Search results for: MICE strategy

Authors: Seunghwan Seo, Woo-Seok Lee, Ji-Sun Shin, Young Kyoung Rhee, Chang-Won Cho, Hee-Do Hong, Kyung-Tae Lee

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Doenjang, known as traditional Korean food, is product of a natural mixed fermentation process carried out by lactic acid bacteria (LAB). Lactobacillus sakei K040706 (K040706) has been accepted as the most populous LAB in over ripened doenjang. Recently, we reported the immunostimulatory effects of K040706 in RAW 264.7 macrophages and in a cyclophosphamide-induced mouse model. In this study, we investigated the ameliorative effects of K040706 in a dextran sulfate sodium (DSS)-induced colitis mouse model. We induced colitis using DSS in 5-week-ICR mice over 14 days with or without 0.1, 1 g/kg/day K040706 orally. The body weight, stool consistency, and gross bleeding were recorded for determination of the disease activity index (DAI). At the end of treatment, animals were sacrificed and colonic tissues were collected and subjected to histological experiments and myeloperoxidase (MPO) accumulation, cytokine determination, qRT-PCR and Western blot analysis. Results showed that K040706 significantly attenuated DSS-induced DAI score, shortening of colon length, enlargement of spleen and immune cell infiltrations into colonic tissues. Histological examinations indicated that K040706 suppressed edema, mucosal damage, and the loss of crypts induced by DSS. These results were correlated with the restoration of tight junction protein expression, such as, ZO-1 and occludin in K040706-treated mice. Moreover, K040706 reduced the abnormal secretions and mRNA expressions of pro-inflammatory mediators, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). DSS-induced mRNA expression of intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in colonic tissues was also downregulated by K040706 treatment. Furthermore, K040706 suppressed the protein and mRNA expression of toll-like receptor 4 (TLR4) and phosphorylation of NF-κB and signal transducer and activator of transcription 3 (STAT3). These results suggest that K040706 has an anti-colitic effect by inhibition of intestinal inflammatory responses in DSS-induced colitic mice.

Keywords: Lactobacillus sakei, NF-κB, STAT3, ulcerative colitis

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Authors: Huan Peng, Chenye Zeng, Zhao Wang

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Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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Authors: Lian Zeng

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Double-Spear 1-H2-1 (DS1-H2-1) is an oncolytic virus and an innovative biological drug candidate. The chemical composition of the drug product is a live attenuated West Nile virus (WNV) containing the human T cell costimulator (CD86) gene. After intratumoral injection, the virus can rapidly self-replicate in the injected site and lyse/kill the tumor by repeated infection among tumor cells. We also established xenograft tumor models in mice to evaluate the drug candidate's efficacy on those tumors. The results from preclinical studies on transplanted tumors in immunodeficient mice showed that DS1-H2-1 had significant oncolytic effects on human-origin cancers: it completely (100%) shrieked human glioma; limited human neuroblastoma growth reached as high as 95% growth inhibition rate (%TGITW). The safety data of preclinical animal experiments confirmed that DS1-H2-1 is safe as a biological drug for clinical use. In the preclinical drug efficacy experiment, virus-drug administration with different doses did not show abnormal signs and disease symptoms in more than 300 tested mice, and no side effects or death occurred through various administration routes. Intravenous administration did not cause acute infectious disease or other side effects. However, the replication capacity of the virus in tumor tissue via intravenous administration is only 1% of that of direct intratumoral administration. The direct intratumoral administration of DS1-H2-1 had a higher rate of viral replication. Therefore, choosing direct intratumoral injection can ensure both efficacy and safety.

Keywords: oncolytic virus, WNV-CD86, immunotherapy drugs, glioma, neuroblastoma

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Authors: Iman Ali Ahmed Al-Rashed

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This paper directs attention to the limitations of the teacher-centered strategy in teaching. The aim of this study is to draw more educational attention to learner-centered strategy in order to shift the emphasis from the traditional concept of teaching to a new concept in teaching. To begin bridging the traditional concept of teaching and the new concept, the study will explore the new concept of teaching to support teaching in Arab World generally and in Iraq specifically. A qualitative case study orientation was used to collect data in the form of classroom observations, interviews and field notes. The teaching practices used by three university instructors are investigated and according to the findings, some explanations and recommendations are made.

Keywords: case study, learner-centered strategy, qualitative study, teacher-centered strategy, traditional teaching

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Authors: Soumeya Krimat, Tahar Dob, Aicha Kesouri, Ahmed Nouasri, Hafidha Metidji

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Lavandula antineae Maire is an endemic medicinal plant of Algeria which is traditionally used for the treatment of chills, bruises, oedema and rheumatism. The objective of this study is to evaluate the anti-inflammatory of hydromethanolic aerial parts extract of Lavandula antineae for the first time using carrageenan-paw edema and croton oil-ear odema models. The plant extract, at the dose of 200 mg/kg, showed a significant anti-inflammatory activity (P˂0.05) in the carrageenan induced edema test in mice, showing 80.74% reduction in the paw thikness comparable to that produced by the standard drug aspirin 83.44% at 4h. When it was applied topically at a dosage of 1 and 2 mg per ear, the percent edema reduction in treated mice was 29.45% and 74.76%, respectively. These results demonstrate that Lavandula antineae Maire extract possess remarkable anti-inflammatory activity, supporting the folkloric usage of the plant to treat various inflammatory and pain diseases.

Keywords: lavandula antineae maire, medicinal plant, anti-inflammatory activity, carrageenan-paw edema, croton oil-ear edema

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Authors: Naufal Ahmad Rijalul Alam

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This article presents a quality of education for the poor people in Indonesia and the offering of strategy to be done. It also investigates the influence of Islamic Education which stands behind the religious values in developing effort of government to respond the problem with using humanities approaches in medium society. The offering strategy resulted in four agenda: 1) building a shared commitment, 2) encouraging the improvement of the quality of public and private schools, 3) encouraging the use of 'the indicator of disaffection' for gifted children, and 4) encouraging the enlargement of vocational training centers and polytechnics. The conclusion is that the quality of education can be increased with these four agenda, although they are not too easy because it deals with other factors such as the economy, politics, and culture which is happening in the country.

Keywords: quality education, poor people, strategy of Islamic education, medium community

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Authors: Ramasamy Tamizhselvi, Leema George, Madhav Bhatia

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We have earlier shown that mouse pancreatic acinar cells produce hydrogen sulfide (H2S) and play a role in the pathogenesis of acute pancreatitis. This study is to determine the effect of H2S on TLR4 mediated innate immune signaling in acute pancreatitis via substance P (SP). Male Swiss mice were treated with hourly intraperitoneal injection of caerulein (50μg/kg) for 10 hour. DL-propargylglycine (PAG) (100 mg/kg i.p.), an inhibitor of H2S formation was administered 1h after the induction of acute pancreatitis. Pancreatic acinar cells from male Swiss mice were incubated with or without caerulein (10–7 M for 60 min) and CP-96345 (NK1R inhibitor). To better understand the effect of H2S in inflammation, acinar cells were stimulated with caerulein after addition of H2S donor, NaHS. In addition, caerulein treated pancreatic acinar cells were pretreated with PAG (30 µM), for 1h. H2S inhibitor, PAG, eliminated TLR4, IRAK4, TRAF6 and NF-kB levels in an in vitro and in vivo model of caerulein-induced acute pancreatitis. PPTA gene deletion reduced TLR4, MyD88, IRAK4, TRAF6, adhesion molecules and NF-kB in caerulein treated pancreatic acinar cells whereas administration of NaHS resulted in further rise in TLR4 and NF-kB levels in caerulein treated pancreatic acinar cells. In addition, acini isolated from mice and treated with PPTA gene receptor NK1R antagonist CP96345 did not exhibit further increase in TLR4, IRAK4, TRAF6, adhesion molecules and NF-kB levels after NaHS pretreatment. The present findings show for the first time that in acute pancreatitis, H2S up-regulates TLR4 pathway and NF-kB via substance P.

Keywords: preprotachykinin-A gene, H2S, TLR4, acute pancreatitis

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Authors: Ben G. Weber, Michael Mateas

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We present a case-based reasoning technique for selecting build orders in a real-time strategy game. The case retrieval process generalizes features of the game state and selects cases using domain-specific recall methods, which perform exact matching on a subset of the case features. We demonstrate the performance of the technique by implementing it as a component of the integrated agent framework of McCoy and Mateas. Our results demonstrate that the technique outperforms nearest-neighbor retrieval when imperfect information is enforced in a real-time strategy game.

Keywords: case based reasoning, real time strategy systems, requirements elicitation, requirement analyst, artificial intelligence

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Authors: Md. M. Hossain, Regan Roat, Jenica Christopherson, Colette Free, Zhiguang Guo

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Long noncoding RNA (lncRNA) mediated post-transcriptional gene regulation, and their epigenetic landscapes have been shown to be involved in many human diseases. However, their regulation in diabetes through governing islet’s β-cell function and survival needs to be elucidated. Due to the technical and ethical constraints, it is difficult to study their role in β-cell function and survival in human under in vivo condition. In this study, humanized mice have been developed through transplanting human pancreatic islet under the kidney capsule of NOD.SCID mice and induced β-cell death leading to diabetes condition to study lncRNA mediated regulation. For this, human islets from 3 donors (3000 IEQ, purity > 80%) were transplanted under the kidney capsule of STZ induced diabetic NOD.scid mice. After at least 2 weeks of normoglycecemia, lymphocytes from diabetic NOD mice were adoptively transferred and islet grafts were collected once blood glucose reached > 200 mg/dl. RNA from human donor islets, islet grafts from humanized mice with either adoptive lymphocyte transfer (ALT) or PBS control (CTL) were ribodepleted; barcoded fragment libraries were constructed and sequenced on the Ion Proton sequencer. lncRNA expression in isolated human islets, islet grafts from humanized mice with and without induced β-cell death and their regulation in human islets function in vitro under glucose challenge, cytokine mediated inflammation and induced apoptotic condition were investigated. Out of 3155 detected lncRNAs, 299 that highly expressed in islets were found to be significantly downregulated and 224 upregulated in ALT compared to CTL. Most of these are found to be collocated within 5 kb upstream and 1 kb downstream of 788 up- and 624 down-regulated mRNAs. Genomic Regions Enrichment of Annotations Analysis revealed deregulated and collocated genes are related to pancreas endocrine development; insulin synthesis, processing, and secretion; pancreatitis and diabetes. Many of them, that found to be located within enhancer domains for islet specific gene activity, are associated to the deregulation of known islet/βcell specific transcription factors and genes that are important for β-cell differentiation, identity, and function. RNA sequencing analysis revealed aberrant lncRNA expression which is associated to the deregulated mRNAs in β-cell function as well as in molecular pathways related to diabetes. A distinct set of candidate lncRNA isoforms were identified as highly enriched and specific to human islets, which are deregulated in human islets from donors with different BMIs and with type 2 diabetes. These RNAs show an interesting regulation in cultured human islets under glucose stimulation and with induced β-cell death by cytokines. Aberrant expression of these lncRNAs was detected in the exosomes from the media of islets cultured with cytokines. Results of this study suggest that the islet specific lncRNAs are deregulated in human islet with β-cell death, hence important in diabetes. These lncRNAs might be important for human β-cell function and survival thus could be used as biomarkers and novel therapeutic targets for diabetes.

Keywords: β-cell, humanized mouse, pancreatic islet, LncRNAs

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Authors: Liqiang Chen

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This study investigates the effects of political connections on the association between firms’ business strategy and their tax aggressiveness in an emerging economy such as China. By studying all public Chinese firms in the period from 2011 to 2017, we find that firms adopting innovative business strategy are more tax aggressive overall, but innovative firms with political connections are less tax aggressive compared to those without political connections. Moreover, we document several channels through which political connections affect the association between innovative business strategy and tax aggressiveness. In particular, we show that the mitigation effect of political connections on tax aggressiveness is stronger for innovative firms located in areas with a lower marketization index and for innovative firms with a lower leverage level or with less earnings management. Our results are robust to an instrumental variable approach to account for possible endogenous bias. Our study contributes to the understanding of firms’ tax behaviors in an emerging economy setting and suggests that there are costs associated with political connections, such as foregone tax saving opportunities, which are understudied in the prior literature.

Keywords: tax aggressiveness, business strategy, political connections, emerging economy

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Authors: Mrinal Gupta, Mohammad Rumman, Babita Singh Abbas Ali Mahdi, Shivani Pandey

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Introduction: Berberine (BBR), a bioactive compound isolated from Coptidis Rhizoma, possesses diverse pharmacological activities, including anti-bacterial, anti-inflammatory, antitumor, hypolipidemic, and anti-diabetic. However, its role as an anti-diabetic agent in animal models of dexamethasone (Dex)-induced diabetes remains unknown. Studies have shown that natural compounds, including aloe, caper, cinnamon, cocoa, green and black tea, and turmeric, can be used for treating Type 2 diabetes mellitus (DM). Compared to conventional drugs, natural compounds have fewer side effects and are easily available. Herein, we studied the anti-diabetic effects of BBR in a mice model of Dex-induced diabetes. Methods: HepG2 cell line was used for glucose release and glycogen synthesis studies. Cell proliferation was measured by methylthiotetrazole (MTT) assay. For animal studies, mice were treated with Dex (2 mg/kg, i.m.) for 30 days and the effect of BBR at the doses 100, 200, and 500 mg/kg (p.o.) was analyzed. Glucose, insulin, and pyruvate tests were performed to evaluate the development of the diabetic model. An echo MRI was performed to assess the fat mass. Further, to elucidate the mechanism of action of BBR, mRNA expression of genes regulating gluconeogenesis, glucose uptake, and glycolysis were analyzed. Results: In vitro BBR had no impact on cell viability up to a concentration of 50μM. Moreover, BBR suppressed the hepatic glucose release and improved glucose tolerance in HepG2 cells. In vivo, BBR improved glucose homeostasis in diabetic mice, as evidenced by enhanced glucose clearance, increased glycolysis, elevated glucose uptake, and decreased gluconeogenesis. Further, Dex treatment increased the total fat mass in mice, which was ameliorated by BBR treatment. Conclusion: BBR improves glucose tolerance by increasing glucose clearance, inhibiting hepatic glucose release, and decreasing obesity. Thus, BBR may become a potential therapeutic agent for treating glucocorticoid-induced diabetes and obesity in the future.

Keywords: glucocorticoid, hyperglycemia, berberine, HepG2 cells, insulin resistance, glucose

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Authors: Dejan Metodijeski, Elizabeta Mitreva, Nako Taskov, Oliver Filiposki

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Tourism development strategies are an important link in the tourism policy that is used to make its management better and easier. A public-public partnership (PUP) is a partnership between two or more public authorities or between a public authority and any non-profit organization with the goal of providing services and facilities or transferring technical skills. The paper presents this kind of partnership between two public authorities in Macedonia, the Municipality of Gazi Baba on one hand, and the University of Goce Delcev on the other. The main idea of this partnership is the development of a tourism strategy for the Municipality of Gazi Baba by the University on one side, and on the other, the construction of a mini park in the court of the University by the Municipality. This paper presents the causes and analyzes the procedures relating to this partnership and the methodology of the tourism development strategy. It contains a relevant literature review related to PUPs and tourism development strategy. The results and benefits of this partnership are presented with figures.

Keywords: public-public partnership, tourism development strategy, municipality of Gazi Baba, Macedonia

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Authors: Mahmood Dehqan, Peyman Peyvasteh

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In recent years there has been a growing interest in issues concerning the impact of sociocultural theory (SCT) of learning on different aspects of second/foreign language learning. This study aimed to find the possible effects of sociocultural teaching techniques on reading strategy of EFL learners. Indeed, the present research compared the impact of peer and teacher scaffolding on EFL learners’ reading strategy use across two proficiency levels. To this end, a pre-test post-test quasi-experimental research design was used and two instruments were utilized to collect the data: Nelson English language test and reading strategy questionnaire. Ninety five university students participated in this study were divided into two groups of teacher and peer scaffolding. Teacher scaffolding group received scaffolded help from the teacher based on three mechanisms of effective help within ZPD: graduated, contingent, dialogic. In contrast, learners of peer scaffolding group were unleashed from the teacher-fronted classroom as they were asked to carry out the reading comprehension tasks with the feedback they provided for each other. Results obtained from ANOVA revealed that teacher scaffolding group outperformed the peer scaffolding group in terms of reading strategy use. It means teacher’s scaffolded help provided within the learners’ ZPD led to better reading strategy improvement compared with the peer scaffolded help. However, the interaction effect between proficiency factor and teaching technique was non-significant, leading to the conclusion that strategy use of the learners was not affected by their proficiency level in either teacher or peer scaffolding groups.

Keywords: peer scaffolding, proficiency level, reading strategy, sociocultural theory, teacher scaffolding

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Authors: M. K. Benhaoua, A. K. Singh, A. E. H. Benyamina, A. Kumar, P. Boulet

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In this paper, we propose a new packing strategy to find free resources for run-time mapping of application tasks on NoC-based Heterogeneous MPSoCs. The proposed strategy minimizes the task mapping time in addition to placing the communicating tasks close to each other. To evaluate our approach, a comparative study is carried out. Experiments show that our strategy provides better results when compared to latest dynamic mapping strategies reported in the literature.

Keywords: heterogeneous MPSoCs, NoC, dynamic mapping, routing

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Authors: Reva Sharan Thakur, Mrinalini Tiwari, Jyoti das

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Cerebral malaria-associated over expression of pro-inflammatory cytokines and chemokines ultimately results in the up-regulation of adhesion molecules in the brain endothelium leading to sequestration of mature parasitized RBCs in the brain. The high-parasitic load subsequently results in increased mortality or development of neurological symptoms within a week of infection. Studies in the human and experimental cerebral malaria have implicated the breakdown of the integrity of blood-brain barrier during the lethal course of infection, cerebral dysfunction, and fatal organ pathologies that result in multi-organ failure. In the present study, using Plasmodium berghei Anka as a mouse model and in vitro conditions, we have investigated the effect of MSCs to attenuate cerebral malaria pathogenesis by diminishing the effect of inflammation altered organ morphology, reduced parasitemia, and increased survival of the mice. MSCs are also validated for their role in preventing BBB dysfunction and reducing malarial toxins. It was observed that administration of MSCs significantly reduced parasitemia and increased survival in Pb A infected mice. It was further demonstrated that MSCs play a significant role in reversing neurological complexities associated with cerebral malaria. Infusion of MSCs in infected mice decreased hemozoin deposition; oedema, and haemorrhagic lesions in vascular organs. MSCs administration also preserved the integrity of the blood-brain barrier and reduced neural inflammation. Taken together, our results demonstrate the potential of MSCs as an emerging anti-malarial candidate.

Keywords: cerebral malaria, mesenchymal stem cells, erythropoesis, cell death

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Authors: Ho-Jun Jo, Wook-Won Kim, Yong-Sung Kim, Jin-O Kim

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The application of ESS (Energy Storage Systems) in the future grids has been the solution of the microgrid. However, high investment costs necessitate accurate modeling and control strategy of ESS to justify its economic viability and further underutilization. Therefore, the reasonable control strategy for ESS which is subjected to generator and usage helps to curtail the cost of investment and operation costs. The rated frequency in power system is decreased when the load is increasing unexpectedly; hence the thermal power is operated at the capacity of only its 95% for the Governor Free (GF) to adjust the frequency as reserve (5%) in practice. The ESS can be utilized with governor at the same time for the frequency response due to characteristic of its fast response speed and moreover, the cost of ESS is declined rapidly to the reasonable price. This paper presents the ESS control strategy to extend usage of the ESS taken account into governor’s ramp rate and reduce the governor’s intervention as well. All results in this paper are simulated by MATLAB.

Keywords: micro grid, energy storage systems, ramp rate, control strategy

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Authors: Roberto Coppo, Francesca Orso, Daniela Dettori, Elena Quaglino, Lei Nie, Mehran M. Sadeghi, Daniela Taverna

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Malignant melanoma is currently the fifth most common cancer in the white population and it is fatal in its metastatic stage. Several research studies in recent years have provided evidence that cancer initiation and progression are driven by genetic alterations of the tumor and paracrine interactions between tumor and microenvironment. Scattered data show that the Endothelial and Smooth muscle cell-Derived Neuropilin-like molecule (ESDN) controls cell proliferation and movement of stroma and tumor cells. To investigate the role of ESDN in the tumor microenvironment during melanoma progression, murine melanoma cells (B16 or B16-F10) were injected in ESDN knockout mice in order to evaluate how the absence of ESDN in stromal cells could influence melanoma progression. While no effect was found on primary tumor growth, increased cell extravasation and lung metastasis formation was observed in ESDN knockout mice compared to wild type controls. In order to understand how cancer cells cross the endothelial barrier during metastatic dissemination in an ESDN-null microenvironment, structure, and permeability of lung blood vessels were analyzed. Interestingly, ESDN knockout mice showed structurally altered and more permeable vessels compared to wild type animals. Since cell surface molecules mediate the process of tumor cell extravasation, the expression of a panel of extravasation-related ligands and receptors was analyzed. Importantly, modulations of N-cadherin, E-selectin, ICAM-1 and VAP-1 were observed in ESDN knockout endothelial cells, suggesting the presence of a favorable tumor microenvironment which facilitates melanoma cell extravasation and metastasis formation in the absence of ESDN. Furthermore, a potential contribution of immune cells in tumor dissemination was investigated. An increased recruitment of macrophages in the lungs of ESDN knockout mice carrying subcutaneous B16-F10 tumors was found. In conclusion, our data suggest a functional role of ESDN in the tumor microenvironment during melanoma progression and the identification of the mechanisms that regulate tumor cell extravasation could lead to the development of new therapies to reduce metastasis formation.

Keywords: melanoma, tumor microenvironment, extravasation, cell surface molecules

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Authors: S. Zolghadri, M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani

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In this study, the absorbed dose of human organs after injection of ¹⁷⁷Lu-DOTATOC was studied based on the biodistribution of the complex in adenocarcinoma breast cancer bearing mice. For this purpose, the biodistribution of the radiolabelled complex was studied and compartmental modeling was applied to calculate the absorbed dose with high precision. As expected, ¹⁷⁷Lu-DOTATOC illustrated a notable specific uptake in tumor and pancreas, organs with high level of somatostatin receptor on their surface and the effectiveness of the radio-conjugate for targeting of the breast adenocarcinoma tumors was indicated. The elicited results of modeling were the exponential equations, and those are utilized for obtaining the cumulated activity data by taking their integral. The results also exemplified that non-target absorbed-doses such as the liver, spleen and pancreas were approximately 0.008, 0.004, and 0.039, respectively. While these values were so much lower than target (tumor) absorbed-dose, it seems due to this low toxicity, this complex is a good agent for therapy.

Keywords: ¹⁷⁷Lu, breast cancer, compartmental modeling, dosimetry

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Authors: Jarunee Wonglimpiyarat

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This paper explores the innovation management strategy of Thailand in moving towards the Detroit of Asia. The study analyses Thailand’s automotive cluster based on Porter’s Diamond Model and national innovation system (NIS) framework. A qualitative methodology was carried out, using semi-structured interviews with the players in the Thai automotive industry. Thailand took a different NIS approach by pursuing an Original Equipment Manufacture (OEM) strategy to attract foreign investments in building its automotive cluster, a different path from other Asian countries that competed with Own Brand Manufacture (OBM) strategies. The findings provide useful lessons for other newly industrialized countries (NICs) in adopting the cluster policies to move up the technological ladders.

Keywords: innovation management strategy, national innovation system (NIS), Detroit of Asia, original equipment manufacturer (OEM)

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Authors: S. K. Ashiquer Rahman

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The paper concentrates on the importance of Sustainable Campus Strategies, emphasizing the significance of mobilizing Innovative technological tools for constructing effectiveness of higher education strategy and institutional cooperation for sustainable campus at the university level and preparing the university’s authority to face the upcoming higher education strategy and institutional cooperation difficulties to the Sustainable Campus Plan. Within a framework of Sustainable Campus Strategies and institutional cooperation, the paper discusses the significance of a set of reference points that will lead to operational activities for multi-stakeholder multi-criteria evaluation of Higher Education and Research Institutions relative to the Sustainable Campus criteria and potential action plan for the University’s Strategy and Institutional Cooperation. It makes mention of the emergence of the effectiveness of Higher Education Strategy and Institutional Cooperation as well as the necessity of mobilizing innovative technological methods and tools for constructing the effectiveness of this Process. The paper outlines the conceptual framing of a Sustainable Campus Strategy, Institutional Cooperation and Action Plan for a sustainable campus. Optimistically, these will be a milestone in higher education, a pathway to meet the imminent Sustainable Campus Strategy and Institutional Cooperation of the completive world, and be able to manage the required criteria for a Sustainable University.

Keywords: higher education strategy, institutional cooperation, sustainable campus, multi-criteria evaluation, innovative method and tools

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Authors: Min Dai, Hong Liu, Shuaijie Qian

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We study a portfolio selection problem of an investor who faces constraints on rebalancing frequency, which is common in pension fund investment. We formulate it as a multiple optimal stopping problem and utilize the dynamic programming principle. By numerically solving the corresponding Hamilton-Jacobi-Bellman (HJB) equation, we find a series of free boundaries characterizing optimal strategy, and the constraints significantly impact the optimal strategy. Even in the absence of transaction costs, there is a no-trading region, depending on the number of the remaining trading chances. We also find that the equivalent wealth loss caused by the constraints is large. In conclusion, our model clarifies the impact of the constraints on transaction frequency on the optimal strategy.

Keywords: portfolio selection, rebalancing frequency, optimal strategy, free boundary, optimal stopping

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Authors: Moustafa Elhamouly, Masayuki Shimada

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The production of competent oocytes is essential for reproductivity in mammals. Maintenance of mitochondrial efficiency is required to supply the ATP necessary for granulosa cell proliferation during the follicular development process. Treatment with Pyrroloquinoline quinone (PQQ) has been reported to increase the number of ovulated oocytes and pups per delivery in mice by maintaining healthy mitochondrial function. This study aimed to elucidate how PQQ maintains mitochondrial function during ovarian follicle growth. To do this, both in vitro and in vivo experiments were performed with granulosa cells from superovulated immature (3-week-old) mice that were pretreated with or without PQQ. The effects of PQQ on beta-oxidation, mitochondrial function, mitophagy, and mitochondrial biogenesis were examined. PQQ increased beta-oxidation-related genes and CPT1 protein content in granulosa cells and this was associated with a decreased phosphorylation of P38 signaling protein. Using the fatty acid oxidation assay on the flux analyzer, PQQ increased the reliance of beta-oxidation on the endogenous fatty acids and was associated with a mild UCP-dependant mitochondrial uncoupling, ATP production, mitophagy, and mitochondrial biogenesis. PQQ also increased the expression of endogenous antioxidant enzymes. Thus, PQQ induced beta-oxidation in growing granulosa cells relying on endogenous fatty acids. And reduced the Reactive oxygen species (ROS) production by inducing a mild mitochondrial uncoupling with keeping high mitochondrial function. Damaged mitochondria were recycled by the induced mitophagy and replaced by the increased mitochondrial biogenesis. Collectively, PQQ may enhance reproductivity by maintaining the efficiency of mitochondria to produce enough ATP required for normal folliculogenesis.

Keywords: granulosa cells, mitochondrial uncoupling, mitophagy, pyrroloquinoline quinone (PQQ), reactive oxygen species (ROS).

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Authors: Xi Yu, Lili Gu, Huizhu Wang, Xiao Wei, Dandan Sheng, Xiaoyan Jiang, Min Hong

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Introduction: Hypersensitivity disease is difficult to cure completely because of its recurrence, yupingfengsan (YPFS) is used to treat the diseases with the advantage of reducing the recurrence,but the precise mechanism is not clear. Previous studies of our laboratory have shown that the extract of YPFS can inhibit Th2-type allergic contact dermatitis(ACD) induced by FITC.Besides, thymic stromal lymphopoietin(TSLP) have been proved to be a master switch for allergic inflammation. Based on these studies, we want to establish a mouse model of TSLP production based on Th2 cell-mediated allergic inflammation to explore the regulating mechanisms of YPFS on TSLP in Th2 cell-mediated allergic inflammation. Methods: Th2-type ACD mouse model: The mice were topically sensitized on the abdomens (induction phase) and elicited on its ears skin 6 day later (excitation phase) with FITC solution, and the ear swelling was measured to evaluate the allergic inflammation；A mouse model of TSLP production based on Th2 cell-mediated allergic inflammation (TSLP production model): the skin of the ear was sensitized on two consecutive days with FITC solution causing the production of TSLP；Mice were treated with YPFS extract，ELISA、Real-time PCR and Western-blotting were using to examine the mRNA and protein levels of TSLP\TSLPR and TLRs ect. Results: YPFS extract can attenuates Th2-type allergic inflammatory in mice；in TSLP production model, YPFS can inhibit the expression of TSLP、 TSLPR、TLRs and MyD88, So we deduce the possible mechanisms of YPFS to play a role of intervention is through TLRs- MyD88 dependent and independent pathway to reduce TSLP production.

Keywords: YPFS, TSLP, TLRs, Th2-type allergic contact dermatitis

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Authors: Adrian Reynaldo Sudirman, Siti Farida, Aisyah Aminy Maulidina, Caren Andika Surbakti

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Sedentary lifestyle and imbalance consumption pattern has made metabolic syndrome as the global time bomb phenomenon in the world. The increasing tendency of people in consuming high amount of fructose and cholesterol food has worsened this issue in the society. Pancreas steatosis become one of the most comorbid when early diagnosis and prompt treatment has not been applied on hyperglycemic and hyperlipidemic condition in metabolic syndrome patient. Gemfibrozil become the drug of choice to prevent this issue, yet the efficacy of this regiment was still questionable. Acalypha indica Linn. is the herb that has protective effect on hyperlipidemic and hyperglycemic condition. This study was aimed to compare therapeutic effect of gemfibrozil (G) and Acalypha indica Linn. (AI) on high fructose and cholesterol diet-induced pancreas steatosis in Sprague-Dawley mice. The post induction mice were divided into four groups: control, gemfibrozil, AI extract, and G+AI combination regiment. Each group received four weeks intervention. The result of statistical analysis using the One-Way ANOVA test and Tukey Post Hoc test showed significant decrease in pancreatic steatosis between the control group and administered Acalypha indica group (p = 0.004, 95% CI: 0.170-0.959) and the group administered with a combination of Gemfibrozil-Acalypha indica (p = 0.023, 95% CI: 0.537-0.813). The protective effect of Acalypha indica Linn. shows that this plant has the potential as therapeutic option in overcoming the condition of pancreas steatosis in metabolic syndrome.

Keywords: Acalypha Indica Linn., Cholesterol, Fructose, Gemfibrozil, Pancreas Steatosis

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Authors: Amir Aziz, Martin Tuner, Sebastian Verhelst, Oivind Andersson

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Partially Premixed Combustion (PPC) is a combustion concept which aims to simultaneously achieve high efficiency and low engine-out emissions. Extending the ignition delay to promote the premixing, has been recognized as one of the key factor to achieve PPC. Fuels with high octane number have been proven to be a good candidates to extend the ignition delay. In this work, E85 (85% ethanol) has been used as a PPC fuel. The aim of this work was to investigate a suitable injection strategy for PPC combustion fueled with E85 in a single-cylinder heavy-duty engine. Single and double injection strategy were applied with different injection timing and the ratio between different injection pulses was varied. The performance and emission were investigated at low load. The results show that the double injection strategy should be preferred for PPC fueled with E85 due to low emissions and high efficiency, while keeping the pressure raise rate at very low levels.

Keywords: E85, partially premixed combustion, injection strategy, performance and emission

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Authors: Hadi Adibi-Asl, Alireza Doosthosseini, Amir Taghavipour

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This paper studies the design of an adaptive control strategy to tune an active steering system for better drivability and maneuverability. In the first step, adaptive control strategy is applied to estimate the uncertain parameters on-line (e.g. cornering stiffness), then the estimated parameters are fed into the pole placement controller to generate corrective feedback gain to improve the steering system dynamic’s characteristics. The simulations are evaluated for three types of road conditions (dry, wet, and icy), and the performance of the adaptive pole placement control (APPC) are compared with pole placement control (PPC) and a passive system. The results show that the APPC strategy significantly improves the yaw rate and side slip angle of a bicycle plant model.

Keywords: adaptive control, active steering, pole placement, vehicle dynamics

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Authors: Walter Vera-Ortega, Idoia Busnadiego, Sam J. Wilson

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Introduction: Human Immunodeficiency Virus type 1 (HIV-1) is responsible for the acquired immunodeficiency syndrome (AIDS), a leading cause of death worldwide infecting millions of people each year. Despite intensive research in vaccine development, therapies against HIV-1 infection are not curative, and the huge genetic variability of HIV-1 challenges to drug development. Current animal models for HIV-1 research present important limitations, impairing the progress of in vivo approaches. Macaques require a CD8+ depletion to progress to AIDS, and the maintenance cost is high. Mice are a cheaper alternative but need to be 'humanized,' and breeding is not possible. The development of an HIV-1 clone able to replicate in mice is a challenging proposal. The lack of human co-factors in mice impedes the function of the HIV-1 accessory proteins, Tat and Rev, hampering HIV-1 replication. However, Tat and Rev function can be replaced by constitutive/chimeric promoters, codon-optimized proteins and the constitutive transport element (CTE), generating a novel HIV-1 clone able to replicate in mice without disrupting the amino acid sequence of the virus. By minimally manipulating the genomic 'identity' of the virus, we propose the generation of an HIV-1 clone able to replicate in mice to assist in antiviral drug development. Methods: i) Plasmid construction: The chimeric promoters and CTE copies were cloned by PCR using lentiviral vectors as templates (pCGSW and pSIV-MPCG). Tat mutants were generated from replication competent HIV-1 plasmids (NHG and NL4-3). ii) Infectivity assays: Retroviral vectors were generated by transfection of human 293T cells and murine NIH 3T3 cells. Virus titre was determined by flow cytometry measuring GFP expression. Human B-cells (AA-2) and Hela cells (TZMbl) were used for infectivity assays. iii) Protein analysis: Tat protein expression was determined by TZMbl assay and HIV-1 capsid by western blot. Results: We have determined that NIH 3T3 cells are able to generate HIV-1 particles. However, they are not infectious, and further analysis needs to be performed. Codon-optimized HIV-1 constructs are efficiently made in 293T cells in a Tat and Rev independent manner and capable of packaging a competent genome in trans. CSGW is capable of generating infectious particles in the absence of Tat and Rev in human cells when 4 copies of the CTE are placed preceding the 3’LTR. HIV-1 Tat mutant clones encoding different promoters are functional during the first cycle of replication when Tat is added in trans. Conclusion: Our findings suggest that the development of an HIV-1 Tat-Rev independent clone is challenging but achievable aim. However, further investigations need to be developed prior presenting our HIV-1 clone as a candidate model for research.

Keywords: codon-optimized, constitutive transport element, HIV-1, long terminal repeats, research model

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Authors: Josephine Hai, Jie Jiang, Karen M. Lyons

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Of the musculoskeletal tissues, tendon is least understood in terms of biological development. The current study examines Cysteine-rich angiogenic inducer 61, or CCN1, a member of the CCN family of secreted matricellular proteins that regulate cell behavior via intercellular signaling. Though CCN1 is notable in limiting fibrosis by inducing senescence in fibroblasts, little is known about its role in normal fibrous tissue, where it may be essential to the development of ECM-rich structures like tendons. We found that CCN1 knockout mice (using limb-specific Prx1-Cre) exhibited clubfoot and waddling gaits, a unique phenotype not described in any other mutant to date. Histological analysis showed that the Achilles and patellar tendons, where we previously found high CCN1 expression in adult reporter mice, were thicker and denser in the Prx1-Cre knockouts than in their wildtype littermates. We then hypothesized that CCN1 is required directly in tendon progenitor cells for normal tendon development and generated tendon-specific CCN1 knockout mice using Scx-Cre. We observed similar Achilles/patellar tendon morphology among the Scx-Cre and Prx1-Cre mutants, indicating that the phenotype is a direct result of CCN1’s loss in tendon. To further study phenotype onset and progression, we will histologically characterize these tendons across different developmental time-points. We will also perform RNA-seq and qPCR to analyze tenocyte gene expression and expect fibrotic marker upregulation in the Scx-Cre mutants if CCN1 is required to maintain a normal tendon phenotype. Thus, our study aims to elucidate the molecular mechanisms underlying tendon formation and maintenance. Understanding tendons at the most basic level invites novel approaches to tendon repair.

Keywords: development, matricellular, musculoskeletal, tendon

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Authors: Riddhi Shah

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Centre-state relations in India are a fascinating area of studies. The structure of the relationship has an effect on every single aspect of life as we know it in India. This paper is an attempt to study centre-state relations in the context of India’s maritime counter-terrorism strategy. Although the Government of India has not publicly stated its counter-terrorism strategy on the sea; intelligence, information sharing, crisis response, finances for internal security and the nation’s legislation for battling terrorism together comprise of India’s maritime-terrorism strategy. Through study of these areas, the paper argues that the centre-state divide has had systemic implications on India’s maritime security and has largely done more harm than good to collective initiatives that aspire to prevent future risk of terrorism from the sea or on the sea.

Keywords: counter-terrorism, maritime terrorism, India, federalism, centre-state relations

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Authors: Johanrik, Arini Aprilliani, Fikri Haikal, Diyas Yuca, Muhammad A. Latif, Edijanti Goenarwo, Nurita P. Sari

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Diarrhea is one of the leading causes of morbidity and mortality in many countries, as well as responsible for the deaths of millions of people each year. Previous research showed that the leaves, bark, and root bark of kedondong contains saponins, tannins, and flavonoids. Tannins have anti-diarrheal effects that work as the freeze of protein / astrigen, and may inhibit the secretion of chloride over the tannate bonding between protein in the intestines. Chemical compounds of flavonoids also have an effect as anti-diarrheal block receptors Cl ˉ in intestinal thus reducing the secretion of Cl ˉ to the intestinal lume. This research aims to know the anti-diarrheal activity of extracts kedondong leaf in mice Balb/C strain males in vivo. This research also proves kedondong leaves as an anti-diarrhea through trial efficacy of kedondong leaves as antisekretori and antimotilitas. This research using post-test only controlled group design. Analysis of statistical data normality and homogenity were tested by Kolmogorov Smirnov. If the data obtained homogenous then using ANOVA test. This research using ethanolic extracts kedondong leaf 200, 400 and 800 mg/kgBW to prove there is anti-diarrhea it makes into six treatment groups, for anti-secretory it makes into five treatment groups and anti-motility became five treatment groups. The result showed dose of ethanolic extracts kedondong leaf 800 mg/kgBW have significant value (p < 0.005). The conclusion from this extracts kedondong leaf research 800 mg/kgBW have pharmacological effects as antidiarrhea on Balb/C strain male mice with a mechanism of action as antisecretory and antimotility.

Keywords: anti-diarrhea, anti-secretory, anti-motility, kedondong leaf

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