437 research outputs found
๊ด๋ํ ์ ๋ ์ธ์คํดํ ๋ฅดํ ํํฉ๋ฌผ์ ์ํ Nrf2 ํ์ฑํ ๋งค๊ฐ ์ ๊ฒฝ๋ณดํธ ๋ฐ ํญ๊ฑด์ ํจ๋ฅ ์ฐ๊ตฌ
ํ์๋
ผ๋ฌธ (๋ฐ์ฌ)-- ์์ธ๋ํ๊ต ๋ํ์ : ์ฝํ๋ํ ์ฝํ๊ณผ, 2019. 2. ๊น์์.Oxidative stress plays a key role in neurodegenerative diseases, such as Alzheimers and Parkinsons disease. It is responsible for the dysfunction or death of neuronal cells that contribute to disease pathogenesis. Skin is the major target of oxidative stress, as it is continuously exposed to exogenous stressors, such as UV radiation and other environmental stresses producing reactive oxygen species. Thus, an efficient antioxidative strategy stimulating an endogenous defense mechanism is important for treatment of neurodegenerative diseases and psoriasis, a chronic inflammatory skin disease. Pharmacological activation of Nrf2, a master regulator of the antioxidant response, can be a beneficial therapeutic strategy. The present study demonstrates that 7ฮฒ-(3โฒ-ethyl-cis-crotonoyloxy)-1ฮฑ-(2โฒ-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN) and tussilagonone (TGN), sesquiterpenoids isolated from the medicinal plant Tussilago farfara, are potent, naturally occurring Nrf2 activators. Furthermore, the underlying mechanisms of Nrf2-mediated neuroprotection by ECN and amelioration of psoriatic features by TGN were investigated.
Phytochemicals are potent antioxidants and act as activators of Nrf2 inducing phase II detoxification enzymes and cytoprotective genes. Terpenoids, including sesquiterpenoids, activate Nrf2 through the Michael reaction of reactive cysteine residues on the Keap1 protein. Because of this common feature, various terpenoids have been reported to possess protective effects. However, Nrf2-mediated pharmacological activities of ECN and TGN have yet to be elucidated. The objective of this study was to i) assess the potency of ECN and TGN as Nrf2 activators and ii) investigate the molecular mechanisms underlying neuroprotective activities of ECN and anti-psoriatic properties of TGN both in vitro and in vivo.
ECN had a protective effect against oxidative stress-induced cell damage. ECN up-regulated Nrf2 and heme oxygenase-1 (HO-1) expression in PC12 cells at the transcriptional level and induced phosphorylation of Akt for Nrf2 activation. Knockdown of Nrf2 by small interfering RNA (siRNA) abrogated the protective effects of ECN, indicating that a neuroprotective effect of ECN against oxidative stress is mediated by Nrf2/HO-1 signaling. In a 6-OHDA-induced mouse model of Parkinsons disease, administration of ECN ameliorated motor impairments and dopaminergic neuronal damage.
TGN showed HO-1-mediated anti-inflammatory properties in macrophages and reduced the expression of inflammatory mediators in a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation mouse model. Furthermore, TGN inhibited NF-kB and STAT3 activation, leading to attenuation of psoriasis-related inflammatory genes and hyperproliferation of keratinocytes. It was identified that inhibition of NF-ฮบB and STAT3 by TGN is mediated through Nrf2 activation. Topical TGN treatment ameliorated imiquimod (IMQ)-induced psoriasis-like skin inflammation in mice. Moreover, TGN reduced inflammatory immune genes and epidermal hyperproliferation in IMQ-induced skin homogenates.
Taken together, these results suggest that ECN and TGN, as potent Nrf2 activators, could be attractive therapeutic candidates for the neuroprotection or treatment of neurodegenerative diseases and psoriasis.์ฐํ ์คํธ๋ ์ค๋ ์์ธ ํ์ด๋จธ ๋ฐ ํํจ์จ ๋ณ๊ณผ ๊ฐ์ ์ ๊ฒฝ ํดํ์ฑ ์งํ์์ ๋ณ์ ๋ฐ๋ณ ๊ธฐ์ ์ ๊ธฐ์ฌํ๋ ์ ๊ฒฝ ์ธํฌ์ ๊ธฐ๋ฅ ์ฅ์ ๋๋ ์ฌ๋ฉธ์ ์ด๋ํ์ฌ, ์ฃผ์ํ ๋ณ์ธ์ผ๋ก ์์ฉํ๋ค. ํผ๋ถ๋ ์์ธ์ ๋ฐ ํ์ฑ ์ฐ์์ข
(ROS)์ ์์ฑํ๋ ์ธ์ธ์ฑ ์คํธ๋ ์ค ์์ธ์ ์ง์์ ์ผ๋ก ๋
ธ์ถ๋๋ฏ๋ก ์ฐํ ์คํธ๋ ์ค์ ์ฃผ๋ ํ์ ์ด ๋๋ ์ ์ฒด ๊ธฐ๊ด์ด๋ค. ๋ฐ๋ผ์, ์ฒด๋ด ํญ์ฐํ ๋ฐฉ์ด ๊ธฐ์์ ํ์ฑํ์ํค๋ ๊ฒ์ ์ ๊ฒฝ ํดํ์ฑ ์งํ ๋ฐ ๋ง์ฑ ์ผ์ฆ์ฑ ํผ๋ถ ์งํ์ธ ๊ฑด์ ์ ์น๋ฃ์ ์์ด ํจ๊ณผ์ ์ธ ์ ๋ต์ด ๋ ์ ์์ผ๋ฉฐ ํญ์ฐํ ๋ฐ์์ ์ฃผ ์กฐ์ ์์ธ Nrf2์ ์ฝ๋ฆฌํ์ ํ์ฑํ๊ฐ ์ฃผ์ ํ์ ์ด ๋ ์ ์๋ค. ๋ณธ ์ฐ๊ตฌ์์๋ ์ฝ์ฉ์๋ฌผ ๊ด๋ํ์ ์ธ์คํดํ
๋ฅดํ ํํฉ๋ฌผ์ธ ECN๊ณผ TGN์ด ๊ฐ๋ ฅํ Nrf2 ํ์ฑํ ๋ฌผ์ง์์ ๋ฐํ๋ค. ๋ํ, ECN๊ณผ TGN์ ๋์์ผ๋ก ์ ๊ฒฝ๋ณดํธ ๋ฐ ํญ๊ฑด์ ํจ๋ฅ๊ณผ ๊ด๋ จ ์์ฉ ๊ธฐ์ ์ ๊ท๋ช
ํ์๊ณ , ๋๋ฌผ ๋ชจ๋ธ์ ์ด์ฉํ์ฌ ์์ฒด ๋ด ํจ๋ฅ์ ํ์ธํ์๋ค.
์๋ฌผ ์ ๋ ์๋ฆฌํ์ฑ ๋ฌผ์ง์ ์ผ์ปซ๋ ํ์ดํ ์ผ๋ฏธ์ปฌ (Phytochemical)์ ๊ฐ๋ ฅํ ํญ์ฐํ ๋ฌผ์ง๋ก ํด๋
ํจ์ ๋ฐ ์ธํฌ ๋ณดํธ ๋จ๋ฐฑ์ง์ ๋ฐํ์ ์ ๋ํ๋ Nrf2์ ํ์ฑํ์ ์ญํ ์ ํ๋ ๊ฒ์ผ๋ก ์ฃผ๋ชฉ๋ฐ๊ณ ์๋ค. ์ธ์คํดํ
๋ฅดํ์ ํฌํจํ๋ ํ
๋ฅดํ๋
ธ์ด๋ ๊ณ์ด ํํฉ๋ฌผ์ Keap1 ๋จ๋ฐฑ์ง์ ์กด์ฌํ๋ ๋ฐ์์ฑ ์์คํ
์ธ ์๊ธฐ์ ๋ง์ดํด ๋ฐ์์ ํตํด Nrf2๋ฅผ ํ์ฑํ์ํฌ ์ ์๋ค. ์ด๋ฌํ ํน์ง์ผ๋ก ์ธํด ๋ค์ํ ํ
๋ฅดํ๋
ธ์ด๋๊ฐ ๋ณดํธ ํจ๊ณผ๋ฅผ ๊ฐ๋ ๊ฒ์ผ๋ก ๋ณด๊ณ ๋์ด์๋ค. ๊ทธ๋ฌ๋, ECN ๋ฐ TGN์ Nrf2 ๋งค๊ฐ ์ฝ๋ฆฌํ์ ํ์ฑ์ ์์ง ๋ฐํ์ง์ง ์์๋ค. ๋ณธ ์ฐ๊ตฌ์ ๋ชฉ์ ์ 1) Nrf2 ํ์ฑํ ๋ฌผ์ง๋ก์์ ECN ๋ฐ TGN์ ํจ๋ฅ์ ํ๊ฐํ๊ณ , 2) ECN์ ์ ๊ฒฝ ๋ณดํธ ํ์ฑ ๋ฐ TGN์ ํญ๊ฑด์ ํจ๋ฅ์ ๋ํ ๋ถ์ ๊ธฐ์ ์ ๋ฐํ๊ณ ๋๋ฌผ ๋ชจ๋ธ์ ์ด์ฉํ์ฌ ์์ฒด ๋ด ๋ฐ์์ ํ์ธํ๊ณ ์ ํ์๋ค.
ECN์ ์ฐํ ์คํธ๋ ์ค์ ์ํด ์ ๋ฐ๋ ์ธํฌ ์์์ ๋ํ ๋ณดํธ ํจ๊ณผ๋ฅผ ๋ํ๋ด์๋ค. ๋ํ, PC12 ์ธํฌ์์ Nrf2 ๋ฐ heme oxygenase-1 (HO-1) ๋ฐํ์ ์ํฅ ์กฐ์ ํ๊ณ Nrf2 ํ์ฑํ์ ์์ ๊ธฐ์ ์ผ๋ก Akt์ ์ธ์ฐํ๋ฅผ ์ ๋ํ์๋ค. Nrf2์ ์ ์์ ํํฅ ์กฐ์ ์ ECN์ ์ํ ๋ณดํธ ํจ๊ณผ๋ฅผ ์ต์ ์ํจ ๊ฒฐ๊ณผ๋ฅผ ํตํด, ์ฐํ ์คํธ๋ ์ค์ ๋ํ ECN์ ์ ๊ฒฝ ๋ณดํธ ํจ๊ณผ๊ฐ Nrf2 / HO-1 ์ ํธ ์ ๋ฌ์ ๋งค๊ฐ๋ก ํ๋ค๋ ๊ฒ์ ๋ฐํ๋ค. 6-OHDA ์ ๋ฐ ํํจ์จ๋ณ ๋๋ฌผ ๋ชจ๋ธ์์, ECN์ ํฌ์ฌ๋ ์ด๋ ์ฅ์ ๋ฐ ๋ํ๋ฏผ์ฑ ์ ๊ฒฝ ์์์ ์ํ์์ผฐ๋ค.
TGN์ ๋์์ธํฌ์์ HO-1 ๋งค๊ฐ ์ผ์ฆ ์ ํญ์ฑ์ ๋ํ๋๊ณ 12-O-tetradecanoylphorbol-13-acetate (TPA)๋ก ์ ๋ํ ๊ธ์ฑ ํผ๋ถ ์ผ์ฆ ์ฅ ๋ชจ๋ธ์์ ์ผ์ฆ ๋งค๊ฐ ๋จ๋ฐฑ์ง์ ๋ฐํ์ ๊ฐ์์์ผฐ๋ค. ๋ํ TGN์ NF-kB ๋ฐ STAT3 ํ์ฑํ๋ฅผ ์ต์ ํ์ฌ ๊ฑด์ ๊ด๋ จ ์ผ์ฆ ์ธ์๋ค์ ๋ฐํ ๋ฐ ๊ฐ์ง ์ธํฌ์ ๊ณผ๋ค ์ฆ์์ ๊ฐ์์์ผฐ๋ค. ์ด์ ๊ฐ์ TGN์ ์ํ NF-kB ๋ฐ STAT3์ ์ต์ ๋ Nrf2 ํ์ฑํ๋ฅผ ํตํด ๋งค๊ฐ๋จ์ด ํ์ธ๋์๋ค. TGN์ ๊ตญ์์ฒ๋ฆฌ๋ ์ฅ์์ ์ด๋ฏธํด๋ชจ๋ ์ ๋ฐ ๊ฑด์ ์ฑ ํผ๋ถ ์ผ์ฆ์ ๊ฐ์ ์์ผฐ๋ค. ๋ํ TGN์ ์ฅ์ ํผ๋ถ ์กฐ์ง์์ ์ผ์ฆ์ฑ ๋ฉด์ญ ์ ์ ์์ ๋ฐํ๊ณผ ํํผ ๊ณผ๋ค ์ฆ์์ ์ต์ ํ์๋ค.
๋ณธ ์ฐ๊ตฌ ๊ฒฐ๊ณผ๋ค์ ์ข
ํฉํ์ฌ ๋ณผ ๋, ๊ด๋ํ ์ ๋ ์ธ์คํดํ
๋ฅดํ ํํฉ๋ฌผECN๊ณผ TGN์ ๊ฐ๋ ฅํ Nrf2 ํ์ฑํ ๋ฌผ์ง๋ก ์์ฉํ๋ฉฐ, Nrf2 ํ์ฑํ๋ฅผ ๋งค๊ฐ๋ก ํ์ฌ ์ ๊ฒฝ๋ณดํธ์ ๊ด๋ จ๋ ํดํ์ฑ ์งํ ๋ฐ ๊ฑด์ ์ ์๋ฐฉ ๋๋ ์น๋ฃ ์์ฌ๋ก์ ๊ฐ์น ์์ ๊ฒ์ผ๋ก ๊ธฐ๋๋๋ค. ์ด๋ ํฅํ ๊ด๋ํ ์ ๋ ์ฒ์ฐ๋ฌผ ์ ์ฝ ๊ฐ๋ฐ์ ์์ด ๊ธฐ์ด๊ฐ ๋๋ ์ค์ํ ์ฐ๊ตฌ๋ก ์ฌ๋ฃ๋๋ค.I. INTRODUCTION 1
1. Neurodegenerative diseases 2
1.1. Parkinsons disease 6
1.2. Phytochemicals for neuroprotection 10
2. Psoriasis 13
2.1. Inflammation 18
2.2. Psoriasis treatment 21
3. Nuclear factor erythroid 2-related factor 2 (Nrf2) 24
3.1. Activation of the Nrf2 pathway for neuroprotection 26
3.2. The role of Nrf2 in skin 27
4. Tussilago farfara L. 28
II. STATE OF THE PROBLEM 31
III. RESULTS AND DISCUSSION 34
1. Neuroprotection against 6-OHDA toxicity in PC12 cells and mice through the Nrf2 pathway by ECN 35
1.1. ECN exerts protective effects against H2O2- or 6-OHDA-induced injury in PC12 cells 35
1.2. ECN up-regulates Nrf2 and HO-1 expression in PC12 cells at the transcriptional level 37
1.3. ECN-induced HO-1 expression is mediated through activation of Nrf2/ARE signaling 39
1.4. ECN may directly modify thiols of Keap1 for Nrf2 activation 41
1.5. ECN induces phosphorylation of Akt for Nrf2 activation 43
1.6. Neuroprotective effect of ECN against oxidative stress is mediated by Nrf2/HO-1 signaling 45
1.7. ECN ameliorates 6-OHDA-induced motor impairments 47
1.8. ECN prevents 6-OHDA-induced dopaminergic neuronal damage in the ST and SN of the mouse brain 49
1.9. Discussion 51
2. Amelioration of psoriasis-like skin lesions in keratinocytes and mice through Nrf2 activation by TGN 56
2.1. Heme oxygenase-1-mediated anti-inflammatory effects of TGN on macrophages and 12-O-tetradecanoylphorbol-13-acetate-induced skin inflammation in mice 56
2.1.1. TGN induces HO-1 expression in RAW 264.7 macrophages at the transcriptional level 56
2.1.2. TGN increases Nrf2 protein expression at the translational level in RAW 264.7 cells 60
2.1.3. TGN-induced HO-1 expression is mediated through activation of Nrf2 62
2.1.4. TGN inhibits the production of NO and PGE2 as well as the expression of iNOS, COX-2, TNF-ฮฑ and IL-6 in LPS-stimulated RAW 264.7 cells 64
2.1.5. TGN suppresses LPS-stimulated activation of NF-ฮบB 67
2.1.6. HO-1 mediates the inhibitory effect of TGN on LPS-induced inflammatory responses 69
2.1.7. TGN inhibits TPA-induced iNOS and COX-2 expression in HaCaT cells and mouse skin 72
2.1.8. Discussion 75
2.2. TGN ameliorates psoriatic features in keratinocytes and an imiquimod-induced psoriasis-like dermatitis in mice mediated through Nrf2 activation 80
2.2.1. TGN inhibits TNF-ฮฑ-induced NF-ฮบB activation and the expression of psoriasis-related pro-inflammatory genes in keratinocytes 80
2.2.2. TGN suppresses IL-6-induced STAT3 activation and keratinocyte proliferation 83
2.2.3. TGN activates Nrf2/ARE signaling pathway 86
2.2.4. Inhibition of NF-ฮบB and STAT3 by TGN is mediated through Nrf2 activation 89
2.2.5. Topical TGN treatment ameliorates IMQ-induced psoriasis-like skin inflammation in mice 91
2.2.6. TGN reduces inflammatory immune genes and epidermal hyperproliferation in IMQ-induced psoriasis-like skin 96
2.2.7. Discussion 103
IV. CONCLUSION 108
V. EXPERIMENTAL SECTION 111
1. Materials 112
1.1. ECN 112
1.2. Isolation and identification of TGN 112
1.3. Preparation of TGN 113
1.4. Chemicals and reagents 113
1.5. Cell culture 114
1.6. Animals 115
1.6.1. 6-OHDA-induced mouse model of PD 115
1.6.2. TPA-induced skin inflammation in mice 116
1.6.3. IMQ-induced psoriasis-like dermatitis model in mice 116
2. Methods 116
2.1. Measurement of cell viability 116
2.2. Western blot analysis 117
2.3. Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) 118
2.4. Luciferase assay 120
2.5. Transient transfection of small interfering RNA 120
2.6. Measurement of ROS accumulation 120
2.7. Measurement of NO, PGE2 production and cell viability 121
2.8. NF-ฮบB SEAP reporter gene assay 122
2.9. Isolation and culture of murine primary epidermal keratinocytes 122
2.10. Chromatin Immunoprecipitation (ChIP) 123
2.11. Animal study 124
2.11.1. 6-OHDA-induced mouse model of PD 124
2.11.1.1. Surgery procedure 124
2.11.1.2. Drug administration 125
2.11.1.3. Rotarod test 125
2.11.1.4. APO-induced rotation test 126
2.11.1.5. Immunohistochemistry 126
2.11.2. TPA-induced skin inflammation in mice 127
2.11.3. IMQ-induced psoriasis-like dermatitis model in mice 128
2.11.3.1. Treatments 128
2.11.3.2. Scoring severity of skin inflammation 129
2.11.3.3. Histology and immunohistochemistry 129
2.12. Statistical analysis 130
REFERENCES 131
ABSTRACT IN KOREAN 152Docto
Use of Topical Rapamycin as Maintenance Treatment after a Single Session of Fractionated CO2 Laser Ablation: A Method to Enhance Percutaneous Drug Delivery
Tuberous sclerosis complex (TSC) is an autosomal dominant
neurocutaneous disorder with an incidence of approximately 1 in 5,000 to 10,000 live births. TSC has various clinical
manifestations such as multiple hamartomas in systemic organs, including the skin. Angiofibromas are the most common skin lesions in patients with TSC. Although benign, angiofibromas develop in childhood and puberty, and can be
psychosocially disfiguring for patients. Skin lesions in TSC,
specifically angiofibromas, have no significant risk of malignant transformation after puberty; thus, they require no treatment if not prominent. However, the presentation of TSC is
important owing to its impact on patient cosmesis. Surgical
treatment and laser therapy are the mainstream treatments
for angiofibromas. Although the evidence is limited, topical
mammalian target of rapamycin inhibitors such as sirolimus
(rapamycin) are effective in facial angiofibroma treatment.
We describe an adult patient with an angiofibroma who had
an excellent response to treatment with topical rapamycin after a single session of carbon dioxide (CO2) laser ablation.
The patient showed no sign of relapse or recurring lesions for
a year. CO2 laser ablation may serve as a new paradigm of
treatment for angiofibromas in TSC. Since the selection of laser devices can be limited for some institutions, we suggest
a rather basic but highly effective approach for angiofibroma
treatment that can be generally applied with the classic CO2
device.ope
Posttraumatic Growth Measures in Breast Cancer Survivors: A Systematic Review
Purpose: The objective of this study was to identify and evaluate the measures used for assessment of posttraumatic growth (PTG) for women survivors with breast cancer and to evaluate the psychometric properties of
each instrument. Methods: A systematic review was conducted to identify measurement instruments used for assessment of PTG using electronic databases such as KoreaMed, DBpia, PubMed, Embase, PsycINFO, CINAHL,
and Cochrane Library. Studied published both in Korean and/or English were included for the analysis. Studies were examined by two independent reviewers and eighty-nine studies met the inclusion criteria. The selection
of the eighty-nine studies was evaluated on methodological and psychometric properties including validity and reliability of the instruments. Results: Three instruments were identified in the review of the eighty-nine studies.
The three instruments were identified as 1) Posttraumatic Growth Inventory (PTGI), 2) Benefit Finding Scale, and 3) Positive Meaning Scale. The PTGI was the most frequently reported instrument used in the review. The majority
of the reported studies were used translation and back-translation, but some of the studies did not report translation methods. Most studies (71.9%) reported reliability, but only 29.2% studies reported validity of the instruments used in the study. Conclusion: This study was conducted to provide an evidence for selection and development of measurement instruments of PTG for breast cancer survivors.ope
์ด์ฐจ์ ์ ์ด๊ธ์ ์นผ์ฝ๊ฒ ํํฉ๋ฌผ์ ์์ด์จ ๊ณต๊ณต ์๋ฆฌ์์์ ์์ ๋ฐ์ ๋ฐ์์ ๋ํ ๊ณ์ฐ ์ฐ๊ตฌ
ํ์๋
ผ๋ฌธ (๋ฐ์ฌ)-- ์์ธ๋ํ๊ต ๋ํ์ ๊ณต๊ณผ๋ํ ์ฌ๋ฃ๊ณตํ๋ถ, 2017. 8. ํ์น์ฐ.Hydrogen is a strong contender for a next-generation clean energy source that may replace the current fossil fuels. However, the low-cost and clean production of hydrogen source is a critical issue. In this regard, the hydrogen production by splitting water, the abundant resource on earth, may resolve many of these problems, particularly if it is driven by the solar energy. To split water using solar energy or electricity, catalysts are necessary to reduce the large overpotential during the hydrogen and oxygen evolution. For several decades, Pt is known to be the best catalyst for hydrogen evolution reaction in water splitting, but the material is very expensive and so might not be suitable for large scale applications. As such, numerous studies searched for alternative catalysts that have potential to replace Pt. Especially, transition metal dichalcogenides (TMDs) are receiving much attention as a new class of two-dimensional catalysts for hydrogen evolution reaction (HER). Despite extensive efforts to find highly efficient catalytic TMD systems, strong candidates to replace Pt have not been suggested yet. In TMD catalysts such as MoS2, edges are believed to be the active sites, but their limited density is a problem. Recently, it was found that the basal plane of MoS2 can also be active for HER by introducing sulfur vacancies in addition to strain.1 Herein, we try to identify the mechanism of HER on sulfur vacancy sites by means of kinetic Monte Carlo simulation using the energetics of first-principles calculations. We find that HER at sulfur vacancy site of MoS2 are dominated by the Volmer-Heyrovsky mechanism, and the vacancy site can be electrically charged, thereby lowering the energy barrier of rate-limiting Heyrovsky step. In addition, when a tensile strain is applied to MoS2, it leads to reaction paths with lower energy barriers in more negatively charged states. We also try to find new defective TMD catalyst for HER by means of computational screening based on the density functional theory. We explore the HER efficiencies of basal planes and anion vacancy sites for various TMD materials by using the hydrogen binding free energy as the descriptor for the HER efficiency. We find hydrogen binding energy is varied by the concentration of vacancy and discover good TMD candidates which are expected to show high HER performance in proper vacancy concentrations. We suggest ZrSe2 and ZrTe2 for low vacancy concentration, and MoSe2, MoTe2, WSe2, ReTe2, MoS2 and ReSe2 when intermediate or high concentration of vacancy is accessible. We expect that these materials could compete with Pt as HER catalyst even without strain engineering. In addition, through multiple linear regression, we identify that the formation energies and the electronic structures of anion vacancies strongly affect the hydrogen adsorption energy.1. Introduction 1
1.1 Hydrogen as a next-generation clean energy source 1
1.2 2D materials as novel catalysts for water splitting 2
1.3 TMD materials for HER 4
1.4 Anion vacancy as a HER active site in TMDs 5
1.5 Goal of the dissertation 7
2. Theoretical backgrounds and methods 8
2.1 Density functional theory (DFT) 8
2.1.1 Hohenberg and Kohn theorem 8
2.1.2 Kohn-Sham equation 9
2.1.3 Exchange-correlation energy 10
2.2 Gibbs free energy 12
2.2.1 Gibbs free energy of intermediates of HER on VS in MoS2 12
3. Mechanism of HER on VS in MoS2 13
3.1 Introduction: Mechanisms of HER 13
3.1.1. HER on VS in MoS2 13
3.2 Theoretical approaches for HER on VS 16
3.2.1. Multiscale simulation 16
3.2.2 HERa stepwise chemical reaction 16
3.2.3 Transition state theory 18
3.2.4 Possible intermediate states of sulfur vacancy in the MoS2 during HER 20
3.2.5 Definition of relative energies of intermediate states 21
3.2.6 Reaction energy and kinetic barrier 23
3.2.7 State transition diagrams of intermediate and transition states 25
3.2.8 Algorithm of KMC 29
3.2.7.1 Rate of event 32
3.2.7.1.1 Reaction barrier 32
3.2.7.1.2 Pre-exponential factors of rates 35
3.3 Result and discussion 38
3.3.1 State change over time and turnover frequency 38
3.3.2 Reaction mechanism 41
3.3.3 Bias dependence 43
3.3.4 Simple model 48
3.3.5 Strain effect 49
3.4 Summary: Mechanisms of HER 55
4. Screening active anion vacancy sites of various TMDs for HER 56
4.1 Introduction: Screening HER catalyst 56
4.2 Computational screening of stable TMDs for HER 59
4.2.1 Computational detail 59
4.2.2 Screening for HER on 40 stable TMD phases 59
4.2.3 Anion vacancy formation 63
4.2.4 Hydrogen adsorption free energy 65
4.2.5 Hydrogen adsorption on TMD basal plane 66
4.2.6 Hydrogen coverage on vacancies of high concentration 67
4.2.6.1 Equilibrium coverage model 67
4.2.6.2 dependence of hydrogen adsorption energy on ฮธ_H 67
4.2.7 Establishing volcano curve 70
4.3 Result and discussion 73
4.3.1 Candidate basal planes of TMD 73
4.3.2 Anion vacancy in TMDs 73
4.3.2.1 Anion vacancy formation energies in TMDs 73
4.3.2.2 Electronic structures of TMDs with anion vacancy 76
4.3.3 Hydrogen adsorption on anion vacancy site in TMD 78
4.3.3.1 Distribution of hydrogen adsorption energies on basal planes and anion vacancy sites 82
4.3.3.2 Candidate TMDs with anion vacancy as an active site 84
4.3.3.3 Classification of candidate TMDs with anion vacancy 86
4.3.3.4 Key physical quantities that affect hydrogen adsorption energy 89
4.4 Conclusion: Screening HER catalyst 92
4.5 Summary: Screening HER catalyst 93
5. Conclusion 94
Bibliography 96
๊ตญ๋ฌธ ์ด๋ก 105Docto
Factors Affecting Clinical Practicum Stress of Nursing Students: Using the Lazarus and Folkman's Stress-Coping Model
PURPOSE: This study was conducted to test a path model for the factors related to undergraduate nursing students' clinical practicum stress, based on Lazarus and Folkman's stress-coping model.
METHODS: This study utilized a path analysis design. A total of 235 undergraduate nursing students participated in this study. The variables in the hypothetical path model consisted of clinical practicum, emotional intelligence, self-efficacy, Nun-chi, and nursing professionalism. We tested the fit of the hypothetical path model using SPSS/WIN 23.0 and AMOS 22.0.
RESULTS: The final model fit demonstrated a satisfactory statistical acceptance level: goodness-of-fit-index=.98, adjusted goodness-of-fit-index=.91, comparative fit index=.98, normed fit index=.95, Tucker-Lewis index=.92, and root mean square error of approximation=.06. Self-efficacy (ฮฒ=-.22, p=.003) and Nun-chi behavior (ฮฒ=-.17, p=.024) were reported as significant factors affecting clinical practicum stress, explaining 10.2% of the variance. Nursing professionalism (ฮฒ=.20, p=.006) and self-efficacy (ฮฒ=.45, p<.001) had direct effects on emotional intelligence, explaining 45.9% of the variance. Self-efficacy had indirect effects on Nun-chi understanding (ฮฒ=.20, p<.001) and Nun-chi behavior (ฮฒ=.09, p=.005) through emotional intelligence. Nursing professionalism had indirect effects on Nun-chi understanding (ฮฒ=.09, p=.005) and Nun-chi behavior (ฮฒ=.09, p=.005) through emotional intelligence. The variables for self-efficacy and nursing professionalism explained 29.1% of the Nun-chi understanding and 18.2% of the Nun-chi behavior, respectively.
CONCLUSION: In undergraduate nursing education, it is important to identify and manage factors that affect clinical practicum stress. The findings of this study emphasize the importance of Nun-chi, self-efficacy, emotional intelligence, and nursing professionalism in the development of an educational strategy for undergraduate nursing students.ope
Assessment of deep neural networks for the diagnosis of benign and malignant skin neoplasms in comparison with dermatologists: A retrospective validation study
Background: The diagnostic performance of convolutional neural networks (CNNs) for diagnosing several types of skin neoplasms has been demonstrated as comparable with that of dermatologists using clinical photography. However, the generalizability should be demonstrated using a large-scale external dataset that includes most types of skin neoplasms. In this study, the performance of a neural network algorithm was compared with that of dermatologists in both real-world practice and experimental settings.
Methods and findings: To demonstrate generalizability, the skin cancer detection algorithm (https://rcnn.modelderm.com) developed in our previous study was used without modification. We conducted a retrospective study with all single lesion biopsied cases (43 disorders; 40,331 clinical images from 10,426 cases: 1,222 malignant cases and 9,204 benign cases); mean age (standard deviation [SD], 52.1 [18.3]; 4,701 men [45.1%]) were obtained from the Department of Dermatology, Severance Hospital in Seoul, Korea between January 1, 2008 and March 31, 2019. Using the external validation dataset, the predictions of the algorithm were compared with the clinical diagnoses of 65 attending physicians who had recorded the clinical diagnoses with thorough examinations in real-world practice. In addition, the results obtained by the algorithm for the data of randomly selected batches of 30 patients were compared with those obtained by 44 dermatologists in experimental settings; the dermatologists were only provided with multiple images of each lesion, without clinical information. With regard to the determination of malignancy, the area under the curve (AUC) achieved by the algorithm was 0.863 (95% confidence interval [CI] 0.852-0.875), when unprocessed clinical photographs were used. The sensitivity and specificity of the algorithm at the predefined high-specificity threshold were 62.7% (95% CI 59.9-65.1) and 90.0% (95% CI 89.4-90.6), respectively. Furthermore, the sensitivity and specificity of the first clinical impression of 65 attending physicians were 70.2% and 95.6%, respectively, which were superior to those of the algorithm (McNemar test; p < 0.0001). The positive and negative predictive values of the algorithm were 45.4% (CI 43.7-47.3) and 94.8% (CI 94.4-95.2), respectively, whereas those of the first clinical impression were 68.1% and 96.0%, respectively. In the reader test conducted using images corresponding to batches of 30 patients, the sensitivity and specificity of the algorithm at the predefined threshold were 66.9% (95% CI 57.7-76.0) and 87.4% (95% CI 82.5-92.2), respectively. Furthermore, the sensitivity and specificity derived from the first impression of 44 of the participants were 65.8% (95% CI 55.7-75.9) and 85.7% (95% CI 82.4-88.9), respectively, which are values comparable with those of the algorithm (Wilcoxon signed-rank test; p = 0.607 and 0.097). Limitations of this study include the exclusive use of high-quality clinical photographs taken in hospitals and the lack of ethnic diversity in the study population.
Conclusions: Our algorithm could diagnose skin tumors with nearly the same accuracy as a dermatologist when the diagnosis was performed solely with photographs. However, as a result of limited data relevancy, the performance was inferior to that of actual medical examination. To achieve more accurate predictive diagnoses, clinical information should be integrated with imaging information.ope
Neuromuscular Characteristics and Physical Function in Participants with Parkinsonโs Disease
PURPOSE: This study aimed to investigate the level of physical function, lower body strength, and muscle activation during various types of muscle contraction in participants with and without Parkinsonโs disease (PD).
METHODS: Twelve participants with PD (mean age=63.17ยฑ6.24 years) and 12 age- and sex-matched healthy adults (mean age = 58.67ยฑ6.39 years) were recruited. An isokinetic dynamometer was used to measure the length- and velocity-dependent maximum voluntary force and the rate of torque development (RTD) of the knee extensor muscles. Muscle activation of the vastus lateralis (VL), vastus medialis (VM), and rectus femoris (RF) muscles of both legs was examined using surface electromyography. The 6-minute walk test, chair stand test, timed up-and-go test, sit-and-reach test, and back-scratch test were performed to assess physical function.
RESULTS: Compared to healthy individuals, participants with PD showed significantly lower maximum voluntary force and RTD (p<.05), performed fewer repetitions in the chair stand test (11.64ยฑ1.75 vs. 17.08ยฑ2.27, p<.001), were slower in the timed up-and go test (8.36ยฑ1.42 vs. 5.65ยฑ1.07, p<.001), and walked shorter distances in the 6-minute walk test (424.17ยฑ65.97 vs. 539.47ยฑ63.18, p<.001). However, activation of the three different muscles during isometric and isokinetic muscle contraction was not different between participants with and without PD.
CONCLUSIONS: Preserved muscle activation and significantly lower muscle strength during various types of muscle contractions may suggest lower muscle strength and efficiency. The lower physical function seen in participants with mild PD could be due to disease and low physical activity-related muscle atrophy rather than lower muscle activation.ope
Vegetative Growth and Inflorescence Emergence of Phalaenopsis 'Mantefon' as Affected by Photoperiod, Light Intensity, and Daily Light Integral
ํ์๋
ผ๋ฌธ (์์ฌ)-- ์์ธ๋ํ๊ต ๋ํ์ : ๋์
์๋ช
๊ณผํ๋ํ ์๋ฌผ์์ฐ๊ณผํ๋ถ, 2018. 2. ๊น๊ธฐ์ .This study was conducted to deterimne how photoperiod, light intensity, and daily light integral (DLI) influence vegetative growth (Experiment 1) and inflorescence emergence (Experiment 2) in Phalaenopsis. In Experiment 1, five-month-old plants were treated with a combination of three photoperiods [8 (short day, SD), 12 (medium day, MD), and 16 h (long day, LD)] and three light intensities (50, 100, and 200 ฮผmolโm-2โs-1), resulting in 7 DLIs ranging from 1.44 to 11.52 molโm-2โd-1. Each light treatment was maintained for 20 weeks at constant 28oC. It was observed that plants grown under longer photoperiod and high light intensity resulted in shorter, wider, and thicker leaves, respectively. Number of new leaves, total leaf area, and shoot and root weights were increased with increasing photoperiod and light intensity. DLI showed higher correlation coefficients with vegetative growth parameters than with photoperiod and light intensity. The regression analysis indicated that increased DLIs promoted vegetative growth. However, it was observed that when DLI reached 11.52 molโm-2โd-1, response slope gradually decreased.
In Experiment 2, twelve-month-old plants were used to investigate the effects of photoperiod, light intensity, and DLI on inflorescence emergence. Plants were treated with combinations of three photoperiods [8/16 (day/night, SD), 8+8 (DE10 ฮผmolโm-2โs-1 for 8 h extension right after the SD), and 16/8 h (LD)] and three light intensities (75, 150, and 300 ฮผmolโm-2โs-1). Each light treatment was maintained for 12 weeks at constant 20oC. Inflorescence emergence percent, the days to emergence, and the number of inflorescences were generally more promoted under LD treatments than SD and DE treatments, indicating that the effect of photoperiod on flower induction of Phalaenopsis was insignificant. Comparing the light intensities, inflorescence emergence was generally promoted as the light intensity was increased. Correlation coefficients of DLIs with days to emergence and number of inflorescences showed the highest values. Regression analysis indicated that as DLI increase from 2 to 17 molโm-2โd-1, the days to inflorescence emergence was shortened by about one month, and average number of the inflorescence was increased more than 2 times. However, they seemed not to be promoted beyond DLI of 12 molโm-2โd-1, suggesting that the DLI reached the maximum (or saturation) point. Thus, inflorescence emergence was promoted with increasing DLI, but the DLI above 12 molโm-2โd-1 was less promotive for inflorescence emergence.INTRODUCTION 1
LITERATURE REVIEW
Characteristics of Phalaenopsis 4
Vegetative Growth in Response to Light Intensity and Photoperiod 5
Reproductive Growth in Response to Light Intensity and Photoperiod 6
Growth and Development in Response to Daily Light Integral (DLI) 7
MATERIALS AND METHODS
Vegetative Growth (Experiment 1) 9
Inflorescence Emergence (Experiment 2) 11
RESULTS AND DISCUSSION
Vegetative Growth (Experiment 1) 13
Inflorescence Emergence (Experiment 2) 30
LITERATURE CITED 48
ABSTRACT IN KOREAN 58Maste
Clinical Efficacy and Tolerance of 1% Nadifloxacin Cream in the Treatment of Mild to Moderate Acne Vulgaris in South Korea
Background: Antimicrobials have been a mainstay of inflammatory acne treatment for more than 30 years. However, antibiotic-resistant propionibacteria had been isolated with increased frequency, and associated with failure to respond to antibiotic therapy. Objective: The aim of this study was to investigate the clinical efficacy and tolerance of 1% nadifloxacin cream. Methods: In the final analysis, 197 patients with mild to moderate facial acne vulgaris were enrolled. The patients were instructed to apply 1% nadifloxacin cream twice daily to the affected skin after washing the face. Following 2 and 4 weeks of treatment, patients were observed for clinical response: number of the acne lesions, Korea acne grading system (KAGS), global improvement, and occurrence of adverse reactions. Results: During 4 weeks of treatment, nadifloxacin caused significant reduction in the number of inflamed papulo-pustular lesions and open/closed comedones. In addition, significant reduction of KAGS was observed. About 96% of patients showed clinical improvement in the overall evaluation of the therapeutic effect by physicians. All reported adverse events were mild. Conclusion: This study shows that 1% nadifloxacin cream can be an effective and safe treatment for mild to moderate acne vulgaris.ope
Impact of Stroke Knowledge, Fear of Recurrence on Health Behavior in patients with ischemic stroke
Purpose: The purpose of this study was to identify the following: knowledge of stroke, fear of recurrence and health behaviors among patients with ischemic stroke. Further, factors influencing health behavior will be described.
Methods: Data were collected from 180 patients with ischemic stroke at a general hospital. The study instruments included items about general and health related characteristics, a Stroke Knowledge Scale, a Stroke Fear of
Recurrence Scale, and a Health Behavior Scale. Hierarchical regression method was conducted to examine predictors of health behavior. Results: The mean age of the participants was 63.62ยฑ11.10 years, and 57.8% of the
sample was men. The mean score for stroke knowledge (possible range=0~17) was 14.99ยฑ1.76, the mean score for fear of recurrence (possible range=0~32) was 23.16ยฑ3.75, and the mean score for health behavior (possible
range=20~80) was 54.69ยฑ6.46. Stroke knowledge and fear of recurrence were associated with health behavior in patients with ischemic stroke (F=9.98, p<.001, Adjusted R2=.43). Conclusion: The results demonstrated that
stroke knowledge and fear of recurrence impacts the health behavior among patients with ischemic stroke. Thus, nursing interventions which focused on fear of recurrence as well as enhancing stroke knowledge could help health
behavior in patients with ischemic stroke.ope
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