Search results for: Zhen-Hua Ming

Authors: Chun Hsien Wu, Guan Xuan Wu, Hsia Ying Cheng, Shyh Ming Kuo

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Articular cartilage is composed of chondrocytes and extracellular matrix, such as collagen fibers, glycosaminoglycans, etc., which play an important role in lubricating and cushion joint activities. The phenotypic expression and metabolic activity of chondrocytes are extremely important in maintaining the functions of articular cartilage. In in vitro passaged culture of chondrocytes, chondrocytes gradually lose their original cell phenotype and morphology, which is called dedifferentiation. After continuous passaged culture of chondrocytes or induction by inflammatory factor IL-1, chondrocytes changed their phenotype and morphology. Also, the extracellular matrix type II collagen and GAG secretion were significantly reduced, while type I and X collagen were synthesized. Farnesol is an anti-inflammatory and antioxidant sesquiterpene compound that has the specific property of promoting collagen production. The purpose of this study was to investigate whether farnesol could restore the original type II collagen synthesis and, furthermore, the mechanisms of farnesol on the synthesis of type II collagen from the de-differentiated chondrocytes. The obtained results showed that the de-differentiated chondrocytes significantly restored to secret type II collagen and GAG (2.5-folds increases), and the secretion of collagen I and X and PGE2 synthesis were also significantly reduced after being treated with farnesol, indicating that farnesol had a restoration/re-differentiation effect on de-differentiated chondrocytes. The de-differentiated chondrocytes exhibited decreased expression of PPAR-γ and upregulated TGF-β expression to increase the MMP-13 expression. Higher expression of MMP-13 caused chondrocytes to secret type X collagen. On the contrary, increasing the expression of PPAR-γ would benefit the production of type II collagen. As shown, the PPAR-γ expression increased, and MMP-13 expression decreased after being treated with farnesol, indicating a possible signal pathway of farnesol to restore the production of type II collagen. However, more detailed mechanisms still need to evaluate.

Keywords: chondrocytes, de-differentiation, farnesol, re-differentiation

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Authors: Wei-Jing Li, Ren-Xuan Yang, Kui-Hao Chuang, Ming-Yen Wey

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Nowadays, plastic product and utilization are extensive and have greatly improved our life. Yet, plastic wastes are stable and non-biodegradable challenging issues to the environment. Waste-to-energy strategies emerge a promising way for waste management. This work investigated the co-production of hydrogen and carbon nanotubes from the syngas which was from the gasification of polypropylene. A nickel-silica core-shell catalyst was applied for syngas reaction from plastic waste gasification in a fixed-bed reactor. SiO2 were prepared through various synthesis solvents by Stöber process. Ni plays a role as modified SiO2 support, which were synthesized by deposition-precipitation method. Core-shell catalysts have strong interaction between active phase and support, in order to avoid catalyst sintering. Moreover, Fe or Co metal acts as promoter to enhance catalytic activity. The effects of calcined atmosphere, second metal addition, and reaction temperature on hydrogen production and carbon yield were examined. In this study, the catalytic activity and carbon yield results revealed that the Ni/SiO2 catalyst calcined under H2 atmosphere exhibited the best performance. Furthermore, Co promoted Ni/SiO2 catalyst produced 3 times more than Ni/SiO2 on carbon yield at long-term operation. The structure and morphological nature of the calcined and spent catalysts were examined using different characterization techniques including scanning electron microscopy, transmission electron microscopy, X-ray diffraction. In addition, the quality and thermal stability of the nano-carbon materials were also evaluated by Raman spectroscopy and thermogravimetric analysis.

Keywords: plastic wastes, hydrogen, carbon nanotube, core-shell catalysts

Procedia PDF Downloads 290

Authors: Adam Y. Sulaiman, Donal F. Cotter, Ming J. Huang, Neil J. Hewitt

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Suitable low global warming potential (GWP) refrigerants that conform to F-gas regulations are required to extend the operational envelope of high-temperature heat pumps (HTHPs) used for industrial waste heat recovery processes. The thermophysical properties and characteristics of these working fluids need to be assessed to provide a comprehensive understanding of operational effectiveness in HTHP applications. This paper presents the results of a theoretical simulation to investigate a range of low-GWP refrigerants and their suitability to supersede refrigerants HFC-245fa and HFC-365mfc. A steady-state thermodynamic model of a single-stage HTHP with an internal heat exchanger (IHX) was developed to assess system cycle characteristics at temperature ranges between 50 to 80 °C heat source and 90 to 150 °C heat sink. A practical approach to maximize the operational efficiency was examined to determine the effects of regulating minimum superheat within the process and subsequent influence on energetic and exergetic efficiencies. A comprehensive map of minimum superheat across the HTHP operating variables were used to assess specific tipping points in performance at 30 and 70 K temperature lifts. Based on initial results, the refrigerants HCFO-1233zd(E) and HFO-1336mzz(Z) were found to be closely aligned matches for refrigerants HFC-245fa and HFC-365mfc. The overall results show effective performance for HCFO-1233zd(E) occurs between 5-7 K minimum superheat, and HFO-1336mzz(Z) between 18-21 K dependant on temperature lift. This work provides a method to optimize refrigerant selection based on operational indicators to maximize overall HTHPs system performance.

Keywords: high-temperature heat pump, minimum superheat, energy & exergy efficiency, low GWP refrigerants

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Authors: Ying-Ming Su, Mei-Shu Huang

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To mitigate the urban heat island effect has become a global issue facing the challenge of climate change. Through literature reviews, plant photosynthesis can reduce the carbon dioxide and mitigate the urban heat island effect relatively. Because there are not enough open space and park, green roof has become an important policy in Taiwan. We selected elementary school buildings in northern New Taipei City as research subjects since elementary school is asked priority to build green roof and important educational place to promote green roof concept. Testo 175-H1 recording device was used to record the temperature and humidity difference between roof surface and interior space below roof with and without green roof for the long-term. We also use questionnaire to investigate the awareness of comfort level of green roof and sensation of teachers and students of the elementary school. The results indicated the temperature of roof without greening was higher than that with greening about 2°C. But sometimes during noontime, the temperature of green roof was higher than that of non-green roof related to the character of the accumulation and dissipation of heat of greening probably. The temperature of interior space below green roof was normally lower than that without green roof about 1°C showed that green roof could lower the temperature. The humidity of the green roof was higher than the one without greening also indicated that green roof retained water better. Teachers liked to combine green roof concept in the curriculum, students wished all classes can take turns to maintain the green roof. Teachers and students that school had integrated green roof concept in the curriculum were more willing to participate in the maintenance work of green roof. Teachers and students who may access and touch the green roof can be more aware of the green roof benefit. We suggest architect to increase the accessibility and visibility of green roof, such as a part of the activity space. This idea can be a reference of the green roof curriculum design.

Keywords: comfort level, elementary school, green roof, heat island effect

Procedia PDF Downloads 382

Authors: Shang-Yu Chiang, Yu-Shan Tsai, Shih-Hsien Sung, Chung-Ming Lo

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Mitral regurgitation (MR) is a heart disorder which the mitral valve does not close properly when the heart pumps out blood. MR is the most common form of valvular heart disease in the adult population. The diagnostic echocardiographic finding of MR is straightforward due to the well-known clinical evidence. In the determination of MR severity, quantification of sonographic findings would be useful for clinical decision making. Clinically, the vena contracta is a standard for MR evaluation. Vena contracta is the point in a blood stream where the diameter of the stream is the least, and the velocity is the maximum. The quantification of vena contracta, i.e. the vena contracta width (VCW) at mitral valve, can be a numeric measurement for severity assessment. However, manually delineating the VCW may not accurate enough. The result highly depends on the operator experience. Therefore, this study proposed an automatic method to quantify VCW to evaluate MR severity. Based on color Doppler ultrasound, VCW can be observed from the blood flows to the probe as the appearance of red or yellow area. The corresponding brightness represents the value of the flow rate. In the experiment, colors were firstly transformed into HSV (hue, saturation and value) to be closely align with the way human vision perceives red and yellow. Using ellipse to fit the high flow rate area in left atrium, the angle between the mitral valve and the ultrasound probe was calculated to get the vertical shortest diameter as the VCW. Taking the manual measurement as the standard, the method achieved only 0.02 (0.38 vs. 0.36) to 0.03 (0.42 vs. 0.45) cm differences. The result showed that the proposed automatic VCW extraction can be efficient and accurate for clinical use. The process also has the potential to reduce intra- or inter-observer variability at measuring subtle distances.

Keywords: mitral regurgitation, vena contracta, color doppler, image processing

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Authors: Hsiao-Chien Tsai, Yu-Pin Chen, Ruei-Ming Chen

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Introduction: Osteoarthritis (OA) is characterized by joint destruction and causes chronic disability. One of the prominent symptoms is pain. Alleviating the pain is necessary and urgent for the therapy of OA patients. However, currently, understanding the mechanisms that drive OA-induced pain remains challenging, which hampers the optimistic management of pain in OA patients. Semaphorin 4D (Sema4D) participates in axon guidance pathway and bone remodeling, thus, may play a role in the regulation of pain in OA. In this study, we have established a rat model of OA to find out the mechanisms of OA-induced pain and to deliberate the roles of Sema4D. Methods: Behavioral changes and the pro-inflammatory cytokines (IL-1β, TNF-α, and IL-17) associated with pain were measured during the development of OA. Sema4D expression in cartilage and synovial membrane at 1, 4, and 12 weeks after inducing OA was analyzed. To assess if Sema4D is related to the neurogenesis in OA as an axon repellant, we analyzed the expression of PGP9.5 as well. Results: Synovitis and cartilage degradation were evident histologically during the development of OA. Mechanical hyperalgesia was most severe at week 1, then persisted thereafter. It was associated with stress coping strategies. Similar to the pain behavioral results, levels of IL-1β and TNF-α in synovial lavage fluid were significantly elevated in the OA group at weeks 1 and 4, respectively. Sema4D expression in cartilage and the synovial membrane was also enhanced in the OA group and was correlated with pain and pro-inflammatory cytokines. The marker of neurogenesis, PGP9.5, was also enhanced during the development of OA. Discussion: OA induced mechanical hyperalgesia, which might be through upregulating IL-1β/TNF-α-mediated Sema4D expressions. If anti-Sema4D treatment could reduce OA-induced mechanical hyperalgesia and prevent the subsequent progression of OA needs to be further investigated. Significance: OA can induce mechanical hyperalgesia through upregulation of IL-1β/TNF-α-mediated Sema4D and PGP9.5 expressions. And the upregulation of Sema4D may indicate the severity or active status of OA and OA-induced pain.

Keywords: traumatic osteoarthritis, mechanical hyperalgesia, Sema4D, inflammatory cytokines

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Authors: Chin-Hsien Yeh, Shao-Wen Chen, Wen-Shu Huang, Chun-Fu Huang, Jong-Rong Wang, Jung-Hua Yang, Yuh-Ming Ferng, Chunkuan Shih

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In this research, a Fukushima-like conditions is simulated with TRACE and RELAP5. Fukushima Daiichi Nuclear Power Plant (NPP) occurred the disaster which caused by the earthquake and tsunami. This disaster caused extended loss of all AC power (ELAP). Hence, loss of ultimate heat sink (LUHS) happened finally. In order to handle Fukushima-like conditions, Taiwan Atomic Energy Council (AEC) commanded that Taiwan Power Company should propose strategies to ensure the nuclear power plant safety. One of the diverse and flexible coping strategies (FLEX) is a different water injection strategy. It can execute core injection at 20 Kg/cm2 without depressurization. In this study, TRACE and RELAP5 were used to simulate Maanshan nuclear power plant, which is a three loops PWR in Taiwan, under Fukushima-like conditions and make sure the success criteria of FLEX. Reducing core cooling ability is due to failure of emergency core cooling system (ECCS) in extended loss of all AC power situation. The core water level continues to decline because of the seal leakage, and then FLEX is used to save the core water level and make fuel rods covered by water. The result shows that this mitigation strategy can cool the reactor pressure vessel (RPV) as soon as possible under Fukushima-like conditions, and keep the core water level higher than Top of Active Fuel (TAF). The FLEX can ensure the peak cladding temperature (PCT) below than the criteria 1088.7 K. Finally, the FLEX can provide protection for nuclear power plant and make plant safety.

Keywords: TRACE, RELAP5/MOD3.3, ELAP, FLEX

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Authors: Teklu Urgessa, Joong Seek Lee

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Social media is becoming the primary choice of activists to make their voices heard. This fact is coupled by two main reasons. The first reason is the emergence web 2.0, which gave the users opportunity to become content creators than passive recipients. Secondly the control of the mainstream mass media outlets by the governments and individuals with their political and economic interests. This paper aimed at exploring twitter data of network actors talking about the marathon silver medalists on Rio2016, who showed solidarity with the Oromo protesters in Ethiopia on the marathon race finish line when he won silver. The aim is to discover important insight using social network analysis and mining. The hashtag #FeyisaLelisa was used for Twitter network search. The actors’ network was visualized and analyzed. It showed the central influencers during first 10 days in August, were international media outlets while it was changed to individual activist in September. The degree distribution of the network is scale free where the frequency of degrees decay by power low. Text mining was also used to arrive at meaningful themes from tweet corpus about the event selected for analysis. The semantic network indicated important clusters of concepts (15) that provided different insight regarding the why, who, where, how of the situation related to the event. The sentiments of the words in the tweets were also analyzed and indicated that 95% of the opinions in the tweets were either positive or neutral. Overall, the finding showed that Olympic stage protest of the marathoner brought the issue of Oromo protest to the global stage. The new research framework is proposed based for event-based social network analysis and mining based on the practical procedures followed in this research for event-based social media sense making.

Keywords: human rights, Olympics, social media, network analysis, social network ming

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Authors: Sophia Ming Lee Wen, Chao-Ching Kuo, Yu-Line Hu, Yu-Lung Ho, Chih-Cheng Huang, Yi-Hwa Lee

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Teaching and learning should involve social issues by which effectiveness and humanity is due consideration as a guideline for sharing and co-creating knowledge. A qualitative method was used after a pioneer study to confirm pre-service teachers’ awareness of open knowledge. There are 17 in-service teacher candidates sampling from 181 schools in Taiwan. Two questions are to resolve: a) How did teachers change their educational ideas, in particular, their attitudes to meet the needs of knowledge sharing and co-creativity; and b) How did they acknowledge the necessity of working out an appropriate way between the educational efficiency and the nature of education for high performance management. This interview investigated teachers’ attitude of sharing and co-creating knowledge. The results show two facts in Taiwan: A) Individuals who must be able to express themselves will be capable of taking part in an open learning environment; and B) Teachers must lead the direction to inspire high performance and improve students’ capacity via knowledge sharing and co-creating knowledge, according to the student-centered philosophy. Collected data from interviewing showed that the teachers were well aware of changing their teaching methods and make some improvements to balance the educational efficiency and the nature of education. Almost all teachers acknowledge that ICT is helpful to motivate learning enthusiasm. Further, teaching integrated with ICT saves teachers’ time and energy on teaching preparation and promoting effectiveness. Teachers are willing to co-create knowledge with students, though using information is not easy due to the lack of operating skills of the website and ICT. Some teachers are against to co-create knowledge in the informational background since they hold that is not feasible for there being a knowledge gap between teachers and students. Technology would easily mislead teachers and students to the goal of instrumental rationality, which makes pedagogy dysfunctional and inhumane; however, any high quality of teaching should take a dialectical balance between effectiveness and humanity.

Keywords: critical thinking, dialectic between effectiveness and humanity, open knowledge, pedagogy

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Authors: Dawei Shen, Ming Xu, Pengfei Liu

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The joints between simply supported bridge decks and abutments need to be regularly repaired, which would greatly increase the cost during the service life of the bridge. Simply supported girder bridges suffered the most severe damage during earthquakes. Another type of bridge, the integral bridge, of which the superstructure and abutment are rigidly connected, was also used in some European countries. Because no bearings or joints exit in the integral bridge, this type of bridge could significantly reduce maintenance requirements and costs. However, conventional integral bridge usually result in high earth pressure on the abutment and surface settlement in the backfill. To solve these problems, a new type of integral bridge, geosynthetic-reinforced soil (GRS) integral bridge, was come up in recent years. This newly invented bridge has not been used in engineering practices. There was a lack of research on the seismic behavior of the conventional and new type of integral abutments. In addition, no common design code could be found for the calculation of seismic pressure of soil behind the abutment. This paper developed a dynamic constitutive model, which can consider the soil behaviors under cyclic loading. Numerical analyses of the seismic response of a full height integral bridge and GRS integral bridge were carried out using the two-dimensional numerical code, FLAC. A parametric study was also performed to investigate the soil-structure interaction. The results are presented below. The seismic responses of GRS integral bridge together with conventional simply supported bridge, GRS conventional bridge and conventional integral bridge were investigated. The results show that the GRS integral bridge holds the highest seismic stability, followed by conventional integral bridge, GRS simply supported bridge and conventional simply supported bridge. Compared with the integral bridge with 1 m thick abutments, the GRS integral bridge with 0.4 m thick abutments is subjected to a smaller bending moment, and the natural frequency and horizontal displacement remains almost the same. Geosynthetic-reinforcement will be more effective when the abutment becomes thinner or the abutment is higher.

Keywords: geosynthetic-reinforced soil integral bridge, nonlinear hysteretic model, numerical analysis, seismic response

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Authors: Hongping Lu, Kelbinur Tursun, Yaru Li, Yu Zhang, Shunai Liu, Ming Han

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Objective: To investigate whether NS5ATP9 is involved in IL-6 mediated autophagy and the relationship between IL-6 and NS5ATP9 in liver cancer cells. Methods: 1. Detect the mRNA and protein levels of Beclin 1 after HepG2 cells were treated with or without recombinant human IL-6 protein. 2. Measure and compare of the changes of autophagy-related genes with their respective control, after IL-6 was silenced or neutralized with monoclonal antibody against human IL-6. 3. HepG2 cells were incubated with 50 ng/ml of IL-6 in the presence or absence of PDTC. The expression of NS5ATP9 was analyzed by Western blot after 48 h. 4. After NS5ATP9-silenced HepG2 cells had been treated with 50 ng/ml recombinant IL-6 protein, we detected the Beclin 1 and LC3B (LC3Ⅱ/Ⅰ) expression. 5. HepG2 cells were transfected with pNS5ATP9, si-NS5ATP9, and their respective control. Total RNA was isolated from cells and analyzed for IL-6. 6. Silence or neutralization of IL-6 in HepG2 cells which has been transfected with NS5ATP9. Beclin 1 and LC3 protein levels were analyzed by Western blot. Result: 1. After HepG2 were treated with recombinant human IL-6 protein, the expression of endogenous Beclin 1 was up-regulated at mRNA and protein level, and the conversion of endogenous LC3-I to LC3-II was also increased. These results indicated that IL-6 could induce autophagy. 2. When HepG2 cells were treated with IL-6 siRNA or monoclonal antibody against human IL-6, the expression of autophagy-related genes were decreased. 3. Exogenous human IL-6 recombinant protein up-regulated NS5ATP9 via NF-κB activation. 4. The expression of Beclin 1 and LC3B was down-regulated after IL-6 treated NS5ATP9-silenced HepG2 cells. 5. NS5ATP9 could reverse regulates IL-6 expression in HepG2 cells. 6. Silence or neutralization of IL-6 attenuates NS5ATP9-induced autophagy slightly. Conclusion: Our results implied that in HCC patients, maybe the higher level of IL-6 in the serum promoted the expression of NS5ATP9 and induced autophagy in cancer cells. And the over-expression of NS5ATP9 which induced by IL-6, in turn, increased IL-6 expression, further, promotes the IL-6/NS5ATP9-mediated autophagy and affects the progression of tumor. Therefore, NS5ATP9 silence might be a potential target for HCC therapy.

Keywords: autophagy, Hepatocellular carcinoma, IL-6, microenvironment, NS5ATP9

Procedia PDF Downloads 224

Authors: Yu-Ju Tsai, Ching-Chun Wang, Wen-Tzu Tang, Huei-Ming Chai

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A pronated foot is frequently associated with a hypermobile first ray, then developing further severe foot problems. Low-Dye taping with athletic tape has been widely used to restrict excessive first ray motion and re-build height of the medial longitudinal arch in general population with pronated foot. It is not the case, however, for sprinters since they feel too much restriction of foot motions. Currently, the kinesio tape, more elastic than the athletic tape, has been widely used to re-adjust joint positions. It was interesting whether modified low-Dye taping using kinesio tape was beneficial for altering first ray mobility and still giving enough arch support. The purpose of this study was to investigate the effect of modified low-Dye taping on first ray mobility test and 60-m sprint time for sprinters with pronated foot. The significance of this study provides new insight into a treatment alternative of modified low-Dye taping for sprinter with pronated foot. Ten young male sprinters, aged 20.8±1.6 years, with pronated foot were recruited for this study. The pronated foot was defined as the foot that the navicular drop test was greater than 1.0 cm. Three optic shutters were placed at the start, 30-m, and 60-m sites to record sprint time. All participants were asked to complete 3 trials of the 60-m dash with both taping and non-taping conditions in a random order. The low-Dye taping was applied using the method postulated by Ralph Dye in 1939 except the kinesio tape was used instead. All outcome variables were recorded for taping and non-taping conditions. Paired t-tests were used to analyze all outcome variables between 2 conditions. Although there were no statistically significant differences in dorsal and plantar mobility between taping and non-taping conditions, a statistical significance was found in a total range of motion (dorsiflexion plus plantarflexion angle) of the first ray when a modified low-Dye taping was applied (p < 0.05). Time to complete 60-m sprint was significantly increased with low-Dye taping (p < 0.05) while no significance was found for time to 30-m. it indicated that modified low-Dye taping changed maximum sprint speed of 60-m dash. Conclusively, modified low-Dye taping was capable of increasing first ray mobility and further altered maximum sprint speed.

Keywords: first ray mobility, kinesio taping, pronated foot, sprint time

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Authors: Ru-Yu Lien, Shih-Hsin Hung, Shu-Fen Lu, Shu-I Chin, Wen-Ju Yang, Wan Ming-Shang, Chien-Ying Wang

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Background: Upon recovery from critical condition, patients are normally transferred from the intensive care units (ICUs) to the general wards. However, transferring patients to a new environment causes stressful experiences for both patients and their families. Therefore, there is a necessity to communicate with the patients and their families to reduce psychological stress and unplanned return. Methods: This study was performed in the general ICUs from January 1, 2021, to December 31, 2021, in Taipei Veteran General Hospital. The patients who were evaluated by doctors and liaison nurses transferred to the general wards were selected as the research objects and ranked by the Critical Care Transition Program (CCTP). The plan was applied to 40 patients in a study group and usual care support for a control group of 40 patients. The psychological condition of patients was evaluated by a migration stress scale and a hospital anxiety and depression scale. In addition, the rate of return to ICU was also measured. Results: A total of 63 patients out of 80 (78.8%) experienced moderate to severe degrees of anxiety, and 42 patients (52.6%) experienced moderate to severe degrees of depression before being transferred. The difference between anxiety and depression changed more after the transfer; moreover, when a transition program was applied, it was lower than without a transition program. The return to ICU rate in the study group was lower than in the usual transition group, with an adjusted odds ratio of 0.21 (95% confidence interval: 0.05-0.888, P=0.034). Conclusion: Our study found that the transfer program could reduce the anxiety and depression of patients and the associated stress on their families during the transition from ICU. Before being transferred out of ICU, the healthcare providers need to assess the needs of patients to set the goals of the care plan and perform patient-centered decision-making with multidisciplinary support.

Keywords: ICU, critical care transition program, healthcare, transition program

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Authors: Ming-Juei Chang, Hui-Ing Ma, Tsung-Hsueh Lu

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Introduction: Because of the advance of medical care (e.g., ventilation techniques and gastrostomy feeding), more and more children with CP can live to adulthood. However, little is known about the use of health care services from children to adults who have CP. The patterns of utilization of ambulatory care are heavily influenced by insurance coverage and primary care gatekeeper regulation. The purpose of this study was to examine patterns of ambulatory care utilization among individuals with CP in Taiwan, a country with universal coverage and no gatekeeper regulation. Methods: A representative sample of one million patients (about 1/23 of total population) covered by Taiwan’s National Health Insurance was used to analyze the ambulatory care utilization in individuals with CP. Data were analyzed by 3 different age groups (children, youth and adults) during 2000 to 2003. Participants were identified by the presence of CP diagnosis made by pediatricians or physicians of physical and rehabilitation medicine and stated at least three times in claims data. Results: Annual rates of outpatient physician visits were 31680 for children, 16492 for youth, and 28617 for adults with CP (per 1000 persons). Individuals with CP received over 50% of their outpatient care from hospital outpatient department. Higher use of specialist physician services was found in children (54.7%) than in the other two age groups (28.4% in youth and 18.8% in adults). Diseases of respiratory system were the most frequent diagnoses for visits in both children and youth with CP. Diseases of the circulatory system were the main reasons (24.3%) that adults with CP visited hospital outpatient care department or clinics. Conclusion: This study showed different patterns of ambulatory care utilization among different age groups. It appears that youth and adults with CP continue to have complex health issues and rely heavily on the health care system. Additional studies are needed to determine the factors which influence ambulatory care utilization among individuals with CP.

Keywords: cerebral palsy, health services, lifespan, universal coverage

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Authors: Long-Shan Wu, Ming-Chen Ko, Chien-Chang Ho, Po-Fu Lee, Jenn-Woei Hsieh, Ching-Yu Tseng

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This study aimed to determine the effects of whole-body vibration (WBV) training on lower-extremity muscle strength and balance control performance among community-dwelling middle-aged and older adults in the United States. Twenty-nine participants without any contraindication of performing WBV exercise completed all the study procedures. Participants were randomly assigned to do body weight exercise with either an individualized vibration frequency and amplitude, a fixed vibration frequency and amplitude, or no vibration. Isokinetic knee extensor power, limits of stability, and sit-to-stand tests were performed at the baseline and after 8 weeks of training. Neither the individualized frequency-amplitude WBV training protocol nor the fixed frequency-amplitude WBV training protocol improved isokinetic knee extensor power. The limits of stability endpoint excursion score for the individualized frequency-amplitude group increased by 8.8 (12.9%; p = 0.025) after training. No significant differences were observed in fixed and control group. The maximum excursion score for the individualized frequency-amplitude group at baseline increased by 9.2 (11.5%; p = 0.006) after training. The average weight transfer time score significantly decreased by 0.21 s in the fixed group. The participants in the individualized group showed a significant increase (3.2%) in weight rising index score after 8 weeks of WBV training. These results suggest that 8 weeks of WBV training improved limit of stability and sit-to-stand performance. Future studies need to determine whether WBV training improves other factors that can influence posture control.

Keywords: whole-body vibration training, muscle strength, balance control, middle-aged and older adults

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Authors: Yi-Shuan ShaoShao, Yen-An Tsai, Chia-Huang Chang, Kai-Wei Liao, Ming-Song Tsai, Mei-Lien Chen

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Organophosphate pesticides (OPs) is an environmental hormone with proven endocrine-disrupting effects that may affect the growth and development in human. A large amount of organophosphate pesticides (OPs) is used throughout Taiwan, and human may be exposed through dietary intake or residential use. During pregnancy, OPs can be transferred to the blood stream reaching the fetus through the placenta. The aim of this study was to explore the association between maternal OPs exposure levels and fetal developments and birth outcomes. A birth cohort was follow-up. Maternal urine sample were collected at the first, second, and third gestational trimester. Fetal growth characteristics were measured by ultrasonic scan and birth outcomes were assessed by pediatrician. Urinary metabolite of organophosphate pesticides were assessed using gas chromatography-mass spectrometry. The analytes included dimethylphosphate (DMP), dimethylthiophosphate (DMTP), dimethyldithiophosphates (DMDTP), diethylphosphate (DEP), diethylthiophosphate (DETP), and diethyldithiophosphate (DEDTP). We found that all of urine samples in each trimester were detected at least one metabolite for dialkyl phosphate (DAP). The detection rate range of OP urinary metabolites were from the lowest 22% DEDTP to the highest 100% DMP and DMTP. And to compared geometric means (GM) of urinary metabolites with three trimesters, that third trimester had the highest concentration for DMPs, DEPs, and DAPs in pregnant women were 368.01, 169.85 and 543.75 nmol/g creatinine, respectively. We observed that DAPs concentration in first and second trimester were significantly negative association with head circumference. DMPs in first trimester was significantly negative association with thoracic circumference (p=0.05) by spearman correlation. Our results support associations with prenatal OPs exposure with fetal head circumference and thoracic circumference. It provided that maternal OPs exposure might affect birth outcomes. Thus, prenatal exposure to OPs and health risk worthy of attention and concern.

Keywords: DAPs, birth outcomes, organophosphate pesticides, prenatal

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Authors: Kuan Yin Hsiao, Shyh Ming Kuo, Yi Jhen Wu, Chin Wen Chuang, Chuen-Fu Lin, Wei-qing Yang, Han Hsiang Huang

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Anti-tumor effects of natural products, like compounds from marine sponges and soft corals, have been investigated for decades. Polymeric nanoparticles prepared from biodegradable and biocompatible molecules, such as Hyaluronan (HA), Chitosan (CHI) and gelatin have been widely studied. Encapsulation of anti-cancer therapies by the biopolymeric nanoparticles in drug delivery system is potentially capable of improving the therapeutic effects and attenuating their toxicity. In the current study, the anti-bladder cancer effects of heteronemin extracted from the sponge Hippospongia sp. with or without HA and CHI nanoparticle encapsulation were assessed and evaluated in vitro. Results showed that IC50 (half maximal inhibitory concentration) of heteronemin toward T24 human bladder cancer cell viability is approximately 0.18 µg/mL. Both plain and HA nanoparticles-encapsulated heteronemin at 0.2 and 0.4 µg/mL significantly reduced T24 cell viability (P<0.001) while HA nanoparticles-encapsulated heteronemin showed weaker viability-inhibitory effects on L929 fibroblasts compared with plain heteronemin at the identical concentrations. HA and CHI nanoparticles-encapsulated heteronemin exhibited significantly stronger inhibitory effects against migration of T24 human bladder cancer cell than those exerted by plain heteronemin at the same concentrations (P<0.001). The flow cytometric results showed that 0.2 µg/mL HA and CHI nanoparticles-encapsulated heteronemin induced higher early apoptosis rate than that induced by plain heteronemin at the same concentration. These results show that HA and CHI nanoparticle encapsulation is able to elevate anti-migratory and apoptosis-inducing effects exerted by heteronemin against bladder cancer cells in vitro. The in vivo anti-bladder cancer effects of the compound with or without HA/CHI nanoparticle encapsulation will be further investigated and examined using murine tumor models. The data obtained from this study will extensively evaluate of the anti-bladder cancer effects of heteronemin as well as HA/CHI-encapsulated heteronemin and pave a way to develop potential bladder cancer treatment.

Keywords: heteronemin, nanoparticles, hyaluronan, chitosan, bladder cancer

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Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee

Abstract:

There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.

Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor

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Authors: Liang-Jen Wang, Sung-Chou Li, Yuan-Ming Yeh, Sheng-Yu Lee, Ho-Chang Kuo, Chia-Yu Yang

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Background: Dysbiosis in the gut microbial community might be involved in the pathophysiology of attention deficit/hyperactivity disorder (ADHD). The fungal component of the gut microbiome, namely the mycobiota, is a hyperdiverse group of multicellular eukaryotes that can influence host intestinal permeability. This study therefore aimed to investigate the impact of fungal mycobiome dysbiosis and intestinal permeability on ADHD. Methods: Faecal samples were collected from 35 children with ADHD and from 35 healthy controls. Total DNA was extracted from the faecal samples, and the internal transcribed spacer (ITS) regions were sequenced using high-throughput next-generation sequencing (NGS). The fungal taxonomic classification was analysed using bioinformatics tools, and the differentially expressed fungal species between the ADHD and healthy control groups were identified. An in vitro permeability assay (Caco-2 cell layer) was used to evaluate the biological effects of fungal dysbiosis on intestinal epithelial barrier function. Results: The β-diversity (the species diversity between two communities), but not α-diversity (the species diversity within a community), reflected the differences in fungal community composition between ADHD and control groups. At the phylum level, the ADHD group displayed a significantly higher abundance of Ascomycota and significantly lower abundance of Basidiomycota than the healthy control group. At the genus level, the abundance of Candida (especially Candida albicans) was significantly increased in ADHD patients compared to the healthy controls. In addition, the in vitro cell assay revealed that C. albicans secretions significantly enhanced the permeability of Caco-2 cells. Conclusions: The current study is the first to explore altered gut mycobiome dysbiosis using the NGS platform in ADHD. The findings from this study indicated that dysbiosis of the fungal mycobiome and intestinal permeability might be associated with susceptibility to ADHD.

Keywords: ADHD, fungus, gut–brain axis, biomarker, child psychiatry

Procedia PDF Downloads 76

Authors: Tong Ming Liu

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Human mesenchymal stem cells (MSCs) represent the most used stem cells for clinical application, which have been used in over 1000 clinical trials to treat over 30 diseases due to multilineage differentiation potential, secretome and immunosuppression. Gene therapies of MSCs hold great promise in the treatment of many diseases due to enhanced MSC-based clinical outcomes. To identify genes for gene therapy of MSCs, by comparing gene expression profile before and after MSC differentiation following by functional screening, we have identified ZNF145 that regulated MSC differentiation. Forced expression of ZNF145 resulted in enhanced in vitro chondrogenesis of MSCs as an upstream factor of SOX9 and improved osteochondral repair upon implant into osteochondral defects in rodents. By comparing gene expression profile during differentiation of iPSCs toward MSCs, we also identified gene HOX regulating MSC stemness, which was much downregulated in late-passaged MSCs. Knockdown of this gene greatly compromised MSC stemness including abolished proliferation, decreased CFU-F, promoted senescence and reduced expression of cell surface antigens linked to the MSC phenotype. In addition, multi-linage differentiation was also greatly impaired. Notably, HOX overexpression resulted in improved multi-lineage differentiation. In the mechanism, HOX expression significantly deceased in late passage of MSCs compared with early passage of MSCs, correlating with MSC important genes. ChIP-seq data shown that HOX binds to genes related to MSC self-renewal and differentiation. Most importantly, most HOX binding sites are lost in late passage of MSCs. HOX exerts its effects by directing binding Twist1, one important gene of MSCs. The identification of the genes regulating MSC differentiation and stemness will provide and promising strategies for gene therapy of MSCs in regenerative medicine.

Keywords: mesenchymal stem cell, novel transcription factor, stemness, gene therapy, cartilage repair, signaling pathway

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Authors: Yu-Wen Cheng, Jau-Der Ho, Liang-Huan Wu, Fan-Li Lin, Li-Huei Chen, Hung-Ming Chang, Yueh-Hsiung Kuo, George Hsiao

Abstract:

Retina glial activation and neuroinflammation have been confirmed to cause devastating responses in retinodegenerative diseases. The expression and activation of matrix metalloproteinase (MMP)-9 and inducible nitric oxide synthase (iNOS) could be exerted as the crucial pathological factors in glaucoma- and blue light-induced retinal injuries. The present study aimed to investigate the retinoprotective effects and mechanisms of fungal ingredient 3,4-dihydroxybenzalacetone (DBL) isolated from Phellinus linteus in the retinal glial activation and retinodegenerative animal models. According to the cellular studies, DBL significantly and concentration-dependently abrogated MMP-9 activation and expression in TNFα-stimulated retinal Müller (rMC-1) cells. We found the inhibitory activities of DBL were strongly through the STAT- and ERK-dependent pathways. Furthermore, DBL dramatically attenuated MMP-9 activation in the stimulated Müller cells exposed to conditioned media from LPS-stimulated microglia BV-2 cells. On the other hand, DBL strongly suppressed LPS-induced production of NO and ROS and expression of iNOS in microglia BV-2 cells. Consistently, the phosphorylation of STAT was substantially blocked by DBL in LPS-stimulated microglia BV-2 cells. In the evaluation of retinoprotective functions, the high IOP-induced scotopic electroretinographic (ERG) deficit and blue light-induced abnormal pupillary light response (PLR) were assessed. The deficit scotopic ERG responses markedly recovered by DBL in a rat model of glaucoma-like ischemia/reperfusion (I/R)-injury. DBL also reduced the aqueous gelatinolytic activity and retinal MMP-9 expression in high IOP-injured conditions. Additionally, DBL could restore the abnormal PLR and reduce retinal MMP-9 activation. In summary, DBL could ameliorate retinal neuroinflammation and MMP-9 activation by predominantly inhibiting STAT3 activation in the retinal Müller cells and microglia, which exhibits therapeutic potential for glaucoma and other retinal degenerative diseases.

Keywords: glaucoma, blue light, DBL, retinal Müller cell, MMP-9, STAT, Microglia, iNOS, ERG, PLR

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Authors: Wann-Ming Wey

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In recent years, in addition to face the external threats such as energy shortages and climate change, traffic congestion and environmental pollution have become anxious problems for many cities. Considering private automobile-oriented urban development had produced many negative environmental and social impacts, the transit-oriented development (TOD) has been considered as a sustainable urban model. TOD encourages public transport combined with friendly walking and cycling environment designs, however, non-motorized modes help improving human health, energy saving, and reducing carbon emissions. Due to environmental changes often affect the planners’ decision-making; this research applies dynamic network process (DNP) which includes the time dependent concept to promoting friendly walking and cycling environmental designs as an advanced planning support system for environment improvements. This research aims to discuss what kinds of design strategies can improve a friendly walking and cycling environment under TOD. First of all, we collate and analyze environment designing factors by reviewing the relevant literatures as well as divide into three aspects of “safety”, “convenience”, and “amenity” from fifteen environment designing factors. Furthermore, we utilize fuzzy Delphi Technique (FDT) expert questionnaire to filter out the more important designing criteria for the study case. Finally, we utilized DNP expert questionnaire to obtain the weights changes at different time points for each design criterion. Based on the changing trends of each criterion weight, we are able to develop appropriate designing strategies as the reference for planners to allocate resources in a dynamic environment. In order to illustrate the approach we propose in this research, Taipei city as one example has been used as an empirical study, and the results are in depth analyzed to explain the application of our proposed approach.

Keywords: environment planning support systems, walking and cycling, transit-oriented development (TOD), dynamic network process (DNP)

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Authors: Dacheng Li, Bo Huang, Qinjin Han, Ming Li

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Remotely sensed imagery with the high spatial and temporal characteristics, which it is hard to acquire under the current land observation satellites, has been considered as a key factor for monitoring environmental changes over both global and local scales. On a basis of the limited high spatial-resolution observations, challenged studies called spatiotemporal fusion have been developed for generating high spatiotemporal images through employing other auxiliary low spatial-resolution data while with high-frequency observations. However, a majority of spatiotemporal fusion approaches yield to satisfactory assumption, empirical but unstable parameters, low accuracy or inefficient performance. Although the spatiotemporal fusion methodology via sparse representation theory has advantage in capturing reflectance changes, stability and execution efficiency (even more efficient when overcomplete dictionaries have been pre-trained), the retrieval of high-accuracy dictionary and its response to fusion results are still pending issues. In this paper, we employ additional image pairs (here each image-pair includes a Landsat Operational Land Imager and a Moderate Resolution Imaging Spectroradiometer acquisitions covering the partial area of Baotou, China) only into the coupled dictionary training process based on K-SVD (K-means Singular Value Decomposition) algorithm, and attempt to improve the fusion results of two existing sparse representation based fusion models (respectively utilizing one and two available image-pair). The results show that more eligible image pairs are probably related to a more accurate overcomplete dictionary, which generally indicates a better image representation, and is then contribute to an effective fusion performance in case that the added image-pair has similar seasonal aspects and image spatial structure features to the original image-pair. It is, therefore, reasonable to construct multi-dictionary training pattern for generating a series of high spatial resolution images based on limited acquisitions.

Keywords: spatiotemporal fusion, sparse representation, K-SVD algorithm, dictionary learning

Procedia PDF Downloads 229

Authors: Na Zhou, Chun-Lai Zhang, Qing Li, Bingqi Zhu, Xun-Ming Wang

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The understanding of the dynamics of aeolian sand in the Yarlung Zangbo River Valley (YLZBV), southern Qinghai-Tibetan Plateau, including its origins, transportation,and deposition, remains preliminary. In this study, we investigated the extensive origin of aeolian sediments in the YLZBV by analyzing the distribution and composition of sediment’s grain size and geochemical composition in dune sediments collected from the wide river terraces. The major purpose is to characterize the sedimentological and geochemical compositions of these aeolian sediments, trace back to their sources, and understand their influencing factors. As a result, the grain size and geochemistry variations, which showed a significant correlation between grain sizes distribution and element abundances, give a strong evidence that the important part of the aeolian sediments in the downstream areas was firstly derived from the upper reaches by intense fluvial processes. However, the sediments experienced significant mixing process with local inputs and reconstructed by regional wind transportation. The diverse compositions and tight associations in the major and trace element geochemistry between the up- and down-stream aeolian sediments and the local detrital rocks, which were collected from the surrounding mountains, suggest that the upstream aeolian sediments had originated from the various close-range rock types, and experienced intensive mixing processes via aeolian- fluvial dynamics. Sand mass transported by water and wind was roughly estimated to qualify the interplay between the aeolian and fluvial processes controlling the sediment transport, yield, and ultimately shaping the aeolian landforms in the mainstream of the YLZBV.

Keywords: grain size distribution, geochemistry, wind and water load, sand source, Yarlung Zangbo River Valley

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Authors: Min-Chien Su, Tzu-Hsuan Hsu, Guan-Xuan Wu, Shyh-Ming Kuo

Abstract:

Lung cancer is one of the clinically challenging malignant diseases worldwide. For efficient therapeutics in cancer, combination therapy has developed to acquire a better outcome. PLK-1 was one of the major factors affecting cell mitosis in cancer cells, its inhibitor Bi6727 was proven effective in treating several different cancers namely oral cancer, colon cancer and lung cancer. Despite its low toxicity toward normal cells compared to traditional chemotherapy, it is still yet to be evaluated in detail. Livistona Chinensis (LC) is a Chinese herb that used as a traditional prescription to treat lung cancer. Due to the uncertainty of the efficacy of LC, we utilized a water extraction method to extract the Livistona Chinensis and then lyophilized into powder for further study. In this study we investigated the antiproliferation activities of Bi6727 and LC extracts (LCE) on A549 non-small lung cancer cells. The IC50 of Bi6727 and LCE on A549 are 60 nM and 0.8 mg/mL, respectively. The fluorescent staining images shown nucleolus damage in cells treated with Bi6727 and mitochondrial damage after treated with LCE. A549 cells treated with Bi6727 and LCE showed increased expression of Bax, Caspase-3 and Caspase-9 proteins from Western blot assay. LCE also inhibited A549 cells growth keeping cells at G2-M phase from cell cycle assay. Apoptosis assay results showed that LCE induced late apoptosis of A549 cells. JC-1 assay showed that the mitochondria damaged at the LCE concentration of 0.4 mg/mL. In our preliminary anti-proliferation test of combined LCE and Bi-6727 on A549 cells, we found a dramatically decrease in proliferation after treated with LCE first for 24-h and then Bi-6727 for extra 24-h. This was an important finding regarding synergistic anti-proliferation effect of these drugs, However, the usage, the application sequence of LCE and Bi-6727 on A549 cells and their related mechanisms still need to be evaluated. In summary, the drugs exerted anti-proliferation effect on A549 cells independently. We hopefully combine the usage of these two drugs will bring a different and potential outcome in treating lung cancer.

Keywords: anti-proliferation, A549, Livistona Chinensis fruit extracts, PLK-1 inhibitor

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Authors: Dounya Barrit, Ming-Chun Tang, Hoang Dang, Kai Wang, Detlef-M. Smilgies, Aram Amassian

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Several deposition methods have been developed for perovskite film preparation. The one-step spin-coating process has emerged as a more popular option thanks to its ability to produce films of different compositions, including mixed cation and mixed halide perovskites, which can stabilize the perovskite phase and produce phases with desired band gap. The two-step method, however, is not understood in great detail. There is a significant need and opportunity to adopt the two-step process toward mixed cation and mixed halide perovskites, but this requires deeper understanding of the two-step conversion process, for instance when using different cations and mixtures thereof, to produce high-quality perovskite films with uniform composition. In this work, we demonstrate using in situ investigations that the conversion of PbI₂ to perovskite is largely dictated by the state of the PbI₂ precursor film in terms of its solvated state. Using time-resolved grazing incidence wide-angle X-Ray scattering (GIWAXS) measurements during spin coating of PbI₂ from a DMF (Dimethylformamide) solution we show the film formation to be a sol-gel process involving three PbI₂-DMF solvate complexes: disordered precursor (P₀), ordered precursor (P₁, P₂) prior to PbI₂ formation at room temperature after 5 minutes. The ordered solvates are highly metastable and eventually disappear, but we show that performing conversion from P₀, P₁, P₂ or PbI₂ can lead to very different conversion behaviors and outcomes. We compare conversion behaviors by using MAI (Methylammonium iodide), FAI (Formamidinium Iodide) and mixtures of these cations, and show that conversion can occur spontaneously and quite rapidly at room temperature without requiring further thermal annealing. We confirm this by demonstrating improvements in the morphology and microstructure of the resulting perovskite films, using techniques such as in situ quartz crystal microbalance with dissipation monitoring, SEM and XRD.

Keywords: in situ GIWAXS, lead iodide, mixed cation, perovskite solar cell, sol-gel process, solvate phase

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Authors: Feng-Ming Fan, Xiu-Hui Wen, Po-Feng Chen, Yi-Ching Tu

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Because of inborn natural conditions and man-made sabotage, the water resources insufficient phenomenon in Taiwan is a very important issue needed to face immediately. The regulations and law of water resources protection and recycling are gradually completed now but still lack of specific water recycling effectiveness checking method. The research focused on the industrial parks that already had been certificated with EIA to establish a professional checking system, carry through and forge ahead to contribute one’s bit in water resources sustainable usage. Taiwan Government Policies of Environmental Impact Assessment established in 1994, some development projects were requested to set certain water recycling ratio for water resources effective usage. The water covers and contains everything because all-inclusive companies enter and be stationed. For control the execution status of industrial park water and waste water recycling ratio about EIA commitment effectively, we invited experts and scholars in this filed to discuss with related organs to formulate the policy and audit plan. Besides, call a meeting to set public version water equilibrium diagrams and recycles parameter. We selected nine industrial parks that were requested set certain water recycling ratio in EIA examination stage and then according to the water usage quantity, we audited 340 factories in these industrial parks with spot and documents examination and got fruitful results – the average water usage of unit area per year of all these examined industrial parks is 31,000 tons/hectare/year, the value is just half of Taiwan industries average. It is obvious that the industrial parks with EIA commitment can decrease the water resources consumption effectively. Taiwan government policies of Environmental Impact Assessment took follow though tracking function into consideration at the beginning. The results of this research verify the importance of the implementing with water recycling to save water resources in EIA commitment. Inducing development units to follow EIA commitment to get the balance between environmental protection and economic development is one of the important EIA value.

Keywords: Taiwan government policies of environmental impact assessment, water recycling ratio of EIA commitment, water resources sustainable usage, water recycling

Procedia PDF Downloads 191

Authors: Dar-Bin Shieh, Gwo-Bin Lee, Chen-Ming Chang, Chen Sheng Yeh, Chih-Chia Huang, Tsung-Ju Li

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Mitochondrial defects have a significant impact in many human diseases and aging associated phenotypes. The pathogenic mitochondrial DNA (mtDNA) mutations are diverse and usually present as heteroplasmic. mtDNA 4977bps deletion is one of the common mtDNA defects, and the ratio of mutated versus normal copy is significantly associated with clinical symptoms thus their quantitative detection has become an important unmet needs for advanced disease diagnosis and therapeutic guidelines. This study revealed a Micro-electro-mechanical-system (MEMS) enabled automatic microfluidic chip that only required minimal sample. The system integrated multiple laboratory operation steps into a Lab-on-a-Chip for high-sensitive and prompt measurement. The entire process including magnetic nanoparticle based mtDNA extraction in chip, mutation selective photonic DNA cleavage, and nanoparticle accelerated photonic quantitative polymerase chain reaction (qPCR). All subsystems were packed inside a miniature three-dimensional micro structured system and operated in an automatic manner. Integration of magnetic beads with microfluidic transportation could promptly extract and enrich the specific mtDNA. The near infrared responsive magnetic nanoparticles enabled micro-PCR to be operated by pulse-width-modulation controlled laser pulsing to amplify the desired mtDNA while quantified by fluorescence intensity captured by a complementary metal oxide system array detector. The proportions of pathogenic mtDNA in total DNA were thus obtained. Micro capillary electrophoresis module was used to analyze the amplicone products. In conclusion, this study demonstrated a new magnetophotonic based qPCR MEMS system that successfully detects and quantify specific disease related DNA mutations thus provides a promising future for rapid diagnosis of mitochondria diseases.

Keywords: mitochondrial DNA, micro-electro-mechanical-system, magnetophotonics, PCR

Procedia PDF Downloads 191

Authors: Chin-Tsu Ma, Yi-Jhen Wu, Hsia Ying Cheng, Han Hsiang Huang, Shyh Ming Kuo

Abstract:

The use of specific molecules including nutrients and pharmacological agents has been tried in modulation of stem cells differentiation (MSCs) to insulin producing cells. The aim of this study is to investigate the ability of nano collagen molecules (nutrient or scaffold) to enhance the MSCs differentiation into insulin-producing cells in combination with nicotinamide and exendin-4 (pharmacological agents) in vitro and in vivo. The results demonstrated that the cells exhibit morphologically islet-like clusters after treatment with nano collagen molecules, nicotinamide and exendin-4. MSCs extra treated with nano collagen molecules showed significant increases in Nkx6.1 and insulin mRNA expression at 14-d and 21-d culture compared with those merely treated with nicotinamide and exendin-4. Early 7-day elevation in PDX-1 mRNA expression was observed. Furthermore, the MSCs exposed to nano collagen molecules produced the highest secretion of insulin (p ＜ 0.05). Type-2 diabetes induced by high-fat diet and low dose of streptozotocin in rat model was built in this study. This rat exhibited higher food intake, water intake, lower glucose tolerance, lower-insulin tolerance, and higher HbA1C (significant increases, p ＜ 0.01) as compared with the normal rat that demonstrated the model of type-2 diabetes was successfully built. Biopsy examinations also showed that obvious destruction of islet. After injection of differentiated MSCs into the destructed pancreas of diabetes rat, more regenerated islet were observed at the rats that treated with nano collagen molecules and exhibited much lower HbA1C as compared with the normal rat and diabetes rat after 4 weeks (significant deceases, p ＜ 0.001). These results indicate that the culturing MSCs with nano collagen molecules, nicotinamide, and exendin-4 are beneficial for MSCs differentiation into islet-like cells. These nano collagen molecules may lead to alternations or up-regulation of gene expression and influence the differentiated outcomes induced by nicotinamide and exendin-4.

Keywords: nano collagen molecules, nicotinamide, MSCs, diabetes

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Authors: Mei-Ling Chan, Jin-Ming Wu, Konstantin V. Kudryavtsev, Jih-Hwa Guh

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Prostate cancer is one of the most common malignant disease in men. KUD983 is an enantiomerically pure β-dipeptide derivative, which may have anti-cancer effects. In the present study, KUD983 exhibits powerful activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells. The IC50 values of KUD983 in PC-3 and DU145 cells are 0.56±0.07M and 0.50±0.04 M respectively. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with the down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB. The protein expressions of nuclear and total c-Myc protein, which was able to regulate the expression of both cyclin D1 and cyclin E, were significantly suppressed by KUD983. Phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is an important signaling pathway that influences the energy metabolism, cell cycle, proliferation, survival and apoptosis of cells, and is associated with numerous other signaling pathways. The Western Blot data revealed that KUD983 inhibited PI3K/Akt and mTOR/p70S6K/4E-BP1 pathways. The transient transfection of constitutively active myristylated Akt (myr-Akt) cDNA significantly reversed KUD983-induced caspase activation but did not abolish the suppression of mTOR/p70S6K/4E-BP1 signaling cascade indicating the presence of both Akt-dependent and -independent pathways. Moreover, KUD983-induced effect was collaborated with the down-regulation of anti-apoptotic Bcl-2 members (e.g., Bcl-2, and Mcl-1) and IAP family members (e.g., survivin). Furthermore, KUD983 induced autophagic cell death using confocal microscopic examination, investigating the level of conversion of LC3-I to LC3-II and flow cytometric detection of AVO-positive cells. Taken together, the data suggest that KUD983 is an anticancer β-dipeptide against HRPCs through the inhibition of cell proliferation and induction of apoptotic and autophagic cell death. The suppression of signaling pathways mediated by c-Myc, PI3K/Akt and mTOR/p70S6K/4E-BP1 and the collaboration with down-regulation of Mcl-1 and survivin may indicate the mechanism of KUD983 against HRPC.

Keywords: β-dipeptide, hormone-refractory prostate cancer, mTOR, PI3K/Akt

Procedia PDF Downloads 248