Search results for: discovery system

Authors: Christina Williams, Mehari Weldemariam, Ann M. Farese, Thomas J. MacVittie, Maureen A. Kane

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Radiation exposure results in dose-dependent and time-dependent multi-organ damage. Drug development of medical countermeasures (MCM) for radiation-induced injury occurs under the FDA Animal Rule because human efficacy studies are not ethical or feasible. The FDA Animal Rule requires the representation of both sexes and describes several uses for biomarkers in MCM drug development studies. Currently, MCMs are limited and there is no FDA-approved biomarker for any radiation injury. Sex as a variable is essential to identifying biomarkers and developing effective MCMs for acute radiation exposure (ARS) and delayed effects of acute radiation exposure (DEARE). These studies aim to address the death of information on sex differences that have not been determined by studies that included only male, single-sex cohorts. Studies have reported differences in radiosensitivity according to sex. As such, biomarker discovery for radiation-induced damage must consider sex as a variable. This study evaluated the plasma proteomic profile of Rhesus macaque non-human primates after different exposures and doses, as well as time points after radiation. Exposures and doses included total body irradiation between 5-7.5 Gy and partial body irradiation with 5% bone marrow sparing at 9, 9.5 and 10 Gy. Timepoints after irradiation included days 1, 3, 60, and 180, which encompassed both acute radiation syndromes and delayed effects of acute radiation exposure. Bottom-up proteomic analyses of plasma included equal numbers of males and females. In the control animals, few proteomic differences are observed between the sexes. In the irradiated animals, there are a few sex differences, with changes mostly consisting of proteins upregulated in the female animals. Multiple canonical pathways were upregulated in irradiated animals relative to the control animals when subjected to pathway analysis, but differential responses between the sexes are limited. These data provide critical baseline differences according to sex and establish sex differences in non-human primate models relevant to drug development of MCM under the FDA Animal Rule.

Keywords: ionizing radiation, sex differences, plasma proteomics, biomarker discovery

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Authors: Carine Cridelich, Pablo Juesas Cano, Emmanuel Ramasso, Noureddine Zerhouni, Bernd Weiler

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Safety is one of the most important considerations when buying a new car. While active safety aims at avoiding accidents, passive safety systems such as airbags and seat belts protect the occupant in case of an accident. In addition to legal regulations, organizations like Euro NCAP provide consumers with an independent assessment of the safety performance of cars and drive the development of safety systems in automobile industry. Those ratings are mainly based on injury assessment reference values derived from physical parameters measured in dummies during a car crash test. The components and sub-systems of a safety system are designed to achieve the required restraint performance. Sled tests and other types of tests are then carried out by car makers and their suppliers to confirm the protection level of the safety system. A Knowledge Discovery in Databases (KDD) process is proposed in order to minimize the number of tests. The KDD process is based on the data emerging from sled tests according to Euro NCAP specifications. About 30 parameters of the passive safety systems from different data sources (crash data, dummy protocol) are first analysed together with experts opinions. A procedure is proposed to manage missing data and validated on real data sets. Finally, a procedure is developed to estimate a set of rough initial parameters of the passive system before testing aiming at reducing the number of tests.

Keywords: KDD process, passive safety systems, sled test, dummy injury assessment reference values, frontal impact

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Authors: Olanrewaju B. Lasisi

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The position of Ijebu-Ode, the historical capital of the Ijebu Kingdom, at the center of gravity of Ijebu land is enclosed by the 180-km-long earthwork and suggests a centrally controlled project. This paper reflects on the first stratigraphic drawing of the banks and ditches of this earthwork, and place its construction mechanism in a chronological framework. Nine radiocarbon dates obtained at the site suggest that the earthwork was built in the late 14th or early 15th century. This suggests a relationship with the Ijebu Kingdom, which pre-existed the opening of the Atlantic trade but first became visible only in the Portuguese records in the 1480s. In June 2017, more earthworks were found but within the core of Ijebu Land. This most recent finding points to an extension of territory from the center to the outlying villages. One central question about this discovery of monumental architectures that was functional around the 14th century or before is in its mode of construction. Apparently, iron tools must have been used in the construction of ‘a 20m deep ditch that runs 180km in circumference.’ Thus, the discovery of iron-working sites around the vicinity of the earthwork is a pointer to this building process that is up till now shrouded in mystery. By comparing the chronology of Ijebu earthworks with the evidence of Iron working in south western Nigeria around the first half of the first millennium AD, it can be thought that the rise in polity triggered the knowledge of metallurgy in the region.

Keywords: archaeology, earthworks, Ijebu, metallurgy

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Authors: Abdul Musaweer Habib, Habibul Hasan Mazumder, Saiful Islam, Sohel Sikder, Omar Faruk Sikder

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The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1499 proteins of Fusobacterium nucleatum, which has no homolog in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the KEGG Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the 3-D structure of these three proteins. Finally, determination of ligand binding sites of the key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against Fusobacterium nucleatum.

Keywords: colorectal cancer, drug target, Fusobacterium nucleatum, homology modeling, ligands

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Authors: Surajit Bhattacharya, Daniel Veltri, Atit A. Patel, Daniel N. Cox

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miRNAs have emerged as key post-transcriptional regulators of gene expression, however identification of biologically-relevant target genes for this epigenetic regulatory mechanism remains a significant challenge. To address this knowledge gap, we have developed a novel tool in R, Intra-miR-ExploreR, that facilitates integrated discovery of miRNA targets by incorporating target databases and novel target prediction algorithms, using statistical methods including Pearson and Distance Correlation on microarray data, to arrive at high confidence intragenic miRNA target predictions. We have explored the efficacy of this tool using Drosophila melanogaster as a model organism for bioinformatics analyses and functional validation. A number of putative targets were obtained which were also validated using qRT-PCR analysis. Additional features of the tool include downloadable text files containing GO analysis from DAVID and Pubmed links of literature related to gene sets. Moreover, we are constructing interaction maps of intragenic miRNAs, using both micro array and RNA-seq data, focusing on neural tissues to uncover regulatory codes via which these molecules regulate gene expression to direct cellular development.

Keywords: miRNA, miRNA:mRNA target prediction, statistical methods, miRNA:mRNA interaction network

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Authors: Reza Ferdousi, Reza Safdari, Yadollah Omidi

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Drug-drug interactions (DDIs) are main cause of the adverse drug reactions and nature of the functional and molecular complexity of drugs behavior in human body make them hard to prevent and treat. With the aid of new technologies derived from mathematical and computational science the DDIs problems can be addressed with minimum cost and efforts. Market basket analysis is known as powerful method to identify co-occurrence of thing to discover patterns and frequency of the elements. In this research, we used market basket analysis to identify important bio-elements in DDIs occurrence. For this, we collected all known DDIs from DrugBank. The obtained data were analyzed by market basket analysis method. We investigated all drug-enzyme, drug-carrier, drug-transporter and drug-target associations. To determine the importance of the extracted bio-elements, extracted rules were evaluated in terms of confidence and support. Market basket analysis of the over 45,000 known DDIs reveals more than 300 important rules that can be used to identify DDIs, CYP 450 family were the most frequent shared bio-elements. We applied extracted rules over 2,000,000 unknown drug pairs that lead to discovery of more than 200,000 potential DDIs. Analysis of the underlying reason behind the DDI phenomena can help to predict and prevent DDI occurrence. Ranking of the extracted rules based on strangeness of them can be a supportive tool to predict the outcome of an unknown DDI.

Keywords: drug-drug interaction, market basket analysis, rule discovery, important bio-elements

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Authors: Kai-Cheng Hsu, Tzu-Ying Sung, Jinn-Moon Yang

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Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Although several drugs have been developed to treat colorectal cancer, such as Regorafenib and 5-FU, their efficacy is often limited by the development of drug resistance. Therefore, development of new drugs with new scaffolds is necessary to treat CRC. Here, we used site-moiety maps to identify inhibitors against PIM1, LIMK1, SRC, and mTOR, which are often overexpressed in CRC. A site-moiety map represents physicochemical properties and moiety preferences of a binding site through anchors. An anchor contains three elements: (1) conserved interacting residues of a binding pocket; (2) moiety preference of the binding pocket; and (3) the type (e.g., hydrogen-bonding or van der Waals interactions) of interaction between the moieties and the binding pocket. Then, we performed a structure-based virtual screening of ~260,000 compounds and selected compound candidates with high site-moiety map scores for bioassays. Among these candidates, compound 1 and compound 2 inhibited the growth of CRC cells with IC50 values of <10 μM. The experimental result of enzyme-based assays indicated that compound 1 is a dual inhibitor against PIM1 (IC50 6 μM) and LIMK1(IC50 11 μM). Compound 2 was predicted as a SRC inhibitor and will be further validated. The compounds inhibited different protein targets compared to the current drugs. We believe that the compounds provide a starting point to design new drugs for CRC treatment.

Keywords: colorectal cancer, drug discovery, site-moiety map, virtual screening, PIM1, LIMK1

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Authors: Thilina Ranaweera, Enes Makalic, John L. Hopper, Adrian Bickerstaffe

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Data are the primary asset of biomedical researchers, and the engine for both discovery and research translation. As the volume and complexity of research datasets increase, especially with new technologies such as large single nucleotide polymorphism (SNP) chips, so too does the requirement for software to manage, process and analyze the data. Researchers often need to execute complicated queries and conduct complex analyzes of large-scale datasets. Existing tools to analyze such data, and other types of high-dimensional data, unfortunately suffer from one or more major problems. They typically require a high level of computing expertise, are too simplistic (i.e., do not fit realistic models that allow for complex interactions), are limited by computing power, do not exploit the computing power of large-scale parallel architectures (e.g. supercomputers, GPU clusters etc.), or are limited in the types of analysis available, compounded by the fact that integrating new analysis methods is not straightforward. Solutions to these problems, such as those developed and implemented on parallel architectures, are currently available to only a relatively small portion of medical researchers with access and know-how. The past decade has seen a rapid expansion of data management systems for the medical domain. Much attention has been given to systems that manage phenotype datasets generated by medical studies. The introduction of heterogeneous genomic data for research subjects that reside in these systems has highlighted the need for substantial improvements in software architecture. To address this problem, we have developed SPARK, an enabling and translational system for medical research, leveraging existing high performance computing resources, and analysis techniques currently available or being developed. It builds these into The Ark, an open-source web-based system designed to manage medical data. SPARK provides a next-generation biomedical data management solution that is based upon a novel Micro-Service architecture and Big Data technologies. The system serves to demonstrate the applicability of Micro-Service architectures for the development of high performance computing applications. When applied to high-dimensional medical datasets such as genomic data, relational data management approaches with normalized data structures suffer from unfeasibly high execution times for basic operations such as insert (i.e. importing a GWAS dataset) and the queries that are typical of the genomics research domain. SPARK resolves these problems by incorporating non-relational NoSQL databases that have been driven by the emergence of Big Data. SPARK provides researchers across the world with user-friendly access to state-of-the-art data management and analysis tools while eliminating the need for high-level informatics and programming skills. The system will benefit health and medical research by eliminating the burden of large-scale data management, querying, cleaning, and analysis. SPARK represents a major advancement in genome research technologies, vastly reducing the burden of working with genomic datasets, and enabling cutting edge analysis approaches that have previously been out of reach for many medical researchers.

Keywords: biomedical research, genomics, information systems, software

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Authors: Salem Ben Said

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In recent times the decimal number system to which we are accustomed has received serious competition from the binary number system. In this note, an approach is suggested to teaching and learning the binary number system using examples from the real world. More precisely, we will demonstrate the utility of the binary system in describing the optimal strategy to win the Chinese Nim game, and in telegraphy by decoding the hidden message on Perseverance’s Mars parachute written in the language of binary system. Finally, we will answer the question, “why do modern computers prefer the ternary number system instead of the binary system?”. All materials are provided in a format that is conductive to classroom presentation and discussion.

Keywords: binary number system, Nim game, telegraphy, computers prefer the ternary system

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Authors: Ayham Fattoum, Simos Chari, Duncan Shaw

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Volatile, uncertain, complex, and ambiguous (VUCA) conditions threaten systems viability with emerging and novel events requiring immediate and localized responses. Such responsiveness is only possible through devolved freedom and emancipated decision-making. The Viable System Model (VSM) recognizes the need and suggests maximizing autonomy to localize decision-making and minimize residual complexity. However, exercising delegated autonomy in VUCA requires confidence and knowledge to use intuition and guidance to maintain systemic coherence. This paper explores the role of intuition as an enabler of emancipated decision-making and autonomy under VUCA. Intuition allows decision-makers to use their knowledge and experience to respond rapidly to novel events. This paper offers three contributions to VSM. First, it designs a system model that illustrates the role of intuitive decision-making in managing complexity and maintaining viability. Second, it takes a black-box approach to theory development in VSM to model the role of autonomy and intuition. Third, the study uses a multi-stage discovery-oriented approach (DOA) to develop theory, with each stage combining literature, data analysis, and model/theory development and identifying further questions for the subsequent stage. We synthesize literature (e.g., VSM, complexity management) with seven months of field-based insights (interviews, workshops, and observation of a live disaster exercise) to develop a framework of intuitive complexity management framework and VSM models. The results have practical implications for enhancing the resilience of organizations and communities.

Keywords: Intuition, complexity management, decision-making, viable system model

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Authors: Oktira Roka Aji, Maelita R. Moeis, Ihsanawati, Ernawati A. Giri-Rachman

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Globally, tuberculosis (TB) remains a leading cause of death. The emergence of multidrug-resistant strains and extensively drug-resistant strains have become a major public concern. One of the potential candidates for drug target is the cytoplasmic domain of PhoR Histidine Kinase, a part of the Two Component System (TCS) PhoR-PhoP in Mycobacterium tuberculosis (Mtb). TCS PhoR-PhoP relay extracellular signal to control the expression of 114 virulent associated genes in Mtb. The 3D structure of PhoR cytoplasmic domain is needed to screen novel drugs using structure based drug discovery. The PhoR cytoplasmic domain from Mtb H37Rv was overexpressed in E. coli BL21(DE3), then purified using IMAC Ni-NTA Agarose his-tag affinity column and DEAE-ion exchange column chromatography. The molecular weight of the purified protein was estimated to be 37 kDa after SDS-PAGE analysis. This sample was used for pre-crystallization screening by applying sitting drop vapor diffusion method using Natrix (HR2-116) 48 solutions crystal screen kit at 25ºC. Needle-like crystals were observed after the seventh day of incubation in test solution No.47 (0.1 M KCl, 0.01 M MgCl2.6H2O, 0.05 M Tris-Cl pH 8.5, 30% v/v PEG 4000). Further testing is required for confirming the crystal.

Keywords: tuberculosis, two component system, histidine kinase, needle-like crystals

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Authors: Paolo Fantozzi, Luigi Laura, Umberto Nanni

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The problem of Entity relation discovery in structured data, a well covered topic in literature, consists in searching within unstructured sources (typically, text) in order to find connections among entities. These can be a whole dictionary, or a specific collection of named items. In many cases machine learning and/or text mining techniques are used for this goal. These approaches might be unfeasible in computationally challenging problems, such as processing massive data streams. A faster approach consists in collecting the cooccurrences of any two words (entities) in order to create a graph of relations - a cooccurrence graph. Indeed each cooccurrence highlights some grade of semantic correlation between the words because it is more common to have related words close each other than having them in the opposite sides of the text. Some authors have used sliding windows for such problem: they count all the occurrences within a sliding windows running over the whole text. In this paper we generalise such technique, coming up to a Weighted-Distance Sliding Window, where each occurrence of two named items within the window is accounted with a weight depending on the distance between items: a closer distance implies a stronger evidence of a relationship. We develop an experiment in order to support this intuition, by applying this technique to a data set consisting in the text of the Bible, split into verses.

Keywords: cooccurrence graph, entity relation graph, unstructured text, weighted distance

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Authors: Abdullah M. Algarni, Yashwant K. Malaiya

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Some of the key aspects of vulnerability-discovery, dissemination, and disclosure-have received some attention recently. However, the role of interaction among the vulnerability discoverers and vulnerability acquirers has not yet been adequately addressed. Our study suggests that a major percentage of discoverers, a majority in some cases, are unaffiliated with the software developers and thus are free to disseminate the vulnerabilities they discover in any way they like. As a result, multiple vulnerability markets have emerged. In some of these markets, the exchange is regulated, but in others, there is little or no regulation. In recent vulnerability discovery literature, the vulnerability discoverers have remained anonymous individuals. Although there has been an attempt to model the level of their efforts, information regarding their identities, modes of operation, and what they are doing with the discovered vulnerabilities has not been explored. Reports of buying and selling of the vulnerabilities are now appearing in the press; however, the existence of such markets requires validation, and the natures of the markets need to be analysed. To address this need, we have attempted to collect detailed information. We have identified the most prolific vulnerability discoverers throughout the past decade and examined their motivation and methods. A large percentage of these discoverers are located in Eastern and Western Europe and in the Far East. We have contacted several of them in order to collect first-hand information regarding their techniques, motivations, and involvement in the vulnerability markets. We examine why many of the discoverers appear to retire after a highly successful vulnerability-finding career. The paper identifies the actual vulnerability markets, rather than the hypothetical ideal markets that are often examined. The emergence of worldwide government agencies as vulnerability buyers has significant implications. We discuss potential factors that can impact the risk to society and the need for detailed exploration.

Keywords: risk management, software security, vulnerability discoverers, vulnerability markets

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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: Shiyun Liu

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Radiant heating systems work fundamentally differently from air systems by taking advantage of both radiant and convective heat transfer to remove space heating load. There are rare studies on differences of heating systems between all-air system and radiant floor system. This paper uses the method of simulation based on state-space to calculate the indoor temperature and wall temperature of each system and shows how the dynamic heat transfer in rooms conditioned by a radiant system is different from an air system. Then this paper analyses the changes of indoor temperature of these two systems, finding out the differences between all-air heating system and radiant floor heating system to help the designer choose a more suitable heating system.

Keywords: radiant floor, all-air system, thermal comfort, simulation, heating system

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Authors: Ahmad Abdul-Razzak Aboudi Al-Issa

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Thermal and Hydrodynamic are basic aspects in any hydraulic system and therefore, they must be assessed with regard to this aspect before constructing the system. This assessment needs a good expertise in this aspect to obtain an efficient hydraulic system. Therefore, this study aims to build an expert system called Hydraulic System Calculations (HSC) to ensure a smooth operation for the hydraulic system. The expert system (HSC) had been designed and coded in an user-friendly interactive program called Microsoft Visual Basic 2010. The suggested code provides the designer with a number of choices to resolve the problem of hydraulic oil overheating which may arise during the continuous operation of the hydraulic unit. As a result, the HSC can minimize the human errors, effort, time and cost of hydraulic machine design.

Keywords: fluid power, hydraulic system, thermal and hydrodynamic, expert system

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Authors: Ayan Giri, Lukaranjan Phukan, Shantanu Karmakar

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Structure and tectonics play a vital role in ore genesis and deposition. The existence of a swelling structure below the current level of a mine leads to the discovery of ores below some permeant developments of the mine. The discovery and the extraction of the ore body are very critical to sustain the business requirement of the mine. The challenge was to extract the ore without hampering the global stability of the mine. In order to do so, different mining options were considered and analysed by numerical modelling in FLAC3d software. The constitutive model prepared for this simulation is the improved unified constitutive model, which can better and more accurately predict the stress-strain relationships in a continuum model. The IUCM employs the Hoek-Brown criterion to determine the instantaneous Mohr-Coulomb parameters cohesion (c) and friction (ɸ) at each level of confining stress. The extra swelled part can be dimensioned as north-south strike width 50m, east-west strike width 50m. On the north side, already a stope (P1) is excavated of the dimension of 25m NS width. The different options considered were (a) Open stoping of extraction of southern part (P0) of 50m to the full extent, (b) Extraction of the southern part of 25m, then filling of both the primaries and extraction of secondary (S0) 25m in between. (c) Extraction of the southern part (P0) completely, preceded by backfill and modify the design of the secondary (S0) for the overall stability of the permanent excavation above the stoping.

Keywords: extraction, IUCM, FLAC 3D, stoping, tectonics

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Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

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The drug discovery and development process is generally known to be a very lengthy and labor-intensive process. Therefore, in order to be able to deliver prompt and effective responses to cure certain diseases, there is an urgent need to reduce the time and resources needed to design, develop, and optimize potential drugs. Computer-aided drug design (CADD) is able to alleviate this issue by applying computational power in order to streamline the whole drug discovery process, starting from target identification to lead optimization. This drug design approach can be predominantly applied to diseases that cause major public health concerns, such as tuberculosis. Hitherto, there has been no concrete cure for this disease, especially with the continuing emergence of drug resistant strains. In this study, CADD is employed for tuberculosis by first identifying a key enzyme in the mycobacterium’s metabolic pathway that would make a good drug target. One such potential target is the lipoate protein ligase B enzyme (LipB), which is a key enzyme in the M. tuberculosis metabolic pathway involved in the biosynthesis of the lipoic acid cofactor. Its expression is considerably up-regulated in patients with multi-drug resistant tuberculosis (MDR-TB) and it has no known back-up mechanism that can take over its function when inhibited, making it an extremely attractive target. Using cutting-edge computational methods, compounds from AnalytiCon Discovery Natural Derivatives database were screened and docked against the LipB enzyme in order to rank them based on their binding affinities. Compounds which have better binding affinities than LipB’s known inhibitor, decanoic acid, were subjected to in silico toxicity evaluation using the ADMET and TOPKAT protocols. Out of the 31,692 compounds in the database, 112 of these showed better binding energies than decanoic acid. Furthermore, 12 out of the 112 compounds showed highly promising ADMET and TOPKAT properties. Future studies involving in vitro or in vivo bioassays may be done to further confirm the therapeutic efficacy of these 12 compounds, which eventually may then lead to a novel class of anti-tuberculosis drugs.

Keywords: pharmacophore, molecular docking, lipoate protein ligase B (LipB), ADMET, TOPKAT

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Authors: Rezky Rifaini, Raden Bagus Fajriya Hakim

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This research was conducted at the Bolo primary health Care in Bima Regency. The purpose of the research is to find out the association pattern that is formed of medical record database from Bolo Primary health care’s patient. The data used is secondary data from medical records database PHC. Sequential pattern mining technique is the method that used to analysis. Transaction data generated from Patient_ID, Check_Date and diagnosis. Sequential Pattern Discovery Algorithms Using Equivalent Classes (SPADE) is one of the algorithm in sequential pattern mining, this algorithm find frequent sequences of data transaction, using vertical database and sequence join process. Results of the SPADE algorithm is frequent sequences that then used to form a rule. It technique is used to find the association pattern between items combination. Based on association rules sequential analysis with SPADE algorithm for minimum support 0,03 and minimum confidence 0,75 is gotten 3 association sequential pattern based on the sequence of patient_ID, check_Date and diagnosis data in the Bolo PHC.

Keywords: diagnosis, primary health care, medical record, data mining, sequential pattern mining, SPADE algorithm

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Authors: Jaemyoung Lee

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We present a method to set up system functions through a near filed communication (NFC) of a smartphone. The short communication distance of the NFC which is usually less than 4 cm could prevent any interferences from other devices and establish a secure communication channel between a system and the smartphone. The proposed set-up method for system function values is demonstrated for a blacbox system in a car. In demonstration, system functions of a blackbox which is manipulated through NFC of a smartphone are controls of image quality, sound level, shock sensing level to store images, etc. The proposed set-up method for system function values can be used for any devices with NFC.

Keywords: system set-up, near field communication, smartphone, android

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Authors: Farahnaz Sadat Golestan Hashemi, Mohd Razi Ismail, Mohd Y. Rafii

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A huge revolution has emerged in genome engineering by the discovery of CRISPR (clustered regularly interspaced palindromic repeats) and CRISPR-associated system genes (Cas) in bacteria. The function of type II Streptococcus pyogenes (Sp) CRISPR/Cas9 system has been confirmed in various species. Other S. thermophilus (St) CRISPR-Cas systems, CRISPR1-Cas and CRISPR3-Cas, have been also reported for preventing phage infection. The CRISPR1-Cas system interferes by cleaving foreign dsDNA entering the cell in a length-specific and orientation-dependant manner. The S. thermophilus CRISPR3-Cas system also acts by cleaving phage dsDNA genomes at the same specific position inside the targeted protospacer as observed in the CRISPR1-Cas system. It is worth mentioning, for the effective DNA cleavage activity, RNA-guided Cas9 orthologs require their own specific PAM (protospacer adjacent motif) sequences. Activity levels are based on the sequence of the protospacer and specific combinations of favorable PAM bases. Therefore, based on the specific length and sequence of PAM followed by a constant length of target site for the three orthogonals of Cas9 protein, a well-organized procedure will be required for high-throughput and accurate mining of possible target sites in a large genomic dataset. Consequently, we created a reliable procedure to explore potential gRNA sequences for type I (Streptococcus thermophiles), II (Streptococcus pyogenes), and III (Streptococcus thermophiles) CRISPR/Cas systems. To mine CRISPR target sites, four different searching modes of sgRNA binding to target DNA strand were applied. These searching modes are as follows: i) coding strand searching, ii) anti-coding strand searching, iii) both strand searching, and iv) paired-gRNA searching. The output of such procedure highlights the power of comparative genome mining for different CRISPR/Cas systems. This could yield a repertoire of Cas9 variants with expanded capabilities of gRNA design, and will pave the way for further advance genome and epigenome engineering.

Keywords: CRISPR/Cas systems, gRNA mining, Streptococcus pyogenes, Streptococcus thermophiles

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Authors: Amir Taghizadeh Vahed, Adithya Thaduri

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Shovels are the main components in the mining transportation system. The productivity of the mines depends on the availability of shovels due to its high capital and operating costs. The unplanned failure/shutdowns of a shovel results in higher repair costs, increase in downtime, as well as increasing indirect cost (i.e. loss of production and company’s reputation). In order to mitigate these failures, predictive maintenance can be useful approach using failure prediction. The modern mining machinery or shovels collect huge datasets automatically; it consists of reliability and maintenance data. However, the gathered datasets are useless until the information and knowledge of data are extracted. Machine learning as well as data mining, which has a major role in recent studies, has been used for the knowledge discovery process. In this study, data mining and machine learning approaches are implemented to detect not only anomalies but also patterns from a dataset and further detection of failures.

Keywords: maintenance, machine learning, shovel, conditional based monitoring

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Authors: Galit Harel

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This article describes the long-term psychoanalytic psychotherapy of a young woman who had experienced trauma during her childhood. The details of the trauma were unknown, as all memory of the trauma had been repressed. Past trauma is analyzable through a prism of transference, dreaming and dreams, mental states, and thinking processes that offer an opportunity to explore and analyze the influence of both reality and fantasy on the patient. The presented case describes a therapeutic process that strives to discover hidden meanings through the unconscious system and illustrates the movement from unconscious to conscious during exploration of the patient’s personal trauma in treatment. The author discusses the importance of classical and contemporary psychoanalytic models of childhood sexual trauma through the discovery of manifest and latent content, unconscious fantasies, and actual events of trauma. It is suggested that the complexity of trauma is clarified by the tension between these models and by the inclusion of aspects of both of them for a complete understanding.

Keywords: dreams, psychoanalytic psychotherapy, thinking processes, transference, trauma

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Authors: Zakir Husain, Neem Sagar, Neeraj Gupta

Abstract:

Due to the increased penetration of renewable energy resources in the distribution system, the system is no longer passive in nature. In this paper, a steady state analysis of the distribution system has been done with the inclusion of wind generation. The modeling of wind turbine generator system and wind generator has been made to obtain the average active and the reactive power injection into the system. The study has been conducted on a IEEE-33 bus system with two wind generators. The present research work is useful not only to utilities but also to customers.

Keywords: distributed generation, distribution network, radial network, wind turbine generating system

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Authors: Karima Sekkoum Abdelkrim Cheriti, Leila Feguigui

Abstract:

Algeria has a large plant biodiversity accounting more than 4125 species (123 Families) and is endowed with resources of medicinal plants growing on various bioclimatic zones from subhumide to semi-arid and Saharan. On the other hand, the ethnopharmacology investigation remains the principal way to improve, evaluate, and finding bioactive substances derived from medicinal plants. In continuation of our works in Saharan ethpharmacopeae and phytochemistry of Saharan medicinal plants, we focus our attention on the importance of local ethnopharmacology especially to treat gastro-intestinal disorders in the south west of Algeria (El Baydh, Naama and Bechar region) as platform for bioactive substances discovery and further development. Our present investigation deals with an ethnopharmacological study on medicinal plants used for the treatment of gastro-intestinal disorders in the south west of Algeria. The study presents the uses of plants in local traditional herbal medicines, determines the homogeneity of informant traditional knowledge and the preferred medicinal plants used to treat gastro-intestinal disorders. The results indicated that Asteraceae and Lamiaceae are the most locally used families and medicines were prepared in the form of powder or infusion and used orally. Aerial parts were the most frequently used plant part. Thus, the results can be used as platform for bioactive substances discovery and further development especially for the preferred plant species used in the treatment of gastro-intestinal disorders.

Keywords: ethnopharmacology, gastro-intestinal, phytochemical, South Algeria, Sahara, endemic species

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Authors: Yaara Oppenheimer-Shaanan, Nimrod Nachmias, Marina Campos Rocha, Neta Schlezinger, Noam Dotan, Asaf Levy

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Fusarium oxysporum, a fungus that attacks a broad range of plants and can cause infections in humans, operates across different kingdoms. This pathogen encounters varied conditions, such as temperature, pH, and nutrient availability, in plant and human hosts. The Fusarium oxysporum species complex, pervasive in soils globally, can affect numerous plants, including key crops like tomatoes and bananas. Controlling Fusarium infections can involve biocontrol agents that hinder the growth of harmful strains. Our research developed a computational method to identify toxin domains within a vast number of microbial genomes, leading to the discovery of nine distinct toxins capable of killing bacteria and fungi, including Fusarium. These toxins appear to function as enzymes, causing significant damage to cellular structures, membranes and DNA. We explored biological control using bacteria that produce polymorphic toxins, finding that certain bacteria, non-pathogenic to plants, offer a safe biological alternative for Fusarium management, as they did not harm macrophage cells or C. elegans. Additionally, we elucidated the 3D structures of two toxins with their protective immunity proteins, revealing their function as unique DNases. These potent toxins are likely instrumental in microbial competition within plant ecosystems and could serve as biocontrol agents to mitigate Fusarium wilt and related diseases.

Keywords: microbial toxins, antifungal, Fusarium oxysporum, bacterial-fungal intreactions

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Authors: Suraj Kumar Mukti

Abstract:

Enterprise Resource Planning (ERP) system is a management tool to integrate all departments in an organization. It integrates business processes, manages resources efficiently and provides an appropriate decision support system to management. ERP system implementation is a typical and time taking process as well as money consuming process. Articles related to key success factors of ERP system implementation are available in the literature, but rare authors have focused on roadmap of successful ERP system implementation. Postponement is better if the organization is not ready to implement ERP system in better way; hence checking of organization’s preparation to adopt new system is an important prerequisite to ensure the success of ERP system implementation in an organization. Then comes what will be called as success of ERP system implementation. Benefits achieved by ERP system may be categorized into two categories; viz. tangible and intangible benefits. This research article presents a roadmap to ensure the success of ERP system implementation and benefits achieved through the new system as in success indicator. A case study is presented to evaluate the success and benefit achieved through the new system. The article gives a comprehensive approach to academicians and a roadmap to the organizations seeking to implement the ERP system.

Keywords: ERP system, decision support system, tangible, intangible

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Authors: Kushakov Kholmurodjon, Muhammadjonov Akbarshox

Abstract:

This present paper is devoted to a system of second-order nonlinear differential equations with a special right-hand side, exactly, the linear part and a third-order polynomial of a special form. It is shown that for some relations between the parameters, there is a second-order curve in which trajectories leaving the points of this curve remain in the same place. Thus, the curve is invariant with respect to the given system. Moreover, this system is invariant under a non-degenerate linear transformation of variables. The form of this curve, depending on the relations between the parameters and the eigenvalues of the matrix, is proved. All solutions of this system of differential equations are shown analytically.

Keywords: dynamic system, ellipse, hyperbola, Hess system, polar coordinate system

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Authors: Farhad Ghasemi

Abstract:

Along with transforming the international system into a complex and chaotic system, the fundamental question arises: how can deterrence be reconstructed conceptually and theoretically in this system model? The deterrence system is much more complex today than it was seven decades ago. This article suggests that the perception of deterrence as a linear system is a fundamental mistake because it does not consider the new dynamics of the international system, including network power dynamics. The author aims to improve this point by focusing on complexity and chaos theories, especially their nonlinearity and cascading failure principles. This article proposes that the perception of deterrence as a linear system is a fundamental mistake, as the new dynamics of the surrounding international system do not take into account. The author recognizes deterrence as a nonlinear system and introduces it as a concept in strategic studies.

Keywords: complexity, international system, deterrence, linear deterrence, nonlinear deterrence

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Authors: Matthias Stange

Abstract:

In the early modern period, a different image of man began to prevail in Europe. The focus was on the self-determined human being and his abilities. At first, these developments could be seen in Italian painting and architecture, which again oriented itself to the concepts and forms of antiquity. For example, through the discovery of perspective representation by Brunelleschi or later the orthogonal projection by Alberti, after the ancient knowledge of optics had been forgotten in the Middle Ages. The understanding of reality in the Middle Ages was not focused on the sensually perceptible world but was determined by ecclesiastical dogmas. The empirical part of this study examines the rediscovery and development of perspective. With the paradigm of antiquity, the figure of the architect was also recognised again - the cultural man trained theoretically and practically in numerous subjects, as Vitruvius describes him. In this context, the role of the architect, the influence on the painting of the Quattrocento as well as the influence on architectural representation in the Baroque period are examined. Baroque is commonly associated with the idea of illusionistic appearance as opposed to the tangible reality presented in the Renaissance. The study has shown that the central perspective projection developed by Filippo Brunelleschi enabled another understanding of seeing and the dissemination of painted images. Brunelleschi's development made it possible to understand the sight of nature as a reflection of what is presented to the viewer's eye. Alberti later shortened Brunelleschi's central perspective representation for practical use in painting. In early modern Italian architecture and painting, these developments apparently supported each other. The pictorial representation of architecture initially served the development of an art form before it became established in building practice itself.

Keywords: Alberti, Brunelleschi, central perspective projection, orthogonal projection, quattrocento, baroque

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