Search results for: non−central nervous system cancers
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 19976

Search results for: non−central nervous system cancers

19706 Optimization Method of Dispersed Generation in Electrical Distribution Systems

Authors: Mahmoud Samkan

Abstract:

Dispersed Generation (DG) is a promising solution to many power system problems such as voltage regulation and power loss. This paper proposes a heuristic two-step method to optimize the location and size of DG for reducing active power losses and, therefore, improve the voltage profile in radial distribution networks. In addition to a DG placed at the system load gravity center, this method consists in assigning a DG to each lateral of the network. After having determined the central DG placement, the location and size of each lateral DG are predetermined in the first step. The results are then refined in the second step. This method is tested for 33-bus system for 100% DG penetration. The results obtained are compared with those of other methods found in the literature.

Keywords: optimal location, optimal size, dispersed generation (DG), radial distribution networks, reducing losses

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19705 Improving Security in Healthcare Applications Using Federated Learning System With Blockchain Technology

Authors: Aofan Liu, Qianqian Tan, Burra Venkata Durga Kumar

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Data security is of the utmost importance in the healthcare area, as sensitive patient information is constantly sent around and analyzed by many different parties. The use of federated learning, which enables data to be evaluated locally on devices rather than being transferred to a central server, has emerged as a potential solution for protecting the privacy of user information. To protect against data breaches and unauthorized access, federated learning alone might not be adequate. In this context, the application of blockchain technology could provide the system extra protection. This study proposes a distributed federated learning system that is built on blockchain technology in order to enhance security in healthcare. This makes it possible for a wide variety of healthcare providers to work together on data analysis without raising concerns about the confidentiality of the data. The technical aspects of the system, including as the design and implementation of distributed learning algorithms, consensus mechanisms, and smart contracts, are also investigated as part of this process. The technique that was offered is a workable alternative that addresses concerns about the safety of healthcare while also fostering collaborative research and the interchange of data.

Keywords: data privacy, distributed system, federated learning, machine learning

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19704 Evidence of the Effect of the Structure of Social Representations on Group Identification

Authors: Eric Bonetto, Anthony Piermatteo, Fabien Girandola, Gregory Lo Monaco

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The present contribution focuses on the effect of the structure of social representations on group identification. A social representation (SR) is defined as an organized and structured set of cognitions, produced and shared by members of a same group about a same social object. Within this framework, the central core theory establishes a structural distinction between central cognitions – or 'core' – and peripheral ones: the former are theoretically considered as more connected than the later to group members’ social identity and may play a greater role in SRs’ ability to allow group identification by means of a common vision of the object of representation. Indeed, the central core provides a reference point for the in-group as it constitutes a consensual vision that gives meaning to a social object particularly important to individuals and to the group. However, while numerous contributions clearly refer to the underlying role of SRs in group identification, there are only few empirical evidences of this aspect. Thus, we hypothesize an effect of the structure of SRs on group identification. More precisely, central cognitions (vs. peripheral ones) will lead to a stronger group identification. In addition, we hypothesize that the refutation of a cognition will lead to a stronger group identification than its activation. The SR mobilized here is that of 'studying' among a population of first-year undergraduate psychology students. Thus, a pretest (N = 82), using an Attribute-Challenge Technique, was designed in order to identify the central and the peripheral cognitions to use in the primings of our main study. The results of this pretest are in line with previous studies. Then, the main study (online; N = 184), using a social priming methodology, was based on a 2 (Structural status of the cognitions belonging to the prime: central vs. peripheral) x 2 (Type of prime: activation vs. refutation) experimental design in order to test our hypotheses. Results revealed, as expected, the main effect of the structure of the SR on group identification. Indeed, central cognitions trigger a higher level of identification than the peripheral ones. However, we observe neither effect of the type of prime, nor interaction effect. These results experimentally demonstrate for the first time the effect of the structure of SRs on group identification and indicate that central cognitions are more connected than peripheral ones to group members’ social identity. These results will be discussed considering the importance of understanding identity as a function of SRs and on their ability to potentially solve the lack of consideration of the definition of the group in Social Representations Theory.

Keywords: group identification, social identity, social representations, structural approach

Procedia PDF Downloads 191
19703 Public and Private Domains: Contradictions and Covenants in Evolution of Game Policy

Authors: Mingzhu Lyu, Runlei Ren, Xinyu Dai, Jiaxuan Pi, Kanghua Li

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The study of video game policy in China has been divided into two branches: "pedagogy" and "game industry". The binary perspective of policy reveals the "contradictory" side of policy performance. Based on this suspicion, this paper constructs a three-dimensional sequence of time, content and institutions of game policy, and establishes the "contradictory" aspects of policy performance between 1949 and 2019. A central-level database of game policies, clarifying that our game policies follow a shift from reactive response to proactive guidance, stigmatization and de-stigmatization, the evolutionary logic. The study found that the central government has always maintained a strict requirement and prudent guidance for game policy, and the deep contradictions in game policy stem from the essential conflict between the natural amusement of games and the seriousness of the educational system, and the Chinese government's use of the understanding of the public and private domains and the Managing of the conflict.

Keywords: game industry, gaming policy, public domain, private domain

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19702 Tuberculosis (TB) and Lung Cancer

Authors: Asghar Arif

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Lung cancer has been recognized as one of the greatest common cancers, causing the annual mortality rate of about 1.2 million people in the world. Lung cancer is the most prevalent cancer in men and the third-most common cancer among women (after breast and digestive cancers).Recent evidences have shown the inflammatory process as one of the potential factors of cancer. Tuberculosis (TB), pneumonia, and chronic bronchitis are among the most important inflammation-inducing factors in the lungs, among which TB has a more profound role in the emergence of cancer.TB is one of the important mortality factors throughout the world, and 205,000 death cases are reported annually due to this disease. Chronic inflammation and fibrosis due to TB can induce genetic mutation and alternations. Parenchyma tissue of lung is involved in both diseases of TB and lung cancer, and continuous cough in lung cancer, morphological vascular variations, lymphocytosis processes, and generation of immune system mediators such as interleukins, are all among the factors leading to the hypothesis regarding the role of TB in lung cancer Some reports have shown that the induction of necrosis and apoptosis or TB reactivation, especially in patients with immune-deficiency, may result in increasing IL-17 and TNF_α, which will either decrease P53 activity or increase the expression of Bcl-2, decrease Bax-T, and cause the inhibition of caspase-3 expression due to decreasing the expression of mitochondria cytochrome oxidase. It has been also indicated that following the injection of BCG vaccine, the host immune system will be reinforced, and in particular, the rates of gamma interferon, nitric oxide, and interleukin-2 are increased. Therefore, CD4 + lymphocyte function will be improved, and the person will be immune against cancer.Numerous prospective studies have so far been conducted on the role of TB in lung cancer, and it seems that this disease is effective in that particular cancer.One of the main challenges of lung cancer is its correct and timely diagnosis. Unfortunately, clinical symptoms (such as continuous cough, hemoptysis, weight loss, fever, chest pain, dyspnea, and loss of appetite) and radiological images are similar in TB and lung cancer. Therefore, anti-TB drugs are routinely prescribed for the patients in the countries with high prevalence of TB, like Pakistan. Regarding the similarity in clinical symptoms and radiological findings of lung cancer, proper diagnosis is necessary for TB and respiratory infections due to nontuberculousmycobacteria (NTM). Some of the drug resistive TB cases are, in fact, lung cancer or NTM lung infections. Acid-fast staining and histological study of phlegm and bronchial washing, culturing and polymerase chain reaction TB are among the most important solutions for differential diagnosis of these diseases. Briefly, it is assumed that TB is one of the risk factors for cancer. Numerous studies have been conducted in this regard throughout the world, and it has been observed that there is a significant relationship between previous TB infection and lung cancer. However, to prove this hypothesis, further and more extensive studies are required. In addition, as the clinical symptoms and radiological findings of TB, lung cancer, and non-TB mycobacteria lung infections are similar, they can be misdiagnosed as TB.

Keywords: TB and lung cancer, TB people, TB servivers, TB and HIV aids

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19701 Correlation of Strength and Change in the Thickness of Back Extensor Muscles during Maximal Isometric Contraction in Healthy and Osteoporotic Postmenopausal Women

Authors: Mohammad Jan-Nataj Zeinab, Kahrizi Sedighe, Bayat Noshin, Giti Torkaman

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According to the importance of the back extensor muscle strength in postmenopausal women, this study aimed to determine the relationship between strength and changes in the thickness of back extensor muscles during isometric contraction in healthy and osteoporotic postmenopausal women. Strength and thickness of the muscles of 42 postmenopausal women were measured respectively, using a handheld dynamometer and ultrasonography. Also, the Pearson correlation coefficient was used to analyze the relationship between the strength and thickness. The results indicated a high reproducibility dynamometer test and ultrasonography. The decrease of strength in people with osteoporosis, occurred more through changes in muscle structure such as reducing the number and size of muscle fibers than changes in the nervous system part.

Keywords: back extensor muscles, strength, thickness, osteoporosis

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19700 The Effects of the New Silk Road Initiatives and the Eurasian Union to the East-Central-Europe’s East Opening Policies

Authors: Tamas Dani

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The author’s research explores the geo-economical role and importance of some small and medium sized states, reviews their adaption strategies in foreign trade and also in foreign affairs in the course of changing into a multipolar world, uses international background. With these, the paper analyses the recent years and the future of ‘Opening towards Eastern foreign economic policies’ from East-Central Europe and parallel with that the ‘Western foreign economy policies’ from Asia, as the Chinese One Belt One Road new silk route plans (so far its huge part is an infrastructural development plan to reach international trade and investment aims). It can be today’s question whether these ideas will reshape the global trade or not. How does the new silk road initiatives and the Eurasian Union reflect the effect of globalization? It is worth to analyse that how did Central and Eastern European countries open to Asia; why does China have the focus of the opening policies in many countries and why could China be seen as the ‘winner’ of the world economic crisis after 2008. The research is based on the following methodologies: national and international literature, policy documents and related design documents, complemented by processing of international databases, statistics and live interviews with leaders from East-Central European countries’ companies and public administration, diplomats and international traders. The results also illustrated by mapping and graphs. The research will find out as major findings whether the state decision-makers have enough margin for manoeuvres to strengthen foreign economic relations. This work has a hypothesis that countries in East-Central Europe have real chance to diversify their relations in foreign trade, focus beyond their traditional partners. This essay focuses on the opportunities of East-Central-European countries in diversification of foreign trade relations towards China and Russia in terms of ‘Eastern Openings’. The effects of the new silk road initiatives and the Eurasian Union to Hungary’s economy with a comparing outlook on East-Central European countries and exploring common regional cooperation opportunities in this area. The essay concentrate on the changing trade relations between East-Central-Europe and China as well as Russia, try to analyse the effects of the new silk road initiatives and the Eurasian Union also. In the conclusion part, it shows how the cooperation is necessary for the East-Central European countries if they want to have a non-asymmetric trade with Russia, China or some Chinese regions (Pearl River Delta, Hainan, …). The form of the cooperation for the East-Central European nations can be Visegrad 4 Cooperation (V4), Central and Eastern European Countries (CEEC16), 3 SEAS Cooperation (or BABS – Baltic, Adriatic, Black Seas Initiative).

Keywords: China, East-Central Europe, foreign trade relations, geoeconomics, geopolitics, Russia

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19699 Research on Transverse Ecological Compensation Mechanism in Yangtze River Economic Belt Based on Evolutionary Game Theory

Authors: Tingyu Zhang

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The cross-basin ecological compensation mechanism is key to stimulating active participation in ecological protection across the entire basin. This study constructs an evolutionary game model of cross-basin ecological compensation in the Yangtze River Economic Belt (YREB), introducing a central government constraint and incentive mechanism (CGCIM) to explore the conditions for achieving strategies of protection and compensation that meet societal expectations. Furthermore, using a water quality-water quantity model combined with factual data from the YREB in 2020, the amount of ecological compensation is calculated. The results indicate that the stability of the evolutionary game model of the upstream and downstream governments in the YREB is closely related to the CGCIM. When the sum of the central government's reward amount to the upstream government and the penalty amount to both sides simultaneously is greater than 39.948 billion yuan, and the sum of the reward amount to the downstream government and the penalty amount to only the lower reaches is greater than 1.567 billion yuan, or when the sum of the reward amount to the downstream government and the penalty amount to both sides simultaneously is greater than 1.567 billion yuan, and the sum of the reward amount to the upstream government and the penalty amount to only the upstream government is greater than 399.48 billion yuan, the protection and compensation become the only evolutionarily stable strategy for the evolutionary game system composed of the upstream and downstream governments in the YREB. At this point, the total ecological compensation that the downstream government of the YREB should pay to the upstream government is 1.567 billion yuan, with Hunan paying 0.03 billion yuan, Hubei 2.53 billion yuan, Jiangxi 0.18 billion yuan, Anhui 1.68 billion yuan, Zhejiang 0.75 billion yuan, Jiangsu 6.57 billion yuan, and Shanghai 3.93 billion yuan. The research results can provide a reference for promoting the improvement and perfection of the cross-basin ecological compensation system in the YREB.

Keywords: ecological compensation, evolutionary game model, central government constraint and incentive mechanism, Yangtze river economic belt

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19698 Upconversion Nanomaterials for Applications in Life Sciences and Medicine

Authors: Yong Zhang

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Light has proven to be useful in a wide range of biomedical applications such as fluorescence imaging, photoacoustic imaging, optogenetics, photodynamic therapy, photothermal therapy, and light controlled drug/gene delivery. Taking photodynamic therapy (PDT) as an example, PDT has been proven clinically effective in early lung cancer, bladder cancer, head, and neck cancer and is the primary treatment for skin cancer as well. However, clinical use of PDT is severely constrained by the low penetration depth of visible light through thick tissue, limiting its use to target regions only a few millimeters deep. One way to enhance the range is to use invisible near-infrared (NIR) light within the optical window (700–1100nm) for biological tissues, extending the depth up to 1cm with no observable damage to the intervening tissue. We have demonstrated use of NIR-to-visible upconversion fluorescent nanoparticles (UCNPs), emitting visible fluorescence when excited by a NIR light at 980nm, as a nanotransducer for PDT to convert deep tissue-penetrating NIR light to visible light suitable for activating photosensitizers. The unique optical properties of UCNPs enable the upconversion wavelength to be tuned and matched to the activation absorption wavelength of the photosensitizer. At depths beyond 1cm, however, tissue remains inaccessible to light even within the NIR window, and this critical depth limitation renders existing phototherapy ineffective against most deep-seated cancers. We have demonstrated some new treatment modalities for deep-seated cancers based on UCNP hydrogel implants and miniaturized, wirelessly powered optoelectronic devices for light delivery to deep tissues.

Keywords: upconversion, fluorescent, nanoparticle, bioimaging, photodynamic therapy

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19697 Dynamic Analysis of Transmission Line Towers

Authors: L. Srikanth, D. Neelima Satyam

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The transmission line towers are one of the important life line structures in the distribution of power from the source to the various places for several purposes. The predominant external loads which act on these towers are wind and earthquake loads. In this present study tower is analyzed using Indian Standards IS: 875:1987 (Wind Load), IS: 802:1995 (Structural Steel), IS:1893:2002 (Earthquake) and dynamic analysis of tower has been performed considering ground motion of 2001 Bhuj Earthquake (India). The dynamic analysis was performed considering a tower system consisting two towers spaced 800m apart and 35m height each. This analysis has been performed using numerical time stepping finite difference method which is central difference method were employed by a developed MATLAB program to get the normalized ground motion parameters includes acceleration, frequency, velocity which are important in designing the tower. The tower is analyzed using response spectrum analysis.

Keywords: response spectra, dynamic analysis, central difference method, transmission tower

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19696 Comprehensive Analysis of RNA m5C Regulator ALYREF as a Suppressive Factor of Anti-tumor Immune and a Potential Tumor Prognostic Marker in Pan-Cancer

Authors: Yujie Yuan, Yiyang Fan, Hong Fan

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Objective: The RNA methylation recognition protein Aly/REF export factor (ALYREF) is considered one type of “reader” protein acting as a recognition protein of m5C, has been reported involved in several biological progresses including cancer initiation and progression. 5-methylcytosine (m5C) is a conserved and prevalent RNA modification in all species, as accumulating evidence suggests its role in the promotion of tumorigenesis. It has been claimed that ALYREF mediates nuclear export of mRNA with m5C modification and regulates biological effects of cancer cells. However, the systematical regulatory pathways of ALYREF in cancer tissues have not been clarified, yet. Methods: The expression level of ALYREF in pan-cancer and their normal tissues was compared through the data acquired from The Cancer Genome Atlas (TCGA). The University of Alabama at Birmingham Cancer data analysis Portal UALCAN was used to analyze the relationship between ALYREF and clinical pathological features. The relationship between the expression level of ALYREF and prognosis of pan-cancer, and the correlation genes of ALYREF were figured out by using Gene Expression Correlation Analysis database GEPIA. Immune related genes were obtained from TISIDB (an integrated repository portal for tumor-immune system interactions). Immune-related research was conducted by using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and TIMER. Results: Based on the data acquired from TCGA, ALYREF has an obviously higher-level expression in various types of cancers compared with relevant normal tissues excluding thyroid carcinoma and kidney chromophobe. The immunohistochemical images on The Human Protein Atlas showed that ALYREF can be detected in cytoplasm, membrane, but mainly located in nuclear. In addition, a higher expression level of ALYREF in tumor tissue generates a poor prognosis in majority of cancers. According to the above results, cancers with a higher expression level of ALYREF compared with normal tissues and a significant correlation between ALYREF and prognosis were selected for further analysis. By using TISIDB, we found that portion of ALYREF co-expression genes (such as BIRC5, H2AFZ, CCDC137, TK1, and PPM1G) with high Pearson correlation coefficient (PCC) were involved in anti-tumor immunity or affect resistance or sensitivity to T cell-mediated killing. Furthermore, based on the results acquired from GEPIA, there was significant correlation between ALYREF and PD-L1. It was exposed that there is a negative correlation between the expression level of ALYREF and ESTIMATE score. Conclusion: The present study indicated that ALYREF plays a vital and universal role in cancer initiation and progression of pan-cancer through regulating mitotic progression, DNA synthesis and metabolic process, and RNA processing. The correlation between ALYREF and PD-L1 implied ALYREF may affect the therapeutic effect of immunotherapy of tumor. More evidence revealed that ALYREF may play an important role in tumor immunomodulation. The correlation between ALYREF and immune cell infiltration level indicated that ALYREF can be a potential therapeutic target. Exploring the regulatory mechanism of ALYREF in tumor tissues may expose the reason for poor efficacy of immunotherapy and offer more directions of tumor treatment.

Keywords: ALYREF, pan-cancer, immunotherapy, PD-L1

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19695 The Response of the Central Bank to the Exchange Rate Movement: A Dynamic Stochastic General Equilibrium-Vector Autoregressive Approach for Tunisian Economy

Authors: Abdelli Soulaima, Belhadj Besma

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The paper examines the choice of the central bank toward the movements of the nominal exchange rate and evaluates its effects on the volatility of the output growth and the inflation. The novel hybrid method of the dynamic stochastic general equilibrium called the DSGE-VAR is proposed for analyzing this policy experiment in a small scale open economy in particular Tunisia. The contribution is provided to the empirical literature as we apply the Tunisian data with this model, which is rarely used in this context. Note additionally that the issue of treating the degree of response of the central bank to the exchange rate in Tunisia is special. To ameliorate the estimation, the Bayesian technique is carried out for the sample 1980:q1 to 2011 q4. Our results reveal that the central bank should not react or softly react to the exchange rate. The variance decomposition displayed that the overall inflation volatility is more pronounced with the fixed exchange rate regime for most of the shocks except for the productivity and the interest rate. The output volatility is also higher with this regime with the majority of the shocks exempting the foreign interest rate and the interest rate shocks.

Keywords: DSGE-VAR modeling, exchange rate, monetary policy, Bayesian estimation

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19694 Artificial Intelligence Based Online Monitoring System for Cardiac Patient

Authors: Syed Qasim Gilani, Muhammad Umair, Muhammad Noman, Syed Bilawal Shah, Aqib Abbasi, Muhammad Waheed

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Cardiovascular Diseases(CVD's) are the major cause of death in the world. The main reason for these deaths is the unavailability of first aid for heart failure. In many cases, patients die before reaching the hospital. We in this paper are presenting innovative online health service for Cardiac Patients. The proposed online health system has two ends. Users through device developed by us can communicate with their doctor through a mobile application. This interface provides them with first aid.Also by using this service, they have an easy interface with their doctors for attaining medical advice. According to the proposed system, we developed a device called Cardiac Care. Cardiac Care is a portable device which a patient can use at their home for monitoring heart condition. When a patient checks his/her heart condition, Electrocardiogram (ECG), Blood Pressure(BP), Temperature are sent to the central database. The severity of patients condition is checked using Artificial Intelligence Algorithm at the database. If the patient is suffering from the minor problem, our algorithm will suggest a prescription for patients. But if patient's condition is severe, patients record is sent to doctor through the mobile Android application. Doctor after reviewing patients condition suggests next step. If a doctor identifies the patient condition as critical, then the message is sent to the central database for sending an ambulance for the patient. Ambulance starts moving towards patient for bringing him/her to hospital. We have implemented this model at prototype level. This model will be life-saving for millions of people around the globe. According to this proposed model patients will be in contact with their doctors all the time.

Keywords: cardiovascular disease, classification, electrocardiogram, blood pressure

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19693 Exploration of Slow-Traffic System Strategies for New Urban Areas Under the Integration of Industry and City - Taking Qianfeng District of Guang’an City as an Example

Authors: Qikai Guan

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With the deepening of China's urbanization process, the development of urban industry has entered a new period, due to the gradual compounding and diversification of urban industrial functions, urban planning has shifted from the previous single industrial space arrangement and functional design to focusing on the upgrading of the urban structure, and on the diversified needs of people. As an important part of urban activity space, ‘slow moving space’ is of great significance in alleviating urban traffic congestion, optimizing residents' travel experience and improving urban ecological space. Therefore, this paper takes the slow-moving transportation system under the perspective of industry-city integration as the starting point, through sorting out the development needs of the city in the process of industry-city integration, analyzing the characteristics of the site base, sorting out a series of compatibility between the layout of the new industrial zone and the urban slow-moving system, and integrating the design concepts. At the same time, through the analysis and summarization of domestic and international experience, the construction ideas are proposed. Finally, the following aspects of planning strategy optimization are proposed: industrial layout, urban vitality, ecological pattern, regional characteristics and landscape image. In terms of specific design, on the one hand, it builds a regional slow-moving network, puts forward a diversified design strategy for the industry-oriented and multi-functional composite central area, realizes the coexistence of pedestrian-oriented and multiple transportation modes, basically covers the public facilities, and enhances the vitality of the city. On the other hand, it improves the landscape ecosystem, creates a healthy, diversified and livable superline landscape system, helps the construction of the ‘green core’ of the central city, and improves the travel experience of the residents.

Keywords: industry-city integration, slow-moving system, public space, functional integration

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19692 Wave Interaction with Defects in Pressurized Composite Structures

Authors: R. K. Apalowo, D. Chronopoulos, V. Thierry

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A wave finite element (WFE) and finite element (FE) based computational method is presented by which the dispersion properties as well as the wave interaction coefficients for one-dimensional structural system can be predicted. The structural system is discretized as a system comprising a number of waveguides connected by a coupling joint. Uniform nodes are ensured at the interfaces of the coupling element with each waveguide. Then, equilibrium and continuity conditions are enforced at the interfaces. Wave propagation properties of each waveguide are calculated using the WFE method and the coupling element is modelled using the FE method. The scattering of waves through the coupling element, on which damage is modelled, is determined by coupling the FE and WFE models. Furthermore, the central aim is to evaluate the effect of pressurization on the wave dispersion and scattering characteristics of the prestressed structural system compared to that which is not prestressed. Numerical case studies are exhibited for two waveguides coupled through a coupling joint.

Keywords: Finite Element, Prestressed Structures, Wave Finite Element, Wave Propagation Properties, Wave Scattering Coefficients.

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19691 A Realist Review of Influences of Community-Based Interventions on Noncommunicable Disease Risk Behaviors

Authors: Ifeyinwa Victor-Uadiale, Georgina Pearson, Sophie Witter, D. Reidpath

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Introduction: Smoking, alcohol misuse, unhealthy diet, and physical inactivity are the primary drivers of noncommunicable diseases (NCD), including cardiovascular diseases, cancers, respiratory diseases, and diabetes, worldwide. Collectively, these diseases are the leading cause of all global deaths, most of which are premature, affecting people between 30 and 70 years. Empirical evidence suggests that these risk behaviors can be modified by community-based interventions (CBI). However, there is little insight into the mechanisms and contextual factors of successful community interventions that impact risk behaviours for chronic diseases. This study examined “Under what circumstances, for whom, and how, do community-based interventions modify smoking, alcohol use, unhealthy diet, and physical inactivity among adults”. Adopting the Capability (C), Opportunity (O), Motivation (M), Behavior (B) (COM-B) framework for behaviour change, it sought to: (1) identify the mechanisms through which CBIs could reduce tobacco use and alcohol consumption and increase physical activity and the consumption of healthy diets and (2) examine the contextual factors that trigger the impact of these mechanisms on these risk behaviours among adults. Methods: Pawson’s realist review method was used to examine the literature. Empirical evidence and theoretical understanding were combined to develop a realist program theory that explains how CBIs influence NCD risk behaviours. Documents published between 2002 and 2020 were systematically searched in five electronic databases (CINAHL, Cochrane Library, Medline, ProQuest Central, and PsycINFO). They were included if they reported on community-based interventions aimed at cardiovascular diseases, cancers, respiratory diseases, and diabetes in a global context; and had an outcome targeted at smoking, alcohol, physical activity, and diet. Findings: Twenty-nine scientific documents were retrieved and included in the review. Over half of them (n = 18; 62%) focused on three of the four risk behaviours investigated in this review. The review identified four mechanisms: capability, opportunity, motivation, and social support that are likely to change the dietary and physical activity behaviours in adults given certain contexts. There were weak explanations of how the identified mechanisms could likely change smoking and alcohol consumption habits. In addition, eight contextual factors that may affect how these mechanisms impact physical activity and dietary behaviours were identified: suitability to work and family obligations, risk status awareness, socioeconomic status, literacy level, perceived need, availability and access to resources, culture, and group format. Conclusion: The findings suggest that CBIs are likely to improve the physical activity and dietary habits of adults if the intervention function seeks to educate, incentivize, change the environment, and model the right behaviours. The review applies and advances theory, realist research, and the design and implementation of community-based interventions for NCD prevention.

Keywords: community-based interventions, noncommunicable disease, realist program theory, risk behaviors

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19690 Monitor Vehicle Speed Using Internet of Things Based Wireless Sensor Network System

Authors: Akber Oumer Abdurezak

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Road traffic accident is a major problem in Ethiopia, resulting in the deaths of many people and potential injuries and crash every year and loss of properties. According to the Federal Transport Authority, one of the main causes of traffic accident and crash in Ethiopia is over speeding. Implementation of different technologies is used to monitor the speed of vehicles in order to minimize accidents and crashes. This research aimed at designing a speed monitoring system to monitor the speed of travelling vehicles and movements, reporting illegal speeds or overspeeding vehicles to the concerned bodies. The implementation of the system is through a wireless sensor network. The proposed system can sense and detect the movement of vehicles, process, and analysis the data obtained from the sensor and the cloud system. The data is sent to the central controlling server. The system contains accelerometer and gyroscope sensors to sense and collect the data of the vehicle. Arduino to process the data and Global System for Mobile Communication (GSM) module for communication purposes to send the data to the concerned body. When the speed of the vehicle exceeds the allowable speed limit, the system sends a message to database as “over speeding”. Both accelerometer and gyroscope sensors are used to collect acceleration data. The acceleration data then convert to speed, and the corresponding speed is checked with the speed limit, and those above the speed limit are reported to the concerned authorities to avoid frequent accidents. The proposed system decreases the occurrence of accidents and crashes due to overspeeding and can be used as an eye opener for the implementation of other intelligent transport system technologies. This system can also integrate with other technologies like GPS and Google Maps to obtain better output.

Keywords: accelerometer, IOT, GSM, gyroscope

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19689 Maryland Restoration of Anterior Tooth Loss as a Minimal Invasive Dentistry: An Alternative Treatment

Authors: B. Oral, C. Bal, M. S. Kar, A. Akgürbüz

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Loss of maxillary central incisors occurs in many patients, and the treatment of young adults with this problem is a challenge for both prosthodontists and orthodontists. Common treatment alternatives are distalization of adjacent teeth and fabrication of a conventional 3-unit fixed partial denture, a single implant supported crown restoration or a resin-bonded fixed partial denture. This case report describes the indication of a resin-bonded fixed partial denture, preparation of the abutment teeth and the prosthetic procedures. The technique described here represents a conservative, esthetically pleasing and rapid solution for the missing maxillary central incisor when implant placement and/or guided bone regeneration techniques are not feasible because of financial, social or time restrictions. In this case a 16 year-old female patient who lost her maxillary left central incisor six years ago in a bicycle accident applied to our clinic with a major complaint of her unaesthetic appearance associated with the loss of her maxillary left central incisor. Although there was an indication for orthodontic treatment because of the limited space at the traumatized area, the patient did not accept to receive any orthodontic procedure. That is why an implant supported restoration could not be an option for the narrow area. Therefore maryland bridge as a minimal invasive dental therapy was preferred as a retention appliance so the patient's aesthetic appearance was restored.

Keywords: Maryland bridge, single tooth restoration, aesthetics, maxillary central incisors

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19688 Chemopreventive Efficacy of Andrographolide in Rat Colon Carcinogenesis Model Using Aberrant Crypt Foci (ACF) as Endpoint Marker

Authors: Maryam Hajrezaie, Mahmood Ameen Abdulla, Nazia Abdul Majid, Hapipa Mohd Ali, Pouya Hassandarvish, Maryam Zahedi Fard

Abstract:

Background: Colon cancer is one of the most prevalent cancers in the world and is the third leading cause of death among cancers in both males and females. The incidence of colon cancer is ranked fourth among all cancers but varies in different parts of the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. Andrographolide is the major labdane diterpenoidal constituent of the plant Andrographis paniculata (family Acanthaceae), used extensively in the traditional medicine. Extracts of the plant and their constituents are reported to exhibit a wide spectrum of biological activities of therapeutic importance. Laboratory animal model studies have provided evidence that Andrographolide play a role in inhibiting the risk of certain cancers. Objective: Our aim was to evaluate the chemopreventive efficacy of the Andrographolide in the AOM induced rat model. Methods: To evaluate inhibitory properties of andrographolide on colonic aberrant crypt foci (ACF), five groups of 7-week-old male rats were used. Group 1 (control group) were fed with 10% Tween 20 once a day, Group 2 (cancer control) rats were intra-peritoneally injected with 15 mg/kg Azoxymethan, Gropu 3 (drug control) rats were injected with 15 mg/kg azoxymethan and 5-Flourouracil, Group 4 and 5 (experimental groups) were fed with 10 and 20 mg/kg andrographolide each once a day. After 1 week, the treatment group rats received subcutaneous injections of azoxymethane, 15 mg/kg body weight, once weekly for 2 weeks. Control rats were continued on Tween 20 feeding once a day and experimental groups 10 and 20 mg/kg andrographolide feeding once a day for 8 weeks. All rats were sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated grossly and histopathologically for ACF. Results: Administration of 10 mg/kg and 20 mg/kg andrographolide were found to be effectively chemoprotective, as evidenced microscopily and biochemically. Andrographolide suppressed total colonic ACF formation up to 40% to 60%, respectively, when compared with control group. Pre-treatment with andrographolide, significantly reduced the impact of AOM toxicity on plasma protein and urea levels as well as on plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GGT) activities. Grossly, colorectal specimens revealed that andrographolide treatments decreased the mean score of number of crypts in AOM-treated rats. Importantly, rats fed andrographolide showed 75% inhibition of foci containing four or more aberrant crypts. The results also showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE2) activities and a decrease in malondialdehyde (MDA) level. Histologically all treatment groups showed a significant decrease of dysplasia as compared to control group. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. Conclusion: The current study demonstrated that Andrographolide reduce the number of ACF. According to these data, Andrographolide might be a promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, andrographolide, colon cancer, aberrant crypt foci (ACF)

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19687 A Study of Interleukin-1β Genetic Polymorphisms in Gastric Carcinoma and Colorectal Carcinoma in Egyptian Patients

Authors: Mariam Khaled, Noha Farag, Ghada Mohamed Abdel Salam, Khaled Abu-Aisha, Mohamed El-Azizi

Abstract:

Gastric and colorectal cancers are among the most frequent causes of cancer-associated mortalities in Africa. They have been considered as a global public health concern, as nearly one million new cases are reported per year. IL-1β is a pro-inflammatory cytokine-produced by activated macrophages and monocytes- and a member of the IL-1 family. The inactive IL-1β precursor is cleaved and activated by caspase-1 enzyme, which itself is activated by the assembly of intracellular structures defined as NLRP3 (Nod Like receptor P3) inflammasomes. Activated IL-1β stimulates the Interleukin-1 receptor type-1 (IL-1R1), which is responsible for the initiation of a signal transduction pathway leading to cell proliferation. It has been proven that the IL-1β gene is a highly polymorphic gene in which single nucleotide polymorphisms (SNPs) may affect its expression. It has been previously reported that SNPs including base transitions between C and T at positions, -511 (C-T; dbSNP: rs16944) and -31 (C-T; dbSNP: rs1143627), from the transcriptional start site, contribute to the pathogenesis of gastric and colorectal cancers by affecting IL-1β levels. Altered production of IL-1β due to such polymorphisms is suspected to stimulate an amplified inflammatory response and promote Epithelial Mesenchymal Transition leading to malignancy. Allele frequency distribution of the IL-1β-31 and -511 SNPs, in different populations, and their correlation to the incidence of gastric and colorectal cancers, has been intriguing to researchers worldwide. The current study aims to investigate allele distributions of the IL-1β SNPs among gastric and colorectal cancers Egyptian patients. In order to achieve to that, 89 Biopsy and surgical specimens from the antrum and corpus mucosa of chronic gastritis subjects and gastric and colorectal carcinoma patients was collected for DNA extraction followed by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). The amplified PCR products of IL-1β-31C > T and IL-1β-511T > C were digested by incubation with the restriction endonuclease enzymes ALu1 and Ava1. Statistical analysis was carried out to determine the allele frequency distribution in the three studied groups. Also, the effect of the IL-1β -31 and -511 SNPs on nuclear factor binding was analyzed using Fluorescence Electrophoretic Mobility Shift Assay (EMSA), preceded by nuclear factor extraction from gastric and colorectal tissue samples and LPS stimulated monocytes. The results of this study showed that a significantly higher percentage of Egyptian gastric cancer patients have a homozygous CC genotype at the IL-1β-31 position and a heterozygous TC genotype at the IL-1β-511 position. Moreover, a significantly higher percentage of the colorectal cancer patients have a homozygous CC genotype at the IL-1β-31 and -511 positions as compared to the control group. In addition, the EMSA results showed that IL-1β-31C/T and IL-1β-511T/C SNPs do not affect nuclear factor binding. Results of this study suggest that the IL-1β-31 C/T and IL-1β-511 T/C may be correlated to the incidence of gastric cancer in Egyptian patients; however, similar findings couldn’t be proven in the colorectal cancer patients group for the IL-1β-511 T/C SNP. This is the first study to investigate IL-1β -31 and -511 SNPs in the Egyptian population.

Keywords: colorectal cancer, Egyptian patients, gastric cancer, interleukin-1β, single nucleotide polymorphisms

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19686 Dietary Flaxseed Decreases Central Blood Pressure and the Concentrations of Plasma Oxylipins Associated with Hypertension in Patients with Peripheral Arterial Disease

Authors: Stephanie PB Caligiuri, Harold M Aukema, Delfin Rodriguez-Leyva, Amir Ravandi, Randy Guzman, Grant N. Pierce

Abstract:

Background: Hypertension leads to cardiac and cerebral events and therefore is the leading risk factor attributed to death in the world. Oxylipins may be mediators in these events as they can regulate vascular tone and inflammation. Oxylipins are derived from fatty acids. Dietary flaxseed is rich in the n3 fatty acid, alpha-linolenic acid, and, therefore, may have the ability to change the substrate profile of oxylipins. As a result, this could alter blood pressure. Methods: A randomized, double-blinded, controlled clinical trial, the Flax-PAD trial, was used to assess the impact of dietary flaxseed on blood pressure (BP), and to also assess the relationship of plasma oxylipins to BP in 81 patients with peripheral arterial disease (PAD). Patients with PAD were chosen for the clinical trial as they are at an increased risk for hypertension and cardiac and cerebral events. Thirty grams of ground flaxseed were added to food products to consume on a daily basis for 6 months. The control food products contained wheat germ, wheat bran, and mixed dietary oils instead of flaxseed. Central BP, which is more significantly associated to organ damage, cardiac, and cerebral events versus brachial BP, was measured by pulse wave analysis at baseline and 6 months. A plasma profile of 43 oxylipins was generated using solid phase extraction, HPLC-MS/MS, and stable isotope dilution quantitation. Results: At baseline, the central BP (systolic/diastolic) in the placebo and flaxseed group were, 131/73 ± 2.5/1.4 mmHg and 128/71 ± 2.6/1.4 mmHg, respectively. After 6 months of intervention, the flaxseed group exhibited a decrease in blood pressure of 4.0/1.0 mmHg. The 6 month central BP in the placebo and flaxseed groups were, 132/74 ± 2.9/1.8 mmHg and 124/70 ± 2.6/1.6 mmHg (P<0.05). Correlation and logistic regression analyses between central blood pressure and oxylipins were performed. Significant associations were observed between central blood pressure and 17 oxylipins, primarily produced from arachidonic acid. Every 1 nM increase in 16-hydroxyeicosatetraenoic acid (HETE) increased the odds of having high central systolic BP by 15-fold, of having high central diastolic BP by 6-fold and of having high central mean arterial pressure by 15-fold. In addition, every 1 nM increase in 5,6-dihydroxyeicosatrienoic acid (DHET) and 11,12-DHET increased the odds of having high central mean arterial pressure by 45- and 18-fold, respectively. Flaxseed induced a significant decrease in these as well as 4 other vasoconstrictive oxylipins. Conclusion: Dietary flaxseed significantly lowered blood pressure in patients with PAD and hypertension. Plasma oxylipins were strongly associated with central blood pressure and may have mediated the flaxseed-induced decrease in blood pressure.

Keywords: hypertension, flaxseed, oxylipins, peripheral arterial disease

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19685 Managing Uncertainty in Unmanned Aircraft System Safety Performance Requirements Compliance Process

Authors: Achim Washington, Reece Clothier, Jose Silva

Abstract:

System Safety Regulations (SSR) are a central component to the airworthiness certification of Unmanned Aircraft Systems (UAS). There is significant debate on the setting of appropriate SSR for UAS. Putting this debate aside, the challenge lies in how to apply the system safety process to UAS, which lacks the data and operational heritage of conventionally piloted aircraft. The limited knowledge and lack of operational data result in uncertainty in the system safety assessment of UAS. This uncertainty can lead to incorrect compliance findings and the potential certification and operation of UAS that do not meet minimum safety performance requirements. The existing system safety assessment and compliance processes, as used for conventional piloted aviation, do not adequately account for the uncertainty, limiting the suitability of its application to UAS. This paper discusses the challenges of undertaking system safety assessments for UAS and presents current and envisaged research towards addressing these challenges. It aims to highlight the main advantages associated with adopting a risk based framework to the System Safety Performance Requirement (SSPR) compliance process that is capable of taking the uncertainty associated with each of the outputs of the system safety assessment process into consideration. Based on this study, it is made clear that developing a framework tailored to UAS, would allow for a more rational, transparent and systematic approach to decision making. This would reduce the need for conservative assumptions and take the risk posed by each UAS into consideration while determining its state of compliance to the SSR.

Keywords: Part 1309 regulations, risk models, uncertainty, unmanned aircraft systems

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19684 Increasing a Computer Performance by Overclocking Central Processing Unit (CPU)

Authors: Witthaya Mekhum, Wutthikorn Malikong

Abstract:

The objective of this study is to investigate the increasing desktop computer performance after overclocking central processing unit or CPU by running a computer component at a higher clock rate (more clock cycles per second) than it was designed at the rate of 0.1 GHz for each level or 100 MHz starting at 4000 GHz-4500 GHz. The computer performance is tested for each level with 4 programs, i.e. Hyper PI ver. 0.99b, Cinebench R15, LinX ver.0.6.4 and WinRAR . After the CPU overclock, the computer performance increased. When overclocking CPU at 29% the computer performance tested by Hyper PI ver. 0.99b increased by 10.03% and when tested by Cinebench R15 the performance increased by 20.05% and when tested by LinX Program the performance increased by 16.61%. However, the performance increased only 8.14% when tested with Winrar program. The computer performance did not increase according to the overclock rate because the computer consists of many components such as Random Access Memory or RAM, Hard disk Drive, Motherboard and Display Card, etc.

Keywords: overclock, performance, central processing unit, computer

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19683 Increasing the System Availability of Data Centers by Using Virtualization Technologies

Authors: Chris Ewe, Naoum Jamous, Holger Schrödl

Abstract:

Like most entrepreneurs, data center operators pursue goals such as profit-maximization, improvement of the company’s reputation or basically to exist on the market. Part of those aims is to guarantee a given quality of service. Quality characteristics are specified in a contract called the service level agreement. Central part of this agreement is non-functional properties of an IT service. The system availability is one of the most important properties as it will be shown in this paper. To comply with availability requirements, data center operators can use virtualization technologies. A clear model to assess the effect of virtualization functions on the parts of a data center in relation to the system availability is still missing. This paper aims to introduce a basic model that shows these connections, and consider if the identified effects are positive or negative. Thus, this work also points out possible disadvantages of the technology. In consequence, the paper shows opportunities as well as risks of data center virtualization in relation to system availability.

Keywords: availability, cloud computing IT service, quality of service, service level agreement, virtualization

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19682 Tourism Area Development Optimation Based on Solar-Generated Renewable Energy Technology at Karimunjawa, Central Java Province, Indonesia

Authors: Yanuar Tri Wahyu Saputra, Ramadhani Pamapta Putra

Abstract:

Karimunjawa is one among Indonesian islands which is lacking of electricity supply. Despite condition above, Karimunjawa is an important tourism object in Indonesia's Central Java Province. Solar Power Plant is a potential technology to be applied in Karimunjawa, in order to fulfill the island's electrical supply need and to increase daily life and tourism quality among tourists and local population. This optimation modeling of Karimunjawa uses HOMER software program. The data we uses include wind speed data in Karimunjawa from BMKG (Indonesian Agency for Meteorology, Climatology and Geophysics), annual weather data in Karimunjawa from NASA, electricity requirements assumption data based on number of houses and business infrastructures in Karimunjawa. This modeling aims to choose which three system categories offer the highest financial profit with the lowest total Net Present Cost (NPC). The first category uses only PV with 8000 kW of electrical power and NPC value of $6.830.701. The second category uses hybrid system which involves both 1000 kW PV and 100 kW generator which results in total NPC of $6.865.590. The last category uses only generator with 750 kW of electrical power that results in total NPC of $ 16.368.197, the highest total NPC among the three categories. Based on the analysis above, we can conclude that the most optimal way to fulfill the electricity needs in Karimunjawa is to use 8000 kW PV with lower maintenance cost.

Keywords: Karimunjawa, renewable energy, solar power plant, HOMER

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19681 Contribution to the Hydrogeochemical Investigations on the Wajid Aquifer System, Southwestern Part of Saudi Arabia

Authors: Mohamed Ahmed, Ezat Korany, Abdelaziz Al Basam, Osama Kasem

Abstract:

The arid climate, low rate of precipitations and population reflect the increasing of groundwater uses as the main source of water in Saudi Arabia. The Wajid Aquifer System represents a regional groundwater aquifer system along the edge of the crystalline Arabian Shield near the southwestern tip of the Arabian Peninsula. The aquifer extends across the border of Saudi Arabia and Yemen from the Asir –Yemen Highlands to the Rub al Khali Depression and possibly to the Gulf coast (at the southwestern tip). The present work is representing a hydrogeochemical investigation on the Wajid Aquifer System. The studied area is being classified into three zones. The 1st zone is West of Wadi Ad Dawasir (Northern part of the studied area), the 2nd is Najran-Asir Zone (southern part of the studied area), and the 3rd zone is the intermediate -central zone (occupying the central area between the last two zones). The groundwater samples were collected and chemically analyzed for physicochemical properties such as pH, electrical conductivity, total hardness (TH), alkalinity (pH), total dissolved solids (TDS), major ions (Ca2+, Mg2+, Na+, K+, HCO3-, SO42- and Cl-), and trace elements. Some parameters such as sodium adsorption ratio (SAR), soluble sodium percentage (Na%), potential salinity, residual sodium carbonate, Kelly's ratio, permeability index and Gibbs ratio, hydrochemical coefficients, hydrochemical formula, ion dominance, salt combinations and water types were also calculated in order to evaluate the quality of the groundwater resources in the selected areas for different purposes. The distribution of the chemical constituents and their interrelationships are illustrated by different hydrochemical graphs. Groundwater depths and the depth to water were measured to study the effect of discharge on both the water level and the salinity of the studied groundwater wells. A detailed comparison between the three studied zones according to the variations shown by the chemical and field investigations are discussed in detailed within the work.

Keywords: Najran-Asir, Wadi Ad Dawasir, Wajid Aquifer System, effect of discharge

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19680 Identification of Shocks from Unconventional Monetary Policy Measures

Authors: Margarita Grushanina

Abstract:

After several prominent central banks including European Central Bank (ECB), Federal Reserve System (Fed), Bank of Japan and Bank of England employed unconventional monetary policies in the aftermath of the financial crisis of 2008-2009 the problem of identification of the effects from such policies became of great interest. One of the main difficulties in identification of shocks from unconventional monetary policy measures in structural VAR analysis is that they often are anticipated, which leads to a non-fundamental MA representation of the VAR model. Moreover, the unconventional monetary policy actions may indirectly transmit to markets information about the future stance of the interest rate, which raises a question of the plausibility of the assumption of orthogonality between shocks from unconventional and conventional policy measures. This paper offers a method of identification that takes into account the abovementioned issues. The author uses factor-augmented VARs to increase the information set and identification through heteroskedasticity of error terms and rank restrictions on the errors’ second moments’ matrix to deal with the cross-correlation of the structural shocks.

Keywords: factor-augmented VARs, identification through heteroskedasticity, monetary policy, structural VARs

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19679 Central Finite Volume Methods Applied in Relativistic Magnetohydrodynamics: Applications in Disks and Jets

Authors: Raphael de Oliveira Garcia, Samuel Rocha de Oliveira

Abstract:

We have developed a new computer program in Fortran 90, in order to obtain numerical solutions of a system of Relativistic Magnetohydrodynamics partial differential equations with predetermined gravitation (GRMHD), capable of simulating the formation of relativistic jets from the accretion disk of matter up to his ejection. Initially we carried out a study on numerical methods of unidimensional Finite Volume, namely Lax-Friedrichs, Lax-Wendroff, Nessyahu-Tadmor method and Godunov methods dependent on Riemann problems, applied to equations Euler in order to verify their main features and make comparisons among those methods. It was then implemented the method of Finite Volume Centered of Nessyahu-Tadmor, a numerical schemes that has a formulation free and without dimensional separation of Riemann problem solvers, even in two or more spatial dimensions, at this point, already applied in equations GRMHD. Finally, the Nessyahu-Tadmor method was possible to obtain stable numerical solutions - without spurious oscillations or excessive dissipation - from the magnetized accretion disk process in rotation with respect to a central black hole (BH) Schwarzschild and immersed in a magnetosphere, for the ejection of matter in the form of jet over a distance of fourteen times the radius of the BH, a record in terms of astrophysical simulation of this kind. Also in our simulations, we managed to get substructures jets. A great advantage obtained was that, with the our code, we got simulate GRMHD equations in a simple personal computer.

Keywords: finite volume methods, central schemes, fortran 90, relativistic astrophysics, jet

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19678 IL6/PI3K/mTOR/GFAP Molecular Pathway Role in COVID-19-Induced Neurodegenerative Autophagy, Impacts and Relatives

Authors: Mohammadjavad Sotoudeheian

Abstract:

COVID-19, which began in December 2019, uses the angiotensin-converting enzyme 2 (ACE2) receptor to enter and spread through the cells. ACE2 mRNA is present in almost every organ, including nasopharynx, lung, as well as the brain. Ports of entry of SARS-CoV-2 into the central nervous system (CNS) may include arterial circulation, while viremia is remarkable. However, it is imperious to develop neurological symptoms evaluation CSF analysis in patients with COVID-19, but theoretically, ACE2 receptors are expressed in cerebellar cells and may be a target for SARS-CoV-2 infection in the brain. Recent evidence agrees that SARS-CoV-2 can impact the brain through direct and indirect injury. Two biomarkers for CNS injury, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NFL) detected in the plasma of patients with COVID-19. NFL, an axonal protein expressed in neurons, is related to axonal neurodegeneration, and GFAP is over-expressed in CNS inflammation. GFAP cytoplasmic accumulation causes Schwan cells to misfunction, so affects myelin generation, reduces neuroskeletal support over NfLs during CNS inflammation, and leads to axonal degeneration. Interleukin-6 (IL-6), which extensively over-express due to interleukin storm during COVID-19 inflammation, regulates gene expression, as well as GFAP through STAT molecular pathway. IL-6 also impresses the phosphoinositide 3-kinase (PI3K)/STAT/smads pathway. The PI3K/ protein kinase B (Akt) pathway is the main modulator upstream of the mammalian target of rapamycin (mTOR), and alterations in this pathway are common in neurodegenerative diseases. Most neurodegenerative diseases show a disruption of autophagic function and display an abnormal increase in protein aggregation that promotes cellular death. Therefore, induction of autophagy has been recommended as a rational approach to help neurons clear abnormal protein aggregates and survive. The mTOR is a major regulator of the autophagic process and is regulated by cellular stressors. The mTORC1 pathway and mTORC2, as complementary and important elements in mTORC1 signaling, have become relevant in the regulation of the autophagic process and cellular survival through the extracellular signal-regulated kinase (ERK) pathway.

Keywords: mTORC1, COVID-19, PI3K, autophagy, neurodegeneration

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19677 Screening for Non-hallucinogenic Neuroplastogens as Drug Candidates for the Treatment of Anxiety, Depression, and Posttraumatic Stress Disorder

Authors: Jillian M. Hagel, Joseph E. Tucker, Peter J. Facchini

Abstract:

With the aim of establishing a holistic approach for the treatment of central nervous system (CNS) disorders, we are pursuing a drug development program rapidly progressing through discovery and characterization phases. The drug candidates identified in this program are referred to as neuroplastogens owing to their ability to mediate neuroplasticity, which can be beneficial to patients suffering from anxiety, depression, or posttraumatic stress disorder. These and other related neuropsychiatric conditions are associated with the onset of neuronal atrophy, which is defined as a reduction in the number and/or productivity of neurons. The stimulation of neuroplasticity results in an increase in the connectivity between neurons and promotes the restoration of healthy brain function. We have synthesized a substantial catalogue of proprietary indolethylamine derivatives based on the general structures of serotonin (5-hydroxytryptamine) and psychedelic molecules such as N,N-dimethyltryptamine (DMT) and psilocin (4-hydroxy-DMT) that function as neuroplastogens. A primary objective in our screening protocol is the identification of derivatives associated with a significant reduction in hallucination, which will allow administration of the drug at a dose that induces neuroplasticity and triggers other efficacious outcomes in the treatment of targeted CNS disorders but which does not cause a psychedelic response in the patient. Both neuroplasticity and hallucination are associated with engagement of the 5HT2A receptor, requiring drug candidates differentially coupled to these two outcomes at a molecular level. We use novel and proprietary artificial intelligence algorithms to predict the mode of binding to the 5HT2A receptor, which has been shown to correlate with the hallucinogenic response. Hallucination is tested using the mouse head-twitch response model, whereas mouse marble-burying and sucrose preference assays are used to evaluate anxiolytic and anti-depressive potential. Neuroplasticity is assays using dendritic outgrowth assays and cell-based ELISA analysis. Pharmacokinetics and additional receptor-binding analyses also contribute the selection of lead candidates. A summary of the program is presented.

Keywords: neuroplastogen, non-hallucinogenic, drug development, anxiety, depression, PTSD, indolethylamine derivatives, psychedelic-inspired, 5-HT2A receptor, computational chemistry, head-twitch response behavioural model, neurite outgrowth assay

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