Search results for: single warp beam
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5432

Search results for: single warp beam

3812 The Droplet Generation and Flow in the T-Shape Microchannel with the Side Wall Fluctuation

Authors: Yan Pang, Xiang Wang, Zhaomiao Liu

Abstract:

Droplet microfluidics, in which nanoliter to picoliter droplets acted as individual compartments, are common to a diverse array of applications such as analytical chemistry, tissue engineering, microbiology and drug discovery. The droplet generation in a simplified two dimension T-shape microchannel with the main channel width of 50 μm and the side channel width of 25 μm, is simulated to investigate effects of the forced fluctuation of the side wall on the droplet generation and flow. The periodic fluctuations are applied on a length of the side wall in the main channel of the T-junction with the deformation shape of the double-clamped beam acted by the uniform force, which varies with the flow time and fluctuation periods, forms and positions. The fluctuations under most of the conditions expand the distribution range of the droplet size but have a little effect on the average size, while the shape of the fixed side wall changes the average droplet size chiefly. Droplet sizes show a periodic pattern along the relative time when the fluctuation is forced on the side wall near the T-junction. The droplet emerging frequency is not varied by the fluctuation of the side wall under the same flow rate and geometry conditions. When the fluctuation period is similar with the droplet emerging period, the droplet size shows a nice stability as the no fluctuation case.

Keywords: droplet generation, droplet size, flow flied, forced fluctuation

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3811 Detecting Memory-Related Gene Modules in sc/snRNA-seq Data by Deep-Learning

Authors: Yong Chen

Abstract:

To understand the detailed molecular mechanisms of memory formation in engram cells is one of the most fundamental questions in neuroscience. Recent single-cell RNA-seq (scRNA-seq) and single-nucleus RNA-seq (snRNA-seq) techniques have allowed us to explore the sparsely activated engram ensembles, enabling access to the molecular mechanisms that underlie experience-dependent memory formation and consolidation. However, the absence of specific and powerful computational methods to detect memory-related genes (modules) and their regulatory relationships in the sc/snRNA-seq datasets has strictly limited the analysis of underlying mechanisms and memory coding principles in mammalian brains. Here, we present a deep-learning method named SCENTBOX, to detect memory-related gene modules and causal regulatory relationships among themfromsc/snRNA-seq datasets. SCENTBOX first constructs codifferential expression gene network (CEGN) from case versus control sc/snRNA-seq datasets. It then detects the highly correlated modules of differential expression genes (DEGs) in CEGN. The deep network embedding and attention-based convolutional neural network strategies are employed to precisely detect regulatory relationships among DEG genes in a module. We applied them on scRNA-seq datasets of TRAP; Ai14 mouse neurons with fear memory and detected not only known memory-related genes, but also the modules and potential causal regulations. Our results provided novel regulations within an interesting module, including Arc, Bdnf, Creb, Dusp1, Rgs4, and Btg2. Overall, our methods provide a general computational tool for processing sc/snRNA-seq data from case versus control studie and a systematic investigation of fear-memory-related gene modules.

Keywords: sc/snRNA-seq, memory formation, deep learning, gene module, causal inference

Procedia PDF Downloads 116
3810 Optoelectronic Hardware Architecture for Recurrent Learning Algorithm in Image Processing

Authors: Abdullah Bal, Sevdenur Bal

Abstract:

This paper purposes a new type of hardware application for training of cellular neural networks (CNN) using optical joint transform correlation (JTC) architecture for image feature extraction. CNNs require much more computation during the training stage compare to test process. Since optoelectronic hardware applications offer possibility of parallel high speed processing capability for 2D data processing applications, CNN training algorithm can be realized using Fourier optics technique. JTC employs lens and CCD cameras with laser beam that realize 2D matrix multiplication and summation in the light speed. Therefore, in the each iteration of training, JTC carries more computation burden inherently and the rest of mathematical computation realized digitally. The bipolar data is encoded by phase and summation of correlation operations is realized using multi-object input joint images. Overlapping properties of JTC are then utilized for summation of two cross-correlations which provide less computation possibility for training stage. Phase-only JTC does not require data rearrangement, electronic pre-calculation and strict system alignment. The proposed system can be incorporated simultaneously with various optical image processing or optical pattern recognition techniques just in the same optical system.

Keywords: CNN training, image processing, joint transform correlation, optoelectronic hardware

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3809 Morphological Studies of the Gills of the Red Swamp Freshwater Crayfish Procambarus clarkii (Crustacea: Decapoda: Cambarids) (Girard 1852) from the River Nile and Its Branches in Egypt

Authors: Mohamed M. A. Abumandour

Abstract:

The red swamp freshwater crayfish breathe through three types of feather-like trichobranchiate gills; podobranchiae, arthrobranchiae and pleurobranchiae. All gills have the same general structure and appearance; plume-like with single broad setiferous, and single axis. The gill consists of axis with numerous finger-like filaments, having three morphological types; round, pointed and somewhat hooked shaped. The direction of filaments vary according their position; in middle region were nearly perpendicular to gill axis while in the apex were nearly parallel to axis. There were characteristic system of gill spines on; central axis (two types were distinguishable by presence of socket), basal plate, setobranch (long non-branched and short multidenticulate) and on the bilobed epipodal plate. There are four shape of spinated-like distal region of setobranch seta; two pointed processes (longitudinal arrangement and irregular arranged) and two broad processes (transverse triangular and multidenticulate). The bilobed epipodal plate devoid from any filaments and extended from outer side of podobranchiae as triangular basal part then extended between the gills as cord-like middle part then pass under the gill to lies against the thoracic body wall. By SEM, the apical part of bilobed epipodal plate have serrated free border and corrugated surface while the middle part have none serrated free border. There are two methods of gill cleaning mechanism in crayfish; passive and active method. The passive method occurred by; setae of setobranch, branchiostegite, bilobed epipodal plate, setiferous arthrodial lamellae and reversing the respiratory water through a narrow spaced branchial chamber.

Keywords: crayfis, gill spines, setobranch, gill setae, cleaning mechanisms

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3808 A Scientific Method of Drug Development Based on Ayurvedic Bhaishajya Knowledge

Authors: Rajesh S. Mony, Vaidyaratnam Oushadhasala

Abstract:

An attempt is made in this study to evolve a drug development modality based on classical Ayurvedic knowledge base as well as on modern scientific methodology. The present study involves (a) identification of a specific ailment condition, (b) the selection of a polyherbal formulation, (c) deciding suitable extraction procedure, (d) confirming the efficacy of the combination by in-vitro trials and (e) fixing up the recommended dose. The ailment segment selected is arthritic condition. The selected herbal combination is Kunturushka, Vibhitaki, Guggulu, Haridra, Maricha and Nirgundi. They were selected as per Classical Ayurvedic references, Authentified as per API (Ayurvedic Pharmacopeia of India), Extraction of each drug was done by different ratios of Hydroalcoholic menstrums, Invitro assessment of each extract after removing residual solvent for anti-Inflammatory, anti-arthritic activities (by UV-Vis. Spectrophotometer with positive control), Invitro assessment of each extract for COX enzyme inhibition (by UV-Vis. Spectrophotometer with positive control), Selection of the extracts was made having good in-vitro activity, Performed the QC testing of each selected extract including HPTLC, that is the in process QC specifications, h. Decision of the single dose with mixtures of selected extracts was made as per the level of in-vitro activity and available toxicology data, Quantification of major groups like Phenolics, Flavonoids, Alkaloids and Bitters was done with both standard Spectrophotometric and Gravimetric methods, Method for Marker assay was developed and validated by HPTLC and a good resolved HPTLC finger print was developed for the single dosage API (Active Pharmaceutical Ingredient mixture of extracts), Three batches was prepared to fix the in process and API (Active Pharmaceutical Ingredient) QC specifications.

Keywords: drug development, antiinflammatory, quality stardardisation, planar chromatography

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3807 Robustness of Steel Beam to Column Moment Resisting Joints

Authors: G. Culache, M. P. Byfield, N. S. Ferguson, A. Tyas

Abstract:

Steel joints in building structures represent a weak link in the case of accidental transient loading. This type of loading can occur due to blast effects or impact with moving vehicles and will result in large deformations in the material as well as large rotations. This paper addresses the lack of experimental investigations into the response of moment resisting connections subjected to such loading. The current design philosophy was used to create test specimens with flush and extended end plates. The specimens were tested in a specially designed testing rig capable of delivering the sustained loading even beyond the point of failure. Types of failure that the authors attempted to obtain were bolt fracture, flange crushing and end plate fracture. Experimental data is presented, described and analyzed. The tests show that the strength and ductility can be significantly improved by replacing ordinary mild-steel bolts with their stainless steel equivalents. This minor modification is demonstrated to significantly improve the robustness when subjected to loading that results in high deformations and rotation, where loading is maintained during failure. Conclusions are drawn about the wider implications of this research and recommendations made on the direction of future research in this field.

Keywords: steel moment connections, high strain rates, dynamic loading, experimental testing

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3806 Optimized Passive Heating for Multifamily Dwellings

Authors: Joseph Bostick

Abstract:

A method of decreasing the heating load of HVAC systems in a single-dwelling model of a multifamily building, by controlling movable insulation through the optimization of flux, time, surface incident solar radiation, and temperature thresholds. Simulations are completed using a co-simulation between EnergyPlus and MATLAB as an optimization tool to find optimal control thresholds. Optimization of the control thresholds leads to a significant decrease in total heating energy expenditure.

Keywords: energy plus, MATLAB, simulation, energy efficiency

Procedia PDF Downloads 170
3805 Competitive DNA Calibrators as Quality Reference Standards (QRS™) for Germline and Somatic Copy Number Variations/Variant Allelic Frequencies Analyses

Authors: Eirini Konstanta, Cedric Gouedard, Aggeliki Delimitsou, Stefania Patera, Samuel Murray

Abstract:

Introduction: Quality reference DNA standards (QRS) for molecular testing by next-generation sequencing (NGS) are essential for accurate quantitation of copy number variations (CNV) for germline and variant allelic frequencies (VAF) for somatic analyses. Objectives: Presently, several molecular analytics for oncology patients are reliant upon quantitative metrics. Test validation and standardisation are also reliant upon the availability of surrogate control materials allowing for understanding test LOD (limit of detection), sensitivity, specificity. We have developed a dual calibration platform allowing for QRS pairs to be included in analysed DNA samples, allowing for accurate quantitation of CNV and VAF metrics within and between patient samples. Methods: QRS™ blocks up to 500nt were designed for common NGS panel targets incorporating ≥ 2 identification tags (IDTDNA.com). These were analysed upon spiking into gDNA, somatic, and ctDNA using a proprietary CalSuite™ platform adaptable to common LIMS. Results: We demonstrate QRS™ calibration reproducibility spiked to 5–25% at ± 2.5% in gDNA and ctDNA. Furthermore, we demonstrate CNV and VAF within and between samples (gDNA and ctDNA) with the same reproducibility (± 2.5%) in a clinical sample of lung cancer and HBOC (EGFR and BRCA1, respectively). CNV analytics was performed with similar accuracy using a single pair of QRS calibrators when using multiple single targeted sequencing controls. Conclusion: Dual paired QRS™ calibrators allow for accurate and reproducible quantitative analyses of CNV, VAF, intrinsic sample allele measurement, inter and intra-sample measure not only simplifying NGS analytics but allowing for monitoring clinically relevant biomarker VAF across patient ctDNA samples with improved accuracy.

Keywords: calibrator, CNV, gene copy number, VAF

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3804 Flexural Behaviour of Normal Strength and High Strength Fibre Concrete Beams

Authors: Mostefa Hamrat, Bensaid Boulekbache, Mohamed Chemrouk, Sofiane Amziane

Abstract:

The paper presents the results of an experimental work on the flexural behaviour of two types of concrete in terms of the progressive cracking process until failure and the crack opening, and beam deflection, using Digital Image Correlation (DIC) technique. At serviceability limit states, comparisons of the building code equations and the equations developed by some researchers for the short-term deflections and crack widths have been made using the reinforced concrete test beams. The experimental results show that the addition of steel fibers increases the first cracking load and amplify the number of cracks that conducts to a remarkable decreasing in the crack width with an increasing in ductility. This study also shows that there is a good agreement between the deflection values for RC beams predicted by the major codes (Eurocode2, ACI 318, and the CAN/CSA-S806) and the experimental results for beams with steel fibers at service load. The most important added benefit of the DIC technique is that it allows detecting the first crack with a high precision easily measures the crack opening and follows the progressive cracking process until failure of reinforced concrete members.

Keywords: beams, digital image correlation (DIC), deflection, crack width, serviceability, codes provisions

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3803 Investigating the Neural Heterogeneity of Developmental Dyscalculia

Authors: Fengjuan Wang, Azilawati Jamaludin

Abstract:

Developmental Dyscalculia (DD) is defined as a particular learning difficulty with continuous challenges in learning requisite math skills that cannot be explained by intellectual disability or educational deprivation. Recent studies have increasingly recognized that DD is a heterogeneous, instead of monolithic, learning disorder with not only cognitive and behavioral deficits but so too neural dysfunction. In recent years, neuroimaging studies employed group comparison to explore the neural underpinnings of DD, which contradicted the heterogenous nature of DD and may obfuscate critical individual differences. This research aimed to investigate the neural heterogeneity of DD using case studies with functional near-infrared spectroscopy (fNIRS). A total of 54 aged 6-7 years old of children participated in this study, comprising two comprehensive cognitive assessments, an 8-minute resting state, and an 8-minute one-digit addition task. Nine children met the criteria of DD and scored at or below 85 (i.e., the 16th percentile) on the Mathematics or Math Fluency subtest of the Wechsler Individual Achievement Test, Third Edition (WIAT-III) (both subtest scores were 90 and below). The remaining 45 children formed the typically developing (TD) group. Resting-state data and brain activation in the inferior frontal gyrus (IFG), superior frontal gyrus (SFG), and intraparietal sulcus (IPS) were collected for comparison between each case and the TD group. Graph theory was used to analyze the brain network under the resting state. This theory represents the brain network as a set of nodes--brain regions—and edges—pairwise interactions across areas to reveal the architectural organizations of the nervous network. Next, a single-case methodology developed by Crawford et al. in 2010 was used to compare each case’s brain network indicators and brain activation against 45 TD children’s average data. Results showed that three out of the nine DD children displayed significant deviation from TD children’s brain indicators. Case 1 had inefficient nodal network properties. Case 2 showed inefficient brain network properties and weaker activation in the IFG and IPS areas. Case 3 displayed inefficient brain network properties with no differences in activation patterns. As a rise above, the present study was able to distill differences in architectural organizations and brain activation of DD vis-à-vis TD children using fNIRS and single-case methodology. Although DD is regarded as a heterogeneous learning difficulty, it is noted that all three cases showed lower nodal efficiency in the brain network, which may be one of the neural sources of DD. Importantly, although the current “brain norm” established for the 45 children is tentative, the results from this study provide insights not only for future work in “developmental brain norm” with reliable brain indicators but so too the viability of single-case methodology, which could be used to detect differential brain indicators of DD children for early detection and interventions.

Keywords: brain activation, brain network, case study, developmental dyscalculia, functional near-infrared spectroscopy, graph theory, neural heterogeneity

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3802 Probabilistic Seismic Loss Assessment of Reinforced Concrete (RC) Frame Buildings Pre- and Post-Rehabilitation

Authors: A. Flora, A. Di Lascio, D. Cardone, G. Gesualdi, G. Perrone

Abstract:

This paper considers the seismic assessment and retrofit of a pilotis-type RC frame building, which was designed for gravity loads only, prior to the introduction of seismic design provisions. Pilotis-type RC frame buildings, featuring an uniform infill throughout the height and an open ground floor, were, and still are, quite popular all over the world, as they offer large open areas very suitable for retail space at the ground floor. These architectural advantages, however, are of detriment to the building seismic behavior, as they can determine a soft-storey collapse mechanism. Extensive numerical analyses are carried out to quantify and benchmark the performance of the selected building, both in terms of overall collapse capacity and expected losses. Alternative retrofit strategies are then examined, including: (i) steel jacketing of RC columns and beam-column joints, (ii) steel bracing and (iv) seismic isolation. The Expected Annual Loss (EAL) of the selected case-study building, pre- and post-rehabilitation, is evaluated, following a probabilistic approach. The breakeven time of each solution is computed, comparing the initial cost of the retrofit intervention with expected benefit in terms of EAL reduction.

Keywords: expected annual loss, reinforced concrete buildings, seismic loss assessment, seismic retrofit

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3801 Time/Temperature-Dependent Finite Element Model of Laminated Glass Beams

Authors: Alena Zemanová, Jan Zeman, Michal Šejnoha

Abstract:

The polymer foil used for manufacturing of laminated glass members behaves in a viscoelastic manner with temperature dependence. This contribution aims at incorporating the time/temperature-dependent behavior of interlayer to our earlier elastic finite element model for laminated glass beams. The model is based on a refined beam theory: each layer behaves according to the finite-strain shear deformable formulation by Reissner and the adjacent layers are connected via the Lagrange multipliers ensuring the inter-layer compatibility of a laminated unit. The time/temperature-dependent behavior of the interlayer is accounted for by the generalized Maxwell model and by the time-temperature superposition principle due to the Williams, Landel, and Ferry. The resulting system is solved by the Newton method with consistent linearization and the viscoelastic response is determined incrementally by the exponential algorithm. By comparing the model predictions against available experimental data, we demonstrate that the proposed formulation is reliable and accurately reproduces the behavior of the laminated glass units.

Keywords: finite element method, finite-strain Reissner model, Lagrange multipliers, generalized Maxwell model, laminated glass, Newton method, Williams-Landel-Ferry equation

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3800 Spatial Differentiation of Elderly Care Facilities in Mountainous Cities: A Case Study of Chongqing

Authors: Xuan Zhao, Wen Jiang

Abstract:

In this study, a web crawler was used to collect POI sample data from 38 districts and counties of Chongqing in 2022, and ArcGIS was combined to coordinate and projection conversion and realize data visualization. Nuclear density analysis and spatial correlation analysis were used to explore the spatial distribution characteristics of elderly care facilities in Chongqing, and K mean cluster analysis was carried out with GeoDa to study the spatial concentration degree of elderly care resources in 38 districts and counties. Finally, the driving force of spatial differentiation of elderly care facilities in various districts and counties of Chongqing is studied by using the method of geographic detector. The results show that: (1) in terms of spatial distribution structure, the distribution of elderly care facilities in Chongqing is unbalanced, showing a distribution pattern of ‘large dispersion and small agglomeration’ and the asymmetric pattern of ‘west dense and east sparse, north dense and south sparse’ is prominent. (2) In terms of the spatial matching between elderly care resources and the elderly population, there is a weak coordination between the input of elderly care resources and the distribution of the elderly population at the county level in Chongqing. (3) The analysis of the results of the geographical detector shows that the single factor influence is mainly the number of elderly population, public financial revenue and district and county GDP. The high single factor influence is mainly caused by the elderly population, public financial income, and district and county GDP. The influence of each influence factor on the spatial distribution of elderly care facilities is not simply superimposed but has a nonlinear enhancement effect or double factor enhancement. It is necessary to strengthen the synergistic effect of two factors and promote the synergistic effect of multiple factors.

Keywords: aging, elderly care facilities, spatial differentiation, geographical detector, driving force analysis, Mountain city

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3799 Characterization of Mg/Sc System for X-Ray Spectroscopy in the Water Window Range

Authors: Hina Verma, Karine Le Guen, Mohammed H. Modi, Rajnish Dhawan, Philippe Jonnard

Abstract:

Periodic multilayer mirrors have potential application as optical components in X-ray microscopy, particularly working in the water window region. The water window range, located between the absorption edges of carbon (285 eV) and oxygen (530eV), along with the presence of nitrogen K absorption edge (395 eV), makes it a powerful method for imaging biological samples due to the natural optical contrast between water and carbon. We characterized bilayer, trilayer, quadrilayer, and multilayer systems of Mg/Sc with ZrC thin layers introduced as a barrier layer and capping layer prepared by ion beam sputtering. The introduction of ZrC as a barrier layer is expected to improve the structure of the Mg/Sc system. The ZrC capping layer also prevents the stack from oxidation. The structural analysis of the Mg/Sc systems was carried out by using grazing incidence X-ray reflectivity (GIXRR) to obtain non-destructively a first description of the structural parameters, thickness, roughness, and density of the layers. Resonant soft X-ray reflectivity measurements in the vicinity of Sc L-absorption edge were performed to investigate and quantify the atomic distribution of deposited layers. Near absorption edge, the atomic scattering factor of an element changes sharply depending on its chemical environment inside the structure.

Keywords: buried interfaces, resonant soft X-ray reflectivity, X-ray optics, X-ray reflectivity

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3798 Application of Building Information Modelling In Analysing IGBC® Ratings (Sustainability Analyses)

Authors: Lokesh Harshe

Abstract:

The building construction sector is using 36% of global energy consumption with 39% of CO₂ emission. Professionals in the Built Environment Sector have long been aware of the industry’s contribution towards CO₂ emissions and are now moving towards more sustainable practices. As a result of this, many organizations have introduced rating systems to address the issue of global warming in the construction sector by ranking construction projects based on sustainability parameters. The pre-construction phase of any building project is the most essential time to make decisions for addressing the sustainability aspects. Traditionally, it is very difficult to collect data from different stakeholders and bring it together to form a decision based on factual data to perform sustainability analyses in the pre-construction phase. Building Information Modelling (BIM) is the solution where one single model is the result of the collaborative approach of BIM processes where all the information is shared, extracted, communicated, and stored on a single platform that everyone can access and make decisions based on real-time data. The focus of this research is on the Indian Green Rating System IGBC® with the objective of understanding IGBC® requirements and developing a framework to create the relationship between the rating processes and BIM. A Hypothetical (Architectural) model of a hostel building is developed using AutoCAD 2019 & Revit Arch. 2019, where the framework is applied to generate results on sustainability analysis using Green Building Studio (GBS) and Revit Add-ins. The results of any sustainability analysis are generated within a fraction of a minute, which is very quick in comparison with traditional sustainability analysis. This may save a considerable amount of time as well as cost. The future scope is to integrate Architectural, Structural, and MEP Models to perform accurate sustainability analyses with inputs from industry professionals working on real-life Green BIM projects.

Keywords: sustainability analyses, BIM, green rating systems, IGBC®, LEED

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3797 Effects of Different Thermal Processing Routes and Their Parameters on the Formation of Voids in PA6 Bonded Aluminum Joints

Authors: Muhammad Irfan, Guillermo Requena, Jan Haubrich

Abstract:

Adhesively bonded aluminum joints are common in automotive and aircraft industries and are one of the enablers of lightweight construction to minimize the carbon emissions during transportation for a sustainable life. This study is focused on the effects of two thermal processing routes, i.e., by direct and induction heating, and their parameters on void formation in PA6 bonded aluminum EN-AW6082 joints. The joints were characterized microanalytically as well as by lap shear experiments. The aging resistance of the joints was studied by accelerated aging tests at 80°C hot water. It was found that the processing of single lap joints by direct heating in a convection oven causes the formation of a large number of voids in the bond line. The formation of voids in the convection oven was due to longer processing times and was independent of any surface pretreatments of the metal as well as the processing temperature. However, when processing at low temperatures, a large number of small-sized voids were observed under the optical microscope, and they were larger in size but reduced in numbers at higher temperatures. An induction heating process was developed, which not only successfully reduced or eliminated the voids in PA6 bonded joints but also reduced the processing times for joining significantly. Consistent with the trend in direct heating, longer processing times and higher temperatures in induction heating also led to an increased formation of voids in the bond line. Subsequent single lap shear tests revealed that the increasing void contents led to a 21% reduction in lap shear strengths (i.e., from ~47 MPa for induction heating to ~37 MPa for direct heating). Also, there was a 17% reduction in lap shear strengths when the consolidation temperature was raised from 220˚C to 300˚C during induction heating. However, below a certain threshold of void contents, there was no observable effect on the lap shear strengths as well as on hydrothermal aging resistance of the joints consolidated by the induction heating process.

Keywords: adhesive, aluminium, convection oven, induction heating, mechanical properties, nylon6 (PA6), pretreatment, void

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3796 Comparative Study of sLASER and PRESS Techniques in Magnetic Resonance Spectroscopy of Normal Brain

Authors: Shin Ku Kim, Yun Ah Oh, Eun Hee Seo, Chang Min Dae, Yun Jung Bae

Abstract:

Objectives: The commonly used PRESS technique in magnetic resonance spectroscopy (MRS) has a limitation of incomplete water suppression. The recently developed sLASER technique is known for its improved effectiveness in suppressing water signal. However, no prior study has compared both sequences in a normal human brain. In this study, we firstly aimed to compare the performances of both techniques in brain MRS. Materials and methods: From January 2023 to July 2023, thirty healthy participants (mean age 38 years, 17 male, 13 female) without underlying neurological diseases were enrolled in this study. All participants underwent single-voxel MRS using both PRESS and sLASER techniques on 3T MRI. Two regions-of-interest were allocated in the left medial thalamus and left parietal white matter (WM) by a single reader. The SpectroView Analysis (SW5, Philips, Netherlands) provided automatic measurements, including signal-to-noise ratio (SNR) and peak_height of water, N-acetylaspartate (NAA)-water/Choline (Cho)-water/Creatine (Cr)-water ratios, and NAA-Cr/Cho-Cr ratios. The measurements from PRESS and sLASER techniques were compared using paired T-tests and Bland-Altman methods, and the variability was assessed using coefficients of variation (CV). Results: SNR and peak_heights of the water were significantly lower with sLASER compared to PRESS (left medial thalamus, sLASER SNR/peak_height 2092±475/328±85 vs. PRESS 2811±549/440±105); left parietal WM, 5422±1016/872±196 vs. 7152±1305/1150±278; all, P<0.001, respectively). Accordingly, NAA-water/Cho-water/Cr-water ratios and NAA-Cr/Cho-Cr ratios were significantly higher with sLASER than with PRESS (all, P< 0.001, respectively). The variabilities of NAA-water/Cho-water/Cr-water ratios and Cho-Cr ratio in the left medial thalamus were lower with sLASER than with PRESS (CV, sLASER vs. PRESS, 19.9 vs. 58.1/19.8 vs. 54.7/20.5 vs. 43.9 and 11.5 vs. 16.2) Conclusion: The sLASER technique demonstrated enhanced background water suppression, resulting in increased signals and reduced variability in brain metabolite measurements of MRS. Therefore, sLASER could offer a more precise and stable method for identifying brain metabolites.

Keywords: Magnetic resonance spectroscopy, Brain, sLASER, PRESS

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3795 Geometric Optimisation of Piezoelectric Fan Arrays for Low Energy Cooling

Authors: Alastair Hales, Xi Jiang

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Numerical methods are used to evaluate the operation of confined face-to-face piezoelectric fan arrays as pitch, P, between the blades is varied. Both in-phase and counter-phase oscillation are considered. A piezoelectric fan consists of a fan blade, which is clamped at one end, and an extremely low powered actuator. This drives the blade tip’s oscillation at its first natural frequency. Sufficient blade tip speed, created by the high oscillation frequency and amplitude, is required to induce vortices and downstream volume flow in the surrounding air. A single piezoelectric fan may provide the ideal solution for low powered hot spot cooling in an electronic device, but is unable to induce sufficient downstream airflow to replace a conventional air mover, such as a convection fan, in power electronics. Piezoelectric fan arrays, which are assemblies including multiple fan blades usually in face-to-face orientation, must be developed to widen the field of feasible applications for the technology. The potential energy saving is significant, with a 50% power demand reduction compared to convection fans even in an unoptimised state. A numerical model of a typical piezoelectric fan blade is derived and validated against experimental data. Numerical error is found to be 5.4% and 9.8% using two data comparison methods. The model is used to explore the variation of pitch as a function of amplitude, A, for a confined two-blade piezoelectric fan array in face-to-face orientation, with the blades oscillating both in-phase and counter-phase. It has been reported that in-phase oscillation is optimal for generating maximum downstream velocity and flow rate in unconfined conditions, due at least in part to the beneficial coupling between the adjacent blades that leads to an increased oscillation amplitude. The present model demonstrates that confinement has a significant detrimental effect on in-phase oscillation. Even at low pitch, counter-phase oscillation produces enhanced downstream air velocities and flow rates. Downstream air velocity from counter-phase oscillation can be maximally enhanced, relative to that generated from a single blade, by 17.7% at P = 8A. Flow rate enhancement at the same pitch is found to be 18.6%. By comparison, in-phase oscillation at the same pitch outputs 23.9% and 24.8% reductions in peak downstream air velocity and flow rate, relative to that generated from a single blade. This optimal pitch, equivalent to those reported in the literature, suggests that counter-phase oscillation is less affected by confinement. The optimal pitch for generating bulk airflow from counter-phase oscillation is large, P > 16A, due to the small but significant downstream velocity across the span between adjacent blades. However, by considering design in a confined space, counterphase pitch should be minimised to maximise the bulk airflow generated from a certain cross-sectional area within a channel flow application. Quantitative values are found to deviate to a small degree as other geometric and operational parameters are varied, but the established relationships are maintained.

Keywords: piezoelectric fans, low energy cooling, power electronics, computational fluid dynamics

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3794 An Investigation on the Pulse Electrodeposition of Ni-TiO2/TiO2 Multilayer Structures

Authors: S. Mohajeri

Abstract:

Electrocodeposition of Ni-TiO2 nanocomposite single layers and Ni-TiO2/TiO2 multilayers from Watts bath containing TiO2 sol was carried out on copper substrate. Pulse plating and pulse reverse plating techniques were applied to facilitate higher incorporations of TiO2 nanoparticles in Ni-TiO2 nanocomposite single layers, and the results revealed that by prolongation of the current-off durations and the anodic cycles, deposits containing 11.58 wt.% and 13.16 wt.% TiO2 were produced, respectively. Multilayer coatings which consisted of Ni-TiO2 and TiO2-rich layers were deposited by pulse potential deposition through limiting the nickel deposition by diffusion control mechanism. The TiO2-rich layers thickness and accordingly, the content of TiO2 reinforcement reached 104 nm and 18.47 wt.%, respectively in the optimum condition. The phase structure and surface morphology of the nanocomposite coatings were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The cross sectional morphology and line scans of the layers were studied by field emission scanning electron microscopy (FESEM). It was confirmed that the preferred orientations and the crystallite sizes of nickel matrix were influenced by the deposition technique parameters, and higher contents of codeposited TiO2 nanoparticles refined the microstructure. The corrosion behavior of the coatings in 1M NaCl and 0.5M H2SO4 electrolytes were compared by means of potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) techniques. Increase of corrosion resistance and the passivation tendency were favored by TiO2 incorporation, while the degree of passivation declined as embedded particles disturbed the continuity of passive layer. The role of TiO2 incorporation on the improvement of mechanical properties including hardness, elasticity, scratch resistance and friction coefficient was investigated by the means of atomic force microscopy (AFM). Hydrophilicity and wettability of the composite coatings were investigated under UV illumination, and the water contact angle of the multilayer was reduced to 7.23° after 1 hour of UV irradiation.

Keywords: electrodeposition, hydrophilicity, multilayer, pulse-plating

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3793 Practical Design Procedures of 3D Reinforced Concrete Shear Wall-Frame Structure Based on Structural Optimization Method

Authors: H. Nikzad, S. Yoshitomi

Abstract:

This study investigates and develops the structural optimization method. The effect of size constraints on practical solution of reinforced concrete (RC) building structure with shear wall is proposed. Cross-sections of beam and column, and thickness of shear wall are considered as design variables. The objective function to be minimized is total cost of the structure by using a simple and efficient automated MATLAB platform structural optimization methodology. With modification of mathematical formulations, the result is compared with optimal solution without size constraints. The most suitable combination of section sizes is selected as for the final design application based on linear static analysis. The findings of this study show that defining higher value of upper bound of sectional sizes significantly affects optimal solution, and defining of size constraints play a vital role in finding of global and practical solution during optimization procedures. The result and effectiveness of proposed method confirm the ability and efficiency of optimal solutions for 3D RC shear wall-frame structure.

Keywords: structural optimization, linear static analysis, ETABS, MATLAB, RC shear wall-frame structures

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3792 Application of GA Optimization in Analysis of Variable Stiffness Composites

Authors: Nasim Fallahi, Erasmo Carrera, Alfonso Pagani

Abstract:

Variable angle tow describes the fibres which are curvilinearly steered in a composite lamina. Significantly, stiffness tailoring freedom of VAT composite laminate can be enlarged and enabled. Composite structures with curvilinear fibres have been shown to improve the buckling load carrying capability in contrast with the straight laminate composites. However, the optimal design and analysis of VAT are faced with high computational efforts due to the increasing number of variables. In this article, an efficient optimum solution has been used in combination with 1D Carrera’s Unified Formulation (CUF) to investigate the optimum fibre orientation angles for buckling analysis. The particular emphasis is on the LE-based CUF models, which provide a Lagrange Expansions to address a layerwise description of the problem unknowns. The first critical buckling load has been considered under simply supported boundary conditions. Special attention is lead to the sensitivity of buckling load corresponding to the fibre orientation angle in comparison with the results which obtain through the Genetic Algorithm (GA) optimization frame and then Artificial Neural Network (ANN) is applied to investigate the accuracy of the optimized model. As a result, numerical CUF approach with an optimal solution demonstrates the robustness and computational efficiency of proposed optimum methodology.

Keywords: beam structures, layerwise, optimization, variable stiffness

Procedia PDF Downloads 132
3791 Synthesis and Characterization of Graphene Composites with Application for Sustainable Energy

Authors: Daniel F. Sava, Anton Ficai, Bogdan S. Vasile, Georgeta Voicu, Ecaterina Andronescu

Abstract:

The energy crisis and environmental contamination are very serious problems, therefore searching for better and sustainable renewable energy is a must. It is predicted that the global energy demand will double until 2050. Solar water splitting and photocatalysis are considered as one of the solutions to these issues. The use of oxide semiconductors for solar water splitting and photocatalysis started in 1972 with the experiments of Fujishima and Honda on TiO2 electrodes. Since then, the evolution of nanoscience and characterization methods leads to a better control of size, shape and properties of materials. Although the past decade advancements are astonishing, for these applications the properties have to be controlled at a much finer level, allowing the control of charge-carrier lives, energy level positions, charge trapping centers, etc. Graphene has attracted a lot of attention, since its discovery in 2004, due to the excellent electrical, optical, mechanical and thermal properties that it possesses. These properties make it an ideal support for photocatalysts, thus graphene composites with oxide semiconductors are of great interest. We present in this work the synthesis and characterization of graphene-related materials and oxide semiconductors and their different composites. These materials can be used in constructing devices for different applications (batteries, water splitting devices, solar cells, etc), thus showing their application flexibility. The synthesized materials are different morphologies and sizes of TiO2, ZnO and Fe2O3 that are obtained through hydrothermal, sol-gel methods and graphene oxide which is synthesized through a modified Hummer method and reduced with different agents. Graphene oxide and the reduced form could also be used as a single material for transparent conductive films. The obtained single materials and composites were characterized through several methods: XRD, SEM, TEM, IR spectroscopy, RAMAN, XPS and BET adsorption/desorption isotherms. From the results, we see the variation of the properties with the variation of synthesis parameters, size and morphology of the particles.

Keywords: composites, graphene, hydrothermal, renewable energy

Procedia PDF Downloads 492
3790 Comparison and Effectiveness of Cranial Electrical Stimulation Treatment, Brain Training and Their Combination on Language and Verbal Fluency of Patients with Mild Cognitive Impairment: A Single Subject Design

Authors: Firoozeh Ghazanfari, Kourosh Amraei, Parisa Poorabadi

Abstract:

Mild cognitive impairment is one of the neurocognitive disorders that go beyond age-related decline in cognitive functions, but in fact, it is not so severe which affects daily activities. This study aimed to investigate and compare the effectiveness of treatment with cranial electrical stimulation, brain training and their double combination on the language and verbal fluency of the elderly with mild cognitive impairment. This is a single-subject method with comparative intervention designs. Four patients with a definitive diagnosis of mild cognitive impairment by a psychiatrist were selected via purposive and convenience sampling method. Addenbrooke's Cognitive Examination Scale (2017) was used to assess language and verbal fluency. Two groups were formed with different order of cranial electrical stimulation treatment, brain training by pencil and paper method and their double combination, and two patients were randomly replaced in each group. The arrangement of the first group included cranial electrical stimulation, brain training, double combination and the second group included double combination, cranial electrical stimulation and brain training, respectively. Treatment plan included: A1, B, A2, C, A3, D, A4, where electrical stimulation treatment was given in ten 30-minutes sessions (5 mA and frequency of 0.5-500 Hz) and brain training in ten 30-minutes sessions. Each baseline lasted four weeks. Patients in first group who first received cranial electrical stimulation treatment showed a higher percentage of improvement in the language and verbal fluency subscale of Addenbrooke's Cognitive Examination in comparison to patients of the second group. Based on the results, it seems that cranial electrical stimulation with its effect on neurotransmitters and brain blood flow, especially in the brain stem, may prepare the brain at the neurochemical and molecular level for a better effectiveness of brain training at the behavioral level, and the selective treatment of electrical stimulation solitude in the first place may be more effective than combining it with paper-pencil brain training.

Keywords: cranial electrical stimulation, treatment, brain training, verbal fluency, cognitive impairment

Procedia PDF Downloads 83
3789 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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3788 Single and Combined Effects of Diclofenac and Ibuprofen on Daphnia Magna and Some Phytoplankton Species

Authors: Ramatu I. Sha’aba, Mathias A. Chia, Abdullahi B. Alhassan, Yisa A. Gana, Ibrahim M. Gadzama

Abstract:

Globally, Diclofenac (DLC) and Ibuprofen (IBU) are the most prescribed drugs due to their antipyretic and analgesic properties. They are, however, highly toxic at elevated doses, with the involvement of an already described oxidative stress pathway. As a result, there is rising concern about the ecological fate of analgesics on non-target organisms such as Daphnia magna and Phytoplankton species. Phytoplankton is a crucial component of the aquatic ecosystem that serves as the primary producer at the base of the food chain. However, the increasing presence and levels of micropollutants such as these analgesics can disrupt their community structure, dynamics, and ecosystem functions. This study presents a comprehensive series of the physiology, antioxidant response, immobilization, and risk assessment of Diclofenac and Ibuprofen’s effects on Daphnia magna and the Phytoplankton community using a laboratory approach. The effect of DLC and IBU at 27.16 µg/L and 20.89 µg/L, respectively, for a single exposure and 22.39 µg/L for combined exposure of DLC and IBU for the experimental setup. The antioxidant response increased with increasing levels of stress. The highest stressor to the organism was 1000 µg/L of DLC and 10,000 µg/L of IBU. Peroxidase and glutathione -S-transferase activity was higher for Diclofenac + Ibuprofen. The study showed 60% and 70% immobilization of the organism at 1000 g L-1 of DLC and IBU. The two drugs and their combinations adversely impacted Phytoplankton biomass with increased exposure time. However, combining the drugs resulted in more significant adverse effects on physiological and pigment content parameters. The risk assessment calculation for the risk quotient and toxic unit of the analgesic reveals from this study was RQ Diclofenac = 8.41, TU Diclofenac = 3.68, and RQ Ibuprofen = 718.05 and TU Ibuprofen = 487.70. Hence, these findings demonstrate that the current exposure concentrations of Diclofenac and Ibuprofen can immobilize D. magna. This study shows the dangers of multiple drugs in the aquatic environment because their combinations could have additive effects on the structure and functions of Phytoplankton and are capable of immobilizing D. magna.

Keywords: algae, analgesic drug, daphnia magna, toxicity

Procedia PDF Downloads 69
3787 Applying Element Free Galerkin Method on Beam and Plate

Authors: Mahdad M’hamed, Belaidi Idir

Abstract:

This paper develops a meshless approach, called Element Free Galerkin (EFG) method, which is based on the weak form Moving Least Squares (MLS) of the partial differential governing equations and employs the interpolation to construct the meshless shape functions. The variation weak form is used in the EFG where the trial and test functions are approximated bye the MLS approximation. Since the shape functions constructed by this discretization have the weight function property based on the randomly distributed points, the essential boundary conditions can be implemented easily. The local weak form of the partial differential governing equations is obtained by the weighted residual method within the simple local quadrature domain. The spline function with high continuity is used as the weight function. The presently developed EFG method is a truly meshless method, as it does not require the mesh, either for the construction of the shape functions, or for the integration of the local weak form. Several numerical examples of two-dimensional static structural analysis are presented to illustrate the performance of the present EFG method. They show that the EFG method is highly efficient for the implementation and highly accurate for the computation. The present method is used to analyze the static deflection of beams and plate hole

Keywords: numerical computation, element-free Galerkin (EFG), moving least squares (MLS), meshless methods

Procedia PDF Downloads 279
3786 Modelling Causal Effects from Complex Longitudinal Data via Point Effects of Treatments

Authors: Xiaoqin Wang, Li Yin

Abstract:

Background and purpose: In many practices, one estimates causal effects arising from a complex stochastic process, where a sequence of treatments are assigned to influence a certain outcome of interest, and there exist time-dependent covariates between treatments. When covariates are plentiful and/or continuous, statistical modeling is needed to reduce the huge dimensionality of the problem and allow for the estimation of causal effects. Recently, Wang and Yin (Annals of statistics, 2020) derived a new general formula, which expresses these causal effects in terms of the point effects of treatments in single-point causal inference. As a result, it is possible to conduct the modeling via point effects. The purpose of the work is to study the modeling of these causal effects via point effects. Challenges and solutions: The time-dependent covariates often have influences from earlier treatments as well as on subsequent treatments. Consequently, the standard parameters – i.e., the mean of the outcome given all treatments and covariates-- are essentially all different (null paradox). Furthermore, the dimension of the parameters is huge (curse of dimensionality). Therefore, it can be difficult to conduct the modeling in terms of standard parameters. Instead of standard parameters, we have use point effects of treatments to develop likelihood-based parametric approach to the modeling of these causal effects and are able to model the causal effects of a sequence of treatments by modeling a small number of point effects of individual treatment Achievements: We are able to conduct the modeling of the causal effects from a sequence of treatments in the familiar framework of single-point causal inference. The simulation shows that our method achieves not only an unbiased estimate for the causal effect but also the nominal level of type I error and a low level of type II error for the hypothesis testing. We have applied this method to a longitudinal study of COVID-19 mortality among Scandinavian countries and found that the Swedish approach performed far worse than the other countries' approach for COVID-19 mortality and the poor performance was largely due to its early measure during the initial period of the pandemic.

Keywords: causal effect, point effect, statistical modelling, sequential causal inference

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3785 Influence of P-Y Curves on Buckling Capacity of Pile Foundation

Authors: Praveen Huded, Suresh Dash

Abstract:

Pile foundations are one of the most preferred deep foundation system for high rise or heavily loaded structures. In many instances, the failure of the pile founded structures in liquefiable soils had been observed even in many recent earthquakes. Recent centrifuge and shake table experiments on two layered soil system have credibly shown that failure of pile foundation can occur because of buckling, as the pile behaves as an unsupported slender structural element once the surrounding soil liquefies. However the buckling capacity depends on largely on the depth of soil liquefied and its residual strength. Hence it is essential to check the pile against the possible buckling failure. Beam on non-linear Winkler Foundation is one of the efficient method to model the pile-soil behavior in liquefiable soil. The pile-soil interaction is modelled through p-y springs, different author have proposed different types of p-y curves for the liquefiable soil. In the present paper the influence two such p-y curves on the buckling capacity of pile foundation is studied considering initial geometric and non-linear behavior of pile foundation. The proposed method is validated against experimental results. Significant difference in the buckling capacity is observed for the two p-y curves used in the analysis. A parametric study is conducted to understand the influence of pile diameter, pile flexural rigidity, different initial geometric imperfections, and different soil relative densities on buckling capacity of pile foundation.

Keywords: Pile foundation , Liquefaction, Buckling load, non-linear py curve, Opensees

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3784 Static and Dynamic Analysis of Hyperboloidal Helix Having Thin Walled Open and Close Sections

Authors: Merve Ermis, Murat Yılmaz, Nihal Eratlı, Mehmet H. Omurtag

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The static and dynamic analyses of hyperboloidal helix having the closed and the open square box sections are investigated via the mixed finite element formulation based on Timoshenko beam theory. Frenet triad is considered as local coordinate systems for helix geometry. Helix domain is discretized with a two-noded curved element and linear shape functions are used. Each node of the curved element has 12 degrees of freedom, namely, three translations, three rotations, two shear forces, one axial force, two bending moments and one torque. Finite element matrices are derived by using exact nodal values of curvatures and arc length and it is interpolated linearly throughout the element axial length. The torsional moments of inertia for close and open square box sections are obtained by finite element solution of St. Venant torsion formulation. With the proposed method, the torsional rigidity of simply and multiply connected cross-sections can be also calculated in same manner. The influence of the close and the open square box cross-sections on the static and dynamic analyses of hyperboloidal helix is investigated. The benchmark problems are represented for the literature.

Keywords: hyperboloidal helix, squared cross section, thin walled cross section, torsional rigidity

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3783 Comparison and Validation of a dsDNA biomimetic Quality Control Reference for NGS based BRCA CNV analysis versus MLPA

Authors: A. Delimitsou, C. Gouedard, E. Konstanta, A. Koletis, S. Patera, E. Manou, K. Spaho, S. Murray

Abstract:

Background: There remains a lack of International Standard Control Reference materials for Next Generation Sequencing-based approaches or device calibration. We have designed and validated dsDNA biomimetic reference materials for targeted such approaches incorporating proprietary motifs (patent pending) for device/test calibration. They enable internal single-sample calibration, alleviating sample comparisons to pooled historical population-based data assembly or statistical modelling approaches. We have validated such an approach for BRCA Copy Number Variation analytics using iQRS™-CNVSUITE versus Mixed Ligation-dependent Probe Amplification. Methods: Standard BRCA Copy Number Variation analysis was compared between mixed ligation-dependent probe amplification and next generation sequencing using a cohort of 198 breast/ovarian cancer patients. Next generation sequencing based copy number variation analysis of samples spiked with iQRS™ dsDNA biomimetics were analysed using proprietary CNVSUITE software. Mixed ligation-dependent probe amplification analyses were performed on an ABI-3130 Sequencer and analysed with Coffalyser software. Results: Concordance of BRCA – copy number variation events for mixed ligation-dependent probe amplification and CNVSUITE indicated an overall sensitivity of 99.88% and specificity of 100% for iQRS™-CNVSUITE. The negative predictive value of iQRS-CNVSUITE™ for BRCA was 100%, allowing for accurate exclusion of any event. The positive predictive value was 99.88%, with no discrepancy between mixed ligation-dependent probe amplification and iQRS™-CNVSUITE. For device calibration purposes, precision was 100%, spiking of patient DNA demonstrated linearity to 1% (±2.5%) and range from 100 copies. Traditional training was supplemented by predefining the calibrator to sample cut-off (lock-down) for amplicon gain or loss based upon a relative ratio threshold, following training of iQRS™-CNVSUITE using spiked iQRS™ calibrator and control mocks. BRCA copy number variation analysis using iQRS™-CNVSUITE™ was successfully validated and ISO15189 accredited and now enters CE-IVD performance evaluation. Conclusions: The inclusion of a reference control competitor (iQRS™ dsDNA mimetic) to next generation sequencing-based sequencing offers a more robust sample-independent approach for the assessment of copy number variation events compared to mixed ligation-dependent probe amplification. The approach simplifies data analyses, improves independent sample data analyses, and allows for direct comparison to an internal reference control for sample-specific quantification. Our iQRS™ biomimetic reference materials allow for single sample copy number variation analytics and further decentralisation of diagnostics to single patient sample assessment.

Keywords: validation, diagnostics, oncology, copy number variation, reference material, calibration

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