Search results for: repeatability
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 104

Search results for: repeatability

14 Development and Validation of a Rapid Turbidimetric Assay to Determine the Potency of Cefepime Hydrochloride in Powder Injectable Solution

Authors: Danilo F. Rodrigues, Hérida Regina N. Salgado

Abstract:

Introduction: The emergence of resistant microorganisms to a large number of clinically approved antimicrobials has been increasing, which restrict the options for the treatment of bacterial infections. As a strategy, drugs with high antimicrobial activities are in evidence. Stands out a class of antimicrobial, the cephalosporins, having as fourth generation cefepime (CEF) a semi-synthetic product which has activity against various Gram-positive bacteria (e.g. oxacillin resistant Staphylococcus aureus) and Gram-negative (e.g. Pseudomonas aeruginosa) aerobic. There are few studies in the literature regarding the development of microbiological methodologies for the analysis of this antimicrobial, so researches in this area are highly relevant to optimize the analysis of this drug in the industry and ensure the quality of the marketed product. The development of microbiological methods for the analysis of antimicrobials has gained strength in recent years and has been highlighted in relation to physicochemical methods, especially because they make possible to determine the bioactivity of the drug against a microorganism. In this context, the aim of this work was the development and validation of a microbiological method for quantitative analysis of CEF in powder lyophilized for injectable solution by turbidimetric assay. Method: For performing the method, Staphylococcus aureus ATCC 6538 IAL 2082 was used as the test microorganism and the culture medium chosen was the Casoy broth. The test was performed using temperature control (35.0 °C ± 2.0 °C) and incubated for 4 hours in shaker. The readings of the results were made at a wavelength of 530 nm through a spectrophotometer. The turbidimetric microbiological method was validated by determining the following parameters: linearity, precision (repeatability and intermediate precision), accuracy and robustness, according to ICH guidelines. Results and discussion: Among the parameters evaluated for method validation, the linearity showed results suitable for both statistical analyses as the correlation coefficients (r) that went 0.9990 for CEF reference standard and 0.9997 for CEF sample. The precision presented the following values 1.86% (intraday), 0.84% (interday) and 0.71% (between analyst). The accuracy of the method has been proven through the recovery test where the mean value obtained was 99.92%. The robustness was verified by the parameters changing volume of culture medium, brand of culture medium, incubation time in shaker and wavelength. The potency of CEF present in the samples of lyophilized powder for injectable solution was 102.46%. Conclusion: The turbidimetric microbiological method proposed for quantification of CEF in lyophilized powder for solution for injectable showed being fast, linear, precise, accurate and robust, being in accordance with all the requirements, which can be used in routine analysis of quality control in the pharmaceutical industry as an option for microbiological analysis.

Keywords: cefepime hydrochloride, quality control, turbidimetric assay, validation

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13 Influence of Glass Plates Different Boundary Conditions on Human Impact Resistance

Authors: Alberto Sanchidrián, José A. Parra, Jesús Alonso, Julián Pecharromán, Antonia Pacios, Consuelo Huerta

Abstract:

Glass is a commonly used material in building; there is not a unique design solution as plates with a different number of layers and interlayers may be used. In most façades, a security glazing have to be used according to its performance in the impact pendulum. The European Standard EN 12600 establishes an impact test procedure for classification under the point of view of the human security, of flat plates with different thickness, using a pendulum of two tires and 50 kg mass that impacts against the plate from different heights. However, this test does not replicate the actual dimensions and border conditions used in building configurations and so the real stress distribution is not determined with this test. The influence of different boundary conditions, as the ones employed in construction sites, is not well taking into account when testing the behaviour of safety glazing and there is not a detailed procedure and criteria to determinate the glass resistance against human impact. To reproduce the actual boundary conditions on site, when needed, the pendulum test is arranged to be used "in situ", with no account for load control, stiffness, and without a standard procedure. Fracture stress of small and large glass plates fit a Weibull distribution with quite a big dispersion so conservative values are adopted for admissible fracture stress under static loads. In fact, test performed for human impact gives a fracture strength two or three times higher, and many times without a total fracture of the glass plate. Newest standards, as for example DIN 18008-4, states for an admissible fracture stress 2.5 times higher than the ones used for static and wing loads. Now two working areas are open: a) to define a standard for the ‘in situ’ test; b) to prepare a laboratory procedure that allows testing with more real stress distribution. To work on both research lines a laboratory that allows to test medium size specimens with different border conditions, has been developed. A special steel frame allows reproducing the stiffness of the glass support substructure, including a rigid condition used as reference. The dynamic behaviour of the glass plate and its support substructure have been characterized with finite elements models updated with modal tests results. In addition, a new portable impact machine is being used to get enough force and direction control during the impact test. Impact based on 100 J is used. To avoid problems with broken glass plates, the test have been done using an aluminium plate of 1000 mm x 700 mm size and 10 mm thickness supported on four sides; three different substructure stiffness conditions are used. A detailed control of the dynamic stiffness and the behaviour of the plate is done with modal tests. Repeatability of the test and reproducibility of results prove that procedure to control both, stiffness of the plate and the impact level, is necessary.

Keywords: glass plates, human impact test, modal test, plate boundary conditions

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12 A Web and Cloud-Based Measurement System Analysis Tool for the Automotive Industry

Authors: C. A. Barros, Ana P. Barroso

Abstract:

Any industrial company needs to determine the amount of variation that exists within its measurement process and guarantee the reliability of their data, studying the performance of their measurement system, in terms of linearity, bias, repeatability and reproducibility and stability. This issue is critical for automotive industry suppliers, who are required to be certified by the 16949:2016 standard (replaces the ISO/TS 16949) of International Automotive Task Force, defining the requirements of a quality management system for companies in the automotive industry. Measurement System Analysis (MSA) is one of the mandatory tools. Frequently, the measurement system in companies is not connected to the equipment and do not incorporate the methods proposed by the Automotive Industry Action Group (AIAG). To address these constraints, an R&D project is in progress, whose objective is to develop a web and cloud-based MSA tool. This MSA tool incorporates Industry 4.0 concepts, such as, Internet of Things (IoT) protocols to assure the connection with the measuring equipment, cloud computing, artificial intelligence, statistical tools, and advanced mathematical algorithms. This paper presents the preliminary findings of the project. The web and cloud-based MSA tool is innovative because it implements all statistical tests proposed in the MSA-4 reference manual from AIAG as well as other emerging methods and techniques. As it is integrated with the measuring devices, it reduces the manual input of data and therefore the errors. The tool ensures traceability of all performed tests and can be used in quality laboratories and in the production lines. Besides, it monitors MSAs over time, allowing both the analysis of deviations from the variation of the measurements performed and the management of measurement equipment and calibrations. To develop the MSA tool a ten-step approach was implemented. Firstly, it was performed a benchmarking analysis of the current competitors and commercial solutions linked to MSA, concerning Industry 4.0 paradigm. Next, an analysis of the size of the target market for the MSA tool was done. Afterwards, data flow and traceability requirements were analysed in order to implement an IoT data network that interconnects with the equipment, preferably via wireless. The MSA web solution was designed under UI/UX principles and an API in python language was developed to perform the algorithms and the statistical analysis. Continuous validation of the tool by companies is being performed to assure real time management of the ‘big data’. The main results of this R&D project are: MSA Tool, web and cloud-based; Python API; New Algorithms to the market; and Style Guide of UI/UX of the tool. The MSA tool proposed adds value to the state of the art as it ensures an effective response to the new challenges of measurement systems, which are increasingly critical in production processes. Although the automotive industry has triggered the development of this innovative MSA tool, other industries would also benefit from it. Currently, companies from molds and plastics, chemical and food industry are already validating it.

Keywords: automotive Industry, industry 4.0, Internet of Things, IATF 16949:2016, measurement system analysis

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11 Numerical Analyses of Dynamics of Deployment of PW-Sat2 Deorbit Sail Compared with Results of Experiment under Micro-Gravity and Low Pressure Conditions

Authors: P. Brunne, K. Ciechowska, K. Gajc, K. Gawin, M. Gawin, M. Kania, J. Kindracki, Z. Kusznierewicz, D. Pączkowska, F. Perczyński, K. Pilarski, D. Rafało, E. Ryszawa, M. Sobiecki, I. Uwarowa

Abstract:

Big amount of space debris constitutes nowadays a real thread for operating space crafts; therefore the main purpose of PW-Sat2’ team was to create a system that could help cleanse the Earth’s orbit after each small satellites’ mission. After 4 years of development, the motorless, low energy consumption and low weight system has been created. During series of tests, the system has shown high reliable efficiency. The PW-Sat2’s deorbit system is a square-shaped sail which covers an area of 4m². The sail surface is made of 6 μm aluminized Mylar film which is stretched across 4 diagonally placed arms, each consisting of two C-shaped flat springs and enveloped in Mylar sleeves. The sail is coiled using a special, custom designed folding stand that provides automation and repeatability of the sail unwinding tests and placed in a container with inner diameter of 85 mm. In the final configuration the deorbit system weights ca. 600 g and occupies 0.6U (in accordance with CubeSat standard). The sail’s releasing system requires minimal amount of power based on thermal knife that burns out the Dyneema wire, which holds the system before deployment. The Sail is being pushed out of the container within a safe distance (20 cm away) from the satellite. The energy for the deployment is completely assured by coiled C-shaped flat springs, which during the release, unfold the sail surface. To avoid dynamic effects on the satellite’s structure, there is the rotational link between the sail and satellite’s main body. To obtain complete knowledge about complex dynamics of the deployment, a number of experiments have been performed in varied environments. The numerical model of the dynamics of the Sail’s deployment has been built and is still under continuous development. Currently, the integration of the flight model and Deorbit Sail is performed. The launch is scheduled for February 2018. At the same time, in cooperation with United Nations Office for Outer Space Affairs, sail models and requested facilities are being prepared for the sail deployment experiment under micro-gravity and low pressure conditions at Bremen Drop Tower, Germany. Results of those tests will provide an ultimate and wide knowledge about deployment in space environment to which system will be exposed during its mission. Outcomes of the numerical model and tests will be compared afterwards and will help the team in building a reliable and correct model of a very complex phenomenon of deployment of 4 c-shaped flat springs with surface attached. The verified model could be used inter alia to investigate if the PW-Sat2’s sail is scalable and how far is it possible to go with enlarging when creating systems for bigger satellites.

Keywords: cubesat, deorbitation, sail, space, debris

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10 Diversification of Productivity of the Oxfordian Subtidal Carbonate Factory in the Holy Cross Mountains

Authors: Radoslaw Lukasz Staniszewski

Abstract:

The aim of the research was to verify lateral extent and thickness variability of individual limestone layers within early-Jurassic medium- and thick-bedded limestone interbedded with marlstones. Location: The main research area is located in the south-central part of Poland in the south-western part of Permo-Mesozoic margin of the Holy Cross Mountains. It includes outcroppings located on the line between Mieczyn and Wola Morawicka. The analyses were carried out on six profiles (Mieczyn, Gniezdziska, Tokarnia, Wola Morawicka, Morawica and Wolica) representing three early-Jurassic links: Jasna Gora layers, grey limestone, Morawica limestone. Additionally, an attempt was made to correlate the thickness sequence from the Holy Cross Mountains to the profile from the quarry in Zawodzie located 3 km east of Czestochowa. The distance between the outermost profiles is 122 km in a straight line. Methodology of research: The Callovian-Oxfordian border was taken as the reference point during the correlation. At the same time, ammonite-based stratigraphic studies were carried out, which allowed to identify individual packages in the remote outcroppings. The analysis of data collected during fieldwork was mainly devoted to the correlation of thickness sequences of limestone layers in subsequent profiles. In order to check the objectivity of the subsequent outcroppings, the profiles have been presented in the form of the thickness functions of the subsequent layers. The generated functions were auto-correlated, and the Pearson correlation coefficient was calculated. The next step in the research was to statistically determine the percentage increment of the individual layers thickness in the subsequent profiles, and on this basis to plot the function of relative carbonate productivity. Results: The result of the above-mentioned procedures consists in illustrating the extent of 34 rock layers across the examined area in demonstrating the repeatability of their success in subsequent outcroppings. It can also be observed that the thickness of individual layers in the Holy Cross Mountains is increasing from north-west towards south-east. Despite changes in the thickness of the layers in the profiles, their relations within the sequence remain constant. The lowest matching ratio of thickness sequence calculated using the Pearson correlation coefficient formula is 0.67, while the highest is 0.84. The thickness of individual layers changes between 4% and 230% over the examined area. Interpretation: Layers in the outcroppings covered by the research show continuity throughout the examined area and it is possible to precisely correlate them, which means that the process determining the formation of the layers was regional and probably included both the fringe of the Holy Cross Mountains and the north-eastern part of the Krakow-Czestochowa Jura Upland. Local changes in the sedimentation environment affecting the productivity of the subtidal carbonate factory only cause the thickness of the layers to change without altering the thickness proportions of the profiles. Based on the percentage of changes in the thickness of individual layers in the subsequent profiles, it can be concluded that the local productivity of the subtidal carbonate factory is increasing logarithmically.

Keywords: Oxfordian, Holy Cross Mountains, carbonate factory, Limestone

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9 Quantification of Magnetic Resonance Elastography for Tissue Shear Modulus using U-Net Trained with Finite-Differential Time-Domain Simulation

Authors: Jiaying Zhang, Xin Mu, Chang Ni, Jeff L. Zhang

Abstract:

Magnetic resonance elastography (MRE) non-invasively assesses tissue elastic properties, such as shear modulus, by measuring tissue’s displacement in response to mechanical waves. The estimated metrics on tissue elasticity or stiffness have been shown to be valuable for monitoring physiologic or pathophysiologic status of tissue, such as a tumor or fatty liver. To quantify tissue shear modulus from MRE-acquired displacements (essentially an inverse problem), multiple approaches have been proposed, including Local Frequency Estimation (LFE) and Direct Inversion (DI). However, one common problem with these methods is that the estimates are severely noise-sensitive due to either the inverse-problem nature or noise propagation in the pixel-by-pixel process. With the advent of deep learning (DL) and its promise in solving inverse problems, a few groups in the field of MRE have explored the feasibility of using DL methods for quantifying shear modulus from MRE data. Most of the groups chose to use real MRE data for DL model training and to cut training images into smaller patches, which enriches feature characteristics of training data but inevitably increases computation time and results in outcomes with patched patterns. In this study, simulated wave images generated by Finite Differential Time Domain (FDTD) simulation are used for network training, and U-Net is used to extract features from each training image without cutting it into patches. The use of simulated data for model training has the flexibility of customizing training datasets to match specific applications. The proposed method aimed to estimate tissue shear modulus from MRE data with high robustness to noise and high model-training efficiency. Specifically, a set of 3000 maps of shear modulus (with a range of 1 kPa to 15 kPa) containing randomly positioned objects were simulated, and their corresponding wave images were generated. The two types of data were fed into the training of a U-Net model as its output and input, respectively. For an independently simulated set of 1000 images, the performance of the proposed method against DI and LFE was compared by the relative errors (root mean square error or RMSE divided by averaged shear modulus) between the true shear modulus map and the estimated ones. The results showed that the estimated shear modulus by the proposed method achieved a relative error of 4.91%±0.66%, substantially lower than 78.20%±1.11% by LFE. Using simulated data, the proposed method significantly outperformed LFE and DI in resilience to increasing noise levels and in resolving fine changes of shear modulus. The feasibility of the proposed method was also tested on MRE data acquired from phantoms and from human calf muscles, resulting in maps of shear modulus with low noise. In future work, the method’s performance on phantom and its repeatability on human data will be tested in a more quantitative manner. In conclusion, the proposed method showed much promise in quantifying tissue shear modulus from MRE with high robustness and efficiency.

Keywords: deep learning, magnetic resonance elastography, magnetic resonance imaging, shear modulus estimation

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8 Rapid Atmospheric Pressure Photoionization-Mass Spectrometry (APPI-MS) Method for the Detection of Polychlorinated Dibenzo-P-Dioxins and Dibenzofurans in Real Environmental Samples Collected within the Vicinity of Industrial Incinerators

Authors: M. Amo, A. Alvaro, A. Astudillo, R. Mc Culloch, J. C. del Castillo, M. Gómez, J. M. Martín

Abstract:

Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) of course comprise a range of highly toxic compounds that may exist as particulates within the air or accumulate within water supplies, soil, or vegetation. They may be created either ubiquitously or naturally within the environment as a product of forest fires or volcanic eruptions. It is only since the industrial revolution, however, that it has become necessary to closely monitor their generation as a byproduct of manufacturing/combustion processes, in an effort to mitigate widespread contamination events. Of course, the environmental concentrations of these toxins are expected to be extremely low, therefore highly sensitive and accurate methods are required for their determination. Since ionization of non-polar compounds through electrospray and APCI is difficult and inefficient, we evaluate the performance of a novel low-flow Atmospheric Pressure Photoionization (APPI) source for the trace detection of various dioxins and furans using rapid Mass Spectrometry workflows. Air, soil and biota (vegetable matter) samples were collected monthly during one year from various locations within the vicinity of an industrial incinerator in Spain. Analytes were extracted and concentrated using soxhlet extraction in toluene and concentrated by rotavapor and nitrogen flow. Various ionization methods as electrospray (ES) and atmospheric pressure chemical ionization (APCI) were evaluated, however, only the low-flow APPI source was capable of providing the necessary performance, in terms of sensitivity, required for detecting all targeted analytes. In total, 10 analytes including 2,3,7,8-tetrachlorodibenzodioxin (TCDD) were detected and characterized using the APPI-MS method. Both PCDDs and PCFDs were detected most efficiently in negative ionization mode. The most abundant ion always corresponded to the loss of a chlorine and addition of an oxygen, yielding [M-Cl+O]- ions. MRM methods were created in order to provide selectivity for each analyte. No chromatographic separation was employed; however, matrix effects were determined to have a negligible impact on analyte signals. Triple Quadrupole Mass Spectrometry was chosen because of its unique potential for high sensitivity and selectivity. The mass spectrometer used was a Sciex´s Qtrap3200 working in negative Multi Reacting Monitoring Mode (MRM). Typically mass detection limits were determined to be near the 1-pg level. The APPI-MS2 technology applied to the detection of PCDD/Fs allows fast and reliable atmospheric analysis, minimizing considerably operational times and costs, with respect other technologies available. In addition, the limit of detection can be easily improved using a more sensitive mass spectrometer since the background in the analysis channel is very low. The APPI developed by SEADM allows polar and non-polar compounds ionization with high efficiency and repeatability.

Keywords: atmospheric pressure photoionization-mass spectrometry (APPI-MS), dioxin, furan, incinerator

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7 Operation System for Aluminium-Air Cell: A Strategy to Harvest the Energy from Secondary Aluminium

Authors: Binbin Chen, Dennis Y. C. Leung

Abstract:

Aluminium (Al) -air cell holds a high volumetric capacity density of 8.05 Ah cm-3, benefit from the trivalence of Al ions. Additional benefits of Al-air cell are low price and environmental friendliness. Furthermore, the Al energy conversion process is characterized of 100% recyclability in theory. Along with a large base of raw material reserve, Al attracts considerable attentions as a promising material to be integrated within the global energy system. However, despite the early successful applications in military services, several problems exist that prevent the Al-air cells from widely civilian use. The most serious issue is the parasitic corrosion of Al when contacts with electrolyte. To overcome this problem, super-pure Al alloyed with various traces of metal elements are used to increase the corrosion resistance. Nevertheless, high-purity Al alloys are costly and require high energy consumption during production process. An alternative approach is to add inexpensive inhibitors directly into the electrolyte. However, such additives would increase the internal ohmic resistance and hamper the cell performance. So far these methods have not provided satisfactory solutions for the problem within Al-air cells. For the operation of alkaline Al-air cell, there are still other minor problems. One of them is the formation of aluminium hydroxide in the electrolyte. This process decreases ionic conductivity of electrolyte. Another one is the carbonation process within the gas diffusion layer of cathode, blocking the porosity of gas diffusion. Both these would hinder the performance of cells. The present work optimizes the above problems by building an Al-air cell operation system, consisting of four components. A top electrolyte tank containing fresh electrolyte is located at a high level, so that it can drive the electrolyte flow by gravity force. A mechanical rechargeable Al-air cell is fabricated with low-cost materials including low grade Al, carbon paper, and PMMA plates. An electrolyte waste tank with elaborate channel is designed to separate the hydrogen generated from the corrosion, which would be collected by gas collection device. In the first section of the research work, we investigated the performance of the mechanical rechargeable Al-air cell with a constant flow rate of electrolyte, to ensure the repeatability experiments. Then the whole system was assembled together and the feasibility of operating was demonstrated. During experiment, pure hydrogen is collected by collection device, which holds potential for various applications. By collecting this by-product, high utilization efficiency of aluminum is achieved. Considering both electricity and hydrogen generated, an overall utilization efficiency of around 90 % or even higher under different working voltages are achieved. Fluidic electrolyte could remove aluminum hydroxide precipitate and solve the electrolyte deterioration problem. This operation system provides a low-cost strategy for harvesting energy from the abundant secondary Al. The system could also be applied into other metal-air cells and is suitable for emergency power supply, power plant and other applications. The low cost feature implies great potential for commercialization. Further optimization, such as scaling up and optimization of fabrication, will help to refine the technology into practical market offerings.

Keywords: aluminium-air cell, high efficiency, hydrogen, mechanical recharge

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6 Design, Fabrication and Analysis of Molded and Direct 3D-Printed Soft Pneumatic Actuators

Authors: N. Naz, A. D. Domenico, M. N. Huda

Abstract:

Soft Robotics is a rapidly growing multidisciplinary field where robots are fabricated using highly deformable materials motivated by bioinspired designs. The high dexterity and adaptability to the external environments during contact make soft robots ideal for applications such as gripping delicate objects, locomotion, and biomedical devices. The actuation system of soft robots mainly includes fluidic, tendon-driven, and smart material actuation. Among them, Soft Pneumatic Actuator, also known as SPA, remains the most popular choice due to its flexibility, safety, easy implementation, and cost-effectiveness. However, at present, most of the fabrication of SPA is still based on traditional molding and casting techniques where the mold is 3d printed into which silicone rubber is cast and consolidated. This conventional method is time-consuming and involves intensive manual labour with the limitation of repeatability and accuracy in design. Recent advancements in direct 3d printing of different soft materials can significantly reduce the repetitive manual task with an ability to fabricate complex geometries and multicomponent designs in a single manufacturing step. The aim of this research work is to design and analyse the Soft Pneumatic Actuator (SPA) utilizing both conventional casting and modern direct 3d printing technologies. The mold of the SPA for traditional casting is 3d printed using fused deposition modeling (FDM) with the polylactic acid (PLA) thermoplastic wire. Hyperelastic soft materials such as Ecoflex-0030/0050 are cast into the mold and consolidated using a lab oven. The bending behaviour is observed experimentally with different pressures of air compressor to ensure uniform bending without any failure. For direct 3D-printing of SPA fused deposition modeling (FDM) with thermoplastic polyurethane (TPU) and stereolithography (SLA) with an elastic resin are used. The actuator is modeled using the finite element method (FEM) to analyse the nonlinear bending behaviour, stress concentration and strain distribution of different hyperelastic materials after pressurization. FEM analysis is carried out using Ansys Workbench software with a Yeon-2nd order hyperelastic material model. FEM includes long-shape deformation, contact between surfaces, and gravity influences. For mesh generation, quadratic tetrahedron, hybrid, and constant pressure mesh are used. SPA is connected to a baseplate that is in connection with the air compressor. A fixed boundary is applied on the baseplate, and static pressure is applied orthogonally to all surfaces of the internal chambers and channels with a closed continuum model. The simulated results from FEM are compared with the experimental results. The experiments are performed in a laboratory set-up where the developed SPA is connected to a compressed air source with a pressure gauge. A comparison study based on performance analysis is done between FDM and SLA printed SPA with the molded counterparts. Furthermore, the molded and 3d printed SPA has been used to develop a three-finger soft pneumatic gripper and has been tested for handling delicate objects.

Keywords: finite element method, fused deposition modeling, hyperelastic, soft pneumatic actuator

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5 Raman Spectral Fingerprints of Healthy and Cancerous Human Colorectal Tissues

Authors: Maria Karnachoriti, Ellas Spyratou, Dimitrios Lykidis, Maria Lambropoulou, Yiannis S. Raptis, Ioannis Seimenis, Efstathios P. Efstathopoulos, Athanassios G. Kontos

Abstract:

Colorectal cancer is the third most common cancer diagnosed in Europe, according to the latest incidence data provided by the World Health Organization (WHO), and early diagnosis has proved to be the key in reducing cancer-related mortality. In cases where surgical interventions are required for cancer treatment, the accurate discrimination between healthy and cancerous tissues is critical for the postoperative care of the patient. The current study focuses on the ex vivo handling of surgically excised colorectal specimens and the acquisition of their spectral fingerprints using Raman spectroscopy. Acquired data were analyzed in an effort to discriminate, in microscopic scale, between healthy and malignant margins. Raman spectroscopy is a spectroscopic technique with high detection sensitivity and spatial resolution of few micrometers. The spectral fingerprint which is produced during laser-tissue interaction is unique and characterizes the biostructure and its inflammatory or cancer state. Numerous published studies have demonstrated the potential of the technique as a tool for the discrimination between healthy and malignant tissues/cells either ex vivo or in vivo. However, the handling of the excised human specimens and the Raman measurement conditions remain challenging, unavoidably affecting measurement reliability and repeatability, as well as the technique’s overall accuracy and sensitivity. Therefore, tissue handling has to be optimized and standardized to ensure preservation of cell integrity and hydration level. Various strategies have been implemented in the past, including the use of balanced salt solutions, small humidifiers or pump-reservoir-pipette systems. In the current study, human colorectal specimens of 10X5 mm were collected from 5 patients up to now who underwent open surgery for colorectal cancer. A novel, non-toxic zinc-based fixative (Z7) was used for tissue preservation. Z7 demonstrates excellent protein preservation and protection against tissue autolysis. Micro-Raman spectra were recorded with a Renishaw Invia spectrometer from successive random 2 micrometers spots upon excitation at 785 nm to decrease fluorescent background and secure avoidance of tissue photodegradation. A temperature-controlled approach was adopted to stabilize the tissue at 2 °C, thus minimizing dehydration effects and consequent focus drift during measurement. A broad spectral range, 500-3200 cm-1,was covered with five consecutive full scans that lasted for 20 minutes in total. The average spectra were used for least square fitting analysis of the Raman modes.Subtle Raman differences were observed between normal and cancerous colorectal tissues mainly in the intensities of the 1556 cm-1 and 1628 cm-1 Raman modes which correspond to v(C=C) vibrations in porphyrins, as well as in the range of 2800-3000 cm-1 due to CH2 stretching of lipids and CH3 stretching of proteins. Raman spectra evaluation was supported by histological findings from twin specimens. This study demonstrates that Raman spectroscopy may constitute a promising tool for real-time verification of clear margins in colorectal cancer open surgery.

Keywords: colorectal cancer, Raman spectroscopy, malignant margins, spectral fingerprints

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4 Mapping Iron Content in the Brain with Magnetic Resonance Imaging and Machine Learning

Authors: Gabrielle Robertson, Matthew Downs, Joseph Dagher

Abstract:

Iron deposition in the brain has been linked with a host of neurological disorders such as Alzheimer’s, Parkinson’s, and Multiple Sclerosis. While some treatment options exist, there are no objective measurement tools that allow for the monitoring of iron levels in the brain in vivo. An emerging Magnetic Resonance Imaging (MRI) method has been recently proposed to deduce iron concentration through quantitative measurement of magnetic susceptibility. This is a multi-step process that involves repeated modeling of physical processes via approximate numerical solutions. For example, the last two steps of this Quantitative Susceptibility Mapping (QSM) method involve I) mapping magnetic field into magnetic susceptibility and II) mapping magnetic susceptibility into iron concentration. Process I involves solving an ill-posed inverse problem by using regularization via injection of prior belief. The end result from Process II highly depends on the model used to describe the molecular content of each voxel (type of iron, water fraction, etc.) Due to these factors, the accuracy and repeatability of QSM have been an active area of research in the MRI and medical imaging community. This work aims to estimate iron concentration in the brain via a single step. A synthetic numerical model of the human head was created by automatically and manually segmenting the human head on a high-resolution grid (640x640x640, 0.4mm³) yielding detailed structures such as microvasculature and subcortical regions as well as bone, soft tissue, Cerebral Spinal Fluid, sinuses, arteries, and eyes. Each segmented region was then assigned tissue properties such as relaxation rates, proton density, electromagnetic tissue properties and iron concentration. These tissue property values were randomly selected from a Probability Distribution Function derived from a thorough literature review. In addition to having unique tissue property values, different synthetic head realizations also possess unique structural geometry created by morphing the boundary regions of different areas within normal physical constraints. This model of the human brain is then used to create synthetic MRI measurements. This is repeated thousands of times, for different head shapes, volume, tissue properties and noise realizations. Collectively, this constitutes a training-set that is similar to in vivo data, but larger than datasets available from clinical measurements. This 3D convolutional U-Net neural network architecture was used to train data-driven Deep Learning models to solve for iron concentrations from raw MRI measurements. The performance was then tested on both synthetic data not used in training as well as real in vivo data. Results showed that the model trained on synthetic MRI measurements is able to directly learn iron concentrations in areas of interest more effectively than other existing QSM reconstruction methods. For comparison, models trained on random geometric shapes (as proposed in the Deep QSM method) are less effective than models trained on realistic synthetic head models. Such an accurate method for the quantitative measurement of iron deposits in the brain would be of important value in clinical studies aiming to understand the role of iron in neurological disease.

Keywords: magnetic resonance imaging, MRI, iron deposition, machine learning, quantitative susceptibility mapping

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3 New Hybrid Process for Converting Small Structural Parts from Metal to CFRP

Authors: Yannick Willemin

Abstract:

Carbon fibre-reinforced plastic (CFRP) offers outstanding value. However, like all materials, CFRP also has its challenges. Many forming processes are largely manual and hard to automate, making it challenging to control repeatability and reproducibility (R&R); they generate significant scrap and are too slow for high-series production; fibre costs are relatively high and subject to supply and cost fluctuations; the supply chain is fragmented; many forms of CFRP are not recyclable, and many materials have yet to be fully characterized for accurate simulation; shelf life and outlife limitations add cost; continuous-fibre forms have design limitations; many materials are brittle; and small and/or thick parts are costly to produce and difficult to automate. A majority of small structural parts are metal due to high CFRP fabrication costs for the small-size class. The fact that CFRP manufacturing processes that produce the highest performance parts also tend to be the slowest and least automated is another reason CFRP parts are generally higher in cost than comparably performing metal parts, which are easier to produce. Fortunately, business is in the midst of a major manufacturing evolution—Industry 4.0— one technology seeing rapid growth is additive manufacturing/3D printing, thanks to new processes and materials, plus an ability to harness Industry 4.0 tools. No longer limited to just prototype parts, metal-additive technologies are used to produce tooling and mold components for high-volume manufacturing, and polymer-additive technologies can incorporate fibres to produce true composites and be used to produce end-use parts with high aesthetics, unmatched complexity, mass customization opportunities, and high mechanical performance. A new hybrid manufacturing process combines the best capabilities of additive—high complexity, low energy usage and waste, 100% traceability, faster to market—and post-consolidation—tight tolerances, high R&R, established materials, and supply chains—technologies. The platform was developed by Zürich-based 9T Labs AG and is called Additive Fusion Technology (AFT). It consists of a design software offering the possibility to determine optimal fibre layup, then exports files back to check predicted performance—plus two pieces of equipment: a 3d-printer—which lays up (near)-net-shape preforms using neat thermoplastic filaments and slit, roll-formed unidirectional carbon fibre-reinforced thermoplastic tapes—and a post-consolidation module—which consolidates then shapes preforms into final parts using a compact compression press fitted with a heating unit and matched metal molds. Matrices—currently including PEKK, PEEK, PA12, and PPS, although nearly any high-quality commercial thermoplastic tapes and filaments can be used—are matched between filaments and tapes to assure excellent bonding. Since thermoplastics are used exclusively, larger assemblies can be produced by bonding or welding together smaller components, and end-of-life parts can be recycled. By combining compression molding with 3D printing, higher part quality with very-low voids and excellent surface finish on A and B sides can be produced. Tight tolerances (min. section thickness=1.5mm, min. section height=0.6mm, min. fibre radius=1.5mm) with high R&R can be cost-competitively held in production volumes of 100 to 10,000 parts/year on a single set of machines.

Keywords: additive manufacturing, composites, thermoplastic, hybrid manufacturing

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2 MusicTherapy for Actors: An Exploratory Study Applied to Students from University Theatre Faculty

Authors: Adriana De Serio, Adrian Korek

Abstract:

Aims: This experiential research work presents a Group-MusicTherapy-Theatre-Plan (MusThePlan) the authors have carried out to support the actors. The MusicTherapy gives rise to individual psychophysical feedback and influences the emotional centres of the brain and the subconsciousness. Therefore, the authors underline the effectiveness of the preventive, educational, and training goals of the MusThePlan to lead theatre students and actors to deal with anxiety and to overcome psychophysical weaknesses, shyness, emotional stress in stage performances, to increase flexibility, awareness of one's identity and resources for a positive self-development and psychophysical health, to develop and strengthen social bonds, increasing a network of subjects working for social inclusion and reduction of stigma. Materials-Methods: Thirty students from the University Theatre Faculty participated in weekly music therapy sessions for two months; each session lasted 120 minutes. MusThePlan: Each session began with a free group rhythmic-sonorous-musical-production by body-percussion, voice-canto, instruments, to stimulate communication. Then, a synchronized-structured bodily-rhythmic-sonorous-musical production also involved acting, dances, movements of hands and arms, hearing, and more sensorial perceptions and speech to balance motor skills and the muscular tone. Each student could be the director-leader of the group indicating a story to inspire the group's musical production. The third step involved the students in rhythmic speech and singing drills and in vocal exercises focusing on the musical pitch to improve the intonation and on the diction to improve the articulation and lead up it to an increased intelligibility. At the end of each musictherapy session and of the two months, the Musictherapy Assessment Document was drawn up by analysis of observation protocols and two Indices by the authors: Patient-Environment-Music-Index (time to - tn) to estimate the behavior evolution, Somatic Pattern Index to monitor subject’s eye and mouth and limb motility, perspiration, before, during and after musictherapy sessions. Results: After the first month, the students (non musicians) learned to play percussion instruments and formed a musical band that played classical/modern music on the percussion instruments with the musictherapist/pianist/conductor in a public concert. At the end of the second month, the students performed a public musical theatre show, acting, dancing, singing, and playing percussion instruments. The students highlighted the importance of the playful aspects of the group musical production in order to achieve emotional contact and harmony within the group. The students said they had improved kinetic and vocal and all the skills useful for acting activity and the nourishment of the bodily and emotional balance. Conclusions: The MusThePlan makes use of some specific MusicTherapy methodological models, techniques, and strategies useful for the actors. The MusThePlan can destroy the individual "mask" and can be useful when the verbal language is unable to undermine the defense mechanisms of the subject. The MusThePlan improves actor’s psychophysical activation, motivation, gratification, knowledge of one's own possibilities, and the quality of life. Therefore, the MusThePlan could be useful to carry out targeted interventions for the actors with characteristics of repeatability, objectivity, and predictability of results. Furthermore, it would be useful to plan a University course/master in “MusicTherapy for the Theatre”.

Keywords: musictherapy, sonorous-musical energy, quality of life, theatre

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1 Utilization of Developed Single Sequence Repeats Markers for Dalmatian Pyrethrum (Tanacetum cinerariifolium) in Preliminary Genetic Diversity Study on Natural Populations

Authors: F. Varga, Z. Liber, J. Jakše, A. Turudić, Z. Šatović, I. Radosavljević, N. Jeran, M. Grdiša

Abstract:

Dalmatian pyrethrum (Tanacetum cinerariifolium (Trevir.) Sch. Bip.; Asteraceae), a source of the commercially dominant plant insecticide pyrethrin, is a species endemic to the eastern Adriatic. Genetic diversity of T. cinerariifolium was previously studied using amplified fragment length polymorphism (AFLP) markers. However, microsatellite markers (single sequence repeats - SSRs) are more informative because they are codominant, highly polymorphic, locus-specific, and more reproducible, and thus are most often used to assess the genetic diversity of plant species. Dalmatian pyrethrum is an outcrossing diploid (2n = 18) whose large genome size and high repeatability have prevented the success of the traditional approach to SSR markers development. The advent of next-generation sequencing combined with the specifically developed method recently enabled the development of, to the author's best knowledge, the first set of SSRs for genomic characterization of Dalmatian pyrethrum, which is essential from the perspective of plant genetic resources conservation. To evaluate the effectiveness of the developed SSR markers in genetic differentiation of Dalmatian pyrethrum populations, a preliminary genetic diversity study was conducted on 30 individuals from three geographically distinct natural populations in Croatia (northern Adriatic island of Mali Lošinj, southern Adriatic island of Čiovo, and Mount Biokovo) based on 12 SSR loci. Analysis of molecular variance (AMOVA) by randomization test with 10,000 permutations was performed in Arlequin 3.5. The average number of alleles per locus, observed and expected heterozygosity, probability of deviations from Hardy-Weinberg equilibrium, and inbreeding coefficient was calculated using GENEPOP 4.4. Genetic distance based on the proportion of common alleles (DPSA) was calculated using MICROSAT. Cluster analysis using the neighbor-joining method with 1,000 bootstraps was performed with PHYLIP to generate a dendrogram. The results of the AMOVA analysis showed that the total SSR diversity was 23% within and 77% between the three populations. A slight deviation from Hardy-Weinberg equilibrium was observed in the Mali Lošinj population. Allele richness ranged from 2.92 to 3.92, with the highest number of private alleles observed in the Mali Lošinj population (17). The average observed DPSA between 30 individuals was 0.557. The highest DPSA (0.875) was observed between several pairs of Dalmatian pyrethrum individuals from the Mali Lošinj and Mt. Biokovo populations, and the lowest between two individuals from the Čiovo population. Neighbor-joining trees, based on DPSA, grouped individuals into clusters according to their population affiliation. The separation of Mt. Biokovo clade was supported (bootstrap value 58%), which is consistent with the previous study on AFLP markers, where isolated populations from Mt. Biokovo differed from the rest of the populations. The developed SSR markers are an effective tool for assessing the genetic diversity and structure of natural Dalmatian pyrethrum populations. These preliminary results are encouraging for a future comprehensive study with a larger sample size across the species' range. Combined with the biochemical data, these highly informative markers could help identify potential genotypes of interest for future development of breeding lines and cultivars that are both resistant to environmental stress and high in pyrethrins. Acknowledgment: This work has been supported by the Croatian Science Foundation under the project ‘Genetic background of Dalmatian pyrethrum (Tanacetum cinerariifolium /Trevir./ Sch. Bip.) insecticidal potential’- (PyrDiv) (IP-06-2016-9034) and by project KK.01.1.1.01.0005, Biodiversity and Molecular Plant Breeding, at the Centre of Excellence for Biodiversity and Molecular Plant Breeding (CoE CroP-BioDiv), Zagreb, Croatia.

Keywords: Asteraceae, genetic diversity, genomic SSRs, NGS, pyrethrum, Tanacetum cinerariifolium

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