Search results for: inborn errors of metabolism (IEM)
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1417

Search results for: inborn errors of metabolism (IEM)

367 Transcriptomic Analysis of Fragrant Rice Reveals the Involvement of Post-transcriptional Regulation in Response to Zn Foliar Application

Authors: Muhammad Imran, Sarfraz Shafiq, Xiangru Tang

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Alternative splicing (AS) is an important post-transcriptional regulatory mechanism to generate transcripts variability and proteome diversity in plants. Fragrant rice (Oryza sativa L.) has a high economic and nutritional value, and the application of micronutrients regulate 2-acetyl-1-pyrroline (2-AP) production, which is responsible for aroma in fragrant rice. However, no systematic investigation of AS events in response to micronutrients (Zn) has been performed in fragrant rice. Furthermore, the post-transcriptional regulation of genes involved in 2-AP biosynthesis is also not known. In this study, a comprehensive analysis of AS events under two gradients of Zn treatment in two different fragrant rice cultivars (Meixiangzhan-2 and Xiangyaxiangzhan) was performed. A total of 386 and 598 significant AS events were found in Meixiangzhan-2 treated with low and high doses of Zn, respectively. In Xiangyaxiangzhan, a total of 449 and 598 significant AS events were found in low and high doses of Zn, respectively. Go analysis indicated that these genes were highly enriched in physiological processes, metabolism, and cellular process in both cultivars. However, genotype and dose-dependent AS events were also detected in both cultivars. By comparing differential AS (DAS) events with differentially expressed genes (DEGs), we found a weak overlap among DAS and DEGs in both fragrant rice cultivars, indicating that only a few genes are post-transcriptionally regulated in response to Zn treatment. We further report that Zn differentially regulates the expression of 2-AP biosynthesis-related genes in both cultivars, and Zn treatment altered the editing frequency of SNPs in the genes involved in 2-AP biosynthesis. Finally, we showed that epigenetic modifications associated with active gene transcription are generally enriched over 2-AP biosynthesis-related genes. Taken together, our results provide evidence of the post-transcriptional gene regulation in fragrant rice in response to Zn treatment and highlight that the 2-AP biosynthesis pathway may also be post-transcriptionally regulated through epigenetic modifications. These findings will serve as a cornerstone for further investigation to understand the molecular mechanisms of 2-AP biosynthesis in fragrant rice.

Keywords: fragrant rice, 2-acetyl-1-pyrroline, gene expression, zinc, alternative splicing, SNPs

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366 The Understanding of Biochemical and Molecular Analysis of Diabetic Rats Treated with Andrographis paniculata and Erythrina indica Methanol Extract

Authors: Chakrapani Pullagummi, Arun Jyothi Bheemagani, B. Chandra Sekhar Singh, Prem Kumar, A. Roja Rani

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Diabetes mellitus describes a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion and its action. The objective of present study was alloxan induced diabetes in S.D (Sprague Dawley) rats, treated with leaf extract of Andrographis paniculata and bark extract of Erythrina indica. Plant extract treated rats were analyzed biochemically and molecularly. on normal and diabetic rats. The changes in MDA (lipid peroxidation) and glucose (by GOD method) levels in blood of both normal and diabetic rat were analyzed. Diabetes induced rats were treated with methanolic extracts of Andrographis paniculata leaf and Erythrina indica bark which are of medicinal importance. Later after inducing diabetes the rats were treated with medicinal plant extracts, Andrographis paniculata leaf and Erythrina indica bark which are well known for their anti diabetic and antioxidative property in order to control the glucose and MDA levels. The blood plasma of diabetic and normal rats was analyzed for the levels of MDA (lipid peroxidation) and glucose levels. Results of this study suggested that the Andrographis paniculata leaf and Erythrina indica can be used as a potential natural antidiabetic agent for treating and postponing the appearance of complications that arise due to Diabetes. Molecular study deals with the analysis of binding mechanism of 2 selected natural compounds from Andrographis and Erythrina extracts against the novel target for type T2D namely PPAR-γ compared with Rosiglitazone (standard compound). The results revealed that most of the selected herbal lead compounds were effective targets against the receptors. These compounds showed favorable interactions with the amino acid residues thereby substantiating their proven efficacy as anti-diabetic compounds.

Keywords: andrographis paniculata, erythrina indica, alloxan, lipid peroxidation, blood glucose level, PPAR-γ

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365 Paramecuim as a Model for the Evaluation of Toxicity (Growth, Total Proteins, Respiratory and GSH Bio Marker Changes) Observed after Treatment with Essential Oils Isolated from Artemisia herba-alba Plant of Algeria

Authors: Bouchiha Hanene, Rouabhi Rachid, Bouchama Khaled, Djebar Berrebbah Houraya, Djebar Mohamed Reda

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Recently, some natural products such as essentials oils (EOs) have been used in the fields as alternative to synthetic compounds, to minimize the negative impacts to the environment. This fact has led to questions about the possible impact of EOs on ecosystems. Currently in toxicology, the use of alternative models can help to understand the mechanisms of toxic action, at different levels of organization of ecosystems. Algae, protozoa and bacteria form the base of the food chain and protozoan cells are used as bioindicators often of pollution in environment. Unicellular organisms offer the possibility of direct study of independent cells with specific characteristics of individual cells and whole organisms at the same time. This unicellular facilitates the study of physiological processes, and effects of pollutants at the cellular level, which makes it widely used to assess the toxic effects of various xenobiotics. This study aimed to verify the effects of EOs of one famous plant used tremendously in our folk medicine, namely Artemisia herba alba in causing acute toxicity (24 hours) and chronic (15 days) toxicity for model cellular (Paramecium sp). To this end, cellular’s of paramecium were exposed to various concentrations (Three doses were chosen) of EOs extracted from plant (Artemisia herba alba). In the first experiment, the cellular s cultures were exposed for 48 hours to different concentrations to determine the median lethal concentration (DL50). We followed the evolution of physiological parameters (growth), biochemical (total proteins, respiratory metabolism), as well as the variations of a bio marker the GSH. Our results highlighted a light inhibition of the growth of the protozoa as well as a disturbance of the contents of total proteins and a reduction in the reduced rate of glutathione. The polarographic study revealed a stimulation of the consumption of O2 and this at the treated cells.

Keywords: essential oils, protozoa, bio indicators, toxicity, Growth, bio marker, proteins, polarographic

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364 Impact Analysis of Quality Control Practices in Veterinary Diagnostic Labs in Lahore, Pakistan

Authors: Faiza Marrium, Masood Rabbani, Ali Ahmad Sheikh, Muhammad Yasin Tipu Javed Muhammad, Sohail Raza

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More than 75% diseases spreading in the past 10 years in human population globally are linked to veterinary sector. Veterinary diagnostic labs are the powerful ally for diagnosis, prevention and monitoring of animal diseases in any country. In order to avoid detrimental effects of errors in disease diagnostic and biorisk management, there is a dire need to establish quality control system. In current study, 3 private and 6 public sectors veterinary diagnostic labs were selected for survey. A questionnaire survey in biorisk management guidelines of CWA 15793 was designed to find quality control breaches in lab design, personal, equipment and consumable, quality control measures adopted in lab, waste management, environmental monitoring and customer care. The data was analyzed through frequency distribution statistically by using (SPSS) version 18.0. A non-significant difference was found in all parameters of lab design, personal, equipment and consumable, quality control measures adopted in lab, waste management, environmental monitoring and customer care with an average percentage of 46.6, 57.77, 52.7, 55.5, 54.44, 48.88 and 60, respectively. A non-significant difference among all nine labs were found, with highest average compliance percentage of all parameters are lab 2 (78.13), Lab 3 (70.56), Lab 5 (57.51), Lab 6 (56.37), Lab 4 (55.02), Lab 9 (49.58), Lab 7 (47.76), Lab 1 (41.01) and Lab 8 (36.09). This study shows that in Lahore district veterinary diagnostic labs are not giving proper attention to quality of their system and there is no significant difference between setups of private and public sector laboratories. These results show that most of parameters are between 50 and 80 percent, which needs some work and improvement as per WHO criteria.

Keywords: veterinary lab, quality management system, accreditation, regulatory body, disease identification

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363 Simulation-Based Validation of Safe Human-Robot-Collaboration

Authors: Titanilla Komenda

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Human-machine-collaboration defines a direct interaction between humans and machines to fulfil specific tasks. Those so-called collaborative machines are used without fencing and interact with humans in predefined workspaces. Even though, human-machine-collaboration enables a flexible adaption to variable degrees of freedom, industrial applications are rarely found. The reasons for this are not technical progress but rather limitations in planning processes ensuring safety for operators. Until now, humans and machines were mainly considered separately in the planning process, focusing on ergonomics and system performance respectively. Within human-machine-collaboration, those aspects must not be seen in isolation from each other but rather need to be analysed in interaction. Furthermore, a simulation model is needed that can validate the system performance and ensure the safety for the operator at any given time. Following on from this, a holistic simulation model is presented, enabling a simulative representation of collaborative tasks – including both, humans and machines. The presented model does not only include a geometry and a motion model of interacting humans and machines but also a numerical behaviour model of humans as well as a Boole’s probabilistic sensor model. With this, error scenarios can be simulated by validating system behaviour in unplanned situations. As these models can be defined on the basis of Failure Mode and Effects Analysis as well as probabilities of errors, the implementation in a collaborative model is discussed and evaluated regarding limitations and simulation times. The functionality of the model is shown on industrial applications by comparing simulation results with video data. The analysis shows the impact of considering human factors in the planning process in contrast to only meeting system performance. In this sense, an optimisation function is presented that meets the trade-off between human and machine factors and aids in a successful and safe realisation of collaborative scenarios.

Keywords: human-machine-system, human-robot-collaboration, safety, simulation

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362 Autophagy Defects That Modify Human Immune Cell Metabolism and Promote Aging-Associated Inflammation

Authors: Grace McCambridge, Alanna Keady, Madhur Agrawal, Dequina Nicholas Alvarado, Barbara Nikolajczyk, Leena Panneerseelan-Bharath

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Age is a non-modifiable risk factor for the inflammation that underlies pathologies such as type 2 diabetes mellitus (T2DM). Inflammation, as indicated by circulating cytokines, rises in aging, but mechanisms that promote this ‘inflammaging’ remain poorly defined. Furthermore, downstream consequences of inflammaging, including the development of an inflammatory profile that predicts comorbidities like T2DM, remain speculative. We tested the possibility that natural aging-associated changes in autophagy, a process that is compromised in both aging and T2DM, regulates inflammatory profiles in older subjects. Our data showed that circulating CD4⁺ T cells from older compared to younger subjects have (i) defects in autophagy; (ii) higher mitochondria accumulation; (iii) a failure to metabolically shift from oxidative phosphorylation to anaerobic glycolysis upon αCD3/CD28 activation; (iv) more reactive oxygen species (ROS) accumulation; and (v) a cytokine profile that recapitulates the Th17 profile that predicts T2DM. ROS scavenging in cells from older subjects restored mitochondrial mass and membrane potential (indicators of improved autophagy) and reduced Th17 cytokines to amounts made by T cells from younger subjects. Knock-down of the autophagy protein Atg3 in T cells from younger subjects increased mitochondrial accumulation and Th17 cytokines. To begin translating these findings to clinical practice, we showed that physiological concentrations of the diabetes drug metformin (100 µM) added in vitro enhanced autophagy, prevented mitochondria and ROS accumulation, increased anaerobic glycolysis, and decreased Th17 cytokines in activated CD4⁺ T cells from older subjects. Metformin therefore improves autophagy and multiple downstream pro-inflammatory mechanisms CD4⁺ T cells from older subjects. We conclude that autophagy improvement ameliorates the development of a T2DM-predictive Th17 profile in aging, and thus holds promise for delay or prevention of aging-associated metabolic decline.

Keywords: autophagy, mitochondrial turnover, ROS, glycolysis

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361 Microalgae for Plant Biostimulants on Whey and Dairy Wastewaters

Authors: Sergejs Kolesovs, Pavels Semjonovs

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Whey and dairy wastewaters if disposed in the environment without proper treatment, cause serious environmental risks contributing to overall and particular environmental pollution and climate change. Biological treatment of wastewater is considered to be most eco-friendly approach, as compared to the chemical treatment methods. Research shows, that dairy wastewater can potentially be remediated by use of microalgae thussignificantly reducing the content of carbohydrates, P, N, K and other pollutants. Moreover, it has been shown, that use of dairy wastewaters results in higher microalgae biomass production. In recent decades microalgal biomass has entailed a big interest for its potential applications in pharmaceuticals, biomedicine, health supplementation, cosmetics, animal feed, plant protection, bioremediation and biofuels. It was shown, that lipids productivity on whey and dairy wastewater is higher as compared with standard cultivation media and occurred without the necessity of inducing specific stress conditions such as N starvation. Moreover, microalgae biomass production as usually associated with high production costs may benefit from perspective of both reasons – enhanced microalgae biomass or target substances productivity on cheap growth substrate and effective management of whey and dairy wastewaters, which issignificant for decrease of total production costs in both processes. Obviously, it became especially important when large volume and low cost industrial microalgal biomass production is anticipated for further use in agriculture of crops as plant growth stimulants, biopesticides soil fertilisers or remediating solutions. Environmental load of dairy wastewaters can be significantly decreased when microalgae are grown in coculture with other microorganisms. This enhances the utilisation of lactose, which is main C source in whey and dairy wastewaters when it is not metabolised easily by most microalgal species chosen. Our study showsthat certain microalgae strains can be used in treatment of residual sugars containing industrial wastewaters and decrease of their concentration thus approving that further extensive research on dairy wastewaters pre-treatment optionsfor effective cultivation of microalgae, carbon uptake and metabolism, strain selection and choice of coculture candidates is needed for further optimisation of the process.

Keywords: microalgae, whey, dairy wastewaters, sustainability, plant biostimulants

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360 Decision Making in Medicine and Treatment Strategies

Authors: Kamran Yazdanbakhsh, Somayeh Mahmoudi

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Three reasons make good use of the decision theory in medicine: 1. Increased medical knowledge and their complexity makes it difficult treatment information effectively without resorting to sophisticated analytical methods, especially when it comes to detecting errors and identify opportunities for treatment from databases of large size. 2. There is a wide geographic variability of medical practice. In a context where medical costs are, at least in part, by the patient, these changes raise doubts about the relevance of the choices made by physicians. These differences are generally attributed to differences in estimates of probabilities of success of treatment involved, and differing assessments of the results on success or failure. Without explicit criteria for decision, it is difficult to identify precisely the sources of these variations in treatment. 3. Beyond the principle of informed consent, patients need to be involved in decision-making. For this, the decision process should be explained and broken down. A decision problem is to select the best option among a set of choices. The problem is what is meant by "best option ", or know what criteria guide the choice. The purpose of decision theory is to answer this question. The systematic use of decision models allows us to better understand the differences in medical practices, and facilitates the search for consensus. About this, there are three types of situations: situations certain, risky situations, and uncertain situations: 1. In certain situations, the consequence of each decision are certain. 2. In risky situations, every decision can have several consequences, the probability of each of these consequences is known. 3. In uncertain situations, each decision can have several consequences, the probability is not known. Our aim in this article is to show how decision theory can usefully be mobilized to meet the needs of physicians. The decision theory can make decisions more transparent: first, by clarifying the data systematically considered the problem and secondly by asking a few basic principles should guide the choice. Once the problem and clarified the decision theory provides operational tools to represent the available information and determine patient preferences, and thus assist the patient and doctor in their choices.

Keywords: decision making, medicine, treatment strategies, patient

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359 Probability Sampling in Matched Case-Control Study in Drug Abuse

Authors: Surya R. Niraula, Devendra B Chhetry, Girish K. Singh, S. Nagesh, Frederick A. Connell

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Background: Although random sampling is generally considered to be the gold standard for population-based research, the majority of drug abuse research is based on non-random sampling despite the well-known limitations of this kind of sampling. Method: We compared the statistical properties of two surveys of drug abuse in the same community: one using snowball sampling of drug users who then identified “friend controls” and the other using a random sample of non-drug users (controls) who then identified “friend cases.” Models to predict drug abuse based on risk factors were developed for each data set using conditional logistic regression. We compared the precision of each model using bootstrapping method and the predictive properties of each model using receiver operating characteristics (ROC) curves. Results: Analysis of 100 random bootstrap samples drawn from the snowball-sample data set showed a wide variation in the standard errors of the beta coefficients of the predictive model, none of which achieved statistical significance. One the other hand, bootstrap analysis of the random-sample data set showed less variation, and did not change the significance of the predictors at the 5% level when compared to the non-bootstrap analysis. Comparison of the area under the ROC curves using the model derived from the random-sample data set was similar when fitted to either data set (0.93, for random-sample data vs. 0.91 for snowball-sample data, p=0.35); however, when the model derived from the snowball-sample data set was fitted to each of the data sets, the areas under the curve were significantly different (0.98 vs. 0.83, p < .001). Conclusion: The proposed method of random sampling of controls appears to be superior from a statistical perspective to snowball sampling and may represent a viable alternative to snowball sampling.

Keywords: drug abuse, matched case-control study, non-probability sampling, probability sampling

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358 Chronolgy and Developments in Inventory Control Best Practices for FMCG Sector

Authors: Roopa Singh, Anurag Singh, Ajay

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Agriculture contributes a major share in the national economy of India. A major portion of Indian economy (about 70%) depends upon agriculture as it forms the main source of income. About 43% of India’s geographical area is used for agricultural activity which involves 65-75% of total population of India. The given work deals with the Fast moving Consumer Goods (FMCG) industries and their inventories which use agricultural produce as their raw material or input for their final product. Since the beginning of inventory practices, many developments took place which can be categorised into three phases, based on the review of various works. The first phase is related with development and utilization of Economic Order Quantity (EOQ) model and methods for optimizing costs and profits. Second phase deals with inventory optimization method, with the purpose of balancing capital investment constraints and service level goals. The third and recent phase has merged inventory control with electrical control theory. Maintenance of inventory is considered negative, as a large amount of capital is blocked especially in mechanical and electrical industries. But the case is different in food processing and agro-based industries and their inventories due to cyclic variation in the cost of raw materials of such industries which is the reason for selection of these industries in the mentioned work. The application of electrical control theory in inventory control makes the decision-making highly instantaneous for FMCG industries without loss in their proposed profits, which happened earlier during first and second phases, mainly due to late implementation of decision. The work also replaces various inventories and work-in-progress (WIP) related errors with their monetary values, so that the decision-making is fully target-oriented.

Keywords: control theory, inventory control, manufacturing sector, EOQ, feedback, FMCG sector

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357 An Experiment Research on the Effect of Brain-Break in the Classroom on Elementary School Students’ Selective Attention

Authors: Hui Liu, Xiaozan Wang, Jiarong Zhong, Ziming Shao

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Introduction: Related research shows that students don’t concentrate on teacher’s speaking in the classroom. The d2 attention test is a time-limited test about selective attention. The d2 attention test can be used to evaluate individual selective attention. Purpose: To use the d2 attention test tool to measure the difference between the attention level of the experimental class and the control class before and after Brain-Break and to explore the effect of Brain-Break in the classroom on students' selective attention. Methods: According to the principle of no difference in pre-test data, two classes in the fourth- grade of Shenzhen Longhua Central Primary School were selected. After 20 minutes of class in the third class in the morning and the third class in the afternoon, about 3-minute Brain-Break intervention was performed in the experimental class for 10 weeks. The normal class in the control class did not intervene. Before and after the experiment, the d2 attention test tool was used to test the attention level of the two-class students. The paired sample t-test and independent sample t-test in SPSS 23.0 was used to test the change in the attention level of the two-class classes around 10 weeks. This article only presents results with significant differences. Results: The independent sample t-test results showed that after ten-week of Brain-Break, the missed errors (E1 t = -2.165 p = 0.042), concentration performance (CP t = 1.866 p = 0.05), and the degree of omissions (Epercent t = -2.375 p = 0.029) in experimental class showed significant differences compared with control class. The students’ error level decreased and the concentration increased. Conclusions: Adding Brain-Break interventions in the classroom can effectively improve the attention level of fourth-grade primary school students to a certain extent, especially can improve the concentration of attention and decrease the error rate in the tasks. The new sport's learning model is worth promoting

Keywords: cultural class, micromotor, attention, D2 test

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356 Behavioral and EEG Reactions in Children during Recognition of Emotionally Colored Sentences That Describe the Choice Situation

Authors: Tuiana A. Aiusheeva, Sergey S. Tamozhnikov, Alexander E. Saprygin, Arina A. Antonenko, Valentina V. Stepanova, Natalia N. Tolstykh, Alexander N. Savostyanov

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Situation of choice is an important condition for the formation of essential character qualities of a child, such as being initiative, responsible, hard-working. We have studied the behavioral and EEG reactions in Russian schoolchildren during recognition of syntactic errors in emotionally colored sentences that describe the choice situation. Twenty healthy children (mean age 9,0±0,3 years, 12 boys, 8 girls) were examined. Forty sentences were selected for the experiment; the half of them contained a syntactic error. The experiment additionally had the hidden condition: 50% of the sentences described the children's own choice and were emotionally colored (positive or negative). The other 50% of the sentences described the forced-choice situation, also with positive or negative coloring. EEG were recorded during execution of error-recognition task. Reaction time and quality of syntactic error detection were chosen as behavioral measures. Event-related spectral perturbation (ERSP) was applied to characterize the oscillatory brain activity of children. There were two time-frequency intervals in EEG reactions: (1) 500-800 ms in the 3-7 Hz frequency range (theta synchronization) and (2) 500-1000 ms in the 8-12 Hz range (alpha desynchronization). We found out that behavioral and brain reactions in child brain during recognition of positive and negative sentences describing forced-choice situation did not have significant differences. Theta synchronization and alpha desynchronization were stronger during recognition of sentences with children's own choice, especially with negative coloring. Also, the quality and execution time of the task were higher for this types of sentences. The results of our study will be useful for improvement of teaching methods and diagnostics of children affective disorders.

Keywords: choice situation, electroencephalogram (EEG), emotionally colored sentences, schoolchildren

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355 Modelling of Heat Generation in a 18650 Lithium-Ion Battery Cell under Varying Discharge Rates

Authors: Foo Shen Hwang, Thomas Confrey, Stephen Scully, Barry Flannery

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Thermal characterization plays an important role in battery pack design. Lithium-ion batteries have to be maintained between 15-35 °C to operate optimally. Heat is generated (Q) internally within the batteries during both the charging and discharging phases. This can be quantified using several standard methods. The most common method of calculating the batteries heat generation is through the addition of both the joule heating effects and the entropic changes across the battery. In addition, such values can be derived by identifying the open-circuit voltage (OCV), nominal voltage (V), operating current (I), battery temperature (T) and the rate of change of the open-circuit voltage in relation to temperature (dOCV/dT). This paper focuses on experimental characterization and comparative modelling of the heat generation rate (Q) across several current discharge rates (0.5C, 1C, and 1.5C) of a 18650 cell. The analysis is conducted utilizing several non-linear mathematical functions methods, including polynomial, exponential, and power models. Parameter fitting is carried out over the respective function orders; polynomial (n = 3~7), exponential (n = 2) and power function. The generated parameter fitting functions are then used as heat source functions in a 3-D computational fluid dynamics (CFD) solver under natural convection conditions. Generated temperature profiles are analyzed for errors based on experimental discharge tests, conducted at standard room temperature (25°C). Initial experimental results display low deviation between both experimental and CFD temperature plots. As such, the heat generation function formulated could be easier utilized for larger battery applications than other methods available.

Keywords: computational fluid dynamics, curve fitting, lithium-ion battery, voltage drop

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354 Investment and Economic Growth: An Empirical Analysis for Tanzania

Authors: Manamba Epaphra

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This paper analyzes the causal effect between domestic private investment, public investment, foreign direct investment and economic growth in Tanzania during the 1970-2014 period. The modified neo-classical growth model that includes control variables such as trade liberalization, life expectancy and macroeconomic stability proxied by inflation is used to estimate the impact of investment on economic growth. Also, the economic growth models based on Phetsavong and Ichihashi (2012), and Le and Suruga (2005) are used to estimate the crowding out effect of public investment on private domestic investment on one hand and foreign direct investment on the other hand. A correlation test is applied to check the correlation among independent variables, and the results show that there is very low correlation suggesting that multicollinearity is not a serious problem. Moreover, the diagnostic tests including RESET regression errors specification test, Breusch-Godfrey serial correlation LM test, Jacque-Bera-normality test and white heteroskedasticity test reveal that the model has no signs of misspecification and that, the residuals are serially uncorrelated, normally distributed and homoskedastic. Generally, the empirical results show that the domestic private investment plays an important role in economic growth in Tanzania. FDI also tends to affect growth positively, while control variables such as high population growth and inflation appear to harm economic growth. Results also reveal that control variables such as trade openness and life expectancy improvement tend to increase real GDP growth. Moreover, a revealed negative, albeit weak, association between public and private investment suggests that the positive effect of domestic private investment on economic growth reduces when public investment-to-GDP ratio exceeds 8-10 percent. Thus, there is a great need for promoting domestic saving so as to encourage domestic investment for economic growth.

Keywords: FDI, public investment, domestic private investment, crowding out effect, economic growth

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353 Improvement of Cardiometabolic after 8 Weeks of Weight Loss Intervention

Authors: Boris Bajer, Andrea Havranova, Miroslav Vlcek, Richard Imrich, Adela Penesova

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Lifestyle interventions can prevent the deterioration of impaired glucose tolerance to manifest type 2 diabetes, and also prevent cardiovascular diseases, as it showed many studies (the Finnish Diabetes Prevention Study, Diabetes Prevention Program (DPP), . the China Da Qing Diabetes Prevention Study, etc.) Therefore the aim of our study was to compare the effect of intensified lifestyle intervention on cardiometabolic parameters. Methods: It is an ongoing randomized interventional clinical study (NCT02325804) focused on the reduction of body weight/fat. Intervention: hypocaloric diet (30% restriction of calories) and physical activity 150 minutes/week. Before and after 8 weeks of intervention all patients underwent complete medical examination (measurement of physical fitness, resting metabolic rate (RMR), body composition analysis, oral glucose tolerance test, parameters of lipid metabolism, and other cardiometabolic risk factors. Results: So far 39 patients finished the intervention. The average reduction of body weight was 6,8 + 4,9 kg (0-15 kg; p=0,0006), accompanied with significant reduction of body fat percentage (p ≤ 0,0001), amount of fat mass (p=0,03), waist circumference (p=0.02). Amount of lean mass and RMR remained unchanged. Heart rate (p=0,02), systolic and diastolic blood pressure was reduced (p=0,01 p=0,02 resp.) as well as insulin sensitivity was improved. Lipid parameters also changed - cholesterol, LDL decreased (p=0,05, p=0,04 resp.), while triglycerides showed tendency to decrease (p=0,055). Liver function improved, alanine aminotrasnferase (ALT) were reduced (p=0,01). Physical fitness significantly improved (as measure VO2 max (p=0,02). Conclusion: Results of our study are in line with previous results about the beneficial effect of intensive lifestyle changes on the reduction of cardiometabolic risk factors and improvement of liver function. Supported by grants APVV 15-0228; VEGA 2/0161/16

Keywords: obesity, weight loss, diet lipids, blood pressure, liver enzymes

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352 Loss Function Optimization for CNN-Based Fingerprint Anti-Spoofing

Authors: Yehjune Heo

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As biometric systems become widely deployed, the security of identification systems can be easily attacked by various spoof materials. This paper contributes to finding a reliable and practical anti-spoofing method using Convolutional Neural Networks (CNNs) based on the types of loss functions and optimizers. The types of CNNs used in this paper include AlexNet, VGGNet, and ResNet. By using various loss functions including Cross-Entropy, Center Loss, Cosine Proximity, and Hinge Loss, and various loss optimizers which include Adam, SGD, RMSProp, Adadelta, Adagrad, and Nadam, we obtained significant performance changes. We realize that choosing the correct loss function for each model is crucial since different loss functions lead to different errors on the same evaluation. By using a subset of the Livdet 2017 database, we validate our approach to compare the generalization power. It is important to note that we use a subset of LiveDet and the database is the same across all training and testing for each model. This way, we can compare the performance, in terms of generalization, for the unseen data across all different models. The best CNN (AlexNet) with the appropriate loss function and optimizers result in more than 3% of performance gain over the other CNN models with the default loss function and optimizer. In addition to the highest generalization performance, this paper also contains the models with high accuracy associated with parameters and mean average error rates to find the model that consumes the least memory and computation time for training and testing. Although AlexNet has less complexity over other CNN models, it is proven to be very efficient. For practical anti-spoofing systems, the deployed version should use a small amount of memory and should run very fast with high anti-spoofing performance. For our deployed version on smartphones, additional processing steps, such as quantization and pruning algorithms, have been applied in our final model.

Keywords: anti-spoofing, CNN, fingerprint recognition, loss function, optimizer

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351 The Use of Unmanned Aerial System (UAS) in Improving the Measurement System on the Example of Textile Heaps

Authors: Arkadiusz Zurek

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The potential of using drones is visible in many areas of logistics, especially in terms of their use for monitoring and control of many processes. The technologies implemented in the last decade concern new possibilities for companies that until now have not even considered them, such as warehouse inventories. Unmanned aerial vehicles are no longer seen as a revolutionary tool for Industry 4.0, but rather as tools in the daily work of factories and logistics operators. The research problem is to develop a method for measuring the weight of goods in a selected link of the clothing supply chain by drones. However, the purpose of this article is to analyze the causes of errors in traditional measurements, and then to identify adverse events related to the use of drones for the inventory of a heap of textiles intended for production purposes. On this basis, it will be possible to develop guidelines to eliminate the causes of these events in the measurement process using drones. In a real environment, work was carried out to determine the volume and weight of textiles, including, among others, weighing a textile sample to determine the average density of the assortment, establishing a local geodetic network, terrestrial laser scanning and photogrammetric raid using an unmanned aerial vehicle. As a result of the analysis of measurement data obtained in the facility, the volume and weight of the assortment and the accuracy of their determination were determined. In this article, this work presents how such heaps are currently being tested, what adverse events occur, indicate and describes the current use of photogrammetric techniques of this type of measurements so far performed by external drones for the inventory of wind farms or construction of the station and compare them with the measurement system of the aforementioned textile heap inside a large-format facility.

Keywords: drones, unmanned aerial system, UAS, indoor system, security, process automation, cost optimization, photogrammetry, risk elimination, industry 4.0

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350 Assessment of Acute Oral Toxicity Studies and Anti Diabetic Activity of Herbal Mediated Nanomedicine

Authors: Shanker Kalakotla, Krishna Mohan Gottumukkala

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Diabetes is a metabolic disorder characterized by hyperglycemia, carbohydrates, altered lipids and proteins metabolism. In recent research nanotechnology is a blazing field for the researchers; latterly there has been prodigious excitement in the nanomedicine and nano pharmacological area for the study of silver nanoparticles synthesis using natural products. Biological methods have been used to synthesize silver nanoparticles in presence of medicinally active antidiabetic plants, and this intention made us assess the biologically synthesized silver nanoparticles from the seed extract of Psoralea corylfolia using 1 mM silver nitrate solution. The synthesized herbal mediated silver nanoparticles (HMSNP’s) then subjected to various characterization techniques such as XRD, SEM, EDX, TEM, DLS, UV and FT-IR respectively. In current study, the silver nanoparticles tested for in-vitro anti-diabetic activity and possible toxic effects in healthy female albino mice by following OECD guidelines-425. Herbal mediated silver nanoparticles were successfully obtained from bioreduction of silver nitrate using Psoralea corylifolia plant extract. Silver nanoparticles have been appropriately characterized and confirmed using different types of equipment viz., UV-vis spectroscopy, XRD, FTIR, DLS, SEM and EDX analysis. From the behavioral observations of the study, the female albino mice did not show sedation, respiratory arrest, and convulsions. Test compounds did not cause any mortality at the dose level tested (i.e., 2000 mg/kg body weight) doses till the end of 14 days of observation and were considered safe. It may be concluded that LD50 of the HMSNPs was 2000mg/kg body weight. Since LD50 of the HMSNPs was 2000mg/kg body weight, so the preferred dose range for HMSNPs falls between the levels of 200 and 400 mg/kg. Further In-vivo pharmacological models and biochemical investigations will clearly elucidate the mechanism of action and will be helpful in projecting the currently synthesized silver nanoparticles as a therapeutic target in treating chronic ailments.

Keywords: herbal mediated silver nanoparticles, HMSNPs, toxicity of silver nanoparticles, PTP1B in-vitro anti-diabetic assay female albino mice, 425 OECD guidelines

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349 Enhancing Warehousing Operation In Cold Supply Chain Through The Use Of IOT And Lifi Technologies

Authors: Sarah El-Gamal, Passent Hossam, Ahmed Abd El Aziz, Rojina Mahmoud, Ahmed Hassan, Dalia Hilal, Eman Ayman, Hana Haytham, Omar Khamis

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Several concerns fall upon the supply chain, especially the cold supply chain. According to the literature, the main challenges in the cold supply chain are the distribution and storage phases. In this research, researchers focused on the storage area, which contains several activities such as the picking activity that faces a lot of obstacles and challenges The implementation of IoT solutions enables businesses to monitor the temperature of food items, which is perhaps the most critical parameter in cold chains. Therefore, researchers proposed a practical solution that would help in eliminating the problems related to ineffective picking for products, especially fish and seafood products, by using IoT technology, most notably LiFi technology. Thus, guaranteeing sufficient picking, reducing waste, and consequently lowering costs. A prototype was specially designed and examined. This research is a single case study research. Two methods of data collection were used; observation and semi-structured interviews. Semi-structured interviews were conducted with managers and decision maker at Carrefour Alexandria to validate the problem and the proposed practical solution using IoTandLiFi technology. A total of three interviews were conducted. As a result, a SWOT analysis was achieved in order to highlight all the strengths and weaknesses of using the recommended Lifi solution in the picking process. According to the investigations, it was found that the use of IoT and LiFi technology is cost effective, efficient, and reduces human errors, minimize the percentage of product waste and thus save money and cost. Thus, increasing customer satisfaction and profits gained.

Keywords: cold supply chain, picking process, temperature control, IOT, warehousing, LIFI

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348 Cellular RNA-Binding Domains with Distant Homology in Viral Proteomes

Authors: German Hernandez-Alonso, Antonio Lazcano, Arturo Becerra

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Until today, viruses remain controversial and poorly understood; about their origin, this problem represents an enigma and one of the great challenges for the contemporary biology. Three main theories have tried to explain the origin of viruses: regressive evolution, escaped host gene, and pre-cellular origin. Under the perspective of the escaped host gene theory, it can be assumed a cellular origin of viral components, like protein RNA-binding domains. These universal distributed RNA-binding domains are related to the RNA metabolism processes, including transcription, processing, and modification of transcripts, translation, RNA degradation and its regulation. In the case of viruses, these domains are present in important viral proteins like helicases, nucleases, polymerases, capsid proteins or regulation factors. Therefore, they are implicated in the replicative cycle and parasitic processes of viruses. That is why it is possible to think that those domains present low levels of divergence due to selective pressures. For these reasons, the main goal for this project is to create a catalogue of the RNA-binding domains found in all the available viral proteomes, using bioinformatics tools in order to analyze its evolutionary process, and thus shed light on the general virus evolution. ProDom database was used to obtain larger than six thousand RNA-binding domain families that belong to the three cellular domains of life and some viral groups. From the sequences of these families, protein profiles were created using HMMER 3.1 tools in order to find distant homologous within greater than four thousand viral proteomes available in GenBank. Once accomplished the analysis, almost three thousand hits were obtained in the viral proteomes. The homologous sequences were found in proteomes of the principal Baltimore viral groups, showing interesting distribution patterns that can contribute to understand the evolution of viruses and their host-virus interactions. Presence of cellular RNA-binding domains within virus proteomes seem to be explained by closed interactions between viruses and their hosts. Recruitment of these domains is advantageous for the viral fitness, allowing viruses to be adapted to the host cellular environment.

Keywords: bioinformatics tools, distant homology, RNA-binding domains, viral evolution

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347 Derivatives Balance Method for Linear and Nonlinear Control Systems

Authors: Musaab Mohammed Ahmed Ali, Vladimir Vodichev

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work deals with an universal control technique or single controller for linear and nonlinear stabilization and tracing control systems. These systems may be structured as SISO and MIMO. Parameters of controlled plants can vary over a wide range. Introduced a novel control systems design method, construction of stable platform orbits using derivative balance, solved transfer function stability preservation problem of linear system under partial substitution of a rational function. Universal controller is proposed as a polar system with the multiple orbits to simplify design procedure, where each orbit represent single order of controller transfer function. Designed controller consist of proportional, integral, derivative terms and multiple feedback and feedforward loops. The controller parameters synthesis method is presented. In generally, controller parameters depend on new polynomial equation where all parameters have a relationship with each other and have fixed values without requirements of retuning. The simulation results show that the proposed universal controller can stabilize infinity number of linear and nonlinear plants and shaping desired previously ordered performance. It has been proven that sensor errors and poor performance will be completely compensated and cannot affect system performance. Disturbances and noises effect on the controller loop will be fully rejected. Technical and economic effect of using proposed controller has been investigated and compared to adaptive, predictive, and robust controllers. The economic analysis shows the advantage of single controller with fixed parameters to drive infinity numbers of plants compared to above mentioned control techniques.

Keywords: derivative balance, fixed parameters, stable platform, universal control

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346 Evaluation of the Inhibitory Activity of Natural Extracts From Spontaneous Plant on the Α-Amylase and Α–Glucosidase and Their Antioxidant Activities

Authors: Ihcen Khacheba, Amar Djeridane, Abdelkarim Kamli, Mohamed Yousfi

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Plant materials constitute an important source of natural bioactive molecules. Thus plants have been used from antiquity as sources of medicament against various diseases. These properties are usually attributed to secondary metabolites that are the subject of a lot of research in this field. This is particularly the case of phenolic compounds plants that are widely renowned in therapeutics as anti-inflammatories, enzyme inhibitors, and antioxidants, particularly flavonoïds. With the aim of acquiring a better knowledge of the secondary metabolism of the vegetable kingdom in the region of Laghouat and of the discovering of new natural therapeutics, 10 extracts from 5 Saharan plant species were submitted to chemical screening.The analysis of the preceding biological targets led to the evaluation of the biological activity of the extracts of the species Genista Corsica. The first step, consists in extracting and quantifying phenolic compounds. The second step has been devoted to stugying the effects of phenolic compounds on the kinetics catalyzed by two enzymes belonging to the class of hydrolase (the α-amylase and α-glucosidase) responsible for the digestion of sugars and finally we evaluate the antiantioxidant potential. The analysis results of phenolic extracts show clearly a low content of phenolic compounds in investigated plants. Average total phenolics ranged from 0.0017 to 11.35 mg equivalent gallic acid/g of the crude extract. Whereas the total flavonoids content lie between 0.0015 and 10.,96 mg/g equivalent of rutin. The results of the kinetic study of enzymatic reactions show that the extracts have inhibitory effects on both enzymes, with IC50 values ranging from 95.03 µg/ml to 1033.53 µg/ml for the α-amylase and 279.99 µg/ml to 1215.43 µg/ml for α-glucosidase whose greatest inhibition was found for the acetone extract of June (IC50 = 95.03 µg/ml). The results the antioxidant activity determined by ABTS, DPPH, and phosphomolybdenum tests clearly showed a good antioxidant capacity comparatively to antioxidants taken as reference the biological potential of these plants and could find their use in medicine to replace synthetic products.

Keywords: phenolic extracts, inhibition effect, α-amylase, α-glucosidase, antioxidant activity

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345 Improved Regression Relations Between Different Magnitude Types and the Moment Magnitude in the Western Balkan Earthquake Catalogue

Authors: Anila Xhahysa, Migena Ceyhan, Neki Kuka, Klajdi Qoshi, Damiano Koxhaj

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The seismic event catalog has been updated in the framework of a bilateral project supported by the Central European Investment Fund and with the extensive support of Global Earthquake Model Foundation to update Albania's national seismic hazard model. The earthquake catalogue prepared within this project covers the Western Balkan area limited by 38.0° - 48°N, 12.5° - 24.5°E and includes 41,806 earthquakes that occurred in the region between 510 BC and 2022. Since the moment magnitude characterizes the earthquake size accurately and the selected ground motion prediction equations for the seismic hazard assessment employ this scale, it was chosen as the uniform magnitude scale for the catalogue. Therefore, proxy values of moment magnitude had to be obtained by using new magnitude conversion equations between the local and other magnitude types to this unified scale. The Global Centroid Moment Tensor Catalogue was considered the most authoritative for moderate to large earthquakes for moment magnitude reports; hence it was used as a reference for calibrating other sources. The best fit was observed when compared to some regional agencies, whereas, with reports of moment magnitudes from Italy, Greece and Turkey, differences were observed in all magnitude ranges. For teleseismic magnitudes, to account for the non-linearity of the relationships, we used the exponential model for the derivation of the regression equations. The obtained regressions for the surface wave magnitude and short-period body-wave magnitude show considerable differences with Global Earthquake Model regression curves, especially for low magnitude ranges. Moreover, a conversion relation was obtained between the local magnitude of Albania and the corresponding moment magnitude as reported by the global and regional agencies. As errors were present in both variables, the Deming regression was used.

Keywords: regression, seismic catalogue, local magnitude, tele-seismic magnitude, moment magnitude

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344 Development of Electric Generator and Water Purifier Cart

Authors: Luisito L. Lacatan, Gian Carlo J. Bergonia, Felipe C. Buado III, Gerald L. Gono, Ron Mark V. Ortil, Calvin A. Yap

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This paper features the development of a Mobile Self-sustaining Electricity Generator for water distillation process with MCU- based wireless controller & indicator designed to solve the problem of scarcity of clean water. It is a fact that pure water is precious nowadays and its value is more precious to those who do not have or enjoy it. There are many water filtration products in existence today. However, none of these products fully satisfies the needs of families needing clean drinking water. All of the following products require either large sums of money or extensive maintenance, and some products do not even come with a guarantee of potable water. The proposed project was designed to alleviate the problem of scarcity of potable water in the country and part of the purpose was also to identify the problem or loopholes of the project such as the distance and speed required to produce electricity using a wheel and alternator, the required time for the heating element to heat up, the capacity of the battery to maintain the heat of the heating element and the time required for the boiler to produce a clean and potable water. The project has three parts. The first part included the researchers’ effort to plan every part of the project from the conversion of mechanical energy to electrical energy, from purifying water to potable drinking water to the controller and indicator of the project using microcontroller unit (MCU). This included identifying the problem encountered and any possible solution to prevent and avoid errors. Gathering and reviewing related studies about the project helped the researcher reduce and prevent any problems before they could be encountered. It also included the price and quantity of materials used to control the budget.

Keywords: mobile, self – sustaining, electricity generator, water distillation, wireless battery indicator, wireless water level indicator

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343 Proprotein Convertase Subtilisin/Kexin Type 9 Enhances Arterial Medial Calcification in a Uremic Rat Model of Chronic Kidney Disease

Authors: Maria Giovanna Lupo, Marina Camera, Marcello Rattazzi, Nicola Ferri

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A complex interplay among chronic kidney disease, lipid metabolism and aortic calcification has been recognized starting from results of many clinical and experimental studies. Here we investigated the influence of kidney function on PCSK9 levels, both in uremic rats and in clinical observation study, and its potential direct action on cultured smooth muscle cells (SMCs) calcification. In a cohort of 594 subjects enrolled in a single centre, observational, cross-sectional and longitudinal study, a negative association between GFR and plasma PCSK9 was found. Atherosclerotic cardiovascular disease (ASCVD), as co-morbidity, further increased PCSK9 plasma levels. Diet-induced uremic condition in rats, induced aortic calcification and increased total cholesterol and PCSK9 levels in plasma, livers and kidneys. Immunohistochemical analysis confirmed PCSK9 expression in aortic SMCs. SMCs overexpressing PCSK9 (SMCsPCSK9), cultured for 7-days in a pro-calcification environment (2.0mM or 2.4mM inorganic phosphate, Pi) showed a significantly higher extracellular calcium (Ca2+) deposition compared to mocked SMCs. Under the same experimental conditions, the addition of exogenous recombinant PCSK9 did not increase the extracellular calcification of SMCs. By flow cytometry analysis we showed that SMCsPCSK9, in response to 2.4mM Pi, released higher number of extracellular vesicles (EVs) positive for three tetraspanin molecules, such as CD63, CD9, and CD81. EVs derived from SMCsPCSK9 tended to be more enriched in calcium and alkaline phosphatase (ALPL), compared to EVs from mocks SMCs. In conclusion, our study reveals a direct role of PCSK9 on vascular calcification induced by higher inorganic phosphate levels associated to CKD condition. This effect appears to be mediated by a positive effect of endogenous PCSK9 on the release of EVs containing Ca2+ and ALP, which facilitate the deposition inorganic calcium phosphate crystals.

Keywords: PCSK9, calcification, extracellular vesicles, chronic kidney disease

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342 Multi-omics Integrative Analysis with Genome-Scale Metabolic Model Simulation Reveals Reaction Essentiality data in Human Astrocytes Under the Lipotoxic Effect of Palmitic Acid

Authors: Janneth Gonzalez, Andres Pinzon Velasco, Maria Angarita, Nicolas Mendoza

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Astrocytes play an important role in various processes in the brain, including pathological conditions such as neurodegenerative diseases. Recent studies have shown that the increase in saturated fatty acids such as palmitic acid (PA) triggers pro-inflammatory pathways in the brain. The use of synthetic neurosteroids such as tibolone has demonstrated neuro-protective mechanisms. However, there are few studies on the neuro-protective mechanisms of tibolone, especially at the systemic (omic) level. In this study, we performed the integration of multi-omic data (transcriptome and proteome) into a human astrocyte genomic scale metabolic model to study the astrocytic response during palmitate treatment. We evaluated metabolic fluxes in three scenarios (healthy, induced inflammation by PA, and tibolone treatment under PA inflammation). We also use control theory to identify those reactions that control the astrocytic system. Our results suggest that PA generates a modulation of central and secondary metabolism, showing a change in energy source use through inhibition of folate cycle and fatty acid β-oxidation and upregulation of ketone bodies formation.We found 25 metabolic switches under PA-mediated cellular regulation, 9 of which were critical only in the inflammatory scenario but not in the protective tibolone one. Within these reactions, inhibitory, total, and directional coupling profiles were key findings, playing a fundamental role in the (de)regulation in metabolic pathways that increase neurotoxicity and represent potential treatment targets. Finally, this study framework facilitates the understanding of metabolic regulation strategies, andit can be used for in silico exploring the mechanisms of astrocytic cell regulation, directing a more complex future experimental work in neurodegenerative diseases.

Keywords: astrocytes, data integration, palmitic acid, computational model, multi-omics, control theory

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341 Portable, Noninvasive and Wireless Near Infrared Spectroscopy Device to Monitor Skeletal Muscle Metabolism during Exercise

Authors: Adkham Paiziev, Fikrat Kerimov

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Near Infrared Spectroscopy (NIRS) is one of the biophotonic techniques which can be used to monitor oxygenation and hemodynamics in a variety of human tissues, including skeletal muscle. In the present work, we are offering tissue oximetry (OxyPrem) to measure hemodynamic parameters of skeletal muscles in rest and exercise. Purpose: - To elaborate the new wireless, portable, noninvasive, wearable NIRS device to measure skeletal muscle oxygenation during exercise. - To test this device on brachioradialis muscle of wrestler volunteers by using combined method of arterial occlusion (AO) and NIRS (AO+NIRS). Methods: Oxyprem NIRS device has been used together with AO test. AO test and Isometric brachioradialis muscle contraction experiments have been performed on one group of wrestler volunteers. ‘Accu- Measure’ caliper (USA) to measure skinfold thickness (SFT) has been used. Results: Elaborated device consists on power supply box, a sensor head and installed ‘Tubis’ software for data acquisition and to compute deoxyhemoglobin ([HHb), oxyhemoglobin ([O2Hb]), tissue oxygenation (StO2) and muscle tissue oxygen consumption (mVO2). Sensor head consists on four light sources with three light emitting diodes with nominal wavelengths of 760 nm, 805 nm, and 870 nm, and two detectors. AO and isometric voluntary forearm muscle contraction (IVFMC) on five healthy male subjects (23,2±0.84 in age, 0.43±0.05cm of SFT ) and four female subjects (22.0±1.0 in age and 0.24±0.04 cm SFT) has been measured. mVO2 for control group has been calculated (-0.65%/sec±0.07) for male and -0.69%/±0.19 for female subjects). Tissue oxygenation index for wrestlers in average about 75% whereas for control group StO2 =63%. Second experiment was connected with quality monitoring muscle activity during IVFMC at 10%,30% and 50% of MVC. It has been shown, that the concentration changes of HbO2 and HHb positively correlated to the contraction intensity. Conclusion: We have presented a portable multi-channel wireless NIRS device for real-time monitoring of muscle activity. The miniaturized NIRS sensor and the usage of wireless communication make the whole device have a compact-size, thus can be used in muscle monitoring.

Keywords: skeletal muscle, oxygenation, instrumentation, near infrared spectroscopy

Procedia PDF Downloads 253
340 Antiproliferative and Apoptotic Effects of an Enantiomerically Pure β-Dipeptide Derivative through PI3K/Akt-Dependent and -Independent Pathways in Human Hormone-Refractory Prostate Cancer Cells

Authors: Mei-Ling Chan, Jin-Ming Wu, Konstantin V. Kudryavtsev, Jih-Hwa Guh

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Prostate cancer is one of the most common malignant disease in men. KUD983 is an enantiomerically pure β-dipeptide derivative, which may have anti-cancer effects. In the present study, KUD983 exhibits powerful activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells. The IC50 values of KUD983 in PC-3 and DU145 cells are 0.56±0.07M and 0.50±0.04 M respectively. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with the down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB. The protein expressions of nuclear and total c-Myc protein, which was able to regulate the expression of both cyclin D1 and cyclin E, were significantly suppressed by KUD983. Phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is an important signaling pathway that influences the energy metabolism, cell cycle, proliferation, survival and apoptosis of cells, and is associated with numerous other signaling pathways. The Western Blot data revealed that KUD983 inhibited PI3K/Akt and mTOR/p70S6K/4E-BP1 pathways. The transient transfection of constitutively active myristylated Akt (myr-Akt) cDNA significantly reversed KUD983-induced caspase activation but did not abolish the suppression of mTOR/p70S6K/4E-BP1 signaling cascade indicating the presence of both Akt-dependent and -independent pathways. Moreover, KUD983-induced effect was collaborated with the down-regulation of anti-apoptotic Bcl-2 members (e.g., Bcl-2, and Mcl-1) and IAP family members (e.g., survivin). Furthermore, KUD983 induced autophagic cell death using confocal microscopic examination, investigating the level of conversion of LC3-I to LC3-II and flow cytometric detection of AVO-positive cells. Taken together, the data suggest that KUD983 is an anticancer β-dipeptide against HRPCs through the inhibition of cell proliferation and induction of apoptotic and autophagic cell death. The suppression of signaling pathways mediated by c-Myc, PI3K/Akt and mTOR/p70S6K/4E-BP1 and the collaboration with down-regulation of Mcl-1 and survivin may indicate the mechanism of KUD983 against HRPC.

Keywords: β-dipeptide, hormone-refractory prostate cancer, mTOR, PI3K/Akt

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339 Molecular Pathogenesis of NASH through the Dysregulation of Metabolic Organ Network in the NASH-HCC Model Mouse Treated with Streptozotocin-High Fat Diet

Authors: Bui Phuong Linh, Yuki Sakakibara, Ryuto Tanaka, Elizabeth H. Pigney, Taishi Hashiguchi

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NASH is an increasingly prevalent chronic liver disease that can progress to hepatocellular carcinoma and now is attracting interest worldwide. The STAM™ model is a clinically-correlated murine NASH model which shows the same pathological progression as NASH patients and has been widely used for pharmacological and basic research. The multiple parallel hits hypothesis suggests abnormalities in adipocytokines, intestinal microflora, and endotoxins are intertwined and could contribute to the development of NASH. In fact, NASH patients often exhibit gut dysbiosis and dysfunction in adipose tissue and metabolism. However, the analysis of the STAM™ model has only focused on the liver. To clarify whether the STAM™ model can also mimic multiple pathways of NASH progression, we analyzed the organ crosstalk interactions between the liver and the gut and the phenotype of adipose tissue in the STAM™ model. NASH was induced in male mice by a single subcutaneous injection of 200 µg streptozotocin 2 days after birth and feeding with high-fat diet after 4 weeks of age. The mice were sacrificed at NASH stage. Colon samples were snap-frozen in liquid nitrogen and stored at -80˚C for tight junction-related protein analysis. Adipose tissue was prepared into paraffin blocks for HE staining. Blood adiponectin was analyzed to confirm changes in the adipocytokine profile. Tight junction-related proteins in the intestine showed that expression of ZO-1 decreased with the progression of the disease. Increased expression of endotoxin in the blood and decreased expression of Adiponectin were also observed. HE staining revealed hypertrophy of adipocytes. Decreased expression of ZO-1 in the intestine of STAM™ mice suggests the occurrence of leaky gut, and abnormalities in adipocytokine secretion were also observed. Together with the liver, phenotypes in these organs are highly similar to human NASH patients and might be involved in the pathogenesis of NASH.

Keywords: Non-alcoholic steatohepatitis, hepatocellular carcinoma, fibrosis, organ crosstalk, leaky gut

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338 Detection of Resistive Faults in Medium Voltage Overhead Feeders

Authors: Mubarak Suliman, Mohamed Hassan

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Detection of downed conductors occurring with high fault resistance (reaching kilo-ohms) has always been a challenge, especially in countries like Saudi Arabia, on which earth resistivity is very high in general (reaching more than 1000 Ω-meter). The new approaches for the detection of resistive and high impedance faults are based on the analysis of the fault current waveform. These methods are still under research and development, and they are currently lacking security and dependability. The other approach is communication-based solutions which depends on voltage measurement at the end of overhead line branches and communicate the measured signals to substation feeder relay or a central control center. However, such a detection method is costly and depends on the availability of communication medium and infrastructure. The main objective of this research is to utilize the available standard protection schemes to increase the probability of detection of downed conductors occurring with a low magnitude of fault currents and at the same time avoiding unwanted tripping in healthy conditions and feeders. By specifying the operating region of the faulty feeder, use of tripping curve for discrimination between faulty and healthy feeders, and with proper selection of core balance current transformer (CBCT) and voltage transformers with fewer measurement errors, it is possible to set the pick-up of sensitive earth fault current to minimum values of few amps (i.e., Pick-up Settings = 3 A or 4 A, …) for the detection of earth faults with fault resistance more than (1 - 2 kΩ) for 13.8kV overhead network and more than (3-4) kΩ fault resistance in 33kV overhead network. By implementation of the outcomes of this study, the probability of detection of downed conductors is increased by the utilization of existing schemes (i.e., Directional Sensitive Earth Fault Protection).

Keywords: sensitive earth fault, zero sequence current, grounded system, resistive fault detection, healthy feeder

Procedia PDF Downloads 96