Search results for: drug policy

Authors: Patrick T. I. Lam, Wenjing Yang

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A smart city project embraces benefits and costs which can be classified under direct and indirect categories. Externalities come into the picture, but they are often difficult to quantify. Despite this barrier, policy makers need to carry out cost-benefit analysis to justify the huge investments needed to make a city smart. The recent trend is towards the engagement of the private sector to utilize their resources and expertise, especially in the Information and Communication Technology (ICT) areas, where innovations blossom. This study focuses on the identification of costs (on a life cycle basis) and benefits associated with smart city project developments based on a comprehensive literature review and case studies, where public-private partnerships would warrant consideration, the related costs and benefits are highlighted. The findings will be useful for policy makers of cities.

Keywords: smart city projects, costs and benefits, identification, public-private partnerships

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Authors: Gaafar Muhammed, N. T. Ersoy

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The role of electricity in the economic development of any country is undeniable. The main goal of utilizing renewable sources in electricity generation, especially in the emerging countries, is to improve electricity access, economic development and energy sustainability. Germany’s recent transition from conventional to renewable energy technologies is overwhelming, this might not be associated with its abundant natural resources but owing to the policies in place. In line with the fast economic and technological developments recorded in recent years, Germany currently produces approximately 1059 GW of its energy from renewable sources. Hence, at the end of 2016, Germany is among the world leaders in terms of installed renewable energy capacity. As one of the most important factors that lead to renewable energy utilization in any nation is an effective policy, this study aims at examining the effect of policies on renewable energy (RE) development in Germany. Also, the study will focus on the evolution of the adopted feed-in tariff policies, as this evolution has affected the renewable energy capacity in Germany over a period of 15 years (2000 to 2015). The main contribution of the study is to establish a link between the feed-in tariff and the increase of RE in Germany’s energy mix. This is done by analyzing the characteristics of various feed-in tariff mechanisms adopted through the years. These characteristics include the feed-in-tariff rate, degression, special conditions, supported technology, etc. Then, the renewable energy development in Germany has been analyzed through the years along with the targets and the progress in reaching these targets. The study reveals that Germany’s renewable energy support policies (especially feed-in tariff) lead to several benefits and contribute towards the targets existing for renewable energy.

Keywords: feed-in tariff, Germany, policy, penewable energy

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Authors: Fouzia Perveen, Rumana Qureshi

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The presently studied twelve anticancer drugs are the cytotoxic agents which inhibit the replication of DNA and activity of enzymes involved in DNA replication namely topoisomerase-II, polymerase and helicase and have shown remarkable anticancer activity in clinical trials. In this study, we performed molecular docking studies of twelve antitumor drugs against DNA and DNA enzymes in the presence and absence of ascorbic acid (AA) and developed the quantitative structure-activity relationship (QSAR) model for anticancer activity screening. A number of electronic and steric descriptors were calculated using MOE software package. QSAR was established showing a correlation of binding strength with various physicochemical descriptors. Out of these twelve, eight cytotoxic drugs were tested on Non-Small Cell Lung Cancer cell lines (H-157 and H-1299) in the absence and presence of ascorbic acid and experimental IC50 values were calculated. From the docking studies, binding constants were calculated indicating the strength of drug-DNA and drug-enzyme complex formation and it was correlated to the IC50 values (both experimental and theoretical). These results can offer useful references for directing the molecular design of DNA enzyme inhibitor with improved anticancer activity.

Keywords: ascorbic acid, binding constant, cytotoxic agents, cell culture, DNA, DNA enzymes, molecular docking

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Authors: Olumide Simeon Ogunnusi, Shukor Abd Razak, Michael Kolade Adu

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Inter-agent communication manager facilitates communication among mobile agents via message passing mechanism. Until now, all Foundation for Intelligent Physical Agents (FIPA) compliant agent systems are capable of exchanging messages following the standard format of sending and receiving messages. Previous works tend to secure messages to be exchanged among a community of collaborative agents commissioned to perform specific tasks using cryptosystems. However, the approach is characterized by computational complexity due to the encryption and decryption processes required at the two ends. The proposed approach to secure agent communication allows only agents that are created by the host agent server to communicate via the agent communication channel provided by the host agent platform. These agents are assumed to be harmless. Therefore, to secure communication of legitimate agents from intrusion by external agents, a 2-phase policy enforcement system was developed. The first phase constrains the external agent to run only on the network server while the second phase confines the activities of the external agent to its execution environment. To implement the proposed policy, a controller agent was charged with the task of screening any external agent entering the local area network and preventing it from migrating to the agent execution host where the legitimate agents are running. On arrival of the external agent at the host network server, an introspector agent was charged to monitor and restrain its activities. This approach secures legitimate agent communication from Man-in-the Middle and Replay attacks.

Keywords: agent communication, introspective agent, isolation of agent, policy enforcement system

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Authors: Mathumalar Loganathan, Lina Syazana, Bryony Dean Franklin

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Background: The therapeutic benefit of self-administered medication for long-term use is limited by an average 50% non-adherence rate. Patient forgetfulness is a common factor in unintentional non-adherence. With a growing ageing population, strategies to improve self-administration of medication adherence are essential. Our aim was to review systematically the effects of interventions to optimise self-administration of medication. Method: Database searched were MEDLINE, EMBASE, PsynINFO, CINAHL from 1980 to 31 October 2013. Search terms included were ‘self-administration’, ‘self-care’, ‘medication adherence’, and ‘intervention’. Two independent reviewers undertook screening and methodological quality assessment, using the Downs and Black rating scale. Results: The search strategy retrieved 6 studies that met the inclusion and exclusion criteria. Three intervention strategies were identified: self-administration medication programme (SAMP), nursing education and medication packaging (pill calendar). A nursing education programme focused on improving patients’ behavioural self-management of drug prescribing. This was the most studied area and three studies highlighting an improvement in self-administration of medication. Conclusion: Results are mixed and there is no one interventional strategy that has proved to be effective. Nevertheless, self-administration of medication programme seems to show most promise. A multi-faceted approach and clearer policy guideline are likely to be required to improve prescribing for these vulnerable patients. Mixed results were found for SAMP. Medication packaging (pill calendar) was evaluated in one study showing a significant improvement in self-administration of medication. A meta-analysis could not be performed due to heterogeneity in the outcome measures.

Keywords: self-administered medication, intervention, prescribing, older patients

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Authors: Maryam Ziaee, Himanshu Shee, Amrik Sohal

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Big Data Analytics (BDA) in supply chain management has recently drawn the attention of academics and practitioners. Big data refers to a massive amount of data from different sources, in different formats, generated at high speed through transactions in business environments and supply chain networks. Traditional statistical tools and techniques find it difficult to analyse this massive data. BDA can assist organisations to capture, store, and analyse data specifically in the field of supply chain. Currently, there is a paucity of research on BDA in the pharmaceutical supply chain context. In this research, the Australian pharmaceutical supply chain was selected as the case study. This industry is highly significant since the right medicine must reach the right patients, at the right time, in right quantity, in good condition, and at the right price to save lives. However, drug shortages remain a substantial problem for hospitals across Australia with implications on patient care, staff resourcing, and expenditure. Furthermore, a massive volume and variety of data is generated at fast speed from multiple sources in pharmaceutical supply chain, which needs to be captured and analysed to benefit operational decisions at every stage of supply chain processes. As the pharmaceutical industry lags behind other industries in using BDA, it raises the question of whether the use of BDA can improve transparency among pharmaceutical supply chain by enabling the partners to make informed-decisions across their operational activities. This presentation explores the impacts of BDA on supply chain management. An exploratory qualitative approach was adopted to analyse data collected through interviews. This study also explores the BDA potential in the whole pharmaceutical supply chain rather than focusing on a single entity. Twenty semi-structured interviews were undertaken with top managers in fifteen organisations (five pharmaceutical manufacturers, five wholesalers/distributors, and five public hospital pharmacies) to investigate their views on the use of BDA. The findings revealed that BDA can enable pharmaceutical entities to have improved visibility over the whole supply chain and also the market; it enables entities, especially manufacturers, to monitor consumption and the demand rate in real-time and make accurate demand forecasts which reduce drug shortages. Timely and precise decision-making can allow the entities to source and manage their stocks more effectively. This can likely address the drug demand at hospitals and respond to unanticipated issues such as drug shortages. Earlier studies explore BDA in the context of clinical healthcare; however, this presentation investigates the benefits of BDA in the Australian pharmaceutical supply chain. Furthermore, this research enhances managers’ insight into the potentials of BDA at every stage of supply chain processes and helps to improve decision-making in their supply chain operations. The findings will turn the rhetoric of data-driven decision into a reality where the managers may opt for analytics for improved decision-making in the supply chain processes.

Keywords: big data analytics, data-driven decision, pharmaceutical industry, supply chain management

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Authors: Jevonte Abioye, Dylan Savary

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The aim of this research is to present a disaggregated geostatistical analysis of the subnational provincial trends of child mortality variation in Zimbabwe from a child health policy perspective. Soon after gaining independence in 1980, the government embarked on efforts towards promoting equitable health care, namely through the provision of primary health care. Government intervention programmes brought hope and promise, but achieving equity in primary health care coverage was hindered by previous existing disparities in maternal health care disproportionately concentrated in urban settings to the detriment of rural communities. The article highlights policies and programs adopted by the government during the millennium development goals period between 1990-2015 as a response to the inequities that characterised the country’s maternal health care. A longitudinal comparative method for a spatial variation on child mortality rates across provinces is developed based on geostatistical analysis. Cross-sectional and time-series data was extracted from the World Health Organisation (WHO) global health observatory data repository, demographic health survey reports, and previous academic and technical publications. Results suggest that although health care policy was uniform across provinces, not all provinces received the same antenatal and perinatal services. Accordingly, provincial rates of child mortality growth between 1994 and 2015 varied significantly. Evidence on the trends of child mortality rates and maternal health policies in Zimbabwe can be valuable for public child health policy planning and public service delivery design both in Zimbabwe and across developing countries pursuing the sustainable development agenda.

Keywords: antenatal care, perinatal care, infant mortality rate, neonatal mortality rate, under-five mortality rate, millennium development goals, sustainable development agenda

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Authors: S. Halioui, I. Arikan, M. Schmidt

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Tourism sector in Tunisia faces several problems that range from economic challenges to environmental degradation and social instability. These problems have been intensified because of the increased competition in the tourism market, the political instability, financial crises, and recently terrorism problems have aggravated the situation. As a consequence, a new framework that promotes sustainable tourism in the country and increases its competitiveness is urgently needed. Planning for sustainable tourism sector requires the integration of complex interactions between economic, social and environmental aspects. Sustainable tourism principles can be implemented with the help of Strategic Environmental Assessment (SEA) process, which ensures the full integration of economic, social and environmental considerations while planning for the tourism sector in Tunisia. Results of the paper have broad implications for policy makers and tourism professionals.

Keywords: sustainable tourism, strategic environmental assessment, tourism planning, policy

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Authors: Klazina T. Havinga, Hilde R. H. de Geus

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Introduction: Pre-operative coagulation management of Apixaban prescribed patients, a new oral anticoagulant (a factor Xa inhibitor), is difficult, especially when chronic kidney disease (CKD) causes drug overdose. Apixaban is not dialyzable due to its high level of protein binding. An antidote, Andexanet α, is available but expensive and has an unfavorable short half-life. We report the successful extracorporeal removal of Apixaban prior to emergency surgery with the CytoSorb® Hemoadsorption device. Methods: A 89-year-old woman with CKD, with an Apixaban prescription for atrial fibrillation, was presented at the ER with traumatic rib fractures, a flail chest, and an unstable spinal fracture (T12) for which emergency surgery was indicated. However, due to very high Apixaban levels, this surgery had to be postponed. Based on the Apixaban-specific anti-factor Xa activity (AFXaA) measurements at admission and 10 hours later, complete clearance was expected after 48 hours. In order to enhance the Apixaban removal and reduce the time to operation, and therefore reduce pulmonary complications, CRRT with CytoSorb® cartridge was initiated. Apixaban-specific anti-factor Xa activity (AFXaA) was measured frequently as a substitute for Apixaban drug concentrations, pre- and post adsorber, in order to calculate the adsorber-related clearance. Results: The admission AFXaA concentration, as a substitute for Apixaban drug levels, was 218 ng/ml, which decreased to 157 ng/ml after ten hours. Due to sustained anticoagulation effects, surgery was again postponed. However, the AFXaA levels decreased quickly to sub-therapeutic levels after CRRT (Multifiltrate Pro, Fresenius Medical Care, Blood flow 200 ml/min, Dialysate Flow 4000 ml/h, Prescribed renal dose 51 ml-kg-h) with Cytosorb® connected in series into the circuit was initiated (within 5 hours). The adsorber-related (indirect) Apixaban clearance was calculated every half hour (Cl=Qe * (AFXaA pre- AFXaA post/ AFXaA pre) with Qe=plasma flow rate calculated with Ht=0.38 and system blood flow rate 200 ml-min): 100 ml/min, 72 ml/min and 57 ml/min. Although, as expected, the adsorber-related clearance decreased quickly due to saturation of the beads, still the reduction rate achieved resulted in a very rapid decrease in AFXaA levels. Surgery was ordered and possible within 5 hours after Cytosorb initiation. Conclusion: The CytoSorb® Hemoadsorption device enabled rapid correction of Apixaban associated anticoagulation.

Keywords: Apixaban, CytoSorb, emergency surgery, Hemoadsorption

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Authors: Lacramioara Ochiuz, Aurelia Vasile, Iulian Stoleriu, Cristina Ghiciuc, Maria Ignat

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Topical administration of chemotherapeutic agents (eg. carmustine, bexarotene, mechlorethamine etc.) in local treatment of cutaneous T-cell lymphoma (CTCL) is accompanied by multiple side effects, such as contact hypersensitivity, pruritus, skin atrophy or even secondary malignancies. A known method of reducing the side effects of anticancer agent is the development of modified drug release systems using drug incapsulation in biocompatible nanoporous inorganic matrices, such as mesoporous MCM-41 silica. Mesoporous MCM-41 silica is characterized by large specific surface, high pore volume, uniform porosity, and stable dispersion in aqueous medium, excellent biocompatibility, in vivo biodegradability and capacity to be functionalized with different organic groups. Therefore, MCM-41 is an attractive candidate for a wide range of biomedical applications, such as controlled drug release, bone regeneration, protein immobilization, enzymes, etc. The main advantage of this material lies in its ability to host a large amount of the active substance in uniform pore system with adjustable size in a mesoscopic range. Silanol groups allow surface controlled functionalization leading to control of drug loading and release. This study shows (I) the amino-grafting optimization of mesoporous MCM-41 silica matrix by means of co-condensation during synthesis and post-synthesis using APTES (3-aminopropyltriethoxysilane); (ii) loading the therapeutic agent (carmustine) obtaining a modified drug release systems; (iii) determining the profile of in vitro carmustine release from these systems; (iv) assessment of carmustine release kinetics by fitting on four mathematical models. Obtained powders have been described in terms of structure, texture, morphology thermogravimetric analysis. The concentration of the therapeutic agent in the dissolution medium has been determined by HPLC method. In vitro dissolution tests have been done using cell Enhancer in a 12 hours interval. Analysis of carmustine release kinetics from mesoporous systems was made by fitting to zero-order model, first-order model Higuchi model and Korsmeyer-Peppas model, respectively. Results showed that both types of highly ordered mesoporous silica (amino grafted by co-condensation process or post-synthesis) are thermally stable in aqueous medium. In what regards the degree of loading and efficiency of loading with the therapeutic agent, there has been noticed an increase of around 10% in case of co-condensation method application. This result shows that direct co-condensation leads to even distribution of amino groups on the pore walls while in case of post-synthesis grafting many amino groups are concentrated near the pore opening and/or on external surface. In vitro dissolution tests showed an extended carmustine release (more than 86% m/m) both from systems based on silica functionalized directly by co-condensation and after synthesis. Assessment of carmustine release kinetics revealed a release through diffusion from all studied systems as a result of fitting to Higuchi model. The results of this study proved that amino-functionalized mesoporous silica may be used as a matrix for optimizing the anti-cancer topical therapy by loading carmustine and developing prolonged-release systems.

Keywords: carmustine, silica, controlled, release

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Authors: Chijioke Oliver Nwodoh, Jonah Ikechukwu Eze, Loretta Chika Ukwuaba, Ifeoma Ndubuisi, Ada Carol Nwaneri, Ijeoma Lewechi Okoronkwo

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Presence of nursing workforce with unequal qualification and status in Nigeria has undermined the growth of nursing profession in the country. Upgrading of the existing basic and post-basic nursing schools to degree-awarding institutions in Nigeria is a way-forward to solving this inequality problem and Nigeria teaching hospitals are in vantage position for this project due to the already existing supportive structure and manpower in those hospitals. What the nurse trainers and the stakeholders of the teaching hospitals may hold for or against the upgrading is a determining factor for the upgrading project, but that is not clear and has not been investigated in Nigeria. The study investigated the perception of nurse trainers and stakeholders of teaching hospitals in Enugu State of Nigeria on the obstacles and ways-forward to upgrading nursing schools to degree-awarding institutions in Nigeria. The study specifically elicited what the subjects may view as obstacles to upgrading basic and post-basic nursing schools to degree-awarding institutions in Nigeria and ascertained their suggestions on the possible ways of overcoming the obstacles. By utilizing cross-sectional descriptive design and a purposive sampling procedure, 78 accessible subjects out of a total population of 87 were used for the study. The generated data from the subjects were analyzed using frequencies, percentages and mean for the research questions and Pearson’s chi-square for the hypotheses, with the aid of Statistical Package for Social Sciences Version 20.0. The result showed that lack of extant policy, fund, and disunity among policy makers and stakeholders of nursing profession are the main obstacles to the upgrading. However, the respondents did not see items like: stakeholders and nurse trainers of basic and post-basic schools of nursing; fear of admitting and producing poor quality nurses; and so forth, as obstacles to the upgrading project. Institution of the upgrading policy by Nursing and Midwifery Council of Nigeria, funding, awareness creation for the upgrading and unison among policy makers and stakeholders of nursing profession are the major possible ways to overcome the obstacles. The difference in the subjects’ perceptions between the two hospitals was found to be statistically insignificant (p > 0.05). It is recommended that the policy makers and stakeholders of nursing in Nigeria should unite and liaise with Federal Ministries of Health and Education for modalities and actualization of upgrading nursing schools to degree-awarding institutions in Nigeria.

Keywords: nurse trainers, obstacles, perception, stakeholders, teaching hospital, upgrading basic nursing schools, ways-forward

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Authors: Olgun Akbulut

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Turkey has entered in the European human rights monitoring in the early 1990s. Since then many improvements have been observed in domestic law. However, one area stays the least developed one: gender discrimination. Although the country is proud of the fact that electoral rights for women were recognized in Turkey even before many developed countries in the west, interestingly the first Turkish case where the European Court of Human Rights (ECrtHR) found discrimination concerned gender discrimination. With the proposed paper, the author is willing to determine and analyze the findings of the ECrtHR in cases decided against Turkey concerning gender discrimination, identify whether Turkish public institutions display coordination in engagement or disengagement in implementing the judgments where the ECrtHR found discrimination on the basis of gender and evaluate the effectiveness of the Court's jurisprudence on Turkish gender policy.

Keywords: equality, gender discrimination, human rights, Turkey

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Authors: Aussara Panya, Nunghathai Sawasdee, Mutita Junking, Chatchawan Srisawat, Kiattawee Choowongkomon, Pa-Thai Yenchitsomanus

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Dengue virus (DENV) infection is a global public health problem with approximately 100 million infected cases a year. Presently, there is no approved vaccine or effective drug available; therefore, the development of anti-DENV drug is urgently needed. The clinical reports revealing the positive association between the disease severity and viral titer has been reported previously suggesting that the anti-DENV drug therapy can possibly ameliorate the disease severity. Although several anti-DENV agents showed inhibitory activities against DENV infection, to date none of them accomplishes clinical use in the patients. The surface envelope (E) protein of DENV is critical for the viral entry step, which includes attachment and membrane fusion; thus, the blocking of envelope protein is an attractive strategy for anti-DENV drug development. To search the safe anti-DENV agent, this study aimed to search for novel peptide inhibitors to counter DENV infection through the targeting of E protein using a structure-based in silico design. Two selected strategies has been used including to identify the peptide inhibitor which interfere the membrane fusion process whereby the hydrophobic pocket on the E protein was the target, the destabilization of virion structure organization through the disruption of the interaction between the envelope and membrane proteins, respectively. The molecular docking technique has been used in the first strategy to search for the peptide inhibitors that specifically bind to the hydrophobic pocket. The second strategy, the peptide inhibitor has been designed to mimic the ectodomain portion of membrane protein to disrupt the protein-protein interaction. The designed peptides were tested for the effects on cell viability to measure the toxic to peptide to the cells and their inhibitory assay to inhibit the DENV infection in Vero cells. Furthermore, their antiviral effects on viral replication, intracellular protein level and viral production have been observed by using the qPCR, cell-based flavivirus immunodetection and immunofluorescence assay. None of tested peptides showed the significant effect on cell viability. The small peptide inhibitors achieved from molecular docking, Glu-Phe (EF), effectively inhibited DENV infection in cell culture system. Its most potential effect was observed for DENV2 with a half maximal inhibition concentration (IC50) of 96 μM, but it partially inhibited other serotypes. Treatment of EF at 200 µM on infected cells also significantly reduced the viral genome and protein to 83.47% and 84.15%, respectively, corresponding to the reduction of infected cell numbers. An additional approach was carried out by using peptide mimicking membrane (M) protein, namely MLH40. Treatment of MLH40 caused the reduction of foci formation in four individual DENV serotype (DENV1-4) with IC50 of 24-31 μM. Further characterization suggested that the MLH40 specifically blocked viral attachment to host membrane, and treatment with 100 μM could diminish 80% of viral attachment. In summary, targeting the hydrophobic pocket and M-binding site on the E protein by using the peptide inhibitors could inhibit DENV infection. The results provide proof of-concept for the development of antiviral therapeutic peptide inhibitors to counter DENV infection through the use of a structure-based design targeting conserved viral protein.

Keywords: dengue virus, dengue virus infection, drug design, peptide inhibitor

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Authors: Ying Sun, Ji-wu Wang

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The establishment of a city is the result of the accumulation of local historical and cultural heritage and the sublimation of settlements. Take history as a mirror, it’s known how the things rise and fall. Based on the perspective of history, the development of the ancient city of Wenzhou was combed, and the urban development history of Wenzhou in 2200 could be divided into seven stages. This paper mainly studies the four stages of germination, formation, initial development and tortuous development, explores the external and internal driving forces of urban development and the structural evolution of urban layout, and discusses how the ancient Wenzhou evolved from a remote town to an important coastal port city. This paper finds that the most important factors affecting the development of ancient cities in Wenzhou are war, policy and geographical environment, and then points out the importance of urban policies to the rise and fall of cities.

Keywords: ancient city development, history, Wenzhou city, city policy

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Authors: Sundaram Arulmozhiraja, Kanade Shimizu, Yuta Yamamoto, Satoshi Ichikawa, Maenaka Katsumi, Hiroaki Tokiwa

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Drug discovery is shifting from small molecule based drugs targeting local active site to middle molecules (MM) targeting large, flat, and groove-shaped binding sites, for example, protein-protein interface because at least half of all targets assumed to be involved in human disease have been classified as “difficult to drug” with traditional small molecules. Hence, MMs such as peptides, natural products, glycans, nucleic acids with various high potent bioactivities become important targets for drug discovery programs in the recent years as they could be used for ‘undruggable” intracellular targets. Cell membrane permeability is one of the key properties of pharmacodynamically active MM drug compounds and so evaluating this property for the potential MMs is crucial. Computational prediction for cell membrane permeability of molecules is very challenging; however, recent advancement in the molecular dynamics simulations help to solve this issue partially. It is expected that MMs with high membrane permeability will enable drug discovery research to expand its borders towards intracellular targets. Further to understand the chemistry behind the permeability of MMs, it is necessary to investigate their conformational changes during the permeation through membrane and for that their interactions with the membrane field should be studied reliably because these interactions involve various non-bonding interactions such as hydrogen bonding, -stacking, charge-transfer, polarization dispersion, and non-classical weak hydrogen bonding. Therefore, parameters-based classical mechanics calculations are hardly sufficient to investigate these interactions rather, quantum mechanical (QM) calculations are essential. Fragment molecular orbital (FMO) method could be used for such purpose as it performs ab initio QM calculations by dividing the system into fragments. The present work is aimed to study the cell permeability of middle molecules using molecular dynamics simulations and FMO-QM calculations. For this purpose, a natural compound syringolin and its analogues were considered in this study. Molecular simulations were performed using NAMD and Gromacs programs with CHARMM force field. FMO calculations were performed using the PAICS program at the correlated Resolution-of-Identity second-order Moller Plesset (RI-MP2) level with the cc-pVDZ basis set. The simulations clearly show that while syringolin could not permeate the membrane, its selected analogues go through the medium in nano second scale. These correlates well with the existing experimental evidences that these syringolin analogues are membrane-permeable compounds. Further analyses indicate that intramolecular -stacking interactions in the syringolin analogues influenced their permeability positively. These intramolecular interactions reduce the polarity of these analogues so that they could permeate the lipophilic cell membrane. Conclusively, the cell membrane permeability of various middle molecules with potent bioactivities is efficiently studied using molecular dynamics simulations. Insight of this behavior is thoroughly investigated using FMO-QM calculations. Results obtained in the present study indicate that non-bonding intramolecular interactions such as hydrogen-bonding and -stacking along with the conformational flexibility of MMs are essential for amicable membrane permeation. These results are interesting and are nice example for this theoretical calculation approach that could be used to study the permeability of other middle molecules. This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 18ae0101047.

Keywords: fragment molecular orbital theory, membrane permeability, middle molecules, molecular dynamics simulation

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Authors: G. Erkomaishvili, M. Kobalava, T. Lazariashvili, N. Damenia

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Current state of foreign direct investment (FDI) in Georgia is analyzed and evaluated in the paper, the existing legislative background for regulating investments and stimulating policies to attract investments are shown. It is noted that in developing countries encouragement of investment activity, support and implementation are of the most important tasks, implying a consistent investment policy, investor-friendly tax regime and the legal system, reducing administrative barriers and restrictions, fare competitive conditions and business development infrastructure. The work deals with the determining factor of FDIs and the main directions of stimulation, as well as prospective industries where new investments are needed. Contributing and hindering factors and stimulating measures are analyzed. As a result of the research, the direct and indirect factors attracting FDI have been identified. Facilitating factors to FDI inflow are as follows: simplicity of starting business, geopolitical location, low taxes, access to credit, ease of ownership registration, natural resources, low burden of regulations, low level of corruption and low crime rates. Hindering factors to FDI inflow are as follows: small market, lack of policy for attracting investments, low qualification of the workforce (despite the large number of unemployed people it is difficult to find workers with necessary special skills and qualifications), high interest rates, instability of national currency exchange rate, presence of conflict zones within the country and so forth.

Keywords: foreign direct investment, investor, investment attracting marketing policies, reinvestment

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Authors: Gift Salawa, Perkins Erhijakpor, Henry Ukwu

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This study will explore child labour issues in Nigeria because it is capable of affecting the physical and general well-being of children who perform hazardous work. This feat will be achieved through qualitative research methodology. Data collection shall be elicited by oral interviews and documental content analysis to delve on the application of the Convention on the Rights of the Child (CRC), International Labour Organization ILO and Geneva Convention relating to child labour practices in Nigeria. This will include the relevance of present domestic laws relating to child labour as implemented in Nigeria, together with factors that contribute to the practice of child labour in the country. The oral interview data analysis will be performed by breaking the interview data into significant statements and themes. This shall be done by comparing and determining the commonalities that are prevalent in the participants’ views regarding child labour menace in Nigeria. Presumably, findings from this study shall unveil that a poor educational policy, a widespread poverty level which is mostly prevalent amongst families in the rural areas of the country, a lack of employment for adults, have led to the ineffectiveness of the local child labour laws in Nigeria. These has in turn culminated into a somewhat non-implementation of the international laws of the CRC, ILO and Geneva Declaration on child labour to which the Nigerian government is a signatory. Based on the finding, this study will calls on the government of Nigeria to extend its free educational policy from the elementary, secondary to tertiary educations. The government also has to ensure that offenders of children’s rights should face a severe punishment.

Keywords: child labour, educational policy, human right, protection right

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Authors: Sadaf Ilyas, Saba Riaz

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The extensive use of antibiotics has led to increases emergence of antibiotic-resistant organisms. Pseudomonas is a notorious opportunistic pathogen involoved in nosocomial infections and exhibit innate resistance to many antibiotics. The present study was conducted to assess the prevalence, levels of antimicrobial susceptibility and resistance mechanisms of Pseudomonas. A total of thirty clinical strains of Pseudomonas were isolated from different clinical sites of infection. All clinical specimens were collected from Chughtais Lahore Lab. Jail road, during 8-07-2010 to 11-01-2011. Biochemical characterization was done using routine biochemical tests. Antimicrobial susceptibility was determined by Kirby-Baeur method. The plasmids were isolated from all the strains and digested with restriction enzyme PstI and EcoRI. Transfer of Multi-resistance plasmid was checked via transformation and conjugation to confirm the plasmid mediated resistance to antibiotics. The prevalence of Pseudomonas in clinical specimens was found out to be 14% of all bacterial infections. IPM has shown to be the most effective drug against Pseudomonas followed by CES, PTB and meropenem, wheareas most of the Pseudomonas strains have developed significant resistance against Penicillins and some Cephalasporins. Antibiotic resistance determinants were carried by plasmids, as they conferred resistance to transformed K1 strains. The isolates readily undergo conjugation, transferring the resistant genes to other strains, illustrating the high rates of cross infection and nosocomial infection in the immunocompromised patients.

Keywords: pseudomonas, antibiotics, drug resistance, horizontal gene transfer

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Authors: S. Mazifah, A. Azahan, A. Kadir

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This paper aims to examine the relationship between the needs of ex-landfill redevelopment and the adequacy of open space provision in the context of sustainable urban development planning in Malaysia as seen from the perspective of the National Urban Policy. With a specific focus on the Action Plan DPN6 and DPN9, ex-landfill redevelopment needs and provision of open space are detailed to identify their potential and constraints in the development of sustainable cities. As a result, this paper found a link between the needs of urban ex-landfill redevelopment and approach to provide adequate urban open space. Through the proposal of the development of public park at urban ex-landfill sites, the needs of ex-landfill redevelopment and the adequacy of urban open space provision is being 'united' and translated as an approach to create a sustainable urban development in Malaysia.

Keywords: ex-landfill redevelopment, open spaces, National Urban Policy, sustainable urban development

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Authors: Bruno Baptista, Andreia S. R. Oliveira, Patricia V. Mendonca, Jorge F. J. Coelho, Fani Sousa

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Drug delivery systems are designed to allow adequate protection and controlled delivery of drugs to specific locations. These systems aim to reduce side effects and control the biodistribution profile of drugs, thus improving therapeutic efficacy. This study involved the synthesis of polymeric nanoparticles, based on amphiphilic diblock copolymers, comprising a biocompatible, poly (oligo (ethylene oxide) methyl ether methacrylate (POEOMA) as hydrophilic segment and a pH-sensitive block, the poly (2-diisopropylamino)ethyl methacrylate) (PDPA). The objective of this work was the development of polymeric pH-responsive nanoparticles to encapsulate and carry small RNAs as a model to further develop non-coding RNAs delivery systems with therapeutic value. The responsiveness of PDPA to pH allows the electrostatic interaction of these copolymers with nucleic acids at acidic pH, as a result of the protonation of the tertiary amine groups of this polymer at pH values below its pKa (around 6.2). Initially, the molecular weight parameters and chemical structure of the block copolymers were determined by size exclusion chromatography (SEC) and nuclear magnetic resonance (1H-NMR) spectroscopy, respectively. Then, the complexation with small RNAs was verified, generating polyplexes with sizes ranging from 300 to 600 nm and with encapsulation efficiencies around 80%, depending on the molecular weight of the polymers, their composition, and concentration used. The effect of pH on the morphology of nanoparticles was evaluated by scanning electron microscopy (SEM) being verified that at higher pH values, particles tend to lose their spherical shape. Since this work aims to develop systems for the delivery of non-coding RNAs, studies on RNA protection (contact with RNase, FBS, and Trypsin) and cell viability were also carried out. It was found that they induce some protection against constituents of the cellular environment and have no cellular toxicity. In summary, this research work contributes to the development of pH-sensitive polymers, capable of protecting and encapsulating RNA, in a relatively simple and efficient manner, to further be applied on drug delivery to specific sites where pH may have a critical role, as it can occur in several cancer environments.

Keywords: drug delivery systems, pH-responsive polymers, POEOMA-b-PDPA, small RNAs

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Authors: Eugenio Ferrer Santiago

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The growing complexities of the modern world on high-end gadgets, software applications, scams, identity theft, and Artificial Intelligence (AI) make the “uninformed” the weak and vulnerable to be victims of cybercrimes. Artificial Intelligence is not a new thing in our daily lives; the principles of database management, logical programming, and garbage in and garbage out are all connected to AI. The Philippines had in place legal safeguards against the abuse of cyberspace, but self-regulation of key industry players and self-protection by individuals are primordial to attain the success of these initiatives. Data protection, Data Privacy, and Research Ethics must work hand in hand during the policy process in the course of urban planning practice in different environments. This paper focuses on the interconnection of data protection, data privacy, and research ethics in coming up with clear-cut policies against perpetrators in the urban planning professional practice relevant in sustainable communities and smart cities. This paper shall use expository methodology under qualitative research using secondary data from related literature, interviews/blogs, and the World Wide Web resources. The claims and recommendations of this paper will help policymakers and implementers in the policy cycle. This paper shall contribute to the body of knowledge as a simple treatise and communication channel to the reading community and future researchers to validate the claims and start an intellectual discourse for better knowledge generation for the good of all in the near future.

Keywords: data privacy, data protection, urban planning, research ethics

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Authors: Hasan Al Banna, Nazmus Sakib, Anjan Roy

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From the perspective of the underdeveloped countries such as Bangladesh, health issue can readily be pointed out as the most demanding but the least promoted concern due to lack of initiatives from both government and NGOs. Furthermore an worldwide scenario is that most death and suffering from various pathogenic and non-pathogenic diseases occur due to delay diagnosis, and this happen for the lacking of regular health check-up facility or tradition. In this epistle, an innovative proposal on social business can be introduced to ensure the one-stop medical facility to the door-step of the rural society and create jobs for the educated rural youths to serve their own people. To illustrate the policy, this newly proposed organization will work as a health club which will offer a life-time membership to villagers within a very affordable fee of 250 BDT (2.63 Euro) per month. In this package the members will get the facility of tri-monthly full health check-up by specialist doctors, a health record book and computerized health database for each member and anytime medical consultancy for the members only. We will also organize free medical campaign and workshops on nutrition, sanitation, adulteration, pregnancy-care, child-health etc with the assistance of different sponsors. Among other services that will be provided on payment include emergency ambulance facility in low rents, quality diagnostic lab and 24-hour dispensary facility. Likewise, this policy will involve local educated people by recruiting them after providing intensive courses on nursing and other medical instrumental skills. Henceforth, the engagement of local youth will make the program more acceptable to the rural community. In the later part of this paper, a survey report on Daragram union of Manikganj district, Bangladesh, having population above 25000, will be presented to delineate the scenario how this policy can repay the initial capital expense of BDT 7 million (around 73381 Euro) within 5 years and how I can realistically earn handsome revenue from the first month of business. To recapitulate, this policy is very promising to enlighten the underprivileged community by providing health assurance, and alleviating unemployment besides the investor’s financial profit.

Keywords: create job for the rural people, handsome financial profit, quality health services, underprivileged areas of underdeveloped countries

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Authors: Zhaojunfeng

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Driven by the national policy of "East Data and Western Calculation", the computing first network will attract a new wave of development. As the foundation of the development of the computing first network, the computing force bearer network has become the key direction of technology research and development in the industry. This article will analyze typical computing force application scenarios and bearing requirements and sort out the SLA indicators of computing force applications. On this basis, this article carries out research and discussion on the key technologies of computing force bearer network in a slice packet network, and finally, gives evolution policy for SPN computing force bearer network to support the development of SPN computing force bearer network technology and network deployment.

Keywords: component-computing force bearing, bearing requirements of computing force application, dual-SLA indicators for computing force applications, SRv6, evolution strategies

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Authors: Carolina B. A. Morais, Antonio Bob Santos

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In order to determine how innovation procurement can strengthen public efficiency and foster the modernization of public services, while at the same time promoting the opening of new private markets, this paper aims to present the two key instruments for the practice of innovation procurement at a European, national, and regional level – Pre-Commercial Procurement (PCP), and Public Procurement of Innovative Solutions (PPI). Thus, it starts with a theoretical framework on the emergence of this topic in the European Innovation Policy (Section 2), then continues with the identification and systematization of the main mechanisms for its effective adoption, both on the demand and supply side of the market (Section 3), as well as to expose and describe methods and tools for positioning innovation at the heart of public entities. The innovative projects best distinguished by the European Commission for their good practices in innovation procurement are identified, and the main methodology for the development and management of innovation procurement – Forward Commitment Procurement (FCP) – is applied to them in a pioneering way (Section 4). The relevance of innovation in public procurement is systematized and reflected upon in Section 5.

Keywords: innovation procurement, innovation policy, innovation, pubic procurement

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Authors: Nagwa Mourad Abdelazeem, Marwa El-hussieny

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Multicomponent reactions (MCRs), one-pot reactions form products from more than two different starting compounds. (MCRs) are ideal reaction systems leading to high structural diversity and molecular complexity through a single transformation. (MCRs) have a lot of advantage such as higher yield, less waste generation, use of readily available starting materials and high atom. (MCRs) provide a rapid process for efficient synthesis of key structures in discovery of drug on the other hand silica sulfuric acid (SSA) has been used as an efficient heterogeneous catalyst for many organic transformations. (SSA) is low cost, ease of preparation, catalyst recycling, and ease of handling, so in this article we used 2-(thiophen-2-yl)-1H-indole, N-substituted anilines and aldehyde in the presence of silica sulfuric acid (SSA) as a catalyst in water as solvent at room temperature to prepare 3,3'-(phenylmethylene)bis(2-(thiophen-2-yl)-1H-indole) and N-methyl-4-(phenyl(2-(thiophen-2-yl)-1H-indol-3-yl)methyl)aniline derivatives Via one-pot reaction. Compound 2-(thiophen-2-yl)-1H-indole belongs to the ubiquitous class of indoles which enjoy broad synthetic, biological and industrial applications ]. Cancer is considered the first or second most common reason of death all through the world. So the synthesized compounds will be tested as anticancer. We expected the synthesized compounds will give good results comparison to the reference drug.

Keywords: aldehydes, aza-friedel-crafts reaction, indole, multicomponent reaction

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Authors: Samia A. El-Fiky, Fouad A. Abou-Zaid, Ibrahim M. Farag, Naira M. El-Fiky

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Clomipramine hydrochloride is one of the most used tricyclic antidepressant drug in Egypt. This drug contains in its chemical structure on two benzene rings. Benzene is considered to be toxic and clastogenic agent. So, the present study was designed to assess the genotoxic effect of Clomipramine hydrochloride on somatic and germ cells in mice. Three dose levels 0.195 (Low), 0.26 (Medium), and 0.65 (High) mg/kg.b.wt. were used. Seven groups of male mice were utilized in this work. The first group was employed as a control. In the remaining six groups, each of the above doses was orally administrated for two groups, one of them was treated for 5 days and the other group was given the same dose for 30 days. At the end of experiments, the animals were sacrificed for cytogenetic and sperm examination as well as histopathological investigations by using hematoxylin and eosin stains (H and E stains) and electron microscope. Concerning the sperm studies, these studies were confined to 5 days treatment with different dose levels. Moreover, the ultrastructural investigation by electron microscope was restricted to 30 days treatment with drug doses. The results of the dose dependent effect of Clomipramine showed that the treatment with three different doses induced increases of frequencies of chromosome aberrations in bone marrow and spermatocyte cells as compared to control. In addition, mitotic and meiotic activities of somatic and germ cells were declined. The treatments with medium or high doses were more effective for inducing significant increases of chromosome aberrations and significant decreases of cell divisions than treatment with low dose. The effect of high dose was more pronounced for causing such genetic deleterious in respect to effect of medium dose. Moreover, the results of the time dependent effect of Clomipramine observed that the treatment with different dose levels for 30 days led to significant increases of genetic aberrations than treatment for 5 days. Sperm examinations revealed that the treatment with Clomipramine at different dose levels caused significant increase of sperm shape abnormalities and significant decrease in sperm count as compared to control. The adverse effects on sperm shape and count were more obviousness by using the treatments with medium or high doses than those found in treatment with low dose. The group of mice treated with high dose had the highest rate of sperm shape abnormalities and the lowest proportion of sperm count as compared to mice received medium dose. In histopathological investigation, hematoxylin and eosin stains showed that, the using of low dose of Clomipramine for 5 or 30 days caused a little pathological changes in liver tissue. However, using medium and high doses for 5 or 30 days induced severe damages than that observed in mice treated with low dose. The treatment with high dose for 30 days gave the worst results of pathological changes in hepatic cells. Moreover, ultrastructure examination revealed, the mice treated with low dose of Clomipramine had little differences in liver histological architecture as compared to control group. These differences were confined to cytoplasmic inclusions. Whereas, prominent pathological changes in nuclei as well as dilated of rough Endoplasmic Reticulum (rER) were observed in mice treated with medium or high doses of Clomipramine drug. In conclusion, the present study adds evidence that treatments with medium or high doses of Clomipramine have genotoxic effects on somatic and germ cells of mice, as unwanted side effects. However, the using of low dose (especially for short time, 5 days) can be utilized as a therapeutic dose, where it caused relatively similar proportions of genetic, sperm, and histopathological changes as those found in normal control.

Keywords: chromosome aberrations, clomipramine, mice, histopathology, sperm abnormalities

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Authors: Debraj Gangopadhyay, Moumita Das, Ranjan K. Singh, Poonam Tandon

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Creatinine is a toxic chemical waste generated from muscle metabolism. Abnormally high levels of creatinine in the body fluid indicate possible malfunction or failure of the kidneys. This leads to a condition termed as creatinine induced nephrotoxicity. N-acetylcysteine is an antioxidant drug which is capable of preventing creatinine induced nephrotoxicity and is helpful to treat renal failure in its early stages. Taurine is another antioxidant drug which serves similar purpose. The kidneys have a natural power that whenever reactive oxygen species radicals increase in the human body, the kidneys make an antioxidant shell so that these radicals cannot harm the kidney function. Taurine plays a vital role in increasing the power of that shell such that the glomerular filtration rate can remain in its normal level. Thus taurine protects the kidneys against several diseases. However, taurine also has some negative effects on the body as its chloramine derivative is a weak oxidant by nature. N-acetylcysteine is capable of inhibiting the residual oxidative property of taurine chloramine. Therefore, N-acetylcysteine is given to a patient along with taurine and this combination is capable of suppressing the negative effect of taurine. Both N-acetylcysteine and taurine being affordable, safe, and widely available medicines, knowledge of the mechanism of their combined effect on creatinine, the favored route of administration, and the proper dose may be highly useful in their use for treating renal patients. Raman spectroscopy is a precise technique to observe minor structural changes taking place when two or more molecules interact. The possibility of formation of a complex between a drug molecule and an analyte molecule in solution can be explored by analyzing the changes in the Raman spectra. The formation of a stable complex of creatinine with N-acetylcysteinein vitroin aqueous solution has been observed with the help of Raman spectroscopic technique. From the Raman spectra of the mixtures of aqueous solutions of creatinine and N-acetylcysteinein different molar ratios, it is observed that the most stable complex is formed at 1:1 ratio of creatinine andN-acetylcysteine. Upon drying, the complex obtained is gel-like in appearance and reddish yellow in color. The complex is hygroscopic and has much better water solubility compared to creatinine. This highlights that N-acetylcysteineplays an effective role in reducing the toxic effect of creatinine by forming this water soluble complex which can be removed through urine. Since the drug taurine is also known to be useful in reducing nephrotoxicity caused by creatinine, the aqueous solution of taurine with those of creatinine and N-acetylcysteinewere mixed in different molar ratios and were investigated by Raman spectroscopic technique. It is understood that taurine itself does not undergo complexation with creatinine as no additional changes are observed in the Raman spectra of creatinine when it is mixed with taurine. However, when creatinine, N-acetylcysteine and taurine are mixed in aqueous solution in molar ratio 1:1:3, several changes occurring in the Raman spectra of creatinine suggest the diminishing toxic effect of creatinine in the presence ofantioxidant drugs N-acetylcysteine and taurine.

Keywords: creatinine, creatinine induced nephrotoxicity, N-acetylcysteine, taurine

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Authors: Benjamin Legros, Jan Fransoo, Oualid Jouini

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This study aims to evaluate street-turn strategies for empty container repositioning in the hinterland. Containers arrive over time at the (importer) consignee, while the demand for containers arises from the (exporter) shipper. A match can be operated between an empty container from the consignee and the load from the shipper. Therefore, we model the system as a double-ended queue with non-zero matching time and a limited number of resources in order to optimize the reposition- ing decisions. We determine the performance measures when the consignee operates using a fixed withholding threshold policy. We show that the matching time mainly plays a role in the matching proportion, while under a certain duration, it only marginally impacts the consignee’s inventory policy and cost per container. Also, the withholding level is mainly determined by the shipper’s production rate.

Keywords: container, double-ended queue, inventory, Markov decision process, non-zero matching time, street-turn

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Authors: Xuechen Chen

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The EU-ASEAN relations which can be dated back to 1972 represents one of the oldest group-to-group relationship in international politics. Despite a longstanding dialogue partnership, the EU and ASEAN have long been reluctant to forge deeper and substantial cooperation in political and security domains. However, the year of 2012 witnessed a salient shift in EU-ASEAN relations, with the EU significantly elevating ASEAN's profile in its external relations. Given the limited scholarly attention that has been devoted to this change in ASEAN-EU relations, this article explores why there has been a greater level of engagement and approximation between the EU and ASEAN. In particular, it asks why the EU, which had long been reluctant to recognize ASEAN as a strategic partner, has changed its policy towards ASEAN. Drawing on social constructivism, this article argues that the EU’s and ASEAN’s evolving identity-formation processes have played a significant role in reshaping their mutual perceptions, which subsequently leads to the modification of the interregional policies of both actors. The methodology of this study is based on content analysis of a wide range of official documents and policy papers from the EU and ASEAN, as well as more than 20 in-depth elite interviews with diplomats and experts working on the EU-ASEAN relationship from both organisations. Departing from the existing works which mainly adopt a Eurocentric perspective when analysing the EU-ASEAN interregionalism, this study suggests that the approximation of the EU-ASEAN relationship between 2012 and 2017 is driven by both actors’ adjustment of international identities, together with the internal dynamics and systematic changes within both regions.

Keywords: Association of Southeast Asia Nations, European Union, EU foreign policy, interregionalism

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Authors: Shao-Hsun Keng, Hwang-Ruey Song

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This paper examines the causal effect of the tenure track system on instructors’ grading practices and teaching effectiveness by taking advantage of a natural experiment in Taiwan. The results show that assistant professors subject to the tenure track policy are more likely to grade leniently and fail fewer students. The course grade is 5% higher in classes taught by assistant professors subject to the tenure system. However, the tendency to grade leniently is reversed after assistant professors subject to the tenure system are promoted to a higher rank. Our findings are consistent with the exchange theory. We also show that teaching and student efforts are adversely affected by the tenure policy, which could reduce student learning and the quality of the workforce in the long run.

Keywords: tenure track system, grading leniency, study time, grade inflation

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