Search results for: discovery of misattributed paternity

Authors: Vani Singhal, Jitendra Parmar, Satyendra Singh Chouhan

Abstract:

Unseen class discovery has now become an important part of a machine-learning algorithm to judge new classes. Unseen classes are the classes on which the machine learning model is not trained on. With the advancement in technology and AI replacing humans, the amount of data has increased to the next level. So while implementing a model on real-world examples, we come across unseen new classes. Our aim is to find the number of unseen classes by using a hierarchical-based active learning algorithm. The algorithm is based on hierarchical clustering as well as active sampling. The number of clusters that we will get in the end will give the number of unseen classes. The total clusters will also contain some clusters that have unseen classes. Instead of first discovering unseen classes and then finding their number, we directly calculated the number by applying the algorithm. The dataset used is for intent classification. The target data is the intent of the corresponding query. We conclude that when the machine learning model will encounter real-world data, it will automatically find the number of unseen classes. In the future, our next work would be to label these unseen classes correctly.

Keywords: active sampling, hierarchical clustering, open world learning, unseen class discovery

Procedia PDF Downloads 137

Authors: Alaaeddeen M. Seufi

Abstract:

Many have been published on therapeutic derivatives from living organisms including insects. In addition to traditional maggot therapy, more than 900 therapeutic products were isolated from insects. Most people look at insects as enemies and others believe that insects are friends. Many beneficial insects rather than Honey Bees, Silk Worms and Shellac insect could insure human-insect friendship. In addition, insects could be MicroFactories, Biosensors or Bioreactors. InsectFarm is an amazing example of the applied research that transfers insects from laboratory to market by Prof Mircea Ciuhrii and co-workers. They worked for 18 years to derive therapeutics from insects. Their research resulted in production of more than 30 commercial medications derived from insects (e.g. Imunomax, Noblesse, etc.). Two general approaches were followed to discover drugs from living organisms. Some laboratories preferred biochemical approach to purify components of the innate immune system of insects and insect metabolites as well. Then the purified components could be tested for many therapeutic trials. Other researchers preferred molecular approach based on proteomic studies. Components of the innate immune system of insects were then tested for their medical activities. Our Laboratory team preferred to induce insect immune system (using oral, topical and injection routes of administration), then a transcriptomic study was done to discover the induced genes and to identify specific biomarkers that can help in drug discovery. Biomarkers play an important role in medicine and in drug discovery and development as well. Optimum biomarker development and application will require a team approach because of the multifaceted nature of biomarker selection, validation, and application. This team uses several techniques such as pharmacoepidemiology, pharmacogenomics, and functional proteomics; bioanalytical development and validation; modeling and simulation to improve and refine drug development. Our Achievements included the discovery of four components of the innate immune system of Spodoptera littoralis and Musca domestica. These components were designated as SpliDef (defesin), SpliLec (lectin), SpliCec (cecropin) and MdAtt (attacin). SpliDef, SpliLec and MdAtt were confirmed as antimicrobial peptides, while SpliCec was additionally confirmed as anticancer peptide. Our current research is going on to achieve something in antioxidants and anticoagulants from insects. Our perspective is to achieve something in the mass production of prototypes of our products and to reach it to the commercial level. These achievements are the integrated contributions of everybody in our team staff.

Keywords: AMPs, insect, innate immunitty, therappeutics

Procedia PDF Downloads 345

Authors: Shasline Gedeon, Tiffany W. Ardley, Ying Wang, Nathan J. Gesmundo, Katarina A. Sarris, Ana L. Aguirre

Abstract:

Drug discovery and delivery involve drug targeting, an approach that helps find a drug against a chosen target through high throughput screening and other methods by way of identifying the physical properties of the potential lead compound. Physical properties of potential drug candidates have been an imperative focus since the unveiling of Lipinski's Rule of 5 for oral drugs. Throughout a compound's journey from discovery, clinical phase trials, then becoming a classified drug on the market, the desirable properties are optimized while minimizing/eliminating toxicity and undesirable properties. In the pharmaceutical industry, the ability to generate molecules in parallel with maximum efficiency is a substantial factor achieved through sp²-sp² carbon coupling reactions, e.g., Suzuki Coupling reactions. These reaction types allow for the increase of aromatic fragments onto a compound. More recent literature has found benefits to decreasing aromaticity, calling for more sp³-sp² carbon coupling reactions instead. The objective of this project is to provide a comparison between various sp³-sp² carbon coupling methods and reaction conditions, collecting data on production of the desired product. There were four different coupling methods being tested amongst three cores and 4-5 installation groups per method; each method ran under three distinct reaction conditions. The tested methods include the Photoredox Decarboxylative Coupling, the Photoredox Potassium Alkyl Trifluoroborate (BF3K) Coupling, the Photoredox Cross-Electrophile (PCE) Coupling, and the Weix Cross-Electrophile (WCE) Coupling. The results concluded that the Decarboxylative method was very difficult in yielding product despite the several literature conditions chosen. The BF3K and PCE methods produced competitive results. Amongst the two Cross-Electrophile coupling methods, the Photoredox method surpassed the Weix method on numerous accounts. The results will be used to build future libraries.

Keywords: drug discovery, high throughput chemistry, photoredox chemistry, sp³-sp² carbon coupling methods

Procedia PDF Downloads 110

Authors: Michio Kurosu

Abstract:

Alterations in glycosylation not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Identification of cell type-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems for certain cancers via immunodetection reagents. N- and O-linked glycans are the most abundant forms of glycoproteins. Recent studies of cancer immunotherapy are based on the immunogenicity of truncated O-glycan chains (e.g., Tn, sTn, T, and sLea/x). The prevalence of N-linked glycan changes in the development of tumor cells is known; however, therapeutic antibodies against N-glycans have not yet been developed. This is due to the lack of specificity of N-linked glycans between normal/healthy and cancer cells. Abnormal branching of N-linked glycans has been observed, particularly in solid cancer cells. While the discovery of drug-like glycosyltransferase inhibitors that block the biosynthesis of specific branching has a very low likelihood of success, altered glycosylation levels can be exploited by suppressing N-glycan biosynthesis through the inhibition of dolichyl-phosphate N-acetylglucosaminephosphotransferase1 (DPAGT1) activity. Inhibition of DPAGT1 function leads to changes of O-glycosylation on proteins associated with mitochondria and zinc finger binding proteins (indirect effects). On the basis of dynamic crosstalk between DPAGT1 and Snail/Slung/ZEB1 (a family of transcription factors that promote the repression of the adhesion molecules), we have developed pharmacologically acceptable selective DPAGT1 inhibitors. Tunicamycin kills a wide range of cancer and healthy cells in a non-selective manner. In sharp contrast, our DPAGT1 inhibitors display strong cytostatic effects against 16 solid cancers, which require the overexpression of DPAGT1 in their progression but do not affect the cell viability of healthy cells. The identified DPAGT1 inhibitors possess impressive anti-metastatic ability in various solid cancer cell lines and induce their mitochondrial structural changes, resulting in apoptosis. A prototype DPAGT1 inhibitor, APPB has already been proven to shrink solid tumors (e.g., pancreatic cancers, triple-negative breast cancers) in vivo while suppressing metastases and has strong synergistic effects when combined with current cytotoxic drugs (e.g., paclitaxel). At this conference, our discovery of selective DPAGT1 inhibitors with drug-like properties and proof-of-pharmaceutical concept studies of a novel DPAGT1 inhibitor are presented.

Keywords: DPAGT1 inhibitors, anti-metastatic drugs, natural product based drug designs, cytostatic effects

Procedia PDF Downloads 45

Authors: S. Nandagopalan, N. Pradeep

Abstract:

The aim of this paper is to propose a general framework for storing, analyzing, and extracting knowledge from two-dimensional echocardiographic images, color Doppler images, non-medical images, and general data sets. A number of high performance data mining algorithms have been used to carry out this task. Our framework encompasses four layers namely physical storage, object identification, knowledge discovery, user level. Techniques such as active contour model to identify the cardiac chambers, pixel classification to segment the color Doppler echo image, universal model for image retrieval, Bayesian method for classification, parallel algorithms for image segmentation, etc., were employed. Using the feature vector database that have been efficiently constructed, one can perform various data mining tasks like clustering, classification, etc. with efficient algorithms along with image mining given a query image. All these facilities are included in the framework that is supported by state-of-the-art user interface (UI). The algorithms were tested with actual patient data and Coral image database and the results show that their performance is better than the results reported already.

Keywords: active contour, Bayesian, echocardiographic image, feature vector

Procedia PDF Downloads 416

Authors: Mehravar Javid

Abstract:

This article delves straight into the fascinating role of dream interpretation in psychotherapy, particularly in the context of trauma and healing. By applying a detailed case study of a 19-year-old Iranian woman who has been undergoing therapy, it can explore to what extent her vivid and symbolic dreams – featuring mermaids, hanging fetuses, and themes of control and domination – serve as a reflection of her innermost fears, unresolved traumas, and struggles with identity and sexuality. Another fact to be highlighted is that the dreams, rich in metaphor and symbolism, offer a unique outlook into the patient's subconscious mind, revealing layers of her psychological state that might otherwise remain obscured and vague. On the other hand, the article examines how the therapist navigates these dreamscapes by utilizing them as a tool to understand and address the patient's deep-seated emotional conflicts, traumatic experiences, and identity issues. By analyzing these dreams, we can demonstrate how such dreams can be a crucial part of the healing process, providing insights that facilitate emotional recovery and self-discovery. This discovery underscores the significance of dreams in psychotherapy, highlighting their potential as a powerful medium for unraveling the complexities of the human psyche and aiding in the journey toward mental health and recovery.

Keywords: dream, interpreting, trauma, healing

Procedia PDF Downloads 44

Authors: Claudia Troccoli

Abstract:

Childbearing constitutes one of the key factors affecting labour market differences between men and women, accounting for almost a quarter of the gender wage gap. Family leave policies, such as maternity, paternity, and parental leave, represent potential key policy tools to address these inequalities, as they can promote mothers' job continuity and career progression. This paper analyses four major reforms implemented in Finland between the 1960s and the early 1980s. It studies the effects of these maternity and parental leave extensions on mothers' short- and long-run labour market outcomes. Eligibility to longer leave was determined on the basis of the child's date of birth. Therefore, estimation of the causal effects of the reforms is possible by exploiting random variation in children's birthdates and comparing the outcomes of mothers giving birth just before and just after the reform cutoff date. Overall, the three maternity leave reforms did not significantly improve mothers' earnings or employment rates. On the contrary, the estimates, although imprecise, seem to indicate negative effects on women's labour market outcomes. The extension of parental leave is, on the other hand, the only reform that improved mothers' short- and long-term labour market outcomes, both in terms of earnings and employment rate. At the same time, fathers appeared to be negatively affected by the reform. These results provide suggestive evidence that shareable parental leave might have more beneficial effects on mothers' job continuity, as it weakens the connotation of childcare as a task reserved for mothers.

Keywords: family policies, Finland, maternal labour market outcomes, maternity leave

Procedia PDF Downloads 113

Authors: S. Nandagopalan, N. Pradeep

Abstract:

The aim of this paper is to propose a general framework for storing, analyzing, and extracting knowledge from two-dimensional echocardiographic images, color Doppler images, non-medical images, and general data sets. A number of high performance data mining algorithms have been used to carry out this task. Our framework encompasses four layers namely physical storage, object identification, knowledge discovery, user level. Techniques such as active contour model to identify the cardiac chambers, pixel classification to segment the color Doppler echo image, universal model for image retrieval, Bayesian method for classification, parallel algorithms for image segmentation, etc., were employed. Using the feature vector database that have been efficiently constructed, one can perform various data mining tasks like clustering, classification, etc. with efficient algorithms along with image mining given a query image. All these facilities are included in the framework that is supported by state-of-the-art user interface (UI). The algorithms were tested with actual patient data and Coral image database and the results show that their performance is better than the results reported already.

Keywords: active contour, bayesian, echocardiographic image, feature vector

Procedia PDF Downloads 389

Authors: Thi Thu Van Nguyen

Abstract:

In South Korea, Confucianism has not only played a crucial position in Korean traditional culture but also deeply rooted in people’s mind. Confucianism bears a special emphasis on the traditional family pattern characterized by paternalism. Therefore, non-paternity families are barely recognized and unwed mothers are faced with numerous prejudices in their life. Prejudice to unwed mothers in Korea is believed to stem from social discourses against lone motherhood which is the way how people look and talk about unwed mothers and from the early time these social discourses have big impacts on their daily lives. However, after the 1990s, along with the rapid transformation of family pattern and support from social welfare organizations, unwed mothers have gradually got to escape from the social prejudice then established themselves as a new family form. This study is aimed at researching social discourses on lone motherhood in Korea and the process of resistance, adaptation and negotiation of unwed mothers in three different stages: the antenatal, postnatal stages and social inclusion. The anthropological method is employed. Twenty single young mothers of the Korean Unwed Mothers Families' Association were engaged in the author’s detailed interviews. The study’s frame analysis is based on the theoretical framework on social discourses on lone motherhood by Simon Duncan and Rosalind Edwards (1999). This study is an effort to comprehend and investigate the difficulties experienced by unwed mothers living in negative social discourses and the way they overcome the difficulties.

Keywords: unwed mothers, gender, social discourses, social prejudice, Confucianism

Procedia PDF Downloads 238

Authors: Hema Bhardwaj, D. Srinivasa Rao

Abstract:

Technology for analysing, processing, and extracting meaningful data from enormous and complicated datasets can be termed as "big data." The technique of big data mining and big data analysis is extremely helpful for business movements such as making decisions, building organisational plans, researching the market efficiently, improving sales, etc., because typical management tools cannot handle such complicated datasets. Special computational and statistical issues, such as measurement errors, noise accumulation, spurious correlation, and storage and scalability limitations, are brought on by big data. These unique problems call for new computational and statistical paradigms. This research paper offers an overview of the literature on big data mining, its process, along with problems and difficulties, with a focus on the unique characteristics of big data. Organizations have several difficulties when undertaking data mining, which has an impact on their decision-making. Every day, terabytes of data are produced, yet only around 1% of that data is really analyzed. The idea of the mining and analysis of data and knowledge discovery techniques that have recently been created with practical application systems is presented in this study. This article's conclusion also includes a list of issues and difficulties for further research in the area. The report discusses the management's main big data and data mining challenges.

Keywords: big data, data mining, data analysis, knowledge discovery techniques, data mining challenges

Procedia PDF Downloads 81

Authors: Elena G. Salina, Vadim A. Makarov

Abstract:

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

Procedia PDF Downloads 145

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

Abstract:

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

Procedia PDF Downloads 77

Authors: Shiori Ishida, Hiromi Okuno, Hisato Igarashi, Akemi Yamazaki, Hiroko Takahashi

Abstract:

The purpose of this study was to clarify the differences and similarities regarding the social support of fathers and mothers towards considering increased assistance for the paternity of children with developmental disabilities. Written questionnaires were completed by fathers (n=85) and mothers (n=101) of children using rehabilitation facilities between infancy and 5 years of age. The survey contained multiple-choice questions on four categories: information support (6 items), emotional support (7 items), evaluation support (3 items), and daily living support (3 items). Regarding information support, fathers answered ‘spouse’ as the provider in over 50% of cases for all 6 items, which was significantly different compared with mothers (all p < 0.001). For emotional support, fathers were significantly more likely to get support from the workplace (p < 0.001) and from spouse (p < 0.001). The ‘evaluation support’ did not have significant differences for fathers in all the items, but the most frequent support providers were ‘spouses’. ‘Daily living support’ was significantly different from fathers in the workplace (p < 0.000) in terms of make allowances for work and duties. Thus, it appeared that fathers had fewer social support sources as compared with mothers and limited non-spouse support. The understanding of developmental disabilities, acquisition of methods of rehabilitation, and sources of support might have been inadequately addressed among fathers, which could be a hindrance to the involvement of fathers in the rearing of children with developmental disabilities. On the other hand, we also observed that some fathers were involved in the care of developmentally troubled children while providing mental support for their spouse, cooperating with housework, and adjusting their work life. However, the results on the external and social backgrounds of fathers indicated a necessity for greater empowerment and peer support to improve the paternal care of children with developmental disabilities in the family survey.

Keywords: children with developmental disabilities, family support, father, social support

Procedia PDF Downloads 108

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

Abstract:

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

Procedia PDF Downloads 60

Authors: Bing Li, Zhi Li, Yilong Yang

Abstract:

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

Procedia PDF Downloads 111

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

Abstract:

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

Procedia PDF Downloads 58

Authors: Olanrewaju B. Lasisi

Abstract:

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

Procedia PDF Downloads 204

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

Abstract:

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

Procedia PDF Downloads 358

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

Abstract:

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

Procedia PDF Downloads 473

Authors: Reza Ferdousi, Reza Safdari, Yadollah Omidi

Abstract:

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

Procedia PDF Downloads 286

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

Abstract:

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

Procedia PDF Downloads 217

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

Abstract:

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

Procedia PDF Downloads 379

Authors: Paolo Fantozzi, Luigi Laura, Umberto Nanni

Abstract:

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

Procedia PDF Downloads 119

Authors: Abdullah M. Algarni, Yashwant K. Malaiya

Abstract:

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

Procedia PDF Downloads 225

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

Abstract:

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

Procedia PDF Downloads 143

Authors: Ayan Giri, Lukaranjan Phukan, Shantanu Karmakar

Abstract:

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

Procedia PDF Downloads 191

Authors: Majid Farsadrooh, Mehran Feizi-Dehnayebi

Abstract:

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

Procedia PDF Downloads 45

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

Abstract:

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

Procedia PDF Downloads 394

Authors: Rezky Rifaini, Raden Bagus Fajriya Hakim

Abstract:

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

Procedia PDF Downloads 372

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

Procedia PDF Downloads 266