Search results for: dopamine modulation
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 555

Search results for: dopamine modulation

105 Modulation of Isoprenaline-Induced Myocardial Damage by Atorvastatin

Authors: Dalia Atallah, Lamiaa Ahmed, Hala Zaki, Mahmoud Khattab

Abstract:

Background: Isoprenaline (ISO) administration induces myocardial damage via oxidative stress and endothelial dysfunction. Atorvastatin (ATV) treatment improves both oxidative stress and endothelial dysfunction yet recent studies have reported a pro-oxidant effect upon ATV administration on both clinical and experimental studies. The present study was directed to investigate the effect of ATV pre-treatment and treatment on ISO-induced myocardial damage. Methods: Male rats were divided into five groups (n = 10). Rats were given ISO (5mg/kg/day, i.p.) for one week with or without ATV (10mg/kg/day, p.o.). ATV was given either as pre-treatment for one week before its co-administration with ISO for another week or as a treatment for two weeks at the end of the ISO administration. At the end of the experiment, the electrocardiographic examination was done and blood was isolated for the estimation of plasma creatine kinase MB (CK-MB) activity. Rats were then sacrificed and the whole ventricles were isolated for histological examination and the estimation of lipid peroxides as malondialdehyde (MDA) level, reduced glutathione (GSH) level, catalase activity, total nitrate-nitrite (NOx), as well as the estimation of both endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) protein expression. Results: ISO-induced myocardial damage showed a significant elevation in ST segment, an increase in CK-MB activity, as well as increased oxidative stress biomarkers. Also, ISO-treated rats showed a significant decrease in myocardial NOx level and eNOS as well as degeneration in the myocardium. ATV pre-treatment didn’t show any protection to ISO-treated rats. On the other hand, ATV treatment showed a significant decrease in both the elevated ST wave and CK-MB activity. Moreover, ATV Treatment succeeded to improve oxidative stress biomarkers, tissue NOx, and eNOS protein expression, as well as amelioration of the histological alterations. Conclusion: Pre-treatment with ATV failed to protect against ISO-induced damage. This might suggest a synergistic pro-oxidant effect upon administration of the pro-oxidant ISO along with ATV as demonstrated by the increased oxidative stress and endothelial dysfunction. On the other side, ATV treatment succeeded to significantly improve oxidative stress biomarkers, endothelial dysfunction and myocardial degeneration.

Keywords: atorvastatin, endothelial dysfunction, isoprenaline, oxidative stress

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104 Evaluation of Alpha-Glucosidase Inhibitory Effect of Two Plants from Brazilian Cerrado

Authors: N. A. P. Camaforte, P. M. P. Vareda, L. L. Saldanha, A. L. Dokkedal, J. M. Rezende-Neto, M. R. Senger, F. P. Silva-Jr, J. R. Bosqueiro

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Diabetes mellitus is a disease characterized by deficiency of insulin secretion and/or action which results in hyperglycemia. Nowadays, acarbose is a medicine used by diabetic people to inhibit alpha-glucosidases leading to the decreasing of post-feeding glycaemia, but with low effectiveness and many side effects. Medicinal plants have been used for the treatment of many diseases including diabetes and their action occurs through the modulation of insulin-depending processes, pancreas regeneration or inhibiting glucose absorption by the intestine. Previous studies in our laboratory showed that the treatment using two crude extracts of plants from Brazilian cerrado was able to decrease fasting blood glucose and improve glucose tolerance in streptozotocin-diabetic mice. Because of this and the importance of the search for new alternatives to decrease the hyperglycemia, we decided to evaluate the inhibitory action of two plants from Brazilian cerrado - B.H. and Myrcia bella. The enzymatic assay was performed in 50 µL of final volume using pancreatic α-amylase and maltase together with theirs commercial substrates. The inhibition potency (IC50) was determined by the incubation of eight different concentrations of both extracts and the enzymes for 5 minutes at 37ºC. After, the substrate was added to start the reaction. Glucosidases assay was evaluated measuring the quantity of p-nitrophenol in 405 nmin 384 wells automatic reader. The in vitro assay with the extracts of B.H. and M. bella showed an IC50 of 28,04µg/mL and 16,93 µg/mL for α-amilase, and 43,01µg/mL and 17 µg/mL for maltase, respectively. M. bella extract showed a higher inhibitory activity for those enzymes than B.H. extract. The crude extracts tested showed a higher inhibition rate to α-amylase, but were less effective against maltase in comparison to acarbose (IC50 36µg/mL and 9 µg/mL, respectively). In conclusion, the crude extract of B.H. and M. bella showed a potent inhibitory effect against α-amylase and showed promising results to the possible development of new medicines to treat diabetes with less or even without side effects.

Keywords: alfa-glucosidases, diabetes mellitus, glycaemia, medicinal plants

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103 Cognitive Dissonance in Robots: A Computational Architecture for Emotional Influence on the Belief System

Authors: Nicolas M. Beleski, Gustavo A. G. Lugo

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Robotic agents are taking more and increasingly important roles in society. In order to make these robots and agents more autonomous and efficient, their systems have grown to be considerably complex and convoluted. This growth in complexity has led recent researchers to investigate forms to explain the AI behavior behind these systems in search for more trustworthy interactions. A current problem in explainable AI is the inner workings with the logic inference process and how to conduct a sensibility analysis of the process of valuation and alteration of beliefs. In a social HRI (human-robot interaction) setup, theory of mind is crucial to ease the intentionality gap and to achieve that we should be able to infer over observed human behaviors, such as cases of cognitive dissonance. One specific case inspired in human cognition is the role emotions play on our belief system and the effects caused when observed behavior does not match the expected outcome. In such scenarios emotions can make a person wrongly assume the antecedent P for an observed consequent Q, and as a result, incorrectly assert that P is true. This form of cognitive dissonance where an unproven cause is taken as truth induces changes in the belief base which can directly affect future decisions and actions. If we aim to be inspired by human thoughts in order to apply levels of theory of mind to these artificial agents, we must find the conditions to replicate these observable cognitive mechanisms. To achieve this, a computational architecture is proposed to model the modulation effect emotions have on the belief system and how it affects logic inference process and consequently the decision making of an agent. To validate the model, an experiment based on the prisoner's dilemma is currently under development. The hypothesis to be tested involves two main points: how emotions, modeled as internal argument strength modulators, can alter inference outcomes, and how can explainable outcomes be produced under specific forms of cognitive dissonance.

Keywords: cognitive architecture, cognitive dissonance, explainable ai, sensitivity analysis, theory of mind

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102 Magnetophotonics 3D MEMS/NEMS System for Quantitative Mitochondrial DNA Defect Profiling

Authors: Dar-Bin Shieh, Gwo-Bin Lee, Chen-Ming Chang, Chen Sheng Yeh, Chih-Chia Huang, Tsung-Ju Li

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Mitochondrial defects have a significant impact in many human diseases and aging associated phenotypes. The pathogenic mitochondrial DNA (mtDNA) mutations are diverse and usually present as heteroplasmic. mtDNA 4977bps deletion is one of the common mtDNA defects, and the ratio of mutated versus normal copy is significantly associated with clinical symptoms thus their quantitative detection has become an important unmet needs for advanced disease diagnosis and therapeutic guidelines. This study revealed a Micro-electro-mechanical-system (MEMS) enabled automatic microfluidic chip that only required minimal sample. The system integrated multiple laboratory operation steps into a Lab-on-a-Chip for high-sensitive and prompt measurement. The entire process including magnetic nanoparticle based mtDNA extraction in chip, mutation selective photonic DNA cleavage, and nanoparticle accelerated photonic quantitative polymerase chain reaction (qPCR). All subsystems were packed inside a miniature three-dimensional micro structured system and operated in an automatic manner. Integration of magnetic beads with microfluidic transportation could promptly extract and enrich the specific mtDNA. The near infrared responsive magnetic nanoparticles enabled micro-PCR to be operated by pulse-width-modulation controlled laser pulsing to amplify the desired mtDNA while quantified by fluorescence intensity captured by a complementary metal oxide system array detector. The proportions of pathogenic mtDNA in total DNA were thus obtained. Micro capillary electrophoresis module was used to analyze the amplicone products. In conclusion, this study demonstrated a new magnetophotonic based qPCR MEMS system that successfully detects and quantify specific disease related DNA mutations thus provides a promising future for rapid diagnosis of mitochondria diseases.

Keywords: mitochondrial DNA, micro-electro-mechanical-system, magnetophotonics, PCR

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101 Effects of Spectrotemporal Modulation of Music Profiles on Coherence of Cardiovascular Rhythms

Authors: I-Hui Hsieh, Yu-Hsuan Hu

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The powerful effect of music is often associated with changes in physiological responses such as heart rate and respiration. Previous studies demonstrate that Mayer waves of blood pressure, the spontaneous rhythm occurring at 0.1 Hz, corresponds to a progressive crescendo of the musical phrase. However, music contain dynamic changes in temporal and spectral features. As such, it remains unclear which aspects of musical structures optimally affect synchronization of cardiovascular rhythms. This study investigates the independent contribution of spectral pattern, temporal pattern, and dissonance level on synchronization of cardiovascular rhythms. The regularity of acoustical patterns occurring at a periodic rhythm of 0.1 Hz is hypothesized to elicit the strongest coherence of cardiovascular rhythms. Music excerpts taken from twelve pieces of Western classical repertoire were modulated to contain varying degrees of pattern regularity of the acoustic envelope structure. Three levels of dissonance were manipulated by varying the harmonic structure of the accompanying chords. Electrocardiogram and photoplethysmography signals were recorded for 5 minutes of baseline and simultaneously while participants listen to music excerpts randomly presented over headphones in a sitting position. Participants were asked to indicate the pleasantness of each music excerpt by adjusting via a slider presented on screen. Analysis of the Fourier spectral power of blood pressure around 0.1 Hz showed a significant difference between music excerpts characterized by spectral and temporal pattern regularity compared to the same content in random pattern. Phase coherence between heart rate and blood pressure increased significantly during listening to spectrally-regular phrases compared to its matched control phrases. The degree of dissonance of the accompanying chord sequence correlated with level of coherence between heart rate and blood pressure. Results suggest that low-level auditory features of music can entrain coherence of autonomic physiological variables. These findings have potential implications for using music as a clinical and therapeutic intervention for regulating cardiovascular functions.

Keywords: cardiovascular rhythms, coherence, dissonance, pattern regularity

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100 In Vitro and in Vivo Evaluation of Nano Collagen Molecules to Enhance Mesenchymal Stem Cells Differentiate into Insulin Producing Cells

Authors: Chin-Tsu Ma, Yi-Jhen Wu, Hsia Ying Cheng, Han Hsiang Huang, Shyh Ming Kuo

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The use of specific molecules including nutrients and pharmacological agents has been tried in modulation of stem cells differentiation (MSCs) to insulin producing cells. The aim of this study is to investigate the ability of nano collagen molecules (nutrient or scaffold) to enhance the MSCs differentiation into insulin-producing cells in combination with nicotinamide and exendin-4 (pharmacological agents) in vitro and in vivo. The results demonstrated that the cells exhibit morphologically islet-like clusters after treatment with nano collagen molecules, nicotinamide and exendin-4. MSCs extra treated with nano collagen molecules showed significant increases in Nkx6.1 and insulin mRNA expression at 14-d and 21-d culture compared with those merely treated with nicotinamide and exendin-4. Early 7-day elevation in PDX-1 mRNA expression was observed. Furthermore, the MSCs exposed to nano collagen molecules produced the highest secretion of insulin (p < 0.05). Type-2 diabetes induced by high-fat diet and low dose of streptozotocin in rat model was built in this study. This rat exhibited higher food intake, water intake, lower glucose tolerance, lower-insulin tolerance, and higher HbA1C (significant increases, p < 0.01) as compared with the normal rat that demonstrated the model of type-2 diabetes was successfully built. Biopsy examinations also showed that obvious destruction of islet. After injection of differentiated MSCs into the destructed pancreas of diabetes rat, more regenerated islet were observed at the rats that treated with nano collagen molecules and exhibited much lower HbA1C as compared with the normal rat and diabetes rat after 4 weeks (significant deceases, p < 0.001). These results indicate that the culturing MSCs with nano collagen molecules, nicotinamide, and exendin-4 are beneficial for MSCs differentiation into islet-like cells. These nano collagen molecules may lead to alternations or up-regulation of gene expression and influence the differentiated outcomes induced by nicotinamide and exendin-4.

Keywords: nano collagen molecules, nicotinamide, MSCs, diabetes

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99 A LED Warning Vest as Safety Smart Textile and Active Cooperation in a Working Group for Building a Normative Standard

Authors: Werner Grommes

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The institute of occupational safety and health works in a working group for building a normative standard for illuminated warning vests and did a lot of experiments and measurements as basic work (cooperation). Intelligent car headlamps are able to suppress conventional warning vests with retro-reflective stripes as a disturbing light. Illuminated warning vests are therefore required for occupational safety. However, they must not pose any danger to the wearer or other persons. Here, the risks of the batteries (lithium types), the maximum brightness (glare) and possible interference radiation from the electronics on the implant carrier must be taken into account. The all-around visibility, as well as the required range, play an important role here. For the study, many luminance measurements of already commercially available LEDs and electroluminescent warning vests, as well as their electromagnetic interference fields and aspects of electrical safety, were measured. The results of this study showed that LED lighting is all far too bright and causes strong glare. The integrated controls with pulse modulation and switching regulators cause electromagnetic interference fields. Rechargeable lithium batteries can explode depending on the temperature range. Electroluminescence brings even more hazards. A test method was developed for the evaluation of visibility at distances of 50, 100, and 150 m, including the interview of test persons. A measuring method was developed for the detection of glare effects at close range with the assignment of the maximum permissible luminance. The electromagnetic interference fields were tested in the time and frequency ranges. A risk and hazard analysis were prepared for the use of lithium batteries. The range of values for luminance and risk analysis for lithium batteries were discussed in the standards working group. These will be integrated into the standard. This paper gives a brief overview of the topics of illuminated warning vests, which takes into account the risks and hazards for the vest wearer or others

Keywords: illuminated warning vest, optical tests and measurements, risks, hazards, optical glare effects, LED, E-light, electric luminescent

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98 Performance Improvement of Long-Reach Optical Access Systems Using Hybrid Optical Amplifiers

Authors: Shreyas Srinivas Rangan, Jurgis Porins

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The internet traffic has increased exponentially due to the high demand for data rates by the users, and the constantly increasing metro networks and access networks are focused on improving the maximum transmit distance of the long-reach optical networks. One of the common methods to improve the maximum transmit distance of the long-reach optical networks at the component level is to use broadband optical amplifiers. The Erbium Doped Fiber Amplifier (EDFA) provides high amplification with low noise figure but due to the characteristics of EDFA, its operation is limited to C-band and L-band. In contrast, the Raman amplifier exhibits a wide amplification spectrum, and negative noise figure values can be achieved. To obtain such results, high powered pumping sources are required. Operating Raman amplifiers with such high-powered optical sources may cause fire hazards and it may damage the optical system. In this paper, we implement a hybrid optical amplifier configuration. EDFA and Raman amplifiers are used in this hybrid setup to combine the advantages of both EDFA and Raman amplifiers to improve the reach of the system. Using this setup, we analyze the maximum transmit distance of the network by obtaining a correlation diagram between the length of the single-mode fiber (SMF) and the Bit Error Rate (BER). This hybrid amplifier configuration is implemented in a Wavelength Division Multiplexing (WDM) system with a BER of 10⁻⁹ by using NRZ modulation format, and the gain uniformity noise ratio (signal-to-noise ratio (SNR)), the efficiency of the pumping source, and the optical signal gain efficiency of the amplifier are studied experimentally in a mathematical modelling environment. Numerical simulations were implemented in RSoft OptSim simulation software based on the nonlinear Schrödinger equation using the Split-Step method, the Fourier transform, and the Monte Carlo method for estimating BER.

Keywords: Raman amplifier, erbium doped fibre amplifier, bit error rate, hybrid optical amplifiers

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97 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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96 Inhibitory Effect of Coumaroyl Lupendioic Acid on Inflammation Mediator Generation in Complete Freund’s Adjuvant-Induced Arthritis

Authors: Rayhana Begum, Manju Sharma

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Careya arborea Roxb. belongs to the Lecythidaceae family, is traditionally used in tumors, anthelmintic, bronchitis, epileptic fits, astringents, inflammation, an antidote to snake-venom, skin disease, diarrhea, dysentery with bloody stools, dyspepsia, ulcer, toothache, and ear pain. The present study was focused on investigating the anti-arthritic effect of coumaroyl lupendioic acid, a new lupane-type triterpene from Careya arborea stem bark in the chronic inflammatory model and further assessing its possible mechanism on the modulation of inflammatory biomarkers. Arthritis was induced by injecting 0.1 ml of Complete Freund’s Adjuvant (5 mg/ml of heat killed Mycobacterium tuberculosis) into the subplantar region of the left hind paw. Treatment with coumaroyl lupendioic acid (10 and 20 mg/kg, p.o.) and reference drugs (indomethacin and dexamethasone at the dose of 5 mg/kg, p.o.) were started on the day of induction and continued up to 28 days. The progression of arthritis was evaluated by measuring paw volume, tibio tarsal joint diameters, and arthritic index. The effect of coumaroyl lupendioic acid (CLA) on the production PGE₂, NO, MPO, NF-κB, TNF-α, IL-1β, and IL-6 on serum level as well as inflamed paw tissue were also assessed. In addition, ankle joints and spleen were collected and prepared for histological examination. CLA in inflamed rats resulted in significant amelioration of paw edema, tibio-tarsal joint swelling and arthritic score as compared to CFA control group. The results indicated that CLA treated groups markedly decreased the levels of inflammatory mediators (PGE₂, NO, MPO and NF-κB levels) and down-regulated the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in paw tissue homogenates as well as in serum. However, the more pronounced effect was observed in the inflamed paw tissue homogenates. CLA also revealed a protective effect to the tibio-tarsal joint cartilage and spleen. These results suggest that coumaroyl lupendioic acid inhibits inflammation may be through the suppression of the cascade of proinflammatory mediators via the down-regulation of NF-ҡB.

Keywords: complete Freund’s adjuvant , Coumaroyl lupendioic acid, pro-inflammatory cytokines, prostaglandin E2

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95 Inverse Saturable Absorption in Non-linear Amplifying Loop Mirror Mode-Locked Fiber Laser

Authors: Haobin Zheng, Xiang Zhang, Yong Shen, Hongxin Zou

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The research focuses on mode-locked fiber lasers with a non-linear amplifying loop mirror (NALM). Although these lasers have shown potential, they still have limitations in terms of low repetition rate. The self-starting of mode-locking in NALM is influenced by the cross-phase modulation (XPM) effect, which has not been thoroughly studied. The aim of this study is two-fold. First, to overcome the difficulties associated with increasing the repetition rate in mode-locked fiber lasers with NALM. Second, to analyze the influence of XPM on self-starting of mode-locking. The power distributions of two counterpropagating beams in the NALM and the differential non-linear phase shift (NPS) accumulations are calculated. The analysis is conducted from the perspective of NPS accumulation. The differential NPSs for continuous wave (CW) light and pulses in the fiber loop are compared to understand the inverse saturable absorption (ISA) mechanism during pulse formation in NALM. The study reveals a difference in differential NPSs between CW light and pulses in the fiber loop in NALM. This difference leads to an ISA mechanism, which has not been extensively studied in artificial saturable absorbers. The ISA in NALM provides an explanation for experimentally observed phenomena, such as active mode-locking initiation through tapping the fiber or fine-tuning light polarization. These findings have important implications for optimizing the design of NALM and reducing the self-starting threshold of high-repetition-rate mode-locked fiber lasers. This study contributes to the theoretical understanding of NALM mode-locked fiber lasers by exploring the ISA mechanism and its impact on self-starting of mode-locking. The research fills a gap in the existing knowledge regarding the XPM effect in NALM and its role in pulse formation. This study provides insights into the ISA mechanism in NALM mode-locked fiber lasers and its role in selfstarting of mode-locking. The findings contribute to the optimization of NALM design and the reduction of self-starting threshold, which are essential for achieving high-repetition-rate operation in fiber lasers. Further research in this area can lead to advancements in the field of mode-locked fiber lasers with NALM.

Keywords: inverse saturable absorption, NALM, mode-locking, non-linear phase shift

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94 Comfort Sensor Using Fuzzy Logic and Arduino

Authors: Samuel John, S. Sharanya

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Automation has become an important part of our life. It has been used to control home entertainment systems, changing the ambience of rooms for different events etc. One of the main parameters to control in a smart home is the atmospheric comfort. Atmospheric comfort mainly includes temperature and relative humidity. In homes, the desired temperature of different rooms varies from 20 °C to 25 °C and relative humidity is around 50%. However, it varies widely. Hence, automated measurement of these parameters to ensure comfort assumes significance. To achieve this, a fuzzy logic controller using Arduino was developed using MATLAB. Arduino is an open source hardware consisting of a 24 pin ATMEGA chip (atmega328), 14 digital input /output pins and an inbuilt ADC. It runs on 5v and 3.3v power supported by a board voltage regulator. Some of the digital pins in Aruduino provide PWM (pulse width modulation) signals, which can be used in different applications. The Arduino platform provides an integrated development environment, which includes support for c, c++ and java programming languages. In the present work, soft sensor was introduced in this system that can indirectly measure temperature and humidity and can be used for processing several measurements these to ensure comfort. The Sugeno method (output variables are functions or singleton/constant, more suitable for implementing on microcontrollers) was used in the soft sensor in MATLAB and then interfaced to the Arduino, which is again interfaced to the temperature and humidity sensor DHT11. The temperature-humidity sensor DHT11 acts as the sensing element in this system. Further, a capacitive humidity sensor and a thermistor were also used to support the measurement of temperature and relative humidity of the surrounding to provide a digital signal on the data pin. The comfort sensor developed was able to measure temperature and relative humidity correctly. The comfort percentage was calculated and accordingly the temperature in the room was controlled. This system was placed in different rooms of the house to ensure that it modifies the comfort values depending on temperature and relative humidity of the environment. Compared to the existing comfort control sensors, this system was found to provide an accurate comfort percentage. Depending on the comfort percentage, the air conditioners and the coolers in the room were controlled. The main highlight of the project is its cost efficiency.

Keywords: arduino, DHT11, soft sensor, sugeno

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93 Modulation of the Interphase in a Glass Epoxy System: Influence of the Sizing Chemistry on Adhesion and Interfacial Properties

Authors: S. Assengone Otogo Be, A. Fahs, L. Belec, T. A. Nguyen Tien, G. Louarn, J-F. Chailan

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Glass fiber-reinforced composite materials have gradually developed in all sectors ranging from consumer products to aerospace applications. However, the weak point is most often the fiber/matrix interface, which can reduce the durability of the composite material. To solve this problem, it is essential to control the interphase and improve our understanding of the adhesion mechanism at the fibre/matrix interface. The interphase properties depend on the nature of the sizing applied on the surface of the glass fibers during their manufacture in order to protect them, facilitate their handling, and ensure fibre/matrix adhesion. The sizing composition, and in particular the nature of the coupling agent and the film-former affects the mechanical properties and the durability of composites. The aim of our study is, therefore, to develop and study composite materials with simplified sizing systems in order to understand how the main constituents modify the mechanical properties and the durability of composites from the nanometric to the macroscopic scale. Two model systems were elaborated: an epoxy matrix reinforced with simplified-sized glass fibres and an epoxy coating applied on glass substrates treated with the same sizings as fibres. For the sizing composition, two configurations were chosen. The first configuration possesses a chemical reactivity to link the glass and the matrix, and the second sizing contains non-reactive agents. The chemistry of the sized glass substrates and fibers was analyzed by FT-IR and XPS spectroscopies. The surface morphology was characterized by SEM and AFM microscopies. The observation of the surface samples reveals the presence of sizings which morphology depends on their chemistry. The evaluation of adhesion of coated substrates and composite materials show good interfacial properties for the reactive configuration. However, the non-reactive configuration exhibits an adhesive rupture at the interface of glass/epoxy for both systems. The interfaces and interphases between the matrix and the substrates are characterized at different scales. Correlations are made between the initial properties of the sizings and the mechanical performances of the model composites.

Keywords: adhesion, interface, interphase, materials composite, simplified sizing systems, surface properties

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92 Dynamic Simulation of a Hybrid Wind Farm with Wind Turbines and Distributed Compressed Air Energy Storage System

Authors: Eronini Iheanyi Umez-Eronini

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Most studies and existing implementations of compressed air energy storage (CAES) coupled with a wind farm to overcome intermittency and variability of wind power are based on bulk or centralized CAES plants. A dynamic model of a hybrid wind farm with wind turbines and distributed CAES, consisting of air storage tanks and compressor and expander trains at each wind turbine station, is developed and simulated in MATLAB. An ad hoc supervisory controller, in which the wind turbines are simply operated under classical power optimizing region control while scheduling power production by the expanders and air storage by the compressors, including modulation of the compressor power levels within a control range, is used to regulate overall farm power production to track minute-scale (3-minutes sampling period) TSO absolute power reference signal, over an eight-hour period. Simulation results for real wind data input with a simple wake field model applied to a hybrid plant composed of ten 5-MW wind turbines in a row and ten compatibly sized and configured Diabatic CAES stations show the plant controller is able to track the power demand signal within an error band size on the order of the electrical power rating of a single expander. This performance suggests that much improved results should be anticipated when the global D-CAES control is combined with power regulation for the individual wind turbines using available approaches for wind farm active power control. For standalone power plant fuel electrical efficiency estimate of up to 60%, the round trip electrical storage efficiency computed for the distributed CAES wherein heat generated by running compressors is utilized in the preheat stage of running high pressure expanders while fuel is introduced and combusted before the low pressure expanders, was comparable to reported round trip storage electrical efficiencies for bulk Adiabatic CAES.

Keywords: hybrid wind farm, distributed CAES, diabatic CAES, active power control, dynamic modeling and simulation

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91 PWM Harmonic Injection and Frequency-Modulated Triangular Carrier to Improve the Lives of the Transformers

Authors: Mario J. Meco-Gutierrez, Francisco Perez-Hidalgo, Juan R. Heredia-Larrubia, Antonio Ruiz-Gonzalez, Francisco Vargas-Merino

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More and more applications power inverters connected to transformers, for example, the connection facilities to the power grid renewable generation. It is well known that the quality of signal power inverters it is not a pure sine. The harmonic content produced negative effects, one of which is the heating of electrical machines and therefore, affects the life of the machines. The decrease of life of transformers can be calculated by Arrhenius or Montsinger equation. Analyzing this expression any (long-term) decrease of a transformer temperature for 6º C - 7º C means doubles its life-expectancy. Methodologies: This work presents the technique of pulse width modulation (PWM) with an injection of harmonic and triangular frequency carrier modulated in frequency. This technique is used to improve the quality of the output voltage signal of the power inverters controlled PWM. The proposed technique increases in the fundamental term and a significant reduction in low order harmonics with the same commutations per time that control sine PWM. To achieve this, the modulating wave is compared to a triangular carrier with variable frequency over the period of the modulator. Therefore, it is, advantageous for the modulating signal to have a large amount of sinusoidal “information” in the areas of greater sampling. A triangular signal with a frequency that varies over the modulator’s period is used as a carrier, for obtaining more samples in the area with the greatest slope. A power inverter controlled by PWM proposed technique is connected to a transformer. Results: In order to verify the derived thermal parameters under different operation conditions, another ambient and loading scenario is involved for a further verification, which was sampled from the same power transformer. Temperatures of different parts of the transformer will be exposed for each PWM control technique analyzed. An assessment of the temperature be done with different techniques PWM control and hence the life of the transformer is calculated for each technique. Conclusion: This paper analyzes such as transformer heating produced by this technique and compared with other forms of PWM control. In it can be seen as a reduction the harmonic content produces less heat transformer and therefore, an increase in the life of the transformer.

Keywords: heating, power-inverter, PWM, transformer

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90 Modulation of the Innate Immune Response in Bovine Udder Tissue by Epigenetic Modifiers

Authors: Holm Zerbe, Laura Macias, Hans-Joachim Schuberth, Wolfram Petzl

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Mastitis is among the most important production diseases in cows. It accounts for large parts of antimicrobial drug use in the dairy industry worldwide. Due to the imminent normative to reduce the use of antimicrobial drugs in livestock, new ways for therapy and prophylaxis of mastitis are needed. Recently epigenetic regulation of inflammation by chromatin modifications has increasingly drawn attention. Currently, some epigenetic modifiers have already been approved for the use in humans, however little is known about their actions in the bovine system. The aim of our study was to investigate whether three selected epigenetic modifiers (Vitamin D3, SAHA and S2101) influence the initial immune response towards mastitis pathogens in bovine udder tissue in vitro. Tissue explants of the teat cistern and udder parenchyma were collected from 21 cows and were incubated for 36 hours in the absence and presence of epigenetic modifiers. Additionally, the tissue was stimulated with heat-inactivated particles of Escherichia coli and Staphylococcus aureus, which are regarded as two of the most important mastitis pathogens. After incubation, the explants were tested by RT-qPCR for transcript abundances of immune-related candidate genes. Gene expression was validated in culture supernatants by an AlphaLISA assay. Furthermore, the culture supernatants were analyzed for their chemotactic capacity through a chemotaxis assay. Statistical analysis of data was performed with the program ‘R’ version 3.2.3. Vitamin D3 had no effect on the immune response of udder tissue in vitro after stimulation with mastitis pathogens. The epigenetic modifiers SAHA and S2101 however significantly blocked the pathogen-induced upregulation of CXCL8, TNFα, S100A9 and LAP (P < 0.05). The regulation of IL10 was not affected by treatment with SAHA and S2101. Transcript abundances for CXCL8 were reflected by IL8 contents and chemotactic activity in culture supernatants. In conclusion, these data show the potential of epigenetic modifiers (SAHA and S2101) to block overshooting inflammation in the udder. Thus epigenetic modifiers may serve in future as immune modulators for the treatment and/or prophylaxis of clinical mastitis. (Funded by Deutsche Forschungsgemeinschaft PE 1495/2-1).

Keywords: mastitis, cattle, epigenetics, immunomodulation

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89 Electrostatic Solitary Waves in Degenerate Relativistic Quantum Plasmas

Authors: Sharmin Sultana, Reinhard Schlickeiser

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A degenerate relativistic quantum plasma (DRQP) system (containing relativistically degenerate electrons, degenerate/non-degenerate light nuclei, and non-degenerate heavy nuclei) is considered to investigate the propagation characteristics of electrostatic solitary waves (in the ionic scale length) theoretically and numerically. The ion-acoustic solitons are found to be associated with the modified ion-acoustic waves (MIAWs) in which inertia (restoring force) is provided by mass density of the light or heavy nuclei (degenerate pressure of the cold electrons). A mechanical-motion analog (Sagdeev-type) pseudo-potential approach is adopted to study the properties of large amplitude solitary waves. The basic properties of the large amplitude MIAWs and their existence domain in terms of soliton speed (Mach number) are examined. On the other hand, a multi-scale perturbation approach, leading to an evolution equation for the envelope dynamics, is adopted to derive the cubic nonlinear Schrödinger equation (NLSE). The criteria for the occurrence of modulational instability (MI) of the MIAWs are analyzed via the nonlinear dispersion relation of the NLSE. The possibility for the formation of highly energetic localized modes (e.g. peregrine solitons, rogue waves, etc.) is predicted in such DRQP medium. Peregrine solitons or rogue waves with amplitudes of several times of the background are observed to form in DRQP. The basic features of these modulated waves (e.g. envelope solitons, peregrine solitons, and rogue waves), which are found to form in DRQP, and their MI criteria (on the basis of different intrinsic plasma parameters), are investigated. It is emphasized that our results should be useful in understanding the propagation characteristics of localized disturbances and the modulation dynamics of envelope solitons, and their instability criteria in astrophysical DRQP system (e.g. white dwarfs, neutron stars, etc., where matters under extreme conditions are assumed to exist) and also in ultra-high density experimental plasmas.

Keywords: degenerate plasma, envelope solitons, modified ion-acoustic waves, modulational instability, rogue waves

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88 Success of Trabeculectomy: May Not Always Depend on Mitomycin C

Authors: Sushma Tejwani, Shoruba Dinakaran, Rupa Rokhade, K. Bhujang Shetty

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Introduction and aim: One of the major causes for failure of trabeculectomy is fibrosis and scarring of subconjunctival tissue around the bleb, and hence intra operative usage of anti-fibrotic agents like Mitomycin C (MMC) has become very popular. However, the long term effects of MMC like thin, avascular bleb, hypotony, bleb leaks and late onset endophthalmitis cannot be ignored, and may preclude its usage in routine trabeculectomy. In this particular study we aim to study the outcomes of trabeculectomy with and without MMC in uncomplicated glaucoma patients. Methods: Retrospective study of series of patients that underwent trabeculectomy with or without cataract surgery in glaucoma department of a tertiary eye care centre by a single surgeon for primary open angle glaucoma (POAG), angle closure glaucoma (PACG), Pseudoexfoliation glaucoma (PXF glaucoma). Patients with secondary glaucoma, juvenile and congenital glaucoma were excluded; also patients undergoing second trabeculectomy were excluded. The outcomes were studied in terms of IOP control at 1 month, 6 months, and 1 year and were analyzed separately for surgical outcomes with and without MMC. Success was considered if IOP was < 16 mmHg on applanation tonometry. Further, the necessity of medication, 5 fluorouracil (5FU) postoperative injections, needling post operatively was noted. Results: Eighty nine patient’s medical records were reviewed, of which 58 patients had undergone trabeculectomy without MMC and 31 with MMC. Mean age was 62.4 (95%CI 61- 64), 34 were females and 55 males. MMC group (n=31): Preoperative mean IOP was 21.1mmHg (95% CI: 17.6 -24.6), and 22 patients had IOP > 16. Three out of 33 patients were on single medication and rests were on multiple drugs. At 1 month (n=27) mean IOP was 12.4 mmHg (CI: 10.7-14), and 31/33 had success. At 6 months (n=18) mean IOP was 13mmHg (CI: 10.3-14.6) and 16/18 had good outcome, however at 1 year only 11 patients were available for follow up and 91% (10/11) had success. Overall, 3 patients required medication and one patient required postoperative injection of 5 FU. No MMC group (n=58): Preoperative mean IOP was 21.9 mmHg (CI: 19.8-24.2), and 42 had IOP > 16 mmHg. 12 out of 58 patients were on single medication and rests were on multiple drugs. At 1 month (n=52) mean IOP was14.6mmHg (CI: 13.2-15.9), and 45/ 58 had IOP < 16mmHg. At 6 months (n=31) mean IOP was 13.5 mmHg (CI: 11.9-15.2) and 26/31 had success, however at 1 year only 23 patients came for follow up and of these 87% (20/23) patients had success. Overall, 1 patient required needling, 5 required 5 FU injections and 5 patients required medication. The success rates at each follow up visit were not significantly different in both the groups. Conclusion: Intra-operative MMC usage may not be required in all patients undergoing trabeculectomy, and the ones without MMC also have fairly good outcomes in primary glaucoma.

Keywords: glaucoma filtration surgery, mitomycin C, outcomes of trabeculectomy, wound modulation

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87 Multi-Omics Integrative Analysis Coupled to Control Theory and Computational Simulation of a Genome-Scale Metabolic Model Reveal Controlling Biological Switches in Human Astrocytes under Palmitic Acid-Induced Lipotoxicity

Authors: Janneth Gonzalez, Andrés Pinzon Velasco, Maria Angarita

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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-inflammatorypathways in the brain. The use of synthetic neurosteroids such as tibolone has demonstrated neuro-protective mechanisms. However, broad studies with a systemic point of view on the neurodegenerative role of PA and the neuro-protective mechanisms of tibolone are lacking. 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 applied a control theory approach to identify those reactions that exert more control in the astrocytic system. Our results suggest that PA generates a modulation of central and secondary metabolism, showing a switch 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 of metabolic pathways that may increase neurotoxicity and represent potential treatment targets. Finally, the overall framework of our approach facilitates the understanding of complex metabolic regulation, and it can be used for in silico exploration of 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

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86 Performance of High Efficiency Video Codec over Wireless Channels

Authors: Mohd Ayyub Khan, Nadeem Akhtar

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Due to recent advances in wireless communication technologies and hand-held devices, there is a huge demand for video-based applications such as video surveillance, video conferencing, remote surgery, Digital Video Broadcast (DVB), IPTV, online learning courses, YouTube, WhatsApp, Instagram, Facebook, Interactive Video Games. However, the raw videos posses very high bandwidth which makes the compression a must before its transmission over the wireless channels. The High Efficiency Video Codec (HEVC) (also called H.265) is latest state-of-the-art video coding standard developed by the Joint effort of ITU-T and ISO/IEC teams. HEVC is targeted for high resolution videos such as 4K or 8K resolutions that can fulfil the recent demands for video services. The compression ratio achieved by the HEVC is twice as compared to its predecessor H.264/AVC for same quality level. The compression efficiency is generally increased by removing more correlation between the frames/pixels using complex techniques such as extensive intra and inter prediction techniques. As more correlation is removed, the chances of interdependency among coded bits increases. Thus, bit errors may have large effect on the reconstructed video. Sometimes even single bit error can lead to catastrophic failure of the reconstructed video. In this paper, we study the performance of HEVC bitstream over additive white Gaussian noise (AWGN) channel. Moreover, HEVC over Quadrature Amplitude Modulation (QAM) combined with forward error correction (FEC) schemes are also explored over the noisy channel. The video will be encoded using HEVC, and the coded bitstream is channel coded to provide some redundancies. The channel coded bitstream is then modulated using QAM and transmitted over AWGN channel. At the receiver, the symbols are demodulated and channel decoded to obtain the video bitstream. The bitstream is then used to reconstruct the video using HEVC decoder. It is observed that as the signal to noise ratio of channel is decreased the quality of the reconstructed video decreases drastically. Using proper FEC codes, the quality of the video can be restored up to certain extent. Thus, the performance analysis of HEVC presented in this paper may assist in designing the optimized code rate of FEC such that the quality of the reconstructed video is maximized over wireless channels.

Keywords: AWGN, forward error correction, HEVC, video coding, QAM

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85 Language Errors Used in “The Space between Us” Movie and Their Effects on Translation Quality: Translation Study toward Discourse Analysis Approach

Authors: Mochamad Nuruz Zaman, Mangatur Rudolf Nababan, M. A. Djatmika

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Both society and education areas teach to have good communication for building the interpersonal skills up. Everyone has the capacity to understand something new, either well comprehension or worst understanding. Worst understanding makes the language errors when the interactions are done by someone in the first meeting, and they do not know before it because of distance area. “The Space between Us” movie delivers the love-adventure story between Mars Boy and Earth Girl. They are so many missing conversations because of the different climate and environment. As the moviegoer also must be focused on the subtitle in order to enjoy well the movie. Furthermore, Indonesia subtitle and English conversation on the movie still have overlapping understanding in the translation. Translation hereby consists of source language -SL- (English conversation) and target language -TL- (Indonesia subtitle). These research gap above is formulated in research question by how the language errors happened in that movie and their effects on translation quality which is deepest analyzed by translation study toward discourse analysis approach. The research goal is to expand the language errors and their translation qualities in order to create a good atmosphere in movie media. The research is studied by embedded research in qualitative design. The research locations consist of setting, participant, and event as focused determined boundary. Sources of datum are “The Space between Us” movie and informant (translation quality rater). The sampling is criterion-based sampling (purposive sampling). Data collection techniques use content analysis and questioner. Data validation applies data source and method triangulation. Data analysis delivers domain, taxonomy, componential, and cultural theme analysis. Data findings on the language errors happened in the movie are referential, register, society, textual, receptive, expressive, individual, group, analogical, transfer, local, and global errors. Data discussions on their effects to translation quality are concentrated by translation techniques on their data findings; they are amplification, borrowing, description, discursive creation, established equivalent, generalization, literal, modulation, particularization, reduction, substitution, and transposition.

Keywords: discourse analysis, language errors, The Space between Us movie, translation techniques, translation quality instruments

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84 Identification and Molecular Profiling of A Family I Cystatin Homologue from Sebastes schlegeli Deciphering Its Putative Role in Host Immunity

Authors: Don Anushka Sandaruwan Elvitigala, P. D. S. U. Wickramasinghe, Jehee Lee

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Cystatins are a large superfamily of proteins which act as reversible inhibitors of cysteine proteases. Papain proteases and cysteine cathepsins are predominant substrates of cystatins. Cystatin superfamily can be further clustered into three groups as Stefins, Cystatins, and Kininogens. Among them, stefines are also known as family 1 cystatins which harbors cystatin Bs and cystatin As. In this study, a homologue of family one cystatins more close to cystatin Bs was identified from Korean black rockfish (Sebastes schlegeli) using a prior constructed cDNA (complementary deoxyribonucleic acid) database and designated as RfCyt1. The full-length cDNA of RfCyt1 consisted of 573 bp, with a coding region of 294 bp. It comprised a 5´-untranslated region (UTR) of 55 bp, and 3´-UTR of 263 bp. The coding sequence encodes a polypeptide consisting of 97 amino acids with a predicted molecular weight of 11kDa and theoretical isoelectric point of 6.3. The RfCyt1 shared homology with other teleosts and vertebrate species and consisted conserved features of cystatin family signature including single cystatin-like domain, cysteine protease inhibitory signature of pentapeptide (QXVXG) consensus sequence and N-terminal two conserved neighboring glycine (⁸GG⁹) residues. As expected, phylogenetic reconstruction developed using the neighbor-joining method showed that RfCyt1 is clustered with the cystatin family 1 members, in which more closely with its teleostan orthologues. An SYBR Green qPCR (quantitative polymerase chain reaction) assay was performed to quantify the RfCytB transcripts in different tissues in healthy and immune stimulated fish. RfCyt1 was ubiquitously expressed in all tissue types of healthy animals with gill and spleen being the highest. Temporal expression of RfCyt1 displayed significant up-regulation upon infection with Aeromonas salmonicida. Recombinantly expressed RfCyt1 showed concentration-dependent papain inhibitory activity. Collectively these findings evidence for detectable protease inhibitory and immunity relevant roles of RfCyt1 in Sebastes schlegeli.

Keywords: Sebastes schlegeli, family 1 cystatin, immune stimulation, expressional modulation

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83 Targeting APP IRE mRNA to Combat Amyloid -β Protein Expression in Alzheimer’s Disease

Authors: Mateen A Khan, Taj Mohammad, Md. Imtaiyaz Hassan

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Alzheimer’s disease is characterized by the accumulation of the processing products of the amyloid beta peptide cleaved by amyloid precursor protein (APP). Iron increases the synthesis of amyloid beta peptides, which is why iron is present in Alzheimer's disease patients' amyloid plaques. Iron misregulation in the brain is linked to the overexpression of APP protein, which is directly related to amyloid-β aggregation in Alzheimer’s disease. The APP 5'-UTR region encodes a functional iron-responsive element (IRE) stem-loop that represents a potential target for modulating amyloid production. Targeted regulation of APP gene expression through the modulation of 5’-UTR sequence function represents a novel approach for the potential treatment of AD because altering APP translation can be used to improve both the protective brain iron balance and provide anti-amyloid efficacy. The molecular docking analysis of APP IRE RNA with eukaryotic translation initiation factors yields several models exhibiting substantial binding affinity. The finding revealed that the interaction involved a set of functionally active residues within the binding sites of eIF4F. Notably, APP IRE RNA and eIF4F interaction were stabilized by multiple hydrogen bonds with residues of APP IRE RNA and eIF4F. It was evident that APP IRE RNA exhibited a structural complementarity that tightly fit within binding pockets of eIF4F. The simulation studies further revealed the stability of the complexes formed between RNA and eIF4F, which is crucial for assessing the strength of these interactions and subsequent roles in the pathophysiology of Alzheimer’s disease. In addition, MD simulations would capture conformational changes in the IRE RNA and protein molecules during their interactions, illustrating the mechanism of interaction, conformational change, and unbinding events and how it may affect aggregation propensity and subsequent therapeutic implications. Our binding studies correlated well with the translation efficiency of APP mRNA. Overall, the outcome of this study suggests that the genomic modification and/or inhibiting the expression of amyloid protein by targeting APP IRE RNA can be a viable strategy to identify potential therapeutic targets for AD and subsequently be exploited for developing novel therapeutic approaches.

Keywords: Alzheimer's disease, Protein-RNA interaction analysis, molecular docking simulations, conformational dynamics, binding stability, binding kinetics, protein synthesis.

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82 Pioneering Technology of Night Photo-Stimulation of the Brain Lymphatic System: Therapy of Brain Diseases during Sleep

Authors: Semyachkina-Glushkovskaya Oxana, Fedosov Ivan, Blokhina Inna, Terskov Andrey, Evsukova Arina, Elovenko Daria, Adushkina Viktoria, Dubrovsky Alexander, Jürgen Kurths

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In modern neurobiology, sleep is considered a novel biomarker and a promising therapeutic target for brain diseases. This is due to recent discoveries of the nighttime activation of the brain lymphatic system (BLS), playing an important role in the removal of wastes and toxins from the brain and contributes neuroprotection of the central nervous system (CNS). In our review, we discuss that night stimulation of BLS might be a breakthrough strategy in a new treatment of Alzheimer’s and Parkinson’s disease, stroke, brain trauma, and oncology. Although this research is in its infancy, however, there are pioneering and promising results suggesting that night transcranial photostimulation (tPBM) stimulates more effectively lymphatic removal of amyloid-beta from mouse brain than daily tPBM that is associated with a greater improvement of the neurological status and recognition memory of animals. In our previous study, we discovered that tPBM modulates the tone and permeability of the lymphatic endothelium by stimulating NO formation, promoting lymphatic clearance of wastes and toxins from the brain tissues. We also demonstrate that tPBM can also lead to angio- and lymphangiogenesis, which is another mechanism underlying tPBM-mediated stimulation of BLS. Thus, photo-augmentation of BLS might be a promising therapeutic target for preventing or delaying brain diseases associated with BLS dysfunction. Here we present pioneering technology for simultaneous tPBM in humans and sleep monitoring for stimulation of BLS to remove toxins from CNS and modulation of brain immunity. The wireless-controlled gadget includes a flexible organic light-emitting diode (LED) source that is controlled directly by a sleep-tracking device via a mobile application. The designed autonomous LED source is capable of providing the required therapeutic dose of light radiation at a certain region of the patient’s head without disturbing of sleeping patient. To minimize patients' discomfort, advanced materials like flexible organic LEDs were used. Acknowledgment: This study was supported by RSF project No. 23-75-30001.

Keywords: brain diseases, brain lymphatic system, phototherapy, sleep

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81 Metformin and Its Combination with Sodium Hydrosulfide Influences Plasma Galectin-3 and CSE/H₂S System in Diabetic Rat's Heart

Authors: I. V. Palamarchuk, N. V. Zaichko

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Background and Aims: Galectin-3 is a marker of subclinical cardiac injury and is elevated in individuals with type 2 diabetes mellitus; while hydrogen sulfide (H₂S), metabolite of sulfur-containing amino acids, is considered having antifibrogenic effects. This study was designed to investigate whether metformin and its combination with NaHS can influence plasma galectin-3 and cystathionine-γ-lyase/hydrogen sulfide (CSE/H₂S) system in diabetic rat’s heart. Methods: 32 healthy male rats (180-250 g) were divided into 4 groups. To induct diabetes, rats (group 2-4) were injected with streptozotocin (STZ, 40 mg/kg/i.p., 0.1 M citrate buffer (pH 4.5). Rats from 3d (STZ+Metf) and 4th (STZ+Metf+NaHS) groups were given metformin (500 mg/kg/day) orally, and rats from 4th (STZ+Metf+NaHS) group were injected sodium hydrosulfide (NaHS, 3 mg/kg/i.p.) once per day starting from 3 to 28 day after streptozotocin injection. Rats of first group (control) were administered the equivalent volumes of 0.9% NaCl. Plasma galectin-3 was measured by ELISA. Rats’ hearts were sampled for determination of H2S by reaction with N,N-Dimethyl-p-phenylenediamine. Determination of CSE gene expression was performed in real time using PCR in the presence of SYBR Green I, using DT-Light detecting amplifier ('DNA-technology', Russia). Results: Induction of streptozotocin diabetes (STZ-diabetes, group 2) was followed by low myocardial H2S concentration and CSE expression (by 35%, p < 0.05 and 60.5%, p < 0.001 respectively, than that in controls), while plasma galectin-3 in this group was significantly higher than in controls (by 3.8 times, p < 0.05). Administration of metformin (group 3) resulted in significantly higher H₂S concentration (by 28.5%, p < 0.05), whereas CSE expression was only by 6% more than that in STZ-diabetes, as well as plasma galectin-3 was only by 14.8% lower in comparison with untreated diabetic rats. The inhibition of H₂S generation and CSE activity by diabetes was greatly attenuated in STZ+Metf+NaHS group. The combination of metformin with NaHS significantly stimulated H₂S production (by 48%, p < 0.05 and 15%, p < 0.05 more than STZ-diabetes and STZ+Metf respectively) and CSE gene expression (by 64.8%, p < 0.05 compared to STZ-diabetes and by 55.4%,p < 0.05 compared to STZ+Metf). Besides, plasma galectin-3 in rats receiving metformin and NaHS was significantly lower by 42%, p < 0.05 and 32.5%, p < 0.05 compared to STZ-diabetes and STZ+Metf groups respectively. Conclusions: To summarize, dysfunction of CSE/H2S system and galectin-3 stimulation was found in streptozotocin-induced diabetic rats. Metformin and its combination with exogenous H2S effectively prevented the development of metabolic changes induced by diabetes. These findings suggest that CSE/H₂S system can be integrated into pathogenesis of diabetic complications through modulation of pro-inflammatory and pro-fibrogenic mediator galectin-3.

Keywords: cystathionine-γ-lyase, diabetic heart, galectin-3, hydrogen sulfide, metformin, sodium hydrosulfide

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80 Pregnancy - The Unique Immunological Paradigm

Authors: Husham Bayazed

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Purpose of presentation: Pregnancy represents the most important period for the conservation of the species. The immune system is one of the most important systems protecting the mother against the environment and preventing damage to the fetus. This presentation aims to review and discuss the role of the immune system during pregnancy, the evolutionary inflammatory process through pregnancy, infectious and environmental exposure influences on the mother and the fetus, and the impacts of sexual dimorphism of the placenta on offspring susceptibility to different disorders. Recent Findings: In 1960, Peter Medawar (Nobel Prize Winner) proposed that the fetus, a semi-allograft, is similar to a tissue graft that escapes rejection through a mechanism involving systemic immune suppression (Graft –Host response). However, recent researchers and studies have documented that implantation means inflammation, and the inflammatory process is considered a breach of tolerance in pregnancy with immune induction, which is necessary for the protection of the mother and the fetus against infections and environmental triggers. This inflammatory process should be maintained during different pregnancy phases till parturition, and any block at any phase will be associated with pregnancy complications, including pregnancy failure or loss, miscarriage, and preterm birth subsequently. Maternal immune activation following any trigger can have a positive effect on the fetus. The old concept of the placenta being asexual is inaccurate, and being with sexual dimorphism with clear differences in susceptibility to different factors that stimulate maternal immunity. Summary: The presence of different immune cells ((i.e., T cells, B cells, NK cells, etc.) at the implantation site is considered proof of a strong maternal immune response to the fetus. Therefore, human pregnancy is considered a unique immunological paradigm requiring maternal immune modulation rather than suppression. So Medawar's postulation of maternal systemic immunosuppression is wrong. Maternal immune system activation triggered by infections, stress, diet, and pollution can have a positive effect on the fetus, with the development of fetal-trained immunity necessary for survival. The sexual dimorphism of the placenta seems to have an impact on the differences in sex susceptible to the environment maternal risk stimuli. This link to why the incidence of autism is increasing more among boys than girls.

Keywords: pregnancy, maternal immunity, implantation and inflammation, placenta sexual dimorphism

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79 Therapeutic Role of T Subpopulations Cells (CD4, CD8 and Treg (CD25 and FOXP3+ Cells) of UC MSC Isolated from Three Different Methods in Various Disease

Authors: Kumari Rekha, Mathur K Dhananjay, Maheshwari Deepanshu, Nautiyal Nidhi, Shubham Smriti, Laal Deepika, Sinha Swati, Kumar Anupam, Biswas Subhrajit, Shiv Kumar Sarin

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Background: Mesenchymal stem cells are multipotent stem cells derived from mesoderm and are used for therapeutic purposes because of their self-renewal, homing capacity, Immunomodulatory capability, low immunogenicity and mitochondrial transfer signaling. MSCs have the ability to regulate the mechanism of both innate as well as adaptive immune responses through the modulation of cellular response and the secretion of inflammatory mediators. Different sources of MSC are UC MSC, BM MSC, Dental Pulp, and Adipose MSC. The most frequent source used is umbilical cord tissue due to its being easily available and free of limitations of collection procedures from respective hospitals. The immunosuppressive role of MSCs is particularly interesting for clinical use since it confers resistance to rejection by the host immune response. Methodology: In this study, T helper cells (TH4), Cytotoxic T cells (CD-8), immunoregulatory cells (CD25 +FOXP3+) are compared from isolated MSC from three different methods, UC Dissociation Kit (Miltenyi), Explant Culture and Collagenase Type-IV. To check the immunomodulatory property, these MSCs were seeded with PBMC(Coculture) in CD3 coated 24 well plates. Cd28 antibody was added in coculture for six days. The coculture was analyzed in FACS Verse flow cytometry. Results: From flow cytometry analysis of coculture, it found that All over T helper cells (CD4+) number p<0.0264 increases in (All Enzymes) MSC rather than explant MSC(p>0.0895) as compared to Collagenase(p>0.7889) in a coculture of Activated T cell and Mesenchymal Stem Cell. Similar T reg cells (CD25+, FOXP3+) expression p<0.0234increases in All Enzymes), decreases in Explant and Collagenase. Experiments have shown that MSCs can also directly prevent the cytotoxic activity of CD8 lymphocytes mainly by blocking their proliferation rather than by inhibiting the cytotoxic effect. And promoting the t-reg cells, which helps in the mediation of immune response in various diseases. Conclusion: MSC suppress Cytotoxic CD8 T cell and Enhance immunoregulatory T reg (CD4+, CD25+, FOXP3+) Cell expression. Thus, MSC maintains a proper balance(ratio) between CD4 T cells and Cytotoxic CD8 T cells.

Keywords: MSC, disease, T cell, T regulatory

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78 The Role of Autophagy Modulation in Angiotensin-II Induced Hypertrophy

Authors: Kitti Szoke, Laszlo Szoke, Attila Czompa, Arpad Tosaki, Istvan Lekli

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Autophagy plays an important role in cardiac hypertrophy, which is one of the most common causes of heart failure in the world. This self-degradative catabolic process, responsible for protein quality control, balancing sources of energy at critical times, and elimination of damaged organelles. The autophagic activity can be triggered by starvation, oxidative stress, or pharmacological agents, like rapamycin. This induced autophagy can promote cell survival during starvation or pathological stress. In this study, it is investigated the effect of the induced autophagic process on angiotensin induced hypertrophic H9c2 cells. In our study, it is used H9c2 cells as an in vitro model. To induce hypertrophy, cells were treated with 10000 nM angiotensin-II, and to activate autophagy, 100 nM rapamycin treatment was used. The following groups were formed: 1: control, 2: 10000 nM AT-II, 3: 100 nM rapamycin, 4: 100 nM rapamycin pretreatment then 10000 nM AT-II. The cell viability was examined via MTT (cell proliferation assay) assay. The cells were stained with rhodamine-conjugated phalloidin and DAPI to visualize F-actin filaments and cell nuclei then the cell size alteration was examined in a fluorescence microscope. Furthermore, the expression levels of autophagic and apoptotic proteins such as Beclin-1, p62, LC3B-II, Cleaved Caspase-3 were evaluated by Western blot. MTT assay result suggests that the used pharmaceutical agents in the tested concentrations did not have a toxic effect; however, at group 3, a slight decrement was detected in cell viability. In response to AT-II treatment, a significant increase was detected in the cell size; cells became hypertrophic. However, rapamycin pretreatment slightly reduced the cell size compared to group 2. Western blot results showed that AT-II treatment-induced autophagy, because the increased expression of Beclin-1, p62, LC3B-II were observed. However, due to the incomplete autophagy, the apoptotic Cleaved Caspase-3 expression also increased. Rapamycin pretreatment up-regulated Beclin-1 and LC3B-II, down-regulated p62 and Cleaved Caspase-3, indicating that rapamycin-induced autophagy can restore the normal autophagic flux. Taken together, our results suggest that rapamycin activated autophagy reduces angiotensin-II induced hypertrophy.

Keywords: angiotensin-II, autophagy, H9c2 cell line, hypertrophy, rapamycin

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77 Anticancer Activity of Milk Fat Rich in Conjugated Linoleic Acid Against Ehrlich Ascites Carcinoma Cells in Female Swiss Albino Mice

Authors: Diea Gamal Abo El-Hassan, Salwa Ahmed Aly, Abdelrahman Mahmoud Abdelgwad

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The major conjugated linoleic acid (CLA) isomers have anticancer effect, especially breast cancer cells, inhibits cell growth and induces cell death. Also, CLA has several health benefits in vivo, including antiatherogenesis, antiobesity, and modulation of immune function. The present study aimed to assess the safety and anticancer effects of milk fat CLA against in vivo Ehrlich ascites carcinoma (EAC) in female Swiss albino mice. This was based on acute toxicity study, detection of the tumor growth, life span of EAC bearing hosts, and simultaneous alterations in the hematological, biochemical, and histopathological profiles. Materials and Methods: One hundred and fifty adult female mice were equally divided into five groups. Groups (1-2) were normal controls, and Groups (3-5) were tumor transplanted mice (TTM) inoculated intraperitoneally with EAC cells (2×106 /0.2 mL). Group (3) was (TTM positive control). Group (4) TTM fed orally on balanced diet supplemented with milk fat CLA (40 mg CLA/kg body weight). Group (5) TTM fed orally on balanced diet supplemented with the same level of CLA 28 days before tumor cells inoculation. Blood samples and specimens from liver and kidney were collected from each group. The effect of milk fat CLA on the growth of tumor, life span of TTM, and simultaneous alterations in the hematological, biochemical, and histopathological profiles were examined. Results: For CLA treated TTM, significant decrease in tumor weight, ascetic volume, viable Ehrlich cells accompanied with increase in life span were observed. Hematological and biochemical profiles reverted to more or less normal levels and histopathology showed minimal effects. Conclusion: The present study proved the safety and anticancer efficiency of milk fat CLA and provides a scientific basis for its medicinal use as anticancer attributable to the additive or synergistic effects of its isomers.

Keywords: anticancer activity, conjugated linoleic acid, Ehrlich ascites carcinoma, % increase in life span, mean survival time, tumor transplanted mice.

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76 Opto-Thermal Frequency Modulation of Phase Change Micro-Electro-Mechanical Systems

Authors: Syed A. Bukhari, Ankur Goswmai, Dale Hume, Thomas Thundat

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Here we demonstrate mechanical detection of photo-induced Insulator to metal transition (MIT) in ultra-thin vanadium dioxide (VO₂) micro strings by using < 100 µW of optical power. Highly focused laser beam heated the string locally resulting in through plane and along axial heat diffusion. Localized temperature increase can cause temperature rise > 60 ºC. The heated region of VO₂ can transform from insulating (monoclinic) to conducting (rutile) phase leading to lattice compressions and stiffness increase in the resonator. The mechanical frequency of the resonator can be tuned by changing optical power and wavelength. The first mode resonance frequency was tuned in three different ways. A decrease in frequency below a critical optical power, a large increase between 50-120 µW followed by a large decrease in frequency for optical powers greater than 120 µW. The dynamic mechanical response was studied as a function of incident optical power and gas pressure. The resonance frequency and amplitude of vibration were found to be decreased with increasing laser power from 25-38 µW and increased by1-2 % when the laser power was further increased to 52 µW. The transition in films was induced and detected by a single pump and probe source and by employing external optical sources of different wavelengths. This trend in dynamic parameters of the strings can be co-related with reversible Insulator to metal transition in VO₂ films which creates change in density of the material and hence the overall stiffness of the strings leading to changes in string dynamics. The increase in frequency at a particular optical power manifests a transition to a more ordered metallic phase which tensile stress onto the string. The decrease in frequency at higher optical powers can be correlated with poor phonon thermal conductivity of VO₂ in conducting phase. Poor thermal conductivity of VO₂ can force in-plane penetration of heat causing the underneath SiN supporting VO₂ which can result as a decrease in resonance frequency. This noninvasive, non-contact laser-based excitation and detection of Insulator to metal transition using micro strings resonators at room temperature and with laser power in few µWs is important for low power electronics, and optical switching applications.

Keywords: thermal conductivity, vanadium dioxide, MEMS, frequency tuning

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