Search results for: epitope candidate
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 717

Search results for: epitope candidate

597 MicroRNA Drivers of Resistance to Androgen Deprivation Therapy in Prostate Cancer

Authors: Philippa Saunders, Claire Fletcher

Abstract:

INTRODUCTION: Prostate cancer is the most prevalent malignancy affecting Western males. It is initially an androgen-dependent disease: androgens bind to the androgen receptor and drive the expression of genes that promote proliferation and evasion of apoptosis. Despite reduced androgen dependence in advanced prostate cancer, androgen receptor signaling remains a key driver of growth. Androgen deprivation therapy (ADT) is, therefore, a first-line treatment approach and works well initially, but resistance inevitably develops. Abiraterone and Enzalutamide are drugs widely used in ADT and are androgen synthesis and androgen receptor signaling inhibitors, respectively. The shortage of other treatment options means acquired resistance to these drugs is a major clinical problem. MicroRNAs (miRs) are important mediators of post-transcriptional gene regulation and show altered expression in cancer. Several have been linked to the development of resistance to ADT. Manipulation of such miRs may be a pathway to breakthrough treatments for advanced prostate cancer. This study aimed to validate ADT resistance-implicated miRs and their clinically relevant targets. MATERIAL AND METHOD: Small RNA-sequencing of Abiraterone- and Enzalutamide-resistant C42 prostate cancer cells identified subsets of miRs dysregulated as compared to parental cells. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to validate altered expression of candidate ADT resistance-implicated miRs 195-5p, 497-5p and 29a-5p in ADT-resistant and -responsive prostate cancer cell lines, patient-derived xenografts (PDXs) and primary prostate cancer explants. RESULTS AND DISCUSSION: This study suggests a possible role for miR-497-5p in the development of ADT resistance in prostate cancer. MiR-497-5p expression was increased in ADT-resistant versus ADT-responsive prostate cancer cells. Importantly, miR-497-5p expression was also increased in Enzalutamide-treated, castrated (ADT-mimicking) PDXs versus intact PDXs. MiR-195-5p was also elevated in ADT-resistant versus -responsive prostate cancer cells, while there was a drop in miR-29a-5p expression. Candidate clinically relevant targets of miR-497-5p in prostate cancer were identified by mining AGO-PAR-CLIP-seq data sets and may include AVL9 and FZD6. CONCLUSION: In summary, this study identified microRNAs that are implicated in prostate cancer resistance to androgen deprivation therapy and could represent novel therapeutic targets for advanced disease.

Keywords: microRNA, androgen deprivation therapy, Enzalutamide, abiraterone, patient-derived xenograft

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596 Robust Half-Metallicity and Magnetic Properties of Cubic PrMnO3 Perovskite

Authors: B. Bouadjemi, S. Bentata, W. Benstaali, A. Abbad, T. Lantri, A. Zitouni

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The purpose of this study was to investigate the structural,electronic and magnetic properties of the cubic praseodymium oxides perovskites PrMnO3. It includes our calculations based on the use of the density functional theory (DFT) with both generalized gradient approximation (GGA) and GGA+U approaches, The spin polarized electronic band structures and densities of states aswellas the integer value of the magnetic moment of the unit cell (6 μB) illustrate that PrMnO3 is half-metallic ferromagnetic. The study shows that the robust half-metallicity makes the cubic PrMnO3 a promising candidate for application in spintronics.

Keywords: Perovskite, DFT, electronic properties, Magnetic moment, half-metallic

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595 Structural, Electronic and Magnetic Properties of Co and Mn Doped CDTE

Authors: A. Zitouni, S. Bentata, B. Bouadjemi, T. Lantri, W. Benstaali, A. Zoubir, S. Cherid, A. Sefir

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The structural, electronic, and magnetic properties of transition metal Co and Mn doped zinc-blende semiconductor CdTe were calculated using the density functional theory (DFT) with both generalized gradient approximation (GGA). We have analyzed the structural parameters, charge and spin densities, total and partial densities of states. We find that the Co and Mn doped zinc blende CdTe show half-metallic behavior with a total magnetic moment of 6.0 and 10.0 µB, respectively.The results obtained, make the Co and Mn doped CdTe a promising candidate for application in spintronics.

Keywords: first-principles, half-metallic, diluted magnetic semiconductor, magnetic moment

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594 Clusterization Probability in 14N Nuclei

Authors: N. Burtebayev, Sh. Hamada, Zh. Kerimkulov, D. K. Alimov, A. V. Yushkov, N. Amangeldi, A. N. Bakhtibaev

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The main aim of the current work is to examine if 14N is candidate to be clusterized nuclei or not. In order to check this attendance, we have measured the angular distributions for 14N ion beam elastically scattered on 12C target nuclei at different low energies; 17.5, 21, and 24.5MeV which are close to the Coulomb barrier energy for 14N+12C nuclear system. Study of various transfer reactions could provide us with useful information about the attendance of nuclei to be in a composite form (core + valence). The experimental data were analyzed using two approaches; Phenomenological (Optical Potential) and semi-microscopic (Double Folding Potential). The agreement between the experimental data and the theoretical predictions is fairly good in the whole angular range.

Keywords: deuteron transfer, elastic scattering, optical model, double folding, density distribution

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593 Graduates Construction of Knowledge and Ability to Act on Employable Opportunities

Authors: Martabolette Stecher

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Introductory: How is knowledge and ability to act on employable opportunities constructed among students and graduates at higher educations? This question have been drawn much attention by researchers, governments and universities in Denmark, since there has been an increases in the rate of unemployment among graduates from higher education. The fact that more than ten thousand graduates from higher education without the opportunity to get a job in these years has a tremendous impact upon the social economy in Denmark. Every time a student graduate from higher education and become unemployed, it is possible to trace upon the person´s chances to get a job many years ahead. This means that the tremendous rate of graduate unemployment implies a decrease in employment and lost prosperity in Denmark within a billion Danish Kroner scale. Basic methodologies: The present study investigates the construction of knowledge and ability to act upon employable opportunities among students and graduates at higher educations in Denmark in a literature review as well as a preliminary study of students from Aarhus University. 15 students from the candidate of drama have been engaging in an introductory program at the beginning of their candidate study, which included three workshops focusing upon the more personal matters of their studies and life. They have reflected upon this process during the intervention and afterwards in a semi-structured interview. Concurrently a thorough literature review has delivered key concepts for the exploration of the research question. Major findings of the study: It is difficult to find one definition of what employability encompasses, hence the overall picture of how to incorporate the concept is difficult. The present theory of employability has been focusing upon the competencies, which students and graduates are going to develop in order to become employable. In recent years there has been an emphasis upon the mechanism which supports graduates to trust themselves and to develop their self-efficacy in terms of getting a sustainable job. However, there has been little or no focus in the literature upon the idea of how students and graduates from higher education construct knowledge about and ability to act upon employable opportunities involving network of actors both material and immaterial network and meaningful relations for students and graduates in developing their enterprising behavior to achieve employment. The Act-network-theory combined with theory of entrepreneurship education suggests an alternative strategy to focus upon when explaining sustainable ways of creating employability among graduates. The preliminary study also supports this theory suggesting that it is difficult to emphasize a single or several factors of importance rather highlighting the effect of a multitude network. Concluding statement: This study is the first step of a ph.d.-study investigating this problem in Denmark and the USA in the period 2015 – 2019.

Keywords: employablity, graduates, action, opportunities

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592 Using Mining Methods of WEKA to Predict Quran Verb Tense and Aspect in Translations from Arabic to English: Experimental Results and Analysis

Authors: Jawharah Alasmari

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In verb inflection, tense marks past/present/future action, and aspect marks progressive/continues perfect/completed actions. This usage and meaning of tense and aspect differ in Arabic and English. In this research, we applied data mining methods to test the predictive function of candidate features by using our dataset of Arabic verbs in-context, and their 7 translations. Weka machine learning classifiers is used in this experiment in order to examine the key features that can be used to provide guidance to enable a translator’s appropriate English translation of the Arabic verb tense and aspect.

Keywords: Arabic verb, English translations, mining methods, Weka software

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591 Seat Assignment Model for Student Admissions Process at Saudi Higher Education Institutions

Authors: Mohammed Salem Alzahrani

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In this paper, student admission process is studied to optimize the assignment of vacant seats with three main objectives. Utilizing all vacant seats, satisfying all program of study admission requirements and maintaining fairness among all candidates are the three main objectives of the optimization model. Seat Assignment Method (SAM) is used to build the model and solve the optimization problem with help of Northwest Coroner Method and Least Cost Method. A closed formula is derived for applying the priority of assigning seat to candidate based on SAM.

Keywords: admission process model, assignment problem, Hungarian Method, Least Cost Method, Northwest Corner Method, SAM

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590 Residual Analysis and Ground Motion Prediction Equation Ranking Metrics for Western Balkan Strong Motion Database

Authors: Manuela Villani, Anila Xhahysa, Christopher Brooks, Marco Pagani

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The geological structure of Western Balkans is strongly affected by the collision between Adria microplate and the southwestern Euroasia margin, resulting in a considerably active seismic region. The Harmonization of Seismic Hazard Maps in the Western Balkan Countries Project (BSHAP) (2007-2011, 2012-2015) by NATO supported the preparation of new seismic hazard maps of the Western Balkan, but when inspecting the seismic hazard models produced later by these countries on a national scale, significant differences in design PGA values are observed in the border, for instance, North Albania-Montenegro, South Albania- Greece, etc. Considering the fact that the catalogues were unified and seismic sources were defined within BSHAP framework, obviously, the differences arise from the Ground Motion Prediction Equations selection, which are generally the component with highest impact on the seismic hazard assessment. At the time of the project, a modest database was present, namely 672 three-component records, whereas nowadays, this strong motion database has increased considerably up to 20,939 records with Mw ranging in the interval 3.7-7 and epicentral distance distribution from 0.47km to 490km. Statistical analysis of the strong motion database showed the lack of recordings in the moderate-to-large magnitude and short distance ranges; therefore, there is need to re-evaluate the Ground Motion Prediction Equation in light of the recently updated database and the new generations of GMMs. In some cases, it was observed that some events were more extensively documented in one database than the other, like the 1979 Montenegro earthquake, with a considerably larger number of records in the BSHAP Analogue SM database when compared to ESM23. Therefore, the strong motion flat-file provided from the Harmonization of Seismic Hazard Maps in the Western Balkan Countries Project was merged with the ESM23 database for the polygon studied in this project. After performing the preliminary residual analysis, the candidate GMPE-s were identified. This process was done using the GMPE performance metrics available within the SMT in the OpenQuake Platform. The Likelihood Model and Euclidean Distance Based Ranking (EDR) were used. Finally, for this study, a GMPE logic tree was selected and following the selection of candidate GMPEs, model weights were assigned using the average sample log-likelihood approach of Scherbaum.

Keywords: residual analysis, GMPE, western balkan, strong motion, openquake

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589 Genetic Dissection of QTLs in Intraspecific Hybrids Derived from Muskmelon (Cucumis Melo L.) and Mangalore Melon (Cucumis Melo Var Acidulus) for Shelflife and Fruit Quality Traits

Authors: Virupakshi Hiremata, Ratnakar M. Shet, Raghavendra Gunnaiah, Prashantha A.

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Muskmelon is a health-beneficial and refreshing dessert vegetable with a low shelf life. Mangalore melon, a genetic homeologue of muskmelon, has a shelf life of more than six months and is mostly used for culinary purposes. Understanding the genetics of shelf life, yield and yield-related traits and identification of markers linked to such traits is helpful in transfer of extended shelf life from Mangalore melon to the muskmelon through intra-specific hybridization. For QTL mapping, 276 F2 mapping population derived from the cross Arka Siri × SS-17 was genotyped with 40 polymorphic markers distributed across 12 chromosomes. The same population was also phenotyped for yield, shelf life and fruit quality traits. One major QTL (R2 >10) and fourteen minor QTLs (R2 <10) localized on four linkage groups, governing different traits were mapped in F2 mapping population developed from the intraspecific cross with a LOD > 5.5. The phenotypic varience explained by each locus varied from 3.63 to 10.97 %. One QTL was linked to shelf-life (qSHL-3-1), five QTLs were linked to TSS (qTSS-1-1, qTSS-3-3, qTSS-3-1, qTSS-3-2 and qTSS-1-2), two QTLs for flesh thickness (qFT-3-1, and qFT-3-2) and seven QTLs for fruit yield per vine (qFYV-3-1, qFYV-1-1, qFYV-3-1, qFYV1-1, qFYV-1-3, qFYV2-1 and qFYV6-1). QTL flanking markers may be used for marker assisted introgression of shelf life into muskmelon. Important QTL will be further fine-mapped for identifying candidate genes by QTLseq and RNAseq analysis. Fine-mapping of Important Quantitative Trait Loci (QTL) holds immense promise in elucidating the genetic basis of complex traits. Leveraging advanced techniques like QTLseq and RNA sequencing (RNA seq) is crucial for this endeavor. QTLseq combines next-generation sequencing with traditional QTL mapping, enabling precise identification of genomic regions associated with traits of interest. Through high-throughput sequencing, QTLseq provides a detailed map of genetic variations linked to phenotypic variations, facilitating targeted investigations. Moreover, RNA seq analysis offers a comprehensive view of gene expression patterns in response to specific traits or conditions. By comparing transcriptomes between contrasting phenotypes, RNA seq aids in pinpointing candidate genes underlying QTL regions. Integrating QTLseq with RNA seq allows for a multi-dimensional approach, coupling genetic variation with gene expression dynamics.

Keywords: QTL, shelf life, TSS, muskmelon and Mangalore melon

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588 Emerging Technology for 6G Networks

Authors: Yaseein S. Hussein, Victor P. Gil Jiménez, Abdulmajeed Al-Jumaily

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Due to the rapid advancement of technology, there is an increasing demand for wireless connections that are both fast and reliable, with minimal latency. New wireless communication standards are developed every decade, and the year 2030 is expected to see the introduction of 6G. The primary objectives of 6G network and terminal designs are focused on sustainability and environmental friendliness. The International Telecommunication Union-Recommendation division (ITU-R) has established the minimum requirements for 6G, with peak and user data rates of 1 Tbps and 10-100 Gbps, respectively. In this context, Light Fidelity (Li-Fi) technology is the most promising candidate to meet these requirements. This article will explore the various advantages, features, and potential applications of Li-Fi technology, and compare it with 5G networking, to showcase its potential impact among other emerging technologies that aim to enable 6G networks.

Keywords: 6G networks, artificial intelligence (AI), Li-Fi technology, Terahertz (THz) communication, visible light communication (VLC)

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587 Differentially Expressed Genes in Atopic Dermatitis: Bioinformatics Analysis Of Pooled Microarray Gene Expression Datasets In Gene Expression Omnibus

Authors: Danna Jia, Bin Li

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Background: Atopic dermatitis (AD) is a chronic and refractory inflammatory skin disease characterized by relapsing eczematous and pruritic skin lesions. The global prevalence of AD ranges from 1~ 20%, and its incidence rates are increasing. It affects individuals from infancy to adulthood, significantly impacting their daily lives and social activities. Despite its major health burden, the precise mechanisms underlying AD remain unknown. Understanding the genetic differences associated with AD is crucial for advancing diagnosis and targeted treatment development. This study aims to identify candidate genes of AD by using bioinformatics analysis. Methods: We conducted a comprehensive analysis of four pooled transcriptomic datasets (GSE16161, GSE32924, GSE130588, and GSE120721) obtained from the Gene Expression Omnibus (GEO) database. Differential gene expression analysis was performed using the R statistical language. The differentially expressed genes (DEGs) between AD patients and normal individuals were functionally analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Furthermore, a protein-protein interaction (PPI) network was constructed to identify candidate genes. Results: Among the patient-level gene expression datasets, we identified 114 shared DEGs, consisting of 53 upregulated genes and 61 downregulated genes. Functional analysis using GO and KEGG revealed that the DEGs were mainly associated with the negative regulation of transcription from RNA polymerase II promoter, membrane-related functions, protein binding, and the Human papillomavirus infection pathway. Through the PPI network analysis, we identified eight core genes: CD44, STAT1, HMMR, AURKA, MKI67, and SMARCA4. Conclusion: This study elucidates key genes associated with AD, providing potential targets for diagnosis and treatment. The identified genes have the potential to contribute to the understanding and management of AD. The bioinformatics analysis conducted in this study offers new insights and directions for further research on AD. Future studies can focus on validating the functional roles of these genes and exploring their therapeutic potential in AD. While these findings will require further verification as achieved with experiments involving in vivo and in vitro models, these results provided some initial insights into dysfunctional inflammatory and immune responses associated with AD. Such information offers the potential to develop novel therapeutic targets for use in preventing and treating AD.

Keywords: atopic dermatitis, bioinformatics, biomarkers, genes

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586 Comparative Exergy Analysis of Vapor Compression Refrigeration System Using Alternative Refrigerants

Authors: Gulshan Sachdeva, Vaibhav Jain

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In present paper, the performance of various alternative refrigerants is compared to find the substitute of R22, the widely used hydrochlorofluorocarbon refrigerant in developing countries. These include the environmentally friendly hydrofluorocarbon (HFC) refrigerants such as R134A, R410A, R407C and M20. In the present study, a steady state thermodynamic model (includes both first and second law analysis) which simulates the working of an actual vapor-compression system is developed. The model predicts the performance of system with alternative refrigerants. Considering the recent trends of replacement of ozone depleting refrigerants and improvement in system efficiency, R407C is found to be potential candidate to replace R22 refrigerant in the present study.

Keywords: refrigeration, compression system, performance study, modeling, R407C

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585 Cassava Plant Architecture: Insights from Genome-Wide Association Studies

Authors: Abiodun Olayinka, Daniel Dzidzienyo, Pangirayi Tongoona, Samuel Offei, Edwige Gaby Nkouaya Mbanjo, Chiedozie Egesi, Ismail Yusuf Rabbi

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Cassava (Manihot esculenta Crantz) is a major source of starch for various industrial applications. However, the traditional cultivation and harvesting methods of cassava are labour-intensive and inefficient, limiting the supply of fresh cassava roots for industrial starch production. To achieve improved productivity and quality of fresh cassava roots through mechanized cultivation, cassava cultivars with compact plant architecture and moderate plant height are needed. Plant architecture-related traits, such as plant height, harvest index, stem diameter, branching angle, and lodging tolerance, are critical for crop productivity and suitability for mechanized cultivation. However, the genetics of cassava plant architecture remain poorly understood. This study aimed to identify the genetic bases of the relationships between plant architecture traits and productivity-related traits, particularly starch content. A panel of 453 clones developed at the International Institute of Tropical Agriculture, Nigeria, was genotyped and phenotyped for 18 plant architecture and productivity-related traits at four locations in Nigeria. A genome-wide association study (GWAS) was conducted using the phenotypic data from a panel of 453 clones and 61,238 high-quality Diversity Arrays Technology sequencing (DArTseq) derived Single Nucleotide Polymorphism (SNP) markers that are evenly distributed across the cassava genome. Five significant associations between ten SNPs and three plant architecture component traits were identified through GWAS. We found five SNPs on chromosomes 6 and 16 that were significantly associated with shoot weight, harvest index, and total yield through genome-wide association mapping. We also discovered an essential candidate gene that is co-located with peak SNPs linked to these traits in M. esculenta. A review of the cassava reference genome v7.1 revealed that the SNP on chromosome 6 is in proximity to Manes.06G101600.1, a gene that regulates endodermal differentiation and root development in plants. The findings of this study provide insights into the genetic basis of plant architecture and yield in cassava. Cassava breeders could leverage this knowledge to optimize plant architecture and yield in cassava through marker-assisted selection and targeted manipulation of the candidate gene.

Keywords: Manihot esculenta Crantz, plant architecture, DArtseq, SNP markers, genome-wide association study

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584 Graphene/ZnO/Polymer Nanocomposite Thin Film for Separation of Oil-Water Mixture

Authors: Suboohi Shervani, Jingjing Ling, Jiabin Liu, Tahir Husain

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Offshore oil-spill has become the most emerging problem in the world. In the current paper, a graphene/ZnO/polymer nanocomposite thin film is coated on stainless steel mesh via layer by layer deposition method. The structural characterization of materials is determined by Scanning Electron Microscopy (SEM) and X-ray diffraction (XRD). The total petroleum hydrocarbons (TPHs) and separation efficiency have been measured via gas chromatography – flame ionization detector (GC-FID). TPHs are reduced to 2 ppm and separation efficiency of the nanocomposite coated mesh is reached ≥ 99% for the final sample. The nanocomposite coated mesh acts as a promising candidate for the separation of oil- water mixture.

Keywords: oil spill, graphene, oil-water separation, nanocomposite

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583 Measuring the Visibility of the European Open Access Journals with Bibliometric Indicators

Authors: Maja Jokić, Andrea Mervar, Stjepan Mateljan

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Peer review journals, as the main communication channel among researchers, fully achieve their objective if they are available to the global research community, which is accomplished through open access. In the EU countries, the idea of open access has spread over the years through various projects, initiatives, and strategic documents. Consequently, in this paper we want to analyze, using various bibliometric indicators, visibility, and significance of open access peer review journals compared to the conventional (non-open access) ones. We examine the sample of open access (OA) journals in 28 EU countries in addition to open access journals in three EU candidate countries (Bosnia and Herzegovina, FYR Macedonia and Serbia), all indexed by Scopus (N=1,522). These journals comprise 42% of the total number of OA journals indexed by Scopus. The distribution of OA journals in our sample according to the subject fields indicates that the largest share has OA journals in Health Sciences, 29% followed by Social Sciences and Physical Sciences with 25%, and 21% in Life Sciences. At the same time, the distribution according to countries (N=31) shows the dominance of EU15 countries with the share of 68.3% (N=1041) while post-socialist European countries (EU11 plus three candidate EU countries) have the share of 31.6% (N=481). Bibliometric indicators are derived from the SCImago Journal Ranking database. The analysis of OA journals according to their quartile scores (that reflect the relation between number of articles and their citations) shows that the largest number of OA journals from our sample was in the third quartile in 2015. For comparison, the majority of all academic journals indexed in Scopus from the countries in our sample were in the same year in the first quartile. The median of SJR indicator (SCImago Journal Rankings) for 2015 that measures the journal's prestige, amounted 0.297 for OA journals from the sample, while it was modestly lower for all OA journals, 0.284. The value of the same indicator for all journals indexed by Scopus (N=11,086) from our group of countries was 0.358, which is significantly different from the one for OA journals. Apart from the number of OA journals we also confirm significant differences between EU15 and post-socialist countries in bibliometric status of OA journals. The median SJR indicator for 2015 for EU15 countries was 0.394, while for post-socialist countries it amounted to 0.226. The changes in bibliometric indicators: quartile score, SJR (SCImago Journal Rankings), SNIP (Sources Normalised Impact by Paper) and IPP (Impact per Publication) of OA journals during 2012-2015 period, as well as H-index for the main four subject fields (Life Sciences, Physical Sciences, Social Sciences and Health Sciences) in the whole sample as well as in two main groups of European countries, show increasing trend of acceptance and visibility of OA journals within the academic community. More comprehensive insights into the visibility of OA journals could be reached by using additional qualitative research methods such as for example, interviews with researchers.

Keywords: bibliometric analysis, European countries, journal evaluation, open access journals

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582 MCD-017: Potential Candidate from the Class of Nitroimidazoles to Treat Tuberculosis

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

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

Keywords: mycobacterium tuberculosis, pharmacokinetics, physicochemical properties, hepatotoxicity

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581 Changing MBA Identities: Using Critical Reflection inside and out in Finding a New Narrative

Authors: Keith Schofield, Leigh Morland

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Storytelling is an established means of leadership and management development and is also considered a form of leadership of self and others in its own right. This study focuses on the utility of storytelling in the development of management narratives in an MBA programme; sources include programme participants as well as international recruiters, whose voices are often only heard in terms of economic contribution and globalisation. For many MBA candidates, the return to study requires the development of a new identity which complements their professional identity; each candidate has their own journey and expectations, the use of story can enable candidates to explore their aspirations and assumptions and give voice to previously unspoken ideas. For international recruitment, the story of market development and change must be captured if MBAs are to remain fit for purpose. If used effectively, story acts as a form of critical reflection that can inform the learning journeys of individuals, emerging identities as well as the ongoing design and development of programmes. The landscape of management education is shifting; the MBA begins to attract a different kind of candidate, some are younger than before, others are seeking validation for their existing work practices, yet more are entrepreneurial and wish to capitalise on an institutional experience to further their career. There is a shift in context, creating uncertainty and ambiguity for programme managers and recruiters, thus requiring institutions to create a new MBA narrative. This study utilises Lego SeriousPlay as the means to engaging programme participants and international agents in telling the story of their MBA. We asked MBA participants to tell the story of their leadership and management aspirations and compare these to stories of their development journeys, allowing for critical reflection of their respective development gaps. We asked international recruiters, who act as university agents and promote courses in the student’s country of origin, to explore their mental models of MBA candidates and their learning agenda. The purpose of this process was to explore the agent’s perception of the MBA programme and to articulate the student journey from a recruitment perspective. The paper’s unique contribution is in combining these stories in order to explore the assumptions that determine programme design. Data drawn from reflective statements together with images of Lego ‘builds’ created the opportunity for reflection between the mental models of these groups. Findings will inform the design of the MBA journey and experience; we review the extent to which the changing identities of learners are congruent with programme design. Data from international recruiters also determines the extent to which marketing and recruitment strategies identify with would be candidates.

Keywords: critical reflection, programme management, recruitment, storytelling

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580 Performance Analysis of Carbon Nanotube for VLSI Interconnects and Their Comparison with Copper Interconnects

Authors: Gagnesh Kumar, Prashant Gupta

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This paper investigates the performance of the bundle of single wall carbon nanotubes (SWCNT) for low-power and high-speed interconnects for future VLSI applications. The power dissipation, delay and power delay product (PDP) of SWCNT bundle interconnects are examined and compared with that of the Cu interconnects at 22 nm technology node for both intermediate and global interconnects. The results show that SWCNT bundle consume less power and also faster than Cu for intermediate and global interconnects. It is concluded that the metallic SWCNT has been regarded as a viable candidate for intermediate and global interconnects in future technologies.

Keywords: carbon nanotube, SWCNT, low power, delay, power delay product, global and intermediate interconnects

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579 Effects of the Natural Compound on SARS-CoV-2 Spike Protein-Mediated Metabolic Alteration in THP-1 Cells Explored by the ¹H-NMR-Based Metabolomics Approach

Authors: Gyaltsen Dakpa, K. J. Senthil Kumar, Nai-Wen Tsao, Sheng-Yang Wang

Abstract:

Context: Coronavirus disease 2019 (COVID-19) is a severe respiratory illness caused by the SARS-CoV-2 virus. One of the hallmarks of COVID-19 is a change in metabolism, which can lead to increased severity and mortality. The mechanism of SARS-CoV-2-mediated perturbations of metabolic pathways has yet to be fully understood. Research Aim: This study aimed to investigate the metabolic alteration caused by SARS-CoV-2 spike protein in Phorbol 12-myristate 13-acetate (PMA)-induced human monocytes (THP-1) and to examine the regulatory effect of natural compounds like Antcins A on SARS-CoV-2 spike protein-induced metabolic alteration. Methodology: The study used a combination of proton nuclear magnetic resonance (1H-NMR) and MetaboAnalyst 5.0 software. THP-1 cells were treated with SARS-CoV-2 spike protein or control, and the metabolomic profiles of the cells were compared. Antcin A was also added to the cells to assess its regulatory effect on SARS-CoV-2 spike protein-induced metabolic alteration. Findings: The study results showed that treatment with SARS-CoV-2 spike protein significantly altered the metabolomic profiles of THP-1 cells. Eight metabolites, including glycerol-phosphocholine, glycine, canadine, sarcosine, phosphoenolpyruvic acid, glutamine, glutamate, and N, N-dimethylglycine, were significantly different between control and spike-protein treatment groups. Antcin A significantly reversed the changes in these metabolites. In addition, treatment with antacid A significantly inhibited SARS-CoV-2 spike protein-mediated up-regulation of TLR-4 and ACE2 receptors. Theoretical Importance The findings of this study suggest that SARS-CoV-2 spike protein can cause significant metabolic alterations in THP-1 cells. Antcin A, a natural compound, has the potential to reverse these metabolic alterations and may be a potential candidate for developing preventive or therapeutic agents for COVID-19. Data Collection: The data for this study was collected from THP-1 cells that were treated with SARS-CoV-2 spike protein or a control. The metabolomic profiles of the cells were then compared using 1H-NMR and MetaboAnalyst 5.0 software. Analysis Procedures: The metabolomic profiles of the THP-1 cells were analyzed using 1H-NMR and MetaboAnalyst 5.0 software. The software was used to identify and quantify the cells' metabolites and compare the control and spike-protein treatment groups. Questions Addressed: The question addressed by this study was whether SARS-CoV-2 spike protein could cause metabolic alterations in THP-1 cells and whether Antcin A can reverse these alterations. Conclusion: The findings of this study suggest that SARS-CoV-2 spike protein can cause significant metabolic alterations in THP-1 cells. Antcin A, a natural compound, has the potential to reverse these metabolic alterations and may be a potential candidate for developing preventive or therapeutic agents for COVID-19.

Keywords: SARS-CoV-2-spike, ¹H-NMR, metabolomics, antcin-A, taiwanofungus camphoratus

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578 CSPG4 Molecular Target in Canine Melanoma, Osteosarcoma and Mammary Tumors for Novel Therapeutic Strategies

Authors: Paola Modesto, Floriana Fruscione, Isabella Martini, Simona Perga, Federica Riccardo, Mariateresa Camerino, Davide Giacobino, Cecilia Gola, Luca Licenziato, Elisabetta Razzuoli, Katia Varello, Lorella Maniscalco, Elena Bozzetta, Angelo Ferrari

Abstract:

Canine and human melanoma, osteosarcoma (OSA), and mammary carcinomas are aggressive tumors with common characteristics making dogs a good model for comparative oncology. Novel therapeutic strategies against these tumors could be useful to both species. In humans, chondroitin sulphate proteoglycan 4 (CSPG4) is a marker involved in tumor progression and could be a candidate target for immunotherapy. The anti-CSPG4 DNA electrovaccination has shown to be an effective approach for canine malignant melanoma (CMM) [1]. An immunohistochemistry evaluation of CSPG4 expression in tumour tissue is generally performed prior to electrovaccination. To assess the possibility to perform a rapid molecular evaluation and in order to validate these spontaneous canine tumors as the model for human studies, we investigate the CSPG4 gene expression by RT qPCR in CMM, OSA, and canine mammary tumors (CMT). The total RNA was extracted from RNAlater stored tissue samples (CMM n=16; OSA n=13; CMT n=6; five paired normal tissues for CMM, five paired normal tissues for OSA and one paired normal tissue for CMT), retro-transcribed and then analyzed by duplex RT-qPCR using two different TaqMan assays for the target gene CSPG4 and the internal reference gene (RG) Ribosomal Protein S19 (RPS19). RPS19 was selected from a panel of 9 candidate RGs, according to NormFinder analysis following the protocol already described [2]. Relative expression was analyzed by CFX Maestro™ Software. Student t-test and ANOVA were performed (significance set at P<0.05). Results showed that gene expression of CSPG4 in OSA tissues is significantly increased by 3-4 folds when compared to controls. In CMT, gene expression of the target was increased from 1.5 to 19.9 folds. In melanoma, although an increasing trend was observed, no significant differences between the two groups were highlighted. Immunohistochemistry analysis of the two cancer types showed that the expression of CSPG4 within CMM is concentrated in isles of cells compared to OSA, where the distribution of positive cells is homogeneous. This evidence could explain the differences in gene expression results.CSPG4 immunohistochemistry evaluation in mammary carcinoma is in progress. The evidence of CSPG4 expression in a different type of canine tumors opens the way to the possibility of extending the CSPG4 immunotherapy marker in CMM, OSA, and CMT and may have an impact to translate this strategy modality to human oncology.

Keywords: canine melanoma, canine mammary carcinomas, canine osteosarcoma, CSPG4, gene expression, immunotherapy

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577 Tunable in Phase, out of Phase and T/4 Square-Wave Pulses in Delay-Coupled Optoelectronic Oscillators

Authors: Jade Martínez-Llinàs, Pere Colet

Abstract:

By exploring the possible dynamical regimes in a prototypical model for mutually delay-coupled OEOs, here it is shown that two mutually coupled non-identical OEOs, besides in- and out-of-phase square-waves, can generate stable square-wave pulses synchronized at a quarter of the period (T/4) in a broad parameter region. The key point to obtain T/4 solutions is that the two OEO operate with mixed feedback, namely with negative feedback in one and positive in the other. Furthermore, the coexistence of multiple solutions provides a large degree of flexibility for tuning the frequency in the GHz range without changing any parameter. As a result the two coupled OEOs system is good candidate to be implemented for information encoding as a high-capacity memory device.

Keywords: nonlinear optics, optoelectronic oscillators, square waves, synchronization

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576 Reclaiming the House with Use of Web 2.0 Tools: Democratic Candidates and Social Media during Midterm Elections in 2018

Authors: Norbert Tomaszewski

Abstract:

Modern politicians tend to resign from the traditional media as Web 2.0 tools allow them to interact with a much bigger audience while spending less money on their campaign. Current studies on this subject prove that in order to win the elections, the candidate needs to show his personal side during the campaign to appeal to the voter as an average citizen. Because of that, the internet user may engage in the politician's campaign by spreading his message along with his followers. The aim of the study is to determine how did the Democratic candidates use the Web 2.0 tools during the 2018 midterm elections campaign and whether they managed to succeed. Taking into consideration the fact that the United States as a country, has always set important milestones for the political marketing as a field of science, the result of the research can set some examples on how to manage the modern internet campaign in less developed countries.

Keywords: political campaign, midterm elections, social media, Web 2.0

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575 Ethylene Sensitivity in Orchids and Its Control Using 1-MCP: A Review

Authors: Parviz Almasi

Abstract:

Ethylene is produced as a gaseous growth regulator in all plants and their constructive parts such as roots, stems, leaves, flowers and fruits. It is considered a multifunctional phytohormone that regulates both growths including flowering, fruit ripening, inhibition of root growth, and senescence such as senescence of leaves and flowers and etc. In addition, exposure to external ethylene is caused some changes that are often undesirable and harmful. Some flowers are more sensitive to others and when exposed to ethylene; their aging process is hastened. 1-MCP is an exogenous and endogenous ethylene action inhibitor, which binds to the ethylene receptors in the plants and prevents ethylene-dependent reactions. The binding affinity of 1- MCP for the receptors is about 10 times more than ethylene. Hence, 1-MCP can be a potential candidate for controlling of ethylene injury in horticultural crops. This review integrates knowledge of ethylene biosynthesis in the plants and also a mode of action of 1-MCP in preventing of ethylene injury.

Keywords: ethylene injury, biosynthesis, ethylene sensitivity, 1-MCP

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574 Molecular Docking Analysis of Flavonoids Reveal Potential of Eriodictyol for Breast Cancer Treatment

Authors: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery

Abstract:

Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.

Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking

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573 Concentric Circle Detection based on Edge Pre-Classification and Extended RANSAC

Authors: Zhongjie Yu, Hancheng Yu

Abstract:

In this paper, we propose an effective method to detect concentric circles with imperfect edges. First, the gradient of edge pixel is coded and a 2-D lookup table is built to speed up normal generation. Then we take an accumulator to estimate the rough center and collect plausible edges of concentric circles through gradient and distance. Later, we take the contour-based method, which takes the contour and edge intersection, to pre-classify the edges. Finally, we use the extended RANSAC method to find all the candidate circles. The center of concentric circles is determined by the two circles with the highest concentricity. Experimental results demonstrate that the proposed method has both good performance and accuracy for the detection of concentric circles.

Keywords: concentric circle detection, gradient, contour, edge pre-classification, RANSAC

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572 Polymer Nanocarrier for Rheumatoid Arthritis Therapy

Authors: Vijayakameswara Rao Neralla, Jueun Jeon, Jae Hyung Park

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To develop a potential nanocarrier for diagnosis and treatment of rheumatoid arthritis (RA), we prepared a hyaluronic acid (HA)-5β-cholanic acid (CA) conjugate with an acid-labile ketal linker. This conjugate could self-assemble in aqueous conditions to produce pH-responsive HA-CA nanoparticles as potential carriers of the anti-inflammatory drug methotrexate (MTX). MTX was rapidly released from nanoparticles under inflamed synovial tissue in RA. In vitro cytotoxicity data showed that pH-responsive HA-CA nanoparticles were non-toxic to RAW 264.7 cells. In vivo biodistribution results confirmed that, after their systemic administration, pH-responsive HA-CA nanoparticles selectively accumulated in the inflamed joints of collagen-induced arthritis mice. These results indicate that pH-responsive HA-CA nanoparticles represent a promising candidate as a drug carrier for RA therapy.

Keywords: rheumatoid arthritis, hyaluronic acid, nanocarrier, self-assembly, MTX

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571 Topology Optimization of Composite Structures with Material Nonlinearity

Authors: Mengxiao Li, Johnson Zhang

Abstract:

Currently, topology optimization technique is widely used to define the layout design of structures that are presented as truss-like topologies. However, due to the difficulty in combining optimization technique with more realistic material models where their nonlinear properties should be considered, the achieved optimized topologies are commonly unable to apply straight towards the practical design problems. This study presented an optimization procedure of composite structures where different elastic stiffness, yield criteria, and hardening models are assumed for the candidate materials. From the results, it can be concluded that a more explicit modeling has the significant influence on the resulting topologies. Also, the isotropic or kinematic hardening is important for elastoplastic structural optimization design. The capability of the proposed optimization procedure is shown through several cases.

Keywords: topology optimization, material composition, nonlinear modeling, hardening rules

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570 Powering Pacemakers from Heart Pressure Variation with Piezoelectric Energy Harvesters

Authors: A. Mathieu, B. Aubry, E. Chhim, M. Jobe, M. Arnaud

Abstract:

Present project consists in a study and a development of piezoelectric devices for supplying power to new generation pacemakers. They are miniaturized leadless implants without battery placed directly in right ventricle. Amongst different acceptable energy sources in cardiac environment, we choose the solution of a device based on conversion of the energy produced by pressure variation inside the heart into electrical energy. The proposed energy harvesters can meet the power requirements of pacemakers, and can be a good solution to solve the problem of regular surgical operation. With further development, proposed device should provide enough energy to allow pacemakers autonomy, and could be good candidate for next pacemaker generation.

Keywords: energy harvester, heart, leadless pacemaker, piezoelectric cells, pressure variation

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569 Microstructural and Transport Properties of La0.7Sr0.3CoO3 Thin Films Obtained by Metal-Organic Deposition

Authors: K. Daoudi, Z. Othmen, S. El Helali, M.Oueslati, M. Oumezzine

Abstract:

La0.7Sr0.3CoO3 thin films have been epitaxially grown on LaAlO3 and SrTiO3 (001) single-crystal substrates by metal organic deposition process. The structural and micro structural properties of the obtained films have been investigated by means of high resolution X-ray diffraction, Raman spectroscopy and transmission microscopy observations on cross-sections techniques. We noted a close dependence of the crystallinity on the used substrate and the film thickness. By increasing the annealing temperature to 1000ºC and the film thickness to 100 nm, the electrical resistivity was decreased by several orders of magnitude. The film resistivity reaches approximately 3~4 x10-4 Ω.cm in a wide interval of temperature 77-320 K, making this material a promising candidate for a variety of applications.

Keywords: cobaltite, thin films, epitaxial growth, MOD, TEM

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568 Nanabis™: A Non-Opioid Alternative for Management of Cancer Bone Pain

Authors: Sean Hall

Abstract:

Prior to COVID-19, the world was preoccupied with opioids, effectiveness versus risk, and specifically toxicity versus abuse. Historically underpinning opioid use was a concept of safety. As use over time and real-world data evolved, a pursuit for efficacy associated with non-opioid alternatives became mainstream. On January 8, 2021, the US signed back into the opioid problem, with these two fundamental questions still unresolved. The author will share the current progression of a lead non-opioid cancer bone pain candidate, NanaBis™. NanaBis™ represents two innovative factors: The active ingredients are from cannabinoids; these ingredients are in a proprietary sub-micron delivery platform, NanoCelle®. The author will offer an opinion piece, potentiating the future role of delivery platforms in medicine to increase both patient safety and compliance.

Keywords: NanaBis, nanoCelle, opioids, toxicity

Procedia PDF Downloads 58