Search results for: Mei Fang Chien

Authors: Mao Zhaofang, Xu Yida, Fang Kan, Fu Enyuan, Zhao Zhao

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Nowadays, last-mile distribution plays an increasingly important role in the whole industrial chain delivery link and accounts for a large proportion of the whole distribution process cost. Promoting the upgrading of logistics networks and improving the layout of final distribution points has become one of the trends in the development of modern logistics. Due to the discrete and heterogeneous needs and spatial distribution of customer demand, which will lead to a higher delivery failure rate and lower vehicle utilization, last-mile delivery has become a time-consuming and uncertain process. As a result, courier companies have introduced a range of innovative parcel storage facilities, including pick-up points and lockers. The introduction of pick-up points and lockers has not only improved the users’ experience but has also helped logistics and courier companies achieve large-scale economy. Against the backdrop of the COVID-19 of the previous period, contactless delivery has become a new hotspot, which has also created new opportunities for the development of collection services. Therefore, a key issue for logistics companies is how to design/redesign their last-mile distribution network systems to create integrated logistics and distribution networks that consider pick-up points and lockers. This paper focuses on the introduction of self-pickup facilities in new logistics and distribution scenarios and the heterogeneous demands of customers. In this paper, we consider two types of demand, including ordinary products and refrigerated products, as well as corresponding transportation vehicles. We consider the constraints associated with self-pickup points and lockers and then address the location-routing problem with self-pickup facilities and heterogeneous demands (LRP-PFHD). To solve this challenging problem, we propose a mixed integer linear programming (MILP) model that aims to minimize the total cost, which includes the facility opening cost, the variable transport cost, and the fixed transport cost. Due to the NP-hardness of the problem, we propose a hybrid adaptive large-neighbourhood search algorithm to solve LRP-PFHD. We evaluate the effectiveness and efficiency of the proposed algorithm by using instances generated based on benchmark instances. The results demonstrate that the hybrid adaptive large neighbourhood search algorithm is more efficient than MILP solvers such as Gurobi for LRP-PFHD, especially for large-scale instances. In addition, we made a comprehensive analysis of some important parameters (e.g., facility opening cost and transportation cost) to explore their impacts on the results and suggested helpful managerial insights for courier companies.

Keywords: city logistics, last-mile delivery, location-routing, adaptive large neighborhood search

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Authors: Huey-Fang Sun, Wei-Kai Weng, Mei-Kuang Chao, Hui-Shan Hsu, Tsai-Yin Shih

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Psycho-social stress is important for mental illness and the presence of emotional and behavioral symptoms to an identifiable event is the central feature of adjustment disorders. However, whether patients with adjustment disorders have been raised in family with poor family functions and social supports and have higher stress perception than their peer group when they both experienced a similar stressful environment remains unknown. The specific aims of the study are to investigate the correlation among the family function, social supports and the level of stress perception and to test the hypothesis that military patients with adjustment disorders would have lower family function, lower social supports and higher stress perception than their healthy colleagues recruited in the same cohort for military services given their common exposure to similar stressful environments. Methods: The study was conducted in four hospitals of northern part of Taiwan from July 1, 2015 to June 30, 2017 and a matched case-control study design was used. The inclusion criteria for potential patient participants were psychiatric inpatients that serviced in military during the study period and met the diagnosis of adjustment disorders. Patients who had been admitted to psychiatric ward before or had illiteracy problem were excluded. A healthy military control sample matched by the same military service unit, gender, and recruited cohort was invited to participate the study as well. Totally 74 participants (37 patients and 37 controls) completed the consent forms and filled out the research questionnaires. Questionnaires used in the study included Perceived Stress Scale (PSS) as a measure of stress perception; Family APGAR as a measure of family function, and Multidimensional Scale of Perceived Social Support (MSPSS) as a measure of social supports. Pearson correlation analysis and t-test were applied for statistical analysis. Results: The analysis results showed that PSS level significantly negatively correlated with three social support subscales (family subscale, r= -.37, P < .05; friend subscale, r= -.38, P < .05; significant other subscale, r= -.39, P < .05). A negative correlation between PSS level and Family APGAR only reached a borderline significant level (P= .06). The t-test results for PSS scores, Family APGAR levels, and three subscale scores of MSPSS between patient and control participants were all significantly different (P < .001, P < .05, P < .05, P < .05, P < .05, respectively) and the patient participants had higher stress perception scores, lower social supports and lower family function scores than the healthy control participants. Conclusions: Our study suggested that family function and social supports were negatively correlated with patients’ subjective stress perception. Military patients with adjustment disorders tended to have higher stress perception and lower family function and social supports than those military peers who remained healthy and still provided services in their military units.

Keywords: adjustment disorders, family function, social support, stress perception

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Authors: Chung-Yuan Wang, Min Hsu, Bo-Ya Juan, Hsiv Ching Lin, Hsveh Min Lin, Hsiu-Fang Yeh

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The success of Taiwan's National Health Insurance (NHI) system attracts widespread praise from the international society. However, the availability of medical care in a emote area is limited. Without the convenient public transportation system and mature social welfare policy, these people are difficult to regain their health and prevent disability. Preterm children have more risk to get development delay. Preterm children in a remote area have the human right to get rehabilitation resources as those in the city area. Therefore, the aim of this study was to show the importance of development screening to preterm children in a remote area and a tract the government to notice the issue. In Pingtung, children who are suspected development delay would be suggested to take a skillful screening evaluation in our hospital. Those preterm children (within 1-year-old) visited our pediatric clinic would also be referred to take the development evaluation. After the physiatrist’s systemic evaluation, the subjects would be scheduled to take the development evaluation. Gross motor, fine motor, speech comprehension/expression and mental study were included. The evaluation was in-charged by a physical therapist, occupational therapy, speech therapist and pediatric psychologist. The tools were Peabody developmental scale, Bayley Scales of Infant and Toddler Development (Bayley-III) and Wechsler Preschool & Primary Scale of Intelligence-Revised (WPPSI-R). In 2013, 459 children received the service in our hospital. Among these children, fifty-seven were noted with preterm baby history (gestation within 37 weeks). Thirty-six of these preterm children, who had never receive development evaluation, were included in this study. Thirty-six subjects (twenty-six male and ten female) were included. Nineteen subjects were found development delay. Six subjects were found suspected development delay. In gross motor, six subjects were development delay and eight were suspected development delay. In fine motor, five subjects were development delay and three were suspected development delay. In speech, sixteen subjects were development delay and six were suspected development delay. In our study, through the provision of development evaluation service, 72.2% preterm baby were found their development delay or suspected delay. They need further early intervention rehabilitation service. We made their parents realize that when development delay was recognized at the early stage, they are often reversible. No only the patients but also their families were improved their health status. The number of the subjects was limited in our study. Further study might be needed. Compared with 770 physical therapist (PT) and 370 occupational therapy (OT) in Taipei, there are only 108 PT and 54 OT in Pingtung. Further, there are much fewer therapists working on the field of pediatric rehabilitation. Living healthy is a human's right, no matter where does he live. For those development delay children in remote area, particularly preterm children, early detection, and early intervention rehabilitation service could play an important role in decreasing their disability and improving their quality of life. Through this study, we suggest the government to add more national resources on the development evaluation to preterm children in a remote area.

Keywords: development, early intervention, preterm children, rehabilitation

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Authors: Nien-Te Kuo, Yi-Sung Cheng, Kuo-Chien Chang

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Cultural festival tourism is now seen by many as an opportunity to facilitate community development because it has significant influences on the economic, social, cultural, and political aspects of local communities. The potential for tourist attraction has been recognized as a useful tool to strengthen local economies from governments. However, most community festivals in Taiwan are short-lived, often only lasting for a few years or occasionally not making it past a one-off event. Researchers suggested that most governments and other stakeholders do not recognize the importance of building a partnership with residents when developing community tourism. Thus, the sustainable community tourism development still remains a key issue in the existing literature. The success of community tourism is related to the attitudes and lifestyles of local residents. In order to maintain sustainable tourism, residents need to be seen as development partners. Residents’ support intention for tourism development not only helps to increase awareness of local culture, history, the natural environment, and infrastructure, but also improves the interactive relationship between the host community and tourists. Furthermore, researchers have identified the social capital theory as the core of sustainable community tourism development. The social capital of residents has been seen as a good way to solve issues of tourism governance, forecast the participation behavior and improve support intention of residents. In addition, previous studies have pointed out the role of community participation and place identity in increasing resident support intention for tourism development. A lack of place identity is one of the main reasons that community tourism has become a mere formality and is not sustainable. It refers to how much residents participate during tourism development and is mainly influenced by individual interest. Scholars believed that the place identity of residents is the soul of community festivals. It shows the community spirit to visitors and has significant impacts on tourism benefits and support intention of residents in community tourism development. Although the importance of community participation and place identity have been confirmed by both governmental and non-governmental organizations, real-life execution still needs to be improved. This study aimed to use social capital theory to investigate the social structure between community residents, participation levels in festival tourism, degrees of place identity, and resident support intention for future community tourism development, and the causal relationship that these factors have with cultural festival tourism. A quantitative research approach was employed to examine the proposed model. Structural equation model was used to test and verify the proposed hypotheses. This was a case study of the Kaohsiung Zuoying Wannian Folklore Festival. The festival was located in the Zuoying District of Kaohsiung City, Taiwan. The target population of this study was residents who attended the festival. The results reveal significant correlations among social capital, community participation, place identity and support intention. The results also confirm that impacts of social capital on support intention were significantly mediated by community participation and place identity. Practical suggestions were provided for tourism operators and policy makers. This work was supported by the Ministry of Science and Technology of Taiwan, Republic of China, under the grant MOST-105-2410-H-328-013.

Keywords: community participation, place identity, social capital, support intention

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Authors: George Zhou, Yunchan Chen, Candace Chien

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Kidney replacement therapy is the current standard of care for end-stage renal diseases. In-center or home hemodialysis remains an integral component of the therapeutic regimen. Arteriovenous fistulas (AVF) make up the vascular circuit through which blood is filtered and returned. Naturally, AVF patency determines whether adequate clearance and filtration can be achieved and directly influences clinical outcomes. Our aim was to build a deep learning model for automated AVF stenosis screening based on the sound of blood flow through the AVF. A total of 311 patients with AVF were enrolled in this study. Blood flow sounds were collected using a digital stethoscope. For each patient, blood flow sounds were collected at 6 different locations along the patient’s AVF. The 6 locations are artery, anastomosis, distal vein, middle vein, proximal vein, and venous arch. A total of 1866 sounds were collected. The blood flow sounds are labeled as “patent” (normal) or “stenotic” (abnormal). The labels are validated from concurrent ultrasound. Our dataset included 1527 “patent” and 339 “stenotic” sounds. We show that blood flow sounds vary significantly along the AVF. For example, the blood flow sound is loudest at the anastomosis site and softest at the cephalic arch. Contextualizing the sound with location metadata significantly improves classification performance. How to encode and incorporate categorical metadata is an active area of research1. Herein, we study ordinal (i.e., integer) encoding schemes. The numerical representation is concatenated to the flattened feature vector. We train a vision transformer (ViT) on spectrogram image representations of the sound and demonstrate that using scalar multiples of our integer encodings improves classification performance. Models are evaluated using a 10-fold cross-validation procedure. The baseline performance of our ViT without any location metadata achieves an AuROC and AuPRC of 0.68 ± 0.05 and 0.28 ± 0.09, respectively. Using the following encodings of Artery:0; Arch: 1; Proximal: 2; Middle: 3; Distal 4: Anastomosis: 5, the ViT achieves an AuROC and AuPRC of 0.69 ± 0.06 and 0.30 ± 0.10, respectively. Using the following encodings of Artery:0; Arch: 10; Proximal: 20; Middle: 30; Distal 40: Anastomosis: 50, the ViT achieves an AuROC and AuPRC of 0.74 ± 0.06 and 0.38 ± 0.10, respectively. Using the following encodings of Artery:0; Arch: 100; Proximal: 200; Middle: 300; Distal 400: Anastomosis: 500, the ViT achieves an AuROC and AuPRC of 0.78 ± 0.06 and 0.43 ± 0.11. respectively. Interestingly, we see that using increasing scalar multiples of our integer encoding scheme (i.e., encoding “venous arch” as 1,10,100) results in progressively improved performance. In theory, the integer values do not matter since we are optimizing the same loss function; the model can learn to increase or decrease the weights associated with location encodings and converge on the same solution. However, in the setting of limited data and computation resources, increasing the importance at initialization either leads to faster convergence or helps the model escape a local minimum.

Keywords: arteriovenous fistula, blood flow sounds, metadata encoding, deep learning

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Authors: Evy Van Puymbroeck, Wim Nagy, Ken Schotte, Heng Fang, Hans De Backer

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The knowledge of residual stresses for welded bridge components is essential to determine the effect of the residual stresses on the fatigue life behavior. The residual stresses of an orthotropic bridge deck are determined by simulating the welding process with finite element modelling. The stiffener is placed on top of the deck plate before welding. A chained thermal-mechanical analysis is set up to determine the distribution of residual stresses for the bridge deck. First, a thermal analysis is used to determine the temperatures of the orthotropic deck for different time steps during the welding process. Twin wire submerged arc welding is used to construct the orthotropic plate. A double ellipsoidal volume heat source model is used to describe the heat flow through a material for a moving heat source. The heat input is used to determine the heat flux which is applied as a thermal load during the thermal analysis. The heat flux for each element is calculated for different time steps to simulate the passage of the welding torch with the considered welding speed. This results in a time dependent heat flux that is applied as a thermal loading. Thermal material behavior is specified by assigning the properties of the material in function of the high temperatures during welding. Isotropic hardening behavior is included in the model. The thermal analysis simulates the heat introduced in the two plates of the orthotropic deck and calculates the temperatures during the welding process. After the calculation of the temperatures introduced during the welding process in the thermal analysis, a subsequent mechanical analysis is performed. For the boundary conditions of the mechanical analysis, the actual welding conditions are considered. Before welding, the stiffener is connected to the deck plate by using tack welds. These tack welds are implemented in the model. The deck plate is allowed to expand freely in an upwards direction while it rests on a firm and flat surface. This behavior is modelled by using grounded springs. Furthermore, symmetry points and lines are used to prevent the model to move freely in other directions. In the thermal analysis, a mechanical material model is used. The calculated temperatures during the thermal analysis are introduced during the mechanical analysis as a time dependent load. The connection of the elements of the two plates in the fusion zone is realized with a glued connection which is activated when the welding temperature is reached. The mechanical analysis results in a distribution of the residual stresses. The distribution of the residual stresses of the orthotropic bridge deck is compared with results from literature. Literature proposes uniform tensile yield stresses in the weld while the finite element modelling showed tensile yield stresses at a short distance from the weld root or the weld toe. The chained thermal-mechanical analysis results in a distribution of residual weld stresses for an orthotropic bridge deck. In future research, the effect of these residual stresses on the fatigue life behavior of welded bridge components can be studied.

Keywords: finite element modelling, residual stresses, thermal-mechanical analysis, welding simulation

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Authors: Rongrong Liu, Li Wang, Hui Xu, Jianpei Fang, Sixi Liu, Xiaolin Yin, Junbin Liang, Gaohui Yan, Yaoyun Li, Yali Zhou, Xinyu Li, Yue Li, Lei Shi, Yongrong Lai, Junjiu Huang, Xinhua Zhang

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Background: Beta-Thalassemia is caused by reduced (β+) or absent (β0) synthesis of the β-globin chains of hemoglobin. Transfusions and oral iron chelation therapy have improved the quality of life for patients with Transfusion-Dependent thalassemia (TDT). Recent advances in genome editing platforms of CRISPR-Cas9 have paved the way for induction of HbF by reactivating expression of γ-chain.Aims: We performed CRISPR-Cas9-mediated genome editing of hematopoietic stem cells to mutate HBG1/HBG2 promoter sequence, thereby representing a naturally occurring HPFH-liked mutation, producing RM-001. Here, we present an initial assessment of safety and efficacy of RM-001 in patients with TDT. Methods: Patients (6–35 y of age) with TDT receiving packed red blood cell (pRBC) transfusions of ≥100 mL/kg/y or ≥10 units/y in the previous 2 y were eligible. CD34+ cells were edited with CRISPR-Cas9 using a guide RNA specific for the binding site of BCL11A on the HBG1/2 promoter. Prior to RM-001 product infusion (day 0), patients received myeloablative conditioning with Busulfan from day-7 to day-4. Patients were monitored for AEs Hb expression.Results: Data cut as of 28 Feb 2024, 16 TDT patients have been treated with RM-001 and followed ≥3 months. 5 of these 16 patients had finished their 24 months follow up. Eleven patients have β0/β0 genotype and five patients have β0/β+ genotype. In addition to β-thalassemia, two patients had α- deletion with the genotype of --/αα. Efficacy:All patients received a single dose intravenous infusion of RM-001 cells. 5 of them had been followed 24 months or longer. All patients achieved transfusion-independent (TI, total Hb continued ≥ 9g/dL) (Figure1). Patients demonstrated sustained and clinically meaningful increases in HbF levels since 4 month post-RM-001 infusion (Figure.2). Total hemoglobin in all patients was stable at 10-12g/dL during the follow-up period. Safety:The adverse events observed after RM-001 infusion were consistent with those that are typical of Busulfan-based myeloablation. The allelic editing analysis at 6-month visit showed that the on-target allelic editing frequency in bone marrow cells was 73.44% (64.65% to 84.6%, n=13).Summary/Conclusion: This interim analysis, in which all the 19 patients age from 7.9 to 25yo met the success criteria for the trial with respect to transfusion independence, showed that autologous HBG1/2 promoter-modified CD34+ HSPCs gene therapy resulted in an adequate amount of HbF as early as 2 months after infusion led to near-normal hemoglobin levels, remained transfusion-free through the reported period without product related SAE. After RM-001 infusion, high levels of HbF proportion and on-target editing in bone marrow cells were maintained. Submitted on behalf of the RM-001 Investigators.

Keywords: thalassemian, genetherapy, CRISPR/Cas9, HbF

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Authors: Colin S. Chen, Chien-Jung Tien, Hsin-Jan Huang

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For weathering studies, the change of chemical constituents by biodegradation effect in diesel-contaminated soils are important factors to be considered, especially when there is a prolonged period of weathering processes. The objective was to evaluate biodegradation effects onto hydrocarbon fingerprinting and distribution patterns of diesel fuels, fuel source screening and differentiation, source-specific marker compounds, and diagnostic ratios of diesel fuel constituents by laboratory and field studies. Biodegradation processes of diesel contaminated soils were evaluated by experiments lasting for 15 and 12 months, respectively. The degradation of diesel fuel in top soils was affected by organic carbon content and biomass of microorganisms in soils. Higher depletion of total petroleum hydrocarbon (TPH), n-alkanes, and polynuclear aromatic hydrocarbons (PAHs) and their alkyl homologues was observed in soils containing higher organic carbon content and biomass. Decreased ratio of selected isoprenoids (i.e., pristane (Pr) and phytane (Ph)) including n-C17/pristane and n-C18/phytane was observed. The ratio of pristane/phytane was remained consistent for a longer period of time. At the end of the experimental period, a decrease of pristane/phytane was observed. Biomarker compounds of bicyclic sesquiterpanes (BS) were less susceptible to the effects of biodegradation. The ratios of characteristic factors such as C15 sesquiterpane/ 8β(H)-drimane (BS3/BS5), C15 sesquiterpane/ 8β(H)-drimane (BS4/BS5), 8β(H)-drimane/8β(H)-homodrimane (BS5/BS10), and C15 sesquiterpane/8β(H)-homodrimane (BS3/BS10) could be adopted for source identification of diesel fuels in top soil. However, for biodegradation processes lasted for six months but shorter than nine months, only BS3/BS5 and BS3/BS10 could be distinguished in two diesel fuels. In subsoil experiments (contaminated soil located 50 cm below), the ratios of characteristic factors including BS3/BS5, BS4/BS5, and BS5/BS10 were valid for source identification of two diesel fuels for nine month biodegradation. At the early stage of contamination, biomass of soil decreased significantly. However, 6 and 7 dominant species were found in soils in top soil experiments, respectively. With less oxygen and nutrients in subsoil, less biomass of microorganisms was observed in subsoils. Only 2 and 4 diesel-degrading species of microorganisms were identified in two soils, respectively. Parameters of double ratio such as fluorene/C1-fluorene: C2-phenanthrene/C3-phenanthrene (C0F/C1F:C2P/C3P) in both top and subsoil, C2-naphthalene/C2-phenanthrene: C1-phenanthrene/C3-phenanthrene (C2N/C2P:C1P/C3P), and C1-phenanthrene/C1-fluorene: C3-naphthalene/C3-phenanthrene (C1P/C1F:C3N/C3P) in subsoil could serve as forensic indicators in diesel contaminated sites. BS3/BS10:BS4/BS5 could be used in 6 to 9 months of biodegradation processes. Results of principal component analysis (PCA) indicated that source identification of diesel fuels in top soil could only be perofrmed for weathering process less than 6 months. For subsoil, identification can be conducted for weathering process less than 9 months. Ratio of isoprenoids (pristane and phytane) and PAHs might be affected by biodegradation in spilled sites. The ratios of bicyclic sesquiterpanes could serve as forensic indicators in diesel-contaminated soils. Finally, source identification was attemped for samples collected from different fuel contaminated sites by using the unique pattern of sesquiterpanes. It was anticipated that the information generated from this study would be adopted by decision makers to evaluate the liability of cleanup in diesel contaminated sites.

Keywords: biodegradation, diagnostic ratio, diesel fuel, environmental forensics

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Authors: Fang Lian, Zefang Chenli, Laijun Ma, Lei Mao

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Up to now, electrolytic process is a popular way to prepare Mn and MnO2 (EMD) with high purity. However, the conventional preparation process of manganese oxide such as Mn3O4 with high purity from electrolytic manganese metal is characterized by long production-cycle, high-pollution discharge and high energy consumption especially initially from low-grade rhodochrosite, the main resources for exploitation and applications in China. Moreover, Mn3O4 prepared from electrolytic manganese shows large particles, single morphology beyond the control and weak chemical activity. On the other hand, hydrometallurgical method combined with thermal decomposition, hydrothermal synthesis and sol-gel processes has been widely studied because of its high efficiency, low consumption and low cost. But the key problem in direct preparation of manganese oxide series from low-grade rhodochrosite is to remove completely the multiple impurities such as iron, silicon, calcium and magnesium. It is urgent to develop a sustainable approach to high pure manganese oxide series with character of short process, high efficiency, environmentally friendly and economical benefit. In our work, the preparation technique of high pure Mn3O4 directly from low-grade rhodochrosite ore (13.86%) was studied and improved intensively, including the effective leaching process and the short purifying process. Based on the same ion effect, the repeated leaching of rhodochrosite with sulfuric acid is proposed to improve the solubility of Mn2+ and inhibit the dissolution of the impurities Ca2+ and Mg2+. Moreover, the repeated leaching process could make full use of sulfuric acid and lower the cost of the raw material. With the aid of theoretical calculation, Ba(OH)2 was chosen to adjust the pH value of manganese sulfate solution and BaF2 to remove Ca2+ and Mg2+ completely in the process of purifying. Herein, the recovery ratio of manganese and removal ratio of the impurity were evaluated via chemical titration and ICP analysis, respectively. Comparison between conventional preparation technique from electrolytic manganese and a sustainable approach directly from low-grade rhodochrosite have also been done herein. The results demonstrate that the extraction ratio and the recovery ratio of manganese reached 94.3% and 92.7%, respectively. The heavy metal impurities has been decreased to less than 1ppm, and the content of calcium, magnesium and sodium has been decreased to less than 20ppm, which meet standards of high pure reagent for energy and electronic materials. In compare with conventional technique from electrolytic manganese, the power consumption has been reduced to ≤2000 kWh/t(product) in our short-process approach. Moreover, comprehensive recovery rate of manganese increases significantly, and the wastewater generated from our short-process approach contains low content of ammonia/ nitrogen about 500 mg/t(product) and no toxic emissions. Our study contributes to the sustainable application of low-grade manganese ore. Acknowledgements: The authors are grateful to the National Science and Technology Support Program of China (No.2015BAB01B02) for financial support to the work.

Keywords: leaching, high purity, low-grade rhodochrosite, manganese oxide, purifying process, recovery ratio

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Authors: Adenike Adesanya, Nonthaphat Wong, Xiang-Yun Lan, Shea Ping Yip, Chien-Ling Huang

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Background: The most challenging mutation of the oncokinase BCR-ABL protein T315I, which is commonly known as the “gatekeeper” mutation and is notorious for its strong resistance to almost all tyrosine kinase inhibitors (TKIs), especially imatinib. Therefore, this study aims to identify T315I-dependent downstream microRNA (miRNA) pathways associated with drug resistance in chronic myeloid leukemia (CML) for prognostic and therapeutic purposes. Methods: T315I-carrying K562 cell clones (K562-T315I) were generated by the CRISPR-Cas9 system. Imatinib-treated K562-T315I cells were subjected to small RNA library preparation and next-generation sequencing. Putative lncRNA-miRNA-mRNA networks were analyzed with (i) DESeq2 to extract differentially expressed miRNAs, using Padj value of 0.05 as cut-off, (ii) STarMir to obtain potential miRNA response element (MRE) binding sites of selected miRNAs on lncRNA H19, (iii) miRDB, miRTarbase, and TargetScan to predict mRNA targets of selected miRNAs, (iv) IntaRNA to obtain putative interactions between H19 and the predicted mRNAs, (v) Cytoscape to visualize putative networks, and (vi) several pathway analysis platforms – Enrichr, PANTHER and ShinyGO for pathway enrichment analysis. Moreover, mitochondria isolation and transcript quantification were adopted to determine the new mechanism involved in T315I-mediated resistance of CML treatment. Results: Verification of the CRISPR-mediated mutagenesis with digital droplet PCR detected the mutation abundance of ≥80%. Further validation showed the viability of ≥90% by cell viability assay, and intense phosphorylated CRKL protein band being detected with no observable change for BCR-ABL and c-ABL protein expressions by Western blot. As reported by several investigations into hematological malignancies, we determined a 7-fold increase of H19 expression in K562-T315I cells. After imatinib treatment, a 9-fold increment was observed. DESeq2 revealed 171 miRNAs were differentially expressed K562-T315I, 112 out of these miRNAs were identified to have MRE binding regions on H19, and 26 out of the 112 miRNAs were significantly downregulated. Adopting the seed-sequence analysis of these identified miRNAs, we obtained 167 mRNAs. 6 hub miRNAs (hsa-let-7b-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-129-5p, and hsa-miR-372-3p) and 25 predicted genes were identified after constructing hub miRNA-target gene network. These targets demonstrated putative interactions with H19 lncRNA and were mostly enriched in pathways related to cell proliferation, senescence, gene silencing, and pluripotency of stem cells. Further experimental findings have also shown the up-regulation of mitochondrial transcript and lncRNA MALAT1 contributing to the lncRNA-miRNA-mRNA networks induced by BCR-ABL T315I mutation. Conclusions: Our results have indicated that lncRNA-miRNA regulators play a crucial role not only in leukemogenesis but also in drug resistance, considering the significant dysregulation and interactions in the K562-T315I cell model generated by CRISPR-Cas9. In silico analysis has further shown that lncRNAs H19 and MALAT1 bear several complementary miRNA sites. This implies that they could serve as a sponge, hence sequestering the activity of the target miRNAs.

Keywords: chronic myeloid leukemia, imatinib resistance, lncRNA-miRNA-mRNA, T315I mutation

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Authors: Fang Bin Guo, Emma Roberts, Haibin Du, Yonggang Wang, Yu Chen, Xiuli Ge

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This paper explores the findings so far from a major externally-funded project which operates internationally in China, Germany and the UK. The research team is working in the context of the redevelopment of post-industrial sites in China and how these might be platforms for creative enterprises and thereby, the economy and welfare to flourish. Results from the project are anticipated to inform urban design policies in China and possibly farther afield. The research has utilised ethnographic studies and participatory design methods to investigate alternative strategies for sustainable urban renewal of China’s post-industrial areas. Additionally, it has undertaken comparative studies of successful examples of European and Chinese urban regeneration cases. The international cross-disciplinary team has been seeking different opportunities for developing relevant creative industries whilst retaining cultural and industrial heritage. This paper will explore the research conducted so far by the team and offer initial findings. Findings point out the development challenges of cities respecting the protection of local culture/heritages, history of the industries and transformation of the local economies. The preliminary results and pilot analysis of the current research have demonstrated that local government policyholders, business investors/developers and creative industry practitioners are the three major stakeholders that will impact city revitalisations. These groups are expected to work together with asynchronous vision in order for redevelopments to be successful. Meanwhile, local geography, history, culture, politics, economy and ethnography have been identified as important factors that impact on project design and development during urban transformations. Data is being processed from the team’s research conducted across the focal Western and Chinese cities. This has provided theoretical guidance and practical support to the development of significant experimental projects. Many were re-examined with a more international perspective, and adjustments have been based on the conclusions of the research. The observations and research are already generating design solutions in terms of ascertaining essential site components, layouts, visual design and practical facilities for regenerated sites. Two significant projects undertaken by this project team have been nominated by the central Chinese government as the most successful exemplars. They have been listed as outstanding national industry heritage projects; in particular, one of them was nominated by ArchDaily as Building of the Year 2019, and so this project outcome has made a substantial contribution to research and innovation. In summary, this paper will outline the funded project, discuss the work conducted so far, and pinpoint the initial discoveries. It will detail the future steps and indicate how these will impact on national and local governments in China, designers, local citizens and building users.

Keywords: cultural & industrial heritages, ethnographic research, participatory design, regeneration of post-industrial sites, sustainable

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Authors: Sachin Mulmi Shrestha, Xin Fang, Hui Ye, Lihua Ren, Qinghua Ji, Ruihua Shi

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Background: Esophageal squamous cell carcinoma (ESCC) is a tumor arising from esophageal epithelial cells and is one of the major disease subtype in Asian countries, including China. Esophageal cancer is the 7th highest incidence based on the 2020 data of GLOBOCAN. The pathogenesis of cancer is still not well understood as many molecular and genetic basis of esophageal carcinogenesis has yet to be clearly elucidated. Circular RNAs are RNA molecules that are formed by back-splicing covalently joined 3′- and 5′-endsrather than canonical splicing, and recent data suggest circular RNAs could sponge miRNAs and are enriched with functional miRNA binding sites. Hence, we studied the mechanism of circular RNA, its biological function, and the relationship between microRNA in the carcinogenesis of ESCC. Methods: 4 pairs of normal and esophageal cancer tissues were collected in Zhongda hospital, affiliated to Southeast University, and high-throughput RNA sequencing was done. The result revealed that circ_0032746 was upregulated, and thus we selected circ_0032746 for further study. The backsplice junction of circRNA was validated by sanger sequence, and stability was determined by RNASE R assay. The binding site of circRNA and microRNA was predicted by circinteractome,mirandaand RNAhybrid database. Furthermore, circRNA was silenced by siRNA and then by lentivirus. The regulatory axis of circ0032746/miR4270 was validated by shRNA, mimic, and inhibitor transfection. Then, in vitro experiments were performed to assess the role of circ0032746 on proliferation (CCK-8 assay and colon formation assay), migration and invasion (Transewell assay), and apoptosis of ESCC. Results: The upregulated circ0032746 was validated in 9 pairs of tissues and 5 types of cell lines by qPCR, which showed high expression and was statistically significant (P<0.005) ). Upregulated circ0032746 was silenced by shRNA, which showed significant knockdown in KYSE 30 and TE-1 cell lines expression compared to control. Nuclear and cytoplasmic mRNA fraction experiment displayed the cytoplasmic location of circ0032746. The sponging of miR4270 was validated by co-transfection of sh-circ0032746 and mimic or inhibitor. Transfection with mimic showed the decreased expression of circ_0032746, whereas inhibitor inhibited the result. In vitro experiments showed that silencing of circ_0032746 inhibited the proliferation, migration, and invasion compared to the negative control group. The apoptosis was seen higher in a knockdown group than in the control group. Furthermore, 11 common mircoRNA target mRNAs were predicted by Targetscan, MirTarbase, and miRanda database, which may further play role in the pathogenesis. Conclusion: Our results showed that novel circ_0032746 is upregulated in ESCC and plays role in itsoncogenicity. Silencing of circ_0032746 inhibits the proliferation and migration of ESCC whereas increases the apoptosis of cancer cells. Hence, circ0032746 acts as an oncogene in ESCC by sponging with miR4270 and could be a potential biomarker in the diagnosis of ESCC in the future.

Keywords: circRNA, esophageal squamous cell carcinoma, microRNA, upregulated

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Authors: Yu-Mei Hsueh, Wei-Jen Chen, Yung-Kai Huang, Cheng-Shiuan Tsai, Kuo-Cheng Yeh

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Prostate cancer occurs in men over the age of 50, and rank sixth of the top ten cancers in Taiwan, and the incidence increased gradually over the past decade in Taiwan. Arsenic is confirmed as a carcinogen by International Agency for Research on (IARC). Arsenic induces oxidative stress may be a risk factor for prostate cancer, but the mechanism is not clear. Selenium is an important antioxidant element. Whether the association between plasma selenium levels and risk of prostate cancer are modified by different genotype of selenoprotein is still unknown. Glutathione peroxidase, selenoprotein P (SEPP1) and 15 kDa selenoprotein (SEP 15) are selenoprotein and regulates selenium transport and the oxidation and reduction reaction. However, the association between gene polymorphisms of selenoprotein and prostate cancer is not yet clear. The aim of this study is to determine the relationship between plasma selenium, polymorphism of selenoprotein, urinary total arsenic concentration and prostate cancer. This study is a hospital-based case-control study. Three hundred twenty-two cases of prostate cancer and age (±5 years) 1:1 matched 322 control group were recruited from National Taiwan University Hospital, Taipei Medical University Hospital, and Wan Fang Hospital. Well-trained personnel carried out standardized personal interviews based on a structured questionnaire. Information collected included demographic and socioeconomic characteristics, lifestyle and disease history. Blood and urine samples were also collected at the same time. The Research Ethics Committee of National Taiwan University Hospital, Taipei, Taiwan, approved the study. All patients provided informed consent forms before sample and data collection. Buffy coat was to extract DNA, and the polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) was used to measure the genotypes of SEPP1 rs3797310, SEP15 rs5859, GPX1 rs1050450, GPX2 rs4902346, GPX3 rs4958872, and GPX4 rs2075710. Plasma concentrations of selenium were determined by inductively coupled plasma mass spectrometry (ICP-MS).Urinary arsenic species concentrations were measured by high-performance liquid chromatography links hydride generator and atomic absorption spectrometer (HPLC-HG-AAS). Subject with high education level compared to those with low educational level had a lower prostate cancer odds ratio (OR) Mainland Chinese and aboriginal people had a lower OR of prostate cancer compared to Fukien Taiwanese. After adjustment for age, educational level, subjects with GPX1 rs1050450 CT and TT genotype compared to the CC genotype have lower, OR of prostate cancer, the OR and 95% confidence interval (Cl) was 0.53 (0.31-0.90). SEPP1 rs3797310 CT+TT genotype compared to those with CC genotype had a marginally significantly lower OR of PC. The low levels of plasma selenium and the high urinary total arsenic concentrations had the high OR of prostate cancer in a significant dose-response manner, and SEPP1 rs3797310 genotype modified this joint association.

Keywords: prostate cancer, plasma selenium concentration, urinary total arsenic concentrations, glutathione peroxidase, selenoprotein P, selenoprotein 15, gene polymorphism

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Authors: Sanaz Moayer, Fang Huang, Scott Gardner

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In the highly leveraged business world of today, an organisation’s success depends on how it can manage and organize its traditional and intangible assets. In the knowledge-based economy, knowledge as a valuable asset gives enduring capability to firms competing in rapidly shifting global markets. It can be argued that ability to create unique knowledge assets by configuring ICT and human capabilities, will be a defining factor for international competitive advantage in the mid-21st century. The concept of KM is recognized in the strategy literature, and increasingly by senior decision-makers (particularly in large firms which can achieve scalable benefits), as an important vehicle for stimulating innovation and organisational performance in the knowledge economy. This thinking has been evident in professional services and other knowledge intensive industries for over a decade. It highlights the importance of social capital and the value of the intellectual capital embedded in social and professional networks, complementing the traditional focus on creation of intellectual property assets. Despite the growing interest in KM within professional services there has been limited discussion in relation to multinational resource based industries such as mining and petroleum where the focus has been principally on global portfolio optimization with economies of scale, process efficiencies and cost reduction. The Australian minerals and metals mining industry, although traditionally viewed as capital intensive, employs a significant number of knowledge workers notably- engineers, geologists, highly skilled technicians, legal, finance, accounting, ICT and contracts specialists working in projects or functions, representing potential knowledge silos within the organisation. This silo effect arguably inhibits knowledge sharing and retention by disaggregating corporate memory, with increased operational and project continuity risk. It also may limit the potential for process, product, and service innovation. In this paper the strategic application of knowledge management incorporating contemporary ICT platforms and data mining practices is explored as an important enabler for knowledge discovery, reduction of risk, and retention of corporate knowledge in resource based industries. With reference to the relevant strategy, management, and information systems literature, this paper highlights possible connections (currently undergoing empirical testing), between an Strategic Knowledge Management (SKM) framework incorporating supportive Data Mining (DM) practices and competitive advantage for multinational firms operating within the Australian resource sector. We also propose based on a review of the relevant literature that more effective management of soft and hard systems knowledge is crucial for major Australian firms in all sectors seeking to improve organisational performance through the human and technological capability captured in organisational networks.

Keywords: competitive advantage, data mining, mining organisation, strategic knowledge management

Procedia PDF Downloads 415

Authors: Chung-Ming Lo, Chung-Chien Lee

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In many countries, the lifetime prevalence of shoulder pain is up to 70%. In America, the health care system spends 7 billion per year about the healthy issues of shoulder pain. With respect to the origin, up to 70% of shoulder pain is attributed to rotator cuff lesions This study proposed a computer-aided diagnosis (CAD) system to assist radiologists classifying rotator cuff lesions with less operator dependence. Quantitative features were extracted from the shoulder ultrasound images acquired using an ALOKA alpha-6 US scanner (Hitachi-Aloka Medical, Tokyo, Japan) with linear array probe (scan width: 36mm) ranging from 5 to 13 MHz. During examination, the postures of the examined patients are standard sitting position and are followed by the regular routine. After acquisition, the shoulder US images were drawn out from the scanner and stored as 8-bit images with pixel value ranging from 0 to 255. Upon the sonographic appearance, the boundary of each lesion was delineated by a physician to indicate the specific pattern for analysis. The three lesion categories for classification were composed of 20 cases of tendon inflammation, 18 cases of calcific tendonitis, and 18 cases of supraspinatus tear. For each lesion, second-order statistics were quantified in the feature extraction. The second-order statistics were the texture features describing the correlations between adjacent pixels in a lesion. Because echogenicity patterns were expressed via grey-scale. The grey-scale co-occurrence matrixes with four angles of adjacent pixels were used. The texture metrics included the mean and standard deviation of energy, entropy, correlation, inverse different moment, inertia, cluster shade, cluster prominence, and Haralick correlation. Then, the quantitative features were combined in a multinomial logistic regression classifier to generate a prediction model of rotator cuff lesions. Multinomial logistic regression classifier is widely used in the classification of more than two categories such as the three lesion types used in this study. In the classifier, backward elimination was used to select a feature subset which is the most relevant. They were selected from the trained classifier with the lowest error rate. Leave-one-out cross-validation was used to evaluate the performance of the classifier. Each case was left out of the total cases and used to test the trained result by the remaining cases. According to the physician’s assessment, the performance of the proposed CAD system was shown by the accuracy. As a result, the proposed system achieved an accuracy of 86%. A CAD system based on the statistical texture features to interpret echogenicity values in shoulder musculoskeletal ultrasound was established to generate a prediction model for rotator cuff lesions. Clinically, it is difficult to distinguish some kinds of rotator cuff lesions, especially partial-thickness tear of rotator cuff. The shoulder orthopaedic surgeon and musculoskeletal radiologist reported greater diagnostic test accuracy than general radiologist or ultrasonographers based on the available literature. Consequently, the proposed CAD system which was developed according to the experiment of the shoulder orthopaedic surgeon can provide reliable suggestions to general radiologists or ultrasonographers. More quantitative features related to the specific patterns of different lesion types would be investigated in the further study to improve the prediction.

Keywords: shoulder ultrasound, rotator cuff lesions, texture, computer-aided diagnosis

Procedia PDF Downloads 284

Authors: Chien Chin-Wen

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Collaborative teaching has different teaching models and station teaching is one type of collaborative teaching. Station teaching is not commonly practiced in elementary school English education and introduced in language teacher education programs in Taiwan. In station teaching, each teacher takes a small part of instructional content, working with a small number of students. Students rotate between stations where they receive the assignments and instruction from different teachers. The teachers provide the same content to each group, but the instructional method can vary based upon the needs of each group of students. This study explores thirty-four Taiwanese pre-service elementary school English teachers’ knowledge about station teaching and their competence demonstrated in designing activities for and delivering of station teaching in an English remedial education to six sixth graders in a local elementary school in northern Taiwan. The participants simultaneously enrolled in this Elementary School English Teaching Materials and Methods class, a part of an elementary school teacher education program in a northern Taiwan city. The instructor (Jennifer, pseudonym) in this Elementary School English Teaching Materials and Methods class collaborated with an English teacher (Olivia, pseudonym) in Maureen Elementary School (pseudonym), an urban elementary school in a northwestern Taiwan city. Of Olivia’s students, four male and two female sixth graders needed to have remedial English education. Olivia chose these six elementary school students because they were in the lowest 5 % of their class in terms of their English proficiency. The thirty-four pre-service English teachers signed up for and took turns in teaching these six sixth graders every Thursday afternoon from four to five o’clock for twelve weeks. While three participants signed up as a team and taught these six sixth graders, the last team consisted of only two pre-service teachers. Each team designed a 40-minute lesson plan on the given language focus (words, sentence patterns, dialogue, phonics) of the assigned unit. Data in this study included the KWLA chart, activity designs, and semi-structured interviews. Data collection lasted for four months, from September to December 2014. Data were analyzed as follows. First, all the notes were read and marked with appropriate codes (e.g., I don’t know, co-teaching etc.). Second, tentative categories were labeled (e.g., before, after, process, future implication, etc.). Finally, the data were sorted into topics that reflected the research questions on the basis of their relevance. This study has the following major findings. First of all, the majority of participants knew nothing about station teaching at the beginning of the study. After taking the course Elementary School English Teaching Materials and Methods and after designing and delivering the station teaching in an English remedial education program to six sixth graders, they learned that station teaching is co-teaching, and that it includes activity designs for different stations and students’ rotating from station to station. They demonstrated knowledge and skills in activity designs for vocabulary, sentence patterns, dialogue, and phonics. Moreover, they learned to interact with individual learners and guided them step by step in learning vocabulary, sentence patterns, dialogue, and phonics. However, they were still incompetent in classroom management, time management, English, and designing diverse and meaningful activities for elementary school students at different English proficiency levels. Hence, language teacher education programs are recommended to integrate station teaching to help pre-service teachers be equipped with eight knowledge and competences, including linguistic knowledge, content knowledge, general pedagogical knowledge, curriculum knowledge, knowledge of learners and their characteristics, pedagogical content knowledge, knowledge of education content, and knowledge of education’s ends and purposes.

Keywords: co-teaching, competence, knowledge, pre-service teachers, station teaching

Procedia PDF Downloads 427

Authors: Dongping Fang, Lian Duan, Xiaojing Yuan, Mike Xu, Allyn Klunder, Kevin Tan, Suiting Cao, Yeqing Ji

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Accurate prediction of a medical condition with straight clinical evidence is a long-sought topic in the medical management and health insurance field. Although great progress has been made with machine learning algorithms, the medical community is still, to a certain degree, suspicious about the model's accuracy and interpretability. This paper presents an innovative hierarchical attention deep learning model to achieve good prediction and clear interpretability that can be easily understood by medical professionals. This deep learning model uses a hierarchical attention structure that matches naturally with the medical history data structure and reflects the member’s encounter (date of service) sequence. The model attention structure consists of 3 levels: (1) attention on the medical code types (diagnosis codes, procedure codes, lab test results, and prescription drugs), (2) attention on the sequential medical encounters within a type, (3) attention on the medical codes within an encounter and type. This model is applied to predict the occurrence of stage 3 chronic kidney disease (CKD3), using three years’ medical history of Medicare Advantage (MA) members from a top health insurance company. The model takes members’ medical events, both claims and electronic medical record (EMR) data, as input, makes a prediction of CKD3 and calculates the contribution from individual events to the predicted outcome. The model outcome can be easily explained with the clinical evidence identified by the model algorithm. Here are examples: Member A had 36 medical encounters in the past three years: multiple office visits, lab tests and medications. The model predicts member A has a high risk of CKD3 with the following well-contributed clinical events - multiple high ‘Creatinine in Serum or Plasma’ tests and multiple low kidneys functioning ‘Glomerular filtration rate’ tests. Among the abnormal lab tests, more recent results contributed more to the prediction. The model also indicates regular office visits, no abnormal findings of medical examinations, and taking proper medications decreased the CKD3 risk. Member B had 104 medical encounters in the past 3 years and was predicted to have a low risk of CKD3, because the model didn’t identify diagnoses, procedures, or medications related to kidney disease, and many lab test results, including ‘Glomerular filtration rate’ were within the normal range. The model accurately predicts members A and B and provides interpretable clinical evidence that is validated by clinicians. Without extra effort, the interpretation is generated directly from the model and presented together with the occurrence date. Our model uses the medical data in its most raw format without any further data aggregation, transformation, or mapping. This greatly simplifies the data preparation process, mitigates the chance for error and eliminates post-modeling work needed for traditional model explanation. To our knowledge, this is the first paper on an interpretable deep-learning model using a 3-level attention structure, sourcing both EMR and claim data, including all 4 types of medical data, on the entire Medicare population of a big insurance company, and more importantly, directly generating model interpretation to support user decision. In the future, we plan to enrich the model input by adding patients’ demographics and information from free-texted physician notes.

Keywords: deep learning, interpretability, attention, big data, medical conditions

Procedia PDF Downloads 91