Search results for: cytotoxic agents

Authors: Sarah Crawford, Gerry Lesley

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This research is a pre-clinical assessment of anti-cancer effects of novel non-steroidal diethyl stilbestrol-like estrogen analogs in estrogen-receptor positive/ progesterone-receptor positive human breast cancer microtumors of MCF 7 cell line. Tamoxifen analog formulation (Tam A1) was used as a single agent or in combination with therapeutic concentrations of 4-hydroxytamoxifen, currently used as a long-term treatment for the prevention of breast cancer recurrence in women with estrogen receptor positive/ progesterone receptor positive malignancies. At concentrations ranging from 30-50 microM, Tam A1 induced microtumor disaggregation and cell death. Incremental cytotoxic effects correlated with increasing concentrations of Tam A1. Live tumor microscopy showed that microtumos displayed diffuse borders and substrate-attached cells were rounded-up and poorly adherent. A complete cytotoxic effect was observed using 40-50 microM Tam A1 with time course kinetics similar to 4-hydroxytamoxifen. Combined treatment with TamA1 (30-50 microM) and 4-hydroxytamoxifen (10-15 microM) induced a highly cytotoxic, synergistic combined treatment response that was more rapid and complete than using 4-hydroxytamoxifen as a single agent therapeutic. Microtumors completely dispersed or formed necrotic foci indicating a highly cytotoxic combined treatment response. Moreover, breast cancer microtumors treated with both 4-hydroxytamoxifen and Tam A1 displayed lower levels of long-term post-treatment regrowth, a critical parameter of primary drug resistance, than observed for 4-hydroxytamoxifen when used as a single agent therapeutic. Tumor regrowth at 6 weeks post-treatment with either single agent 4-hydroxy tamoxifen, Tam A1 or a combined treatment was assessed for the development of drug resistance. Breast cancer cells treated with both 4-hydroxytamoxifen and Tam A1 displayed significantly lower levels of post-treatment regrowth, indicative of decreased drug resistance, than observed for either single treatment modality. The preclinical data suggest that combined treatment involving the use of tamoxifen analogs may be a novel clinical approach for long-term maintenance therapy in patients with estrogen-receptor positive/progesterone-receptor positive breast cancer receiving hormonal therapy to prevent disease recurrence. Detailed data on time-course, IC50 and tumor regrowth assays post- treatment as well as a proposed mechanism of action to account for observed synergistic drug effects will be presented.

Keywords: 4-hydroxytamoxifen, tamoxifen analog, drug-resistance, microtumors

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Authors: Ashish Jain, Satish Nayak

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Transdermal iontophoretic drug delivery system is viable drug delivery platform technology and has a strong market worldwide. Transdermal drug delivery system is particularly desirable for therapeutic agents that need prolonged administration at controlled plasma level. This makes appropriateness to antihypertensive and anti-diabetic agents for their transdermal development. Controlled zero order absorption, easily termination of drug delivery and easy to administration also support for popularity of transdermal delivery. In this current research iontophoretic delivery of various anti diabetic agents like glipizide, glibenclamide and glimepiride were carried out. The experiments were carried out at different drug concentrations and different current densities using cathodal iontophoresis. Diffusion cell for iontophoretic permeation study was modified according to Glikfield Design. Pig skin was used for in vitro permeation study and for the in-vivo study New Zealand rabbits were used. At all concentration level iontophoresis showed enhanced permeation rate compared to passive controls. Iontophoretic transports of selected drugs were found to be increased with the current densities. Results showed that target permeation rate for selected drugs could be achieved with the aid of iontophoresis by increasing the area in an appreciable range.

Keywords: transdermal, iontophoresis, pig skin, rabbits, glipizide, glibeclamide

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Authors: Ahilya Singh, Brad Carte, Ramesh Subramani, William Aalbersberg

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A total of 37 actinomycete strains were purified from 25 Solomon Islands marine sediments using four different types of isolation media. Among them, 54% of the strains had obligate requirement of seawater for growth. The ethyl acetate extract of 100 ml fermentation product of each strain was screened for antimicrobial activity against multidrug resistant human pathogens and cytotoxic activity against brine shrimps. A total of 67% of the ethyl acetate extracts showed antimicrobial and/or cytotoxic activities. A strain F-1915 was selected for isolation and evaluation of bioactive compound(s) based on its bioactive properties and chemical profile analysis using the LC-MS. The strain F-1915 was identified to have 96% sequence similarity to Streptomyces violaceusniger on the basis of 16S rDNA sequences using BLAST analysis. The 16S rDNA revealed that the strain F-1915 is a new member of MAR4 clade of actinomycetes. The MAR4 clade is an interesting clade of actinomycetes known for the production of pharmaceutically important hybrid isoprenoid compounds. The ethyl acetate extract of the fermentation product of this strain was purified by silica gel column chromatography and afforded the isolation of one bioactive pure compound. Based on the 1D and 2D NMR spectral data of compound 1 it was identified as a new mono-brominated phenazinone, Marinophenazimycin A, a structure which has already been studied by external collaborators at Scripps Institution of Oceanography but is yet to be published. Compound 1 displayed significant antimicrobial activity against drug resistant human pathogens. The minimum inhibitory concentration (MIC) of compound 1 was against Methicillin Resistant Staphylococcus aureus (MRSA) was about 1.9 μg/ml and MIC recorded against Amphotericin Resistant Candida albicans (ARCA) was about 0.24 μg/ml. The bioactivity of compound 1 against ARCA was found to be better than the standard antifungal agent amphotericin B. Compound 1 however did not show any cytotoxic activity against brine shrimps.

Keywords: actinomycetes, antimicrobial activity, brominated phenazine, MAR4 clade, marine natural products, multidrug resistent, 1D and 2D NMR

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Authors: Jurica Hižak

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Getting to know the agents, i.e., identifying the free riders in a population, can be considered one of the main challenges in establishing cooperation. An ordinary memory-one agent such as Tit-for-tat may learn “who is who” in the population through direct interactions. Past experiences serve them as a landmark to know with whom to cooperate and against whom to retaliate in the next encounter. However, this kind of learning is risky and expensive. A cheaper and less painful way to detect free riders may be achieved by gossiping. For this reason, as part of this research, a special type of Tit-for-tat agent was designed – a “Gossip-Tit-for-tat” agent that can share data with other agents of its kind. The performances of both strategies, ordinary Tit-for-tat and Gossip-Tit-for-tat, against Always-defect have been compared in the finite-game framework of the Iterated Prisoner’s Dilemma via the Moran process. Agents were able to move in a random-walk fashion, and they were programmed to play Prisoner’s Dilemma each time they met. Moreover, at each step, one randomly selected individual was eliminated, and one individual was reproduced in accordance with the Moran process of selection. In this way, the size of the population always remained the same. Agents were selected for reproduction via the roulette wheel rule, i.e., proportionally to the relative fitness of the strategy. The absorption probability was calculated after the population had been absorbed completely by cooperators, which means that all the states have been occupied and all of the transition probabilities have been determined. It was shown that gossip increases absorption probabilities and therefore enhances the evolution of cooperation in the population.

Keywords: cooperation, gossip, indirect reciprocity, Moran process, prisoner’s dilemma, tit-for-tat

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Authors: Jer Ping Ooi, Shah Rizal Bin Kasim, Nor Aini Saidin

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The objective of this study was to synthesize nano-sized β-tricalcium phosphate (β-TCP) powder and assess its cytotoxic effects on human osteoblast (hFOB1.19) by using four cytotoxicity assays, namely, lactose dehydrogenase (LDHe), tetrazolium hydroxide (XTT), neutral red (NR), and sulforhodamine B (SRB) assays. β-tricalcium phosphate (β-TCP) is a calcium phosphate compound commonly used as an implant material. To date, bulk-sized β-TCP is reported to be readily tolerated by the osteogenic cells and body based on in vitro, in vivo experiments and clinical studies. However, to what extent of nano-sized β-TCP will react in models as compared to bulk β-TCP is yet to be investigated. Thus, in this project, the cells were treated with nano β-TCP powder within a range of concentrations from 0 to 1000 μg/mL for 24, 48, and 72 h. The cytotoxicity tests showed that loss of cell viability ( > 50%) was high for hFOB1.19 cells in all assays. Cell cycle and apoptosis analysis of hFOB1.19 cells revealed that 50 μg/mL of the compound led to 30.5% of cells being apoptotic after 72 h of incubation, and the percentage was increased to 58.6% when the concentration was increased to 200 μg/mL. When the incubation time was increased from 24 to 72 h, the percentage of apoptotic cells increased from 17.3% to 58.6% when the hFOB1.19 were exposed with 200 μg/mL of nano β-TCP powder. Thus, both concentration and exposure duration affected the cytotoxicity effects of the nano β-TCP powder on hFOB1.19. We hypothesize that these cytotoxic effects on hFOB1.19 are related to the nano-scale size of the β-TCP.

Keywords: β-tricalcium phosphate, hFOB1.19, adipose-derived mesenchymal stem cells, cytotoxicity

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Authors: Mohamed R. Mhereeg

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The paper discusses the design of a .NET Windows Service based agent system called MACS (Multi-Agent Classification System). MACS is a system aims to accurately classify spread-sheet developers competency over a network. It is designed to automatically and autonomously monitor spread-sheet users and gather their development activities based on the utilization of the software Multi-Agent Technology (MAS). This is accomplished in such a way that makes management capable to efficiently allow for precise tailor training activities for future spread-sheet development. The monitoring agents of MACS are intended to be distributed over the WWW in order to satisfy the monitoring and classification of the multiple developer aspect. The Prometheus methodology is used for the design of the agents of MACS. Prometheus has been used to undertake this phase of the system design because it is developed specifically for specifying and designing agent-oriented systems. Additionally, Prometheus specifies also the communication needed between the agents in order to coordinate to achieve their delegated tasks.

Keywords: classification, design, MACS, MAS, prometheus

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Authors: H. Yousefnia, S. Zolghadri, N. Amraee, Z. Naseri, Ar. Jalilian

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The purpose of this study was to calculate the absorbed dose to each human organ for two new Sm-153 bone-seeking agents in order to evaluate their effectiveness in bone pain palliation therapy. In this work, the absorbed dose of 153Sm-TTHMP and 153Sm-PDTMP to each human organ was evaluated based on biodistribution studies in rats by radiation dose assessment resource (RADAR) method. The highest absorbed dose for 153Sm-TTHMP and 153Sm-PDTMP is observed in trabecular bone with 1.844 and 3.167 mGy/MBq, respectively. Bone/red marrow dose ratio, as the target/critical organ dose ratio, for 153Sm-PDTMP is greater than 153Sm-TTHMP and is compatible with 153Sm-EDTMP. The results showed that these bone-seeking agents, specially 153Sm-PDTMP, have considerable characteristics compared to the most clinically used bone pain palliative radiopharmaceutical, and therefore, can be good candidates for bone pain palliation in patients with bone metastasis; however, further biological studies in other mammals are still needed.

Keywords: internal dosimetry, PDTMP, 153Sm, TTHMP

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Authors: Mauricio Filho, Carina Castro

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The object of this project is to analyze long-time public agents that passed through several governments and see themselves in the position of having to deliberate with new agents, recently settled in the public administration. For theoretical ends, internal deliberation is understood as the one practiced on the public administration agencies, without any direct participation from the general public in the process. The assumption is: agents with longer periods of public service tend to step away from momentary political discussions that guide the current administration and seek to concentrate on institutionalized routines and procedures, making the most politically aligned individuals with the current government deliberate with less "passion" and more exchanging of knowledge and information. The theoretical framework of this research is institutionalism, which is guided by a more pragmatic view, facing the fluidity of reality in ways showing the multiple relations between agents and their respective institutions. The critical aspirations of this project rest on the works of professors Cass Sunstein, Adrian Vermeule, Philipp Pettit and in literature from both institutional theory and economic analysis of law, greatly influenced by the Chicago Law School. Methodologically, the paper is a theoretical review and pretends to be unfolded, in a future moment, in empirical tests for verification. This work has as its main analytical tool the appeal to theoretical and doctrinaire areas from the Juridical Sciences, by adopting the deductive and analytical method.

Keywords: institutions, state, law, agencies

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Authors: Nkechi V. Enwuru, Bullum Nkeki, Elizabeth A. Adekoya, Olumide A. Adebesin, Rebecca F. Peters, Victoria A. Aikhomu, Mendie E. U.

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Background: Probiotics are live microbial feed supplement beneficial for host. Probiotics and their postbiotic products have been used to prevent or treat various health conditions. However, the products cell viability is often low due to harsh conditions subjected during processing, handling, storage, and gastrointestinal transit. These strongly influence probiotics’ benefits; thus, viability is essential for probiotics to produce health benefits for the host. Microencapsulation is a promising technique with considerable effects on probiotic survival. The study is aimed to formulate a microencapsulated probiotic and evaluate its viability, antimicrobial efficacy, and cytotoxic activity of its postbiotic on the MCF-7 breast cancer cell line. Method: Human and animal raw milk were sampled for lactic acid bacteria. The isolated bacteria were identified using conventional and VITEK 2 systems. The identified lactic acid bacterium was encapsulated using spray-dried and extrusion methods. The free, encapsulated, and chitosan-coated encapsulated probiotics were tested for viability in simulated-gastric intestinal (SGI) fluid and different storage conditions at refrigerated (4oC) and room (25oC) temperatures. The disintegration time and weight uniformity of the spray-dried hard gelatin capsules were tested. The antimicrobial property of free and encapsulated probiotics was tested against enteric pathogenic isolates from antiretroviral therapy (ART) treated HIV-positive patients. The postbiotic of the free cells was extracted, and its cytotoxic effect on the MCF-7 breast cancer cell line was tested through an MTT assay. Result: The Lactobacillus plantarum was isolated from animal raw milk. Zero-size hard gelatin L. plantarum capsules with granules within a size range of 0.71–1.00 mm diameter was formulated. The disintegration time ranges from 2.14±0.045 to 2.91±0.293 minutes, while the average weight is 502.1mg. Simulated gastric solution significantly affected viability of both free and microcapsules. However, the encapsulated cells were more protected and viable due to impermeability in the microcapsules. Furthermore, the viability of free cells stored at 4oC and 25oC were less than 4 log CFU/g and 6 log CFU/g respectively after 12 weeks. However, the microcapsules stored at 4oC achieved the highest viability among the free and microcapsules stored at 25oC and the free cells stored at 4oC. Encapsulated cells were released in the simulated gastric fluid, viable and effective against the enteric pathogens tested. However, chitosan-coated calcium alginate encapsulated probiotics significantly inhibited Shigella flexneri, Candida albicans, and Escherichia coli. The Postbiotic Metabolites (PM) of L. plantarum produced a cytotoxic effect on the MCF-7 breast cancer cell line. The postbiotic showed significant cytotoxic activity similar to 5FU, a standard antineoplastic agent. The inhibition concentration of 50% growth (IC50) of postbiotic metabolite K3 is low and consistent with the IC50 of the positive control (Cisplatin). Conclusions: Lactobacillus plantarum postbiotic exhibited a cytotoxic effect on the MCF-7 breast cancer cell line and could be used as combined adjuvant therapy in breast cancer management. The microencapsulation technique protects the probiotics, improving their viability and delivery to the gastrointestinal tract. Chitosan enhances antibacterial efficacy; thus, chitosan-coated microencapsulated L. plantarum probiotics could be more effective and used as a combined therapy in HIV management of opportunistic enteric infection.

Keywords: probiotics, encapsulation, gastrointestinal conditions, antimicrobial effect, postbiotic, cytotoxicity effect

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Authors: Cristine P. Canlas, Crislene Mae L. Gever, Patricia Bea R. Rosialda, Ma. Nina Regina M. Quibod, Perry Archival C. Buenavente, Normandy M. Barbecho, Cynthia Adeline A. Layusa, Michael Day

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Invasive plants have an impact on global biodiversity and ecosystem function, and their management is a complex and formidable task. Two of these invasive plant species, Lantana camara and Chromolaena odorata, are found in the Philippines. Lantana camara has the ability to suppress the growth of and outcompete neighboring plants. Chromolaena odorata causes serious agricultural and economical damage and causes fire hazards during dry season. In addition, both species has been reported to poison livestock. One of the known global management strategies to control invasive plants is the introduction of biological control agents. These natural enemies of the invasive plants reduce population density and impacts of the invasive plants, resulting in the balance of the nature in their invasion. Through secondary data sources, interviews, and field validation (e.g. microhabitat searches, sweep netting, opportunistic sampling, photo-documentation), we investigated whether the biocontrol agents previously released by the Philippine Coconut Authority (PCA) in their Davao Research Center to control these invasive plants are still present and are affecting their respective host weeds. We confirm the presence of the biocontrol agent of L. camara, Uroplata girardi, which was introduced in 1985, and Cecidochares connexa, a biocontrol agent of C. odorata released in 2003. Four other biocontrol agents were found to affect L. camara. Signs of damage (e.g. stem galls in C. odorata, and leaf mines in L. camara) signify that these biocontrol agents have successfully established outside of their release site in Davao. Further investigating the extent of the spread of these biocontrol agents in the Philippines and their damage to the two weeds will contribute to the management of invasive plant species in the country.

Keywords: invasive alien species, biological control agent, entomology, worst weeds

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Authors: Jawad Alzeer

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Natural products are well recognized as sources of drugs in several human ailments. To investigate the impact of variable extraction techniques on the cytotoxic effects of medicinal plant extracts, 5 well-known medicinal plants from Palestine were extracted with 90% ethanol, 80% methanol, acetone, coconut water, apple vinegar, grape vinegar or 5% acetic acid. The resulting extracts were screened for cytotoxic activities against three different cancer cell lines (B16F10, MCF-7, and HeLa) using a standard resazurin-based cytotoxicity assay and Nile Blue A as the positive control. Highly variable toxicities and tissue sensitivity were observed, depending upon the solvent used for extraction. Acetone consistently gave lower extraction yields but higher cytotoxicity, whereas other solvent systems gave much higher extraction yields with lower cytotoxicity. Interestingly, coconut water was found to offer a potential alternative to classical organic solvents; it gave consistently highest extraction yields, and in the case of S. officinalis L., highly toxic extracts towards MCF-7 cells derived from human breast cancer. These results demonstrate how the cytotoxicity of plant extracts can be inversely proportional to the yield, and that solvent selection plays an important role in both factors.

Keywords: plant extract, natural products, anti cancer drug, cytotoxicity

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Authors: Yosra Mefteh Rekik

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A computational agent-based model of financial markets stresses interactions and dynamics among a very diverse set of traders. The growing body of research in this area relies heavily on computational tools which by-pass the restrictions of an analytical method. The main goal of this research is to understand how the stock market operates and behaves how to invest in the stock market and to study traders’ behavior within the context of the artificial stock markets populated by heterogeneous agents. All agents are characterized by adaptive learning behavior represented by the Artificial Neuron Networks. By using agent-based simulations on artificial market, we show that the existence of heterogeneous agents can explain the price dynamics in the financial market. We investigate the relation between market diversity and market efficiency. Our empirical findings demonstrate that greater market heterogeneity play key roles in market efficiency.

Keywords: agent-based modeling, artificial stock market, heterogeneous expectations, financial stylized facts, computational finance

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Authors: Harsha Kumar H. N., Anshu Kumar Jha, Khushboo Kamal Taneja, Krishan Kabra, Mohamed Hafeez Sadiq

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Introduction: The increasing use of preservatives and flavouring agents has the potential to cause health problem among the people. There are no published studies from India exploring the awareness, safety perception, & practices about Food Preservatives (FPs) and Flavouring Agents (FAs). So this study was conducted with the objectives of assessing the awareness, safety perceptions & practices about Food Preservatives (FPs), Flavouring Agents (FAs) in commonly bought / purchased packed food items. Materials & method: This cross-sectional study was conducted in January 2012. Sample size of 126 was computed using the formula for infinite population. People who bought packed food items in malls were approached and requested to fill a pre-tested semi-structured questionnaire. The questionnaire explored awareness, safety perception & practices of FPs & FAs. Data was then analyzed using SPSS version 10.0. Chi-square test was used to know if the observed differences were statistically significant. ‘p’ value <0.05 was considered significant. Results: Totally 123 people (males- 48.8% and females-51.2%) participated (response rate of 97.6%) in the study. Majority of the people were aware about presence of ‘FPs’ (91.7%) and ‘FAs’ (84.9%) though their knowledge was inadequate. Breakup of the study subjects according to level of awareness about FPs was as follows (%): Good (37.4), Satisfactory (40.6), Poor (22) & FAs (%): Good (49.6), Satisfactory (36) & Poor (14). Distribution according to type of practices for FPs was as follows (%): Favourable (14), Unfavourable (86) & FAs (%): Favourable (30.5), Unfavourable (69.5). There was a gap between knowledge and practices. Conclusion: Though there was awareness, the knowledge was inadequate. Unfavourable practices were observed. The gaps in the knowledge and unhealthy practices need to be addressed by public awareness campaign.

Keywords: food preservatives, flavouring agents, knowledge and practices, general population

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Authors: Hyeongbok Kim, Lingling Zhao, Xiaohong Su

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Deep reinforcement learning has been applied to address various problems in robotics, such as autonomous driving and unmanned aerial vehicle. However, because of the sparse reward penalty for a collision with obstacles during the navigation mission, the agent fails to learn the optimal policy or requires a long time for convergence. Therefore, using obstacles and enemy agents, in this paper, we present a curriculum-based boost learning method to effectively train compound skills during multi-agent reinforcement learning. First, to enable the agents to solve challenging tasks, we gradually increased learning difficulties by adjusting reward shaping instead of constructing different learning environments. Then, in a benchmark environment with static obstacles and moving enemy agents, the experimental results showed that the proposed curriculum learning strategy enhanced cooperative navigation and compound collision avoidance skills in uncertain environments while improving learning efficiency.

Keywords: curriculum learning, hard exploration, multi-agent reinforcement learning, robotic navigation, sparse reward

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Authors: Eslam Dabbish, Fortuna Ponte, Stefano Scoditti, Emilia Sicilia, Gloria Mazzone

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The medical techniques based on the use of light for activating the drug are occupying a prominent place in the cancer treatment due to their selectivity that contributes to reduce undesirable side effects of conventional chemotherapy. Among these therapeutic treatments, photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) are emerging as complementary approaches for selective destruction of neoplastic tissue through direct cellular damage. Both techniques rely on the employment of a molecule, photosensitizer (PS), able to absorb within the so-called therapeutic window. Thus, the exposure to light of otherwise inert molecules promotes the population of excited states of the drug, that in PDT are able to produce the cytotoxic species, such as 1O2 and other ROS, in PACT can be responsible of the active species release or formation. Following the success of cisplatin in conventional treatments, many other transition metal complexes were explored as anticancer agents for applications in different medical approaches, including PDT and PACT, in order to improve their chemical, biological and photophysical properties. In this field, several crucial characteristics of candidate PSs can be accurately predicted from first principle calculations, especially in the framework of density functional theory and its time-dependent formulation, contributing to the understanding of the entire photochemical pathways involved which can ultimately help in improving the efficiency of a drug. A brief overview of the outcomes on some platinum and ruthenium-based PSs proposed for the application in the two phototherapies will be provided.

Keywords: TDDFT, metal complexes, PACT, PDT

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Authors: Silvia Tamayo-Moreno, Diana Pérez-Marín

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In this paper, the possibility of children studying by using an interactive learning technology called Pedagogic Conversational Agent is presented. The main benefit is that the agent is able to adapt the dialogue to each student and to provide automatic feedback. Moreover, according to Math teachers, in many cases students are unable to solve the problems even knowing the procedure to solve them, because they do not understand what they have to do. The hypothesis is that if students are helped to understand what they have to solve, they will be able to do it. Taken that into account, we have started the development of Dr. Roland, an agent to help students understand Math problems following a User-Centered Design methodology. The use of this methodology is proposed, for the first time, to design pedagogic agents to teach any subject from Secondary down to Pre-Primary education. The reason behind proposing a methodology is that while working on this project, we noticed the lack of literature to design and evaluate agents. To cover this gap, we describe how User-Centered Design can be applied, and which usability techniques can be applied to evaluate the agent.

Keywords: pedagogic conversational agent, human-computer interaction, user-centered design, natural language interface

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Authors: A. Jamsheera, F. Arjmand, D. K. Mohapatra

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Small molecules binding to specific sites along DNA molecule are considered as potential chemotherapeutic agents. Their role as mediators of key biological functions and their unique intrinsic properties make them particularly attractive therapeutic agents. Keeping in view, novel dipeptide complexes Cu(II)-Val-Pro (1), Zn(II)-Val-Pro (2), Cu(II)-Ala-Pro (3) and Zn(II)-Ala-Pro (4) were synthesized and thoroughly characterized using different spectroscopic techniques including elemental analyses, IR, NMR, ESI–MS and molar conductance measurements. The solution stability study carried out by UV–vis absorption titration over a broad range of pH proved the stability of the complexes in solution. In vitro DNA binding studies of complexes 1–4 carried out employing absorption, fluorescence, circular dichroism and viscometric studies revealed the binding of complexes to DNA via groove binding. UV–vis titrations of 1–4 with mononucleotides of interest viz., 5´-GMP and 5´-TMP were also carried out. The DNA cleavage activity of the complexes 1 and 2 were ascertained by gel electrophoresis assay which revealed that the complexes are good DNA cleavage agents and the cleavage mechanism involved a hydrolytic pathway. Furthermore, in vitro antitumor activity of complex 1 was screened against human cancer cell lines of different histological origin.

Keywords: dipeptide Cu(II) and Zn(II) complexes, DNA binding profile, pBR322 DNA cleavage, in vitro anticancer activity

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Authors: Siming Xie

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In social networks, the term homophily refers to the tendency of agents with similar characteristics to link with one another and is so robustly observed across many contexts and dimensions. The starting point of my research is the observation that the “type” of agents is not a single exogenous variable. Agents, despite their differences in race, religion, and other hard to alter characteristics, may share interests and engage in activities that cut across those predetermined lines. This research aims to capture the interactions of homophily effects in a model where agents have two-dimension characteristics (i.e., race and personal hobbies such as basketball, which one either likes or dislikes) and with biases in meeting opportunities and in favor of same-type friendships. A novel feature of my model is providing a matching process with biased meeting probability on different dimensions, which could help to understand the structuring process in multidimensional networks without missing layer interdependencies. The main contribution of this study is providing a welfare based matching process for agents with multi-dimensional characteristics. In particular, this research shows that the biases in meeting opportunities on one dimension would lead to the emergence of homophily on the other dimension. The objective of this research is to determine the pattern of homophily in network formations, which will shed light on our understanding of segregation and its remedies. By constructing a two-dimension matching process, this study explores a method to describe agents’ homophilous behavior in a social network with multidimension and construct a game in which the minorities and majorities play different strategies in a society. It also shows that the optimal strategy is determined by the relative group size, where society would suffer more from social segregation if the two racial groups have a similar size. The research also has political implications—cultivating the same characteristics among agents helps diminishing social segregation, but only if the minority group is small enough. This research includes both theoretical models and empirical analysis. Providing the friendship formation model, the author first uses MATLAB to perform iteration calculations, then derives corresponding mathematical proof on previous results, and last shows that the model is consistent with empirical evidence from high school friendships. The anonymous data comes from The National Longitudinal Study of Adolescent Health (Add Health).

Keywords: homophily, multidimension, social networks, friendships

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Authors: Francisco J. García-de-Quirós, Gianmarco Radice

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When considering small robots working in a cooperative community for Moon surface exploration, navigation and inter-nodes communication aspects become a critical issue for the mission success. For this approach to succeed, it is necessary however to deploy the required infrastructure for the robotic community to achieve efficient self-localization as well as relative positioning and communications between nodes. In this paper, an exploration mission concept in which two cooperative robotic systems co-exist is presented. This paradigm hinges on a community of reference agents that provide support in terms of communication and navigation to a second agent community tasked with exploration goals. The work focuses on the role of the agent community in charge of the overall support and, more specifically, will focus on the positioning and navigation methods implemented in RF microwave bands, which are combined with the communication services. An analysis of the different methods for range and position calculation are presented, as well as the main limiting factors for precision and resolution, such as phase and frequency noise in RF reference carriers and drift mechanisms such as thermal drift and random walk. The effects of carrier frequency instability due to phase noise are categorized in different contributing bands, and the impact of these spectrum regions are considered both in terms of the absolute position and the relative speed. A mission scenario is finally proposed, and key metrics in terms of mass and power consumption for the required payload hardware are also assessed. For this purpose, an application case involving an RF communication network in UHF Band is described, in coexistence with a communications network used for the single agents to communicate within the both the exploring agents as well as the community and with the mission support agents. The proposed approach implements a substantial improvement in planetary navigation since it provides self-localization capabilities for robotic agents characterized by very low mass, volume and power budgets, thus enabling precise navigation capabilities to agents of reduced dimensions. Furthermore, a common and shared localization radiofrequency infrastructure enables new interaction mechanisms such as spatial arrangement of agents over the area of interest for distributed sensing.

Keywords: cooperative robotics, localization, robot navigation, surface exploration

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Authors: Maryam Zahedifard, Fadhil Lafta Faraj, Maryam Hajrezaie, Nazia Abdul Majid, Mahmood Ameen Abdulla, Hapipah Mohd Ali

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In the current study, we prepared two new quinazoline schiff bases through condensation reaction of 2-aminobenzhydrazide with 5-bromosalicylaldehyde and 3-methoxy-5-bromosalicylaldehyde. The chemical structures of both newly synthesized compounds (1 and 2) were confirmed by FT-IR and X-ray crystallography studies. The cytotoxic effect of compounds was investigated against MCF-7 human breast cancer cells. MTT results showed that (1) and (2) decreased the viability of MCF-7 cells in a time-dependent manner, exhibiting an IC50 value of 3.23 ± 0.28 µg/mL and 3.41 ± 0.34 µg/mL, respectively, after a 72-hours treatment period. In contrast, they did not show significant anti-proliferative effect towards MCF-10A normal breast cells and WRL-68 normal liver cells. We found a perturbation in mitochondrial membrane potential and increased cytochrome c release from the mitochondria to the cytosol, suggesting an activation of apoptosis by compounds, which was confirmed by activation of the initiator caspase-9 and the executioner caspases-3/7. (1) was also able to trigger extrinsic pathway via activation of caspase-8 and inhibition of NF-κB translocation. The acute toxicity test showed no toxicity effect of the compounds in rats. Our results showed that the selected synthesized compounds are highly potent to induce apoptosis in MCF-7 cells via either intrinsic or extrinsic mitochondrial pathway.

Keywords: Quinazoline Schiff base, apoptosis, MCF-7 human breast cancer cell line, caspase, NF-κB translocation

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Authors: Karen L. Rincon-Granados, América R. Vázquez-Olmos, Adriana-Patricia Rodríguez-Hernández, Gina Prado-Prone, Margarita Rivera, Roberto Y. Sato-Berrú

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In this work, a hybrid film based on poly-3-hydroxybutyrate (P3HB) and nickel ferrite (NiFe₂O₄) nanoparticles (NPs) was obtained by a simple and reproducible methodology in order to study its antibacterial and cytotoxic properties. The motivation for this research is the current antimicrobial resistance (RAM). This is a threat to human health and development worldwide. RAM is caused by the emergence of bacterial strains resistant to traditional antibiotics that were used as treatment. Due to this, the need to investigate new alternatives for preventing and treating bacterial infections emerges. In this sense, metal oxide NPs have aroused great interest due to their unique physicochemical properties. However, their use is limited by the nanostructured nature, commonly obtained by chemical and physical synthesis methods, as powders or colloidal dispersions. Therefore, the incorporation of nanostructured materials in polymer matrices to obtain hybrid materials that allow disinfecting and preventing the spread of bacteria on various surfaces. Accordingly, this work presents the synthesis and study of the antibacterial properties of the P3HB@NiFe₂O₄ hybrid film as a potential material to inhibit bacterial growth. The NiFe₂O₄ NPs were previously synthesized by a mechanochemical method. The P3HB and P3HB@NiFe₂O₄ films were obtained by the solvent casting method. The films were characterized by X-ray diffraction (XRD), Raman scattering, and scanning electron microscopy (SEM). The XRD pattern showed that the NiFe₂O₄ NPs were incorporated into the P3HB polymer matrix and retained their nanometric sizes. By energy dispersive X-ray spectroscopy (EDS), it was observed that the NPs are homogeneously distributed in the film. The bactericidal effect of the films obtained was evaluated in vitro using the broth surface method against two opportunistic and nosocomial pathogens, Staphylococcus aureus and Pseudomonas aeruginosa. The bacterial growth results showed that the P3HB@NiFe₂O₄ hybrid film was inhibited by 97% and 96% for S. aureus and P. aeruginosa, respectively. Surprisingly, the P3HB film inhibited both bacterial strains by around 90%. The cytotoxicity of the NiFe₂O₄ NPs, P3HB@NiFe₂O₄ hybrid film, and the P3HB film was evaluated using human skin cells, keratinocytes, and fibroblasts, finding that the NPs are biocompatible. The P3HB film and hybrids are cytotoxic, which demonstrated that although P3HB is known and reported as a biocompatible polymer, under our work conditions, P3HB was cytotoxic. Its bactericidal effect could be related to this activity. Its films are bactericidal and cytotoxic to keratinocytes and fibroblasts, the first barrier of human skin. Despite this, the hybrid film of P3HB@NiFe₂O₄ presents synergy with the bactericidal effect between P3HB and NPs, increasing bacterial inhibition. In addition, NPs decrease the cytotoxicity of P3HB to keratinocytes. The methodology used in this work was successful in producing hybrid films with antibacterial activity. However, future challenges are generated to find relationships between NPs and P3HB that allow taking advantage of their bactericidal properties and do not compromise biocompatibility.

Keywords: poly-3-hydroxybutyrate, nanoparticles, hybrid film, antibacterial

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Authors: Jarel Elgin Tolentino, Arby Denise Nera, Mary Rose Roco, Angela Vianca Aspa, Nikko Beltran, Else Dapat

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Drug resistance by cells has been the problem in the medical field for decades now. The use of medicinal plants as a source of creating powerful drugs has been nowadays recognized worldwide to treat such resistant diseases. In the present study, the potential for Diospyros philippinensis A. DC. to inhibit growth of both bacteria and cancer cell line was conducted. The leaf crude extracts were screened for the presence of phytochemicals and examined for potential bioactivities by employing several assays like Kirby-Bauer disc diffusion method, DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) assay and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium assay for the antibacterial, antioxidant and cytotoxic activities of the extract, respectively. Phytochemical test results of the extracts revealed the presence of alkaloids, flavonoids, saponins, phenols, quinones, cardiac glycosides, phlobatannins, carbohydrate, cardenolides and proteins. The leaf extracts were found to exhibit antibacterial activity against gram-positive bacteria, high antioxidant activity (99.22% ± 0.005) but did not show any sign of cytotoxicity towards HCT116 (ATCC CCL-247). The study therefore concludes that D. philippinensis A. DC. leaf extract can be a source of antibacterial and chemopreventive agents. This claim may be used as basis for future investigation.

Keywords: bioassay, medicinal plants, plant crude extracts, phytochemical screening

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Authors: C. W. Kan

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This study examines the results of optical whitening process of different textiles such as cotton, wool and polyester. The optical whitening agents used are commercially available products, and the optical whitening agents were applied to the textiles with manufacturers’ suggested methods. The aim of this study is to illustrate the proper application methods of optical whitening agent to different textiles and hence to provide guidance note to the students in learning this topic. Acknowledgment: Authors would like to thank the financial support from the Hong Kong Polytechnic University for this work.

Keywords: learning materials, optical whitening agent, wool, cotton, polyester

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Authors: Ibrahim Aliyu Isah, Mohd Mansor Ismail, Salim Hassan, Norsida Man, Oluwatoyin Olagunju

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Stingless beekeeping is not only a profitable activity for Malaysian beekeepers but also for the Malaysian economy. However, natural honey has faced some difficulties, which resulted in low production due to a lack of information on improved technology as well as the capacity and potential building of stingless beekeeping farmers, which depend mostly on information received from the extension agents. Hence, it is the responsibility of the extension agents to give useful information on the available technology and develop the capacity of the farmers to make the right decision that will improve their level of production. This study assessed how technology transfer and human resource development skills influence the work performance of the extension agents toward sustainable beekeeping production among beekeepers. The study sought to establish the role of relevant technology transfer and human resource development skills in effective performance. The research design was a descriptive and quantitative survey of stingless beekeepers on technology transfer and human resource development by the extension agent. Data was obtained from 54 beekeeping farmers and was analyzed using descriptive and inferential statistics. The results revealed that technology skill, technology dissemination skill, technology evaluation skill, Decision-making process skill, Leadership development skill and work performance were rated moderate by stingless beekeeping farmers, while Social skill was rated high. A significant and positive correlation (P<0.01) existed between all variables and performance. Regression results showed that leadership development skills, Decision-making process skills, and social skills are significant (P=.05), while technology skills, technology dissemination skills, and technology evaluation skills are not significant. The highest contributing factor is social skill (β=.446). Beekeeping is a profitable project in Malaysia and can be sustained if the extension services and programs are well carried out by competent extension agents and relevant agricultural government agencies.

Keywords: beekeeping, extension agents, human resource development, sustainable, technology transfer, work performance

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Authors: Abhijit Trailokya, Kamlesh Patel

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Background: Hypertension is a common disease seen in clinical practice and is associated with high morbidity and mortality. Many patients require combination therapy for the management of hypertension. Objective: To evaluate co-morbidities, risk factors and management practices of hypertension in Indian population. Material and methods: A total of 1596 hypertensive adult patients received anti-hypertensive medications were studied in a cross-sectional, multi-centric, non-interventional, observational registry. Statistical analysis: Categories or nominal data was expressed as numbers with percentages. Continuous variables were analyzed by descriptive statistics using mean, SD, and range Chi square test was used for in between group comparison. Results: The study included 73.50% males and 26.50% females. Overweight (50.50%) and obesity (30.01%) was common in the hypertensive patients (n=903). A total of 54.76% patients had history of smoking. Alcohol use (33.08%), sedentary life style (32.96%) and history of tobacco chewing (17.92%) were the other lifestyle habits of hypertensive patients. Diabetes (36.03%) and dyslipidemia (39.79%) history was common in these patients. Family history of hypertension and diabetes was seen in 82.21% and 45.99% patients respectively. Most (89.16%) patients were treated with combination of antihypertensive agents. ARBs were the by far most commonly used agents (91.98%) followed by calcium channel blockers (68.23%) and diuretics (60.21%). ARB was the most (80.35%) preferred agent as monotherapy. ARB was also the most common agent as a component of dual therapy, four drug and five drug combinations. Conclusion: Most of the hypertensive patients need combination treatment with antihypertensive agents. ARBs are the most preferred agents as monotherapy for the management of hypertension. ARBs are also very commonly used as a component of combination therapy during hypertension management.

Keywords: antihypertensive, hypertension, management, ARB

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Authors: A. Zuchowska, A. Buta, M. Mazurkiewicz-Pawlicka, A. Malolepszy, L. Stobinski, Z. Brzozka

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In recent years, graphene-based materials are finding more and more applications in biological science. As a thin, tough, transparent and chemically resistant materials, they appear to be a very good material for the production of implants and biosensors. Interest in graphene derivatives also resulted at the beginning of research about the possibility of their application in cancer therapy. Currently, the analysis of their potential use in photothermal therapy and as a drug carrier is mostly performed. Moreover, the direct anticancer properties of graphene-based materials are also tested. Nowadays, cytotoxic studies are conducted on in vitro cell culture in standard culture vessels (macroscale). However, in this type of cell culture, the cells grow on the synthetic surface in static conditions. For this reason, cell culture in macroscale does not reflect in vivo environment. The microfluidic systems, called Lab-on-a-chip, are proposed as a solution for improvement of cytotoxicity analysis of new compounds. Here, we present the evaluation of cytotoxic properties of graphene oxide (GO) on breast, liver and colon cancer cell line in a microfluidic system in two spatial models (2D and 3D). Before cell introduction, the microchambers surface was modified by the fibronectin (2D, monolayer) and poly(vinyl alcohol) (3D, spheroids) covering. After spheroid creation (3D) and cell attachment (2D, monolayer) the selected concentration of GO was introduced into microsystems. Then monolayer and spheroids viability/proliferation using alamarBlue® assay and standard microplate reader was checked for three days. Moreover, in every day of the culture, the morphological changes of cells were determined using microscopic analysis. Additionally, on the last day of the culture differential staining using Calcein AM and Propidium iodide were performed. We were able to note that the GO has an influence on all tested cell line viability in both monolayer and spheroid arrangement. We showed that GO caused higher viability/proliferation decrease for spheroids than a monolayer (this was observed for all tested cell lines). Higher cytotoxicity of GO on spheroid culture can be caused by different geometry of the microchambers for 2D and 3D cell cultures. Probably, GO was removed from the flat microchambers for 2D culture. Those results were also confirmed by differential staining. Comparing our results with the studies conducted in the macroscale, we also proved that the cytotoxic properties of GO are changed depending on the cell culture conditions (static/ flow).

Keywords: cytotoxicity, graphene oxide, monolayer, spheroid

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Authors: Joanna Cydejko, Paulina Mika

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Hypersensitivity reactions are side effects of medications that resemble an allergic reaction. Anaphylaxis is a generalized, severe allergic reaction of the body caused by exposure to a specific agent at a dose tolerated by a healthy body. The most common causes of anaphylaxis are food (about 70%), Hymenoptera venoms (22%), and medications (7%), despite detailed diagnostics in 1% of people, the cause of the anaphylactic reaction was not indicated. Contrast media are anaphylactic agents of unknown mechanism. Hypersensitivity reactions can occur with both immunological and non-immunological mechanisms. Symptoms of anaphylaxis occur within a few seconds to several minutes after exposure to the allergen. Contrast agents are chemical compounds that make it possible to visualize or improve the visibility of anatomical structures. In the diagnosis of computed tomography, the preparations currently used are derivatives of the triiodide benzene ring. Pharmacokinetic and pharmacodynamic properties, i.e., their osmolality, viscosity, low chemotoxicity and high hydrophilicity, have an impact on better tolerance of the substance by the patient's body. In MRI diagnostics, macrocyclic gadolinium contrast agents are administered during examinations. The aim of this study is to present the results of the number and severity of anaphylactic reactions that occurred in patients in all age groups undergoing diagnostic imaging with intravenous administration of contrast agents. In non-ionic iodine CT and in macrocyclic gadolinium MRI. A retrospective assessment of the number of adverse reactions after contrast administration was carried out on the basis of data from the Department of Radiology of the University Clinical Center in Gdańsk, and it was assessed whether their different physicochemical properties had an impact on the incidence of acute complications. Adverse reactions are divided according to the severity of the patient's condition and the diagnostic method used in a given patient. Complications following the administration of a contrast medium in the form of acute anaphylaxis accounted for less than 0.5% of all diagnostic procedures performed with the use of a contrast agent. In the analysis period from January to December 2022, 34,053 CT scans and 15,279 MRI examinations with the use of contrast medium were performed. The total number of acute complications was 21, of which 17 were complications of iodine-based contrast agents and 5 of gadolinium preparations. The introduction of state-of-the-art contrast formulations was an important step toward improving the safety and tolerability of contrast agents used in imaging. Currently, contrast agents administered to patients are considered to be one of the best-tolerated preparations used in medicine. However, like any drug, they can be responsible for the occurrence of adverse reactions resulting from their toxic effects. The increase in the number of imaging tests performed with the use of contrast agents has a direct impact on the number of adverse events associated with their administration. However, despite the low risk of anaphylaxis, this risk should not be marginalized. The growing threat associated with the mass performance of radiological procedures with the use of contrast agents forces the knowledge of the rules of conduct in the event of symptoms of hypersensitivity to these preparations.

Keywords: anaphylactic, contrast medium, diagnostic, medical imagine

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Authors: Craig A. Kaplan

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If AGI proves to be a “winner-take-all” scenario where the first company or country to develop AGI dominates, then the first AGI must also be the safest. The safest, and fastest, path to Artificial General Intelligence (AGI) may be to harness the collective intelligence of multiple AI and human agents in an AGI network. This approach has roots in seminal ideas from four of the scientists who founded the field of Artificial Intelligence: Allen Newell, Marvin Minsky, Claude Shannon, and Herbert Simon. Extrapolating key insights from these founders of AI, and combining them with the work of modern researchers, results in a fast and safe path to AGI. The seminal ideas discussed are: 1) Society of Mind (Minsky), 2) Information Theory (Shannon), 3) Problem Solving Theory (Newell & Simon), and 4) Bounded Rationality (Simon). Society of Mind describes a collective intelligence approach that can be used with AI and human agents to create an AGI network. Information theory helps address the critical issue of how an AGI system will increase its intelligence over time. Problem Solving Theory provides a universal framework that AI and human agents can use to communicate efficiently, effectively, and safely. Bounded Rationality helps us better understand not only the capabilities of SuperIntelligent AGI but also how humans can remain relevant in a world where the intelligence of AGI vastly exceeds that of its human creators. Each key idea can be combined with recent work in the fields of Artificial Intelligence, Machine Learning, and Large Language Models to accelerate the development of a working, safe, AGI system.

Keywords: AI Agents, Collective Intelligence, Minsky, Newell, Shannon, Simon, AGI, AGI Safety

Procedia PDF Downloads 51

Authors: Chema Segovia, Pau Díaz-Solano, Tony Ramos Murphy

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The PALIMPSEST project, funded by Horizon 2020 and associated with the New European Bauhaus, aims to revitalize sustainability practices in heritage landscapes through co-creation processes led by creative agents. Specifically, PALIMPSEST focuses on the pivotal roles of architecture, design, and art in addressing sustainability challenges. The project aims to demonstrate that these creative disciplines can generate a distinctive kind of value while addressing environmental needs, enhancing societal engagement, supporting foresighting activities, and increasing awareness. In the summer of 2023, Palimpsest launched an open call to select the teams that will lead the development of three creativity-based sustainability processes in three different pilot cities: Jerez de la Frontera (Spain), Lodz (Poland), and Milan (Italy). The call received 141 applications. Through a survey conducted among the candidates and an in-depth analysis of their proposals, we assessed the level of engagement that European creative agents have in tackling sustainability challenges, as well as their alignment with the principles advocated by the New European Bauhaus.

Keywords: arts, architecture, co-creation, design, new European Bauhaus, sustainability

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Authors: Rabindranath Jana, Plabani Basu, Keka Rana

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Nucleating agents are widely used to modify the properties of various polymers. The rate of crystallization and the size of the crystals have a strong impact on mechanical and optical properties of a polymer. The addition of nucleating agents to the semi-crystalline polymers provides a surface on which the crystal growth can start easily. As a consequence, fast crystal formation will result in many small crystal domains so that the cycle times for injection molding may be reduced. Moreover, the mechanical properties e.g., modulus, tensile strength, heat distortion temperature and hardness may increase. In the present work, multi-walled carbon nanotubes (MWNTs) as nucleating agents for the crystallization of poly (e-caprolactone)diol (PCL). Thus nanocomposites of PCL filled with MWNTs were prepared by solution blending. Differential scanning calorimetry (DSC) tests were carried out to study the effect of CNTs on on-isothermal crystallization of PCL. The polarizing optical microscopy (POM), and wide-angle X-ray diffraction (WAXD) were used to study the morphology and crystal structure of PCL and its nanocomposites. It is found that MWNTs act as effective nucleating agents that significantly shorten the induction period of crystallization and however, decrease the crystallization rate of PCL, exhibiting a remarkable decrease in the Avrami exponent n, surface folding energy σe and crystallization activation energy ΔE. The carbon-based fillers act as templates for hard block chains of PCL to form an ordered structure on the surface of nanoparticles during the induction period, bringing about some increase in equilibrium temperature. The melting process of PCL and its nanocomposites are also studied; the nanocomposites exhibit two melting peaks at higher crystallization temperature which mainly refer to the melting of the crystals with different crystal sizes however, PCL shows only one melting temperature.

Keywords: poly(e-caprolactone)diol, multiwalled carbon nanotubes, composite materials, nonisothermal crystallization, crystal structure, nucleation

Procedia PDF Downloads 462