Search results for: cooperation against drugs trafficking at sea

Authors: Asmaa Mandour, Ramzia El-Bagary, Asmaa El-Zaher, Ehab Elkady

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Background: An UHPLC (ultra high performance liquid chromatography) method for the simultaneous determination of norfloxacin (NOR), metronidazole (MET) and tinidazole (TNZ) using monolithic column is presented. Purpose: The method is considered an environmentally friendly method with relatively low organic composition of the mobile phase. Methods: The chromatographic separation was performed using Phenomenex® Onyex Monolithic C18 (50mmx 20mm) column. An elution program of mobile phase consisted of 0.5% aqueous phosphoric acid : methanol (85:15, v/v). Where elution of all drugs was completed within 3.5 min with 1µL injection volume. The UHPLC method was applied for the stability indication of NOR in the presence of its acid degradation product ND. Results: Retention times were 0.69, 1.19 and 3.23 min for MET, TNZ and NOR, respectively. While ND retention time was 1.06 min. Linearity, accuracy, and precision were acceptable over the concentration range of 5-50µg mL-1for all drugs. Conclusions: The method is simple, sensitive and suitable for the routine quality control and dosage form assay of the three drugs and can also be used for the stability indication of NOR in the presence of its acid degradation product.

Keywords: antibacterial, monolithic cilumn, simultaneous determination, UHPLC

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Authors: Khaled Sellami, Lynda Sellami, Pierre F. Tiako

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Ubiquitous computing helps make data and services available to users anytime and anywhere. This makes the cooperation of devices a crucial need. In return, such cooperation causes an overload of the devices and/or networks, resulting in network malfunction and suspension of its activities. Our goal in this paper is to propose an approach of devices reconfiguration in order to help to reduce the energy consumption in ubiquitous environments. The idea is that when high-energy consumption is detected, we proceed to a change in component distribution on the devices to reduce and/or balance the energy consumption. We also investigate the possibility to detect high-energy consumption of devices/network based on devices abilities. As a result, our idea realizes a reconfiguration of devices aimed at reducing the consumption of energy and/or load balancing in ubiquitous environments.

Keywords: ubiquitous computing, load balancing, device energy consumption, reconfiguration

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Authors: Luphumlo Ncanywa, Paul Watts

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Malaria is a disease that kills approximately one million people annually. Children and pregnant women in sub-Saharan Africa lost their lives due to malaria. Malaria continues to be one of the major causes of death, especially in poor countries in Africa. Decrease the burden of malaria and save lives is very essential. There is a major concern about malaria parasites being able to develop resistance towards antimalarial drugs. People are still dying due to lack of medicine affordability in less well-off countries in the world. If more people could receive treatment by reducing the cost of drugs, the number of deaths in Africa could be massively reduced. There is a shortage of pharmaceutical manufacturing capability within many of the countries in Africa. However one has to question how Africa would actually manufacture drugs, active pharmaceutical ingredients or medicines developed within these research programs. It is quite likely that such manufacturing would be outsourced overseas, hence increasing the cost of production and potentially limiting the full benefit of the original research. As a result the last few years has seen major interest in developing more effective and cheaper technology for manufacturing generic pharmaceutical products. Micro-reactor technology (MRT) is an emerging technique that enables those working in research and development to rapidly screen reactions utilizing continuous flow, leading to the identification of reaction conditions that are suitable for usage at a production level. This emerging technique will be used to develop antimalarial drugs. It is this system flexibility that has the potential to reduce both the time was taken and risk associated with transferring reaction methodology from research to production. Using an approach referred to as scale-out or numbering up, a reaction is first optimized within the laboratory using a single micro-reactor, and in order to increase production volume, the number of reactors employed is simply increased. The overall aim of this research project is to develop and optimize synthetic process of antimalarial drugs in the continuous processing. This will provide a step change in pharmaceutical manufacturing technology that will increase the availability and affordability of antimalarial drugs on a worldwide scale, with a particular emphasis on Africa in the first instance. The research will determine the best chemistry and technology to define the lowest cost manufacturing route to pharmaceutical products. We are currently developing a method to synthesize Lumefantrine in continuous flow using batch process as bench mark. Lumefantrine is a dichlorobenzylidine derivative effective for the treatment of various types of malaria. Lumefantrine is an antimalarial drug used with artemether for the treatment of uncomplicated malaria. The results obtained when synthesizing Lumefantrine in a batch process are transferred into a continuous flow process in order to develop an even better and reproducible process. Therefore, development of an appropriate synthetic route for Lumefantrine is significant in pharmaceutical industry. Consequently, if better (and cheaper) manufacturing routes to antimalarial drugs could be developed and implemented where needed, it is far more likely to enable antimalarial drugs to be available to those in need.

Keywords: antimalarial, flow, lumefantrine, synthesis

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Authors: Ana M. Prieto del Pino

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As is well known, UN Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances (1988) was a landmark regarding the seizure of proceeds of crime. Depriving criminals of the profits from their activity became a priority at an international level in the fight against organised crime. Enabling confiscation of proceeds of illicit traffic in narcotic drugs and psychotropic substances, criminalising money laundering and confiscating the proceeds thereof are the three measures taken in order to achieve that purpose. The beginning of 21st century brought the declaration of war on corruption and on the illicit enjoyment of the profits thereof onto the international scene. According to the UN Convention against Transnational Organised Crime (2000), States Parties should adopt the necessary measures to enable the confiscation of proceeds of crime derived from offences (or property of equivalent value) and property, equipment and other instrumentalities used in offences covered by that Convention. The UN Convention against Corruption (2003) states asset recovery explicitly as a fundamental principle and sets forth measures aiming at the direct recovery of property through international cooperation in confiscation. Furthermore, European legislation has made many significant strides forward in less than twenty years concerning money laundering, confiscation, and asset recovery. Crime does not pay, let there be no doubt about it. Nevertheless, we must be very careful not to sing out of tune with individual rights and legal guarantees. On the one hand, innocent individuals and businesses must be protected, since they should not pay for the guilty ones’ faults. On the other hand, the rule of law must be preserved and not be tossed aside regarding those who have carried out criminal activities. An in-depth analysis of judicial decisions on money laundering and confiscation of proceeds of crime issued by European national courts and by the European Court of Human Rights in the last decade has been carried out from a human rights, legal guarantees and criminal law basic principles’ perspective. The undertaken study has revealed the violation of the right to property, of the proportionality principle legal and the infringement of basic principles of states’ domestic substantive and procedural criminal law systems. The most relevant ones have to do with the punishment of money laundering committed through negligence, non-conviction based confiscation and a too-far reaching interpretation of the notion of ‘proceeds of crime’. Almost everything in life has a bright and a dark side. Confiscation of criminal proceeds and asset recovery are not an exception to this rule.

Keywords: confiscation, human rights, money laundering, organized crime

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Authors: Ibtihaj Al-Siyabi

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The crisis of COVID-19 posed enormous challenges to the statistical providers. While official statistics were disrupted by the pandemic and related containment measures, there was a growing and pressing need for real-time data and statistics to inform decisions. This paper gives an account of the way the pandemic impacted the operations of the National Statistical Offices (NSOs) in general in terms of data collection and methods used and the main challenges encountered by them based on international surveys. It highlights the performance of the Statistical Centre for the Cooperation Council for the Arab Countries of the Gulf, GCC-STAT, and its responsiveness to the pandemic placing special emphasis on environmental statistics. The paper concludes by confirming the GCC-STAT’s resilience and success in facing the challenges.

Keywords: NSO, COVID-19, statistics, crisis, pandemic

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Authors: Takashi Kaminagayoshi, Shigeyuki Haruyama

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To improve the manufacturing efficiency of biologics, such as antibody drugs, a quality engineering framework was designed. Within this framework, critical steps and parameters in the manufacturing process were studied. Identification of these critical steps and critical parameters allows a deeper understanding of manufacturing capabilities, and suggests to process development department process control standards based on actual manufacturing capabilities as part of a PDCA (plan-do-check-act) cycle. This cycle can be applied to each manufacturing process so that it can be standardized, reducing the time needed to establish each new process.

Keywords: antibody drugs, biologics, manufacturing efficiency, PDCA cycle, quality engineering

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Authors: Moetazza M. Al-Shafei, Hala Abdel Karim, Eitedal M. Daoud, Hassan Zaki Hassuna

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Epilepsy is a common neurological disorder affecting all age groups. It is one of the world's most prevalent non-communicable diseases. Increased evidence suggesting that long term usage of anti-epileptic drugs can have adverse effects on bone mineralization and bone molding .Aiming to study these effects and to give guide lines to support bone health through early intervention. From Neurology Out-Patient Clinic kaser Elaini University Hospital, 60 Patients were enrolled, 40 patients on antiepileptic drugs for at least two years and 20 controls matched with age and sex, epileptic but before starting treatment both chosen under specific criteria. Patients were divided into four groups, three groups with monotherapy treated with either Phynetoin, Valporic acid or Carbamazipine and fourth group treated with both Valporic acid and Carbamazipine. Estimation of serum Carboxy-Terminal Telopeptide of Type I- Collagen(ICTP) bone resorption marker, serum 25(OH )vit D3, calcium ,magnesium and phosphorus were done .Results showed that all patients on AED had significant low levels of 25(OH) vit D3 (p<0.001) ,with significant elevation of ICTP (P<0.05) versus controls. In group treated with Phynotoin highly significant elevation of (ICTP) marker and decrease of both serum 25(OH) vit D3 (P<0, 0001) and serum calcium(P<0.05)versus control. Double drug group showed significant decrease of serum 25(OH) vit D3 (P<0.0001) and decrease in Phosphorus (P<0.05) versus controls. Serum magnesium showed no significant differences between studied groups. We concluded that Anti- epileptic drugs appears to be an aggravating factor on bone mineralization ,so therapeutically it can be worth wile to supplement calcium and vitamin D even before initiation of antiepileptic therapy. ICTP marker can be used to evaluate change in bone resorption before and during AED therapy.

Keywords: antiepileptic drugs, bone minerals, carboxy teminal telopeptidetype-1-collagen bone resorption marker, vitamin D

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Authors: Salwa M. Almomen, Mona A. Almaghrabi, Saja M. Alhabardi, Adel A. Alrwisan

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Background: Hepatotoxicity is a major reason for medication withdrawal from the markets. Unfortunately, serious adverse hepatic effects can occur after marketing with limited indicators during clinical development. Therefore, finding possible predictors for hepatotoxicity might guide the monitoring program of various stakeholders. Methods: We examined the clinical review documents for drugs approved in the US from 2011 to 2016 to evaluate their hepatic safety profile. Predictors: we assessed whether these medications meet Hy’s Law with hepatotoxicity grade ≥ 3, labeled hepatic adverse effects at approval, or accelerated approval status. Outcome: post-marketing regulatory action related to hepatotoxicity, including product withdrawal or updates to warning, precaution, or adverse effects sections. Statistical analysis: drugs were included in the analysis from the time of approval until the end of 2019 or the first post-marketing regulatory action related to hepatotoxicity, whichever occurred first. The hazard ratio (HR) was estimated using Cox-regression analysis. Results: We included 192 medications in the study. We classified 48 drugs as having grade ≥ 3 hepatotoxicities, 43 had accelerated approval status, and 74 had labeled information about hepatotoxicity prior to marketing. The adjusted HRs for post-marketing regulatory action for products with grade ≥ 3 hepatotoxicity was 0.61 (95% confidence interval [CI], 0.17-2.23), 0.92 (95%CI, 0.29-2.93) for a drug approved via accelerated approval program, and was 0.91 (95%CI, 0.33-2.56) for drugs with labeled hepatotoxicity information at approval time. Conclusion: This study does not provide conclusive evidence on the association between post-marketing regulatory action and grade ≥ 3 hepatotoxicity, accelerated approval status, or availability of labeled information at approval due to sampling size and channeling bias.

Keywords: accelerated approvals, hepatic adverse effects, drug-induced liver injury, hepatotoxicity predictors, post-marketing withdrawal

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Authors: V. Surena, B. Nazemisalman, F. Noghrehkar

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Introduction: Gingival overgrowth (GO) is a common side effect involving users of antiepileptic, immunosuppressive and calcium channel blocker drugs. Cyclosporine and phenytoin are amongst the most widely used drugs associated with GO. Gingival fibroblasts seem to have a significant role in the production of certain enzymes after administration of the drugs contributing to GO. Previous studies have shown a higher prevalence of GO in children and adolescents. The aim of this study was to compare normal human gingival fibroblasts with those exposed to Cyclosporine or phenytoin in measuring the production levels of certain enzymes that could have a possible role in GO. Methods: samples were obtained from the gingival biopsies of seven adult and seven children and were cultured into plates. With the growth of fibroblast cells, they were treated with or without either Cyclosporine or phenytoin. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine the expressed levels of R-EGF, cathepsin B,L, Lysyl oxidase, COL1, TGF β1, MMP-1,2, and TIMP1. Results: according to RT-PCR analyses, the expressed levels of R-EGF, cathepsin B, L, Lysyl oxidase, COL1, TGF β1, MMP-1, 2 and TIMP1 were affected by Cyclosporine and phenytoin. TGF-β1, TIMP, Cathepsin B and EGF showed comparable values in the adult and pediatric groups. Conclusions: Different expressed levels of enzymes after treatment of the gingival fibroblasts of adults and pediatrics with phenytoin or Cyclosporine could be the reason for the higher severity of GO in children. More studies need to be performed on the pathogenesis of GO at different age groups.

Keywords: cyclosporine, fibroblasts, phenytoin, gingivae

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Authors: In Hoi Lee, Seong Baeg Kim, Je Eung Jeon, Gwang Yong Choi, Joo Sub Lee, Ik Sang Kim

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Recently, the interest of globalization in the field of teacher education has increased. In the U.S., the government is trying to enhance the quality of education through a global approach in education. To do so, the schools in the U.S. are recruiting teachers with global capability from countries like Korea where competent teachers are being trained. Meanwhile, in the case of Korea, although excellent teachers have been cultivated every year, due to a low birth rate it is not easy to become a domestic teacher. To solve the trouble that the two countries are facing, the study first examines the demand and necessity of globalization in the field of teacher education between Korea and the U.S. Second, we propose a new project, called the ‘Global Teachers University (GTU)’ program to satisfy the demands of both countries. Finally, we provide its implications to build the future educational cooperation for teacher training in a global context.

Keywords: educational cooperation, globalization, teachers education program, teacher training institutions

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Authors: Ankita Singh

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Sex trafficking and child pornography are those kinds of borderless crimes which can not be effectively prevented only through the laws and efforts of one country because it requires a proper and smooth collaboration among countries. Eradication of international human trafficking syndicates, criminalisation of international cyber offenders, and effective ban on child pornography is not possible without applying effective universal laws; hence, continuous collaboration of all countries is much needed to adopt and routinely update these universal laws. Congregation of countries on an international platform is very necessary from time to time, where they can simultaneously adopt international agendas and create powerful universal laws to prevent sex trafficking and child pornography in this modern digital era. In the past, some international steps have been taken through The Convention on the Rights of the Child (CRC) and through The Optional Protocol to the Convention on the Rights of the Child on the Sale of Children, Child Prostitution, and Child Pornography, but in reality, these measures are quite weak and are not capable in effectively protecting children from sexual abuse in this modern & highly advanced digital era. The uncontrolled growth of artificial intelligence (AI) and its misuse, lack of proper legal jurisdiction over foreign child abusers and difficulties in their extradition, improper control over international trade of digital child pornographic content, etc., are some prominent issues which can only be controlled through some new, effective and powerful universal laws. Due to a lack of effective international standards and a lack of improper collaboration among countries, Indian laws are also not capable of taking effective actions against child abusers. This research will be conducted through both doctrinal as well as empirical methods. Various literary sources will be examined, and a questionnaire survey will be conducted to analyse the effectiveness of international standards and Indian laws against child pornography. Participants in this survey will be Indian University students. In this work, the existing international norms made for protecting children from sexual abuse will be critically analysed. It will explore why effective and strong collaboration between countries is required in modern times. It will be analysed whether existing international steps are enough to protect children from getting trafficked or being subjected to pornography, and if these steps are not found to be sufficient enough, then suggestions will be given on how international standards and protections can be made more effective and powerful in this digital era. The approach of India towards the existing international standards, the Indian laws to protect children from being subjected to pornography, and the contributions & capabilities of India in strengthening the international standards will also be analysed.

Keywords: child pornography, prevention of children from sexual offences act, the optional protocol to the convention on the rights of the child on the sale of children, child prostitution and child pornography, the convention on the rights of the child

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Authors: Jerzy Bański

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The purpose of the paper is to describe the role of urban-rural partnership in social and economic development. The concept of urban-rural collaboration is relatively new and assumes the need to link large metropolitan areas with surrounding rural areas in a number of ways. It is strongly related to the existing concept of polycentric spatial development. At the European Union level, the first document to address the need for urban-rural partnerships was the European Spatial Development Perspective from 1999. The paper focuses on factors that generate social and economic success on examples of several metropolitan territories in Poland (Warsaw, Poznan, Wroclaw, Krakow). A survey focused on rural communes made it possible to assess key success factors (location, social and economic, technological and organizational) that could be later used to determine the right course of action in the area of urban-rural cooperation, with the desired outcome being effective metropolitan area development. The main challenges to urban-rural partnership are issues associated with spatial planning, infrastructure and public services. These are areas of the greatest conflict of interest, too. Any analysis of urban-rural cooperation in metropolitan areas really needs to focus on the unique nature of this type of relationship. This includes issues such as commuting to work in the urban core and vice versa, complementarity of technical infrastructure, and joint strategic planning. Other forms of cooperation should focus on the tourist and recreational aspects of areas surrounding the urban core.

Keywords: partnership, rural areas, urbanization, metropolitan areas, Poland

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Authors: Zane Bulderberga

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Spatial dimension in development planning is becoming more topical in 21st century as a result of changes in population structure. Sustainable spatial development focuses on identifying and using territorial advantages to foster the harmonized development of the entire country, reducing negative effects of population concentration, increasing availability and mobility. EU and national development planning documents state polycentrism as main tool for balance spatial development, including investment concentration in growth centres. If mutual cooperation of growth centres as well as urban-rural cooperation is not fostered, then territorial differences can deepen and create unbalanced development. The aim of research: to evaluate the urban-rural interaction, elaborating spatial development scenarios in framework of Latvian regional policy. To perform the research monographic, comparison, abstract-logical method, synthesis and analysis will be used when studying the theoretical aspects of research aiming at collecting the ideas of scientists from different countries, concepts, regulations as well as to create meaningful scientific discussion. Hierarchy analysis process (AHP) will be used to state further scenarios of spatial development in Latvia. Experts from various institutions recognized urban-rural interaction and co-operation as an essential tool for the development. The most important factors for balanced spatial development in Latvia are availability of public transportation and improvement of service availability. Evaluating the three alternative scenarios, it was concluded that the urban-rural partnership will ensure a balanced development in Latvian regions.

Keywords: rural-urban interaction, rural-urban cooperation, spatial development, AHP

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Authors: Jay Ananth

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The drug discovery process currently requires numerous years of clinical testing as well as money just for a single drug to earn FDA approval. For drugs that even make it this far in the process, there is a very slim chance of receiving FDA approval, resulting in detrimental hurdles to drug accessibility. To minimize these inefficiencies, numerous studies have implemented computational methods, although few computational investigations have focused on a crucial feature of drugs: lipophilicity. Lipophilicity is a physical attribute of a compound that measures its solubility in lipids and is a determinant of drug efficacy. This project leverages Artificial Intelligence to predict the impact of a drug’s lipophilicity on its performance by accounting for factors such as binding affinity and toxicity. The model predicted lipophilicity and binding affinity in the validation set with very high R² scores of 0.921 and 0.788, respectively, while also being applicable to a variety of target receptors. The results expressed a strong positive correlation between lipophilicity and both binding affinity and toxicity. The model helps in both drug development and discovery, providing every pharmaceutical company with recommended lipophilicity levels for drug candidates as well as a rapid assessment of early-stage drugs prior to any testing, eliminating significant amounts of time and resources currently restricting drug accessibility.

Keywords: drug discovery, lipophilicity, ligand-receptor interactions, machine learning, drug development

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Authors: Abhishek Pandey

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Capping and lamination are the most common tablet defects with poorly compressible drugs the common example of that Ibuprofen and Acetaminophen. Generally both these drugs are compressed by wet granulation method which is very time consuming process Ibuprofen and Acetaminophen is widely used as prescription & non-prescription medicine. Ibuprofen mainly used in the treatment of mild to moderate pain related to headache, migraine, postoperative condition and in the management of spondylitis, osteoarthritis Acetaminophen used as an analgesic and antipyretic drug. Ibuprofen having high tendency of sticking to punches of tablet punching machine while Acetaminophen is not ordinarily compressible to tablet formulation because Acetaminophen crystals are very hard and brittle in nature and fracture very easily when compressed producing capping and laminating tablet defects therefore wet granulation method is used to make them compressible. The aim of study was to prepare Ibuprofen and Acetaminophen tablets by direct compression technique and their evaluation. In this Investigation tablets were prepared by using directly compressible grade excipients. Dibasic calcium phosphate, lactose anhydrous (DCL21), microcrystalline cellulose (Avicel PH 101). In order to obtain best or optimize formulation nine different formulations were generated among them batch F5, F6, F7 shows good results and within the acceptable limit. Formulation (F7) selected as optimize product on the basis of evaluation parameters.

Keywords: capping, lamination, tablet defects, direct compression

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Authors: Shabeer Khan

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The main objective of Islamic Finance is to promote social justice thorough financial inclusion and redistribution of economic resources between rich and poor. The approach of Islamic finance is more comprehensive in nature and covers both formal and informal sectors of the economy, first, through reducing the gap between both sectors, and second by using specific Islamic values to reallocate the wealth between formal and informal sectors. Applying Generalized Method of Movements (GMM) to the annual data spanning from 1995-2015 for 141 countries, this study explores the determinants of informal business sector in Organization of Islamic Cooperation (OIC) countries and then compares with Non-OIC countries. Economic freedom and institutions variables as well as economic growth and money supply are found to reduce informal business sector in both OIC and Non-OIC nations while government expenditure are found to increase informal business sector in both group of nations. Informal Business sector remain the same in both types of countries but still the majority Muslim population in OIC economies create main difference between both groups of nations and justify the potential role of Islamic Finance in informal business sector in OIC nations. The study suggests that institutions quality should be improved and entrepreneurs’ friendly business environment must be provided. This study refines the main features of informal business sector and discuss their implications on policy designing and implementation, particularly in the context of Islamic finance fight against poverty, inequality and improving living standards of informal sector participants in OIC countries.

Keywords: Islamic finance, informal Business Sector, Generalized Method of Movements (GMM) and OIC

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Authors: Sridhar A. Malkaram, Tamer E. Fandy

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Purpose: 5-Azacytidine (5AC) and decitabine (DC) are DNA hypomethylating agents. We recently demonstrated that both drugs increase the enzymatic activity of the histone deacetylase enzyme SIRT6. Accordingly, we are comparing the changes H3K9 acetylation changes in the whole genome induced by both drugs using leukemia cells. Description of Methods & Materials: Mononuclear cells from the bone marrow of six de-identified naive acute myeloid leukemia (AML) patients were cultured with either 500 nM of DC or 5AC for 72 h followed by ChIP-Seq analysis using a ChIP-validated acetylated-H3K9 (H3K9ac) antibody. Chip-Seq libraries were prepared from treated and untreated cells using SMARTer ThruPLEX DNA- seq kit (Takara Bio, USA) according to the manufacturer’s instructions. Libraries were purified and size-selected with AMPure XP beads at 1:1 (v/v) ratio. All libraries were pooled prior to sequencing on an Illumina HiSeq 1500. The dual-indexed single-read Rapid Run was performed with 1x120 cycles at 5 pM final concentration of the library pool. Sequence reads with average Phred quality < 20, with length < 35bp, PCR duplicates, and those aligning to blacklisted regions of the genome were filtered out using Trim Galore v0.4.4 and cutadapt v1.18. Reads were aligned to the reference human genome (hg38) using Bowtie v2.3.4.1 in end-to-end alignment mode. H3K9ac enriched (peak) regions were identified using diffReps v1.55.4 software using input samples for background correction. The statistical significance of differential peak counts was assessed using a negative binomial test using all individuals as replicates. Data & Results: The data from the six patients showed significant (Padj<0.05) acetylation changes at 925 loci after 5AC treatment versus 182 loci after DC treatment. Both drugs induced H3K9 acetylation changes at different chromosomal regions, including promoters, coding exons, introns, and distal intergenic regions. Ten common genes showed H3K9 acetylation changes by both drugs. Approximately 84% of the genes showed an H3K9 acetylation decrease by 5AC versus 54% only by DC. Figures 1 and 2 show the heatmaps for the top 100 genes and the 99 genes showing H3K9 acetylation decrease after 5AC treatment and DC treatment, respectively. Conclusion: Despite the similarity in hypomethylating activity and chemical structure, the effect of both drugs on H3K9 acetylation change was significantly different. More changes in H3K9 acetylation were observed after 5 AC treatments compared to DC. The impact of these changes on gene expression and the clinical efficacy of these drugs requires further investigation.

Keywords: DNA methylation, leukemia, decitabine, 5-Azacytidine, epigenetics

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Authors: Aleksandra Ibragimow, Moritz Albrecht, Eerika Albrecht

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Close international cooperation between all countries within a river basin has become one of the key aspects of sustainable cross-border water management. This is due to the fact that water does not stop at administrative or political boundaries. Therefore, the preferred mode to protect and manage transnational water bodies is close cooperation between all countries and stakeholders within the natural hydrological unit of the river basin. However, past practices have demonstrated that combining interests of different countries and stakeholders with differing political systems and management approaches to environmental issues upstream as well as downstream can be challenging. The study focuses on particular problems and challenges of water management in international river basin districts by the example of the International Oder River Basin District. The Oder River is one of the largest cross-border rivers of the Baltic Sea basin passing through Poland, Germany, and the Czech Republic. Attention is directed towards the activities and the actions that were carried out during the Districts' first management cycle of transnational river basin management (2009-2015). The results show that actions of individual countries have been focused on the National Water Management Plans while a common appointment about identified supra-regional water management problems has not been solved, and conducted actions can be considered as preliminary and merely a basis for future management. This present state raises the question whether the achievement of main objectives of Water Framework Directive (2000/60/EC) can be a realistic task.

Keywords: International River Basin Districts, water management, water frameworkdirective, water management plans

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Authors: A. Julio, R. Caparica, S. Costa Lima, S. Reis, J. G. Costa, P. Fonte, T. Santos De Almeida

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The Mycobacterium leprae causes a chronic and infectious disease called leprosy, which the most common symptoms are peripheral neuropathy and deformation of several parts of the body. The pharmacological treatment of leprosy is a combined therapy with three different drugs, rifampicin, clofazimine, and dapsone. However, clofazimine and dapsone have poor solubility in water and also low bioavailability. Thus, it is crucial to develop strategies to overcome such drawbacks. The use of ionic liquids (ILs) may be a strategy to overcome the low solubility since they have been used as solubility promoters. ILs are salts, liquid below 100 ºC or even at room temperature, that may be placed in water, oils or hydroalcoholic solutions. Another approach may be the encapsulation of drugs into polymeric nanoparticles, which improves their bioavailability. In this study, two different classes of ILs were used, the imidazole- and the choline-based ionic liquids, as solubility enhancers of the poorly soluble antileprotic drugs. Thus, after the solubility studies, it was developed IL-PLGA nanoparticles hybrid systems to deliver such drugs. First of all, the solubility studies of clofazimine and dapsone were performed in water and in water: IL mixtures, at ILs concentrations where cell viability is maintained, at room temperature for 72 hours. For both drugs, it was observed an improvement on the drug solubility and [Cho][Phe] showed to be the best solubility enhancer, especially for clofazimine, where it was observed a 10-fold improvement. Later, it was produced nanoparticles, with a polymeric matrix of poly(lactic-co-glycolic acid) (PLGA) 75:25, by a modified solvent-evaporation W/O/W double emulsion technique in the presence of [Cho][Phe]. Thus, the inner phase was an aqueous solution of 0.2 % (v/v) of the above IL with each drug to its maximum solubility determined on the previous study. After the production, the nanosystem hybrid was physicochemically characterized. The produced nanoparticles had a diameter of around 580 nm and 640 nm, for clofazimine and dapsone, respectively. Regarding the polydispersity index, it was in agreement of the recommended value of this parameter for drug delivery systems (around 0.3). The association efficiency (AE) of the developed hybrid nanosystems demonstrated promising AE values for both drugs, given their low solubility (64.0 ± 4.0 % for clofazimine and 58.6 ± 10.0 % for dapsone), that prospects the capacity of these delivery systems to enhance the bioavailability and loading of clofazimine and dapsone. Overall, the study achievement may signify an upgrading of the patient’s quality of life, since it may mean a change in the therapeutic scheme, not requiring doses of drug so high to obtain a therapeutic effect. The authors would like to thank Fundação para a Ciência e a Tecnologia, Portugal (FCT/MCTES (PIDDAC), UID/DTP/04567/2016-CBIOS/PRUID/BI2/2018).

Keywords: ionic liquids, ionic liquids-PLGA nanoparticles hybrid systems, leprosy treatment, solubility

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Authors: Cleto J. Sauer Jr., Rita C. Sauer, Chaider G. Andrade, Doris F. Rabelo

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Introduction: Endotracheal Intubation (ETI) is a procedure for clinical management of patients with severe clinical presentation of COVID-19 disease. Realistic simulation (RS) is an active learning methodology utilized for clinical skill's improvement. To improve ETI skills of public health network's physicians from Recôncavo da Bahia region in Brazil, during COVID-19 outbreak, RS training was planned and carried out. Training scenario included the Nasco Lifeform realistic simulator, and three actions were simulated: ETI procedure, sedative drugs management, and bougie guide utilization. Training intervention occurred between May and June 2020, as an interinstitutional cooperation between the Health's Department of Bahia State and the Federal University from Recôncavo da Bahia. Objective: The main objective is to report the effects on participants' self-confidence perception for ETI procedure after RS based training. Methods: This is a descriptive study, with secondary data extracted from questionnaires applied throughout RS training. Priority workplace, time from last intubation, and knowledge about bougie were reported on a preparticipation questionnaire. Additionally, participants completed pre- and post-training qualitative self-assessment (10-point Likert scale) regarding self-confidence perception in performing each of simulated actions. Distribution analysis for qualitative data was performed with Wilcoxon Signed Rank Test, and self-confidence increase analysis in frequency contingency tables with Fisher's Exact Test. Results: 36 physicians participated of training, 25 (69%) from primary care setting, 25 (69%) performed ETI over a year ago, and only 4 (11%) had previous knowledge about the bougie guide utilization. There was an increase in self-confidence medians for all three simulated actions. Medians (variation) for self-confidence before and after training, for each simulated action were as follows: ETI [5 (1-9) vs. 8 (6-10) (p < 0.0001)]; Sedative drug management [5 (1-9) vs. 8 (4-10) (p < 0.0001)]; Bougie guide utilization [2.5 (1-7) vs. 8 (4-10) (p < 0.0001)]. Among those who performed ETI over a year ago (n = 25), an increase in self-confidence greater than 3 points for ETI was reported by 23 vs. 2 physicians (p = 0.0002), and by 21 vs. 4 (p = 0.03) for sedative drugs management. Conclusions: RS training contributed to self-confidence increase in performing ETI. Among participants who performed ETI over a year, there was a significant association between RS training and increase of more than 3 points in self-confidence, both for ETI and sedative drug management. Training with RS methodology is suitable for ETI confidence enhancement during COVID-19 outbreak.

Keywords: confidence, COVID-19, endotracheal intubation, realistic simulation

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Authors: M. A. Sohaly, M. A. Elfouly

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Parkinson's disease (PD) is a heterogeneous movement disorder that often appears in the elderly. PD is induced by a loss of dopamine secretion. Some drugs increase the secretion of dopamine. In this paper, we will simply study the stability of PD models as a nonlinear delay differential equation. After a period of taking drugs, these act as positive feedback and increase the tremors of patients, and then, the differential equation has positive coefficients and the system is unstable under these conditions. We will present a set of suggested modifications to make the system more compatible with the biodynamic system. When giving a set of numerical examples, this research paper is concerned with the mathematical analysis, and no clinical data have been used.

Keywords: Parkinson's disease, stability, simulation, two delay differential equation

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Authors: Young Sik Kim, Tae Kwon Ha

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This article considers the problems of economic growth and Russian energy strategy. Also in this paper, the issues related to the economic growth prospects of Russian were discussed. Russian energy strategy without standing Russia`s stature in global energy markets, at the current production and extraction rates, will not be able to sustain its own production as well as fulfil its energy strategy. Indeed, Russia’s energy sector suffers from a chronic lack of investments which are necessary to modernize its energy supply system. In recent years, especially since the international financial crisis, Russia-EU energy cooperation has made substantive progress. Recently the break-through progress has been made, resulting mainly from long-term contributing factors between the countries and recent international economic and political situation changes. Analytical material presented in the article is intended for a more detailed or substantive analysis related to foreign economic relations of the countries and Russia as well.

Keywords: Russia, energy strategy, economic growth, cooperation

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Authors: Tadesse Eguale, Ephrem Engdawork, Wondwossen Gebreyes, Dainel Asrat, Hile Alemayehu, John Gunn

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Salmonella is one of the major zoonotic pathogens affecting wide range of vertebrates and humans worldwide. Consumption of contaminated dairy products and contact with dairy cattle represent the common sources of non-typhoidal Salmonella infection in humans. Fecal samples were collected from 132 dairy herds in central Ethiopia and cultured for Salmonella to determine the prevalence, serotype distribution and antimicrobial susceptibility. Salmonella was recovered from the feces of at least one cattle in 10(7.6%) of the dairy farms. Out of 1193 fecal samples 30(2.5%) were positive for Salmonella. Large farm size, detection of diarrhea in one or more animals during sampling and keeping animals completely indoor compared to occasional grazing outside were associated with Salmonella positivity of the farms. Farm level prevalence of Salmonella was significantly higher in young animals below 6 months of age compared to other age groups(X2=10.24; p=0.04). Nine different serotypes were isolated. The four most frequently recovered serotypes were S. Typhimurium (23.3%),S. Saintpaul (20%) and S. Kentucky and S. Virchow (16.7%) each. All isolates were resistant or intermediately resistant to at least one of the 18 drugs tested. Twenty-six (86.7%), 20(66.7%), 18(60%), 16(53.3%) of the isolates were resistant to streptomycin, nitrofurantoin, sulfisoxazole and tetracycline respectively. Resistance to 2 drugs was detected in 93.3% of the isolates. Resistance to 3 or more drugs were detected in 21(70%) of the total isolates while multi-drug resistance (MDR) to 7 or more drugs were detected in 12 (40%) of the isolates. The rate of occurrence of MDR in Salmonella strains isolated from dairy farms in Addis Ababa was significantly higher than those isolated from farms outside of Addis Ababa((p= 0.009). The detection of high MDR in Salmonella isolates originating from dairy farms warrants the need for strict pathogen reduction strategy in dairy cattle and spread of these MDR strains to human population.

Keywords: salmonella, antimicrobial resistance, fecal prevalence

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Authors: Itze Coronel Salomon

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The rise of organized crime and violence related to drug cartels in Mexico has created serious challenges for the authorities to provide security to those who live within its borders. However, to achieve a significant improvement in security is absolute respect for fundamental human rights by the authorities. Irregular migrants in Mexico are at serious risk of abuse. Research by Amnesty International as well as reports of the NHRC (National Human Rights) in Mexico, have indicated the major humanitarian crisis faced by thousands of migrants traveling in the shadows. However, the true extent of the problem remains invisible to the general population. The fact that federal and state governments leave no proper record of abuse and do not publish reliable data contributes to ignorance and misinformation, often spread by the media that portray migrants as the source of crime rather than their victims. Discrimination and intolerance against irregular migrants can generate greater hostility and exclusion. According to the modus operandi that has been recorded criminal organizations and criminal groups linked to drug trafficking structures deprive migrants of their liberty for forced labor and illegal activities related to drug trafficking, even some have been kidnapped for be trained as murderers . If the victim or their family cannot pay the ransom, the kidnapped person may suffer torture, mutilation and amputation of limbs or death. Migrant women are victims of sexual abuse during her abduction as well. In 2011, at least 177 bodies were identified in the largest mass grave found in Mexico, located in the town of San Fernando, in the border state of Tamaulipas, most of the victims were killed by blunt instruments, and most seemed to be immigrants and travelers passing through the country. With dozens of small graves discovered in northern Mexico, this may suggest a change in tactics between organized crime groups to the different means of obtaining revenue and reduce murder profile methods. Competition and conflict over territorial control drug trafficking can provide strong incentives for organized crime groups send signals of violence to the authorities and rival groups. However, as some Mexican organized crime groups are increasingly looking to take advantage of income and vulnerable groups, such as Central American migrants seem less interested in advertising his work to authorities and others, and more interested in evading detection and confrontation. This paper pretends to analyze the introduction of this new trend of kidnapping migrants for forced labors by drug cartels in Mexico into the forms of contemporary slavery and its implications.

Keywords: international law, migration, transnational organized crime

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Authors: Syeda Kiran Shahzadi, Nasir Mahmood, Muhammad Abdul Qadir

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In the current research, three recombinant human interferon alpha-2b proteins (two modified and one normal form) were produced and Pegylated with an aim to produce more effective drugs against viral infections and cancers. The modified recombinant human interferon alpha-2b proteins were produced by site-directed modifications of interferon alpha 2b gene, targeting the amino acids at positions ‘R23’ and ‘H34’. The resulting chemically modified and unmodified forms of human interferon alpha 2b were conjugated with methoxy-polyethylene glycol propanealdehyde (400 KDa) and methoxy-polyethylene glycol succinimidyl succinate (400 KDa). Pegylation of normal and modified forms of Interferon alpha-2b prolong their release time and enhance their efficacy. The conjugation of PEG with modified and unmodified human interferon alpha 2b protein drugs was also characterized with 1H-NMR, HPLC, and SDS-PAGE. Antiproliferative assays of modified and unmodified forms of drugs were performed in cell based bioassays using MDBK cell lines. The results indicated that experimentally produced recombinant human interferon alpha-2b proteins were biologically active and resulted in significant inhibition of cell growth.

Keywords: protein refolding, antiproliferative activities, biomedical applications, human interferon alpha-2b, pegylation, mPEG-propionaldehyde, site directed mutagenesis, E. coli expression

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Authors: Stanely Nsubuga

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Background In Uganda, injection drug use is a growing but less studied problem. Preventing the transition to injection drug use may help prevent blood-borne viral transmission, but little is known about when and how people transition to injection drug use. A greater understanding of this transition process may aid in the country’s efforts to prevent the continued growth of injection drug use, HIV, and hepatitis C Virus (HCV) infection among people who inject drugs (PWID). Methods Using a rapid situation assessment framework, we conducted semi-structured interviews among 125 PWID (102 males and 23 females)—recruited through outreach and snow-ball sampling. Participants were interviewed about their experiences on when and how they transitioned into injection drug use and these issues were also discussed in 12 focus groups held with the participants. Results All the study participants started their drug use career with non-injecting forms including chewing, smoking, and sniffing before transitioning to injecting. Transitioning was generally described as a peer-driven and socially learnt behavior. The participants’ social networks and accessibility to injectable drugs on the market and among close friends influenced the time lag between first regular drug use and first injecting—which took an average of 4.5 years. By the age of 24, at least 81.6% (95.7% for females and 78.4% for males) had transitioned into injecting. Over 84.8% shared injecting equipment during their first injection, 47.2% started injecting because a close friend was already injecting, 26.4% desired to achieve a greater “high” (26.4%) which could reflect drug-tolerance, and 12% out of curiosity.

Keywords: People who Use Drugs, transition, injection drug use, Uganda

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Authors: K. R. Thabethe, G. A. Adefolaju, M. J. Hosie

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Cervical cancer is the third most commonly diagnosed cancer globally and it is one of three AIDS defining malignancies. Highly active antiretroviral therapy (HAART) is a combination of three or more antiretroviral drugs and has been shown to play a significant role in reducing the incidence of some AIDS defining malignancies, although its effect on cervical cancer is still unclear. The aim of this study was to investigate the relationship between cervical cancer and HAART. This was achieved by studying the expression of two signalling molecules expressed in cervical cancer; MUC1 and P65. Following the 24 hour treatment of a cervical cancer cell line, HCS-2, with drugs which are commonly used as part of HAART at their clinical plasma concentrations, real-time qPCR and immunofluorescence were used in order to study gene and protein expression. A one way ANOVA followed by a Tukey Kramer Post Hoc test was conducted using JMP 11 software on both sets of data. The drug classified as a protease inhibitor (PI) (i.e. LPV/r) reduced MUC1 and P65 gene and protein expression more than the other drug tested. PIs are known to play a significant role in cell death, therefore the cells were thought to be more susceptible to cell death following treatment with PIs. In conclusion, the drugs used, especially the PI showed some anticancer effects by facilitating cell death through decreased gene and protein expression of MUC1 and P65 and present promising agents for cancer treatment.

Keywords: cervical cancer, haart, MUC1, P65

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Authors: Monika Szpringer, Aneta Pawlinska

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Adverse childhood experiences are linked to various types of health and adapt problems at different stages of life. They include various types of abuse, neglect, and dysfunctional environment. They have an unfavorable impact on the development of a child and his future functioning in society. Adolescents who were exposed to bad treatment may suffer from health problems during adulthood, like chronic diseases, psychological disorders, drug addiction, and suicide attempts. Objective: The aim of the project is to assess the relationship between adverse childhood experiences and the sense of efficacy and coping with emotions among teenagers aged 16-18 taking drugs. Material And Methods: The research was carried out in the period from March to December 2018 in Mazowieckie, Świętokrzyskie, Łódzkie, and Lubelskie Voivodship. The group consisted of 600 people aged 16-18 (M=16,58; SD=0, 78), men (63,2%) aged 16-18 (M=16,60;SD= 0,78) and women (35,5%) aged 16-18 (M16,55;SD=0,79). Participants included residents from Youth Educational Centers and Youth Sociotherapy Centers. Each participant filled in Author's Questionnaire, Adverse Childhood Questionnaire, then Courtland Emotional Control Scale-CECS and Generalized Self Efficacy Scale-GSES. Results and conclusions: The most common adverse experiences, according to teenagers, were family abuse, divorce/separation/parent's death, overuse of alcohol or drugs by an inmate, and emotional neglect. Adolescents who suffered from five to twelve adverse experiences had a higher level of depression's control. Adverse childhood experiences have an importance for the level of anger and depression's control among teenagers taking drugs. The greatest importance of the level of anger's control has emotional neglect. A higher level of emotional neglect is linked to a lower ability to control anger. The greatest importance of the level of depression's control has physical abuse and emotional neglect. The higher physical abuse during childhood, and the higher frequency of emotional neglect, the bigger the depression's control. The sense of efficacy in the group of people who suffered from one to four adverse experiences is close to the sense of efficacy that suffered people from five to twelve adverse experiences. The most important factor lowering the sense of one's efficacy was the intensification of sexual abuse. It was confirmed that the intensification and frequency of adverse childhood experiences were higher among women than men. Women also characterized lower anger control and greater depression's control. The authors’ own analyses confirmed the relationship between adverse childhood experiences and the sense of efficacy and coping with emotions among teenagers aged 16-18 taking drugs.

Keywords: adolescences, adverse childhood experiences, coping with emotions, drugs

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Authors: Tsugunosuke Sakai, Haruya Tamaki, Ryuichi Yoshida, Ryohei Egusa, Etsuji Yamaguchi, Shigenori Inagaki, Fusako Kusunoki, Miki Namatame, Masanori Sugimoto, Hiroshi Mizoguchi

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We aim to develop a full-body interaction game that could let children cooperate and interact with other children in small groups. As the first step for our aim, the objective of the full-body interaction game developed in this study is to make interaction between children. The game requires two children to jump together with the same timing. We let children experience the game and answer the questionnaires. The children using several strategies to coordinate the timing of their jumps were observed. These included shouting time, watching each other, and jumping in a constant rhythm as if they were skipping rope. In this manner, we observed the children playing the game while cooperating with each other. The results of a questionnaire to evaluate the proposed interactive game indicate that the jumping game was a very enjoyable experience in which the participants could immerse themselves. Therefore, the game enabled children to experience cooperation with others by using body movements.

Keywords: children, cooperation, full-body interaction game, kinect sensor

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Authors: S. Roy, R. Rekha, K. Sriram, G. Subhadra, R. Johana

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Cardiovascular disease remains a leading cause of death in most industrialized countries. Many chemical drugs are available in the market which targets different receptor proteins related to cardiovascular diseases. Of late the traditional herbal drugs are safer when compared to chemical drugs because of its side effects. However, many herbal remedies used in treating cardiovascular diseases have not undergone scientific assessment to prove its pharmacological activities. There are many natural compounds, nature derived and Natural product mimic compounds are available which are in the market as approved drug. In the most of the cases drug activity at the molecular level are not known. Here we have categorized those compounds with our experimental compounds in different classes based on the structural similarity and physicochemical properties, using a tool, Chemmine and has attempted to understand the mechanism of the action of a experimental compound, which are clustered with Simvastatin, Lovastatin, Mevastatin and Pravastatin. Target protein molecule for Simvastatin, Lovastatin, Mevastatin and Pravastatin is HMG-CoA reductase, so we concluded that the experimental compound may be able to bind to the same target. Molecular docking and atomic interaction studies with simvastatin and our experimental compound were compared. A pharmacophore modeling was done based on the experimental compound and HMG-CoA reductase inhibitor.

Keywords: molecular docking, physicochemical properties, pharmacophore modeling structural similarity, pravastatin

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