Search results for: nociceptive agent
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1510

Search results for: nociceptive agent

1180 Multiple Etiologies and Incidences of Co-Infections in Childhood Diarrhea in a Hospital Based Screening Study in Odisha, India

Authors: Arpit K. Shrivastava, Nirmal K. Mohakud, Subrat Kumar, Priyadarshi S. Sahu

Abstract:

Acute diarrhea is one of the major causes of morbidity and mortality among children less than five years of age. Multiple etiologies have been implicated for infectious gastroenteritis causing acute diarrhea. In our study fecal samples (n=165) were collected from children (<5 years) presenting with symptoms of acute diarrhea. Samples were screened for viral, bacterial, and parasitic etiologies such as Rotavirus, Adenovirus, Diarrhoeagenic Escherichia coli (EPEC, EHEC, STEC, O157, O111), Shigella spp., Salmonella spp., Vibrio cholera, Cryptosporidium spp., and Giardia spp. The overall results from our study showed that 57% of children below 5 years of age with acute diarrhea were positive for at least one infectious etiology. Diarrhoeagenic Escherichia coli was detected to be the major etiological agent (29.09%) followed by Rotavirus (24.24%), Shigella (21.21%), Adenovirus (5.45%), Cryptosporidium (2.42%), and Giardia (0.60%). Among the different DEC strains, EPEC was detected significantly higher in <2 years children in comparison to >2 years age group (p =0.001). Concurrent infections with two or more pathogens were observed in 47 of 160 (28.48%) cases with a predominant incidence particularly in <2-year-old children (66.66%) compared to children of 2 to 5 years age group. Co-infection of Rotavirus with Shigella was the most frequent combination, which was detected in 17.94% cases, followed by Rotavirus with EPEC (15.38%) and Shigella with STEC (12.82%). Detection of multiple infectious etiologies and diagnosis of the right causative agent(s) can immensely help in better management of acute childhood diarrhea. In future more studies focusing on the detection of cases with concurrent infections must be carried out, as we believe that the etiological agents might be complementing each other’s strategies of pathogenesis resulting in severe diarrhea.

Keywords: children, co-infection, infectious diarrhea, Odisha

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1179 Investigating the Characteristics of Multi-Plastic Composites Prepared from a Mixture of Silk Fibers and Recycled Polycarbonate

Authors: Razieh Shamsi, Mehdi Faezipour, Ali Abdolkhani

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In this research, the characteristics of composites prepared from waste silk fibers and recycled polycarbonate polymer (used compacted boards) at four levels of 0, 10, 20, and 30% (silk fibers) and using 2% N- 2-Aminoethyl-3-Aminopropyltrimethoxysilane was investigated as a coupling agent and melt process method. Silk fibers (carpet weaving waste) with dimensions of 8-18 mm were prepared, and recycled polymer with 9 mesh grading was ground. Production boards in 3 thicknesses, 3 mm (tensile test samples), 5 mm (bending test samples, water absorption, and thickness shrinkage), 7 mm (impact resistance test samples) ) with a specific weight of 1 gram per cubic centimeter, hot pressing time and temperature of 12 minutes and 190 degrees Celsius with a pressure of 130 bar, cold pressing time of 6 minutes with a pressure of 50 bar and using the coupling agent N- (2- Aminoethyl)-3-aminopropyltrimethoxysilane was prepared in a constant amount of 2% of the dry weight of the filler. The results showed that, in general, by adding silk fibers to the base polymer, compared to the control samples (pure recycled polycarbonate polymer) and also by increasing the amount of silk fibers, almost all the resistances increased. The amount of water absorption of the constructed composite increased with the increase in the amount of silk fibers, and the thickness absorption was equal to 0% even after 72 hours of immersion in water. The thermal resistance of the pure recycled polymer was higher than the prepared composites, and by adding silk fibers to the base polymer and also by increasing the amount of silk fibers from 10 to 30%, the thermal resistance of the composites decreased.

Keywords: wood composite, recycled polycarbonate, silk fibers, polymer

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1178 Catalytic Synthesis and Characterization of N-(4-(Tert-Butyl) Benzyl)-1-(4-Tert-Butyl) Phenyl)-N-Methyl Methanaminium Chloride from Tert-Butyl Benzyl Derivatives

Authors: Muhammad A. Muhammad

Abstract:

Butenafine (N-4-tert-butyl benzyl-N-methyl-1-naphthylene methylamine hydrochloride) is a benzylamine antimycotic (antifungal) agent that has a broad spectrum of action. The quest for improved antimycotic action brought about many research on the structure-activity properties of butenafine in relation to other antifungal agents. Of all those research, only little or no effort was recorded on the substituents attached to the aromatic systems in butenafine. In this research, N-(4-(tert-butyl) benzyl)-1-(4-tert-butyl) phenyl)-N-methyl methanaminium chloride, which is a butenafine analogue was synthesised from tert-butyl benzyl derivatives, by reductive amination using various solvents through a direct approach, where 1,2-dichloroethane gave the best solvent action at 40 °C (Yield: 75%) and of all the reducing agents used, sodium borohydride was found to give the best reducing action in the presence of silica chloride at room temperature (Yield: 50%). Characterization of the compound by 1H NMR showed a singlet peak of 18 hydrogen atoms with a chemical shift at 1.3-1.5 ppm for the presence of 6 methyl groups in the two tert-butyl substituents, the 13C NMR also indicated the presence of the two tert-butyl substituents by the peak with a chemical shift at 31-32 ppm for the six methyl carbon atoms, the IR indicated the presence of a tertiary ammonium ion by a strong band at 2460 cm-1 and finally the EIS-MS confirmed the molar mass of the compound by a mass to charge ratio of 324.2693. These results suggested that the target molecule was actually synthesised and therefore, 1,2-dichloroethane is a good solvent for this synthesis, and the most suitable reducing agent is sodium borohydride.

Keywords: antimicrobial agents, antimycotic agents, butenafine, chemotherapeutic agents, semisynthetic agents

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1177 High Performance Computing Enhancement of Agent-Based Economic Models

Authors: Amit Gill, Lalith Wijerathne, Sebastian Poledna

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This research presents the details of the implementation of high performance computing (HPC) extension of agent-based economic models (ABEMs) to simulate hundreds of millions of heterogeneous agents. ABEMs offer an alternative approach to study the economy as a dynamic system of interacting heterogeneous agents, and are gaining popularity as an alternative to standard economic models. Over the last decade, ABEMs have been increasingly applied to study various problems related to monetary policy, bank regulations, etc. When it comes to predicting the effects of local economic disruptions, like major disasters, changes in policies, exogenous shocks, etc., on the economy of the country or the region, it is pertinent to study how the disruptions cascade through every single economic entity affecting its decisions and interactions, and eventually affect the economic macro parameters. However, such simulations with hundreds of millions of agents are hindered by the lack of HPC enhanced ABEMs. In order to address this, a scalable Distributed Memory Parallel (DMP) implementation of ABEMs has been developed using message passing interface (MPI). A balanced distribution of computational load among MPI-processes (i.e. CPU cores) of computer clusters while taking all the interactions among agents into account is a major challenge for scalable DMP implementations. Economic agents interact on several random graphs, some of which are centralized (e.g. credit networks, etc.) whereas others are dense with random links (e.g. consumption markets, etc.). The agents are partitioned into mutually-exclusive subsets based on a representative employer-employee interaction graph, while the remaining graphs are made available at a minimum communication cost. To minimize the number of communications among MPI processes, real-life solutions like the introduction of recruitment agencies, sales outlets, local banks, and local branches of government in each MPI-process, are adopted. Efficient communication among MPI-processes is achieved by combining MPI derived data types with the new features of the latest MPI functions. Most of the communications are overlapped with computations, thereby significantly reducing the communication overhead. The current implementation is capable of simulating a small open economy. As an example, a single time step of a 1:1 scale model of Austria (i.e. about 9 million inhabitants and 600,000 businesses) can be simulated in 15 seconds. The implementation is further being enhanced to simulate 1:1 model of Euro-zone (i.e. 322 million agents).

Keywords: agent-based economic model, high performance computing, MPI-communication, MPI-process

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1176 Quartz Crystal Microbalance Based Hydrophobic Nanosensor for Lysozyme Detection

Authors: F. Yılmaz, Y. Saylan, A. Derazshamshir, S. Atay, A. Denizli

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Quartz crystal microbalance (QCM), high-resolution mass-sensing technique, measures changes in mass on oscillating quartz crystal surface by measuring changes in oscillation frequency of crystal in real time. Protein adsorption techniques via hydrophobic interaction between protein and solid support, called hydrophobic interaction chromatography (HIC), can be favorable in many cases. Some nanoparticles can be effectively applied for HIC. HIC takes advantage of the hydrophobicity of proteins by promoting its separation on the basis of hydrophobic interactions between immobilized hydrophobic ligands and nonpolar regions on the surface of the proteins. Lysozyme is found in a variety of vertebrate cells and secretions, such as spleen, milk, tears, and egg white. Its common applications are as a cell-disrupting agent for extraction of bacterial intracellular products, as an antibacterial agent in ophthalmologic preparations, as a food additive in milk products and as a drug for treatment of ulcers and infections. Lysozyme has also been used in cancer chemotherapy. The aim of this study is the synthesis of hydrophobic nanoparticles for Lysozyme detection. For this purpose, methacryoyl-L-phenylalanine was chosen as a hydrophobic matrix. The hydrophobic nanoparticles were synthesized by micro-emulsion polymerization method. Then, hydrophobic QCM nanosensor was characterized by Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, atomic force microscopy (AFM) and zeta size analysis. Hydrophobic QCM nanosensor was tested for real-time detection of Lysozyme from aqueous solution. The kinetic and affinity studies were determined by using Lysozyme solutions with different concentrations. The responses related to a mass (Δm) and frequency (Δf) shifts were used to evaluate adsorption properties.

Keywords: nanosensor, HIC, lysozyme, QCM

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1175 Agency Beyond Metaphysics of Subjectivity

Authors: Erik Kuravsky

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One of the problems with a post-structuralist account of agency is that it appears to reject the freedom of an acting subject, thus seeming to deny the very phenomenon of agency. However, this is only a problem if we think that human beings can be agents exclusively in terms of being subjects, that is, if we think agency subjectively. Indeed, we tend to understand traditional theories of human freedom (e.g., Plato’s or Kant’s) in terms of a peculiar ability of the subject. The paper suggests to de-subjectivize agency with the help of Heidegger’s later thought. To do it, ir argues that classical theories of agency may indeed be interpreted as subject-oriented (sometimes even by their authors), but do not have to be read as such. Namely, the claim is that what makes agency what it is, what is essential in agency, is not its belonginess to a subject, but its ontological configuration. We may say that agency “happens,” and that there is a very specific ontological characteristics to this happening. The argument of the paper is that we can find these characteristic in the classical accounts of agency and that these characteristics are sufficient to distinguish human freedom from other natural phenomena. In particular, it offers to think agency not as one of human characteristics, but as an ontological event in which human beings take part. Namely, agency is a (non-human) characteristic of the different modes in which the experienceable existence of beings is determined by Being. To be an agent then is to participate in such ontological determination. What enables this participation is the ways human beings non-thematically understand the ontological difference. For example, for Plato, one acts freely only if one is led by an idea of the good, while for Kant the imperative for free action is categorial. The agency of an agent is thus dependent on the differentiation between ideas/categories and beings met in experience – one is “free” from contingent sensibility in terms of what is different from it ontologically. In this light, modern dependence on subjectivity is evident in the fact that the ontological difference is thought as belonging to one’s thinking, consciousness etc. That is, it is taken subjectively. A non-subjective account of agency, on the other hand, requires thinking this difference as belonging to Being itself, and thinking human beings as a medium within which occurs the non-human force of ontological differentiation.

Keywords: Heidegger, freedom, agency, poststructuralism

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1174 Evaluation of Chemopreventive Activity of Medicinal Plant, Gromwell Seed against Tumor Promoting Stage

Authors: Harukuni Tokuda, Takanari Arai, Xu FengHao, Nobutaka Suzuki

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In our continuous search for anti-tumor promoting, chemopreventive active potency from natural source material, a kind of healthy tea, Gromwell seed (Coix lachryma-jobi) ext., and including compounds Monoolein and Trilinolein have been screened using the in vitro synergistic assay indicated by inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by TPA. In assay, Gromwell seed aqueous extract and hot aqueous extract exhibited the potential inhibitory effects on EBV-EA activation without strong cytotoxicity on Raji cells. In our experimental system, the inhibitory effects of both Gromwell extracts and compounds were greater than that of beta-carotene, which is known anti-tumor promoting agent and/or chemopreventive agent. These compounds were evaluated for their in vitro inhibitory effect on EBV-EA activation induced by TPA. The percentages of the inhibition of TPA-induced EBV-EA activation for these materials were 60% and 30% at concentration 100 μg. Based on the results obtained in vitro, we studied the inhibitory effect of compounds, in an in vivo two-stage carcinogenesis test of mouse skin papilloma using DMBA as an initiator and TPA as a potential promoter. The control animals showed a 100% incidence of papilloma at 20 weeks after DMBA-TPA tumor promotion, while treatment with compounds reduced the percentage of number of tumor to 60 % after 20 weeks. Results from in vitro and in vivo studies showing chemopreventive activity against TPA promoting stage and these data support the effective potency of carcinogenic stage in clinical evaluation of integrative oncology.

Keywords: gromwell seed, medicinal plant, chemoprevention, pharmaceutical medicine

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1173 Mineralized Nanoparticles as a Contrast Agent for Ultrasound and Magnetic Resonance Imaging

Authors: Jae Won Lee, Kyung Hyun Min, Hong Jae Lee, Sang Cheon Lee

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To date, imaging techniques have attracted much attention in medicine because the detection of diseases at an early stage provides greater opportunities for successful treatment. Consequently, over the past few decades, diverse imaging modalities including magnetic resonance (MR), positron emission tomography, computed tomography, and ultrasound (US) have been developed and applied widely in the field of clinical diagnosis. However, each of the above-mentioned imaging modalities possesses unique strengths and intrinsic weaknesses, which limit their abilities to provide accurate information. Therefore, multimodal imaging systems may be a solution that can provide improved diagnostic performance. Among the current medical imaging modalities, US is a widely available real-time imaging modality. It has many advantages including safety, low cost and easy access for patients. However, its low spatial resolution precludes accurate discrimination of diseased region such as cancer sites. In contrast, MR has no tissue-penetrating limit and can provide images possessing exquisite soft tissue contrast and high spatial resolution. However, it cannot offer real-time images and needs a comparatively long imaging time. The characteristics of these imaging modalities may be considered complementary, and the modalities have been frequently combined for the clinical diagnostic process. Biominerals such as calcium carbonate (CaCO3) and calcium phosphate (CaP) exhibit pH-dependent dissolution behavior. They demonstrate pH-controlled drug release due to the dissolution of minerals in acidic pH conditions. In particular, the application of this mineralization technique to a US contrast agent has been reported recently. The CaCO3 mineral reacts with acids and decomposes to generate calcium dioxide (CO2) gas in an acidic environment. These gas-generating mineralized nanoparticles generated CO2 bubbles in the acidic environment of the tumor, thereby allowing for strong echogenic US imaging of tumor tissues. On the basis of this previous work, it was hypothesized that the loading of MR contrast agents into the CaCO3 mineralized nanoparticles may be a novel strategy in designing a contrast agent for dual imaging. Herein, CaCO3 mineralized nanoparticles that were capable of generating CO2 bubbles to trigger the release of entrapped MR contrast agents in response to tumoral acidic pH were developed for the purposes of US and MR dual-modality imaging of tumors. Gd2O3 nanoparticles were selected as an MR contrast agent. A key strategy employed in this study was to prepare Gd2O3 nanoparticle-loaded mineralized nanoparticles (Gd2O3-MNPs) using block copolymer-templated CaCO3 mineralization in the presence of calcium cations (Ca2+), carbonate anions (CO32-) and positively charged Gd2O3 nanoparticles. The CaCO3 core was considered suitable because it may effectively shield Gd2O3 nanoparticles from water molecules in the blood (pH 7.4) before decomposing to generate CO2 gas, triggering the release of Gd2O3 nanoparticles in tumor tissues (pH 6.4~7.4). The kinetics of CaCO3 dissolution and CO2 generation from the Gd2O3-MNPs were examined as a function of pH and pH-dependent in vitro magnetic relaxation; additionally, the echogenic properties were estimated to demonstrate the potential of the particles for the tumor-specific US and MR imaging.

Keywords: calcium carbonate, mineralization, ultrasound imaging, magnetic resonance imaging

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1172 Regret-Regression for Multi-Armed Bandit Problem

Authors: Deyadeen Ali Alshibani

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In the literature, the multi-armed bandit problem as a statistical decision model of an agent trying to optimize his decisions while improving his information at the same time. There are several different algorithms models and their applications on this problem. In this paper, we evaluate the Regret-regression through comparing with Q-learning method. A simulation on determination of optimal treatment regime is presented in detail.

Keywords: optimal, bandit problem, optimization, dynamic programming

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1171 Simulating Human Behavior in (Un)Built Environments: Using an Actor Profiling Method

Authors: Hadas Sopher, Davide Schaumann, Yehuda E. Kalay

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This paper addresses the shortcomings of architectural computation tools in representing human behavior in built environments, prior to construction and occupancy of those environments. Evaluating whether a design fits the needs of its future users is currently done solely post construction, or is based on the knowledge and intuition of the designer. This issue is of high importance when designing complex buildings such as hospitals, where the quality of treatment as well as patient and staff satisfaction are of major concern. Existing computational pre-occupancy human behavior evaluation methods are geared mainly to test ergonomic issues, such as wheelchair accessibility, emergency egress, etc. As such, they rely on Agent Based Modeling (ABM) techniques, which emphasize the individual user. Yet we know that most human activities are social, and involve a number of actors working together, which ABM methods cannot handle. Therefore, we present an event-based model that manages the interaction between multiple Actors, Spaces, and Activities, to describe dynamically how people use spaces. This approach requires expanding the computational representation of Actors beyond their physical description, to include psychological, social, cultural, and other parameters. The model presented in this paper includes cognitive abilities and rules that describe the response of actors to their physical and social surroundings, based on the actors’ internal status. The model has been applied in a simulation of hospital wards, and showed adaptability to a wide variety of situated behaviors and interactions.

Keywords: agent based modeling, architectural design evaluation, event modeling, human behavior simulation, spatial cognition

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1170 Safety Validation of Black-Box Autonomous Systems: A Multi-Fidelity Reinforcement Learning Approach

Authors: Jared Beard, Ali Baheri

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As autonomous systems become more prominent in society, ensuring their safe application becomes increasingly important. This is clearly demonstrated with autonomous cars traveling through a crowded city or robots traversing a warehouse with heavy equipment. Human environments can be complex, having high dimensional state and action spaces. This gives rise to two problems. One being that analytic solutions may not be possible. The other is that in simulation based approaches, searching the entirety of the problem space could be computationally intractable, ruling out formal methods. To overcome this, approximate solutions may seek to find failures or estimate their likelihood of occurrence. One such approach is adaptive stress testing (AST) which uses reinforcement learning to induce failures in the system. The premise of which is that a learned model can be used to help find new failure scenarios, making better use of simulations. In spite of these failures AST fails to find particularly sparse failures and can be inclined to find similar solutions to those found previously. To help overcome this, multi-fidelity learning can be used to alleviate this overuse of information. That is, information in lower fidelity can simulations can be used to build up samples less expensively, and more effectively cover the solution space to find a broader set of failures. Recent work in multi-fidelity learning has passed information bidirectionally using “knows what it knows” (KWIK) reinforcement learners to minimize the number of samples in high fidelity simulators (thereby reducing computation time and load). The contribution of this work, then, is development of the bidirectional multi-fidelity AST framework. Such an algorithm, uses multi-fidelity KWIK learners in an adversarial context to find failure modes. Thus far, a KWIK learner has been used to train an adversary in a grid world to prevent an agent from reaching its goal; thus demonstrating the utility of KWIK learners in an AST framework. The next step is implementation of the bidirectional multi-fidelity AST framework described. Testing will be conducted in a grid world containing an agent attempting to reach a goal position and adversary tasked with intercepting the agent as demonstrated previously. Fidelities will be modified by adjusting the size of a time-step, with higher-fidelity effectively allowing for more responsive closed loop feedback. Results will compare the single KWIK AST learner with the multi-fidelity algorithm with respect to number of samples, distinct failure modes found, and relative effect of learning after a number of trials.

Keywords: multi-fidelity reinforcement learning, multi-fidelity simulation, safety validation, falsification

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1169 Study of the Protective Effects of Summer Savory against Multiple Organ Damage Induced by Lead Acetate in Rats

Authors: Bassant M. M. Ibrahim, Doha H. Abou Baker, Ahmed Abd Elghafour

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Excessive exposure to heavy metals contributes to the occurrence of deleterious health problems that affect vital organs like the brain, liver, kidneys, and heart. The use of natural products that have antioxidant capabilities may contribute to the protection of these organs. In the present study, the essential oil of summer savory (Satureja hortensis) was used to evaluate its protective effects against lead acetate induced damaging effect on rats’ vital organs, due to its high contents of carvacrol, y-terpinene, and p-cymene. Forty female Wister Albino rats were classified into five equal groups, the 1st served as normal group, the 2nd served as positive control group was given lead acetate (60 mg/kg) intra-peritoneal (IP), the third to fifth groups were treated with calcium disodium (EDTA) as chelating agent and summer savory essential oil in doses of (50 and 100mg/kg) respectively. All treatments were given IP concomitant with lead acetate for ten successive days. At the end of the experiment duration electrocardiogram (ECG), an open field test for the evaluation of psychological state, rotarod test as for the evaluation of locomotor coordination ability as well as anti-inflammatory and oxidative stress biomarkers in serum and histopathology of vital organs were performed. The investigations in this study show that the protective effect of high dose of summer savory essential oil is more than the low dose and that the essential oil of summer savory is a promising agent that can contribute to the protection of vital organs against the hazardous damaging effects of lead acetate.

Keywords: brain, heart, kidneys, lead acetate, liver, protective, summer savory

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1168 Osmotic Dehydration of Fruit Slices in Concentrated Sugar Solution

Authors: Neda Amidi Fazli, Farid Amidi Fazli

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Enriched fruits by minerals provide minerals which are needed to human body the minerals are used by body cells for daily activities. This paper indicates the result of mass transfer in fruit slices in 55% sucrose syrup in presence of calcium and phosphorus ions. Osmosis agent 55% (w/w) was prepared by solving sucrose in deionized water and adding calcium or phosphorus in 1 and 2% concentration. Dry matter, solid gain, water loss as well as weight reduction were calculated. Results showed that by increasing of calcium concentration in osmosis solution solid gain, water loss and weight reduction were increased in short experiment time in kiwi fruit but the parameters decreased in long experiment time by concentration increasing and rise of calcium concentration caused decrease of osmosis parameters in banana. In the case of phosphorus, increasing of ion concentration had adverse effect on all treatments, this may be due to different osmosis force that is created by two types of ions. The mentioned parameters decreased in all treatments by increasing of ion concentration. Highest mass transfer in kiwi fruit occurs when 1% calcium solution applied for 60 minutes, values obtained for solid gain, water loss and weight reduction were 42.60, 51.97, and 9.37 respectively. In the case of banana, when 2% phosphorus concentration was applied as osmosis agent for 60 minutes highest values for solid gain, water loss and weight reduction obtained as 21, 25.84, and 4.84 respectively.

Keywords: calcium, concentration, osmotic dehydration, phosphorus

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1167 Exploring 1,2,4-Triazine-3(2H)-One Derivatives as Anticancer Agents for Breast Cancer: A QSAR, Molecular Docking, ADMET, and Molecular Dynamics

Authors: Said Belaaouad

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This study aimed to explore the quantitative structure-activity relationship (QSAR) of 1,2,4-Triazine-3(2H)-one derivative as a potential anticancer agent against breast cancer. The electronic descriptors were obtained using the Density Functional Theory (DFT) method, and a multiple linear regression techniques was employed to construct the QSAR model. The model exhibited favorable statistical parameters, including R2=0.849, R2adj=0.656, MSE=0.056, R2test=0.710, and Q2cv=0.542, indicating its reliability. Among the descriptors analyzed, absolute electronegativity (χ), total energy (TE), number of hydrogen bond donors (NHD), water solubility (LogS), and shape coefficient (I) were identified as influential factors. Furthermore, leveraging the validated QSAR model, new derivatives of 1,2,4-Triazine-3(2H)-one were designed, and their activity and pharmacokinetic properties were estimated. Subsequently, molecular docking (MD) and molecular dynamics (MD) simulations were employed to assess the binding affinity of the designed molecules. The Tubulin colchicine binding site, which plays a crucial role in cancer treatment, was chosen as the target protein. Through the simulation trajectory spanning 100 ns, the binding affinity was calculated using the MMPBSA script. As a result, fourteen novel Tubulin-colchicine inhibitors with promising pharmacokinetic characteristics were identified. Overall, this study provides valuable insights into the QSAR of 1,2,4-Triazine-3(2H)-one derivative as potential anticancer agent, along with the design of new compounds and their assessment through molecular docking and dynamics simulations targeting the Tubulin-colchicine binding site.

Keywords: QSAR, molecular docking, ADMET, 1, 2, 4-triazin-3(2H)-ones, breast cancer, anticancer, molecular dynamic simulations, MMPBSA calculation

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1166 A Multi-Templated Fe-Ni-Cu Ion Imprinted Polymer for the Selective and Simultaneous Removal of Toxic Metallic Ions from Wastewater

Authors: Morlu Stevens, Bareki Batlokwa

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The use of treated wastewater is widely employed to compensate for the scarcity of safe and uncontaminated freshwater. However, the existence of toxic heavy metal ions in the wastewater pose a health hazard to animals and the environment, hence, the importance for an effective technique to tackle the challenge. A multi-templated ion imprinted sorbent (Fe,Ni,Cu-IIP) for the simultaneous removal of heavy metal ions from waste water was synthesised employing molecular imprinting technology (MIT) via thermal free radical bulk polymerization technique. Methacrylic acid (MAA) was employed as the functional monomer, and ethylene glycol dimethylacrylate (EGDMA) as cross-linking agent, azobisisobutyronitrile (AIBN) as the initiator, Fe, Ni, Cu ions as template ions, and 1,10-phenanthroline as the complexing agent. The template ions were exhaustively washed off the synthesized polymer by solvent extraction in several washing steps, while periodically increasing solvent (HCl) concentration from 1.0 M to 10.0 M. The physical and chemical properties of the sorbents were investigated using Fourier Transform Infrared Spectroscopy (FT-IR), X-ray Diffraction (XRD) and Atomic Force Microscopy (AFM) were employed. Optimization of operational parameters such as time, pH and sorbent dosage to evaluate the effectiveness of sorbents were investigated and found to be 15 min, 7.5 and 666.7 mg/L respectively. Selectivity of ion-imprinted polymers and competitive sorption studies between the template and similar ions were carried out and showed good selectivity towards the targeted metal ion by removing 90% - 98% of the templated ions as compared to 58% - 62% of similar ions. The sorbents were further applied for the selective removal of Fe, Ni and Cu from real wastewater samples and recoveries of 92.14 ± 0.16% - 106.09 ± 0.17% and linearities of R2 = 0.9993 - R2 = 0.9997 were achieved.

Keywords: ion imprinting, ion imprinted polymers, heavy metals, wastewater

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1165 Phase Changing Dicationic Polymeric Ionic Liquid with CO2 Capture Abilities

Authors: Swati Sundararajan, Asit B. Samui, Prashant S. Kulkarni

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Polymeric ionic liquids combine the properties of ionic liquids and polymers into a single material which has gained massive interest in the recent years. These ionic liquids offer several advantages such as high phase change enthalpy, wide temperature range, chemical and thermal stability, non-volatility and the ability to make them task-specific. Separation of CO2 is an area of critical importance due to the concerns over greenhouse gasses leading to global warming. Thermal energy storage materials, also known as phase change materials absorb latent heat during fusion process and release the absorbed energy to the surrounding environment during crystallization. These materials retain this property over a number of cycles and therefore, are useful for bridging the gap between energy requirement and use. In an effort to develop materials, which will help in minimizing the growing energy demand and environmental concerns, a series of dicationic poly(ethylene glycol) based polymeric ionic liquids were synthesized. One part of an acrylate of poly(ethylene glycol) was reacted with imidazolium quarternizing agent and the second part was reacted with triazolium quarternizing agent. These two different monomers were then copolymerized to prepare dicationic polymeric ionic liquid. These materials were characterized for solid-liquid phase transition and the enthalpy by using differential scanning calorimetry. The CO2 capture studies were performed on a fabricated setup with varying pressure range from 1-20 atm. The findings regarding the prepared materials, having potential dual applications in the fields of thermal energy storage and CO2 capture, will be discussed in the presentation.

Keywords: CO2 capture, phase change materials, polyethylene glycol, polymeric ionic liquids, thermal energy storage

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1164 The Ideology of the Jordanian Media Women’s Discourse: Lana Mamkgh as an Example

Authors: Amani Hassan Abu Atieh

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This study aims at examining the patterns of ideology reflected in the written discourse of women writers in the media of Jordan; Lana Mamkgh is taken as an example. This study critically analyzes the discursive, linguistic, and cognitive representations that she employs as an agent in the institutionalized discourse of the media. Grounded in van Dijk’s critical discourse analysis approach to Sociocognitive Discourse Studies, the present study builds a multilayer framework that encompasses van Dijk’s triangle: discourse, society, and cognition. Specifically, the study attempts to analyze, at both micro and macro levels, the underlying cognitive processes and structures, mainly ideology and discursive strategies, which are functional in the production of women’s discourse in terms of meaning, forms, and functions. Cognitive processes that social actors adopt are underlined by experience/context and semantic mental models on the one hand and social cognition on the other. This study is based on qualitative research and adopts purposive sampling, taking as an example a sample of an opinion article written by Lana Mamkgh in the Arabic Jordanian Daily, Al Rai. Taking her role as an agent in the public sphere, she stresses the National and feminist ideologies, demonstrating the use of assertive, evaluative, and expressive linguistic and rhetorical devices that appeal to the logic, ethics, and emotions of the addressee. Highlighting the agency of Jordanian writers in the media, the study sought to achieve the macro goal of dispensing political and social justice to the underprivileged. Further, the study seeks to prove that the voice of Jordanian women, viewed as underrepresented and invisible in the public arena, has come through clearly.

Keywords: critical discourse analysis, sociocognitive theory, ideology, women discourse, media

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1163 The Effect of Filter Cake Powder on Soil Stability Enhancement in Active Sand Dunes, In the Long and Short Term

Authors: Irit Rutman Halili, Tehila Zvulun, Natali Elgabsi, Revaya Cohen, Shlomo Sarig

Abstract:

Active sand dunes (ASD) may cause significant damage to field crops and livelihood, and therefore, it is necessary to find a treatment that would enhance ADS soil stability. Biological soil crusts (biocrusts) contain microorganisms on the soil surface. Metabolic polysaccharides secreted by biocrust cyanobacteria glue the soil particles into aggregates, thereby stabilizing the soil surface. Filter cake powder (FCP) is a waste by-product in the final stages of the production of sugar from sugarcane, and its disposal causes significant environmental pollution. FCP contains high concentrations of polysaccharides and has recently been shown to be soil stability enhancing agent in ASD. It has been reported that adding FCP to the ASD soil surface by dispersal significantly increases the level of penetration resistance of soil biocrust (PRSB) nine weeks after a single treatment. However, it was not known whether a similar effect could be obtained by administering the FCP in liquid form by means of spraying. It has now been found that spraying a water solution of FCP onto the ASD soil surface significantly increased the level of penetration resistance of soil biocrust (PRSB) three weeks after a single treatment. These results suggest that FCP spraying can be used as a short-term soil stability-enhancing agent for ASD, while administration by dispersal might be more efficient over the long term. Finally, an additional benefit of using FCP as a soil stabilizer, either by dispersal or by spraying, is the reduction in environmental pollution that would otherwise result from the disposal of FCP solid waste.

Keywords: active sand dunes, filter cake powder, biological soil crusts, penetration resistance of soil biocrust

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1162 Applications of Evolutionary Optimization Methods in Reinforcement Learning

Authors: Rahul Paul, Kedar Nath Das

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The paradigm of Reinforcement Learning (RL) has become prominent in training intelligent agents to make decisions in environments that are both dynamic and uncertain. The primary objective of RL is to optimize the policy of an agent in order to maximize the cumulative reward it receives throughout a given period. Nevertheless, the process of optimization presents notable difficulties as a result of the inherent trade-off between exploration and exploitation, the presence of extensive state-action spaces, and the intricate nature of the dynamics involved. Evolutionary Optimization Methods (EOMs) have garnered considerable attention as a supplementary approach to tackle these challenges, providing distinct capabilities for optimizing RL policies and value functions. The ongoing advancement of research in both RL and EOMs presents an opportunity for significant advancements in autonomous decision-making systems. The convergence of these two fields has the potential to have a transformative impact on various domains of artificial intelligence (AI) applications. This article highlights the considerable influence of EOMs in enhancing the capabilities of RL. Taking advantage of evolutionary principles enables RL algorithms to effectively traverse extensive action spaces and discover optimal solutions within intricate environments. Moreover, this paper emphasizes the practical implementations of EOMs in the field of RL, specifically in areas such as robotic control, autonomous systems, inventory problems, and multi-agent scenarios. The article highlights the utilization of EOMs in facilitating RL agents to effectively adapt, evolve, and uncover proficient strategies for complex tasks that may pose challenges for conventional RL approaches.

Keywords: machine learning, reinforcement learning, loss function, optimization techniques, evolutionary optimization methods

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1161 Molecular Epidemiology of Circulating Adenovirus Types in Acute Conjunctivitis Cases in Chandigarh, North India

Authors: Mini P. Singh, Jagat Ram, Archit Kumar, Tripti Rungta, Jasmine Khurana, Amit Gupta, R. K. Ratho

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Introduction: Human adenovirus is the most common agent involved in viral conjunctivitis. The clinical manifestations vary with different serotypes. The identification of the circulating strains followed by phylogenetic analysis can be helpful in understanding the origin and transmission of the disease. The present study aimed to carry out molecular epidemiology of the adenovirus types in the patients with conjunctivitis presenting to the eye centre of a tertiary care hospital in North India. Materials and Methods: The conjunctival swabs were collected from 23 suspected adenoviral conjunctivitis patients between April-August, 2014 and transported in viral transport media. The samples were subjected to nested PCR targeting hexon gene of human adenovirus. The band size of 956bp was eluted and 8 representative positive samples were subjected to sequencing. The sequences were analyzed by using CLUSTALX2.1 and MEGA 5.1 software. Results: The male: female ratio was found to be 3.6:1. The mean age of presenting patients was 43.95 years (+17.2). Approximately 52.1% (12/23) of patients presented with bilateral involvement while 47.8% (11/23) with unilateral involvement of the eye. Human adenovirus DNA could be detected in 65.2% (15/23) of the patients. The phylogenetic analysis revealed presence of serotype 8 in 7 patients and serotype 4 in one patient. The serotype 8 sequences showed 99-100% identity with Tunisian, Indian and Japanese strains. The adenovirus serotype 4 strains had 100% identity with strains from Tunisia, China and USA. Conclusion: Human adenovirus was found be an important etiological agent for conjunctivitis in our set up. The phylogenetic analysis showed that the predominant circulating strains in our epidemic keratoconjunctivitis were serotypes 8 and 4.

Keywords: conjunctivitis, human adenovirus, molecular epidemiology, phylogenetics

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1160 Bionaut™: A Microrobotic Drug-Device Platform for the Local Treatment of Brainstem Gliomas

Authors: Alex Kiselyov, Suehyun Cho, Darrell Harrington; Florent Cros, Olin Palmer, John Caputo, Michael Kardosh, Eran Oren, William Loudon, Michael Shpigelmacher

Abstract:

Despite the most aggressive surgical and adjuvant therapeutic strategies, treatment of both pediatric and adult brainstem tumors remains problematic. Novel strategies, including targeted biologics, immunotherapy, and specialized delivery systems such as convection-enhanced delivery (CED), have been proposed. While some of these novel treatments are entering phase I trials, the field is still in need of treatment(s) that exhibits dramatically enhanced potency with optimal therapeutic ratio. Bionaut Labs has developed a modular microrobotic platform for performing localized delivery of diverse therapeutics in vivo. Our biocompatible particles (Bionauts™) are externally propelled and visualized in real-time. Bionauts™ are specifically designed to enhance the effect of radiation therapy via anatomically precise delivery of a radiosensitizing agent, as exemplified by temozolomide (TMZ) and Avastin™ to the brainstem gliomas of diverse origin. The treatment protocol is designed to furnish a better therapeutic outcome due to the localized (vs systemic) delivery of the drug to the neoplastic lesion(s) for use as a synergistic combination of radiation and radiosensitizing agent. In addition, the procedure is minimally invasive and is expected to be appropriate for both adult and pediatric patients. Current progress, including platform optimization, selection of the lead radiosensitizer as well as in vivo safety studies of the Bionauts™ in large animals, specifically the spine and the brain of porcine and ovine models, will be discussed.

Keywords: Bionaut, brainstem, glioma, local delivery, micro-robot, radiosensitizer

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1159 Cement Bond Characteristics of Artificially Fabricated Sandstones

Authors: Ashirgul Kozhagulova, Ainash Shabdirova, Galym Tokazhanov, Minh Nguyen

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The synthetic rocks have been advantageous over the natural rocks in terms of availability and the consistent studying the impact of a particular parameter. The artificial rocks can be fabricated using variety of techniques such as mixing sand and Portland cement or gypsum, firing the mixture of sand and fine powder of borosilicate glass or by in-situ precipitation of calcite solution. In this study, sodium silicate solution has been used as the cementing agent for the quartz sand. The molded soft cylindrical sandstone samples are placed in the gas-tight pressure vessel, where the hardening of the material takes place as the chemical reaction between carbon dioxide and the silicate solution progresses. The vessel allows uniform disperse of carbon dioxide and control over the ambient gas pressure. Current paper shows how the bonding material is initially distributed in the intergranular space and the surface of the sand particles by the usage of Electron Microscopy and the Energy Dispersive Spectroscopy. During the study, the strength of the cement bond as a function of temperature is observed. The impact of cementing agent dosage on the micro and macro characteristics of the sandstone is investigated. The analysis of the cement bond at micro level helps to trace the changes to particles bonding damage after a potential yielding. Shearing behavior and compressional response have been examined resulting in the estimation of the shearing resistance and cohesion force of the sandstone. These are considered to be main input values to the mathematical prediction models of sand production from weak clastic oil reservoir formations.

Keywords: artificial sanstone, cement bond, microstructure, SEM, triaxial shearing

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1158 Spectrum and Prevalence of Candida Infection in Diabetic Foot Ulcers

Authors: Seyed Reza Aghili, Tahereh Shokohi, Lotfollah Davoodi, Zahra Kashi, Azam Moslemi, Mahdi Abastabar, Iman Haghani, Sabah Mayahi, Asoudeh A.

Abstract:

Introduction: In diabetic foot ulcers, if fungal agents such as Candida species penetrate into the cutaneous or depth of ulcer, can increase the degree of the wound and cause Candia infection and make it more difficult to heal. Material & Methods: A cross-sectional study was performed on 100 diabetic foot ulcer patients in 2020 in Sari, Iran. patient's data and wound grade were recorded in a questionnaire. Candida infection was diagnosed with direct microscopic examination and culture of samples. Colony-PCR molecular method was used for ITS region of DNA and then PCR-RFLP with Msp1 enzyme and using HWP1 specific gene to determine species of Candida agent. Results: Of 100 patients, the mean age 62.1 ± 10.8 years, 95% type 2 diabetes, 83%>10 years duration diabetes, 59% male, 66%> poor education level, 99% married, 52% rural, 95% neuropathic symptoms, 88% using antibiotics, 69%HbA1C >9%, and mean ulcer degree 2.6±1.05 were. Candida infection was seen in 13% of the deep tissue of the wound and 7% cutaneous around the wound. The predominant Candida isolated was C. parapsilosis (71.5%), C .albicans (14.3%). Fungal infections caused by mold fungi were not detected. There was a statistically significant relationship between yeast infection and gender, rural, HbA1C and ulcer degree. Conclusion: Mycological evaluations often are ignored. Candida parapsilosis is the most common infectious agent in these patients and may require specific treatment. Therefore, more attention of physicians to Candida infections particularly, early diagnosis and effective treatment can help faster recovery and prevent amputation.

Keywords: diabetic foot ulcer, candida infection, risk factors, c. parapsilosis

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1157 Widely Diversified Macroeconomies in the Super-Long Run Casts a Doubt on Path-Independent Equilibrium Growth Model

Authors: Ichiro Takahashi

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One of the major assumptions of mainstream macroeconomics is the path independence of capital stock. This paper challenges this assumption by employing an agent-based approach. The simulation results showed the existence of multiple "quasi-steady state" equilibria of the capital stock, which may cast serious doubt on the validity of the assumption. The finding would give a better understanding of many phenomena that involve hysteresis, including the causes of poverty. The "market-clearing view" has been widely shared among major schools of macroeconomics. They understand that the capital stock, the labor force, and technology, determine the "full-employment" equilibrium growth path and demand/supply shocks can move the economy away from the path only temporarily: the dichotomy between the short-run business cycles and the long-run equilibrium path. The view then implicitly assumes the long-run capital stock to be independent of how the economy has evolved. In contrast, "Old Keynesians" have recognized fluctuations in output as arising largely from fluctuations in real aggregate demand. It will then be an interesting question to ask if an agent-based macroeconomic model, which is known to have path dependence, can generate multiple full-employment equilibrium trajectories of the capital stock in the super-long run. If the answer is yes, the equilibrium level of capital stock, an important supply-side factor, would no longer be independent of the business cycle phenomenon. This paper attempts to answer the above question by using the agent-based macroeconomic model developed by Takahashi and Okada (2010). The model would serve this purpose well because it has neither population growth nor technology progress. The objective of the paper is twofold: (1) to explore the causes of long-term business cycle, and (2) to examine the super-long behaviors of the capital stock of full-employment economies. (1) The simulated behaviors of the key macroeconomic variables such as output, employment, real wages showed widely diversified macro-economies. They were often remarkably stable but exhibited both short-term and long-term fluctuations. The long-term fluctuations occur through the following two adjustments: the quantity and relative cost adjustments of capital stock. The first one is obvious and assumed by many business cycle theorists. The reduced aggregate demand lowers prices, which raises real wages, thereby decreasing the relative cost of capital stock with respect to labor. (2) The long-term business cycles/fluctuations were synthesized with the hysteresis of real wages, interest rates, and investments. In particular, a sequence of the simulation runs with a super-long simulation period generated a wide range of perfectly stable paths, many of which achieved full employment: all the macroeconomic trajectories, including capital stock, output, and employment, were perfectly horizontal over 100,000 periods. Moreover, the full-employment level of capital stock was influenced by the history of unemployment, which was itself path-dependent. Thus, an experience of severe unemployment in the past kept the real wage low, which discouraged a relatively costly investment in capital stock. Meanwhile, a history of good performance sometimes brought about a low capital stock due to a high-interest rate that was consistent with a strong investment.

Keywords: agent-based macroeconomic model, business cycle, hysteresis, stability

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1156 Analysis of Factors Influencing the Response Time of an Aspirating Gaseous Agent Concentration Detection Method

Authors: Yu Guan, Song Lu, Wei Yuan, Heping Zhang

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Gas fire extinguishing system is widely used due to its cleanliness and efficiency, and since its spray will be affected by many factors such as convection and obstacles in jetting region, so in order to evaluate its effectiveness, detecting concentration distribution in the jetting area is indispensable, which is commonly achieved by aspirating concentration detection technique. During the concentration measurement, the response time of detector is a very important parameter, especially for those fire-extinguishing systems with rapid gas dispersion. Long response time will not only underestimate its concentration but also prolong the change of concentration with time. Therefore it is necessary to analyze the factors influencing the response time. In the paper, an aspirating concentration detection method was introduced, which is achieved by using a small critical nozzle and a laminar flowmeter, and because of the response time is mainly related to the gas transport process from sampling site to the sensor, the effects of exhaust pipe size, gas flow rate, and gas concentration on its response time were analyzed. During the research, Bromotrifluoromethane (CBrF₃) was used. The effect of the sampling tube was investigated with different length of 1, 2, 3, 4 and 5 m (5mm in pipe diameter) and different pipe diameter of 3, 4, 5, 6 and 8 mm (3m in length). The effect of gas flow rate was analyzed by changing the throat diameter of the critical nozzle with 0.5, 0.682, 0.75, 0.8, 0.84 and 0.88 mm. The effect of gas concentration on response time was studied with the concentration range of 0-25%. The result showed that the response time increased with the increase of both the length and diameter of the sampling pipe, and the effect of length on response time was linear, but for the effect of diameter, it was exponential. It was also found that as the throat diameter of critical nozzle increased, the response time reduced a lot, in other words, gas flow rate has a great influence on response time. For the effect of gas concentration, the response time increased with the increase of the CBrF₃ concentration, and the slope of the curve was reduced.

Keywords: aspirating concentration detection, fire extinguishing, gaseous agent, response time

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1155 Therapeutic Challenges in Treatment of Adults Bacterial Meningitis Cases

Authors: Sadie Namani, Lindita Ajazaj, Arjeta Zogaj, Vera Berisha, Bahrije Halili, Luljeta Hasani, Ajete Aliu

Abstract:

Background: The outcome of bacterial meningitis is strongly related to the resistance of bacterial pathogens to the initial antimicrobial therapy. The objective of the study was to analyze the initial antimicrobial therapy, the resistance of meningeal pathogens and the outcome of adults bacterial meningitis cases. Materials/methods: This prospective study enrolled 46 adults older than 16 years of age, treated for bacterial meningitis during the years 2009 and 2010 at the infectious diseases clinic in Prishtinë. Patients are categorized into specific age groups: > 16-26 years of age (10 patients), > 26-60 years of age (25 patients) and > 60 years of age (11 patients). All p-values < 0.05 were considered statistically significant. Data were analyzed using Stata 7.1 and SPSS 13. Results: During the two year study period 46 patients (28 males) were treated for bacterial meningitis. 33 patients (72%) had a confirmed bacterial etiology; 13 meningococci, 11 pneumococci, 7 gram-negative bacilli (Ps. aeruginosa 2, Proteus sp. 2, Acinetobacter sp. 2 and Klebsiella sp. 1 case) and 2 staphylococci isolates were found. Neurological complications developed in 17 patients (37%) and the overall mortality rate was 13% (6 deaths). Neurological complications observed were: cerebral abscess (7/46; 15.2%), cerebral edema (4/46; 8.7%); haemiparesis (3/46; 6.5%); recurrent seizures (2/46; 4.3%), and single cases of thrombosis sinus cavernosus, facial nerve palsy and decerebration (1/46; 2.1%). The most common meningeal pathogens were meningococcus in the youngest age group, gram negative-bacilli in second age group and pneumococcus in eldery age group. Initial single-agent antibiotic therapy (ceftriaxone) was used in 17 patients (37%): in 60% of patients in the youngest age group and in 44% of cases in the second age group. 29 patients (63%) were treated with initial dual-agent antibiotic therapy; ceftriaxone in combination with vancomycin or ampicillin. Ceftriaxone and ampicillin were the most commonly used antibiotics for the initial empirical therapy in adults > 50 years of age. All adults > 60 years of age were treated with the initial dual-agent antibiotic therapy as in this age group was recorded the highest mortality rate (M=27%) and adverse outcome (64%). Resistance of pathogens to antimicrobics was recorded in cases caused by gram-negative bacilli and was associated with greater risk for developing neurological complications (p=0.09). None of the gram-negative bacilli were resistant to carbapenems; all were resistant to ampicillin while 5/7 isolates were resistant to cefalosporins. Resistance of meningococci and pneumococci to beta-lactams was not recorded. There were no statistical differences in the occurrence of neurological complications (p > 0.05), resistance of meningeal pathogens to antimicrobics (p > 0.05) and the inital antimicrobial therapy (one vs. two antibiotics) concerning group-ages in adults. Conclusions: The initial antibiotic therapy with ceftriaxone alone or in combination with vancomycin or ampicillin did not cover cases caused by gram-negative bacilli.

Keywords: adults, bacterial meningitis, outcomes, therapy

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1154 The Optimization of Topical Antineoplastic Therapy Using Controlled Release Systems Based on Amino-functionalized Mesoporous Silica

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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1153 Effect of Modification and Expansion on Emergence of Cooperation in Demographic Multi-Level Donor-Recipient Game

Authors: Tsuneyuki Namekata, Yoko Namekata

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It is known that the mean investment evolves from a very low initial value to some high level in the Continuous Prisoner's Dilemma. We examine how the cooperation level evolves from a low initial level to a high level in our Demographic Multi-level Donor-Recipient situation. In the Multi-level Donor-Recipient game, one player is selected as a Donor and the other as a Recipient randomly. The Donor has multiple cooperative moves and one defective move. A cooperative move means the Donor pays some cost for the Recipient to receive some benefit. The more cooperative move the Donor takes, the higher cost the Donor pays and the higher benefit the Recipient receives. The defective move has no effect on them. Two consecutive Multi-level Donor-Recipient games, one as a Donor and the other as a Recipient, can be viewed as a discrete version of the Continuous Prisoner's Dilemma. In the Demographic Multi-level Donor-Recipient game, players are initially distributed spatially. In each period, players play multiple Multi-level Donor-Recipient games against other players. He leaves offspring if possible and dies because of negative accumulated payoff of him or his lifespan. Cooperative moves are necessary for the survival of the whole population. There is only a low level of cooperative move besides the defective move initially available in strategies of players. A player may modify and expand his strategy by his recent experiences or practices. We distinguish several types of a player about modification and expansion. We show, by Agent-Based Simulation, that introducing only the modification increases the emergence rate of cooperation and introducing both the modification and the expansion further increases it and a high level of cooperation does emerge in our Demographic Multi-level Donor-Recipient Game.

Keywords: agent-based simulation, donor-recipient game, emergence of cooperation, spatial structure, TFT, TF2T

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1152 The Effect of the Combination of Methotrexate Nanoparticles and TiO2 on Breast Cancer

Authors: Nusaiba Al-Nemrawi, Belal Al-Husein

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Methotrexate (MTX) is a stoichiometric inhibitor of dihydrofolate reductase, which is essential for DNA synthesis. MTX is a chemotherapeutic agent used for treating many types of cancer cells. However, cells’ resistant to MTX is very common and its pharmacokinetic behavior is highly problematic. of MTX within tumor cells, we propose encapsulation of antitumor drugs in nanoparticulated systems. Chitosan (CS) is a naturally occurring polymer that is biocompatibe, biodegradable, non-toxic, cationic and bioadhesive. CS nanoparticles (CS-NPs) have been used as drug carrier for targeted delivery. Titanium dioxide (TiO2), a natural mineral oxide, which is used in biomaterials due to its high stability and antimicrobial and anticorrosive properties. TiO2 showed a potential as a tumor suppressor. In this study a new formulation of MTX loaded in CS NPs (CS-MTX NPs) and coated with Titanium oxide (TiO2) was prepared. The mean particle size, zeta potential, polydispersity index were measured. The interaction between CS NPs and TiO2 NPs was confirmed using FTIR and XRD. CS-MTX NPs was studied in vitro using the tumor cell line MCF-7 (human breast cancer). The results showed that CS-MTX has a size around 169 nm and as they were coated with TiO2, the size ranged between and depending on the ratio of CS-MTX to TiO2 ratio used in the preparation. All NPs (uncoated and coated carried positive charges and were monodispersed. The entrapment efficacy was around 65%. Both FTIR and XRD proved that TiO2 interacted with CS-MTX NPs. The drug invitro release was controlled and sustained over days. Finally, the studied in vitro using the tumor cell line MCF-7 suggested that combining nanomaterials with anticancer drugs CS-MTX NPs may be more effective than free MTX for cancer treatment. In conclusion, the combination of CS-MTX NPs and TiO2 NPs showed excellent time-dependent in vitro antitumor behavior, therefore, can be employed as a promising anticancer agent to attain efficient results towards MCF-7 cells.

Keywords: Methotrexate, Titanium dioxide, Chitosan nanoparticles, cancer

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1151 Egyptian Soil Isolate Shows Promise as a Source of a New Broad-spectrum Antimicrobial Agent Against Multidrug-resistant Pathogens

Authors: Norhan H. Mahdally, Bathini Thissera Riham A. ElShiekh, Noha M. Elhosseiny, Mona T. Kashef, Ali M. El Halawany, Mostafa E. Rateb, Ahmed S. Attia

Abstract:

Multidrug-resistant (MDR) pathogens pose a global threat to healthcare settings. The exhaustion of the current antibiotic arsenal and the scarcity of new antimicrobials in the pipeline aggravate this threat and necessitate a prompt and effective response. This study focused on two major pathogens that can cause serious infections: carbapenem-resistant Acinetobacter baumannii (CRAB) and methicillin-resistant Staphylococcus aureus (MRSA). Multiple soil isolates were collected from several locations throughout Egypt and screened for their conventional and non-conventional antimicrobial activities against MDR pathogens. One isolate exhibited potent antimicrobial activity and was subjected to multiple rounds of fractionation. After fermentation and bio-guided fractionation, we identified pure microbial secondary metabolites with two scaffolds that exhibited promising effects against CRAB and MRSA. Scaling up and chemical synthesis of derivatives of the identified metabolite resulted in obtaining a more potent derivative, which we designated as 2HP. Cytotoxicity studies indicated that 2HP is well-tolerated by human cells. Ongoing work is focusing on formulating the new compound into a nano-formulation to enhance its delivery. Also, to have a better idea about how this compound works, a proteomic approach is currently underway. Our findings suggest that 2HP is a potential new broad-spectrum antimicrobial agent. Further studies are needed to confirm these findings and to develop 2HP into a safe and effective treatment for MDR infections.

Keywords: broad-spectrum antimicrobials, carbapenem-resistant acinetobacter baumannii, drug discovery, methicillin-resistant staphylococcus aureus, multidrug-resistant, natural products

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