Search results for: discovery

Authors: Elena G. Salina, Vadim A. Makarov

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With the emergence of primary resistance to the current drugs and wide distribution of latent tuberculosis infection, a need for new compounds with a novel mode of action is growing steadily. Copper-mediated innate immunity and antibacterial toxicity propose novel strategies in TB drug discovery and development. Transcriptome of M. tuberculosis was obtained by RNA-seq, intracellular copper content was measured by ISP MS and complexes of 1-hydroxy-2-thiopyridines with copper were detected by HPLC.1-hydroxy-2-thiopyridine derivatives were found to be highly active in vitro against both actively growing and dormant non-culturable M. tuberculosis. Transcriptome response to 1-hydroxy-2-thiopyridines revealed signs of copper toxicity in M. tuberculosis bacilli. Indeed, Cu was found to accumulate inside cells treated with 1-hydroxy-2-thiopyridines. These compounds were found to form stable charged lipophylic complexes with Cu²⁺ ions which transport into mycobacterial cell. Subsequent metabolic destruction of the complex led to transformation of 1-hydroxy-2-thiopyridines into 2-methylmercapto-2-ethoxycarbonylpyridines, which did not possess antitubercular activity and releasing of free Cu²⁺ in the cytoplasm. 1-hydroxy-2-thiopyridines are a potent class of Cu-dependent inhibitors of M. tuberculosis which may control M. tuberculosis infection by impairment of copper homeostasis. Acknowledgment: This work was financially supported by the Ministry of Education and Science of the RussianFederation (Agreement No 14.616.21.0065; unique identifier RFMEFI61616X0065).

Keywords: copper toxicity, drug discovery, M. tuberculosis inhibitors, 2-thiopyridines

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Authors: Reem Al-Shidhani, Isabelle S. R. Storer, Michael J. Bromley, Lydia Tabernero

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Invasive fungal diseases are an increasing global health concern that contributes to the high mortality rates in immunocompromised patients. The rising of antifungal resistance severely lowers the efficacy of the limited antifungal agents available. New antifungal drugs that target new mechanisms are necessary to tackle the current shortfalls. Amongst post- modifications, phosphorylation is a predominant and an outstanding protein alteration in all eukaryotes. In fungi, protein phosphorylation plays a vital role in many signal transduction pathways, including cell cycle, cell growth, metabolism, transcription, differentiation, proliferation, and virulence. The investigation of Aspergillus fumigatus phosphatases revealed seven genes essential for viability. Inhibiting one of these phosphatases is a new interesting route to develop novel antifungal drugs. In this study, we carried out an early drug discovery process targeting oneessential phosphatase, GlcA. Here, we report the identification of new GlcA inhibitors that show antifungal activity. These important finding open a new avenue to the development of novel antifungals to expand the current narrow arsenal of clinical candidates.

Keywords: invasive fungal diseases, phosphatases, GlcA, competitive inhibitors

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Authors: Luís Antonio de Almeida Rodriguez, José Maria Parente de Oliveira, Ednelson Oliveira

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In the last two decades, the world’s aviation authorities have made several attempts to create consensus about a global and accepted approach for applying semantics to web services registry descriptions. This problem has led communities to face a fat and disorganized infrastructure to describe aeronautical web services. It is usual for developers to implement ad-hoc connections among consumers and providers and manually create non-standardized service compositions, which need some particular approach to compose and semantically discover a desired web service. Current practices are not precise and tend to focus on lightweight specifications of some parts of the OWL-S and embed them into syntactic descriptions (SOAP artifacts and OWL language). It is necessary to have the ability to manage the use of both technologies. This paper presents an implementation of the ontology OWL-S that describes a Brazilian Aeronautical Web Service Registry, which makes it able to publish, advertise, make multi-criteria semantic discovery aligned with the ideas of the System Wide Information Management (SWIM) Program, and invoke web services within the Air Traffic Management context. The proposal’s best finding is a generic approach to describe semantic web services. The paper also presents a set of functional requirements to guide the ontology development and to compare them to the results to validate the implementation of the OWL-S Ontology.

Keywords: aeronautical web services, OWL-S, semantic web services discovery, ontologies

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Authors: Bing Li, Zhi Li, Yilong Yang

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Web classification can promote the quality of service discovery and management in the service repository. It is widely used to locate developers desired services. Although traditional classification methods based on supervised learning models can achieve classification tasks, developers need to manually mark web services, and the quality of these tags may not be enough to establish an accurate classifier for service classification. With the doubling of the number of web services, the manual tagging method has become unrealistic. In recent years, the attention mechanism has made remarkable progress in the field of deep learning, and its huge potential has been fully demonstrated in various fields. This paper designs a multi-head attention graph convolutional network (MHAGCN) service classification method, which can assign different weights to the neighborhood nodes without complicated matrix operations or relying on understanding the entire graph structure. The framework combines the advantages of the attention mechanism and graph convolutional neural network. It can classify web services through automatic feature extraction. The comprehensive experimental results on a real dataset not only show the superior performance of the proposed model over the existing models but also demonstrate its potentially good interpretability for graph analysis.

Keywords: attention mechanism, graph convolutional network, interpretability, service classification, service discovery

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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: 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: Gabriela V. Angeles Perez, Jose Castillejos Lopez, Araceli L. Reyes Cabello, Emilio Bravo Grajales, Adriana Perez Espinosa, Jose L. Quiroz Fabian

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Road traffic accidents are among the principal causes of traffic congestion, causing human losses, damages to health and the environment, economic losses and material damages. Studies about traditional road traffic accidents in urban zones represents very high inversion of time and money, additionally, the result are not current. However, nowadays in many countries, the crowdsourced GPS based traffic and navigation apps have emerged as an important source of information to low cost to studies of road traffic accidents and urban congestion caused by them. In this article we identified the zones, roads and specific time in the CDMX in which the largest number of road traffic accidents are concentrated during 2016. We built a database compiling information obtained from the social network known as Waze. The methodology employed was Discovery of knowledge in the database (KDD) for the discovery of patterns in the accidents reports. Furthermore, using data mining techniques with the help of Weka. The selected algorithms was the Maximization of Expectations (EM) to obtain the number ideal of clusters for the data and k-means as a grouping method. Finally, the results were visualized with the Geographic Information System QGIS.

Keywords: data mining, k-means, road traffic accidents, Waze, Weka

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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: S. Niamkaeo, O. Robert, O. Chaowalit

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In this investigation, we focus on discovering spatial relationship of drug smuggling along the northern border of Thailand. Thailand is no longer a drug production site, but Thailand is still one of the major drug trafficking hubs due to its topographic characteristics facilitating drug smuggling from neighboring countries. Our study areas cover three districts (Mae-jan, Mae-fahluang, and Mae-sai) in Chiangrai city and four districts (Chiangdao, Mae-eye, Chaiprakarn, and Wienghang) in Chiangmai city where drug smuggling of methamphetamine crystal and amphetamine occurs mostly. The data on drug smuggling incidents from 2011 to 2017 was collected from several national and local published news. Geo-spatial drug smuggling database was prepared. Decision tree algorithm was applied in order to discover the spatial relationship of factors related to drug smuggling, which was converted into rules using rule-based system. The factors including land use type, smuggling route, season and distance within 500 meters from check points were found that they were related to drug smuggling in terms of rules-based relationship. It was illustrated that drug smuggling was occurred mostly in forest area in winter. Drug smuggling exhibited was discovered mainly along topographic road where check points were not reachable. This spatial relationship of drug smuggling could support the Thai Office of Narcotics Control Board in surveillance drug smuggling.

Keywords: decision tree, drug smuggling, Geographic Information System, GIS knowledge discovery, rule-based 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: Majid Farsadrooh, Mehran Feizi-Dehnayebi

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Serum albumin is the most abundant protein that is present in the circulatory system of a wide variety of organisms. Although it is a significant macromolecule, it can contribute to osmotic blood pressure and also, plays a superior role in drug disposition and efficiency. Molecular docking simulation can improve in silico drug design and discovery procedures to propound a lead compound and develop it from the discovery step to the clinic. In this study, the molecular docking simulation was applied to select a lead molecule through an investigation of the interaction of the two anticancer drugs (Alitretinoin and Abemaciclib) with Human Serum Albumin (HSA). Then, a series of new compounds (a-e) were suggested using lead molecule modification. Density functional theory (DFT) including MEP map and HOMO-LUMO analysis were used for the newly proposed compounds to predict the reactivity zones on the molecules, stability, and chemical reactivity. DFT calculation illustrated that these new compounds were stable. The estimated binding free energy (ΔG) values for a-e compounds were obtained as -5.78, -5.81, -5.95, -5,98, and -6.11 kcal/mol, respectively. Finally, the pharmaceutical properties and toxicity of these new compounds were estimated through OSIRIS DataWarrior software. The results indicated no risk of tumorigenic, irritant, or reproductive effects and mutagenicity for compounds d and e. As a result, compounds d and e, could be selected for further study as potential therapeutic candidates. Moreover, employing molecular docking simulation with the prediction of pharmaceutical properties helps to discover new potential drug compounds.

Keywords: drug design, anticancer, computational studies, DFT analysis

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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: Karima Sekkoum Abdelkrim Cheriti, Leila Feguigui

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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: Matthias Stange

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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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Authors: Parthiban Srinivasan

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With recent advances in computational power and access to enough data in biosciences, artificial intelligence methods are increasingly being used in drug discovery research. These methods are essentially a series of advanced statistics based exercises that review the past to indicate the likely future. Our goal is to develop a model that accurately predicts biological activity and toxicity parameters for novel compounds. We have compiled a robust library of over 150,000 chemical compounds with different pharmacological properties from literature and public domain databases. The compounds are stored in simplified molecular-input line-entry system (SMILES), a commonly used text encoding for organic molecules. We utilize an automated process to generate an array of numerical descriptors (features) for each molecule. Redundant and irrelevant descriptors are eliminated iteratively. Our prediction engine is based on a portfolio of machine learning algorithms. We found Random Forest algorithm to be a better choice for this analysis. We captured non-linear relationship in the data and formed a prediction model with reasonable accuracy by averaging across a large number of randomized decision trees. Our next step is to apply deep neural network (DNN) algorithm to predict the biological activity and toxicity properties. We expect the DNN algorithm to give better results and improve the accuracy of the prediction. This presentation will review all these prominent machine learning and deep learning methods, our implementation protocols and discuss these techniques for their usefulness in biomedical and health informatics.

Keywords: deep learning, drug discovery, health informatics, machine learning, toxicity prediction

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Authors: Yumeng Ma, Fang Wang, Jinxia Huang

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Researchers put forward higher requirements for efficient acquisition and utilization of domain knowledge in the big data era. As literature is an effective way for researchers to quickly and accurately understand the research situation in their field, the knowledge discovery based on literature has become a new research method. As a tool to organize and manage knowledge in a specific domain, the subject knowledge base can be used to mine and present the knowledge behind the literature to meet the users' personalized needs. This study designs the construction route of the subject knowledge base for specific research problems. Information extraction method based on knowledge engineering is adopted. Firstly, the subject knowledge model is built through the abstraction of the research elements. Then under the guidance of the knowledge model, extraction rules of knowledge points are compiled to analyze, extract and correlate entities, relations, and attributes in literature. Finally, a database platform based on this structured knowledge is developed that can provide a variety of services such as knowledge retrieval, knowledge browsing, knowledge q&a, and visualization correlation. Taking the construction practices in the field of activating blood circulation and removing stasis as an example, this study analyzes how to construct subject knowledge base based on literature knowledge extraction. As the system functional test shows, this subject knowledge base can realize the expected service scenarios such as a quick query of knowledge, related discovery of knowledge and literature, knowledge organization. As this study enables subject knowledge base to help researchers locate and acquire deep domain knowledge quickly and accurately, it provides a transformation mode of knowledge resource construction and personalized precision knowledge services in the data-intensive research environment.

Keywords: knowledge model, literature knowledge extraction, precision knowledge services, subject knowledge base

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Authors: Fahad Hanash Alzahrani

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This paper describes some recent advances in a quickly developing area of data storing and processing based on Data Warehouses and Data Mining techniques, which are associated with software, hardware, data mining algorithms and visualisation techniques having common features for any specific problems and tasks of their implementation.

Keywords: data warehouse, data mining, knowledge discovery in databases, on-line analytical processing

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Authors: Muhammad Ishaqa, Quanchao Zhanga, Qian Wangb

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The Indus Valley Civilization is predominantly found in the northeast of Afghanistan, Pakistan, and the northwest of India and is considered one of the four ancient civilizations of the Old World, as well as the first urban civilization in South Asia. In 1920, John Marshall and other archaeologists established the existence of this civilization. Over the course of a century, India and Pakistan have made significant advancements in their joint archaeological investigation and excavation, contributing to the study of the Indus Valley Civilization. Given the importance of early discovery and confirmation of this civilization, our research focuses on the academic history of its archaeology by gathering published research material. Our research begins by collecting research data associated with the Indus Valley Civilization and documenting the process of archaeological investigations and excavations from the 19th century until the present day. We also summarize the archaeological works conducted during different periods. Furthermore, we present the primary academic views on the Indus Civilization from the 19th century until the present, explaining their developmental process and highlighting recent research. This forms a foundation for further study. We discovered that the archaeological research of the Indus Civilization is significantly influenced by Western archaeology and has yet to establish an independent, local research system. We delve into the three primary sites of the Indus Valley Civilization - Harappa, Mohenjo-Daro, and Chanhudaro - discussing their history and archaeological excavation records. Our findings indicate that the Indus Civilization is solely dependent on archaeology, distinguishing it from the Sumerian Civilization and verifying that it originates from the Bronze Age of the Indus Valley. Lastly, we examine the primary academic issues associated with the Indus Civilization in greater depth. These issues include climate environment, political system, primitive religion, and academic contribution.

Keywords: Indus Valley civilization, archaeology, Harappa, Mohenjo-Daro

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Authors: Chih-Ping Chang

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Different from traditional objective evidence, social media evidence has its own characteristics with easily tampering, recoverability, and cannot be read without using other devices (such as a computer). Simply taking a screenshot from social network sites must be questioned its original identity. When the police search and seizure digital information, a common way they use is to directly print out digital data obtained and ask the signature of the parties at the presence, without taking original digital data back. In addition to the issue on its original identity, this conduct to obtain evidence may have another two results. First, it will easily allege that is tampering evidence because the police wanted to frame the suspect and falsified evidence. Second, it is not easy to discovery hidden information. The core evidence associated with crime may not appear in the contents of files. Through discovery the original file, data related to the file, such as the original producer, creation time, modification date, and even GPS location display can be revealed from hidden information. Therefore, how to show this kind of evidence in the courtroom will be arguably the most important task for ruling social media evidence. This article, first, will introduce forensic software, like EnCase, TCT, FTK, and analyze their function to prove the identity with another digital data. Then turning back to the court, the second part of this article will discuss legal standard for authentication of social media evidence and application of that forensic software in the courtroom. As the conclusion, this article will provide a rethinking, that is, what kind of authenticity is this rule of evidence chase for. Does legal system automatically operate the transcription of scientific knowledge? Or furthermore, it wants to better render justice, not only under scientific fact, but through multivariate debating.

Keywords: federal rule of evidence, internet forensic, printouts as evidence, social media evidence, United States v. Vayner

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Authors: Adegoke Yinka Adebayo

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An understanding of the critical product attributes that impact on in vivo performance is key to the production of safe and effective medicines. Thus, a key driver for our research is the development of new basic science and technology underpinning the development of new pharmaceutical products. Research includes the structure and properties of drugs and excipients, biopharmaceutical characterisation, pharmaceutical processing and technology and formulation and analysis.

Keywords: drug discovery, drug development, drug delivery

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Authors: K. S. Suganya, R. Nedunchezhian

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In recent years, blockchain technology has been found to be the most significant discovery in this digital era, after the discovery of the Internet and Cloud Computing. Blockchain is a simple, distributed public ledger that contains all the user’s transaction details in a block. The global copy of the block is then shared among all its peer-peer network users after validation by the Blockchain miners. Once a block is validated and accepted, it cannot be altered by any users making it a trust-free transaction. It also resolves the problem of double-spending by using traditional cryptographic methods. Since the advent of bitcoin, blockchain has been the backbone for all its transactions. But in recent years, it has found its roots and uses in many fields like Smart Contracts, Smart City management, healthcare, etc. Identity management against digital identity theft has become a major concern among financial and other organizations. To solve this digital identity theft, blockchain technology can be employed with existing identity management systems, which maintain a distributed public ledger containing details of an individual’s identity containing information such as Digital birth certificates, Citizenship number, Bank details, voter details, driving license in the form of blocks verified on the blockchain becomes time-stamped, unforgeable and publicly visible for any legitimate users. The main challenge in using blockchain technology to prevent digital identity theft is ensuring the pseudo-anonymity and privacy of the users. This survey paper will exert to study the blockchain concepts, consensus protocols, and various blockchain-based Digital Identity Management systems with their research scope. This paper also discusses the role of Blockchain in COVID-19 pandemic management by self-sovereign identity and supply chain management.

Keywords: blockchain, consensus protocols, bitcoin, identity theft, digital identity management, pandemic, COVID-19, self-sovereign identity

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Authors: Peng Hou

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Natural products produced from marine bacteria serve as an immense reservoir for anti-infective drugs and therapeutic agents. Nowadays, heterologous expression of gene clusters of interests has been widely adopted as an effective strategy for natural product discovery. Briefly, the heterologous expression flowchart would be: biosynthetic gene cluster identification, pathway construction and expression, and product detection. However, gene cluster capture using traditional Transformation-associated recombination (TAR) protocol is low-efficient (0.5% positive colony rate). To make things worse, most of these putative new natural products are only predicted by bioinformatics analysis such as antiSMASH, and their corresponding natural products biosynthetic pathways are either not expressed or expressed at very low levels under laboratory conditions. Those setbacks have inspired us to focus on seeking new technologies to efficiently edit and refractor of biosynthetic gene clusters. Recently, two cutting-edge techniques have attracted our attention - the CRISPR-Cas9 and Gibson Assembly. By now, we have tried to pretreat Brevibacillus laterosporus strain genomic DNA with CRISPR-Cas9 nucleases that specifically generated breaks near the gene cluster of interest. This trial resulted in an increase in the efficiency of gene cluster capture (9%). Moreover, using Gibson Assembly by adding/deleting certain operon and tailoring enzymes regardless of end compatibility, the silent construct (~80kb) has been successfully refactored into an active one, yielded a series of analogs expected. With the appearances of the novel molecular tools, we are confident to believe that development of a high throughput mature pipeline for DNA assembly, transformation, product isolation and identification would no longer be a daydream for marine natural product discovery.

Keywords: biosynthesis, CRISPR-Cas9, DNA assembly, refactor, TAR cloning

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Authors: Kanduru Lokesh, Venkitasamy Kesavan

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The unique structural features of spiro-oxindoles with diverse biological activities have made them privileged structures in new drug discovery. The key structural characteristic of these compounds is the spiro ring fused at the C-3 position of the oxindole core with varied heterocyclic motifs. Structural diversification of heterocyclic scaffolds to synthesize new chemical entities as pharmaceuticals and agrochemicals is one of the important goals of synthetic organic chemists. Nitrogen and oxygen containing heterocycles are by far the most widely occurring privileged structures in medicinal chemistry. The structural complexity and distinct three-dimensional arrangement of functional groups of these privileged structures are generally responsible for their specificity against biological targets. Structurally diverse compound libraries have proved to be valuable assets for drug discovery against challenging biological targets. Thus, identifying a new combination of substituents at C-3 position on oxindole moiety is of great importance in drug discovery to improve the efficiency and efficacy of the drugs. The development of suitable methodology for the synthesis of spiro-oxindole compounds has attracted much interest often in response to the significant biological activity displayed by the both natural and synthetic compounds. So creating structural diversity of oxindole scaffolds is need of the decade and formidable challenge. A general way to improve synthetic efficiency and also to access diversified molecules is through the annulation reactions. Annulation reactions allow the formation of complex compounds starting from simple substrates in a single transformation consisting of several steps in an ecologically and economically favorable way. These observations motivated us to develop the annulation reaction protocol to enable the synthesis of a new class of spiro-oxindole motifs which in turn would enable the enhancement of molecular diversity. As part of our enduring interest in the development of novel, efficient synthetic strategies to enable the synthesis of biologically important oxindole fused spirocarbocyclic systems, We have developed an efficient methodology for the construction of highly functionalized spirocarbocyclic oxindoles through [4+2] annulation of phthalides via Hauser annulation. functionalized spirocarbocyclic oxindoles was accomplished for the first time in the literature using Hauser annulation strategy. The reaction between methyleneindolinones and arylsulfonylphthalides catalyzed by cesium carbonate led to the access of new class of biologically important spiro[indoline-3,2'-naphthalene] derivatives in very good yields. The synthetic utility of the annulated product was further demonstrated by fluorination Using NFSI as a fluorinating agent to furnish corresponding fluorinated product.

Keywords: Hauser-Kraus annulation, spiro carbocyclic oxindoles, oxindole-ester, fluoridation

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