only one specific gene or pathway, but multiple genes and pathways that change. The findings above lay the foundation for study of AIPC mechanism and development of AIPC targeting drugs.

• Quality Improvement in Health Care
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• v.18 no.1
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• pp.37-55
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• 2012

Objectives : This study was conducted to evaluate the effect of fixed critical pathway with emr (electronic medical record) on the length of hospital stay, the cost and quality of care provided to gastrectomy patients in a university hospital and to develop flexible critical pathway with emr which can be used excluded or drop-out patients. Methods : Thirty-eight patients with gastrectomy were included as case group and Thirty-four patients included as control group. The comparison between control and case with using fixed critical pathway were done. To develop and to evaluate usefulness of flexible critical pathway with flexible data base, simulation was done for flexible critical pathway with drop-out patients. Result : The major results of this study were as follows: There were no significant differences in patient clinical conditions and no sign of deterioration of quality from critical pathway. The length of hospital stay was 11 days in control group, 8 days in path group(P<0.01). The total costs during the hospital stay were reduced in path group. However the cost per day was significantly increased from reduction of hospital stay(554,352 won in control, 645,669 won in path group). One hundred percentage of drop out patients(60) in the simulation of flexible critical pathway was successful. Conclusion : Computerized critical pathway reduced the length of hospital stay, total hospital costs and resource utilization without harming quality of patient care. The flexible critical pathway program can be used as one of the powerful management tools for reducing the practice variations and increasing the efficiency of care process and decreasing the workload of doctors and nurses in Korean hospital settings.

• Journal of the Korean housing association
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• v.14 no.3
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• pp.41-49
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• 2003

An evaluation of the environments in the wandering pathway of the dementia units was carried out. It is revealed that the quality of the environment for the wandering pathway of the sample units was very low. In particular, lacks of social environments in Unit-B and Unit-C, and lacks of orientation aids in all the sample units were shown. Therefore, re-design for the wandering pathway of the sample units is needed. Recommendations for improving the wandering pathway and having appropriate wandering pathway without any abrupt change in existing layout of the sample units were suggested, and the limits of this research is diagnosed. It is also shown that since evaluation categories used in this paper had very closed relationship each other, those evaluation categories can be used in other settings.

• Quality Improvement in Health Care
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• v.9 no.1
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• pp.66-73
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• 2002

The current health care system demands provisions for patient care in perspectives of a cost-effectiveness and patient satisfaction. Critical pathway implementation facilitates optimal sequencing and intervention timing of patient care, and makes medical team and patients participate in a treatment actively. In this study, a critical pathway was developed and implemented to patients with osmidrosis who undertake operation. Sixty patients were included in the study. The critical pathway was implemented for care of 26 patients while the traditional care was implemented for 34 patients. In the critical pathway implemented group, time needed for charting and unessential working was reduced. Mean time amount of time for patient nursing was increased. The critical pathway implementation is an effective method to utilize time of medical team. Also it increases the satisfaction index of patients and medical team simultaneously.

• Journal of Institute of Control, Robotics and Systems
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• v.10 no.12
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• pp.1155-1163
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• 2004

Extracellular signal-regulated kinase (ERK) signaling pathway is one of the mitogen-activated protein kinase (MAPK) signal transduction pathways. This pathway is known as pivotal in many signaling networks that govern proliferation, differentiation and cell survival. The ERK signaling pathway comprises positive and negative feedback loops, depending on whether the terminal kinase stimulates or inhibits the activation of the initial level. In this paper, we attempt to model the ERK pathway by considering both of the positive and negative feedback mechanisms based on Michaelis-Menten kinetics. In addition, we propose a fraction ratio model based on the mass action law. We first develop a mathematical model of the ERK pathway with fraction ratios. Secondly, we analyze the dynamical properties of the fraction ratio model based on simulation studies. Furthermore, we propose a concept of an inhibitor, catalyst, and substrate (ICS) controller which regulates the inhibitor, catalyst, and substrate concentrations of the ERK signal transduction pathway. The ICS controller can be designed through dynamical analysis of the ERK signaling transduction pathway within limited concentration ranges.