Search results for: discovery of misattributed paternity

Authors: Sheraz Gul

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The requirements for progressing a compound to clinical trials is well established and relies on the results from in-vitro and in-vivo animal tests to indicate that it is likely to be safe and efficacious when testing in humans. The typical data package required will include demonstrating compound safety, toxicity, bioavailability, pharmacodynamics (potential effects of the compound on body systems) and pharmacokinetics (how the compound is potentially absorbed, distributed, metabolised and eliminated after dosing in humans). If the desired criteria are met and the compound meets the clinical Candidate criteria and is deemed worthy of further development, a submission to regulatory bodies such as the US Food & Drug Administration for an exploratory Investigational New Drug Study can be made. The purpose of this study is to collect data to establish that the compound will not expose humans to unreasonable risks when used in limited, early-stage clinical studies in patients or normal volunteer subjects (Phase I). These studies are also designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on their effectiveness. In order to reach the above goals, we have developed a pre-clinical high throughput Absorption, Distribution, Metabolism and Excretion–Toxicity (ADME–Toxicity) panel of assays to identify compounds that are likely to meet the Lead and Candidate compound acceptance criteria. This panel includes solubility studies in a range of biological fluids, cell viability studies in cancer and primary cell-lines, mitochondrial toxicity, off-target effects (across the kinase, protease, histone deacetylase, phosphodiesterase and GPCR protein families), CYP450 inhibition (5 different CYP450 enzymes), CYP450 induction, cardio-toxicity (hERG) and gene-toxicity. This panel of assays has been applied to multiple compound series developed in a number of projects delivering Lead and clinical Candidates and examples from these will be presented.

Keywords: absorption, distribution, metabolism and excretion–toxicity , drug discovery, food and drug administration , pharmacodynamics

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Authors: Alaa Eddien Abdallah, Bajes Yousef Alskarnah

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Ant colony based routing algorithms are known to grantee the packet delivery, but they suffer from the huge overhead of control messages which are needed to discover the route. In this paper we utilize the network nodes positions to group the nodes in connected clusters. We use clusters-heads only on forwarding the route discovery control messages. Our simulations proved that the new algorithm has decreased the overhead dramatically without affecting the delivery rate.

Keywords: ad-hoc network, MANET, ant colony routing, position based routing

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Authors: Yang Yang, Lu Xin

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The study of extant musical sites can provide a side-by-side picture of historical ethnomusicological information. In their data collection on Chinese opera houses, researchers found that one Ming Dynasty opera house reached a width of nearly 18 meters, while all opera houses of the same period and after it was far from such a width, being significantly smaller than 18 meters. The historical transient fluctuations in the data dimension of width that caused Chinese theatres to fluctuate in the absence of construction scale constraints have piqued the interest of researchers as to why there is data variation in width. What factors have contributed to the lack of further expansion in the width of theatres? To address this question, this study used a comparative approach to conduct a venue experiment between this theater stage and another theater stage for non-heritage opera performances, collecting the subjective perceptions of performers and audiences at different theater stages, as well as combining BK Connect platform software to measure data such as echo and delay. From the subjective and objective results, it is inferred that the Chinese ancients discovered and understood the acoustical phenomenon of the Haas effect by exploring the effect of stage width on musical performance and appreciation of listening states during the Ming Dynasty and utilized this discovery to serve music in subsequent stage construction. This discovery marked a node of evolution in Chinese architectural acoustics technology driven by musical demands. It is also instructive to note that, in contrast to many of the world's "unsuccessful civilizations," China can use a combination of heritage and intangible cultural research to chart a clear, demand-driven course for the evolution of human music technology, and that the findings of such research will complete the course of human exploration of music acoustics. The findings of such research will complete the journey of human exploration of music acoustics, and this practical experience can be applied to the exploration and understanding of other musical heritage base data.

Keywords: Haas effect, musical acoustics, history of acoustical technology, Chinese opera stage, structure

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Authors: Fatima Al-Aswadi, Chan Yong

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With the large volume of unstructured data that increases day by day on the web, the motivation of representing the knowledge in this data in the machine processable form is increased. Ontology is one of the major cornerstones of representing the information in a more meaningful way on the semantic Web. The goal of Ontology learning from text is to elicit and represent domain knowledge in the machine readable form. This paper aims to give a follow-up review on the ontology learning systems from text and some of their defects. Furthermore, it discusses how far the ontology learning process will enhance in the future.

Keywords: concept discovery, deep learning, ontology learning, semantic relation, semantic web

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Authors: Esna B. Buğday, Niray Tunçel

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Spirituality has a motivational influence on consumers' psychological states, lifestyles, and behavioral intentions. Spirituality refers to the feeling that there is a divine power greater than ourselves and a connection among oneself, others, nature, and the sacred. In addition, spirituality concerns the human soul and spirit against the material and physical world and consists of three dimensions: self-discovery, relationships, and belief in a higher power. Of them, self-discovery is to explore the meaning and the purpose of life. Relationships refer to the awareness of the connection between human beings and nature as well as respect for them. In addition, higher power represents the transcendent aspect of spirituality, which means to believe in a holy power that creates all the systems in the universe. Furthermore, a voluntary simplicity lifestyle is (1) to adopt a simple lifestyle by minimizing the attachment to and the consumption of material things and possessions, (2) to have an ecological awareness respecting all living creatures, and (3) to express the desire for exploring and developing the inner life. Voluntary simplicity is a multi-dimensional construct that consists of a desire for a voluntarily simple life (e.g., avoiding excessive consumption), cautious attitudes in shopping (e.g., not buying unnecessary products), acceptance of self-sufficiency (e.g., being self-sufficient individual), and rejection of highly developed functions of products (e.g., preference for simple functioned products). One of the main reasons for living simply is to sustain a spiritual life, as voluntary simplicity provides the space for achieving psychological and spiritual growth, cultivating self-reliance since voluntary simplifier frees themselves from the overwhelming externals and takes control of their daily lives. From this point of view, it is expected that people with a strong sense of spirituality will be likely to adopt a simple lifestyle. In this respect, the study aims to examine the impact of spirituality on consumers' voluntary simple lifestyle tendencies. As consumers' consumption attitudes and behaviors depend on their lifestyles, exploring the factors that lead them to embrace voluntary simplicity significantly predicts their purchase behavior. In this respect, this study presents empirical research based on a data set collected from 478 Turkish consumers through an online survey. First, exploratory factor analysis is applied to the data to reveal the dimensions of spirituality and voluntary simplicity scales. Second, confirmatory factor analysis is conducted to assess the measurement model. Last, the hypotheses are analyzed using partial least square structural equation modeling (PLS-SEM). The results confirm that spirituality's self-discovery and relationships dimensions positively impact both cautious attitudes in shopping and acceptance of self-sufficiency dimensions of voluntary simplicity. In contrast, belief in a higher power does not significantly influence consumers' voluntary simplicity tendencies. Even though there has been theoretical support drawing a positive relationship between spirituality and voluntary simplicity, to the best of the authors' knowledge, this has not been empirically tested in the literature before. Hence, this study contributes to the current knowledge by analyzing the direct influence of spirituality on consumers' voluntary simplicity tendencies. Additionally, analyzing this impact on the consumers of an emerging market is another contribution to the literature.

Keywords: spirituality, voluntary simplicity, self-sufficiency, conscious shopping, Turkish consumers

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Authors: Helena Maragou

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Introducing Toni Morrison’s fiction to a classroom overseas entails a significant pedagogical investment, from monitoring students’ uncertain journey through Morrison’s shifty semantics to filling in the gaps of cultural knowledge and understanding for the students to be able to relate text to context. A rewarding process, as Morrison’s works present a tremendous opportunity for transnational dialogue, an opportunity that hinges upon Toni Morrison’s bringing to the fore the untold and unspeakable lives of racial ‘Others’, but also, crucially, upon her broader critique of Western ideological hegemony. This critique is a fundamental aspect of Toni Morrison’s politics and one that appeals to young readers of Toni Morrison in Greece at a time when the questioning of institutions and ideological traditions is precipitated by regional and global change. It is more or less self-evident that to help a class of international students get aboard a Morrison novel, an instructor should begin by providing them with cultural context. These days, students’ exposure to Hollywood representations of the African American past and present, as well as the use of documentaries, photography, music videos, etc., as supplementary class material, provide a starting point, a workable historical and cultural framework for textual comprehension. The true challenge, however, lies ahead: it is one thing for students to intellectually grasp the historical hardships and traumas of Morrison’s characters and to even engage in aesthetic appreciation of Morrison’s writing; quite another to relate to her works as articulations of experiences akin to their own. The great challenge, then, is in facilitating students’ discovery of the universal Morrison, the author who speaks across cultures while voicing the untold tales of her own people; this process of discovery entails, on a pedagogical level, that students be guided through the works’ historical context, to plunge into the intricacies of Morrison’s discourse, itself an elaborate linguistic booby trap, so as to be finally brought to reconsider their own historical experiences using the lens of Morrison’s fiction. The paper will be based on experience of teaching a Toni Morrison seminar to a class of Greek students at the American College of Greece and will draw from students’ exposure and responses to Toni Morrison’s “Nobel Prize Lecture,” as well as her novels Song of Solomon and Home.

Keywords: toni morrison, international classroom, pedagogy, African American literature

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Authors: Pablo Chico De Guzman, Cesar Sanchez

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Microservice architectures are increasingly in distributed cloud applications due to the advantages on the software composition, development speed, release cycle frequency and the business logic time to market. On the other hand, these architectures also introduce some challenges on the testing and release phases of applications. Container technology solves some of these issues by providing reproducible environments, easy of software distribution and isolation of processes. However, there are other issues that remain unsolved in current container technology when dealing with multiple machines, such as networking for multi-host communication, service discovery, load balancing or data persistency (even though some of these challenges are already solved by traditional cloud vendors in a very mature and widespread manner). Container cluster management tools, such as Kubernetes, Mesos or Docker Swarm, attempt to solve these problems by introducing a new control layer where the unit of deployment is the container (or the pod — a set of strongly related containers that must be deployed on the same machine). These tools are complex to configure and manage and they do not follow a pure immutable infrastructure approach since servers are reused between deployments. Indeed, these tools introduce dependencies at execution time for solving networking or service discovery problems. If an error on the control layer occurs, which would affect running applications, specific expertise is required to perform ad-hoc troubleshooting. As a consequence, it is not surprising that container cluster support is becoming a source of revenue for consulting services. This paper presents i2kit, a deployment tool based on the immutable infrastructure pattern, where the virtual machine is the unit of deployment. The input for i2kit is a declarative definition of a set of microservices, where each microservice is defined as a pod of containers. Microservices are built into machine images using linuxkit —- a tool for creating minimal linux distributions specialized in running containers. These machine images are then deployed to one or more virtual machines, which are exposed through a cloud vendor load balancer. Finally, the load balancer endpoint is set into other microservices using an environment variable, providing service discovery. The toolkit i2kit reuses the best ideas from container technology to solve problems like reproducible environments, process isolation, and software distribution, and at the same time relies on mature, proven cloud vendor technology for networking, load balancing and persistency. The result is a more robust system with no learning curve for troubleshooting running applications. We have implemented an open source prototype that transforms i2kit definitions into AWS cloud formation templates, where each microservice AMI (Amazon Machine Image) is created on the fly using linuxkit. Even though container cluster management tools have more flexibility for resource allocation optimization, we defend that adding a new control layer implies more important disadvantages. Resource allocation is greatly improved by using linuxkit, which introduces a very small footprint (around 35MB). Also, the system is more secure since linuxkit installs the minimum set of dependencies to run containers. The toolkit i2kit is currently under development at the IMDEA Software Institute.

Keywords: container, deployment, immutable infrastructure, microservice

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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: Ugo Rovigatti

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Neuroblastoma (NBL) has epitomized for at least 40 years our understanding of cancer cellular and molecular biology and its potential applications to novel therapeutic strategies. This includes the discovery of the very first oncogene aberrations and tumorigenesis suppression by differentiation in the 80s; the potential role of suppressor genes in the 90s; the relevance of immunotherapy in the millennium first, and the discovery of additional mutations by NGS technology in the millennium second decade. Similar discoveries were achieved in the majority of human cancers, and similar therapeutic interventions were obtained subsequently to NBL discoveries. Unfortunately, targeted therapies suggested by specific mutations (such as MYCN amplification –MNA- present in ¼ or 1/5 of cases) have not elicited therapeutic successes in aggressive NBL, where the prognosis is still dismal. The reasons appear to be linked to Tumor Heterogeneity, which is particularly evident in NBL but also a clear hallmark of aggressive human cancers generally. The new avenue of cancer immunotherapy (CIT) provided new hopes for cancer patients, but we still ignore the cellular or molecular targets. CIT is emblematic of high-risk disease (HR-NBL) since the mentioned GD2 passive immunotherapy is still providing better survival. We recently critically reviewed and evaluated the literature depicting the genomic landscapes of HR-NBL, coming to the qualified conclusion that among hundreds of affected genes, potential targets, or chromosomal sites, none correlated with anti-GD2 sensitivity. A better explanation is provided by the Micro-Foci inducing Virus (MFV) model, which predicts that neuroblasts infection with the MFV, an RNA virus isolated from a cancer-cluster (space-time association) of HR-NBL cases, elicits the appearance of MNA and additional genomic aberrations with mechanisms resembling chromothripsis. Neuroblasts infected with low titers of MFV amplified MYCN up to 100 folds and became highly transformed and malignant, thus causing neuroblastoma in young rat pups of strains SD and Fisher-344 and larger tumor masses in nu/nu mice. An association was discovered with GD2 since this glycosphingolipid is also the receptor for the family of MFV virus (dsRNA viruses). It is concluded that a dsRNA virus, MFV, appears to provide better explicatory mechanisms for the genesis of i) specific genomic aberrations such as MNA; ii) extensive tumor heterogeneity and chromothripsis; iii) the effects of passive immunotherapy with anti-GD2 monoclonals and that this and similar models should be further investigated in both pediatric and adult cancers.

Keywords: neuroblastoma, MYCN, amplification, viruses, GD2

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Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang

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Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.

Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation

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Authors: Peter Pfeifer, Julian Pfeifer, Niko Pfeifer

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Information processing is the focus of brain and cognition research. This work has a different perspective; it starts with behaviors. The detailed analysis of behaviors leads to the discovery that a significant proportion of them are based on only five basic drives. These basic drives are combinable, and the combinations result in the diversity of human behavior and thinking. The key elements are drive memories. They collect memories of drive-related situations and feelings. They contain variations of basic drives in numerous areas of life and build combinations with different meanings depending on the area. Human thinking could be explained with variations on these nested combinations of basic drives.

Keywords: cognition, psycholinguistics, psychology, psychophysiology of cognition

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Authors: Alexander Gretchenko, Liudmila Goncharenko, Sergey Sybachin

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This article summarizes the history of the discovery of N.D. Kondratiev of large cycles of economic conditions, as well as the creation and justification of the theory of innovation-cyclical economic development of Kondratiev-Schumpeter. An analysis of it in modern conditions is providing. The main conclusion in this article is that in general terms today it can be argued that the Kondratiev-Schumpeter theory is sufficiently substantiated. Further, the possibility of making a forecast of the development of the economic situation in the direction of applying this theory in practice, which demonstrate its effectiveness, is considered.

Keywords: Kondratiev's big cycles of economic conjuncture, Schumpeter's theory of innovative economic development, long-term cyclical forecasting, dating of Kondratiev cycles

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Authors: Mansir Abubakar, Hazlina Hamdan, Norwati Mustapha, Teh Noranis Mohd Aris

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In order to build a matching pattern for each class correspondences of ontology, it is required to specify a set of attribute correspondences across two corresponding classes by clustering. Clustering reduces the size of potential attribute correspondences considered in the matching activity, which will significantly reduce the computation workload; otherwise, all attributes of a class should be compared with all attributes of the corresponding class. Most existing ontology matching approaches lack scalable attributes discovery methods, such as cluster-based attribute searching. This problem makes ontology matching activity computationally expensive. It is therefore vital in ontology matching to design a scalable element or attribute correspondence discovery method that would reduce the size of potential elements correspondences during mapping thereby reduce the computational workload in a matching process as a whole. The objective of this work is 1) to design a clustering method for discovering similar attributes correspondences and relationships between ontologies, 2) to discover element correspondences by classifying elements of each class based on element’s value features using K-medoids clustering technique. Discovering attribute correspondence is highly required for comparing instances when matching two ontologies. During the matching process, any two instances across two different data sets should be compared to their attribute values, so that they can be regarded to be the same or not. Intuitively, any two instances that come from classes across which there is a class correspondence are likely to be identical to each other. Besides, any two instances that hold more similar attribute values are more likely to be matched than the ones with less similar attribute values. Most of the time, similar attribute values exist in the two instances across which there is an attribute correspondence. This work will present how to classify attributes of each class with K-medoids clustering, then, clustered groups to be mapped by their statistical value features. We will also show how to map attributes of a clustered group to attributes of the mapped clustered group, generating a set of potential attribute correspondences that would be applied to generate a matching pattern. The K-medoids clustering phase would largely reduce the number of attribute pairs that are not corresponding for comparing instances as only the coverage probability of attributes pairs that reaches 100% and attributes above the specified threshold can be considered as potential attributes for a matching. Using clustering will reduce the size of potential elements correspondences to be considered during mapping activity, which will in turn reduce the computational workload significantly. Otherwise, all element of the class in source ontology have to be compared with all elements of the corresponding classes in target ontology. K-medoids can ably cluster attributes of each class, so that a proportion of attribute pairs that are not corresponding would not be considered when constructing the matching pattern.

Keywords: attribute correspondence, clustering, computational workload, k-medoids clustering, ontology matching

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Authors: Jing Zhang, Daniel Nikovski

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We propose an approximation algorithm called LINKUMP to compute the Pan Matrix Profile (PMP) under the unnormalized l∞ distance (useful for value-based similarity search) using double-ended queue and linear interpolation. The algorithm has comparable time/space complexities as the state-of-the-art algorithm for typical PMP computation under the normalized l₂ distance (useful for shape-based similarity search). We validate its efficiency and effectiveness through extensive numerical experiments and a real-world anomaly detection application.

Keywords: pan matrix profile, unnormalized euclidean distance, double-ended queue, discord discovery, anomaly detection

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Authors: Kanyarat Bussaban, Kunyanuth Kularbphettong

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This research aims to create a model for analysis of student behavior using Library resources based on data mining technique in case of Suan Sunandha Rajabhat University. The model was created under association rules, apriori algorithm. The results were found 14 rules and the rules were tested with testing data set and it showed that the ability of classify data was 79.24 percent and the MSE was 22.91. The results showed that the user’s behavior model by using association rule technique can use to manage the library resources.

Keywords: behavior, data mining technique, a priori algorithm, knowledge discovery

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Authors: Stefano Fantin

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The present analysis outcomes from the research undertaken in the course of the European-funded project EUNITY, which targets the gaps in research and development on cybersecurity and privacy between Europe and Japan. Under these auspices, the research presents a study on the policy approach of Japan, the EU and a number of Member States of the Union with regard to the handling and discovery of software vulnerabilities, with the aim of identifying methodological differences and similarities. This research builds upon a functional comparative analysis of both public policies and legal instruments from the identified jurisdictions. The result of this analysis is based on semi-structured interviews with EUNITY partners, as well as by the participation of the researcher to a recent report from the Center for EU Policy Study on software vulnerability. The European Union presents a rather fragmented legal framework on software vulnerabilities. The presence of a number of different legislations at the EU level (including Network and Information Security Directive, Critical Infrastructure Directive, Directive on the Attacks at Information Systems and the Proposal for a Cybersecurity Act) with no clear focus on such a subject makes it difficult for both national governments and end-users (software owners, researchers and private citizens) to gain a clear understanding of the Union’s approach. Additionally, the current data protection reform package (general data protection regulation), seems to create legal uncertainty around security research. To date, at the member states level, a few efforts towards transparent practices have been made, namely by the Netherlands, France, and Latvia. This research will explain what policy approach such countries have taken. Japan has started implementing a coordinated vulnerability disclosure policy in 2004. To date, two amendments can be registered on the framework (2014 and 2017). The framework is furthermore complemented by a series of instruments allowing researchers to disclose responsibly any new discovery. However, the policy has started to lose its efficiency due to a significant increase in reports made to the authority in charge. To conclude, the research conducted reveals two asymmetric policy approaches, time-wise and content-wise. The analysis therein will, therefore, conclude with a series of policy recommendations based on the lessons learned from both regions, towards a common approach to the security of European and Japanese markets, industries and citizens.

Keywords: cybersecurity, vulnerability, European Union, Japan

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Authors: Evelyn Asante Yeboah, Kwabena O. Asubonteng, Justice Camillus Mensah, Christine Furst

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Smallholder-dominated mosaic landscapes in rural Africa are relevant for food production, biodiversity conservation, and climate regulation. Land-use transitions threaten the multifunctionality of such landscapes, especially the production capacity of arable lands resulting in food security challenges. Using land-cover maps derived from maximum likelihood classification of Landsat satellite images for the years 2002, 2015, and 2020, post-classification change detection, landscape metrics, and key informant interviews, the study assessed the implications of rubber plantation expansion and oil business development on the food production capacity of Ahanta West District, Ghana. The analysis reveals that settlement and rubber areas expanded by 5.82% and 10.33% of the landscape area, respectively, between 2002 and 2020. This increase translates into over twice their initial sizes (144% in settlement change and 101% in rubber change). Rubber plantation spread dominates the north and southwestern areas, whereas settlement is widespread in the eastern parts of the landscape. Rubber and settlement expanded at the expense of cropland, palm, and shrublands. Land-use transitions between cropland, palm, and shrubland were targeting each other, but the net loss in shrubland was higher (-17.27%). Isolation, subdivision, connectedness, and patch adjacency indices showed patch consolidation in the landscape configuration from 2002 to 2015 and patch fragmentation from 2015 to 2020. The study also found patches with consistent increasing connectivity in settlement areas indicating the influence of oil discovery developments and fragmentation tendencies in rubber, shrubland, cropland, and palm, indicating springing up of smaller rubber farms, the disappearance of shrubland, and splitting up of cropland and palm areas respectively. The results revealed a trend in land-use transitions in favor of smallholder rubber plantation expansion and oil discovery developments, which suggest serious implications on food production systems and poses a risk for food security and landscape multifunctional characteristics. To ensure sustainability in land uses, this paper recommends the enforcement of legislative instruments governing spatial planning and land use in Ghana as embedded in the 2016 land-use and spatial planning act.

Keywords: food production systems, food security, Ghana’s west coast, land-use transitions, multifunctional rural landscapes

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Authors: Paula Verdugo-Hernandez, Patricio Cumsille

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We analyze a first-class on the convergence of real number sequences, named hereafter sequences, to foster exploration and discovery of concepts through graphical representations before engaging students in proving. The main goal was to differentiate between sequences and continuous functions-of-a-real-variable and better understand concepts at an initial stage. We applied the analytic frame of mathematical working spaces, which we expect to contribute to extending to sequences since, as far as we know, it has only developed for other objects, and which is relevant to analyze how mathematical work is built systematically by connecting the epistemological and cognitive perspectives, and involving the semiotic, instrumental, and discursive dimensions.

Keywords: convergence, graphical representations, mathematical working spaces, paradigms of real analysis, real number sequences

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Authors: Margareta Simina Stanc, Aurel Mototolea, Tiberiu Potarniche

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The city of Constanta (former Köstence) is located in the Dobrogea region, on the west shore of the Black Sea. Between 1420-1878, Dobrogea was a possession of the Ottoman Empire. Archaeological researches starting with the second half of the 20th century revealed various traces of the Ottoman period in this region. Between 2016-2018, preventive archaeological research conducted in the perimeter of the old Ottoman city of Köstence led to the discovery of structures of habitation as well as of numerous artifacts of the Ottoman period (pottery, coins, buckles, etc.). This study uses the analysis of these new discoveries to complete the picture of daily life in the Ottoman period. In 2017, in the peninsular area of Constanta, preventive archaeological research began at a point in the former Ottoman area. In the range between the current ironing level and the -1.5m depth, the Ottoman period materials appeared constantly. It is worth noting the structure of a large building that has been repaired at least once but could not be fully investigated. In parallel to this wall, there was arranged a transversally arranged brick-lined drainage channel. The drainage channel is poured into a tank (hazna), filled with various vintage materials, but mainly gilded ceramics and iron objects. This type of hazna is commonly found in Constanta for the pre-modern and modern period due to the lack of a sewage system in the peninsular area. A similar structure, probably fountain, was discovered in 2016 in another part of the old city. An interesting piece is that of a cup (probably) Persians and a bowl belonging to Kütahya style, both of the 17th century, proof of commercial routes passing through Constanta during that period and indirectly confirming the documentary testimonies of the time. Also, can be mentioned the discovery, in the year 2016, on the occasion of underwater research carried out by specialists of the department of the Constanta Museum, at a depth of 15 meters, a Turkish oil lamp (17th - the beginning of the 18th century), among other objects of a sunken ship. The archaeological pieces, in a fragmentary or integral state, found in research campaigns 2016-2018, are undergoing processing or restoration, leaving out all the available information, and establishing exact analogies. These discoveries bring new data to the knowledge of daily life during the Ottoman administration in the former Köstence, a locality on the periphery of the Islamic world.

Keywords: habitation, material culture, Ottoman administration, Ottoman archaeology, periphery

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Authors: Khadidja Belbachir, Hafida Belbachir

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subsequently the expansion of the physical supports storage and the needs ceaseless to accumulate several data, the sequential algorithms of associations’ rules research proved to be ineffective. Thus the introduction of the new parallel versions is imperative. We propose in this paper, a parallel version of a sequential algorithm “Partition”. This last is fundamentally different from the other sequential algorithms, because it scans the data base only twice to generate the significant association rules. By consequence, the parallel approach does not require much communication between the sites. The proposed approach was implemented for an experimental study. The obtained results, shows a great reduction in execution time compared to the sequential version and Count Distributed algorithm.

Keywords: association rules, distributed data mining, partition, parallel algorithms

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Authors: Gurleen Kour, Mowkshi Khullar, B. K. Chandan, Parvinder Pal Singh, Kushalava Reddy Yumpalla, Gurunadham Munagala, Ram A. Vishwakarma, Zabeer Ahmed

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New chemotherapeutic compounds against multidrug-resistant Mycobacterium tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis (TB). Apart from in-vitro potency against the target, physiochemical properties and pharmacokinetic properties play an imperative role in the process of drug discovery. We have identified novel nitroimidazole derivatives with potential activity against mycobacterium tuberculosis. One lead candidates, MCD-017, which showed potent activity against H37Rv strain (MIC=0.5µg/ml) and was further evaluated in the process of drug development. Methods: Basic physicochemical parameters like solubility and lipophilicity (LogP) were evaluated. Thermodynamic solubility was determined in PBS buffer (pH 7.4) using LC/MS-MS. The partition coefficient (Log P) of the compound was determined between octanol and phosphate buffered saline (PBS at pH 7.4) at 25°C by the microscale shake flask method. The compound followed Lipinski’s rule of five, which is predictive of good oral bioavailability and was further evaluated for metabolic stability. In-vitro metabolic stability was determined in rat liver microsomes. The hepatotoxicity of the compound was also determined in HepG2 cell line. In vivo pharmacokinetic profile of the compound after oral dosing was also obtained using balb/c mice. Results: The compound exhibited favorable solubility and lipophilicity. The physical and chemical properties of the compound were made use of as the first determination of drug-like properties. The compound obeyed Lipinski’s rule of five, with molecular weight < 500, number of hydrogen bond donors (HBD) < 5 and number of hydrogen bond acceptors(HBA) not more then 10. The log P of the compound was less than 5 and therefore the compound is predictive of exhibiting good absorption and permeation. Pooled rat liver microsomes were prepared from rat liver homogenate for measuring the metabolic stability. 99% of the compound was not metabolized and remained intact. The compound did not exhibit cytoxicity in hepG2 cells upto 40 µg/ml. The compound revealed good pharmacokinetic profile at a dose of 5mg/kg administered orally with a half life (t1/2) of 1.15 hours, Cmax of 642ng/ml, clearance of 4.84 ml/min/kg and a volume of distribution of 8.05 l/kg. Conclusion : The emergence of multi drug resistance (MDR) and extensively drug resistant (XDR) Tuberculosis emphasize the requirement of novel drugs active against tuberculosis. Thus, the need to evaluate physicochemical and pharmacokinetic properties in the early stages of drug discovery is required to reduce the attrition associated with poor drug exposure. In summary, it can be concluded that MCD-017 may be considered a good candidate for further preclinical and clinical evaluations.

Keywords: mycobacterium tuberculosis, pharmacokinetics, physicochemical properties, hepatotoxicity

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Authors: Elsayeda M. Elgaml, Dina M. Ibrahim, Elsayed A. Sallam

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Association rule mining is one of the most important fields of data mining and knowledge discovery. In this paper, we propose an efficient multiple support frequent pattern growth algorithm which we called “MSFP-growth” that enhancing the FP-growth algorithm by making infrequent child node pruning step with multiple minimum support using maximum constrains. The algorithm is implemented, and it is compared with other common algorithms: Apriori-multiple minimum supports using maximum constraints and FP-growth. The experimental results show that the rule mining from the proposed algorithm are interesting and our algorithm achieved better performance than other algorithms without scarifying the accuracy.

Keywords: association rules, FP-growth, multiple minimum supports, Weka tool

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Authors: Inna Kornienko, Svetlana Guryeva, Natalia Danilova, Elena Petersen

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Drug toxicity often goes undetected until clinical trials, the most expensive and dangerous phase of drug development. Both human cell culture and animal studies have limitations that cannot be overcome by improvements in drug testing protocols. Tissue engineering is an emerging alternative approach to creating models of human malignant tumors for experimental oncology, personalized medicine, and drug discovery studies. This new generation of bioengineered tumors provides an opportunity to control and explore the role of every component of the model system including cell populations, supportive scaffolds, and signaling molecules. An area that could greatly benefit from these models is cancer research. Recent advances in tissue engineering demonstrated that decellularized tissue is an excellent scaffold for tissue engineering. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. Decellularized Organs preserve organ microenvironment, which is critical for cancer metastasis. Utilizing 3D tumor models results greater proximity of cell culture morphological characteristics in a model to its in vivo counterpart, allows more accurate simulation of the processes within a functioning tumor and its pathogenesis. 3D models allow study of migration processes and cell proliferation with higher reliability as well. Moreover, cancer cells in a 3D model bear closer resemblance to living conditions in terms of gene expression, cell surface receptor expression, and signaling. 2D cell monolayers do not provide the geometrical and mechanical cues of tissues in vivo and are, therefore, not suitable to accurately predict the responses of living organisms. 3D models can provide several levels of complexity from simple monocultures of cancer cell lines in liquid environment comprised of oxygen and nutrient gradients and cell-cell interaction to more advanced models, which include co-culturing with other cell types, such as endothelial and immune cells. Following this reasoning, spheroids cultivated from one or multiple patient-derived cell lines can be utilized to seed the matrix rather than monolayer cells. This approach furthers the progress towards personalized medicine. As an initial step to create a new ex vivo tissue engineered model of a cancer tumor, optimized protocols have been designed to obtain organ-specific acellular matrices and evaluate their potential as tissue engineered scaffolds for cultures of normal and tumor cells. Decellularized biomatrix was prepared from animals’ kidneys, urethra, lungs, heart, and liver by two decellularization methods: perfusion in a bioreactor system and immersion-agitation on an orbital shaker with the use of various detergents (SDS, Triton X-100) in different concentrations and freezing. Acellular scaffolds and tissue engineered constructs have been characterized and compared using morphological methods. Models using decellularized matrix have certain advantages, such as maintaining native extracellular matrix properties and biomimetic microenvironment for cancer cells; compatibility with multiple cell types for cell culture and drug screening; utilization to culture patient-derived cells in vitro to evaluate different anticancer therapeutics for developing personalized medicines.

Keywords: 3D models, decellularization, drug discovery, drug toxicity, scaffolds, spheroids, tissue engineering

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Authors: Rajib Mia, Badam Singh Kushvah

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The present research was motivated by the recent discovery of the binary star systems. In this paper, we use the restricted three-body problem in the binary stellar systems, considering photogravitational effects of both the stars. The aim of this study is to investigate the motion of the infinitesimal mass in the vicinity of the Lagrangian points. The stability and periodic orbits of collinear points and the stability and trajectories of the triangular points are studied in stellar binary systems Kepler-34, Kepler-35, Kepler-413 and Kepler-16 systems. A detailed comparison is made among periodic orbits and trajectories.

Keywords: exoplanetary systems, lagrangian points, periodic orbit, restricted three body problem, stability

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Authors: Rida Ahmad, Areej S. Habib, Sohail A. Dogar, Saqib H. Qazi

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Transverse testicular ectopia is a rare congenital disorder involving mal descent and mal-positioning of the testes, reported in the medical literature about 300 times. Many theories attempt to explain the failure of the testes to migrate to their correct location. While the age at presentation can vary; most cases present in early adolescents or late adulthood. It is often an incidental discovery made during an operative intervention, most commonly during hernia exploration. It can be isolated or present with a plethora of anomalies. We present the case of a 2-year-old male with transverse testicular ectopia who presented with vague abdominal pain. He was managed successfully with the Modified Ombredanne procedure and good outcome 6 months after the procedure.

Keywords: cryptorchidism, persistent Mullerian duct syndrome, transverse testicular ectopia, testicular mal-descent

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Authors: Aravind Mohan Krishnan

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This paper identifies a research gap in the literature on tourism entrepreneurship in Malawi, Africa, and investigates how entrepreneurs from the Malawian tourism sector discover and exploit business opportunities. In particular, the importance of prior experience and business networks in the opportunity development process is debated. Another area of empirical research examined here is the opportunity recognition-venture creation sequence. While Malawi presents fruitful business opportunities, exploiting these opportunities into fully realized business ideas is a real challenge due to the country’s difficult business environment and poor promotional and marketing efforts. The study concludes by calling for further research in Sub-Saharan Africa in order to develop our understanding of entrepreneurship in this (African) context.

Keywords: entrepreneurship, Malawi, opportunities, tourism

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Authors: Brahim Merdas, Abdelhak Boutaleb

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Polymetallic mineralizations with Zn, Sb, Pb boxed in miopliocene limestones of Hammam N’bails’s basin are regarded as the youngest mineralizations of North East of Algeria and are characterized by the presence of rather rare mineral phases throughout the world such as nadorite and flajolotite. Mineralization seems to have a bond with thermal springs emergent within the basin and with the faults which limit the basin. The comparison between mineralizations and similar ore deposits known in the world and which are characterized by the presence of the noble metals such as gold and the discovery of traces of this metal (1.4g/t) enables us to start again the problems of the noble metals of the type “low sulfidation” related to the thermal springs in the area in particular and in all Algerian North generally.

Keywords: Nadorite, galana, gold, dolomitisation, epigenétic, hot springs, , miopliocene, Hammam N’bails, algeria

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Authors: Maryam Mostafaee, Hassan Sadeghi Naeini, Sara Mostowfi

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Today’s Knowledge management (KM), plays an important role in organizations. Basically, knowledge management is in the relation of using it for taking advantage of work forces in an organization for forwarding the goals and demand of that organization used at the most. The purpose of knowledge management is not only to manage existing documentation, information, and Data through an organization, but the most important part of KM is to control most important and key factor of those information and Data. For sure it is to chase the information needed for the employees in the right time of needed to take from genuine source for bringing out the best performance and result then in this matter the performance of organization will be at most of it. There are a lot of definitions over the objective of management released. Management is the science that in force the accurate knowledge with repeating to the organization to shape it and take full advantages for reaching goals and targets in the organization to be used by employees and users, but the definition of Knowledge based on Kalinz dictionary is: Facts, emotions or experiences known by man or group of people is ‘ knowledge ‘: Based on the Merriam Webster Dictionary: the act or skill of controlling and making decision about a business, department, sport team, etc, based on the Oxford Dictionary: Efficient handling of information and resources within a commercial organization, and based on the Oxford Dictionary: The art or process of designing manufactured products: the scale is a beautiful work of industrial design. When knowledge management performed executive in universities, discovery and create a new knowledge be facilitated. Make procedures between different units for knowledge exchange. College's officials and employees understand the importance of knowledge for University's success and will make more efforts to prevent the errors. In this strategy, is explored factors and affective trends and manage of it in University. In this research, Iranian universities for a time being analyzed that over usage of knowledge management, how they are behaving and having understood this matter: 1. Discovery of knowledge management in Iranian Universities, 2. Transferring exciting knowledge between faculties and unites, 3. Participate of employees for getting and using and transferring knowledge, 4.The accessibility of valid sources, 5. Researching over factors and correct processes in the university. We are pointing in some examples that we have already analyzed which is: -Enabling better and faster decision-making, -Making it easy to find relevant information and resources, -Reusing ideas, documents, and expertise, -Avoiding redundant effort. Consequence: It is found that effectiveness of knowledge management in the Industrial design field is low. Based on filled checklist by Education officials and professors in universities, and coefficient of effectiveness Calculate, knowledge management could not get the right place.

Keywords: knowledge management, industrial design, educational curriculum, learning performance

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Authors: Sapir Handelman

Abstract:

Brief Solution Focused Negotiation is a powerful conflict resolution tool. It can be applied in almost all dimensions of our social life, from politics to family. The initiative invites disputing parties to negotiate practical solutions to their conflict. The negotiation is conducted in a framework of rules, structure, and timeline. The paper presents a model of Brief Solution Focused Negotiation that rests on three pillars: Transformation – turning opposing parties into a negotiating cooperative; Practicality – focusing on practical solutions to a negotiable problem; Discovery – discovering key game changers. This paper introduces these three building blocks. It demonstrates the potential contribution of each one of them to negotiation success. It shows that an effective combination of these three elements has the greatest potential to build, maintain and successfully conclude Brief Solution Focused Negotiation.

Keywords: conflict, negotiation, negotiating cooperative, game changer

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Authors: Boulis M. Ibrahim, Iordanis A. Kalaitzoglou

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A micro structural pricing model is proposed in which price components account for learning by incorporating changing expectations of the trading intensity and the risk level of incoming trades. An analysis of European carbon futures transactions finds expected trading intensity to increase the information component and decrease the liquidity component of price changes, but at different rates. Among the results, the expected persistence in trading intensity explains the majority of the auto correlations in the level and the conditional volatility of price changes, helps predict hourly patterns in the bid–ask spread and differentiates between the impact of buy versus sell and continuing versus reversing trades.

Keywords: CO2 emission allowances, market microstructure, duration, price discovery

Procedia PDF Downloads 371