Search results for: physiological signals
Commenced in January 2007
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Edition: International
Paper Count: 1857

Search results for: physiological signals

27 Partial Discharge Characteristics of Free- Moving Particles in HVDC-GIS

Authors: Philipp Wenger, Michael Beltle, Stefan Tenbohlen, Uwe Riechert

Abstract:

The integration of renewable energy introduces new challenges to the transmission grid, as the power generation is located far from load centers. The associated necessary long-range power transmission increases the demand for high voltage direct current (HVDC) transmission lines and DC distribution grids. HVDC gas-insulated switchgears (GIS) are considered being a key technology, due to the combination of the DC technology and the long operation experiences of AC-GIS. To ensure long-term reliability of such systems, insulation defects must be detected in an early stage. Operational experience with AC systems has proven evidence, that most failures, which can be attributed to breakdowns of the insulation system, can be detected and identified via partial discharge (PD) measurements beforehand. In AC systems the identification of defects relies on the phase resolved partial discharge pattern (PRPD). Since there is no phase information within DC systems this method cannot be transferred to DC PD diagnostic. Furthermore, the behaviour of e.g. free-moving particles differs significantly at DC: Under the influence of a constant direct electric field, charge carriers can accumulate on particles’ surfaces. As a result, a particle can lift-off, oscillate between the inner conductor and the enclosure or rapidly bounces at just one electrode, which is known as firefly motion. Depending on the motion and the relative position of the particle to the electrodes, broadband electromagnetic PD pulses are emitted, which can be recorded by ultra-high frequency (UHF) measuring methods. PDs are often accompanied by light emissions at the particle’s tip which enables optical detection. This contribution investigates PD characteristics of free moving metallic particles in a commercially available 300 kV SF6-insulated HVDC-GIS. The influences of various defect parameters on the particle motion and the PD characteristic are evaluated experimentally. Several particle geometries, such as cylinder, lamella, spiral and sphere with different length, diameter and weight are determined. The applied DC voltage is increased stepwise from inception voltage up to UDC = ± 400 kV. Different physical detection methods are used simultaneously in a time-synchronized setup. Firstly, the electromagnetic waves emitted by the particle are recorded by an UHF measuring system. Secondly, a photomultiplier tube (PMT) detects light emission with a wavelength in the range of λ = 185…870 nm. Thirdly, a high-speed camera (HSC) tracks the particle’s motion trajectory with high accuracy. Furthermore, an electrically insulated electrode is attached to the grounded enclosure and connected to a current shunt in order to detect low frequency ion currents: The shunt measuring system’s sensitivity is in the range of 10 nA at a measuring bandwidth of bw = DC…1 MHz. Currents of charge carriers, which are generated at the particle’s tip migrate through the gas gap to the electrode and can be recorded by the current shunt. All recorded PD signals are analyzed in order to identify characteristic properties of different particles. This includes e.g. repetition rates and amplitudes of successive pulses, characteristic frequency ranges and detected signal energy of single PD pulses. Concluding, an advanced understanding of underlying physical phenomena particle motion in direct electric field can be derived.

Keywords: current shunt, free moving particles, high-speed imaging, HVDC-GIS, UHF

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26 Calpoly Autonomous Transportation Experience: Software for Driverless Vehicle Operating on Campus

Authors: F. Tang, S. Boskovich, A. Raheja, Z. Aliyazicioglu, S. Bhandari, N. Tsuchiya

Abstract:

Calpoly Autonomous Transportation Experience (CATE) is a driverless vehicle that we are developing to provide safe, accessible, and efficient transportation of passengers throughout the Cal Poly Pomona campus for events such as orientation tours. Unlike the other self-driving vehicles that are usually developed to operate with other vehicles and reside only on the road networks, CATE will operate exclusively on walk-paths of the campus (potentially narrow passages) with pedestrians traveling from multiple locations. Safety becomes paramount as CATE operates within the same environment as pedestrians. As driverless vehicles assume greater roles in today’s transportation, this project will contribute to autonomous driving with pedestrian traffic in a highly dynamic environment. The CATE project requires significant interdisciplinary work. Researchers from mechanical engineering, electrical engineering and computer science are working together to attack the problem from different perspectives (hardware, software and system). In this abstract, we describe the software aspects of the project, with a focus on the requirements and the major components. CATE shall provide a GUI interface for the average user to interact with the car and access its available functionalities, such as selecting a destination from any origin on campus. We have developed an interface that provides an aerial view of the campus map, the current car location, routes, and the goal location. Users can interact with CATE through audio or manual inputs. CATE shall plan routes from the origin to the selected destination for the vehicle to travel. We will use an existing aerial map for the campus and convert it to a spatial graph configuration where the vertices represent the landmarks and edges represent paths that the car should follow with some designated behaviors (such as stay on the right side of the lane or follow an edge). Graph search algorithms such as A* will be implemented as the default path planning algorithm. D* Lite will be explored to efficiently recompute the path when there are any changes to the map. CATE shall avoid any static obstacles and walking pedestrians within some safe distance. Unlike traveling along traditional roadways, CATE’s route directly coexists with pedestrians. To ensure the safety of the pedestrians, we will use sensor fusion techniques that combine data from both lidar and stereo vision for obstacle avoidance while also allowing CATE to operate along its intended route. We will also build prediction models for pedestrian traffic patterns. CATE shall improve its location and work under a GPS-denied situation. CATE relies on its GPS to give its current location, which has a precision of a few meters. We have implemented an Unscented Kalman Filter (UKF) that allows the fusion of data from multiple sensors (such as GPS, IMU, odometry) in order to increase the confidence of localization. We also noticed that GPS signals can easily get degraded or blocked on campus due to high-rise buildings or trees. UKF can also help here to generate a better state estimate. In summary, CATE will provide on-campus transportation experience that coexists with dynamic pedestrian traffic. In future work, we will extend it to multi-vehicle scenarios.

Keywords: driverless vehicle, path planning, sensor fusion, state estimate

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25 Impact of Elevated Temperature on Spot Blotch Development in Wheat and Induction of Resistance by Plant Growth Promoting Rhizobacteria

Authors: Jayanwita Sarkar, Usha Chakraborty, Bishwanath Chakraborty

Abstract:

Plants are constantly interacting with various abiotic and biotic stresses. In changing climate scenario plants are continuously modifying physiological processes to adapt to changing environmental conditions which profoundly affect plant-pathogen interactions. Spot blotch in wheat is a fast-rising disease in the warmer plains of South Asia where the rise in minimum average temperature over most of the year already affecting wheat production. Hence, the study was undertaken to explore the role of elevated temperature in spot blotch disease development and modulation of antioxidative responses by plant growth promoting rhizobacteria (PGPR) for biocontrol of spot blotch at high temperature. Elevated temperature significantly increases the susceptibility of wheat plants to spot blotch causing pathogen Bipolaris sorokiniana. Two PGPR Bacillus safensis (W10) and Ochrobactrum pseudogrignonense (IP8) isolated from wheat (Triticum aestivum L.) and blady grass (Imperata cylindrical L.) rhizophere respectively, showing in vitro antagonistic activity against Bipolaris sorokiniana were tested for growth promotion and induction of resistance against spot blotch in wheat. GC-MS analysis showed that Bacillus safensis (W10) and Ochrobactrum pseudogrignonense (IP8) produced antifungal and antimicrobial compounds in culture. Seed priming with these two bacteria significantly increase growth, modulate antioxidative signaling and induce resistance and eventually reduce disease incidence in wheat plants at optimum as well as elevated temperature which was further confirmed by indirect immunofluorescence assay using polyclonal antibody raised against Bipolaris sorokiniana. Application of the PGPR led to enhancement in activities of plant defense enzymes- phenylalanine ammonia lyase, peroxidase, chitinase and β-1,3 glucanase in infected leaves. Immunolocalization of chitinase and β-1,3 glucanase in PGPR primed and pathogen inoculated leaf tissue was further confirmed by transmission electron microscopy using PAb of chitinase, β-1,3 glucanase and gold labelled conjugates. Activity of ascorbate-glutathione redox cycle related enzymes such as ascorbate peroxidase, superoxide dismutase and glutathione reductase along with antioxidants such as carotenoids, glutathione and ascorbate and osmolytes like proline and glycine betain accumulation were also increased during disease development in PGPR primed plant in comparison to unprimed plants at high temperature. Real-time PCR analysis revealed enhanced expression of defense genes- chalcone synthase and phenyl alanineammonia lyase. Over expression of heat shock proteins like HSP 70, small HSP 26.3 and heat shock factor HsfA3 in PGPR primed plants effectively protect plants against spot blotch infection at elevated temperature as compared with control plants. Our results revealed dynamic biochemical cross talk between elevated temperature and spot blotch disease development and furthermore highlight PGPR mediated array of antioxidative and molecular alterations responsible for induction of resistance against spot blotch disease at elevated temperature which seems to be associated with up-regulation of defense genes, heat shock proteins and heat shock factors, less ROS production, membrane damage, increased expression of redox enzymes and accumulation of osmolytes and antioxidants.

Keywords: antioxidative enzymes, defense enzymes, elevated temperature, heat shock proteins, PGPR, Real-Time PCR, spot blotch, wheat

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24 Removing Maturational Influences from Female Youth Swimming: The Application of Corrective Adjustment Procedures

Authors: Clorinda Hogan, Shaun Abbott, Mark Halaki, Marcela Torres Catiglioni, Goshi Yamauchi, Lachlan Mitchell, James Salter, Michael Romann, Stephen Cobley

Abstract:

Introduction: Common annual age-group competition structures unintentionally introduce participation inequalities, performance (dis)advantages and selection biases due to the effect of maturational variation between youth swimmers. On this basis, there are implications for improving performance evaluation strategies. Therefore the aim was to: (1) To determine maturity timing distributions in female youth swimming; (2) quantify the relationship between maturation status and 100-m FC performance; (3) apply Maturational-based Corrective Adjustment Procedures (Mat-CAPs) for removal of maturational status performance influences. Methods: (1) Cross-sectional analysis of 663 female (10-15 years) swimmers who underwent assessment of anthropometrics (mass, height and sitting height) and estimations of maturity timing and offset. (2) 100-m front-crawl performance (seconds) was assessed at Australian regional, state, and national-level competitions between 2016-2020. To determine the relationship between maturation status and 100-m front-crawl performance, MO was plotted against 100-m FC performance time. The expected maturity status - performance relationship for females aged 10-15 years of age was obtained through a quadratic function (y = ax2 + bx + c) from unstandardized coefficients. The regression equation was subsequently used for Mat-CAPs. (3) Participants aged 10-13 years were categorised into maturity-offset categories. Maturity offset distributions for Raw (‘All’, ‘Top 50%’ & ‘Top 25%’) and Correctively Adjusted swim times were examined. Chi-square, Cramer’s V and ORs determined the occurrence of maturation biases for each age group and selection level. Results—: (1) Maturity timing distributions illustrated overrepresentation of ‘normative’ maturing swimmers (11.82 ± 0.40 years), with a descriptive shift toward the early maturing relative to the normative population. (2) A curvilinear relationship between maturity-offset and swim performance was identified (R2 = 0.53, P < 0.001) and subsequently utilised for Mat-CAPs. (3) Raw maturity offset categories identified partial maturation status skewing towards biologically older swimmers at 10/11 and 12 years, with effect magnitudes increasing in the ‘Top 50%’ and ‘25%’ of performance times. Following Mat-CAPs application, maturity offset biases were removed in similar age groups and selection levels. When adjusting performance times for maturity offset, Mat-CAPs was successful in mitigating against maturational biases until approximately 1-year post Peak Height Velocity. The overrepresentation of ‘normative’ maturing female swimmers contrasted with the substantial overrepresentation of ‘early’ maturing male swimmers found previously in 100-m front-crawl. These findings suggest early maturational timing is not advantageous in females, but findings associated with Aim 2, highlight how advanced maturational status remained beneficial to performance. Observed differences between female and male maturational biases may relate to the differential impact of physiological development during pubertal years. Females experience greater increases of fat mass and potentially differing changes in body shape which can negatively affect swim performance. Conclusions: Transient maturation status-based participation and performance advantages were apparent within a large sample of Australian female youth 100-m FC swimmers. By removing maturity status performance biases within female youth swimming, Mat-CAPs could help improve participation experiences and the accuracy of identifying genuinely skilled female youth swimmers.

Keywords: athlete development, long-term sport participation, performance evaluation, talent identification, youth competition

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23 Redox-labeled Electrochemical Aptasensor Array for Single-cell Detection

Authors: Shuo Li, Yannick Coffinier, Chann Lagadec, Fabrizio Cleri, Katsuhiko Nishiguchi, Akira Fujiwara, Soo Hyeon Kim, Nicolas Clément

Abstract:

The need for single cell detection and analysis techniques has increased in the past decades because of the heterogeneity of individual living cells, which increases the complexity of the pathogenesis of malignant tumors. In the search for early cancer detection, high-precision medicine and therapy, the technologies most used today for sensitive detection of target analytes and monitoring the variation of these species are mainly including two types. One is based on the identification of molecular differences at the single-cell level, such as flow cytometry, fluorescence-activated cell sorting, next generation proteomics, lipidomic studies, another is based on capturing or detecting single tumor cells from fresh or fixed primary tumors and metastatic tissues, and rare circulating tumors cells (CTCs) from blood or bone marrow, for example, dielectrophoresis technique, microfluidic based microposts chip, electrochemical (EC) approach. Compared to other methods, EC sensors have the merits of easy operation, high sensitivity, and portability. However, despite various demonstrations of low limits of detection (LOD), including aptamer sensors, arrayed EC sensors for detecting single-cell have not been demonstrated. In this work, a new technique based on 20-nm-thick nanopillars array to support cells and keep them at ideal recognition distance for redox-labeled aptamers grafted on the surface. The key advantages of this technology are not only to suppress the false positive signal arising from the pressure exerted by all (including non-target) cells pushing on the aptamers by downward force but also to stabilize the aptamer at the ideal hairpin configuration thanks to a confinement effect. With the first implementation of this technique, a LOD of 13 cells (with5.4 μL of cell suspension) was estimated. In further, the nanosupported cell technology using redox-labeled aptasensors has been pushed forward and fully integrated into a single-cell electrochemical aptasensor array. To reach this goal, the LOD has been reduced by more than one order of magnitude by suppressing parasitic capacitive electrochemical signals by minimizing the sensor area and localizing the cells. Statistical analysis at the single-cell level is demonstrated for the recognition of cancer cells. The future of this technology is discussed, and the potential for scaling over millions of electrodes, thus pushing further integration at sub-cellular level, is highlighted. Despite several demonstrations of electrochemical devices with LOD of 1 cell/mL, the implementation of single-cell bioelectrochemical sensor arrays has remained elusive due to their challenging implementation at a large scale. Here, the introduced nanopillar array technology combined with redox-labeled aptamers targeting epithelial cell adhesion molecule (EpCAM) is perfectly suited for such implementation. Combining nanopillar arrays with microwells determined for single cell trapping directly on the sensor surface, single target cells are successfully detected and analyzed. This first implementation of a single-cell electrochemical aptasensor array based on Brownian-fluctuating redox species opens new opportunities for large-scale implementation and statistical analysis of early cancer diagnosis and cancer therapy in clinical settings.

Keywords: bioelectrochemistry, aptasensors, single-cell, nanopillars

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22 Study of the Biological Activity of a Ganglioside-Containing Drug (Cronassil) in an Experimental Model of Multiple Sclerosis

Authors: Hasmik V. Zanginyan, Gayane S. Ghazaryan, Laura M. Hovsepyan

Abstract:

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system that is induced in laboratory animals by developing an immune response against myelin epitopes. The typical clinical course is ascending palsy, which correlates with inflammation and tissue damage in the thoracolumbar spinal cord, although the optic nerves and brain (especially the subpial white matter and brainstem) are also often affected. With multiple sclerosis, there is a violation of lipid metabolism in myelin. When membrane lipids (glycosphingolipids, phospholipids) are disturbed, metabolites not only play a structural role in membranes but are also sources of secondary mediators that transmit multiple cellular signals. The purpose of this study was to investigate the effect of ganglioside as a therapeutic agent in experimental multiple sclerosis. The biological activity of a ganglioside-containing medicinal preparation (Cronassial) was evaluated in an experimental model of multiple sclerosis in laboratory animals. An experimental model of multiple sclerosis in rats was obtained by immunization with myelin basic protein (MBP), as well as homogenization of the spinal cord or brain. EAE was induced by administering a mixture of an encephalitogenic mixture (EGM) with Complete Freund’s Adjuvant. Mitochondrial fraction was isolated in a medium containing 0,25 M saccharose and 0, 01 M tris buffer, pH - 7,4, by a method of differential centrifugation on a K-24 centrifuge. Glutathione peroxidase activity was assessed by reduction reactions of hydrogen peroxide (H₂O₂) and lipid hydroperoxides (ROOH) in the presence of GSH. LPO activity was assessed by the amount of malondialdehyde (MDA) in the total homogenate and mitochondrial fraction of the spinal cord and brain of control and experimental autoimmune encephalomyelitis rats. MDA was assessed by a reaction with Thiobarbituric acid. For statistical data analysis on PNP, SPSS (Statistical Package for Social Science) package was used. The nature of the distribution of the obtained data was determined by the Kolmogorov-Smirnov criterion. The comparative analysis was performed using a nonparametric Mann-Whitney test. The differences were statistically significant when р ≤ 0,05 or р ≤ 0,01. Correlational analysis was conducted using a nonparametric Spearman test. In the work, refrigeratory centrifuge, spectrophotometer LKB Biochrom ULTROSPECII (Sweden), pH-meter PL-600 mrc (Israel), guanosine, and ATP (Sigma). The study of the process of lipid peroxidation in the total homogenate of the brain and spinal cord in experimental animals revealed an increase in the content of malonic dialdehyde. When applied, Cronassial observed normalization of lipid peroxidation processes. Reactive oxygen species, causing lipid peroxidation processes, can be toxic both for neurons and for oligodendrocytes that form myelin, causing a violation of their lipid composition. The high content of lipids in the brain and the uniqueness of their structure determines the nature of the development of LPO processes. The lipid layer of cellular and intracellular membranes performs two main functions -barrier and matrix (structural). Damage to the barrier leads to dysregulation of intracellular processes and severe disorders of cellular functions.

Keywords: experimental autoimmune encephalomyelitis, multiple sclerosis, neuroinflammation, therapy

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21 Evaluation of Random Forest and Support Vector Machine Classification Performance for the Prediction of Early Multiple Sclerosis from Resting State FMRI Connectivity Data

Authors: V. Saccà, A. Sarica, F. Novellino, S. Barone, T. Tallarico, E. Filippelli, A. Granata, P. Valentino, A. Quattrone

Abstract:

The work aim was to evaluate how well Random Forest (RF) and Support Vector Machine (SVM) algorithms could support the early diagnosis of Multiple Sclerosis (MS) from resting-state functional connectivity data. In particular, we wanted to explore the ability in distinguishing between controls and patients of mean signals extracted from ICA components corresponding to 15 well-known networks. Eighteen patients with early-MS (mean-age 37.42±8.11, 9 females) were recruited according to McDonald and Polman, and matched for demographic variables with 19 healthy controls (mean-age 37.55±14.76, 10 females). MRI was acquired by a 3T scanner with 8-channel head coil: (a)whole-brain T1-weighted; (b)conventional T2-weighted; (c)resting-state functional MRI (rsFMRI), 200 volumes. Estimated total lesion load (ml) and number of lesions were calculated using LST-toolbox from the corrected T1 and FLAIR. All rsFMRIs were pre-processed using tools from the FMRIB's Software Library as follows: (1) discarding of the first 5 volumes to remove T1 equilibrium effects, (2) skull-stripping of images, (3) motion and slice-time correction, (4) denoising with high-pass temporal filter (128s), (5) spatial smoothing with a Gaussian kernel of FWHM 8mm. No statistical significant differences (t-test, p < 0.05) were found between the two groups in the mean Euclidian distance and the mean Euler angle. WM and CSF signal together with 6 motion parameters were regressed out from the time series. We applied an independent component analysis (ICA) with the GIFT-toolbox using the Infomax approach with number of components=21. Fifteen mean components were visually identified by two experts. The resulting z-score maps were thresholded and binarized to extract the mean signal of the 15 networks for each subject. Statistical and machine learning analysis were then conducted on this dataset composed of 37 rows (subjects) and 15 features (mean signal in the network) with R language. The dataset was randomly splitted into training (75%) and test sets and two different classifiers were trained: RF and RBF-SVM. We used the intrinsic feature selection of RF, based on the Gini index, and recursive feature elimination (rfe) for the SVM, to obtain a rank of the most predictive variables. Thus, we built two new classifiers only on the most important features and we evaluated the accuracies (with and without feature selection) on test-set. The classifiers, trained on all the features, showed very poor accuracies on training (RF:58.62%, SVM:65.52%) and test sets (RF:62.5%, SVM:50%). Interestingly, when feature selection by RF and rfe-SVM were performed, the most important variable was the sensori-motor network I in both cases. Indeed, with only this network, RF and SVM classifiers reached an accuracy of 87.5% on test-set. More interestingly, the only misclassified patient resulted to have the lowest value of lesion volume. We showed that, with two different classification algorithms and feature selection approaches, the best discriminant network between controls and early MS, was the sensori-motor I. Similar importance values were obtained for the sensori-motor II, cerebellum and working memory networks. These findings, in according to the early manifestation of motor/sensorial deficits in MS, could represent an encouraging step toward the translation to the clinical diagnosis and prognosis.

Keywords: feature selection, machine learning, multiple sclerosis, random forest, support vector machine

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20 In-Process Integration of Resistance-Based, Fiber Sensors during the Braiding Process for Strain Monitoring of Carbon Fiber Reinforced Composite Materials

Authors: Oscar Bareiro, Johannes Sackmann, Thomas Gries

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Carbon fiber reinforced polymer composites (CFRP) are used in a wide variety of applications due to its advantageous properties and design versatility. The braiding process enables the manufacture of components with good toughness and fatigue strength. However, failure mechanisms of CFRPs are complex and still present challenges associated with their maintenance and repair. Within the broad scope of structural health monitoring (SHM), strain monitoring can be applied to composite materials to improve reliability, reduce maintenance costs and safely exhaust service life. Traditional SHM systems employ e.g. fiber optics, piezoelectrics as sensors, which are often expensive, time consuming and complicated to implement. A cost-efficient alternative can be the exploitation of the conductive properties of fiber-based sensors such as carbon, copper, or constantan - a copper-nickel alloy – that can be utilized as sensors within composite structures to achieve strain monitoring. This allows the structure to provide feedback via electrical signals to a user which are essential for evaluating the structural condition of the structure. This work presents a strategy for the in-process integration of resistance-based sensors (Elektrisola Feindraht AG, CuNi23Mn, Ø = 0.05 mm) into textile preforms during its manufacture via the braiding process (Herzog RF-64/120) to achieve strain monitoring of braided composites. For this, flat samples of instrumented composite laminates of carbon fibers (Toho Tenax HTS40 F13 24K, 1600 tex) and epoxy resin (Epikote RIMR 426) were manufactured via vacuum-assisted resin infusion. These flat samples were later cut out into test specimens and the integrated sensors were wired to the measurement equipment (National Instruments, VB-8012) for data acquisition during the execution of mechanical tests. Quasi-static tests were performed (tensile, 3-point bending tests) following standard protocols (DIN EN ISO 527-1 & 4, DIN EN ISO 14132); additionally, dynamic tensile tests were executed. These tests were executed to assess the sensor response under different loading conditions and to evaluate the influence of the sensor presence on the mechanical properties of the material. Several orientations of the sensor with regards to the applied loading and sensor placements inside the laminate were tested. Strain measurements from the integrated sensors were made by programming a data acquisition code (LabView) written for the measurement equipment. Strain measurements from the integrated sensors were then correlated to the strain/stress state for the tested samples. From the assessment of the sensor integration approach it can be concluded that it allows for a seamless sensor integration into the textile preform. No damage to the sensor or negative effect on its electrical properties was detected during inspection after integration. From the assessment of the mechanical tests of instrumented samples it can be concluded that the presence of the sensors does not alter significantly the mechanical properties of the material. It was found that there is a good correlation between resistance measurements from the integrated sensors and the applied strain. It can be concluded that the correlation is of sufficient accuracy to determinate the strain state of a composite laminate based solely on the resistance measurements from the integrated sensors.

Keywords: braiding process, in-process sensor integration, instrumented composite material, resistance-based sensor, strain monitoring

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19 Surface Plasmon Resonance Imaging-Based Epigenetic Assay for Blood DNA Post-Traumatic Stress Disorder Biomarkers

Authors: Judy M. Obliosca, Olivia Vest, Sandra Poulos, Kelsi Smith, Tammy Ferguson, Abigail Powers Lott, Alicia K. Smith, Yang Xu, Christopher K. Tison

Abstract:

Post-Traumatic Stress Disorder (PTSD) is a mental health problem that people may develop after experiencing traumatic events such as combat, natural disasters, and major emotional challenges. Tragically, the number of military personnel with PTSD correlates directly with the number of veterans who attempt suicide, with the highest rate in the Army. Research has shown epigenetic risks in those who are prone to several psychiatric dysfunctions, particularly PTSD. Once initiated in response to trauma, epigenetic alterations in particular, the DNA methylation in the form of 5-methylcytosine (5mC) alters chromatin structure and represses gene expression. Current methods to detect DNA methylation, such as bisulfite-based genomic sequencing techniques, are laborious and have massive analysis workflow while still having high error rates. A faster and simpler detection method of high sensitivity and precision would be useful in a clinical setting to confirm potential PTSD etiologies, prevent other psychiatric disorders, and improve military health. A nano-enhanced Surface Plasmon Resonance imaging (SPRi)-based assay that simultaneously detects site-specific 5mC base (termed as PTSD base) in methylated genes related to PTSD is being developed. The arrays on a sensing chip were first constructed for parallel detection of PTSD bases using synthetic and genomic DNA (gDNA) samples. For the gDNA sample extracted from the whole blood of a PTSD patient, the sample was first digested using specific restriction enzymes, and fragments were denatured to obtain single-stranded methylated target genes (ssDNA). The resulting mixture of ssDNA was then injected into the assay platform, where targets were captured by specific DNA aptamer probes previously immobilized on the surface of a sensing chip. The PTSD bases in targets were detected by anti-5-methylcytosine antibody (anti-5mC), and the resulting signals were then enhanced by the universal nanoenhancer. Preliminary results showed successful detection of a PTSD base in a gDNA sample. Brighter spot images and higher delta values (control-subtracted reflectivity signal) relative to those of the control were observed. We also implemented the in-house surface activation system for detection and developed SPRi disposable chips. Multiplexed PTSD base detection of target methylated genes in blood DNA from PTSD patients of severity conditions (asymptomatic and severe) was conducted. This diagnostic capability being developed is a platform technology, and upon successful implementation for PTSD, it could be reconfigured for the study of a wide variety of neurological disorders such as traumatic brain injury, Alzheimer’s disease, schizophrenia, and Huntington's disease and can be extended to the analyses of other sample matrices such as urine and saliva.

Keywords: epigenetic assay, DNA methylation, PTSD, whole blood, multiplexing

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18 Colloid-Based Biodetection at Aqueous Electrical Interfaces Using Fluidic Dielectrophoresis

Authors: Francesca Crivellari, Nicholas Mavrogiannis, Zachary Gagnon

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Portable diagnostic methods have become increasingly important for a number of different purposes: point-of-care screening in developing nations, environmental contamination studies, bio/chemical warfare agent detection, and end-user use for commercial health monitoring. The cheapest and most portable methods currently available are paper-based – lateral flow and dipstick methods are widely available in drug stores for use in pregnancy detection and blood glucose monitoring. These tests are successful because they are cheap to produce, easy to use, and require minimally invasive sampling. While adequate for their intended uses, in the realm of blood-borne pathogens and numerous cancers, these paper-based methods become unreliable, as they lack the nM/pM sensitivity currently achieved by clinical diagnostic methods. Clinical diagnostics, however, utilize techniques involving surface plasmon resonance (SPR) and enzyme-linked immunosorbent assays (ELISAs), which are expensive and unfeasible in terms of portability. To develop a better, competitive biosensor, we must reduce the cost of one, or increase the sensitivity of the other. Electric fields are commonly utilized in microfluidic devices to manipulate particles, biomolecules, and cells. Applications in this area, however, are primarily limited to interfaces formed between immiscible interfaces. Miscible, liquid-liquid interfaces are common in microfluidic devices, and are easily reproduced with simple geometries. Here, we demonstrate the use of electrical fields at liquid-liquid electrical interfaces, known as fluidic dielectrophoresis, (fDEP) for biodetection in a microfluidic device. In this work, we apply an AC electric field across concurrent laminar streams with differing conductivities and permittivities to polarize the interface and induce a discernible, near-immediate, frequency-dependent interfacial tilt. We design this aqueous electrical interface, which becomes the biosensing “substrate,” to be intelligent – it “moves” only when a target of interest is present. This motion requires neither labels nor expensive electrical equipment, so the biosensor is inexpensive and portable, yet still capable of sensitive detection. Nanoparticles, due to their high surface-area-to-volume ratio, are often incorporated to enhance detection capabilities of schemes like SPR and fluorimetric assays. Most studies currently investigate binding at an immobilized solid-liquid or solid-gas interface, where particles are adsorbed onto a planar surface, functionalized with a receptor to create a reactive substrate, and subsequently flushed with a fluid or gas with the relevant analyte. These typically involve many preparation and rinsing steps, and are susceptible to surface fouling. Our microfluidic device is continuously flowing and renewing the “substrate,” and is thus not subject to fouling. In this work, we demonstrate the ability to electrokinetically detect biomolecules binding to functionalized nanoparticles at liquid-liquid interfaces using fDEP. In biotin-streptavidin experiments, we report binding detection limits on the order of 1-10 pM, without amplifying signals or concentrating samples. We also demonstrate the ability to detect this interfacial motion, and thus the presence of binding, using impedance spectroscopy, allowing this scheme to become non-optical, in addition to being label-free.

Keywords: biodetection, dielectrophoresis, microfluidics, nanoparticles

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17 Investigation of the Controversial Immunomodulatory Potential of Trichinella spiralis Excretory-Secretory Products versus Extracellular Vesicles Derived from These Products in vitro

Authors: Natasa Ilic, Alisa Gruden-Movsesijan, Maja Kosanovic, Sofija Glamoclija, Marina Bekic, Ljiljana Sofronic-Milosavljevic, Sergej Tomic

Abstract:

As a very promising candidate for modulation of immune response in the sense of biasing the inflammatory towards an anti-inflammatory type of response, Trichinella spiralis infection was shown to successfully alleviate the severity of experimental autoimmune encephalomyelitis, the animal model of human disease multiple sclerosis. This effect is achieved via its excretory-secretory muscle larvae (ES L1) products which affect the maturation status and function of dendritic cells (DCs) by inducing the tolerogenic status of DCs, which leads to the mitigation of the Th1 type of response and the activation of a regulatory type of immune response both in vitro and in vivo. ES L1 alone or via treated DCs successfully mitigated EAE in the same manner as the infection itself. On the other hand, it has been shown that T. spiralis infection slows down the tumour growth and significantly reduces the tumour size in the model of mouse melanoma, while ES L1 possesses a pro-apoptotic and anti-survival effect on melanoma cells in vitro. Hence, although the mechanisms still need to be revealed, T. spiralis infection and its ES L1 products have a bit of controversial potential to modulate both inflammatory diseases and malignancies. The recent discovery of T. spiralis extracellular vesicles (TsEVs) suggested that the induction of complex regulation of the immune response requires simultaneous delivery of different signals in nano-sized packages. This study aimed to explore whether TsEVs bare the similar potential as ES L1 to influence the status of DCs in initiation, progression and regulation of immune response, but also to investigate the effect of both ES L1 and TsEVs on myeloid derived suppressor cells (MDSC) which present the regular tumour tissue environment. TsEVs were enriched from the conditioned medium of T. spiralis muscle larvae by differential centrifugation and used for the treatment of human monocyte-derived DCs and MDSC. On DCs, TsEVs induced low expression of HLA DR and CD40, moderate CD83 and CD86, and increased expression of ILT3 and CCR7 on treated DCs, i.e., they induced tolerogenic DCs. Such DCs possess the capacity to polarize T cell immune response towards regulatory type, with an increased proportion of IL-10 and TGF-β producing cells, similarly to ES L1. These findings indicated that the ability of TsEVs to induce tolerogenic DCs favoring anti-inflammatory responses may be helpful in coping with diseases that involve Th1/Th17-, but also Th2-mediated inflammation. In MDSC in vitro model, although both ES L1 and TsEVs had the same impact on MDSC phenotype i.e., they acted suppressive, ES L1 treated MDSC, unlike TsEVs treated ones, induced T cell response characterized by the increased RoRγT and IFN-γ, while the proportion of regulatory cells was decreased followed by the decrease in IL-10 and TGF-β positive cells proportion within this population. These findings indicate the interesting ability of ES L1 to modulate T cells response via MDSC towards pro-inflamatory type, suggesting that, unlike TsEVs which consistently demonstrate the suppresive effect on inflammatory response, it could be used also for the development of new approaches aimed for the treatment of malignant diseases. Acknowledgment: This work was funded by the Promis project – Nano-MDCS-Thera, Science Fund, Republic of Serbia.

Keywords: dendritic cells, myeloid derived suppressor cells, immunomodulation, Trichinella spiralis

Procedia PDF Downloads 178
16 PsyVBot: Chatbot for Accurate Depression Diagnosis using Long Short-Term Memory and NLP

Authors: Thaveesha Dheerasekera, Dileeka Sandamali Alwis

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The escalating prevalence of mental health issues, such as depression and suicidal ideation, is a matter of significant global concern. It is plausible that a variety of factors, such as life events, social isolation, and preexisting physiological or psychological health conditions, could instigate or exacerbate these conditions. Traditional approaches to diagnosing depression entail a considerable amount of time and necessitate the involvement of adept practitioners. This underscores the necessity for automated systems capable of promptly detecting and diagnosing symptoms of depression. The PsyVBot system employs sophisticated natural language processing and machine learning methodologies, including the use of the NLTK toolkit for dataset preprocessing and the utilization of a Long Short-Term Memory (LSTM) model. The PsyVBot exhibits a remarkable ability to diagnose depression with a 94% accuracy rate through the analysis of user input. Consequently, this resource proves to be efficacious for individuals, particularly those enrolled in academic institutions, who may encounter challenges pertaining to their psychological well-being. The PsyVBot employs a Long Short-Term Memory (LSTM) model that comprises a total of three layers, namely an embedding layer, an LSTM layer, and a dense layer. The stratification of these layers facilitates a precise examination of linguistic patterns that are associated with the condition of depression. The PsyVBot has the capability to accurately assess an individual's level of depression through the identification of linguistic and contextual cues. The task is achieved via a rigorous training regimen, which is executed by utilizing a dataset comprising information sourced from the subreddit r/SuicideWatch. The diverse data present in the dataset ensures precise and delicate identification of symptoms linked with depression, thereby guaranteeing accuracy. PsyVBot not only possesses diagnostic capabilities but also enhances the user experience through the utilization of audio outputs. This feature enables users to engage in more captivating and interactive interactions. The PsyVBot platform offers individuals the opportunity to conveniently diagnose mental health challenges through a confidential and user-friendly interface. Regarding the advancement of PsyVBot, maintaining user confidentiality and upholding ethical principles are of paramount significance. It is imperative to note that diligent efforts are undertaken to adhere to ethical standards, thereby safeguarding the confidentiality of user information and ensuring its security. Moreover, the chatbot fosters a conducive atmosphere that is supportive and compassionate, thereby promoting psychological welfare. In brief, PsyVBot is an automated conversational agent that utilizes an LSTM model to assess the level of depression in accordance with the input provided by the user. The demonstrated accuracy rate of 94% serves as a promising indication of the potential efficacy of employing natural language processing and machine learning techniques in tackling challenges associated with mental health. The reliability of PsyVBot is further improved by the fact that it makes use of the Reddit dataset and incorporates Natural Language Toolkit (NLTK) for preprocessing. PsyVBot represents a pioneering and user-centric solution that furnishes an easily accessible and confidential medium for seeking assistance. The present platform is offered as a modality to tackle the pervasive issue of depression and the contemplation of suicide.

Keywords: chatbot, depression diagnosis, LSTM model, natural language process

Procedia PDF Downloads 33
15 Large-Scale Simulations of Turbulence Using Discontinuous Spectral Element Method

Authors: A. Peyvan, D. Li, J. Komperda, F. Mashayek

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Turbulence can be observed in a variety fluid motions in nature and industrial applications. Recent investment in high-speed aircraft and propulsion systems has revitalized fundamental research on turbulent flows. In these systems, capturing chaotic fluid structures with different length and time scales is accomplished through the Direct Numerical Simulation (DNS) approach since it accurately simulates flows down to smallest dissipative scales, i.e., Kolmogorov’s scales. The discontinuous spectral element method (DSEM) is a high-order technique that uses spectral functions for approximating the solution. The DSEM code has been developed by our research group over the course of more than two decades. Recently, the code has been improved to run large cases in the order of billions of solution points. Running big simulations requires a considerable amount of RAM. Therefore, the DSEM code must be highly parallelized and able to start on multiple computational nodes on an HPC cluster with distributed memory. However, some pre-processing procedures, such as determining global element information, creating a global face list, and assigning global partitioning and element connection information of the domain for communication, must be done sequentially with a single processing core. A separate code has been written to perform the pre-processing procedures on a local machine. It stores the minimum amount of information that is required for the DSEM code to start in parallel, extracted from the mesh file, into text files (pre-files). It packs integer type information with a Stream Binary format in pre-files that are portable between machines. The files are generated to ensure fast read performance on different file-systems, such as Lustre and General Parallel File System (GPFS). A new subroutine has been added to the DSEM code to read the startup files using parallel MPI I/O, for Lustre, in a way that each MPI rank acquires its information from the file in parallel. In case of GPFS, in each computational node, a single MPI rank reads data from the file, which is specifically generated for the computational node, and send them to other ranks on the node using point to point non-blocking MPI communication. This way, communication takes place locally on each node and signals do not cross the switches of the cluster. The read subroutine has been tested on Argonne National Laboratory’s Mira (GPFS), National Center for Supercomputing Application’s Blue Waters (Lustre), San Diego Supercomputer Center’s Comet (Lustre), and UIC’s Extreme (Lustre). The tests showed that one file per node is suited for GPFS and parallel MPI I/O is the best choice for Lustre file system. The DSEM code relies on heavily optimized linear algebra operation such as matrix-matrix and matrix-vector products for calculation of the solution in every time-step. For this, the code can either make use of its matrix math library, BLAS, Intel MKL, or ATLAS. This fact and the discontinuous nature of the method makes the DSEM code run efficiently in parallel. The results of weak scaling tests performed on Blue Waters showed a scalable and efficient performance of the code in parallel computing.

Keywords: computational fluid dynamics, direct numerical simulation, spectral element, turbulent flow

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14 The Use of Rule-Based Cellular Automata to Track and Forecast the Dispersal of Classical Biocontrol Agents at Scale, with an Application to the Fopius arisanus Fruit Fly Parasitoid

Authors: Agboka Komi Mensah, John Odindi, Elfatih M. Abdel-Rahman, Onisimo Mutanga, Henri Ez Tonnang

Abstract:

Ecosystems are networks of organisms and populations that form a community of various species interacting within their habitats. Such habitats are defined by abiotic and biotic conditions that establish the initial limits to a population's growth, development, and reproduction. The habitat’s conditions explain the context in which species interact to access resources such as food, water, space, shelter, and mates, allowing for feeding, dispersal, and reproduction. Dispersal is an essential life-history strategy that affects gene flow, resource competition, population dynamics, and species distributions. Despite the importance of dispersal in population dynamics and survival, understanding the mechanism underpinning the dispersal of organisms remains challenging. For instance, when an organism moves into an ecosystem for survival and resource competition, its progression is highly influenced by extrinsic factors such as its physiological state, climatic variables and ability to evade predation. Therefore, greater spatial detail is necessary to understand organism dispersal dynamics. Understanding organisms dispersal can be addressed using empirical and mechanistic modelling approaches, with the adopted approach depending on the study's purpose Cellular automata (CA) is an example of these approaches that have been successfully used in biological studies to analyze the dispersal of living organisms. Cellular automata can be briefly described as occupied cells by an individual that evolves based on proper decisions based on a set of neighbours' rules. However, in the ambit of modelling individual organisms dispersal at the landscape scale, we lack user friendly tools that do not require expertise in mathematical models and computing ability; such as a visual analytics framework for tracking and forecasting the dispersal behaviour of organisms. The term "visual analytics" (VA) describes a semiautomated approach to electronic data processing that is guided by users who can interact with data via an interface. Essentially, VA converts large amounts of quantitative or qualitative data into graphical formats that can be customized based on the operator's needs. Additionally, this approach can be used to enhance the ability of users from various backgrounds to understand data, communicate results, and disseminate information across a wide range of disciplines. To support effective analysis of the dispersal of organisms at the landscape scale, we therefore designed Pydisp which is a free visual data analytics tool for spatiotemporal dispersal modeling built in Python. Its user interface allows users to perform a quick and interactive spatiotemporal analysis of species dispersal using bioecological and climatic data. Pydisp enables reuse and upgrade through the use of simple principles such as Fuzzy cellular automata algorithms. The potential of dispersal modeling is demonstrated in a case study by predicting the dispersal of Fopius arisanus (Sonan), endoparasitoids to control Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) in Kenya. The results obtained from our example clearly illustrate the parasitoid's dispersal process at the landscape level and confirm that dynamic processes in an agroecosystem are better understood when designed using mechanistic modelling approaches. Furthermore, as demonstrated in the example, the built software is highly effective in portraying the dispersal of organisms despite the unavailability of detailed data on the species dispersal mechanisms.

Keywords: cellular automata, fuzzy logic, landscape, spatiotemporal

Procedia PDF Downloads 52
13 Musictherapy and Gardentherapy: A Systemic Approach for the Life Quality of the PsychoPhysical Disability

Authors: Adriana De Serio, Donato Forenza

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Aims. In this experimental research the Authors present the methodological plan “Musictherapy and Gardentherapy” that they created interconnected with the garden landscape ecosystems and aimed at PsychoPhysical Disability (MusGarPPhyD). In the context of the environmental education aimed at spreading the landscape culture and its values, it’s necessary to develop a solid perception of the environment sustainability to implement a multidimensional approach that pays attention to the conservation and enhancement of gardens and natural environments. The result is an improvement in the life quality also in compliance with the objectives of the European Agenda 2030. The MusGarPPhyD can help professionals such as musictherapists and environmental and landscape researchers strengthen subjects' motivation to learn to deal with the psychophysical discomfort associated with disability and to cope with the distress and the psychological fragility and the loneliness and the social seclusion and to promote productive social relationships. Materials and Methods. The MusGarPPhyD was implemented in multiple spaces. The musictherapy treatments took place first inside residential therapeutic centres and then in the garden landscape ecosystem. Patients: twenty, set in two groups. Weekly-sessions (50’) for three months. Methodological phases: - Phase P1. MusicTherapy treatments for each group in the indoor spaces. - Phase P2. MusicTherapy sessions inside the gardens. After each Phase, P1 and P2: - a Questionnaire for each patient (ten items / liking-indices) was administrated at t0 time, during the treatment and at tn time at the end of the treatment. - Monitoring of patients' behavioral responses through assessment scales, matrix, table and graph system. MusicTherapy methodology: pazient Sonorous-Musical Anamnesis, Musictherapy Assessment Document, Observation Protocols, Bodily-Environmental-Rhythmical-Sonorous-Vocal-Energy production first indoors and then outside, sonorous-musical instruments and edible instruments made by the Author/musictherapist with some foods; Administration of Patient-Environment-Music Index at time to and tn, to estimate the patient’s behavior evolution, Musictherapeutic Advancement Index. Results. The MusGarPPhyD can strengthen the individual sense of identity and improve the psychophysical skills and the resilience to face and to overcome the difficulties caused by the congenital /acquired disability. The multi-sensory perceptions deriving from contact with the plants in the gardens improve the psychological well-being and regulate the physiological parameters such as blood pressure, cardiac and respiratory rhythm, reducing the cholesterol levels. The secretions of the peptide hormones endorphins and the endogenous opioids enkephalins increase and bring a state of patient’s tranquillity and a better mood. The subjects showed a preference for musictherapy treatments within a setting made up of gardens and peculiar landscape systems. This resulted in greater health benefits. Conclusions. The MusGarPPhyD contributes to reduce psychophysical tensions, anxiety, depression and stress, facilitating the connections between the cerebral hemispheres, thus also improving intellectual performances, self-confidence, motor skills and social interactions. Therefore it is necessary to design hospitals, rehabilitation centers, nursing homes, surrounded by gardens. Ecosystems of natural and urban parks and gardens create fascinating skyline and mosaics of landscapes rich in beauty and biodiversity. The MusGarPPhyD is useful for the health management promoting patient’s psychophysical activation, better mood/affective-tone and relastionships and contributing significantly to improving the life quality.

Keywords: musictherapy, gardentherapy, disability, life quality

Procedia PDF Downloads 33
12 Anajaa-Visual Substitution System: A Navigation Assistive Device for the Visually Impaired

Authors: Juan Pablo Botero Torres, Alba Avila, Luis Felipe Giraldo

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Independent navigation and mobility through unknown spaces pose a challenge for the autonomy of visually impaired people (VIP), who have relied on the use of traditional assistive tools like the white cane and trained dogs. However, emerging visually assistive technologies (VAT) have proposed several human-machine interfaces (HMIs) that could improve VIP’s ability for self-guidance. Hereby, we introduce the design and implementation of a visually assistive device, Anajaa – Visual Substitution System (AVSS). This system integrates ultrasonic sensors with custom electronics, and computer vision models (convolutional neural networks), in order to achieve a robust system that acquires information of the surrounding space and transmits it to the user in an intuitive and efficient manner. AVSS consists of two modules: the sensing and the actuation module, which are fitted to a chest mount and belt that communicate via Bluetooth. The sensing module was designed for the acquisition and processing of proximity signals provided by an array of ultrasonic sensors. The distribution of these within the chest mount allows an accurate representation of the surrounding space, discretized in three different levels of proximity, ranging from 0 to 6 meters. Additionally, this module is fitted with an RGB-D camera used to detect potentially threatening obstacles, like staircases, using a convolutional neural network specifically trained for this purpose. Posteriorly, the depth data is used to estimate the distance between the stairs and the user. The information gathered from this module is then sent to the actuation module that creates an HMI, by the means of a 3x2 array of vibration motors that make up the tactile display and allow the system to deliver haptic feedback. The actuation module uses vibrational messages (tactones); changing both in amplitude and frequency to deliver different awareness levels according to the proximity of the obstacle. This enables the system to deliver an intuitive interface. Both modules were tested under lab conditions, and the HMI was additionally tested with a focal group of VIP. The lab testing was conducted in order to establish the processing speed of the computer vision algorithms. This experimentation determined that the model can process 0.59 frames per second (FPS); this is considered as an adequate processing speed taking into account that the walking speed of VIP is 1.439 m/s. In order to test the HMI, we conducted a focal group composed of two females and two males between the ages of 35-65 years. The subject selection was aided by the Colombian Cooperative of Work and Services for the Sightless (COOTRASIN). We analyzed the learning process of the haptic messages throughout five experimentation sessions using two metrics: message discrimination and localization success. These correspond to the ability of the subjects to recognize different tactones and locate them within the tactile display. Both were calculated as the mean across all subjects. Results show that the focal group achieved message discrimination of 70% and a localization success of 80%, demonstrating how the proposed HMI leads to the appropriation and understanding of the feedback messages, enabling the user’s awareness of its surrounding space.

Keywords: computer vision on embedded systems, electronic trave aids, human-machine interface, haptic feedback, visual assistive technologies, vision substitution systems

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11 Multiaxial Stress Based High Cycle Fatigue Model for Adhesive Joint Interfaces

Authors: Martin Alexander Eder, Sergei Semenov

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Many glass-epoxy composite structures, such as large utility wind turbine rotor blades (WTBs), comprise of adhesive joints with typically thick bond lines used to connect the different components during assembly. Performance optimization of rotor blades to increase power output by simultaneously maintaining high stiffness-to-low-mass ratios entails intricate geometries in conjunction with complex anisotropic material behavior. Consequently, adhesive joints in WTBs are subject to multiaxial stress states with significant stress gradients depending on the local joint geometry. Moreover, the dynamic aero-elastic interaction of the WTB with the airflow generates non-proportional, variable amplitude stress histories in the material. Empiricism shows that a prominent failure type in WTBs is high cycle fatigue failure of adhesive bond line interfaces, which in fact over time developed into a design driver as WTB sizes increase rapidly. Structural optimization employed at an early design stage, therefore, sets high demands on computationally efficient interface fatigue models capable of predicting the critical locations prone for interface failure. The numerical stress-based interface fatigue model presented in this work uses the Drucker-Prager criterion to compute three different damage indices corresponding to the two interface shear tractions and the outward normal traction. The two-parameter Drucker-Prager model was chosen because of its ability to consider shear strength enhancement under compression and shear strength reduction under tension. The governing interface damage index is taken as the maximum of the triple. The damage indices are computed through the well-known linear Palmgren-Miner rule after separate rain flow-counting of the equivalent shear stress history and the equivalent pure normal stress history. The equivalent stress signals are obtained by self-similar scaling of the Drucker-Prager surface whose shape is defined by the uniaxial tensile strength and the shear strength such that it intersects with the stress point at every time step. This approach implicitly assumes that the damage caused by the prevailing multiaxial stress state is the same as the damage caused by an amplified equivalent uniaxial stress state in the three interface directions. The model was implemented as Python plug-in for the commercially available finite element code Abaqus for its use with solid elements. The model was used to predict the interface damage of an adhesively bonded, tapered glass-epoxy composite cantilever I-beam tested by LM Wind Power under constant amplitude compression-compression tip load in the high cycle fatigue regime. Results show that the model was able to predict the location of debonding in the adhesive interface between the webfoot and the cap. Moreover, with a set of two different constant life diagrams namely in shear and tension, it was possible to predict both the fatigue lifetime and the failure mode of the sub-component with reasonable accuracy. It can be concluded that the fidelity, robustness and computational efficiency of the proposed model make it especially suitable for rapid fatigue damage screening of large 3D finite element models subject to complex dynamic load histories.

Keywords: adhesive, fatigue, interface, multiaxial stress

Procedia PDF Downloads 140
10 Optimal Pressure Control and Burst Detection for Sustainable Water Management

Authors: G. K. Viswanadh, B. Rajasekhar, G. Venkata Ramana

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Water distribution networks play a vital role in ensuring a reliable supply of clean water to urban areas. However, they face several challenges, including pressure control, pump speed optimization, and burst event detection. This paper combines insights from two studies to address these critical issues in Water distribution networks, focusing on the specific context of Kapra Municipality, India. The first part of this research concentrates on optimizing pressure control and pump speed in complex Water distribution networks. It utilizes the EPANET- MATLAB Toolkit to integrate EPANET functionalities into the MATLAB environment, offering a comprehensive approach to network analysis. By optimizing Pressure Reduce Valves (PRVs) and variable speed pumps (VSPs), this study achieves remarkable results. In the Benchmark Water Distribution System (WDS), the proposed PRV optimization algorithm reduces average leakage by 20.64%, surpassing the previous achievement of 16.07%. When applied to the South-Central and East zone WDS of Kapra Municipality, it identifies PRV locations that were previously missed by existing algorithms, resulting in average leakage reductions of 22.04% and 10.47%. These reductions translate to significant daily Water savings, enhancing Water supply reliability and reducing energy consumption. The second part of this research addresses the pressing issue of burst event detection and localization within the Water Distribution System. Burst events are a major contributor to Water losses and repair expenses. The study employs wireless sensor technology to monitor pressure and flow rate in real time, enabling the detection of pipeline abnormalities, particularly burst events. The methodology relies on transient analysis of pressure signals, utilizing Cumulative Sum and Wavelet analysis techniques to robustly identify burst occurrences. To enhance precision, burst event localization is achieved through meticulous analysis of time differentials in the arrival of negative pressure waveforms across distinct pressure sensing points, aided by nodal matrix analysis. To evaluate the effectiveness of this methodology, a PVC Water pipeline test bed is employed, demonstrating the algorithm's success in detecting pipeline burst events at flow rates of 2-3 l/s. Remarkably, the algorithm achieves a localization error of merely 3 meters, outperforming previously established algorithms. This research presents a significant advancement in efficient burst event detection and localization within Water pipelines, holding the potential to markedly curtail Water losses and the concomitant financial implications. In conclusion, this combined research addresses critical challenges in Water distribution networks, offering solutions for optimizing pressure control, pump speed, burst event detection, and localization. These findings contribute to the enhancement of Water Distribution System, resulting in improved Water supply reliability, reduced Water losses, and substantial cost savings. The integrated approach presented in this paper holds promise for municipalities and utilities seeking to improve the efficiency and sustainability of their Water distribution networks.

Keywords: pressure reduce valve, complex networks, variable speed pump, wavelet transform, burst detection, CUSUM (Cumulative Sum), water pipeline monitoring

Procedia PDF Downloads 49
9 4-Channel CWDM Optical Transceiver Applying Silicon Photonics Ge-Photodiode and MZ-Modulator

Authors: Do-Won Kim, Andy Eu Jin Lim, Raja Muthusamy Kumarasamy, Vishal Vinayak, Jacky Wang Yu-Shun, Jason Liow Tsung Yang, Patrick Lo Guo Qiang

Abstract:

In this study, we demonstrate 4-channel coarse wavelength division multiplexing (CWDM) optical transceiver based on silicon photonics integrated circuits (PIC) of waveguide Ge-photodiode (Ge-PD) and Mach Zehnder (MZ)-modulator. 4-channel arrayed PICs of Ge-PD and MZ-modulator are verified to operate at 25 Gbps/ch achieving 4x25 Gbps of total data rate. 4 bare dies of single-channel commercial electronics ICs (EICs) of trans-impedance amplifier (TIA) for Ge-PD and driver IC for MZ-modulator are packaged with PIC on printed circuit board (PCB) in a chip-on-board (COB) manner. Each single-channel EIC is electrically connected to the one channel of 4-channel PICs by wire bonds to trace. The PICs have 4-channel multiplexer for MZ-modulator and 4-channel demultiplexer for Ge-PD. The 4-channel multiplexer/demultiplexer have echelle gratings for4 CWDM optic signals of which center wavelengths are 1511, 1531, 1553, and 1573 nm. Its insertion loss is around 4dB with over 15dB of extinction ratio.The dimension of 4-channel Ge-PD is 3.6x1.4x0.3mm, and its responsivity is 1A/W with dark current of less than 20 nA.Its measured 3dB bandwidth is around 20GHz. The dimension of the 4-channel MZ-modulator is 3.6x4.8x0.3mm, and its 3dB bandwidth is around 11Ghz at -2V of reverse biasing voltage. It has 2.4V•cmbyVπVL of 6V for π shift to 4 mm length modulator.5x5um of Inversed tapered mode size converter with less than 2dB of coupling loss is used for the coupling of the lensed fiber which has 5um of mode field diameter.The PCB for COB packaging and signal transmission is designed to have 6 layers in the hybrid layer structure. 0.25 mm-thick Rogers Duroid RT5880 is used as the first core dielectric layer for high-speed performance over 25 Gbps. It has 0.017 mm-thick of copper layers and its dielectric constant is 2.2and dissipation factor is 0.0009 at 10 GHz. The dimension of both single ended and differential microstrip transmission lines are calculated using full-wave electromagnetic (EM) field simulator HFSS which RF industry is using most. It showed 3dB bandwidth at around 15GHz in S-parameter measurement using network analyzer. The wire bond length for transmission line and ground connection from EIC is done to have less than 300 µm to minimize the parasitic effect to the system.Single layered capacitors (SLC) of 100pF and 1000pF are connected as close as possible to the EICs for stabilizing the DC biasing voltage by decoupling. Its signal transmission performance is under measurement at 25Gbps achieving 100Gbps by 4chx25Gbps. This work can be applied for the active optical cable (AOC) and quad small form-factor pluggable (QSFP) for high-speed optical interconnections. Its demands are quite large in data centers targeting 100 Gbps, 400 Gbps, and 1 Tbps. As the demands of high-speed AOC and QSFP for the application to intra/inter data centers increase, this silicon photonics based high-speed 4 channel CWDM scheme can have advantages not only in data throughput but also cost effectiveness since it reduces fiber cost dramatically through WDM.

Keywords: active optical cable(AOC), 4-channel coarse wavelength division multiplexing (CWDM), communication system, data center, ge-photodiode, Mach Zehnder (MZ) modulator, optical interconnections, optical transceiver, photonics integrated circuits (PIC), quad small form-factor pluggable (QSFP), silicon photonics

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8 Effect of Degree of Phosphorylation on Electrospinning and In vitro Cell Behavior of Phosphorylated Polymers as Biomimetic Materials for Tissue Engineering Applications

Authors: Pallab Datta, Jyotirmoy Chatterjee, Santanu Dhara

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Over the past few years, phosphorous containing polymers have received widespread attention for applications such as high performance optical fibers, flame retardant materials, drug delivery and tissue engineering. Being pentavalent, phosphorous can exist in different chemical environments in these polymers which increase their versatility. In human biochemistry, phosphorous based compounds exert their functions both in soluble and insoluble form occurring as inorganic or as organophosphorous compounds. Specifically in case of biomacromolecules, phosphates are critical for functions of DNA, ATP, phosphoproteins, phospholipids, phosphoglycans and several coenzymes. Inspired by the role of phosphorous in functional biomacromolecules, design and synthesis of biomimetic materials are thus carried out by several authors to study macromolecular function or as substitutes in clinical tissue regeneration conditions. In addition, many regulatory signals of the body are controlled by phoshphorylation of key proteins present either in form of growth factors or matrix-bound scaffold proteins. This inspires works on synthesis of phospho-peptidomimetic amino acids for understanding key signaling pathways and this is extended to obtain molecules with potentially useful biological properties. Apart from above applications, phosphate groups bound to polymer backbones have also been demonstrated to improve function of osteoblast cells and augment performance of bone grafts. Despite the advantages of phosphate grafting, however, there is limited understanding on effect of degree of phosphorylation on macromolecular physicochemical and/or biological properties. Such investigations are necessary to effectively translate knowledge of macromolecular biochemistry into relevant clinical products since they directly influence processability of these polymers into suitable scaffold structures and control subsequent biological response. Amongst various techniques for fabrication of biomimetic scaffolds, nanofibrous scaffolds fabricated by electrospinning technique offer some special advantages in resembling the attributes of natural extracellular matrix. Understanding changes in physico-chemical properties of polymers as function of phosphorylation is therefore going to be crucial in development of nanofiber scaffolds based on phosphorylated polymers. The aim of the present work is to investigate the effect of phosphorous grafting on the electrospinning behavior of polymers with aim to obtain biomaterials for bone regeneration applications. For this purpose, phosphorylated derivatives of two polymers of widely different electrospinning behaviors were selected as starting materials. Poly(vinyl alcohol) is a conveniently electrospinnable polymer at different conditions and concentrations. On the other hand, electrospinning of chitosan backbone based polymers have been viewed as a critical challenge. The phosphorylated derivatives of these polymers were synthesized, characterized and electrospinning behavior of various solutions containing these derivatives was compared with electrospinning of pure poly (vinyl alcohol). In PVA, phosphorylation adversely impacted electrospinnability while in NMPC, higher phosphate content widened concentration range for nanofiber formation. Culture of MG-63 cells on electrospun nanofibers, revealed that degree of phosphate modification of a polymer significantly improves cell adhesion or osteoblast function of cultured cells. It is concluded that improvement of cell response parameters of nanofiber scaffolds can be attained as a function of controlled degree of phosphate grafting in polymeric biomaterials with implications for bone tissue engineering applications.

Keywords: bone regeneration, chitosan, electrospinning, phosphorylation

Procedia PDF Downloads 194
7 [Keynote Talk]: Bioactive Cyclic Dipeptides of Microbial Origin in Discovery of Cytokine Inhibitors

Authors: Sajeli A. Begum, Ameer Basha, Kirti Hira, Rukaiyya Khan

Abstract:

Cyclic dipeptides are simple diketopiperazine derivatives being investigated by several scientists for their biological effects which include anticancer, antimicrobial, haematological, anticonvulsant, immunomodulatory effect, etc. They are potentially active microbial metabolites having been synthesized too, for developing into drug candidates. Cultures of Pseudomonas species have earlier been reported to produce cyclic dipeptides, helping in quorum sensing signals and bacterial–host colonization phenomena during infections, causing cell anti-proliferation and immunosuppression. Fluorescing Pseudomonas species have been identified to secrete lipid derivatives, peptides, pyrroles, phenazines, indoles, aminoacids, pterines, pseudomonic acids and some antibiotics. In the present work, results of investigation on the cyclic dipeptide metabolites secreted by the culture broth of Pseudomonas species as potent pro-inflammatory cytokine inhibitors are discussed. The bacterial strain was isolated from the rhizospheric soil of groundnut crop and identified as Pseudomonas aeruginosa by 16S rDNA sequence (GenBank Accession No. KT625586). Culture broth of this strain was prepared by inoculating into King’s B broth and incubating at 30 ºC for 7 days. The ethyl acetate extract of culture broth was prepared and lyophilized to get a dry residue (EEPA). Lipopolysaccharide (LPS)-induced ELISA assay proved the inhibition of tumor necrosis factor-alpha (TNF-α) secretion in culture supernatant of RAW 264.7 cells by EEPA (IC50 38.8 μg/mL). The effect of oral administration of EEPA on plasma TNF-α level in rats was tested by ELISA kit. The LPS mediated plasma TNF-α level was reduced to 45% with 125 mg/kg dose of EEPA. Isolation of the chemical constituents of EEPA through column chromatography yielded ten cyclic dipeptides, which were characterized using nuclear magnetic resonance and mass spectroscopic techniques. These cyclic dipeptides are biosynthesized in microorganisms by multifunctional assembly of non-ribosomal peptide synthases and cyclic dipeptide synthase. Cyclo (Gly-L-Pro) was found to be more potentially (IC50 value 4.5 μg/mL) inhibiting TNF-α production followed by cyclo (trans-4-hydroxy-L-Pro-L-Phe) (IC50 value 14.2 μg/mL) and the effect was equal to that of standard immunosuppressant drug, prednisolone. Further, the effect was analyzed by determining mRNA expression of TNF-α in LPS-stimulated RAW 264.7 macrophages using quantitative real-time reverse transcription polymerase chain reaction. EEPA and isolated cyclic dipeptides demonstrated diminution of TNF-α mRNA expression levels in a dose-dependent manner under the tested conditions. Also, they were found to control the expression of other pro-inflammatory cytokines like IL-1β and IL-6, when tested through their mRNA expression levels in LPS-stimulated RAW 264.7 macrophages under LPS-stimulated conditions. In addition, significant inhibition effect was found on Nitric oxide production. Further all the compounds exhibited weak toxicity to LPS-induced RAW 264.7 cells. Thus the outcome of the study disclosed the effectiveness of EEPA and the isolated cyclic dipeptides in down-regulating key cytokines involved in pathophysiology of autoimmune diseases.In another study led by the investigators, microbial cyclic dipeptides were found to exhibit excellent antimicrobial effect against Fusarium moniliforme which is an important causative agent of Sorghum grain mold disease. Thus, cyclic dipeptides are emerging small molecular drug candidates for various autoimmune diseases.

Keywords: cyclic dipeptides, cytokines, Fusarium moniliforme, Pseudomonas, TNF-alpha

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6 Cycleloop Personal Rapid Transit: An Exploratory Study for Last Mile Connectivity in Urban Transport

Authors: Suresh Salla

Abstract:

In this paper, author explores for most sustainable last mile transport mode addressing present problems of traffic congestion, jams, pollution and travel stress. Development of energy-efficient sustainable integrated transport system(s) is/are must to make our cities more livable. Emphasis on autonomous, connected, electric, sharing system for effective utilization of systems (vehicles and public infrastructure) is on the rise. Many surface mobility innovations like PBS, Ride hailing, ride sharing, etc. are, although workable but if we analyze holistically, add to the already congested roads, difficult to ride in hostile weather, causes pollution and poses commuter stress. Sustainability of transportation is evaluated with respect to public adoption, average speed, energy consumption, and pollution. Why public prefer certain mode over others? How commute time plays a role in mode selection or shift? What are the factors play-ing role in energy consumption and pollution? Based on the study, it is clear that public prefer a transport mode which is exhaustive (i.e., less need for interchange – network is widespread) and intensive (i.e., less waiting time - vehicles are available at frequent intervals) and convenient with latest technologies. Average speed is dependent on stops, number of intersections, signals, clear route availability, etc. It is clear from Physics that higher the kerb weight of a vehicle; higher is the operational energy consumption. Higher kerb weight also demands heavier infrastructure. Pollution is dependent on source of energy, efficiency of vehicle, average speed. Mode can be made exhaustive when the unit infrastructure cost is less and can be offered intensively when the vehicle cost is less. Reliable and seamless integrated mobility till last ¼ mile (Five Minute Walk-FMW) is a must to encourage sustainable public transportation. Study shows that average speed and reliability of dedicated modes (like Metro, PRT, BRT, etc.) is high compared to road vehicles. Electric vehicles and more so battery-less or 3rd rail vehicles reduce pollution. One potential mode can be Cycleloop PRT, where commuter rides e-cycle in a dedicated path – elevated, at grade or underground. e-Bike with kerb weight per rider at 15 kg being 1/50th of car or 1/10th of other PRT systems makes it sustainable mode. Cycleloop tube will be light, sleek and scalable and can be modular erected, either on modified street lamp-posts or can be hanged/suspended between the two stations. Embarking and dis-embarking points or offline stations can be at an interval which suits FMW to mass public transit. In terms of convenience, guided e-Bike can be made self-balancing thus encouraging driverless on-demand vehicles. e-Bike equipped with smart electronics and drive controls can intelligently respond to field sensors and autonomously move reacting to Central Controller. Smart switching allows travel from origin to destination without interchange of cycles. DC Powered Batteryless e-cycle with voluntary manual pedaling makes it sustainable and provides health benefits. Tandem e-bike, smart switching and Platoon operations algorithm options provide superior through-put of the Cycleloop. Thus Cycleloop PRT will be exhaustive, intensive, convenient, reliable, speedy, sustainable, safe, pollution-free and healthy alternative mode for last mile connectivity in cities.

Keywords: cycleloop PRT, five-minute walk, lean modular infrastructure, self-balanced intelligent e-cycle

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5 Multimodal Integration of EEG, fMRI and Positron Emission Tomography Data Using Principal Component Analysis for Prognosis in Coma Patients

Authors: Denis Jordan, Daniel Golkowski, Mathias Lukas, Katharina Merz, Caroline Mlynarcik, Max Maurer, Valentin Riedl, Stefan Foerster, Eberhard F. Kochs, Andreas Bender, Ruediger Ilg

Abstract:

Introduction: So far, clinical assessments that rely on behavioral responses to differentiate coma states or even predict outcome in coma patients are unreliable, e.g. because of some patients’ motor disabilities. The present study was aimed to provide prognosis in coma patients using markers from electroencephalogram (EEG), blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) and [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). Unsuperwised principal component analysis (PCA) was used for multimodal integration of markers. Methods: Approved by the local ethics committee of the Technical University of Munich (Germany) 20 patients (aged 18-89) with severe brain damage were acquired through intensive care units at the Klinikum rechts der Isar in Munich and at the Therapiezentrum Burgau (Germany). At the day of EEG/fMRI/PET measurement (date I) patients (<3.5 month in coma) were grouped in the minimal conscious state (MCS) or vegetative state (VS) on the basis of their clinical presentation (coma recovery scale-revised, CRS-R). Follow-up assessment (date II) was also based on CRS-R in a period of 8 to 24 month after date I. At date I, 63 channel EEG (Brain Products, Gilching, Germany) was recorded outside the scanner, and subsequently simultaneous FDG-PET/fMRI was acquired on an integrated Siemens Biograph mMR 3T scanner (Siemens Healthineers, Erlangen Germany). Power spectral densities, permutation entropy (PE) and symbolic transfer entropy (STE) were calculated in/between frontal, temporal, parietal and occipital EEG channels. PE and STE are based on symbolic time series analysis and were already introduced as robust markers separating wakefulness from unconsciousness in EEG during general anesthesia. While PE quantifies the regularity structure of the neighboring order of signal values (a surrogate of cortical information processing), STE reflects information transfer between two signals (a surrogate of directed connectivity in cortical networks). fMRI was carried out using SPM12 (Wellcome Trust Center for Neuroimaging, University of London, UK). Functional images were realigned, segmented, normalized and smoothed. PET was acquired for 45 minutes in list-mode. For absolute quantification of brain’s glucose consumption rate in FDG-PET, kinetic modelling was performed with Patlak’s plot method. BOLD signal intensity in fMRI and glucose uptake in PET was calculated in 8 distinct cortical areas. PCA was performed over all markers from EEG/fMRI/PET. Prognosis (persistent VS and deceased patients vs. recovery to MCS/awake from date I to date II) was evaluated using the area under the curve (AUC) including bootstrap confidence intervals (CI, *: p<0.05). Results: Prognosis was reliably indicated by the first component of PCA (AUC=0.99*, CI=0.92-1.00) showing a higher AUC when compared to the best single markers (EEG: AUC<0.96*, fMRI: AUC<0.86*, PET: AUC<0.60). CRS-R did not show prediction (AUC=0.51, CI=0.29-0.78). Conclusion: In a multimodal analysis of EEG/fMRI/PET in coma patients, PCA lead to a reliable prognosis. The impact of this result is evident, as clinical estimates of prognosis are inapt at time and could be supported by quantitative biomarkers from EEG, fMRI and PET. Due to the small sample size, further investigations are required, in particular allowing superwised learning instead of the basic approach of unsuperwised PCA.

Keywords: coma states and prognosis, electroencephalogram, entropy, functional magnetic resonance imaging, machine learning, positron emission tomography, principal component analysis

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4 Developing a Cloud Intelligence-Based Energy Management Architecture Facilitated with Embedded Edge Analytics for Energy Conservation in Demand-Side Management

Authors: Yu-Hsiu Lin, Wen-Chun Lin, Yen-Chang Cheng, Chia-Ju Yeh, Yu-Chuan Chen, Tai-You Li

Abstract:

Demand-Side Management (DSM) has the potential to reduce electricity costs and carbon emission, which are associated with electricity used in the modern society. A home Energy Management System (EMS) commonly used by residential consumers in a down-stream sector of a smart grid to monitor, control, and optimize energy efficiency to domestic appliances is a system of computer-aided functionalities as an energy audit for residential DSM. Implementing fault detection and classification to domestic appliances monitored, controlled, and optimized is one of the most important steps to realize preventive maintenance, such as residential air conditioning and heating preventative maintenance in residential/industrial DSM. In this study, a cloud intelligence-based green EMS that comes up with an Internet of Things (IoT) technology stack for residential DSM is developed. In the EMS, Arduino MEGA Ethernet communication-based smart sockets that module a Real Time Clock chip to keep track of current time as timestamps via Network Time Protocol are designed and implemented for readings of load phenomena reflecting on voltage and current signals sensed. Also, a Network-Attached Storage providing data access to a heterogeneous group of IoT clients via Hypertext Transfer Protocol (HTTP) methods is configured to data stores of parsed sensor readings. Lastly, a desktop computer with a WAMP software bundle (the Microsoft® Windows operating system, Apache HTTP Server, MySQL relational database management system, and PHP programming language) serves as a data science analytics engine for dynamic Web APP/REpresentational State Transfer-ful web service of the residential DSM having globally-Advanced Internet of Artificial Intelligence (AI)/Computational Intelligence. Where, an abstract computing machine, Java Virtual Machine, enables the desktop computer to run Java programs, and a mash-up of Java, R language, and Python is well-suited and -configured for AI in this study. Having the ability of sending real-time push notifications to IoT clients, the desktop computer implements Google-maintained Firebase Cloud Messaging to engage IoT clients across Android/iOS devices and provide mobile notification service to residential/industrial DSM. In this study, in order to realize edge intelligence that edge devices avoiding network latency and much-needed connectivity of Internet connections for Internet of Services can support secure access to data stores and provide immediate analytical and real-time actionable insights at the edge of the network, we upgrade the designed and implemented smart sockets to be embedded AI Arduino ones (called embedded AIduino). With the realization of edge analytics by the proposed embedded AIduino for data analytics, an Arduino Ethernet shield WizNet W5100 having a micro SD card connector is conducted and used. The SD library is included for reading parsed data from and writing parsed data to an SD card. And, an Artificial Neural Network library, ArduinoANN, for Arduino MEGA is imported and used for locally-embedded AI implementation. The embedded AIduino in this study can be developed for further applications in manufacturing industry energy management and sustainable energy management, wherein in sustainable energy management rotating machinery diagnostics works to identify energy loss from gross misalignment and unbalance of rotating machines in power plants as an example.

Keywords: demand-side management, edge intelligence, energy management system, fault detection and classification

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3 Full Characterization of Heterogeneous Antibody Samples under Denaturing and Native Conditions on a Hybrid Quadrupole-Orbitrap Mass Spectrometer

Authors: Rowan Moore, Kai Scheffler, Eugen Damoc, Jennifer Sutton, Aaron Bailey, Stephane Houel, Simon Cubbon, Jonathan Josephs

Abstract:

Purpose: MS analysis of monoclonal antibodies (mAbs) at the protein and peptide levels is critical during development and production of biopharmaceuticals. The compositions of current generation therapeutic proteins are often complex due to various modifications which may affect efficacy. Intact proteins analyzed by MS are detected in higher charge states that also provide more complexity in mass spectra. Protein analysis in native or native-like conditions with zero or minimal organic solvent and neutral or weakly acidic pH decreases charge state value resulting in mAb detection at higher m/z ranges with more spatial resolution. Methods: Three commercially available mAbs were used for all experiments. Intact proteins were desalted online using size exclusion chromatography (SEC) or reversed phase chromatography coupled on-line with a mass spectrometer. For streamlined use of the LC- MS platform we used a single SEC column and alternately selected specific mobile phases to perform separations in either denaturing or native-like conditions: buffer A (20 % ACN, 0.1 % FA) with Buffer B (100 mM ammonium acetate). For peptide analysis mAbs were proteolytically digested with and without prior reduction and alkylation. The mass spectrometer used for all experiments was a commercially available Thermo Scientific™ hybrid Quadrupole-Orbitrap™ mass spectrometer, equipped with the new BioPharma option which includes a new High Mass Range (HMR) mode that allows for improved high mass transmission and mass detection up to 8000 m/z. Results: We have analyzed the profiles of three mAbs under reducing and native conditions by direct infusion with offline desalting and with on-line desalting via size exclusion and reversed phase type columns. The presence of high salt under denaturing conditions was found to influence the observed charge state envelope and impact mass accuracy after spectral deconvolution. The significantly lower charge states observed under native conditions improves the spatial resolution of protein signals and has significant benefits for the analysis of antibody mixtures, e.g. lysine variants, degradants or sequence variants. This type of analysis requires the detection of masses beyond the standard mass range ranging up to 6000 m/z requiring the extended capabilities available in the new HMR mode. We have compared each antibody sample that was analyzed individually with mixtures in various relative concentrations. For this type of analysis, we observed that apparent native structures persist and ESI is benefited by the addition of low amounts of acetonitrile and formic acid in combination with the ammonium acetate-buffered mobile phase. For analyses on the peptide level we analyzed reduced/alkylated, and non-reduced proteolytic digests of the individual antibodies separated via reversed phase chromatography aiming to retrieve as much information as possible regarding sequence coverage, disulfide bridges, post-translational modifications such as various glycans, sequence variants, and their relative quantification. All data acquired were submitted to a single software package for analysis aiming to obtain a complete picture of the molecules analyzed. Here we demonstrate the capabilities of the mass spectrometer to fully characterize homogeneous and heterogeneous therapeutic proteins on one single platform. Conclusion: Full characterization of heterogeneous intact protein mixtures by improved mass separation on a quadrupole-Orbitrap™ mass spectrometer with extended capabilities has been demonstrated.

Keywords: disulfide bond analysis, intact analysis, native analysis, mass spectrometry, monoclonal antibodies, peptide mapping, post-translational modifications, sequence variants, size exclusion chromatography, therapeutic protein analysis, UHPLC

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2 A Spatial Repetitive Controller Applied to an Aeroelastic Model for Wind Turbines

Authors: Riccardo Fratini, Riccardo Santini, Jacopo Serafini, Massimo Gennaretti, Stefano Panzieri

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This paper presents a nonlinear differential model, for a three-bladed horizontal axis wind turbine (HAWT) suited for control applications. It is based on a 8-dofs, lumped parameters structural dynamics coupled with a quasi-steady sectional aerodynamics. In particular, using the Euler-Lagrange Equation (Energetic Variation approach), the authors derive, and successively validate, such model. For the derivation of the aerodynamic model, the Greenbergs theory, an extension of the theory proposed by Theodorsen to the case of thin airfoils undergoing pulsating flows, is used. Specifically, in this work, the authors restricted that theory under the hypothesis of low perturbation reduced frequency k, which causes the lift deficiency function C(k) to be real and equal to 1. Furthermore, the expressions of the aerodynamic loads are obtained using the quasi-steady strip theory (Hodges and Ormiston), as a function of the chordwise and normal components of relative velocity between flow and airfoil Ut, Up, their derivatives, and section angular velocity ε˙. For the validation of the proposed model, the authors carried out open and closed-loop simulations of a 5 MW HAWT, characterized by radius R =61.5 m and by mean chord c = 3 m, with a nominal angular velocity Ωn = 1.266rad/sec. The first analysis performed is the steady state solution, where a uniform wind Vw = 11.4 m/s is considered and a collective pitch angle θ = 0.88◦ is imposed. During this step, the authors noticed that the proposed model is intrinsically periodic due to the effect of the wind and of the gravitational force. In order to reject this periodic trend in the model dynamics, the authors propose a collective repetitive control algorithm coupled with a PD controller. In particular, when the reference command to be tracked and/or the disturbance to be rejected are periodic signals with a fixed period, the repetitive control strategies can be applied due to their high precision, simple implementation and little performance dependency on system parameters. The functional scheme of a repetitive controller is quite simple and, given a periodic reference command, is composed of a control block Crc(s) usually added to an existing feedback control system. The control block contains and a free time-delay system eτs in a positive feedback loop, and a low-pass filter q(s). It should be noticed that, while the time delay term reduces the stability margin, on the other hand the low pass filter is added to ensure stability. It is worth noting that, in this work, the authors propose a phase shifting for the controller and the delay system has been modified as e^(−(T−γk)), where T is the period of the signal and γk is a phase shifting of k samples of the same periodic signal. It should be noticed that, the phase shifting technique is particularly useful in non-minimum phase systems, such as flexible structures. In fact, using the phase shifting, the iterative algorithm could reach the convergence also at high frequencies. Notice that, in our case study, the shifting of k samples depends both on the rotor angular velocity Ω and on the rotor azimuth angle Ψ: we refer to this controller as a spatial repetitive controller. The collective repetitive controller has also been coupled with a C(s) = PD(s), in order to dampen oscillations of the blades. The performance of the spatial repetitive controller is compared with an industrial PI controller. In particular, starting from wind speed velocity Vw = 11.4 m/s the controller is asked to maintain the nominal angular velocity Ωn = 1.266rad/s after an instantaneous increase of wind speed (Vw = 15 m/s). Then, a purely periodic external disturbance is introduced in order to stress the capabilities of the repetitive controller. The results of the simulations show that, contrary to a simple PI controller, the spatial repetitive-PD controller has the capability to reject both external disturbances and periodic trend in the model dynamics. Finally, the nominal value of the angular velocity is reached, in accordance with results obtained with commercial software for a turbine of the same type.

Keywords: wind turbines, aeroelasticity, repetitive control, periodic systems

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1 Identification of the Antimicrobial Property of Double Metal Oxide/Bioactive Glass Nanocomposite Against Multi Drug Resistant Staphylococcus aureus Causing Implant Infections

Authors: M. H. Pazandeh, M. Doudi, S. Barahimi, L. Rahimzadeh Torabi

Abstract:

The use of antibiotics is essential in reducing the occurrence of adverse effects and inhibiting the emergence of antibiotic resistance in microbial populations. The necessity for a novel methodology concerning local administration of antibiotics has arisen, with particular focus on dealing with localized infections prompted by bacterial colonization of medical devices or implant materials. Bioactive glasses (BG) are extensively employed in the field of regenerative medicine, encompassing a diverse range of materials utilized for drug delivery systems. In the present investigation, various drug carriers for imipenem and tetracycline, namely single systems BG/SnO2, BG/NiO with varying proportions of metal oxide, and nanocomposite BG/SnO2/NiO, were synthesized through the sol-gel technique. The antibacterial efficacy of the synthesized samples was assessed through the utilization of the disk diffusion method with the aim of neutralizing Staphylococcus aureus as the bacterial model. The current study involved the examination of the bioactivity of two samples, namely BG10SnO2/10NiO and BG20SnO2, which were chosen based on their heightened bacterial inactivation properties. This evaluation entailed the employment of two techniques: the measurement of the pH of simulated body fluid (SBF) solution and the analysis of the sample tablets through X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy. The sample tablets were submerged in SBF for varying durations of 7, 14, and 28 days. The bioactivity of the composite bioactive glass sample was assessed through characterization of alterations in its surface morphology, structure, and chemical composition. This evaluation was performed using scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, and X-ray diffraction spectroscopy. Subsequently, the sample was immersed in simulated liquids to simulate its behavior in biological environments. The specific body fat percentage (SBF) was assessed over a 28-day period. The confirmation of the formation of a hydroxyapatite surface layer serves as a distinct indicator of bioactivity. The infusion of antibiotics into the composite bioactive glass specimen was done separately, and then the release kinetics of tetracycline and imipenem were tested in simulated body fluid (SBF). Antimicrobial effectiveness against various bacterial strains have been proven in numerous instances using both melt and sol-gel techniques to create multiple bioactive glass compositions. An elevated concentration of calcium ions within a solution has been observed to cause an increase in the pH level. In aqueous suspensions, bioactive glass particles manifest a significant antimicrobial impact. The composite bioactive glass specimen exhibits a gradual and uninterrupted release, which is highly desirable for a drug delivery system over a span of 72 hours. The reduction in absorption, which signals the loss of a portion of the antibiotic during the loading process from the initial phosphate-buffered saline solution, indicates the successful bonding of the two antibiotics to the surfaces of the bioactive glass samples. The sample denoted as BG/10SnO2/10NiO exhibits a higher loading of particles compared to the sample designated as BG/20SnO2 in the context of bioactive glass. The enriched sample demonstrates a heightened bactericidal impact on the bacteria under investigation while concurrently preserving its antibacterial characteristics. Tailored bioactive glass that incorporates hydroxyapatite, with a regulated and efficient release of drugs targeting bacterial infections, holds promise as a potential framework for bone implant scaffolds following rigorous clinical evaluation, thereby establishing potential future biomedical uses. During the modification process, the introduction of metal oxides into bioactive glass resulted in improved antibacterial characteristics, particularly in the composite bioactive glass sample that displayed the highest level of efficiency.

Keywords: antibacterial, bioactive glasses, implant infections, multi drug resistant

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