Search results for: drug target

Authors: Mehdi Jalalpour, Mazdak Tootkaboni

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We present a computationally efficient method for reliability-based topology optimization under material properties uncertainty, which is assumed to be lognormally distributed and correlated within the domain. Computational efficiency is achieved through estimating the response statistics with stochastic perturbation of second order, using these statistics to fit an appropriate distribution that follows the empirical distribution of the response, and employing an efficient gradient-based optimizer. The proposed algorithm is utilized for design of new structures and the changes in the optimized topology is discussed for various levels of target reliability and correlation strength. Predictions were verified thorough comparison with results obtained using Monte Carlo simulation.

Keywords: material uncertainty, stochastic perturbation, structural reliability, topology optimization

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Authors: Joao Ferreira Do Rosario, Nuno Gustavo, Ana Machado, Lurdes Calisto, Luisa Carvalho, Georgette Andraz

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Currently, tourism small and medium enterprises (TSMEs) face serious economic and financial problems, making recovery efforts difficult. How the pandemic will affect tourists' behavior is still to be known. Will tourists be even more cautious regarding their choices or, on the contrary, will they be more adventurers with an enormous desire to travel in search of the lost freedom? Tourists may become even more demanding when traveling, more austere, or less concerned and eager to socialize. Adjusting to this "new tourist" is an added challenge for tourism service providers. Generation Z made up of individuals born in 1995 and following years, currently tends to assume a particular role and meaning in the present and future economic and social context, considering that we are facing the youngest workforce as well as tomorrow's consumers. This generation is distinguished from others as it is the first generation to combine a high level of education and technological knowledge and to fully experience the digital world. These young people are framed by a new value system that can explain new behaviours and consumption, namely, in the context of tourism. All these considerations point to the importance of investigating this target group as it is essential to understand how these individuals perceive, understand, act, and can be involved in a new environment built around a society regulated by new priorities and challenges of a sustainable nature. This leads not only to a focus on short-term market choices but mainly to predict future choices from a longer-term perspective. Together with the social background of a person, values are considered a stable antecedent of behavior and might therefore predict not just immediate, but also future choices. Furthermore, the meaning attributed to travel has a general connotation and goes beyond a specific travel choice or experience. In other words, values and travel's meaning form a chain of influences on the present and future travel behavior. This study explores the social background and values of Generation Z travelers vs the meaning these tourists give to travel. The aim is to discover in their present behavior cues to predict travel choices so that the future of tourism can be secured. This study also provides data for predicting the tourism choices of youngsters in the more immediate future. Methodologically, a quantitative approach was adopted based on the collection of data through a survey. Since academic research on Generation Z of tourists is still scarce, it is expected to contribute to deepening scientific knowledge in this area. Furthermore, it is expected that this research will support tourism professionals in defining differentiated marketing strategies and adapted to the requirements of this target, in a new time.

Keywords: Generation Z, travel behavior, travel meaning, Generation Z Values

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Authors: Mikhail S. Zastrozhin, Valery V. Smirnov, Dmitry A. Sychev, Ludmila M. Savchenko, Evgeny A. Bryun, Mark O. Nechaev

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Cytochrome P-450 isoenzyme 3A4 takes part in the biotransformation of medical drugs. The activity of CYP isoenzymes depends on genetic (polymorphisms of genes which encoded it) and phenotypic factors (a kind of food, a concomitant drug therapy). The aim of the study was to evaluate a carbamazepine effect on the CYP3A4 activity in patients with alcohol addiction. The study included 25 men with alcohol dependence, who received haloperidol during the exacerbation of the addiction. CYP3A4 activity was assessed by urinary 6-beta-hydroxycortisol/cortisol ratios measured by high performance liquid chromatography with mass spectrometry. The study modeled a graph and an equation of the logarithmic regression, that reflects the dependence of CYP3A4 activity on a dose of carbamazepine: y = 5,5 * 9,1 * 10-5 * x2. The study statistically significant demonstrates the effect of carbamazepine on CYP2D6 isozyme activity in patients with alcohol addiction.

Keywords: CYP3A4, biotransformation, carbamazepine, alcohol abuse

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Authors: Temesgen Geremew

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Functionalized nanoparticles have emerged as a revolutionary class of materials with immense potential in various biomedical applications. These engineered nanoparticles possess unique properties tailored to interact with biological systems, offering unprecedented opportunities in drug delivery, imaging, diagnostics, and therapy. This research delves into the design, synthesis, and characterization of functionalized nanoparticles for targeted biomedical applications. The primary focus lies on developing nanoparticles with precisely controlled size, surface chemistry, and biocompatibility for specific medical purposes. The research will also explore the crucial interaction of these nanoparticles with biological systems, encompassing cellular uptake, biodistribution, and potential toxicity evaluation. The successful development of functionalized nanoparticles holds the promise to revolutionize various aspects of healthcare. This research aspires to contribute significantly to this advancement by providing valuable insights into the design and application of these versatile materials within the ever-evolving field of biomedicine.

Keywords: nanoparticles, biomedicals, cancer, biocompatibility

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Authors: Tuji Jemal Ahmed

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Food quality and safety challenges are prevalent in Ethiopia's food processing industry, which can have adverse effects on consumers' health and wellbeing. The country is known for its diverse range of agricultural products, which are essential to its economy. However, poor food quality and safety policies and management systems in the food processing industry have led to several health problems, foodborne illnesses, and economic losses. This paper aims to highlight the causes and effects of food safety and quality issues in the food processing industry of Ethiopia and discuss potential solutions to address these issues. One of the main causes of poor food quality and safety in Ethiopia's food processing industry is the lack of adequate regulations and enforcement mechanisms. The absence of comprehensive food safety and quality policies and guidelines has led to substandard practices in the food manufacturing process. Moreover, the lack of monitoring and enforcement of existing regulations has created a conducive environment for unscrupulous businesses to engage in unsafe practices that endanger the public's health. The effects of poor food quality and safety are significant, ranging from the loss of human lives, increased healthcare costs, and loss of consumer confidence in the food processing industry. Foodborne illnesses, such as diarrhea, typhoid fever, and cholera, are prevalent in Ethiopia, and poor food quality and safety practices contribute significantly to their prevalence. Additionally, food recalls due to contamination or mislabeling often result in significant economic losses for businesses in the food processing industry. To address these challenges, the Ethiopian government has begun to take steps to improve food quality and safety in the food processing industry. One of the most notable initiatives is the Ethiopian Food and Drug Administration (EFDA), which was established in 2010 to regulate and monitor the quality and safety of food and drug products in the country. The EFDA has implemented several measures to enhance food safety, such as conducting routine inspections, monitoring the importation of food products, and enforcing strict labeling requirements. Another potential solution to improve food quality and safety in Ethiopia's food processing industry is the implementation of food safety management systems (FSMS). An FSMS is a set of procedures and policies designed to identify, assess, and control food safety hazards throughout the food manufacturing process. Implementing an FSMS can help businesses in the food processing industry identify and address potential hazards before they cause harm to consumers. Additionally, the implementation of an FSMS can help businesses comply with existing food safety regulations and guidelines. In conclusion, improving food quality and safety policies and management systems in Ethiopia's food processing industry is critical to protecting public health and enhancing the country's economy. Addressing the root causes of poor food quality and safety and implementing effective solutions, such as the establishment of regulatory agencies and the implementation of food safety management systems, can help to improve the overall safety and quality of the country's food supply.

Keywords: food quality, food safety, policy, management system, food processing industry

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Authors: Anatoly D. Pluzhnikov, Elena N. Pribludova, Alexander G. Ryndyk

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In conjunction with the problem of the target selection on a clutter background, the analysis of the scanning rate influence on the spatial-temporal signal structure, the generalized multivariate correlation function and the quality of the resolution with the increase pulse repetition frequency is made. The possibility of the object space-distance resolution, which is conditioned by the range-to-angle conversion with an increased scanning rate, is substantiated. The calculations for the real cylindrical array at high scanning rate are presented. The high scanning rate let to get the signal to noise improvement of the order of 10 dB for the space-time signal processing.

Keywords: antenna pattern, array, signal processing, spatial resolution

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Authors: Kanogkan Leerojanaprapa

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Textile and garment industry is used to a major exporting industry of Thailand. According to lacking of the nation's price-competitiveness by stopping the EU's GSP (Generalised Scheme of Preferences) and ‘Nationwide Minimum Wage Policy’ that Thailand’s employers must pay all employees at least 300 baht (about $10) a day, the supply chains of the Thai textile and garment industry is affected and need to be reformed. Therefore, either Thai textile or garment industry will be existed or not would be concerned. This is also challenged for the government to decide which industries should be promoted the future industries of Thailand. Recently Thai government launch The Cluster-based Special Economic Development Zones Policy for promoting business cluster (effect on September 16, 2015). They define a cluster as the concentration of interconnected businesses and related institutions that operate within the same geographic areas and textiles and garment is one of target industrial clusters and 9 provinces are targeted (Bangkok, Kanchanaburi, Nakhon Pathom, Ratchaburi, Samut Sakhon, Chonburi, Chachoengsao, Prachinburi, and Sa Kaeo). The cluster zone are defined to link west-east corridor connected to manufacturing source in Cambodia and Mynmar to Bangkok where are promoted to be design, sourcing, and trading hub. The Thai government will provide tax and non-tax incentives for targeted industries within the clusters and expects these businesses are scattered to where they can get the most benefit which will identify future industrial cluster. This research will show the difference between the current cluster and future cluster following the target provinces of the textile and garment. The current cluster is analysed from secondary data. The four characteristics of the numbers of plants in Spinning, weaving and finishing of textiles, Manufacture of made-up textile articles, except apparel, Manufacture of knitted and crocheted fabrics, and Manufacture of other textiles, not elsewhere classified in particular 77 provinces (in total) are clustered by K-means cluster analysis and Hierarchical Cluster Analysis. In addition, the cluster can be confirmed and showed which variables contribute the most to defined cluster solution with ANOVA test. The results of analysis can identify 22 provinces (which the textile or garment plants are located) into 3 clusters. Plants in cluster 1 tend to be large numbers of plants which is only Bangkok, Next plants in cluster 2 tend to be moderate numbers of plants which are Samut Prakan, Samut Sakhon and Nakhon Pathom. Finally plants in cluster 3 tend to be little numbers of plants which are other 18 provinces. The same methodology can be implemented in other industries for future study.

Keywords: ANOVA, hierarchical cluster analysis, industrial clusters, K -means cluster analysis, textile and garment industry

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Authors: Marianne Miguet, Gaël Plantard, Yves Jaeger, Vincent Goetz

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The contamination of groundwater is a major concern. A common pollutant, the perchloroethylene, is the target contaminant. Water treatment process as Granular Activated Carbons are very efficient but requires pilot-scale testing to determine the full-scale GAC performance. First, the batch mode was used to get a reliable experimental method to estimate the adsorption capacity of a common volatile compound is settled. The Langmuir model is acceptable to fit the isotherms. Dynamic tests were performed with three columns and different operating conditions. A database of concentration profiles and breakthroughs were obtained. The resolution of the set of differential equations is acceptable to fit the dynamics tests and could be used for a full-scale adsorber.

Keywords: activated carbon, groundwater, perchloroethylene, full-scale

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Authors: Isa Moazen, Ali Nahvi

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Driver drowsiness is a major cause of vehicle accidents, and facial images are highly valuable to detect drowsiness. In this paper, we perform our research via a thermal camera to record drivers' facial images on a driving simulator. A robust real-time algorithm extracts the features using horizontal and vertical integration projection, contours, contour orientations, and cropping tools. The features are included four target areas on the cheeks and forehead. Qt compiler and OpenCV are used with two cameras with different resolutions. A high-resolution thermal camera is used for fifteen subjects, and a low-resolution one is used for a person. The results are investigated by four temperature plots and evaluated by observer rating of drowsiness.

Keywords: advanced driver assistance systems, thermal imaging, driver drowsiness detection, feature extraction

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Authors: Adrian Florin Busu

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The communicative approach, or communicative language teaching, used for enhancing communicative skills in students in automatics is a modern teaching approach based on the concept of learning a language through having to communicate real meaning. In the communicative approach, real communication is both the objective of learning and the means through which it takes place. This approach was initiated during the 1970’s and quickly became prominent, as it proposed an alternative to the previous systems-oriented approaches. In other words, instead of focusing on the acquisition of grammar and vocabulary, the communicative approach aims at developing students’ competence to communicate in the target language with an enhanced focus on real-life situations. To put it in an nutshell, CLT considers using the language to be just as important as actually learning the language.

Keywords: communication, approach, objective, learning

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Authors: Mazhar Hamayun

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Organizations need to take a holistic approach to their Zero Trust strategic and tactical security needs. This includes using a framework-agnostic model that will ensure all enterprise resources are being accessed securely, regardless of their location. Such can be achieved through the implementation of a security posture, monitoring the posture, and adjusting the posture through the Identify, Detect, Protect, Respond, and Recover Methods, The target audience of this document includes those involved in the management and operational functions of risk, information security, and information technology. This audience consists of the chief information security officer, chief information officer, chief technology officer, and those leading digital transformation initiatives where Zero Trust methods can help protect an organization’s data assets.

Keywords: ZTNA, zerotrust architecture, microsegmentation, NIST SP 800-207

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Authors: R. D. Esposito, P. Dorado Rodriguez, D. Planes Meseguer

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In this work, we compare the contour of Internal Target Volume (ITV), for Stereotactic Body Radiation Therapy (SBRT) of a patient affected by a single liver metastasis, obtained from two different patient data acquisition techniques. The first technique consists in a free breathing Computer Tomography (CT) scan acquisition, followed by exhalation breath-hold and inhalation breath-hold CT scans, all of them applying abdominal compression while the second technique consists in a free breathing 4D CT-PET (Positron Emission Tomography) scan. Results obtained with these two methods are consistent, which demonstrate that at least for this specific case, both techniques are adequate for ITV contouring in SBRT treatments.

Keywords: 4D CT-PET, abdominal compression, ITV, SBRT

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Authors: Luphumlo Ncanywa, Paul Watts

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Malaria is a disease that kills approximately one million people annually. Children and pregnant women in sub-Saharan Africa lost their lives due to malaria. Malaria continues to be one of the major causes of death, especially in poor countries in Africa. Decrease the burden of malaria and save lives is very essential. There is a major concern about malaria parasites being able to develop resistance towards antimalarial drugs. People are still dying due to lack of medicine affordability in less well-off countries in the world. If more people could receive treatment by reducing the cost of drugs, the number of deaths in Africa could be massively reduced. There is a shortage of pharmaceutical manufacturing capability within many of the countries in Africa. However one has to question how Africa would actually manufacture drugs, active pharmaceutical ingredients or medicines developed within these research programs. It is quite likely that such manufacturing would be outsourced overseas, hence increasing the cost of production and potentially limiting the full benefit of the original research. As a result the last few years has seen major interest in developing more effective and cheaper technology for manufacturing generic pharmaceutical products. Micro-reactor technology (MRT) is an emerging technique that enables those working in research and development to rapidly screen reactions utilizing continuous flow, leading to the identification of reaction conditions that are suitable for usage at a production level. This emerging technique will be used to develop antimalarial drugs. It is this system flexibility that has the potential to reduce both the time was taken and risk associated with transferring reaction methodology from research to production. Using an approach referred to as scale-out or numbering up, a reaction is first optimized within the laboratory using a single micro-reactor, and in order to increase production volume, the number of reactors employed is simply increased. The overall aim of this research project is to develop and optimize synthetic process of antimalarial drugs in the continuous processing. This will provide a step change in pharmaceutical manufacturing technology that will increase the availability and affordability of antimalarial drugs on a worldwide scale, with a particular emphasis on Africa in the first instance. The research will determine the best chemistry and technology to define the lowest cost manufacturing route to pharmaceutical products. We are currently developing a method to synthesize Lumefantrine in continuous flow using batch process as bench mark. Lumefantrine is a dichlorobenzylidine derivative effective for the treatment of various types of malaria. Lumefantrine is an antimalarial drug used with artemether for the treatment of uncomplicated malaria. The results obtained when synthesizing Lumefantrine in a batch process are transferred into a continuous flow process in order to develop an even better and reproducible process. Therefore, development of an appropriate synthetic route for Lumefantrine is significant in pharmaceutical industry. Consequently, if better (and cheaper) manufacturing routes to antimalarial drugs could be developed and implemented where needed, it is far more likely to enable antimalarial drugs to be available to those in need.

Keywords: antimalarial, flow, lumefantrine, synthesis

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Authors: Sarah Atalla, Shubham Gupta, Kim Alipio, Tanya Maric

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Background: Chelsea and Westminster Hospital have introduced the Birmingham Symptom Specific Obstetric Triage System (BSOTS) for patients who present acutely to the Maternity Assessment Suite (MAS) to prioritise care by urgency. The primary objective was to evaluate whether BSOTS was used appropriately to assess patients (defined as a 90% threshold). The secondary objective was to assess whether patients were seen within their designated triaged timeframe (defined as a 90% threshold). Methodology: MAS records were retrospectively reviewed for a randomly selected one-week period of data from 2020 (21/09/2020 - 27/09/2020). 189 patients presented to MAS during this time. Data were collected on the presenting complaint, time of attendance (divided into four time categories), and triage colour code for the urgency of a review by a doctor (red: immediately, orange: within 15 minutes, yellow: within 1 hour, green: within 4 hours). The number of triage waiting times that were breached and the outcome of the attendance was noted. Results: 49% of patients presenting to MAS during this time period were triaged, which therefore did not meet the 90% target. 67% of patients who were triaged were seen within their allocated timeframe as designated by their triage colour code, which therefore did not meet the 90% target. The most frequent reason for patient attendance was reduced fetal movements (30.5% of attendances). The busiest time of day (when most patients presented) was between 06:01-12:00, and this was also when the highest number of patients were not triaged (26 patients or 54% of patients presenting in this time category). The most used triage category (59%) was the green colour code (to be seen by a doctor within 4 hours), followed by orange (24%), yellow (14%), and red (3%). 45% of triaged patients were admitted, whilst 55% were discharged. 62% of patients allocated to the green triage category were discharged, as compared to 56% of yellow category patients, 27% of orange category patients, and 50% of red category patients. The time of patient presentation to the hospital was also associated with the level of urgency and outcome. Patients presenting from 12:01 to 18:00 were more likely to be discharged (72% discharged) compared to 00:01-06:00 where only 12.5% of patients were discharged. Conclusion: The triage system for assessing the urgency of acutely presenting obstetric patients is only being effectively utilised for 49% of patients. There is potential for enhancing the employment of the triage system to enable further efficiency and boost the promotion of patient safety. It is noted that MAS was busiest at 06:01 - 12:00 when there was also the highest number of non-triaged patients – this highlights some areas where we can improve, including higher levels of staffing, better use of BSOTS to triage patients, and patient education.

Keywords: birmingham, BSOTS, maternal, obstetric, pregnancy, specific, symptom, triage

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Authors: Kirti Hira, A. Sajeli Begum, S. Mahibalan, Poorna Chandra Rao

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Introduction: Cancer is one of the leading causes of death worldwide. Although existing therapy effectively kills cancer cells, they do affect normal growing cells leading to many undesirable side effects. Hence there is need to develop effective as well as safe drug molecules to combat cancer, which is possible through phyto-research. The currently available plant-derived blockbuster drugs are the example for this. In view of this, an investigation was done to identify cytotoxic lead molecules from Hedyotis umbellata (Family Rubiaceae), a widely distributed weed in India. Materials and Methods: The methanolic extract of the whole plant of H. umbellata (MHU), prepared through Soxhlet extraction method was further fractionated with diethyl ether and n-butanol, successively. MHU, ether fraction (EMHU) and butanol fraction (BMHU) were lyophilized and were tested for the cytotoxic effect using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay against non-small cell lung cancer (NSCLC) A549 cell lines. The potentially active EMHU was subjected to chromatographic purification using normal-phase silica columns, in order to isolate the responsible bioactive compounds. The isolated pure compounds were tested for their cytotoxic effect by MTT assay against A549 cells. Compound-3, which was found to be most active, was characterized using IR, 1H- and 13C-NMR and MS analysis. The study was further extended to decipher the mechanism of action of cytotoxicity of compound-3 against A549 cells through various in vitro cellular models. Cell cycle analysis was done using flow cytometry following PI (Propidium Iodide) staining. Protein analysis was done using Western blot technique. Results: Among MHU, EMHU, and BMHU, the non-polar fraction EMHU demonstrated a significant dose-dependent cytotoxic effect with IC50 of 67.7μg/ml. Chromatography of EMHU yielded seven compounds. MTT assay of isolated compounds explored compound-3 as potentially active one, which inhibited the growth of A549 cells with IC50value of 14.2μM. Further, compound-3 was identified as cedrelopsin, a coumarin derivative having molecular weight of 260. Results of in vitro mechanistic studies explained that cedrelopsin induced cell cycle arrest at G2/M phase and down-regulated the expression of G2/M regulatory proteins such as cyclin B1, cdc2, and cdc25C, dose dependently. This is the first report that explores the cytotoxic mechanism of cedrelopsin. Conclusion: Thus a potential small lead molecule, cedrelopsin isolated from H. umbellata, showing antiproliferative effect mediated by G2/M arrest in A549 cells was discovered. The effect of cedrelopsin against other cancer cell lines followed by in vivo studies can be performed in future to develop a new drug candidate.

Keywords: A549, cedrelopsin, G2/M phase, Hedyotis umbellata

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Authors: G. Battistoni, F. Collamati, E. De Lucia, R. Faccini, C. Mancini-Terracciano, M. Marafini, I. Mattei, S. Muraro, V. Patera, A. Sarti, A. Sciubba, E. Solfaroli Camillocci, M. Toppi, G. Traini, S. M. Valle, C. Voena

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Accelerated charged particles, mainly protons and carbon ions, are presently used in Particle Therapy (PT) to treat solid tumors. The precision of PT exploiting the charged particle high localized dose deposition in tissues and biological effectiveness in killing cancer cells demands for an online dose monitoring technique, crucial to improve the quality assurance of treatments: possible patient mis-positionings and biological changes with respect to the CT scan could negatively affect the therapy outcome. In PT the beam range confined in the irradiated target can be monitored thanks to the secondary radiation produced by the interaction of the projectiles with the patient tissue. The Dose Profiler (DP) is a novel device designed to track charged secondary particles and reconstruct their longitudinal emission distribution, correlated to the Bragg peak position. The feasibility of this approach has been demonstrated by dedicated experimental measurements. The DP has been developed in the framework of the INSIDE project, MIUR, INFN and Centro Fermi, Museo Storico della Fisica e Centro Studi e Ricerche 'E. Fermi', Roma, Italy and will be tested at the Proton Therapy center of Trento (Italy) within the end of 2017. The DP combines a tracker, made of six layers of two-view scintillating fibers with square cross section (0.5 x 0.5 mm2) with two layers of two-view scintillating bars (section 12.0 x 0.6 mm2). The electronic readout is performed by silicon photomultipliers. The sensitive area of the tracking planes is 20 x 20 cm2. To optimize the detector layout, a Monte Carlo (MC) simulation based on the FLUKA code has been developed. The complete DP geometry and the track reconstruction code have been fully implemented in the MC. In this contribution, the DP hardware will be described. The expected detector performance computed using a dedicated simulation of a 220 MeV/u carbon ion beam impinging on a PMMA target will be presented, and the result will be discussed in the standard clinical application framework. A possible procedure for real-time beam range monitoring is proposed, following the expectations in actual clinical operation.

Keywords: online range monitoring, particle therapy, quality assurance, tracking detector

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Authors: Stefan Nicolae, Cristina Cirtoaje, Emil Petrescu, Florin-Razvan Duca

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In the context of the accelerated expansion of urban agglomerations and the exponential development of industry, a huge amount of water is used, and a crisis of drinking water may occur any time. Classic wastewater treatment removes most pollutants but, for some chemical residues, special methods are needed. Carbon nanotubes and other carbon materials might be used in many cases [1-2], especially for heavy metals removal but also on pharmaceutical products such as paracetamol [3]. Our research has confirmed the better efficiency of nanotubes compared to graphene on paracetamol removal from water, but even better results were obtained on single-walled nanotubes (SWCNTs) and graphene nanoplatelets. This can be due to their better dispersion in water which leads to an increased contact surface, so we propose a filtration system of membranes and carbon materials that can be used for paracetamol removal from wastewater but also for other drugs that affect the aquatic life as well as terrestrial animals and people who use this contaminated water.

Keywords: applied physics, wastewater, nanomaterials, enviromental science

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Authors: H. Heydari, B. Konuklugil, P. Proksch

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Marine-derived fungi can produce interesting bioactive secondary metabolites that can be considered the potential for drug development. Turkey is a country of a peninsula surrounded by the Black Sea at the north, the Aegean Sea at the west, and the Mediterranean Sea at the south. Despite the approximately 8400 km of coastline, studies on marine secondary metabolites and their biological activity are limited. In our ongoing search for new natural products with different bioactivities produced by the marine-derived fungi, we have investigated secondary metabolites of Turkish collection of the marine sea slug (Peltodoris atromaculata) associated fungi Hypocrea nigricans collected from Seferihisar in the Egean sea. According to the author’s best knowledge, no study was found on this fungal species in terms of secondary metabolites. Isolated from ethyl acetate extract of the culture of Hypocrea nigricans were (isodihydroauroglaucin,tetrahydroauroglaucin and dihydroauroglaucin. The structures of the compounds were established based on an NMR and MS analysis. Structural elucidation of another isolated secondary metabolite/s continues.

Keywords: Hypocrea nigricans, isolation, marine fungi, secondary metabolites

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Authors: M. Kalyan Raj, Vinay Umesh Rao, M. Sudhakar

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The work focuses on the development of a directly compressible controlled release co-processed excipient using melt granulation technique. Erodible wax matrix systems are fabricated in which three different types of waxes are co processed separately with Maize starch in different ratios by melt granulation. The resultant free flowing powder is characterized by FTIR, NMR, Mass spectrophotometer and gel permeation chromatography. Also, controlled release tablets of Aripiprazole were formulated and dissolution profile was compared with that of the target product profile given in Zysis patent (Patent no. 20100004262) for Aripiprazole once a week formulation.

Keywords: co-processing, hot melt extrusion, direct compression, maize starch, stearic acid, aripiprazole

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Authors: N. Dahbi, R. B. Taleb

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This study concerns the ion implantation of oxygen in two semiconductors Si and GaAs realized by a simulation using the SRIM tool. The goal of this study is to compare the effect of implantation energy on the distribution of implant ions in the two targets and to examine the different processes resulting from the interaction between the ions of oxygen and the target atoms (Si, GaAs). SRIM simulation results indicate that the implanted ions have a profile as a function of Gaussian-type; oxygen produced more vacancies and implanted deeper in Si compared to GaAs. Also, most of the energy loss is due to ionization and phonon production, where vacancy production amounts to few percent of the total energy.

Keywords: defect profile, GaAs, ion implantation, SRIM, phonon production, vacancies

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Authors: Muhammad Zaman Shakir, Mingfa Yao, Zohaib Iqbal

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This study proposed four Jet fuel surrogate (S1, S2 S3, and 4) with careful selection of seven large hydrocarbon fuel components, ranging from C₉-C₁₆ of higher molecular weight and higher boiling point, adapting the standard molecular distribution size of the actual jet fuel. The surrogate was composed of seven components, including n-propyl cyclohexane (C₉H₁₈), n- propylbenzene (C₉H₁₂), n-undecane (C₁₁H₂₄), n- dodecane (C₁₂H₂₆), n-tetradecane (C₁₄H₃₀), n-hexadecane (C₁₆H₃₄) and iso-cetane (iC₁₆H₃₄). The skeletal jet fuel surrogate reaction mechanism was developed by two approaches, firstly based on a decoupling methodology by describing the C₄ -C₁₆ skeletal mechanism for the oxidation of heavy hydrocarbons and a detailed H₂ /CO/C₁ mechanism for prediction of oxidation of small hydrocarbons. The combined skeletal jet fuel surrogate mechanism was compressed into 128 species, and 355 reactions and thereby can be used in computational fluid dynamics (CFD) simulation. The extensive validation was performed for individual single-component including ignition delay time, species concentrations profile and laminar flame speed based on various fundamental experiments under wide operating conditions, and for their blended mixture, among all the surrogate, S1 has been extensively validated against the experimental data in a shock tube, rapid compression machine, jet-stirred reactor, counterflow flame, and premixed laminar flame over wide ranges of temperature (700-1700 K), pressure (8-50 atm), and equivalence ratio (0.5-2.0) to capture the properties target fuel Jet-A, while the rest of three surrogate S2, S3 and S4 has been validated for Shock Tube ignition delay time only to capture the ignition characteristic of target fuel S-8 & GTL, IPK and RP-3 respectively. Based on the newly proposed HyChem model, another four surrogate with similar components and composition, was developed and parallel validations data was used as followed for previously developed surrogate but at high-temperature condition only. After testing the mechanism prediction performance of surrogates developed by the decoupling methodology, the comparison was done with the results of surrogates developed by the HyChem model. It was observed that all of four proposed surrogates in this study showed good agreement with the experimental measurements and the study comes to this conclusion that like the decoupling methodology HyChem model also has a great potential for the development of oxidation mechanism for heavy alkanes because of applicability, simplicity, and compactness.

Keywords: computational fluid dynamics, decoupling methodology Hychem, jet fuel, surrogate, skeletal mechanism

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Authors: Djamila Chabane, Asma Rouane, Karim Arab

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Depending of the chemical substances responsible for the pharmacological effects, a future therapeutic drug might be produced by extraction from whole plants or by callus initiated from some parts. The optimized callus culture protocols now offer the possibility to use cell culture techniques for vegetative propagation and open minds for further studies on secondary metabolites and drug establishment. In Algerian traditional medicine, Pulicaria incisa (Asteraceae) is used in the treatment of daily troubles (stomachache, headhache., cold, sore throat and rheumatic arthralgia). Field findings revealed that many healers use some fresh parts (leaves, flowers) of this plant to treat skin wounds. This study aims to evaluate the healing efficiency of artisanal cream prepared from sticky mucilage isolated from calluses on dermal wounds of animal models. Callus cultures were initiated from reproductive explants (young inflorescences) excised from adult plants and transferred to a MS basal medium supplemented with growth regulators and maintained under dark for for months. Many calluses types were obtained with various color and aspect (friable, compact). Several subcultures of calli were performed to enhance the mucilage accumulation. After extraction, the mucilage extracts were tested on animal models as follows. The wound healing potential was studied by causing dermal wounds (1 cm diameter) at the dorsolumbar part of Rattus norvegicus; different samples of the cream were applied after hair removal on three rats each, including two controls (one treated by Vaseline and one without any treatment), two experimental groups (experimental group 1, treated with a reference ointment "Madecassol® and experimental group 2 treated by callus mucilage cream for a period of seventeen days. The evolution of the healing activity was estimated by calculating the percentage reduction of the area wounds treated by all compounds tested compared to the controls by using AutoCAD software. The percentage of healing effect of the cream prepared from callus mucilage was (99.79%) compared to that of Madecassol® (99.76%). For the treatment time, the significant healing activity was observed after 17 days compared to that of the reference pharmaceutical products without any wound infection. The healing effect of Madecassol® is more effective because it stimulates and regulates the production of collagen, a fibrous matrix essential for wound healing. Mucilage extracts also showed a high capacity to heal the skin without any infection. According to this pharmacological activity, we suggest to use calluses produced by in vitro culture to producing new compounds for the skin care and treatment.

Keywords: calluses, Pulicaria incisa, mucilage, Wounds

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Authors: Elly Usman, S. Dante, Diah Purnamasari

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Type 2 diabetes mellitus ( T2DM ) is a syndrome characterized by a state of increased blood sugar levels due to chronic disorders of insulin secretion by pancreatic beta cells and insulin action or a combination of both. The organic cation transporter 1, encoded by the SLC22A1 gene, responsible for the uptake of the antihyperglycemic drug, metformin, in the hepatocyte. We assessed whether a genetic variation in the SLC22A1 gene was associated with the glucose - lowering effect of metformin. Method case study research design. Samples are children with type 2 diabetes mellitus who meet the inclusion criteria. The results proportions SLC22A1 gene polymorphisms in children with diabetes mellitus type 2 amounted to 52.04 % at position 400T/C, there is one heterozygous and one at position 595T/C Conclusion The presence of SLC22A1 gene polymorphisms in children with diabetes mellitus type 2.

Keywords: diabetes Mellitus type 2, metformin, organic cation transporter 1, pharmacogenomics

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Authors: Iman I. Salama, Samia M. Sami, Somaia I. Salama, Zeinab N. Said, Thanaa M. Rabah, Aida M. Abdel-Mohsin

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This is a national community-based project to evaluate the effectiveness of HBV vaccination program in prevention of infection. HBV markers were tested in the sera of 3600 vaccinated children. Infected children were followed up for 1 year. Prevalence of HBV infection was 0.39 % (0.28% positive for anti-HBc, 0.03% positive for HBsAg and 0.08% positive for both). One year later, 50% of positive anti-HBc children turned negative with sustained positivity for positive HBsAg cases. HBV infection was significantly higher at age above 9 years (0.6%) compared to 0.2% at age 3-9 years and 0% at younger age (P < 0.05). Logistic analysis revealed that predictors for HBV infection were history of blood transfusion, regular medical injection, and family history of either HBV infection or drug abuse (adjusted odds ratios 6.2, 5.6, 7.6 & 19.1 respectively). HBV vaccination program produced adequate protection. Adherence to infection control measures and safe blood transfusion are recommended.

Keywords: HBV infection, HBV vaccine, children, Egypt

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Authors: Sukrat Sinha, Abhay Kumar, Shanthy Sundaram

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The Leishmania homologue of activated C kinase (LACK) is known T cell epitope from soluble Leishmania antigens (SLA) that confers protection against Leishmania challenge. This antigen has been found to be highly conserved among Leishmania strains. LACK has been shown to be protective against L. donovani challenge. A comprehensive analysis of several LACK sequences was completed. The analysis shows a high level of conservation, lower variability and higher antigenicity in specific portions of the LACK protein. This information provides insights for the potential consideration of LACK as a putative candidate in the context of visceral Leishmaniasis vaccine target.

Keywords: bioinformatics, genome assembly, leishmania activated protein kinase c (lack), next-generation sequencing

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Authors: Mohamed Amine Ben Abdallah, Imed Khemili, Nizar Aifaoui

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This work denotes an insight into dynamic synthesis of multibody systems. A set of mechanism parameters design variable are synthetized based on a desired mechanism response, such as, velocity, acceleration and bodies deformations. Moreover, knowing the work space, for a robot, and mechanism response allow defining optimal parameters mechanism handling with the desired target response. To this end, evolutionary genetic algorithm has been deployed. A demonstrative example for imperfect mechanism has been treated, mainly, a slider crank mechanism with a flexible connecting rod. The transversal deflection of the connecting rod has been chosen as response to identify the mechanism design parameters.

Keywords: dynamic response, evolutionary genetic algorithm, flexible bodies, optimization

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Authors: S. Takaidza, M. Pillay, F. Mtunzi

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Since time immemorial, plants have been used by several communities to treat a large number of diseases. Numerous studies on the pharmacology of medicinal plants have been done. Medicinal plants constitute a potential source for the production of new medicines and may complement conventional antimicrobials and probably decrease health costs. Phytochemical compounds in plants are known to be biologically active aiding, for example, as antioxidants and antimicrobials. The overwhelming challenge of drug resistance has resulted in an increasing trend towards using medicinal plants to treat various diseases, especially in developing countries. Species of the genus Tulbaghia has been widely used in traditional medicine to treat various ailments such rheumatism, fits, fever, earache, tuberculosis etc. It is believed that the species possess several therapeutic properties. This paper evaluates some of the biological activities of the genus Tulbaghia. It is evident from current literature that T. violacea is the most promising species. The other species of Tulbaghia still require further studies to ascertain their medicinal potential.

Keywords: biological activities, antimicrobial, antioxidant, phytochemicals, tulbaghia

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Authors: Qi Wang

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Accurate pronunciation is the first condition of communication. Compared with the alphabetic languages, Chinese is more difficult for the foreigners to study as a second language, due to the tonal language with the meaningful characters as the written system, especially speaking. This research first presents the statistics of the typical errors of the pronunciations, based on the data of our two- year program of graduate students, which shown 90% of their speaking with strong foreign accents and no obvious change of the pitches, even if they could speak Chinese fluently. Second part, analyzed the caused reasons in the learning and teaching processes. Third part, this result of this research, based the theory of Chinese prosodic words, shown that the earlier the students get trained on prosodics at the beginning and suprasegmentals at intermediate and advanced levels, the better effects for them to communicate in Chinese as a second language.

Keywords: second language, prosodic word, foot, suprasegmental

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Authors: Giulia Bonaldo, Alberto Vaccheri, Ottavio D'Annibali, Domenico Motola

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The Human Papilloma Virus (HPV) was shown to be the cause of different types of carcinomas, first of all of the cervical intraepithelial neoplasia. Since the early 80s to today, thanks first to the preventive screening campaigns (pap-test) and following to the introduction of HPV vaccines on the market; the number of new cases of cervical cancer has decreased significantly. The HPV vaccines currently approved are three: Cervarix® (HPV2 - virus type: 16 and 18), Gardasil® (HPV4 - 6, 11, 16, 18) and Gardasil 9® (HPV9 - 6, 11, 16, 18, 31, 33, 45, 52, 58), which all protect against the two high-risk HPVs (6, 11) that are mainly involved in cervical cancers. Despite the remarkable effectiveness of these vaccines has been demonstrated, in the recent years, there have been many complaints about their risk-benefit profile due to Adverse Events Following Immunization (AEFI). The purpose of this study is to provide a support about the ongoing discussion on the safety profile of HPV vaccines based on real life data deriving from spontaneous reports of suspected AEFIs collected in the Vaccine Adverse Events Reporting System (VAERS). VAERS is a freely-available national vaccine safety surveillance database of AEFI, co-administered by the Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA). We collected all the reports between January 2007 to December 2017 related to the HPV vaccines with a brand name (HPV2, HPV4, HPV9) or without (HPVX). A disproportionality analysis using Reporting Odds Ratio (ROR) with 95% confidence interval and p value ≤ 0.05 was performed. Over the 10-year period, 54889 reports of AEFI related to HPV vaccines reported in VAERS, corresponding to 224863 vaccine-event pairs, were retrieved. The highest number of reports was related to Gardasil (n = 42244), followed by Gardasil 9 (7212) and Cervarix (3904). The brand name of the HPV vaccine was not reported in 1529 cases. The two events more frequently reported and statistically significant for each vaccine were: dizziness (n = 5053) ROR = 1.28 (CI95% 1.24 – 1.31) and syncope (4808) ROR = 1.21 (1.17 – 1.25) for Gardasil. For Gardasil 9, injection site pain (305) ROR = 1.40 (1.25 – 1.57) and injection site erythema (297) ROR = 1.88 (1.67 – 2.10) and for Cervarix, headache (672) ROR = 1.14 (1.06 – 1.23) and loss of consciousness (528) ROR = 1.71 (1.57 – 1.87). In total, we collected 406 reports of death and 2461 cases of permanent disability in the ten-year period. The events consisting of incorrect vaccine storage or incorrect administration were not considered. The AEFI analysis showed that the most frequently reported events are non-serious and listed in the corresponding SmPCs. In addition to these, potential safety signals arose regarding less frequent and severe AEFIs that would deserve further investigation. This already happened with the referral of the European Medicines Agency (EMA) for the adverse events POTS (Postural Orthostatic Tachycardia Syndrome) and CRPS (Complex Regional Pain Syndrome) associated with anti-papillomavirus vaccines.

Keywords: adverse drug reactions, pharmacovigilance, safety, vaccines

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Authors: Yung-Chih Kuo, Che-Yu Lin, Jay-Shake Li, Yung-I Lou

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Curcumin (CRM) and nerve growth factor (NGF) were entrapped in liposomes (LIP) with cardiolipin (CL) to downregulate the phosphorylation of mitogen-activated protein kinases for Alzheimer’s disease (AD) management. AD belongs to neurodegenerative disorder with a gradual loss of memory, yielding irreversible dementia. CL-conjugated LIP loaded with CRM (CRM-CL/LIP) and that with NGF (NGF-CL/LIP) were applied to AD models of SK-N-MC cells and Wistar rats with an insult of β-amyloid peptide (Aβ). Lipids comprising 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (Avanti Polar Lipids, Alabaster, AL), 1',3'-bis[1,2- dimyristoyl-sn-glycero-3-phospho]-sn-glycerol (CL; Avanti Polar Lipids), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethylene glycol)-2000] (Avanti Polar Lipids), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000] (Avanti Polar Lipids) and CRM (Sigma–Aldrich, St. Louis, MO) were dissolved in chloroform (J. T. Baker, Phillipsburg, NJ) and condensed using a rotary evaporator (Panchum, Kaohsiung, Taiwan). Human β-NGF (Alomone Lab, Jerusalem, Israel) was added in the aqueous phase. Wheat germ agglutinin (WGA; Medicago AB, Uppsala, Sweden) was grafted on LIP loaded with CRM for (WGA-CRM-LIP) and CL-conjugated LIP loaded with CRM (WGA-CRM-CL/LIP) using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (Sigma–Aldrich) and N-hydroxysuccinimide (Alfa Aesar, Ward Hill, MA). The protein samples of SK-N-MC cells (American Type Tissue Collection, Rockville, MD) were used for sodium dodecyl sulfate (Sigma–Aldrich) polyacrylamide gel (Sigma–Aldrich) electrophoresis. In animal study, the LIP formulations were administered by intravenous injection via a tail vein of male Wistar rats (250–280 g, 8 weeks, BioLasco, Taipei, Taiwan), which were housed in the Animal Laboratory of National Chung Cheng University in accordance with the institutional guidelines and the guidelines of Animal Protection Committee under the Council of Agriculture of the Republic of China. We found that CRM-CL/LIP could inhibit the expressions of phosphorylated p38 (p-p38), p-Jun N-terminal kinase (p-JNK), and p-tau protein at serine 202 (p-Ser202) to retard the neuronal apoptosis. Free CRM and released CRM from CRM-LIP and CRM-CL/LIP were not in a straightforward manner to effectively inhibit the expression of p-p38 and p-JNK in the cytoplasm. In addition, NGF-CL/LIP enhanced the quantities of p-neurotrophic tyrosine kinase receptor type 1 (p-TrkA) and p-extracellular-signal-regulated kinase 5 (p-ERK5), preventing the Aβ-induced degeneration of neurons. The membrane fusion of NGF-LIP activated the ERK5 pathway and the targeting capacity of NGF-CL/LIP enhanced the possibility of released NGF to affect the TrkA level. Moreover, WGA-CRM-LIP improved the permeation of CRM across the blood–brain barrier (BBB) and significantly reduced the Aβ plaque deposition and malondialdehyde level and increased the percentage of normal neurons and cholinergic function in the hippocampus of AD rats. This was mainly because the encapsulated CRM was protected by LIP against a rapid degradation in the blood. Furthermore, WGA on LIP could target N-acetylglucosamine on endothelia and increased the quantity of CRM transported across the BBB. In addition, WGA-CRM-CL/LIP could be effective in suppressing the synthesis of acetylcholinesterase and reduced the decomposition of acetylcholine for better neurotransmission. Based on the in vitro and in vivo evidences, WGA-CRM-CL/LIP can rescue neurons from apoptosis in the brain and can be a promising drug delivery system for clinical AD therapy.

Keywords: Alzheimer’s disease, β-amyloid, liposome, mitogen-activated protein kinase

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