Search results for: ErbB/HER-targeted therapeutic agents

Authors: Kyriaki Hatziagapiou, Konstantinos Bethanis, Olti Nikola, Elias Christoforides, Eleni Koniari, Eleni Kakouri, George Lambrou, Christina Kanaka-Gantenbein

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Glioblastoma multiforme (GBM) remains a serious health challenge, as current therapeutic modalities continue to yield unsatisfactory results, with the average survival rarely exceeding 1-2 years. Natural compounds still provide some of the most promising approaches for discovering new drugs. The non-psychotropic cannabidiol (CBD) deriving from Cannabis sativa L. provides such promise. CBD is endowed with anticancer, antioxidant, and genoprotective properties as established in vitro and in in vivo experiments. CBD’s selectivity towards cancer cells and its safe profile suggest its usage in cancer therapies. However, the bioavailability of oral CBD is low due to poor aqueous solubility, erratic gastrointestinal absorption, and significant first-pass metabolism, hampering its therapeutic potential and resulting in a variable pharmacokinetic profile. In this context, CBD can take great advantage of nanomedicine-based formulation strategies. Cyclodextrins (CDs) are cyclic oligosaccharides used in the pharmaceutical industry to incorporate apolar molecules inside their hydrophobic cavity, increasing their stability, water solubility, and bioavailability or decreasing their side effects. CBD-inclusion complexes with CDs could be a good strategy to improve its properties, like solubility and stability to harness its full therapeutic potential. The current research aims to study the potential cytotoxic effect of CBD and CBD-CDs complexes CBD-RMβCD (randomly methylated β-cyclodextrin) and CBD-HPβCD (hydroxypropyl-b-CD) on the A172 glioblastoma cell line. CBD is diluted in 10% DMSO, and CBD/CDs solutions are prepared by mixing solid CBD, solid CDs, and dH2O. For the biological assays, A172 cells are incubated at a range of concentrations of CBD, CBD-RMβCD and CBD-HPβCD, RMβCD, and HPβCD (0,03125-4 mg/ml) at 24, 48, and 72 hours. Analysis of cell viability after incubation with the compounds is performed with Alamar Blue viability assay. CBD’s dilution to DMSO 10% was inadequate, as crystals are observed; thus cytotoxicity experiments are not assessed. CBD’s solubility is enhanced in the presence of both CDs. CBD/CDs exert significant cytotoxicity in a dose and time-dependent manner (p < 0.005 for exposed cells to any concentration at 48, 72, and 96 hours versus cells not exposed); as their concentration and time of exposure increases, the reduction of resazurin to resofurin decreases, indicating a reduction in cell viability. The cytotoxic effect is more pronounced in cells exposed to CBD-HPβCD for all concentrations and time-points. RMβCD and HPβCD at the highest concentration of 4 mg/ml also exerted antitumor action per se since manifesting cell growth inhibition. The results of our study could afford the basis of research regarding the use of natural products and their inclusion complexes as anticancer agents and the shift to targeted therapy with higher efficacy and limited toxicity. Acknowledgments: The research is partly funded by ΙΚΥ (State Scholarships Foundation) – Post-doc Scholarships-Partnership Agreement 2014-2020.

Keywords: cannabidiol, cyclodextrins, glioblastoma, hydroxypropyl-b-Cyclodextrin, randomly-methylated-β-cyclodextrin

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Authors: Josiah Damisa, Michelle Louise Richardson, Morenike Adewuyi

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Lower back pain is a significant cause of disability worldwide and associated with great implications in terms of the well-being of affected individuals and society as a whole due to its undeniable socio-economic impact. With its prevalence on the increase as a result of an aging global population, the need for novel forms of pain management is ever paramount. This review aims to provide further insight into current research regarding a role for the endocannabinoid signaling pathway as a target in the treatment of chronic pain, with particular emphasis on its potential use as part of the treatment of lower back pain. Potential advantages and limitations of cannabis-based medicines over other forms of analgesia currently licensed for medical use are discussed in addition to areas that require ongoing consideration and research. To evaluate the efficacy of cannabis-based medicines in chronic pain, studies pertaining to the role of medical cannabis in chronic disease were reviewed. Standard searches of PubMed, Google Scholar and Web of Science databases were undertaken with peer-reviewed journal articles reviewed based on the indication for pain management, cannabis treatment modality used and study outcomes. Multiple studies suggest an emerging role for cannabis-based medicines as therapeutic agents in the treatment of chronic back pain. A potential synergistic effect has also been purported if these medicines are co-administered with opiate analgesia due to the similarity of the opiate and endocannabinoid signaling pathways. However, whilst recent changes to legislation in the United Kingdom mean that cannabis is now licensed for medicinal use on NHS prescription for a number of chronic health conditions, concerns remain as to the efficacy and safety of cannabis-based medicines. Research is lacking into both their side effect profiles and the long-term effects of cannabis use. Legal and ethical considerations to the use of these products in standardized medical practice also persist due to the notoriety of cannabis as a drug of abuse. Despite this, cannabis is beginning to gain traction as an alternative or even complementary drug to opiates, with some preclinical studies showing opiate-sparing effects. Whilst there is a paucity of clinical trials in this field, there is scope for cannabinoids to be successful anti-nociceptive agents in managing chronic back pain. The ultimate aim would be to utilize cannabis-based medicines as alternative or complementary therapies, thereby reducing opiate over-reliance and providing hope to individuals who have exhausted all other forms of standard treatment.

Keywords: endocannabinoids, cannabis-based medicines, chronic pain, lower back pain

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Authors: Safia Rabaaoui, Héla Hachicha, Ezzeddine Zagrouba

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Nowadays, cloud computing is becoming the more popular technology to various companies and consumers, which benefit from its increased efficiency, cost optimization, data security, unlimited storage capacity, etc. One of the biggest challenges of cloud computing is resource allocation. Its efficiency directly influences the performance of the whole cloud environment. Finding an effective method to address these critical issues and increase cloud performance was necessary. This paper proposes a mobile agents-based framework for dynamic resource allocation in cloud computing to minimize both the cost of using virtual machines and the makespan. Furthermore, its impact on the best response time and power consumption has been studied. The simulation showed that our method gave better results than here.

Keywords: cloud computing, multi-agent system, mobile agent, dynamic resource allocation, cost, makespan

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Authors: Joshua Garba Dodo

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Corruption has become endemic in Nigeria, affecting almost all facets of the society, thereby thwarting the effort of national development. The thrust of this paper, therefore, is to see how corruption can be brought to its barest minimum if not totally eradicated using social studies and other agents of socialization. In doing that, the paper defines the concepts of corruption, social studies, and socialization. Discourse on the causes of corruption and the effect on national development is made. The paper examines the role of social studies, family, and the mass media in tackling corruption. The paper also asserts that if an aggressive campaign is mounted by the mass media as a way of supporting the present government in her effort to solve the corruption problem in the country, it will help in changing the psyche of the citizenry about corruption. Finally, the paper recommends, among others, that families and communities should sanction their sons and daughters involved in corrupt practices if proven by a competent court of law.

Keywords: corruption, social studies, family, mass media, socialization

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Authors: Mark Berry

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A number of studies have identified several factors involved in the malignant progression of cancer cells. The Primary modulator in driving inflammation to these transformed cells has been identified as the transcription factor known as nuclear factor-κB. This essential regulator of inflammation and the development of cancer, combined with a microenvironment of inflammation and signaling molecules, plays a major role in the malignant progression of cancer, and this progression is the result of the mutagenic predisposition of persistent substances that combat infection at tumor sites and other areas of chronic inflammation. Inflammation-induced tumors, and their inflammatory cells and regulators may be the primary source of metastasis of tumor cells through angiogenesis. Previous research on cytokines and chemokines, including their downstream targets, has been the focus of the cancer/inflammation connection. The identification of the biological mechanisms of other proteins vital to the inflammation cascade and their interactions are crucial to novel and effective therapeutic protocols for the treatment of inflammation-induced cancers. The Ancelim HSRP Protocol is just such a therapeutic intervention.

Keywords: ancelim, cancer, inflammation, tumor

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Authors: David Gottlieb, Jason Yoder

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The feeling of loneliness is not uncommon in modern society, and yet, there is a fundamental lack of understanding in its origins and purpose in nature. One interpretation of loneliness is that it is a subjective experience that punishes a lack of social behavior, and thus its emergence in human evolution is seemingly tied to the survival of early human tribes. Still, a common counterintuitive response to loneliness is a state of hypervigilance, resulting in social withdrawal, which may appear maladaptive to modern society. So far, no computational model of loneliness’ effect during evolution yet exists; however, agent-based models (ABM) can be used to investigate social behavior, and applying evolution to agents’ behaviors can demonstrate selective advantages for particular behaviors. We propose an ABM where each agent contains four social behaviors, and one goal-seeking behavior, letting evolution select the best behavioral patterns for resource allocation. In our paper, we use an algorithm similar to the boid model to guide the behavior of agents, but expand the set of rules that govern their behavior. While we use cohesion, separation, and alignment for simple social movement, our expanded model adds goal-oriented behavior, which is inspired by particle swarm optimization, such that agents move relative to their personal best position. Since agents are given the ability to form connections by interacting with each other, our final behavior guides agent movement toward its social connections. Finally, we introduce a mechanism to represent a state of loneliness, which engages when an agent's perceived social involvement does not meet its expected social involvement. This enables us to investigate a minimal model of loneliness, and using evolution we attempt to elucidate its value in human survival. Agents are placed in an environment in which they must acquire resources, as their fitness is based on the total resource collected. With these rules in place, we are able to run evolution under various conditions, including resource-rich environments, and when disease is present. Our simulations indicate that there is strong selection pressure for social behavior under circumstances where there is a clear discrepancy between initial resource locations, and against social behavior when disease is present, mirroring hypervigilance. This not only provides an explanation for the emergence of loneliness, but also reflects the diversity of response to loneliness in the real world. In addition, there is evidence of a richness of social behavior when loneliness was present. By introducing just two resource locations, we observed a divergence in social motivation after agents became lonely, where one agent learned to move to the other, who was in a better resource position. The results and ongoing work from this project show that it is possible to glean insight into the evolutionary advantages of even simple mechanisms of loneliness. The model we developed has produced unexpected results and has led to more questions, such as the impact loneliness would have at a larger scale, or the effect of creating a set of rules governing interaction beyond adjacency.

Keywords: agent-based, behavior, evolution, loneliness, social

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Authors: E. O. Fakoya, B. G. Abiona, J. O. Soetan

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The study determined Perception of Agricultural Extension Agents of Private Sector Participation in Extension Services in Ogun State, Nigeria. Data were collected from 80 respondents with a well-structured questionnaire. The result of the findings showed that there is need for private sector participation in extension services (=4.313), private extension services has facilities than public extension services (=4.97). Private sector participated in extension services by: giving of loans and credits to farmers (=4.50). Major constraints identified by the respondents were: Transportation problem (=2.88) and lack of fund (=2.77) A significant relationship (P<0.05) exists between factors affecting public extension services(r = 0.641, p = 0.00) and private sector participation in extension services. It was concluded from the study that there is need for private sector to participate in extension service in order to improve productivity of the farmers.

Keywords: agricultural extension, extension agent, private sector, perception

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Authors: Abigail Tan, Heng Liang Tan, Vanessa Ding, James Hui, Eng Hin Lee, Andre Choo

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Introduction: Comparative oncology investigates the similarities in spontaneous carcinogenesis between humans and animals, in order to identify treatments that can benefit these patients. Companion animals (CA), like canines and felines, are of special interest when it comes to studying human cancers due to their exposure to the same environmental factors and develop tumours with similar features. The purpose of this study is to explore the cross-reactivity of monoclonal antibodies (mAbs) across cancers in humans and CA. Material and Methods: A panel of CA mAbs generated in the lab was screened on multiple human cancer cell lines through flow cytometry to identify for positive binders. Shortlisted candidates were then characterised by biochemical and functional assays e.g., antibody-drug conjugate (ADC) and western blot assays, including glycan studies. Results: Candidate mAb KP52 was generated from whole-cell immunisation using feline mammary carcinoma. KP52 showed strong positive binding to human cancer cells, such as breast cancer and ovarian cancer. Furthermore, KP52 demonstrated strong killing ( > 50%) as an ADC with Saporin as the payload. Western blot results revealed the molecular weight of the antigen targets to be approximately 45kD and 50kD under reduced conditions. Glycan studies suggest that the epitope is glycan in nature, specifically an O-linked glycan. Conclusion: Candidate mAb KP52 has a therapeutic potential as an ADC against feline mammary cancer, human ovarian cancer, human mammary cancer, human pancreatic cancer, and human gastric cancer.

Keywords: ADC, comparative oncology, mAb, therapeutic

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Authors: Talal Alsulaiman, Khaldoun Khashanah

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In this paper, we provided a literature survey on the artificial stock problem (ASM). The paper began by exploring the complexity of the stock market and the needs for ASM. ASM aims to investigate the link between individual behaviors (micro level) and financial market dynamics (macro level). The variety of patterns at the macro level is a function of the AFM complexity. The financial market system is a complex system where the relationship between the micro and macro level cannot be captured analytically. Computational approaches, such as simulation, are expected to comprehend this connection. Agent-based simulation is a simulation technique commonly used to build AFMs. The paper proceeds by discussing the components of the ASM. We consider the roles of behavioral finance (BF) alongside the traditionally risk-averse assumption in the construction of agent's attributes. Also, the influence of social networks in the developing of agents’ interactions is addressed. Network topologies such as a small world, distance-based, and scale-free networks may be utilized to outline economic collaborations. In addition, the primary methods for developing agents learning and adaptive abilities have been summarized. These incorporated approach such as Genetic Algorithm, Genetic Programming, Artificial neural network and Reinforcement Learning. In addition, the most common statistical properties (the stylized facts) of stock that are used for calibration and validation of ASM are discussed. Besides, we have reviewed the major related previous studies and categorize the utilized approaches as a part of these studies. Finally, research directions and potential research questions are argued. The research directions of ASM may focus on the macro level by analyzing the market dynamic or on the micro level by investigating the wealth distributions of the agents.

Keywords: artificial stock markets, market dynamics, bounded rationality, agent based simulation, learning, interaction, social networks

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Authors: Joshua Chew, Vesa Cheng, David Thomson

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Background: Hereditary angioedema (HAE) or C1 esterase deficiency is a relatively rare entity that has a potential for significant anesthetic complications. Methods: A literature review was performed of published cases of surgery in patients with HAE. Results were limited to English language only and cases were examined for management strategies and successful prevention of acute attacks. Results: The literature revealed the successful use of C1 esterase inhibitors as the most common agent in surgical prophylaxis therapy. Other therapeutic targets described included kallikrein inhibitors and bradykinin B2 receptor antagonists. Conclusions: Therapeutic targets that exist for the management of acute attacks in HAE have been successfully employed in the setting of surgery. The data is currently limited and could not be used as a firm evidence base, but the limited outcomes seen are positive and reassuring for the prospective anesthetic management of this potentially fatal condition.

Keywords: anesthesia, C1 esterase deficiency, hereditary angioedema, surgical prophylaxis

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Authors: Yamani Amal, Lazaae Jamila, Elachouri Mostafa

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Plants and their active agents – especially polyphenols – may have a principal role in the treatment of diseases that result from the defect of physiological antioxidant mechanisms. Bryonia dioica is well known in Moroccan traditional medicine for alleviatin pain and traiting many diseases. We have focused on plant belonging to Cucurbitaceae Family from around the world to understand their therapeutic uses and their potential antioxidant activities Although several biological activities and Chemical composition of Bryonia dioica are well characterized, no direct, in vitro study, of this natural product examined the antioxydant effect of the extract from the roots of Bryonia dioica. The aim of this study was to determine in vitro antioxidant activity of the B.dioica root, using antioxidant analysis methods based on determination of Hydroxyradical Scavenging, 1,1-diphenyl-2-picrylhydrazine (DPPH) radical scavenging, Hydrogenperoxide Scavenging and Nitric Oxide Scavenging. In this study, it was demonstrated, that, B. dioica root extract showed excellent antioxidant properties. This investigation showed that the roots of this plant contain potent natural scavengers R. It may represent an interesting source of antioxidant phenolics that may favour the extension of their cultivation as new source of natural antioxidants in addition to containing high quality proteins for human or animal nutrition. Therefore, there is need for all stakeholders on the Morocco to strive towards taking advantage of our enormous biodiversity resources to free our people from diseases, abject poverty and stagnation.

Keywords: Morocco, bryoniadioica, in vitro, antioxydant

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Authors: Deepti Kohli, Meeta Keswani Mehra

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The paper develops a theoretical model of electoral competition with purely opportunistic candidates and a uni-dimensional policy using the probability voting approach while focusing on the aspect of lobby formation to analyze the inherent complex interactions between centripetal and centrifugal forces and their effects on equilibrium policy platforms. There exist three types of agents, namely, Left-wing, Moderate and Right-wing who comprise of the total voting population. Also, it is assumed that the Left and Right agents are free to initiate a lobby of their choice. If initiated, these lobbies generate donations which in turn can be contributed to one (or both) electoral candidates in order to influence them to implement the lobby’s preferred policy. Four different lobby formation scenarios have been considered: no lobby formation, only Left, only Right and both Left and Right. The equilibrium policy platforms, amount of individual donations by agents to their respective lobbies and the contributions offered to the electoral candidates have been solved for under each of the above four cases. Since it is assumed that the agents cannot coordinate each other’s actions during the lobby formation stage, there exists a probability with which a lobby would be formed, which is also solved for in the model. The results indicate that the policy platforms of the two electoral candidates converge completely under the cases of no lobby and both (extreme) formations but diverge under the cases of only one (Left or Right) lobby formation. This is because in the case of no lobby being formed, only the centripetal forces (emerging from the election-winning aspect) are present while in the case of both extreme (Left-wing and Right-wing) lobbies being formed, centrifugal forces (emerging from the lobby formation aspect) also arise but cancel each other out, again resulting in a pure policy convergence phenomenon. In contrast, in case of only one lobby being formed, both centripetal and centrifugal forces interact strategically, leading the two electoral candidates to choose completely different policy platforms in equilibrium. Additionally, it is found that in equilibrium, while the donation by a specific agent type increases with the formation of both lobbies in comparison to when only one lobby is formed, the probability of implementation of the policy being advocated by that lobby group falls.

Keywords: electoral competition, equilibrium policy platforms, lobby formation, opportunistic candidates

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Authors: Ayman M. Mansour

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In this paper, we propose a multi-agent intelligent system that is used for monitoring the health conditions of elderly people. Monitoring the health condition of elderly people is a complex problem that involves different medical units and requires continuous monitoring. Such expert system is highly needed in rural areas because of inadequate number of available specialized physicians or nurses. Such monitoring must have autonomous interactions between these medical units in order to be effective. A multi-agent system is formed by a community of agents that exchange information and proactively help one another to achieve the goal of elderly monitoring. The agents in the developed system are equipped with intelligent decision maker that arms them with the rule-based reasoning capability that can assist the physicians in making decisions regarding the medical condition of elderly people.

Keywords: fuzzy logic, inference system, monitoring system, multi-agent system

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Authors: Agnieszka Stempniewicz, Piotr Ceranowicz, Wojciech Macyk, Jakub Cieszkowski, Beata Kuśnierz-Cabała, Katarzyna Gałązka, Zygmunt Warzecha

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Objectives: There are numerous strategies for the prevention or treatment of oral mucositis. However, their effectiveness is limited and does not correspond to expectations. Recent studies have shown that obestatin exhibits a protective effect and accelerates the healing of gastrointestinal mucosa. The aim of the present study was to examine the influence of obestatin administration on oral ulcers in rats. Methods: lingual ulcers were induced by the use of acetic acid. Rats were treated twice a day intraperitoneally with saline or obestatin(4, 8, or 16 nmol/kg/dose) for five days. The study determined: lingual mucosa morphology, cell proliferation, mucosal blood flow, and mucosal pro-inflammatory interleukin-1β level(IL-1β). Results: In animals without induction of oral ulcers, treatment with obestatin was without any effect. Obestatin administration in rats with lingual ulcers increased the healing rate of these ulcers. Obestatin given at the dose of 8 or 16 nmol/kg/dose caused the strongest and similar therapeutic effect. This result was associated with a significant increase in blood flow and cell proliferation in gingival mucosa, as well as a significant decrease in IL-1β level. Conclusions: Obestatin accelerates the healing of lingual ulcers in rats. This therapeutic effect is well-correlated with an increase in blood flow and cell proliferation in oral mucosa, as well as a decrease in pro-inflammatory IL-1β levels. Obestatin is a potentially useful candidate for the prevention and treatment of oral mucositis. Acknowledgment: Agnieszka Stempniewicz acknowledges the support of InterDokMed project no. POWR.03.02.00- 00-I013/16.

Keywords: oral mucositis, ulcers, obestatin, lingual mucosa

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Authors: Lacramioara Ochiuz, Aurelia Vasile, Iulian Stoleriu, Cristina Ghiciuc, Maria Ignat

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Topical administration of chemotherapeutic agents (eg. carmustine, bexarotene, mechlorethamine etc.) in local treatment of cutaneous T-cell lymphoma (CTCL) is accompanied by multiple side effects, such as contact hypersensitivity, pruritus, skin atrophy or even secondary malignancies. A known method of reducing the side effects of anticancer agent is the development of modified drug release systems using drug incapsulation in biocompatible nanoporous inorganic matrices, such as mesoporous MCM-41 silica. Mesoporous MCM-41 silica is characterized by large specific surface, high pore volume, uniform porosity, and stable dispersion in aqueous medium, excellent biocompatibility, in vivo biodegradability and capacity to be functionalized with different organic groups. Therefore, MCM-41 is an attractive candidate for a wide range of biomedical applications, such as controlled drug release, bone regeneration, protein immobilization, enzymes, etc. The main advantage of this material lies in its ability to host a large amount of the active substance in uniform pore system with adjustable size in a mesoscopic range. Silanol groups allow surface controlled functionalization leading to control of drug loading and release. This study shows (I) the amino-grafting optimization of mesoporous MCM-41 silica matrix by means of co-condensation during synthesis and post-synthesis using APTES (3-aminopropyltriethoxysilane); (ii) loading the therapeutic agent (carmustine) obtaining a modified drug release systems; (iii) determining the profile of in vitro carmustine release from these systems; (iv) assessment of carmustine release kinetics by fitting on four mathematical models. Obtained powders have been described in terms of structure, texture, morphology thermogravimetric analysis. The concentration of the therapeutic agent in the dissolution medium has been determined by HPLC method. In vitro dissolution tests have been done using cell Enhancer in a 12 hours interval. Analysis of carmustine release kinetics from mesoporous systems was made by fitting to zero-order model, first-order model Higuchi model and Korsmeyer-Peppas model, respectively. Results showed that both types of highly ordered mesoporous silica (amino grafted by co-condensation process or post-synthesis) are thermally stable in aqueous medium. In what regards the degree of loading and efficiency of loading with the therapeutic agent, there has been noticed an increase of around 10% in case of co-condensation method application. This result shows that direct co-condensation leads to even distribution of amino groups on the pore walls while in case of post-synthesis grafting many amino groups are concentrated near the pore opening and/or on external surface. In vitro dissolution tests showed an extended carmustine release (more than 86% m/m) both from systems based on silica functionalized directly by co-condensation and after synthesis. Assessment of carmustine release kinetics revealed a release through diffusion from all studied systems as a result of fitting to Higuchi model. The results of this study proved that amino-functionalized mesoporous silica may be used as a matrix for optimizing the anti-cancer topical therapy by loading carmustine and developing prolonged-release systems.

Keywords: carmustine, silica, controlled, release

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Authors: João Rato, Nuno Costa

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The human verbal communication is a two-way process which requires a mutual understanding that will result in some considerations. This kind of communication, also called dialogue, besides the supposed human agents it can also be performed between human agents and machines. The interaction between Men and Machines, by means of a natural language, has an important role concerning the improvement of the communication between each other. Aiming at knowing the performance of some speech recognition systems, this document shows the results of the accomplished tests according to the Word Error Rate evaluation method. Besides that, it is also given a set of information linked to the systems of Man-Machine communication. After this work has been made, conclusions were drawn regarding the Speech Recognition Systems, among which it can be mentioned their poor performance concerning the voice interpretation in noisy environments.

Keywords: automatic speech recognition, man-machine conversation, speech recognition, spoken dialogue systems, word error rate

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Authors: Mohamad F. Jamiluddin, Emeline Sarry, Ana Bejanariu, Cécile Bauche

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Introduction: Over 360 million people are chronically infected with hepatitis B virus (HBV), of whom 1 million die each year from HBV-associated liver cirrhosis or hepatocellular carcinoma. Current treatment options for chronic hepatitis B depend on interferon-α (IFNα) or nucleos(t)ide analogs, which control virus replication but rarely eliminate the virus. Treatment with PEG-IFNα leads to a sustained antiviral response in only one third of patients. After withdrawal of the drugs, the rebound of viremia is observed in the majority of patients. Furthermore, the long-term treatment is subsequently associated with the appearance of drug resistant HBV strains that is often the cause of the therapy failure. Among the new therapeutic avenues being developed, therapeutic vaccine aimed at inducing immune responses similar to those found in resolvers is of growing interest. The high prevalence of chronic hepatitis B necessitates the design of better vaccination strategies capable of eliciting broad-spectrum of cell-mediated immunity(CMI) and humoral immune response that can control chronic hepatitis B. Induction of HBV-specific T cells and B cells by therapeutic vaccination may be an innovative strategy to overcome virus persistence. Lentiviral vectors developed and optimized by THERAVECTYS, due to their ability to transduce non-dividing cells, including dendritic cells, and induce CMI response, have demonstrated their effectiveness as vaccination tools. Method: To develop a HBV therapeutic vaccine that can induce a broad but specific immune response, we generated recombinant lentiviral vector carrying IRES(Internal Ribosome Entry Site)-containing bicistronic constructs which allow the coexpression of two vaccine products, namely HBV T- cell epitope vaccine and HBV virus like particle (VLP) vaccine. HBV T-cell epitope vaccine consists of immunodominant cluster of CD4 and CD8 epitopes with spacer in between them and epitopes are derived from HBV surface protein, HBV core, HBV X and polymerase. While HBV VLP vaccine is a HBV core protein based chimeric VLP with surface protein B-cell epitopes displayed. In order to evaluate the immunogenicity, mice were immunized with lentiviral constructs by intramuscular injection. The T cell and antibody immune responses of the two vaccine products were analyzed using IFN-γ ELISpot assay and ELISA respectively to quantify the adaptive response to HBV antigens. Results: Following a single administration in mice, lentiviral construct elicited robust antigen-specific IFN-γ responses to the encoded antigens. The HBV T- cell epitope vaccine demonstrated significantly higher T cell immunogenicity than HBV VLP vaccine. Importantly, we demonstrated by ELISA that antibodies are induced against both HBV surface protein and HBV core protein when mice injected with vaccine construct (p < 0.05). Conclusion: Our results highlight that THERAVECTYS lentiviral vectors may represent a powerful platform for immunization strategy against chronic hepatitis B. Our data suggests the likely importance of Lentiviral vector based novel bicistronic construct for further study, in combination with drugs or as standalone antigens, as a therapeutic lentiviral based HBV vaccines. THERAVECTYS bicistronic HBV vaccine will be further evaluated in animal efficacy studies.

Keywords: chronic hepatitis B, lentiviral vectors, therapeutic vaccine, virus-like particle

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Authors: Yulin Rao, Zhixuan Li, Burra Venkata Durga Kumar

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Intrusion detection refers to monitoring the actions of internal and external intruders on the system and detecting the behaviours that violate security policies in real-time. In intrusion detection, there has been much discussion about the application of neural network technology and artificial immune system (AIS). However, many solutions use static methods (signature-based and stateful protocol analysis) or centralized intrusion detection systems (CIDS), which are unsuitable for real-time intrusion detection systems that need to process large amounts of data and detect unknown intrusions. This article proposes a framework for a distributed intrusion detection system (DIDS) with multi-agents based on the concept of AIS and neural network technology to detect anomalies and intrusions. In this framework, multiple agents are assigned to each host and work together, improving the system's detection efficiency and robustness. The trainer agent in the central server of the framework uses the artificial neural network (ANN) rather than the negative selection algorithm of AIS to generate mature detectors. Mature detectors can distinguish between self-files and non-self-files after learning. Our analyzer agents use genetic algorithms to generate memory cell detectors. This kind of detector will effectively reduce false positive and false negative errors and act quickly on known intrusions.

Keywords: artificial immune system, distributed artificial intelligence, multi-agent, intrusion detection system, neural network

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Authors: Gulshad Azatova, Aleksandr Kapitonov, Natig Aminov

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Multiagent systems have gained significant attention in various fields, such as robotics, autonomous vehicles, and distributed computing, where multiple agents cooperate and communicate to achieve complex tasks. Efficient communication among agents is a crucial aspect of these systems, as it directly impacts their overall performance and scalability. This scholarly work provides an exploration of essential communication elements and conducts a comparative assessment of diverse protocols utilized in multiagent systems. The emphasis lies in scrutinizing the strengths, weaknesses, and applicability of these protocols across various scenarios. The research also sheds light on emerging trends within communication protocols for multiagent systems, including the incorporation of machine learning methods and the adoption of blockchain-based solutions to ensure secure communication. These trends provide valuable insights into the evolving landscape of multiagent systems and their communication protocols.

Keywords: communication, multi-agent systems, protocols, consensus

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Authors: Gheorghe Giurgiu, Manole Cojocaru, Mihnea Andrei Nicodin

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Background: Inflammation has the main role in the progression of endometriosis. The mechanisms by which endometriosis induces a chronic pain state remain poorly understood. Unfortunately, there is no known cure for endometriosis. But you can manage it with medication and at-home treatments. Some findings have highlighted the main role of inflammation in endometriosis by acting on proliferation, apoptosis, and angiogenesis. The introduction of new agents can be effective in improving the condition of patients; for example, plants are promising sources of bioactive natural components. Objectives: These natural compounds could be interesting strategies in therapy. While there is no absolute cure for this condition, some home remedies can relieve the pain and discomfort it brings. The purpose of this study is to summarize the potential action of Deniplant nutraceuticals in endometriosis by acting on inflammation. Materials and Methods: The primary symptoms of endometriosis are pelvic pain and infertility. The use of Deniplant nutraceuticals could be interesting in disease management for women. Results: Treating pain-related aspects of endometriosis would contribute to the improvement of mental health and daytime function. Because the microbiome can influence inflammation, new therapies can develop through its natural modulation. There are other options, including natural remedies, herbs like cinnamon twigs or licorice root, or supplements such as thiamine, magnesium, or omega-3 fatty acids. Conclusion: Deniplant nutraceuticals can downregulate inflammation in endometriosis. Nevertheless, the limited number of studies focusing on the different interactions of Deniplant nutraceuticals in endometriosis restricts its clear and immediate use in a therapeutic strategy.

Keywords: endometriosis, diet, Deniplant nutraceuticals, pain

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Authors: M. Mlhem

Abstract:

Geotechnical engineers face many problematic soils upon construction and they have the choice for replacing these soils with more appropriate soils or attempting to improve the engineering properties of the soil through a suitable soil stabilization technique. Mostly, improving soils is environmental, easier and more economical than other solutions. Stabilization soils technique is applied by introducing a cementing agent or by injecting a substance to fill the pore volume. Chemical stabilizers are divided into two groups: traditional agents such as cement or lime and non-traditional agents such as polymers. This paper studies the effect of epoxy additives on the compression strength of four types of soil and then compares with the effect of cement on the compression strength for the same soils. Overall, the epoxy additives are more effective in increasing the strength for different types of soils regardless its classification. On the other hand, there was no clear relation between studied parameters liquid limit, passing No.200, unit weight and between the strength of samples for different types of soils.

Keywords: additives, clay, compression strength, epoxy, stabilization

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Authors: Preecha Phongpeng

Abstract:

The objectives of this research are to assess the prevalence of travel businesses websites in Thailand, investigate and evaluate the quality of travel business websites in Thailand. The sample size includes 323 websites from the population of 1,458 websites. The study covers 4 types of travel business websites including: 78 general travel agents, 30 online reservation travel agents, 205 hotels, 7 airlines, and 3 car-rental companies with nation-wide operation. The findings indicated that e-tourism in Thailand is at its growth stage, with only 13% of travel businesses having websites, 28% of them providing e-mail and the quality of travel business websites in Thailand was at the average level. Seven common problems were found in websites: lack of travel essential information, insufficient transportation information, lack of navigation tools, lack of link pages to other organizations, lack of safety features, unclear online booking functions, and lack of special features also as well.

Keywords: traveling business, website evaluation, e-commerce, e-tourism

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Authors: Leili Iranirad, Mohammad Saleh Sadeghi, Seyed Fakhreddin Hejazi, Negar Vakili Razlighi

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Objective: Contrast-induced nephropathy (CIN) or contrast-induced acute kidney injury (CI-AKI) is an unknown acute kidney injury (AKI) occurring after exposure to contrast media (CM). Contrast agents are most often used for diagnostic procedures or therapeutic angiographic interventions. Recently, Na/K citrate as a urine alkalinization has been evaluated for the prevention of CIN. We conducted this experiment to evaluate the efficiency of Na/K citrate on CIN in high-risk patients treated with cardiac catheterization. Methods: A prospective randomized clinical trial was conducted on 400 patients having moderate to high-risk factors for CIN treated with elective percutaneous coronary intervention (PCI) and were assigned randomly to the control group or the Na/K citrate group. The Na/K citrate group (n=200) received 5 g Na/K citrate solution, which was diluted in 200 mL water two h before and four hours after the first administration and intravenous hydration for two h prior to and six h after the procedure, while the control group (n=200) only received intravenous hydration. Serum creatinine (SCr) was calculated prior to the contrast exposure and after 48 h. CIN was described as a 25% increase in creatinine of serum (SCr) or >0.5 mg/dl 48 h after contrast administration. Results: CIN was observed in 33 patients (16.5%) in the control group and in 6 patients (3%) in the Na/K citrate group. A significant variation was recorded in the CIN incidence between the two groups 48 h after the radiocontrast agent administration (p < 0.001). Conclusion: Our results show that Na/K citrate is useful and substantially reduces the incidence of CIN.

Keywords: contrast media, citrate, PCI

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Authors: Blessing Atim Aderibigbe

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A series of amine/ester-linked hybrid compounds containing pharmacophores, such as ursolic acid, oleanolic acid, ferrocene and bisphosphonates, were synthesized in an attempt to develop potent antibacterial and anticancer agents. Their structures were analyzed and confirmed using Nuclear Magnetic Resonance, Fourier Transform Infrared Spectroscopy, and mass spectroscopy. All the synthesized hybrid compounds were evaluated for their antibacterial activities against eleven selected bacterial strains using a serial dilution method. Some of the compounds displayed significant antibacterial activity against most of the bacterial and fungal strains. In addition, the in vitro cytotoxicity of these compounds was also performed against selected cancer cell lines. Some of the compounds were also found to be more active than their parent compounds, revealing the efficacy of designing hybrid molecules using plant-based bioactive agents.

Keywords: ursolic acid, hybrid drugs, oleanolic acid, bisphosphonates

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Authors: Hye Kyung Kim, Myung-Gyou Kim, Kang-Hyun Leem

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The deer velvet antler is well known for its traditional medicinal value and is widely used in the clinic. It has been considered to possess bone-strengthening activity. The goal of this study was to investigate the anti-osteoporotic effect of deer antler velvet on ovariectomized rats (OVX), and their possible mechanism of the action. In the first step, the in vitro effects of DAE on bone loss were determined. The proliferation, collagen content and alkaline phosphatase (ALP) activity of human osteoblastic MG-63 cells and osteoclastogenesis from bone marrow-derived precursor cells were measured. The in vivo experiment confirmed the positive effect of DAE on bone tissue. 3-month old female Sparague-Dawley rats were either sham operated or OVX, and administered DAE (20 and 100 mg/kg) for 4 weeks. DAE increased MG-63 cell proliferation and ALP activity in a dose-dependent manner. Collagen content was also increased by DAE treatment. However, the effect of DAE on bone resorption was not observed. OVX rats supplemented with DAE showed osteoprotective effects as the bone ALP level was increased and c-terminal telopeptide level was decreased by 100 mg/kg DAE treatment compared with OVX controls. Moreover, the tartrate-resistant acid phosphatase-5b level was also decreased by DAE treatment. The present study suggests that DAE is effective in preventing bone loss in OVX rats, and may be potential therapeutic agents for the treatment of postmenopausal osteoporosis.

Keywords: bone ALP, c-terminal telopeptide, deer antler, osteoporosis, ovariectomy, tartrate-resistant acid phosphatase-5b

Procedia PDF Downloads 247

Authors: Arslan Masood Pirzada, Muhammad Naeem, Hafiz Haider Ali, Muhammad Latif, Aown Sammar Raza, Asad Hussain Bukhari, Muhammad Saqib, Muhammad Ijaz

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Cyperus rotundus (Cyperaceae), a medicinal herb, is being traditionally used as a home remedy for the treatment of various clinical conditions like diarrhea, diabetic, pyretic, inflammation, malaria, and for treating stomach and bowel disorders. Its current status is one of the most widespread, troublesome, and economically damaging agronomic weeds, growing wildly in various tropical and sub-tropical regions of the world. Tuber and rhizomes of Cyperus rotundus possess a higher concentration of active ingredients in the form of essential oils, phenolic acids, ascorbic acids and flavonoids, responsible for its remedial properties. Exploitation of any medicinal plant application depends on the crucial and comprehensive information about the therapeutic potential of a plant. Researchers have evaluated and characterized the significance of Cyperus rotundus as an anti-androgenic, anti-bacterial, anti-cancerous, anti-convulsant, anti-diabetic, anti-diarrheal, anti-genotoxic, anti-inflammatory, anti-lipidemic, anti-malarial, anti-mutagenic, anti-obesity, anti-oxidant, anti-uropathogenic, hepato-, cardio-, neuroprotective, and nootropic agent. This paper comprises a broad review to summarize the current state of knowledge about chemical constituents, potential economic uses and therapeutic aspects of Cyperus rotundus that will aid in the development of bioethanol and modern herbal medicine through latest technologies that will promote the ability of this plant in the cure of many clinical disorders.

Keywords: purple nutsedge, chemical composition, economic uses, therapeutic values, future directions

Procedia PDF Downloads 517

Authors: E. Y. Jo, S. M. Park, I. S. Yeo, K. K. Kim, S. J. Park, Y. K. Kim, Y. D. Kim, C. G. Park

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SO3 is created in small quantities during the combustion of fuel that contains sulfur, with the quantity produced a function of the boiler design, fuel sulfur content, excess air level, and the presence of oxidizing agents. Typically, about 1% of the fuel sulfur will be oxidized to SO3, but it can range from 0.5% to 1.5% depending on various factors. Combustion of fuels that contain oxidizing agents, such as certain types of fuel oil or petroleum coke, can result in even higher levels of oxidation. SO3 levels in the flue gas emitted by combustion are very high, which becomes a cause of machinery corrosion or a visible blue plume. Because of that, power plants firing petroleum residues need to installation of SO3 removal system. In this study, SO3 removal system using salt solution was developed and several salts solutions were tested for obtain optimal solution for SO3 removal system. Response surface methodology was used to optimize the operation parameters such as gas-liquid ratio, concentration of salts.

Keywords: flue gas desulfurization, petroleum cokes, Sulfur trioxide, SO3 removal

Procedia PDF Downloads 523

Authors: Maria Lucia G. Lourenco, Keylla H. N. P. Pereira, Vivane Y. Hibaru, Fabiana F. Souza, Joao C. P. Ferreira, Simone B. Chiacchio, Luiz H. A. Machado

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Neonatal sepsis is a systemic response to the acute generalized infection caused by one or more bacterial agents, representing the main infectious cause of neonatal mortality in dogs during the first three weeks of life. This study aims to describe the incidence of sepsis in neonate dogs, as well as the main clinical signs and mortality rates. The study included 735 neonates admitted to the Sao Paulo State University (UNESP) Veterinary Hospital, Botucatu, Sao Paulo, Brazil, between January 2018 and November 2019. Seven hundred thirty-five neonates, 14% (98/703) presented neonatal sepsis. The main sources of infection for the neonates were intrauterine (72.5%, 71/98), lactogenic (13.2%, 13/98), umbilical (5.1%, 5/98) and unidentified sources (9.2%, 9/98). The main non-specific clinical signs observed in the newborns were weakness, depression, impaired or absent reflexes, hypothermia, hypoglycemia, dehydration, reduced muscle tonus and diarrhea. The newborns also manifested clinical signs of severe infection, such as hyperemia in the abdominal and anal regions, omphalitis, hematuria, abdomen and extremities with purplish-blue coloration necrosing injuries in the pads, bradycardia, dyspnea, epistaxis, hypotension and evolution to septic shock. Infections acquired during intrauterine life led to the onset of the clinical signs at the time of birth, with fast evolution during the first hours of life. On the other hand, infections acquired via milk or umbilical cord presented clinical signs later. The total mortality rate was 5.4% (38/703) and the mortality rate among the neonates with sepsis was 38.7% (38/98). The early mortality rate (0 to 2 days) accounted for 86.9% (33/38) and the late mortality rate (3 to 30 days) for 13.1% (5/38) of the deaths among the newborns with sepsis. The main bacterial agents observed were Staphylococcus spp., Streptococcus spp., Proteus spp. Mannheimia spp. and Escherichia coli. Neonatal sepsis evolves quickly and may lead to high mortality in a litter. The prognosis is usually favorable if the diagnosis is reached early and the antibiotic therapy instituted as soon as possible, even before the results of blood cultures and antibiograms. The therapeutic recommendations should meet the special physiological conditions of a neonate in terms of metabolism and excretion of medication. Therefore, it is of utmost importance that the veterinarian is knowledgeable regarding neonatology to provide effective intervention and improve the survival rates of these patients.

Keywords: Neonatal infection , bacteria, puppies, newborn

Procedia PDF Downloads 119

Authors: Abbas Pourreza

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MicroRNAs (miRNAs) are small single-stranded non-coding RNAs. They are almost 18-25 nucleotides long and very conservative through evolution. They are involved in adjusting the expression of numerous genes due to the existence of a complementary region, generally in the 3' untranslated regions (UTR) of target genes, against particular mRNAs in the cell. Also, miRNAs have been proven to be involved in cell development, differentiation, proliferation, and apoptosis. More than 2000 miRNAs have been recognized in human cells, and these miRNAs adjust approximately one-third of all genes in human cells. Dysregulation of miRNA originated from abnormal DNA methylation patterns of the locus, cause to down-regulated or overexpression of miRNAs, and it may affect tumor formation or development of it. Breast cancer (BC) is the most commonly identified cancer, the most prevalent cancer (23%), and the second-leading (14%) mortality in all types of cancer in females. BC can be classified based on the status (+/−) of the hormone receptors, including estrogen receptor (ER), progesterone receptor (PR), and the Receptor tyrosine-protein kinase erbB-2 (ERBB2 or HER2). Currently, there are four main molecular subtypes of BC: luminal A, approximately 50–60 % of BCs; luminal B, 10–20 %; HER2 positive, 15–20 %, and 10–20 % considered Basal (triple-negative breast cancer (TNBC)) subtype. Aberrant expression of miR-145, miR-21, miR-10b, miR-125a, and miR-206 was detected by Stem-loop real-time RT-PCR in BC cases. Breast tumor formation and development may result from down-regulation of a tumor suppressor miRNA such as miR-145, miR-125a, and miR-206 and/or overexpression of an oncogenic miRNA such as miR-21 and miR-10b. MiR-125a, miR-206, miR-145, miR-21, and miR-10b are hugely predicted to be new tumor markers for the diagnosis and prognosis of BC. MiR-21 and miR-125a could play a part in the treatment of HER-2-positive breast cancer cells, while miR-145 and miR-206 could speed up the evolution of cure techniques for TNBC. To conclude, miRNAs will be presented as hopeful molecules to be used in the primary diagnosis, prognosis, and treatment of BC and battle as opposed to its developed drug resistance.

Keywords: breast cancer, HER2 positive, miRNA, TNBC

Procedia PDF Downloads 100

Authors: Shabnam Naderi

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Traditional understandings of ethics considered translators, translations, technologies and other agents as separate and prioritized human agents. In fact, ethics was equated with morality. This disengaged understanding of ethics is superseded by an ethics of relation/entanglement in the posthuman philosophy. According to this ethics of entanglement, human and nonhuman agents are in constant ‘intra-action’. The human is not separate from nature, from technology and from other nonhuman entities, and an ethics of translation in this regard cannot be separated from technology and ecology and get defined merely within the realm of human-human encounter. As such, a posthuman ethics offers opportunities for change and responds to the changing nature of reality, it is negotiable and reveals itself as a moment-by-moment practice (i.e. as temporally emergent and beyond determinacy and permanence). Far from the linguistic or cultural, or individual concerns, posthuman translational ethics discusses how the former rigid norms and laws are challenged in a process ontology which puts emphasis on activity and activation and considers ethics as surfacing in activity, not as a predefined set of rules and values. In this sense, traditional ethical principles like faithfulness, accuracy and representation are superseded by principles of privacy, sustainability, multiplicity and decentralization. The present conceptual study, drawing on Ferrando’s philosophical posthumanism (as a post-humanism, as a post-dualism and as a post-anthropocentrism), Deleuze-Guattarian philosophy of immanence and Barad’s physics-philosophy strives to destabilize traditional understandings of translation ethics and bring an ethics that has loose ends and revolves around multiplicity and decentralization into the picture.

Keywords: ethics of entanglement, post-anthropocentrism, post-dualism, post-humanism, translation

Procedia PDF Downloads 81