Search results for: functionally graded beams

Authors: Mehrnaz Mostafavi

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Recent advances in single-molecule protein identification (ID) and quantification techniques are poised to revolutionize proteomics, enabling researchers to delve into single-cell proteomics and identify low-abundance proteins crucial for biomedical and clinical research. This paper introduces a different approach to single-molecule protein ID and quantification using tri-color amino acid tags and a plasmonic nanopore device. A comprehensive simulator incorporating various physical phenomena was designed to predict and model the device's behavior under diverse experimental conditions, providing insights into its feasibility and limitations. The study employs a whole-proteome single-molecule identification algorithm based on convolutional neural networks, achieving high accuracies (>90%), particularly in challenging conditions (95–97%). To address potential challenges in clinical samples, where post-translational modifications affecting labeling efficiency, the paper evaluates protein identification accuracy under partial labeling conditions. Solid-state nanopores, capable of processing tens of individual proteins per second, are explored as a platform for this method. Unlike techniques relying solely on ion-current measurements, this approach enables parallel readout using high-density nanopore arrays and multi-pixel single-photon sensors. Convolutional neural networks contribute to the method's versatility and robustness, simplifying calibration procedures and potentially allowing protein ID based on partial reads. The study also discusses the efficacy of the approach in real experimental conditions, resolving functionally similar proteins. The theoretical analysis, protein labeler program, finite difference time domain calculation of plasmonic fields, and simulation of nanopore-based optical sensing are detailed in the methods section. The study anticipates further exploration of temporal distributions of protein translocation dwell-times and the impact on convolutional neural network identification accuracy. Overall, the research presents a promising avenue for advancing single-molecule protein identification and quantification with broad applications in proteomics research. The contributions made in methodology, accuracy, robustness, and technological exploration collectively position this work at the forefront of transformative developments in the field.

Keywords: nano proteomics, nanopore-based optical sensing, deep learning, artificial intelligence

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Authors: Jikhil Joseph, Satish Kumar S R.

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Cold-formed steel frames are preferable for framed constructions due to its low seismic weights and results into low seismic forces, but on the contrary, significant lateral deflections are expected under seismic/wind loading. The various factors affecting the lateral stiffness of steel frames are the stiffness of connections, beams and columns. So, by increasing the stiffness of beam, column and making the connections rigid will enhance the lateral stiffness. The present study focused on Structural elements made of rectangular hollow sections and fastened with screwed in-plane moment connections for the building frames. The self-drilling screws can be easily drilled on either side of the connection area with the help of gusset plates. The strength of screwed connections can be made 1.2 times the connecting elements. However, achieving high stiffness in connections is also a challenging job. Hence in addition to beam and column stiffness’s the connection stiffness are also going to be a governing parameter in the lateral deflections of the frames. SAP 2000 Non-linear static analysis has been planned to study the seismic behavior of steel frames. The SAP model will be consisting of nonlinear spring model for the connection to account the semi-rigid connections and the nonlinear hinges will be assigned for beam and column sections according to FEMA 273 guidelines. The reliable spring and hinge parameters will be assigned based on an experimental and analytical database. The non-linear static analysis is mainly focused on the identification of various hinge formations and the estimation of lateral deflection and these will contribute as an inputs for the direct displacement-based Seismic design. The research output from this study are the modelling techniques and suitable design guidelines for the performance-based seismic design of cold-formed steel frames.

Keywords: buckling, cold formed steel, nonlinear static analysis, screwed connections

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Authors: Fagner O. Serrano, Danielle R. Bouchard, Todd A. Duhame

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Walking cadence (steps/min) is an effective way to prescribe exercise so an individual can reach a moderate intensity, which is recommended to optimize health benefits. To our knowledge, there is no study on the required walking cadence to reach a moderate intensity for people that present chronic conditions or risk factors for chronic conditions such as Cardiovascular Diseases (CVD). The objectives of this study were: 1- to identify the walking cadence needed for people at risk of CVD to a reach moderate intensity, and 2- to develop and test an equation using clinical variables to help professionals working with individuals at risk of CVD to estimate the walking cadence needed to reach moderate intensity. Ninety-one people presenting a minimum of two risk factors for CVD completed a medically supervised graded exercise test to assess maximum oxygen consumption at the first visit. The last visit consisted of recording walking cadence using a foot pod Garmin FR-60 and a Polar heart rate monitor, aiming to get participants to reach 40% of their maximal oxygen consumption using a portable metabolic cart on an indoor flat surface. The equation to predict the walking cadence needed to reach moderate intensity in this sample was developed as follows: The sample was randomly split in half and the equation was developed with one half of the participants, and validated using the other half. Body mass index, height, stride length, leg height, body weight, fitness level (VO2max), and self-selected cadence (over 200 meters) were measured using objective measured. Mean walking cadence to reach moderate intensity for people age 64.3 ± 10.3 years old at risk of CVD was 115.8  10.3 steps per minute. Body mass index, height, body weight, fitness level, and self-selected cadence were associated with walking cadence at moderate intensity when evaluated in bivariate analyses (r ranging from 0.22 to 0.52; all P values ≤0.05). Using linear regression analysis including all clinical variables associated in the bivariate analyses, body weight was the significant predictor of walking cadence for reaching a moderate intensity (ß=0.24; P=.018) explaining 13% of walking cadence to reach moderate intensity. The regression model created was Y = 134.4-0.24 X body weight (kg).Our findings suggest that people presenting two or more risk factors for CVD are reaching moderate intensity while walking at a cadence above the one officially recommended (116 steps per minute vs. 100 steps per minute) for healthy adults.

Keywords: cardiovascular disease, moderate intensity, older adults, walking cadence

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Authors: Shoukat Ali, Abdul Qadir Jandga, Amjad Hussain

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Objective: The main purpose of this study is to compare the Percent Depth dose (PDD) and In-plane and cross-plane profiles of Varian Golden beam data to the measured data of 6 and 18 MV photons for the commissioning of Eclipse treatment planning system. Introduction: Commissioning of treatment planning system requires an extensive acquisition of beam data for the clinical use of linear accelerators. Accurate dose delivery require to enter the PDDs, Profiles and dose rate tables for open and wedges fields into treatment planning system, enabling to calculate the MUs and dose distribution. Varian offers a generic set of beam data as a reference data, however not recommend for clinical use. In this study, we compared the generic beam data with the measured beam data to evaluate the reliability of generic beam data to be used for the clinical purpose. Methods and Material: PDDs and Profiles of Open and Wedge fields for different field sizes and at different depths measured as per Varian’s algorithm commissioning guideline. The measurement performed with PTW 3D-scanning water phantom with semi-flex ion chamber and MEPHYSTO software. The online available Varian Golden Beam Data compared with the measured data to evaluate the accuracy of the golden beam data to be used for the commissioning of Eclipse treatment planning system. Results: The deviation between measured vs. golden beam data was in the range of 2% max. In PDDs, the deviation increases more in the deeper depths than the shallower depths. Similarly, profiles have the same trend of increasing deviation at large field sizes and increasing depths. Conclusion: Study shows that the percentage deviation between measured and golden beam data is within the acceptable tolerance and therefore can be used for the commissioning process; however, verification of small subset of acquired data with the golden beam data should be mandatory before clinical use.

Keywords: percent depth dose, flatness, symmetry, golden beam data

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Authors: Ying Shi, June Zhang, Lu Shao, Xiyan Xie, Aidi Lao, Zhangan Wang

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Background: Low levels of physical activity are associated with poorer health outcomes, and this situation is more critical in older adults living in long‐term care facilities. Objectives: To systematically identify, appraise, and synthesize current qualitative research evidence regarding the barriers and facilitators to physical activity as reported by older adults and care staff in long‐term care facilities. Design: This is a systematic review with qualitative evidence synthesis adhering to PRISMA guidelines. Methods: We conducted a systematic search on PubMed, Science Citation Index Expanded, Social Sciences Citation Index, EMBASE, CINAHL, and PsychInfo databases from inception until 30 June 2023. Thematic synthesis was undertaken to identify the barriers and facilitators relating to physical activity. Then, we mapped them onto the Capability, Opportunity, Motivation, and Behavior model and Theoretical Domains Framework. Methodological quality was assessed using the CASP Qualitative Studies Checklist, and confidence in review findings was assessed using the GRADE-CERQual approach. Results: We included 32 studies after screening 10496 citations and 177 full texts. Seven themes and 17 subthemes were identified relating to barriers and facilitators influencing physical activity in elderly residents. The main themes were mapped onto COM-B) model-Capability (physical activity knowledge gaps and individual health issues), Opportunity (social support and macro-level resources) and Motivation (health beliefs, fear of falling or injury, and personal and social incentives to physical activity). Most subthemes were graded as high (n = 9) or moderate (n = 3) confidence. Conclusions and Implications: Our comprehensive synthesis of 32 studies provides a wealth of knowledge of barriers and facilitators to physical activity from both residents and care staff’s perspectives. Intervention components were also suggested within the context of long‐term care facilities. End users such as older residents, care staff, and researchers can have confidence in our findings when formulating policies and guidance on promoting physical activity among elderly residents in long‐term care facilities.

Keywords: long‐term care, older adults, physical activity, qualitative, systematic review

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Authors: Harish Kuruva, Vedasri Bai Khavala, Tiju Thomas, K. Murugan, B. S. Murty

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Industries are growing day to day to increase the economy of the country. The biggest problem with industries is wastewater treatment. Releasing these wastewater directly into the river is more harmful to human life and a threat to aquatic life. These industrial effluents contain many dissolved solids, organic/inorganic compounds, salts, toxic metals, etc. Phenols, pesticides, dioxins, herbicides, pharmaceuticals, and textile dyes were the types of industrial effluents and more challenging to degrade eco-friendly. So many advanced techniques like electrochemical, oxidation process, and valorization have been applied for industrial wastewater treatment, but these are not cost-effective. Industrial effluent degradation is complicated compared to commercially available pollutants (dyes) like methylene blue, methylene orange, rhodamine B, etc. TiO₂ is one of the widely used photocatalysts which can degrade organic compounds using solar light and moisture available in the environment (organic compounds converted to CO₂ and H₂O). TiO₂ is widely studied in photocatalysis because of its low cost, non-toxic, high availability, and chemically and physically stable in the atmosphere. This study mainly focused on valorizing the mineralogical product TiO₂ (IREL, India). This mineralogical graded TiO₂ was characterized and compared with its structural and photocatalytic properties (industrial effluent degradation) with the commercially available Degussa P-25 TiO₂. It was testified that this mineralogical TiO₂ has the best photocatalytic properties (particle shape - spherical, size - 30±5 nm, surface area - 98.19 m²/g, bandgap - 3.2 eV, phase - 95% anatase, and 5% rutile). The industrial effluent was characterized by TDS (total dissolved solids), ICP-OES (inductively coupled plasma – optical emission spectroscopy), CHNS (Carbon, Hydrogen, Nitrogen, and sulfur) analyzer, and FT-IR (fourier-transform infrared spectroscopy). It was observed that it contains high sulfur (S=11.37±0.15%), organic compounds (C=4±0.1%, H=70.25±0.1%, N=10±0.1%), heavy metals, and other dissolved solids (60 g/L). However, the organo-sulfur industrial effluent was degraded by photocatalysis with the industrial mineralogical product TiO₂. In this study, the industrial effluent pH value (2.5 to 10), catalyst concentration (50 to 150 mg) were varied, and effluent concentration (0.5 Abs) and light exposure time (2 h) were maintained constant. The best degradation is about 80% of industrial effluent was achieved at pH 5 with a concentration of 150 mg - TiO₂. The FT-IR results and CHNS analyzer confirmed that the sulfur and organic compounds were degraded.

Keywords: wastewater treatment, industrial mineralogical product TiO₂, photocatalysis, organo-sulfur industrial effluent

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Authors: Astrid Tannert, Anuradha Ramoji, Christina Ebert, Frederike Gladigau, Lorena Tuchscherr, Jürgen Popp, Ute Neugebauer

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Staphylococcus aureus is a facultative intracellular pathogen, which by entering host cells may evade immunologic host response as well as antimicrobial treatment. In that way, S. aureus can cause persistent intracellular infections which are difficult to treat. Depending on the strain, S. aureus may persist at different intracellular locations like the phagolysosome. The first barrier invading pathogens from the blood stream that they have to cross are the endothelial cells lining the inner surface of blood and lymphatic vessels. Upon proceeding from an acute to a chronic infection, intracellular pathogens undergo certain biochemical and structural changes including a deceleration of metabolic processes to adopt for long-term intracellular survival and the development of a special phenotype designated as small colony variant. In this study, the endothelial cell line Ea.hy 926 was used as a model for acute and chronic S. aureus infection. To this end, Ea.hy 926 cells were cultured on QIAscout™ Microraft Arrays, a special graded cell culture substrate that contains around 12,000 microrafts of 200 µm edge length. After attachment to the substrate, the endothelial cells were infected with GFP-expressing S. aureus for 3 weeks. The acute infection and the development of persistent bacteria was followed by confocal laser scanning microscopy, scanning the whole Microraft Array for the presence and for detailed determination of the intracellular location of fluorescent intracellular bacteria every second day. After three weeks of infection representative microrafts containing infected cells, cells with protruded infections and cells that did never show any infection were isolated and fixed for Raman micro-spectroscopic investigation. For comparison, also microrafts with acute infection were isolated. The acquired Raman spectra are correlated with the fluorescence microscopic images to give hints about a) the molecular alterations in endothelial cells during acute and chronic infection compared to non-infected cells, and b) metabolic and structural changes within the pathogen when entering a mode of persistence within host cells. We thank Dr. Ruth Kläver from QIAGEN GmbH for her support regarding QIAscout technology. Financial support by the BMBF via the CSCC (FKZ 01EO1502) and from the DFG via the Jena Biophotonic and Imaging Laboratory (JBIL, FKZ PO 633/29-1, BA 1601/10-1) is highly acknowledged.

Keywords: correlative image analysis, intracellular infection, pathogen-host adaption, Raman micro-spectroscopy

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Authors: Konstantin S. Vainutis, Mark E. Andreev, Anastasia N. Voronova, Mikhail Yu. Shchelkanov

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Introduction: The trematodes from the family Cyclocoelidae (cyclocoelids) belong to the superfamily Echinostomatoidea infecting air sacs and trachea of wild birds. At present, the family Cyclocoelidae comprises nine valid genera in three subfamilies: Cyclocoelinae (type taxon), Haematotrephinae, and Typhlocoelinae. To our best knowledge, in this study, molecular genetic methods were used for the first time for studying cyclocoelids from the Russian Far East. Here we provide the data on the morphology and phylogeny of cyclocoelids from gadwall from the Russian Far East. The morphological and genetic data obtained for cyclocoelids indicated the necessity to revise the previously proposed classification within the family Cyclocoelidae. Objectives: The first objective was performing the morphological study of cyclocoelids found in M. strepera from the Russian Far East. The second objective is to reconstruct the phylogenetic relationships of the studied trematodes with other cyclocoelids using the 28S gene. Material and methods: During the field studies in the Khasansky district of the Primorsky region, 21 cyclocoelids were recovered from the air sacs of a single gadwall Mareca strepera. Seven samples of cyclocoelids were overstained in alum carmine, dehydrated in a graded ethanol series, cleared in clove oil, and mounted in Canada balsam. Genomic DNA was extracted from four cyclocoelids using the alkaline lysis method HotShot. The 28S rDNA fragment was amplified using the forward primer Digl2 and the reverse primer 1500R. Results: According to morphological features (ovary intratesticular, forming a triangle with the testes), the studied worms belong to the subfamily Cyclocoelinae Stossich, 1902. In particular, the highest morphological similarity was observed in relation to the trematodes of the genus Cyclocoelum Brandes, 1892 – genital pores are pharyngeal. However, the genetic analysis has shown significant discrepancies between the trematodes studied regarding the genus Cyclocoelum. On the phylogenetic tree, these trematodes took the sister position in relation to the genus Morishitium (previously considered in the subfamily Szidatitrematinae). Conclusion: Based on the results of the morphological and genetic studies, cyclocoelids isolated from Mareca strepera are suggested to be described in the previously unknown genus and differentiated from the type genus Cyclocoelum of the type subfamily Cyclocoelinae. Considering the available molecular data, including described cyclocoelids, the family Cyclocoelidae comprises ten valid genera in the three subfamilies mentioned above.

Keywords: new species, trematoda, phylogeny, cyclocoelidae

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Authors: Byl Farney Cunha Junior

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In this work the dynamic three-dimensional analysis of a 47-story building located in Goiania city when subjected to wind loads generated using both the Wind Brazilian code, NBR6123 (ABNT, 1988) and the Synthetic-Wind method is realized. To model the frames three different methodologies are used: the shear building model and both bi and three-dimensional finite element models. To start the analysis, a plane frame is initially studied to validate the shear building model and, in order to compare the results of natural frequencies and displacements at the top of the structure the same plane frame was modeled using the finite element method through the SAP2000 V10 software. The same steps were applied to an idealized 20-story spacial frame that helps in the presentation of the stiffness correction process applied to columns. Based on these models the two methods used to generate the Wind loads are presented: a discrete model proposed in the Wind Brazilian code, NBR6123 (ABNT, 1988) and the Synthetic-Wind method. The method uses the Davenport spectrum which is divided into a variety of frequencies to generate the temporal series of loads. Finally, the 47- story building was analyzed using both the three-dimensional finite element method through the SAP2000 V10 software and the shear building model. The models were loaded with Wind load generated by the Wind code NBR6123 (ABNT, 1988) and by the Synthetic-Wind method considering different wind directions. The displacements and internal forces in columns and beams were compared and a comparative study considering a situation of a full elevated reservoir is realized. As can be observed the displacements obtained by the SAP2000 V10 model are greater when loaded with NBR6123 (ABNT, 1988) wind load related to the permanent phase of the structure’s response.

Keywords: finite element method, synthetic wind, tall buildings, shear building

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Authors: Mattea Carmen Castrovilli, Antonella Cartoni

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Electrospray ionisation (ESI), a well-established technique widely used to produce ion beams of biomolecules in mass spectrometry (ESI-MS), can be used for ambient soft landing of enzymes on a specific substrate. In this work, we show how the ambient electrospray deposition (ESD) technique can be successfully exploited for manufacturing a promising, green-friendly electrochemical amperometric laccase-based biosensor with unprecedented reuse and storage performance. These biosensors have been manufactured by spraying a laccase solution of 2μg/μL at 20% of methanol on a commercial carbon screen printed electrode (C-SPE) using a custom ESD set-up. The laccase-based ESD biosensor has been tested against catechol compounds in the linear range 2-100 μM, with a limit of detection of 1.7 μM, without interference from cadmium, chrome, arsenic, and zinc and without any memory effects, but showing a matrix effect in lake and well water. The ESD biosensor shows enhanced performances compared to the ones fabricated with other immobilization methods, like drop-casting. Indeed, it retains 100% activity up to two months of storage at ambient conditions without any special care and working stability up to 63 measurements on the same electrode just prepared and 20 on a one-year-old electrode subjected to redeposition together with a 100% resistance to use of the same electrode in subsequent days. The ESD method is a one-step, environmentally friendly method that allows the deposition of the bio-recognition layer without using any additional chemicals. The promising results in terms of storage and working stability also obtained with the more fragile lactate oxidase enzyme suggest these improvements should be attributed to the ESD technique rather than to the bioreceptor, highlighting how the ESD could be useful in reducing pollution from disposable devices. Acknowledgment: The understanding at the molecular level of this promising biosensor by using different spectroscopies, microscopies and analytical techniques is the subject of our PRIN 2022 project ESILARANTE.

Keywords: reuse, storage performance, immobilization, electrospray deposition, biosensor, laccase, catechol detection, green chemistry

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Authors: Darshana Sharma

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Distance Education has emerged as a viable alternative to serve the higher educational needs of the socially and economically disadvantaged people of the remote, rural areas of Jammu region. The University of Jammu is a National Accreditation, and Assessment Council accredited, A+ university and has been accorded graded autonomy by the University Grants Commission. It is a dual mode university offering academic programmes through the regular departments and through the Directorate of Distance Education. The Directorate of Distance Education, University of Jammu still uses printed study material as a mode of instructional delivery. The development of technologies has assured increased interaction and communication for distance learners throughout the distance open learning institutions. Though it is tempting and convenient to adopt technology already being used by others, it may not prove effective for the simple reason that two institutions may be unlike in some respect. The use of technology must be conceived in view of the needs of the learners; geographical socio-economic-cultural and technological contexts and financial, administrative and academic resources of the institution. Mobile learning (m-learning) is a novel approach to knowledge acquisition and dissemination and is gaining global attention. It has evolved as one of the useful channels of distance learning promoting interaction between learners and teachers. It is felt that the Directorate of Distance Education, University of Jammu also needs to adopt new technologies to provide more effective academic and information support to distance learners in order to keep them motivated and also to develop self-learning skills. The chief objective of the research on which this paper is based was to measure the opinion of the distance learners of the DDE, the University of Jammu about the merits of mobile learning. It also explores their preferences for implementing mobile learning. The survey research design of descriptive research has been used. The data was collected from 400 distance learners enrolled with undergraduate and post-graduate programmes using self-constructed questionnaire containing five-point Likert scale items arranging from strongly agree, agree, indifferent, disagree and strongly disagree. Percentages were used to analyze the data. The findings lead to conclude that mobile learning has a great potential for the DDE for reaching out to the rural, remotely located distance learners of the Jammu region and also to improve the teaching-learning environment. The paper also finds out the challenges in the implementation of mobile learning in the region and further makes suggestions for effective implementation of mobile learning in DDE, University of Jammu.

Keywords: directorate of distance education, mobile learning, national accreditation and assessment council, university of Jammu

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Authors: Arto Grasten

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Given the rising trend in obesity in children and youth, age-related decline in moderate- to- vigorous-intensity physical activity (MVPA) in several Western, African, and Asian countries in addition to limited evidence of behavioral, affective, cognitive outcomes in physical education, it is important to clarify the motivational processes in physical education classes behind total MVPA engagement. The present study examined the full sequence of the Hierarchical Model of Motivation in physical education including motivational climate, basic psychological needs, intrinsic motivation, contextual behavior, affect, cognition, total MVPA, and associated links to body mass index (BMI) and gender differences. A cross-sectional data comprised self-reports and objective assessments of 770 middle school students (Mage = 13.99 ± .81 years, 52% of girls) in North-East Finland. In order to test the associations between motivational climate, psychological needs, intrinsic motivation, cognition, behavior, affect, and total MVPA, a path model was implemented. Indirect effects between motivational climate and cognition, behavior, affect and total MVPA were tested by setting basic needs and intrinsic motivation as mediators into the model. The findings showed that direct and indirect paths for girls and boys associated with different contextual outcomes and girls’ indirect paths were not related with total MVPA. Precisely, task-involving climate-mediated by physical competence and intrinsic motivation related to enjoyment, importance, and graded assessments within girls, whereas task-involving climate associated with enjoyment and importance via competence and autonomy, and total MVPA via autonomy, intrinsic motivation, and importance within boys. Physical education assessments appeared to be essential in motivating students to participate in greater total MVPA. BMI was negatively linked with competence and relatedness only among girls. Although, the current and previous empirical findings supported task-involving teaching methods in physical education, in some cases, ego-involving climate should not be totally avoided. This may indicate that girls and boys perceive physical education classes in a different way. Therefore, both task- and ego-involving teaching practices can be useful ways of driving behavior in physical education classes.

Keywords: achievement goal theory, assessment, enjoyment, hierarchical model of motivation, physical activity, self-determination theory

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Authors: P. Caimmi, E. Bele, A. Abolfathi

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Lattice materials are cellular structures composed of a periodic network of beams. They offer high weight-specific mechanical properties and lend themselves to numerous weight-sensitive applications. The periodic internal structure responds to external vibrations through characteristic frequency bandgaps, making these materials suitable for the reduction of noise and vibration. However, the deviation from architectural homogeneity, due to, e.g., manufacturing imperfections, has a strong influence on the mechanical properties and vibration response of these materials. In this work, we present results on the influence of geometric imperfections on the vibration response of hexagonal lattices. Three classes of geometrical variables are used: the characteristics of the architecture (relative density, ligament length/cell size ratio), imperfection type (degree of non-periodicity, cracks, hard inclusions) and defect morphology (size, distribution). Test specimens with controlled size and distribution of imperfections are manufactured through selective laser sintering. The Frequency Response Functions (FRFs) in the form of accelerance are measured, and the modal shapes are captured through a high-speed camera. The finite element method is used to provide insights on the extension of these results to semi-infinite lattices. An updating procedure is conducted to increase the reliability of numerical simulation results compared to experimental measurements. This is achieved by updating the boundary conditions and material stiffness. Variations in FRFs of periodic structures due to changes in the relative density of the constituent unit cell are analysed. The effects of geometric imperfections on the dynamic response of periodic structures are investigated. The findings can be used to open up the opportunity for tailoring these lattice materials to achieve optimal amplitude attenuations at specific frequency ranges.

Keywords: lattice architectures, geometric imperfections, vibration attenuation, experimental modal analysis

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Authors: Angel Champion

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Chemotherapy and radiation use an acidified approach to induce apoptosis, which only kills mature cancer cells while resulting in gene and cell damage with significant levels of toxicity in tumor-affected tissues and organs. The acid approach, where the cells exterminated are not differentiated, induces the disappearance of white blood cells from the blood. This increases susceptibility to infection in severe forms of cancer spread. However, chemotherapy and radiation cannot kill cancer stem cells that metastasize, being the leading cause of 98% of cancer fatalities. With over 12 million new cancer cases symptomatic each year, including common malignancies such as Hepatocellular Carcinoma (HCC), this study aims to assess the bioactive constituents and phytochemical composition of Taraxacum Officinale (Dandelion). This analysis enables pharmaceutical quality and potency to be applied to studies on cancer cell proliferation and apoptosis. A phytochemical screening is carried out to identify the antioxidant components of Dandelion root, stem, and flower extract. The constituents tested for are phlorotannins, carbohydrates, glycosides, saponins, flavonoids, alkaloids, sterols, triterpenes, and anthraquinone glycosides. To conserve the existing phenolic compounds, a portion of the constituent tests will be examined with an acid, alcohol, or aqueous solvent. As a result, the qualitative and quantitative variations within the Dandelion extract that measure uniform effective potency are vital to the conformity for producing medicinal products. These medicines will be constructed with a consistent, uniform composition that physicians can use to control and effectively eradicate malignant diseases safely. Taraxacum Officinale's phytochemical composition comprises a highly-graded potency due to present bioactive contents that will essentially drive out malignant disease within the human body. Its high potency rate is powerful enough to eliminate both mature cancer cells and cancer stem cells without the cell and gene damage induced by chemotherapy and radiation. Correspondingly, the high margins of cancer mortality on a global scale are mitigated. This remarkable contribution to modern therapeutics will essentially optimize the margins of natural products and their derivatives, which account for 50% of pharmaceuticals in modern therapeutics, while preventing the adverse effects of radiation and chemotherapy drugs.

Keywords: antioxidant, apoptosis, metastasize, phytochemical, proliferation, potency

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Authors: Parvesh Singh, Vipan Kumar, Vishu Mehra

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Quinoline-4-ones represent an important class of heterocyclic scaffolds that have attracted significant interest due to their various biological and pharmacological activities. This heterocyclic unit also constitutes an integral component in drugs used for the treatment of neurodegenerative diseases, sleep disorders and in antibiotics viz. norfloxacin and ciprofloxacin. The synthetic accessibility and possibility of fictionalization at varied positions in quinoline-4-ones exemplifies an elegant platform for the designing of combinatorial libraries of functionally enriched scaffolds with a range of pharmacological profles. They are also considered to be attractive precursors for the synthesis of medicinally imperative molecules such as non-steroidal androgen receptor antagonists, antimalarial drug Chloroquine and martinellines with antibacterial activity. 2-Aryl-2,3-dihydroquinolin-4(1H)-ones are present in many natural and non-natural compounds and are considered to be the aza-analogs of favanones. The β-lactam class of antibiotics is generally recognized to be a cornerstone of human health care due to the unparalleled clinical efficacy and safety of this type of antibacterial compound. In addition to their biological relevance as potential antibiotics, β-lactams have also acquired a prominent place in organic chemistry as synthons and provide highly efficient routes to a variety of non-protein amino acids, such as oligopeptides, peptidomimetics, nitrogen-heterocycles, as well as biologically active natural and unnatural products of medicinal interest such as indolizidine alkaloids, paclitaxel, docetaxel, taxoids, cyptophycins, lankacidins, etc. A straight forward route toward the synthesis of quinoline-4-ones via the triflic acid assisted Fries rearrangement of N-aryl-βlactams has been reported by Tepe and co-workers. The ring expansion observed in this case was solely attributed to the inherent ring strain in β-lactam ring because -lactam failed to undergo rearrangement under reaction conditions. Theabovementioned protocol has been recently extended by our group for the synthesis of benzo[b]-azocinon-6-ones via a tandem Michael addition–Fries rearrangement of sorbyl anilides as well as for the single-pot synthesis of 2-aryl-quinolin-4(3H)-ones through the Fries rearrangement of 3-dienyl-βlactams. In continuation with our synthetic endeavours with the β-lactam ring and in view of the lack of convenient approaches for the synthesis of C-3 functionalized quinolin-4(1H)-ones, the present work describes the single-pot synthesis of C-3 functionalized quinolin-4(1H)-ones via the trific acid promoted Fries rearrangement of C-3 vinyl/isopropenyl substituted β-lactams. In addition, DFT calculations and MD simulations were performed to investigate the stability profles of synthetic compounds.

Keywords: dihydroquinoline, fries rearrangement, azetidin-2-ones, quinoline-4-ones

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Authors: M. R. Akbari , H. Yousefnia, E. Mirrezaei

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Range uncertainties of protons are currently a topic of interest in proton therapy. Two of the parameters that are often used to specify proton range are water equivalent thickness (WET) and water equivalent ratio (WER). Since WER values for a specific material is nearly constant at different proton energies, it is a more useful parameter to compare. In this study, WER values were calculated for different proton energies in polymethyl methacrylate (PMMA), polystyrene (PS) and aluminum (Al) using FLUKA and TRIM codes. The results were compared with analytical, experimental and simulated SEICS code data obtained from the literature. In FLUKA simulation, a cylindrical phantom, 1000 mm in height and 300 mm in diameter, filled with the studied materials was simulated. A typical mono-energetic proton pencil beam in a wide range of incident energies usually applied in proton therapy (50 MeV to 225 MeV) impinges normally on the phantom. In order to obtain the WER values for the considered materials, cylindrical detectors, 1 mm in height and 20 mm in diameter, were also simulated along the beam trajectory in the phantom. In TRIM calculations, type of projectile, energy and angle of incidence, type of target material and thickness should be defined. The mode of 'detailed calculation with full damage cascades' was selected for proton transport in the target material. The biggest difference in WER values between the codes was 3.19%, 1.9% and 0.67% for Al, PMMA and PS, respectively. In Al and PMMA, the biggest difference between each code and experimental data was 1.08%, 1.26%, 2.55%, 0.94%, 0.77% and 0.95% for SEICS, FLUKA and SRIM, respectively. FLUKA and SEICS had the greatest agreement (≤0.77% difference in PMMA and ≤1.08% difference in Al, respectively) with the available experimental data in this study. It is concluded that, FLUKA and TRIM codes have capability for Bragg curves simulation and WER values calculation in the studied materials. They can also predict Bragg peak location and range of proton beams with acceptable accuracy.

Keywords: water equivalent ratio, dosimetric materials, proton therapy, Monte Carlo simulations

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Authors: Vaikunthan Rajaratnam

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Maintaining continuous professional development among clinicians has been a challenge. Hand surgery is a unique speciality with the coming together of orthopaedics, plastics and trauma surgeons. The requirements for a team-based approach to care with the inclusion of other experts such as occupational, physiotherapist and orthotic and prosthetist provide the impetus for the creation of communities of practice. This study analysed the community of practice in hand surgery that was created through a social networking website for professionals. The main objectives were to discover the usefulness of this community of practice created in the platform of the group function of LinkedIn. The second objective was to determine the usability of this platform for the purposes of continuing professional development among members of this community of practice. The methodology used was one of mixed methods which included a quantitative analysis on the usefulness of the social network website as a community of practice, using the analytics provided by the LinkedIn platform. Further qualitative analysis was performed on the various postings that were generated by the community of practice within the social network website. This was augmented by a respondent driven survey conducted online to assess the usefulness of the platform for continuous professional development. A total of 31 respondents were involved in this study. This study has shown that it is possible to create an engaging and interactive community of practice among hand surgeons using the group function of this professional social networking website LinkedIn. Over three years the group has grown significantly with members from multiple regions and has produced engaging and interactive conversations online. From the results of the respondents’ survey, it can be concluded that there was satisfaction of the functionality and that it was an excellent platform for discussions and collaboration in the community of practice with a 69 % of satisfaction. Case-based discussions were the most useful functions of the community of practice. This platform usability was graded as excellent using the validated usability tool. This study has shown that the social networking site LinkedIn’s group function can be easily used as a community of practice effectively and provides convenience to professionals and has made an impact on their practice and better care for patients. It has also shown that this platform was easy to use and has a high level of usability for the average healthcare professional. This platform provided the improved connectivity among professionals involved in hand surgery care which allowed for the community to grow and with proper support and contribution of relevant material by members allowed for a safe environment for the exchange of knowledge and sharing of experience that is the foundation of a community practice.

Keywords: community of practice, online community, hand surgery, lifelong learning, LinkedIn, social media, continuing professional development

Procedia PDF Downloads 302

Authors: Hannele Kuusisto, Paivi Makila, Ursula Hyrkkanen

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Introduction: There have been arguments about the skills university students should have when graduated. Current trends argue that as well as the specific job-related skills the graduated students need problem-solving, interaction and networking skills as well as self-management skills. Skills required in working life are also considered in the Finnish national project called VALTE (short for 'prepared for working life'). The project involves 11 Finnish school organizations. As one result of this project, a five-credit independent online course in study and job engagement as well as in study and job crafting was developed at Turku University of Applied Sciences. The aim of the oral or e-poster presentation is to present the online course developed in the project. The purpose of this abstract is to present the development work of the online course and the feedback received from the pilots. Method: As the University of Turku is the leading partner of the VALTE project, the collaborative education platform ViLLE (https://ville.utu.fi, developed by the University of Turku) was chosen as the online platform for the course. Various exercise types with automatic assessment were used; for example, quizzes, multiple-choice questions, classification exercises, gap filling exercises, model answer questions, self-assessment tasks, case tasks, and collaboration in Padlet. In addition, the free material and free platforms on the Internet were used (Youtube, Padlet, Todaysmeet, and Prezi) as well as the net-based questionnaires about the study engagement and study crafting (made with Webropol). Three teachers with long teaching experience (also with job crafting and online pedagogy) and three students working as trainees in the project developed the content of the course. The online course was piloted twice in 2017 as an elective course for the students at Turku University of Applied Sciences, a higher education institution of about 10 000 students. After both pilots, feedback from the students was gathered and the online course was developed. Results: As the result, the functional five-credit independent online course suitable for students of different educational institutions was developed. The student feedback shows that students themselves think that the developed online course really enhanced their job and study crafting skills. After the course, 91% of the students considered their knowledge in job and study engagement as well as in job and study crafting to be at a good or excellent level. About two-thirds of the students were going to exploit their knowledge significantly in the future. Students appreciated the variability and the game-like feeling of the exercises as well as the opportunity to study online at the time and place they chose themselves. On a five-point scale (1 being poor and 5 being excellent), the students graded the clarity of the ViLLE platform as 4.2, the functionality of the platform as 4.0 and the easiness of operating as 3.9.

Keywords: job crafting, job engagement, online course, study crafting, study engagement

Procedia PDF Downloads 141

Authors: Madre Paarlber, Alwiena Blignaut

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Background: Medication administration errors remains a global patient safety problem targeted by the WHO (World Health Organization), yet research on this matter is sparce within the South African context. Objective: The aim was to explore and describe nurses’ (medication administrators) perceptions regarding medication administration safety-related culture, incidence, causes, and reporting in the Gauteng Province of South Africa, and to determine any relationships between perceived variables concerned with medication safety (safety culture, incidences, causes, reporting of incidences, and reasons for non-reporting). Method: A quantitative research design was used through which self-administered online surveys were sent to 768 nurses (medication administrators) (n=217). The response rate was 28.26%. The survey instrument was synthesised from the Agency of Healthcare Research and Quality (AHRQ) Hospital Survey on Patient Safety Culture, the Registered Nurse Forecasting (RN4CAST) survey, a survey list prepared from a systematic review aimed at generating a comprehensive list of medication administration error causes and the Medication Administration Error Reporting Survey from Wakefield. Exploratory and confirmatory factor analyses were used to determine the validity and reliability of the survey. Descriptive and inferential statistical data analysis were used to analyse quantitative data. Relationships and correlations were identified between items, subscales and biographic data by using Spearmans’ Rank correlations, T-Tests and ANOVAs (Analysis of Variance). Nurses reported on their perceptions of medication administration safety-related culture, incidence, causes, and reporting in the Gauteng Province. Results: Units’ teamwork deemed satisfactory, punitive responses to errors accentuated. “Crisis mode” working, concerns regarding mistake recording and long working hours disclosed as impacting patient safety. Overall medication safety graded mostly positively. Work overload, high patient-nurse ratios, and inadequate staffing implicated as error-inducing. Medication administration errors were reported regularly. Fear and administrative response to errors effected non-report. Non-report of errors’ reasons was affected by non-punitive safety culture. Conclusions: Medication administration safety improvement is contingent on fostering a non-punitive safety culture within units. Anonymous medication error reporting systems and auditing nurses’ workload are recommended in the quest of improved medication safety within Gauteng Province private hospitals.

Keywords: incidence, medication administration errors, medication safety, reporting, safety culture

Procedia PDF Downloads 29

Authors: Abbas Ali Husseini, Ali Mohammad Yazdani, Fatemeh Ghadiri, Alper Şişman

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We developed a microchip device that uses surface acoustic waves for rapid lysis of low level of cell samples. The device incorporates sharp-edge glass microparticles for improved performance. We optimized the lysis conditions for high efficiency and evaluated the device's feasibility for point-of-care applications. The microchip contains a 13-finger pair interdigital transducer with a 30-degree focused angle. It generates high-intensity acoustic beams that converge 6 mm away. The microchip operates at a frequency of 16 MHz, exciting Rayleigh waves with a 250 µm wavelength on the LiNbO3 substrate. Cell lysis occurs when Candida albicans cells and glass particles are placed within the focal area. The high-intensity surface acoustic waves induce centrifugal forces on the cells and glass particles, resulting in cell lysis through lateral forces from the sharp-edge glass particles. We conducted 42 pilot cell lysis experiments to optimize the surface acoustic wave-induced streaming. We varied electrical power, droplet volume, glass particle size, concentration, and lysis time. A regression machine-learning model determined the impact of each parameter on lysis efficiency. Based on these findings, we predicted optimal conditions: electrical signal of 2.5 W, sample volume of 20 µl, glass particle size below 10 µm, concentration of 0.2 µg, and a 5-minute lysis period. Downstream analysis successfully amplified a DNA target fragment directly from the lysate. The study presents an efficient microchip-based cell lysis method employing acoustic streaming and microparticle collisions within microdroplets. Integration of a surface acoustic wave-based lysis chip with an isothermal amplification method enables swift point-of-care applications.

Keywords: cell lysis, surface acoustic wave, micro-glass particle, droplet

Procedia PDF Downloads 64

Authors: Kemal Efe Eseller, Göktuğ Yazici

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Laser-induced breakdown spectroscopy (LIBS) is a rapid optical atomic emission spectroscopy which is used for material identification and analysis with the advantages of in-situ analysis, elimination of intensive sample preparation, and micro-destructive properties for the material to be tested. LIBS delivers short pulses of laser beams onto the material in order to create plasma by excitation of the material to a certain threshold. The plasma characteristics, which consist of wavelength value and intensity amplitude, depends on the material and the experiment’s environment. In the present work, medicine samples’ spectrum profiles were obtained via LIBS. Medicine samples’ datasets include two different concentrations for both paracetamol based medicines, namely Aferin and Parafon. The spectrum data of the samples were preprocessed via filling outliers based on quartiles, smoothing spectra to eliminate noise and normalizing both wavelength and intensity axis. Statistical information was obtained and principal component analysis (PCA) was incorporated to both the preprocessed and raw datasets. The machine learning models were set based on two different train-test splits, which were 70% training – 30% test and 80% training – 20% test. Cross-validation was preferred to protect the models against overfitting; thus the sample amount is small. The machine learning results of preprocessed and raw datasets were subjected to comparison for both splits. This is the first time that all supervised machine learning classification algorithms; consisting of Decision Trees, Discriminant, naïve Bayes, Support Vector Machines (SVM), k-NN(k-Nearest Neighbor) Ensemble Learning and Neural Network algorithms; were incorporated to LIBS data of paracetamol based pharmaceutical samples, and their different concentrations on preprocessed and raw dataset in order to observe the effect of preprocessing.

Keywords: machine learning, laser-induced breakdown spectroscopy, medicines, principal component analysis, preprocessing

Procedia PDF Downloads 72

Authors: E. T. Carvalho Filho, J. T. N. Medeiros, L. G. Martinez

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Residual stresses are self equilibrating in a rigid body that acts on the microstructure of the material without application of an external load. They are elastic stresses and can be induced by mechanical, thermal and chemical processes causing a deformation gradient in the crystal lattice favoring premature failure in mechanicals components. The search for measurements with good reliability has been of great importance for the manufacturing industries. Several methods are able to quantify these stresses according to physical principles and the response of the mechanical behavior of the material. The diffraction X-ray technique is one of the most sensitive techniques for small variations of the crystalline lattice since the X-ray beam interacts with the interplanar distance. Being very sensitive technique is also susceptible to variations in measurements requiring a study of the factors that influence the final result of the measurement. Instrumental, operational factors, form deviations of the samples and geometry of analyzes are some variables that need to be considered and analyzed in order for the true measurement. The aim of this work is to analyze the sources of errors inherent to the residual stress measurement process by X-ray diffraction technique making an interlaboratory comparison to verify the reproducibility of the measurements. In this work, two specimens were machined, differing from each other by the surface finishing: grinding and polishing. Additionally, iron powder with particle size less than 45 µm was selected in order to be a reference (as recommended by ASTM E915 standard) for the tests. To verify the deviations caused by the equipment, those specimens were positioned and with the same analysis condition, seven measurements were carried out at 11Ψ tilts. To verify sample positioning errors, seven measurements were performed by positioning the sample at each measurement. To check geometry errors, measurements were repeated for the geometry and Bragg Brentano parallel beams. In order to verify the reproducibility of the method, the measurements were performed in two different laboratories and equipments. The results were statistically worked out and the quantification of the errors.

Keywords: residual stress, x-ray diffraction, repeatability, reproducibility, error analysis

Procedia PDF Downloads 165

Authors: I. Bochev, A. Shterev, S. Kyurkchiev

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One of the factors associated with poor success rates in human in vitro fertilization (IVF) is the suboptimal culture conditions in which fertilization and early embryonic growth occur. Co-culture systems with helper cell lines appear to enhance the in vitro conditions and allow embryos to demonstrate improved in vitro development. The co-culture of human embryos with monolayers of autologous endometrial stromal cell (EnSCs) results in increased blastocyst development with a larger number of blastomeres, lower incidence of fragmentation and higher pregnancy rates in patients with recurrent implantation failure (RIF). The aim of the study was to examine the influence of autologous endometrial stromal cell (EnSC) co-culture on day 3 embryo quality by comparing the morphological status of the embryos from the same patients undergoing consecutive IVF/Intracytoplasmic sperm injection (ICSI) cycles without and with EnSC co-culture. This retrospective randomized study (2015-2017) includes 20 couples and a total of 46 IVF/ICSI cycles. Each patient couple included had at least two IVF/ICSI procedures – one with and one without autologous EnSC co-culture. Embryo quality was assessed at 68±1 hours in culture, according to Istanbul consensus criteria (2010). Day 3 embryos were classified into three groups: good – grade 1; fair – grade 2; poor – grade 3. Embryos from all cycles were divided into two groups (A – co-cultivated; B – not co-cultivated) and analyzed. Second, for each patient couple, embryos from matched IVF/ICSI cycles (with and without co-culture) were analyzed separately. When an analysis of co-cultivated day 3 embryos from all cycles was performed (n=137; group A), 43.1% of the embryos were graded as “good”, which was not significantly different from the respective embryo quality rate of 42.2% (p = NS) in group B (n=147) with non-co-cultivated embryos. The proportions of fair and poor quality embryos in group A and group B were similar as well – 11.7% vs 10.2% and 45.2% vs 47.6% (p=NS), respectively. Nevertheless, the separate embryo analysis by matched cycles for each couple revealed that in 65% of the cases the proportion of morphologically better embryos was increased in cycles with co-culture in comparison with those without co-culture. A decrease in this proportion after endometrial stromal cell co-cultivation was found in 30% of the cases, whereas no difference was observed in only one couple. The results demonstrated that there is no marked difference in the overall morphological quality between co-cultured and non-co-cultured embryos on day 3. However, in significantly greater percentage of couples the process of autologous EnSC co-culture could increase the proportion of morphologically improved day 3 embryos. By mimicking the in vivo relationship between embryo and maternal environment, co-culture in autologous EnSC system represents a perspective approach to improve the quality of embryos in cases with elevated risk for development of embryos with impaired morphology.

Keywords: autologous endometrial stromal cells, co-culture, day 3 embryo, morphological quality

Procedia PDF Downloads 208

Authors: I. C. Cho, W. H. Wen, H. Y. Tsai, T. C. Chao, C. J. Tung

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Tissue-equivalent proportional counter (TEPC) is a useful instrument used to measure radiation single-event energy depositions in a subcellular target volume. The quantity of measurements is the microdosimetric lineal energy, which determines the relative biological effectiveness, RBE, for radiation therapy or the radiation-weighting factor, WR, for radiation protection. TEPC is generally used in a mixed radiation field, where each component radiation has its own RBE or WR value. To reduce the pile-up effect during radiotherapy measurements, a miniature TEPC (mini TEPC) with cavity size in the order of 1 mm may be required. In the present work, a homemade mini TEPC with a cylindrical cavity of 1 mm in both the diameter and the height was constructed to measure the lineal energy spectrum of a mixed radiation field with high- and low-LET radiations. Instead of using external radiation beams to penetrate the detector wall, mixed radiation fields were produced by the interactions of neutrons with TEPC walls that contained small plugs of different materials, i.e. Li, B, A150, Cd and N. In all measurements, mini TEPC was placed at the beam port of the Tsing Hua Open-pool Reactor (THOR). Measurements were performed using the propane-based tissue-equivalent gas mixture, i.e. 55% C3H8, 39.6% CO2 and 5.4% N2 by partial pressures. The gas pressure of 422 torr was applied for the simulation of a 1 m diameter biological site. The calibration of mini TEPC was performed using two marking points in the lineal energy spectrum, i.e. proton edge and electron edge. Measured spectra revealed high lineal energy (> 100 keV/m) peaks due to neutron-capture products, medium lineal energy (10 – 100 keV/m) peaks from hydrogen-recoil protons, and low lineal energy (< 10 keV/m) peaks of reactor photons. For cases of Li and B plugs, the high lineal energy peaks were quite prominent. The medium lineal energy peaks were in the decreasing order of Li, Cd, N, A150, and B. The low lineal energy peaks were smaller compared to other peaks. This study demonstrated that internally produced mixed radiations from the interactions of neutrons with different plugs in the TEPC wall provided a useful approach for TEPC measurements of lineal energies.

Keywords: TEPC, lineal energy, microdosimetry, radiation quality

Procedia PDF Downloads 454

Authors: Bahram Besharti, Hossein Navid, Hadi Karimi, Hossein Behfar, Iraj Eskandari

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Multiple or miss sowing by seed drills is a common problem on the farm. This problem causes overuse of seeds, wasting energy, rising crop treatment cost and reducing crop yield in harvesting. To be informed of mentioned faults and monitoring the performance of seed drills during sowing, developing a seed sensor for detecting seed mass flow rate and monitoring in a delivery tube is essential. In this research, an infrared seed sensor was developed to estimate seed mass flow rate in seed drills. The developed sensor comprised of a pair of spaced apart circuits one acting as an IR transmitter and the other acting as an IR receiver. Optical coverage in the sensing section was obtained by setting IR LEDs and photo-diodes directly on opposite sides. Passing seeds made interruption in radiation beams to the photo-diode which caused output voltages to change. The voltage difference of sensing units summed by a microcontroller and were converted to an analog value by DAC chip. The sensor was tested by using a roller seed metering device with three types of seeds consist of chickpea, wheat, and alfalfa (representing large, medium and fine seed, respectively). The results revealed a good fitting between voltage received from seed sensor and mass flow of seeds in the delivery tube. A linear trend line was set for three seeds collected data as a model of the mass flow of seeds. A final mass flow model was developed for various size seeds based on receiving voltages from the seed sensor, thousand seed weight and equivalent diameter of seeds. The developed infrared seed sensor, besides monitoring mass flow of seeds in field operations, can be used for the assessment of mechanical planter seed metering unit performance in the laboratory and provide an easy calibrating method for seed drills before planting in the field.

Keywords: seed flow, infrared, seed sensor, seed drills

Procedia PDF Downloads 340

Authors: Paula I. Buonfiglio, Carlos David Bruque, Lucia Salatino, Vanesa Lotersztein, Sebastián Menazzi, Paola Plazas, Ana Belén Elgoyhen, Viviana Dalamón

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Hearing loss (HL) is the most prevalent sensorineural disorder affecting about 10% of the global population, with more than half due to genetic causes. About 1 in 500-1000 newborns present congenital HL. Most of the patients are non-syndromic with an autosomal recessive mode of inheritance. To date, more than 100 genes are related to HL. Therefore, the Whole-exome sequencing (WES) technique has become a cost-effective alternative approach for molecular diagnosis. Nevertheless, new challenges arise from the detection of novel variants, in particular missense changes, which can lead to a spectrum of genotype-to-phenotype correlations, which is not always straightforward. In this work, we aimed to identify the genetic causes of HL in isolated and familial cases by designing a multistep approach to analyze target genes related to hearing impairment. Moreover, we performed in silico and in vivo analyses in order to further study the effect of some of the novel variants identified in the hair cell function using the zebrafish model. A total of 650 patients were studied by Sanger Sequencing and Gap-PCR in GJB2 and GJB6 genes, respectively, diagnosing 15.5% of sporadic cases and 36% of familial ones. Overall, 50 different sequence variants were detected. Fifty of the undiagnosed patients with moderate HL were tested for deletions in STRC gene by Multiplex ligation-dependent probe amplification technique (MLPA), leading to 6% of diagnosis. After this initial screening, 50 families were selected to be analyzed by WES, achieving diagnosis in 44% of them. Half of the identified variants were novel. A missense variant in MYO6 gene detected in a family with postlingual HL was selected to be further analyzed. A protein modeling with AlphaFold2 software was performed, proving its pathogenic effect. In order to functionally validate this novel variant, a knockdown phenotype rescue assay in zebrafish was carried out. Injection of wild-type MYO6 mRNA in embryos rescued the phenotype, whereas using the mutant MYO6 mRNA (carrying c.2782C>A variant) had no effect. These results strongly suggest the deleterious effect of this variant on the mobility of stereocilia in zebrafish neuromasts, and hence on the auditory system. In the present work, we demonstrated that our algorithm is suitable for the sequential multigenic approach to HL in our cohort. These results highlight the importance of a combined strategy in order to identify candidate variants as well as the in silico and in vivo studies to analyze and prove their pathogenicity and accomplish a better understanding of the mechanisms underlying the physiopathology of the hearing impairment.

Keywords: diagnosis, genetics, hearing loss, in silico analysis, in vivo analysis, WES, zebrafish

Procedia PDF Downloads 74

Authors: Helnaz Soltani, J. N. Reddy

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Presence of fluid medium interacting with a structure can lead to failure of the structure. Since developing efficient computational model for fluid-structure interaction (FSI) problems has broader impact to realistic problems encountered in aerospace industry, ship industry, oil and gas industry, and so on, one can find an increasing need to find a method in order to investigate the effect of fluid domain on structural response. A coupled finite element formulation of problems involving FSI issue is an accurate method to predict the response of structures in contact with a fluid medium. This study proposes a finite element approach in order to study the transient response of the structures interacting with a fluid medium. Since beam and plate are considered to be the fundamental elements of almost any structure, the developed method is applied to beams and plates benchmark problems in order to demonstrate its efficiency. The formulation is a combination of the various structure theories and the solid-fluid interface boundary condition, which is used to represent the interaction between the solid and fluid regimes. Here, three different beam theories as well as three different plate theories are considered to model the solid medium, and the Navier-Stokes equation is used as the theoretical equation governed the fluid domain. For each theory, a coupled set of equations is derived where the element matrices of both regimes are calculated by Gaussian quadrature integration. The main feature of the proposed methodology is to model the fluid domain as an added mass; the external distributed force due to the presence of the fluid. We validate the accuracy of such formulation by means of some numerical examples. Since the formulation presented in this study covers several theories in literature, the applicability of our proposed approach is independent of any structure geometry. The effect of varying parameters such as structure thickness ratio, fluid density and immersion depth, are studied using numerical simulations. The results indicate that maximum vertical deflection of the structure is affected considerably in the presence of a fluid medium.

Keywords: beam and plate, finite element analysis, fluid-structure interaction, transient response

Procedia PDF Downloads 548

Authors: Nashaat A. Deiab, Aida Radwan, Mohamed Elnagdy, Mohamed S. Yahiya, Rasha Moustafa

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This study is to evaluate and investigate the dosimetric performance of our institution's 3D treatment planning system, Elekta PrecisePLAN, for open 6MV fields including square, rectangular, variation in SSD, centrally blocked, missing tissue, square MLC and MLC shaped fields guided by the recommended QA tests prescribed in AAPM TG53, NCS report 15 test packages, IAEA TRS 430 and ESTRO booklet no.7. The study was performed for Elekta Precise linear accelerator designed for clinical range of 4, 6 and 15 MV photon beams with asymmetric jaws and fully integrated multileaf collimator that enables high conformance to target with sharp field edges. Seven different tests were done applied on solid water equivalent phantom along with 2D array dose detection system, the calculated doses using 3D treatment planning system PrecisePLAN, compared with measured doses to make sure that the dose calculations are accurate for open fields including square, rectangular, variation in SSD, centrally blocked, missing tissue, square MLC and MLC shaped fields. The QA results showed dosimetric accuracy of the TPS for open fields within the specified tolerance limits. However large square (25cm x 25cm) and rectangular fields (20cm x 5cm) some points were out of tolerance in penumbra region (11.38 % and 10.9 %, respectively). For the test of SSD variation, the large field resulted from SSD 125 cm for 10cm x 10cm filed the results recorded an error of 0.2% at the central axis and 1.01% in penumbra. The results yielded differences within the accepted tolerance level as recommended. Large fields showed variations in penumbra. These differences between dose values predicted by the TPS and the measured values at the same point may result from limitations of the dose calculation, uncertainties in the measurement procedure, or fluctuations in the output of the accelerator.

Keywords: quality assurance, dose calculation, 3D treatment planning system, photon beam

Procedia PDF Downloads 496

Authors: Nigar Kantarci Carsibasi

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Coarse-grained elastic network models, namely Gaussian network model (GNM) and Anisotropic network model (ANM), are utilized in order to investigate the fluctuation dynamics of Murine Double Minute 2 (MDM2), which is the native inhibitor of p53. Conformational dynamics of MDM2 are elucidated in unbound, p53 bound, and non-peptide small molecule inhibitor bound forms. With this, it is aimed to gain insights about the alterations brought to global dynamics of MDM2 by native peptide inhibitor p53, and two small molecule inhibitors (HDM201 and NVP-CGM097) that are undergoing clinical stages in cancer studies. MDM2 undergoes significant conformational changes upon inhibitor binding, carrying pieces of evidence of induced-fit mechanism. Small molecule inhibitors examined in this work exhibit similar fluctuation dynamics and characteristic mode shapes with p53 when complexed with MDM2, which would shed light on the design of novel small molecule inhibitors for cancer therapy. The results showed that residues Phe 19, Trp 23, Leu 26 reside in the minima of slowest modes of p53, pointing to the accepted three-finger binding model. Pro 27 displays the most significant hinge present in p53 and comes out to be another functionally important residue. Three distinct regions are identified in MDM2, for which significant conformational changes are observed upon binding. Regions I (residues 50-77) and III (residues 90-105) correspond to the binding interface of MDM2, including (α2, L2, and α4), which are stabilized during complex formation. Region II (residues 77-90) exhibits a large amplitude motion, being highly flexible, both in the absence and presence of p53 or other inhibitors. MDM2 exhibits a scattered profile in the fastest modes of motion, while binding of p53 and inhibitors puts restraints on MDM2 domains, clearly distinguishing the kinetically hot regions. Mode shape analysis revealed that the α4 domain controls the size of the cleft by keeping the cleft narrow in unbound MDM2; and open in the bound states for proper penetration and binding of p53 and inhibitors, which points to the induced-fit mechanism of p53 binding. P53 interacts with α2 and α4 in a synchronized manner. Collective modes are shifted upon inhibitor binding, i.e., second mode characteristic motion in MDM2-p53 complex is observed in the first mode of apo MDM2; however, apo and bound MDM2 exhibits similar features in the softest modes pointing to pre-existing modes facilitating the ligand binding. Although much higher amplitude motions are attained in the presence of non-peptide small molecule inhibitor molecules as compared to p53, they demonstrate close similarity. Hence, NVP-CGM097 and HDM201 succeed in mimicking the p53 behavior well. Elucidating how drug candidates alter the MDM2 global and conformational dynamics would shed light on the rational design of novel anticancer drugs.

Keywords: cancer, drug design, elastic network model, MDM2

Procedia PDF Downloads 115

Authors: Christopher Baiyegunhi, Kuiwu Liu, Oswald Gwavava

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Grain size analysis is a vital sedimentological tool used to unravel the hydrodynamic conditions, mode of transportation and deposition of detrital sediments. In this study, detailed grain-size analysis was carried out on thirty-five sandstone samples from the Ecca Group in the Eastern Cape Province of South Africa. Grain-size statistical parameters, bivariate analysis, linear discriminate functions, Passega diagrams and log-probability curves were used to reveal the depositional processes, sedimentation mechanisms, hydrodynamic energy conditions and to discriminate different depositional environments. The grain-size parameters show that most of the sandstones are very fine to fine grained, moderately well sorted, mostly near-symmetrical and mesokurtic in nature. The abundance of very fine to fine grained sandstones indicates the dominance of low energy environment. The bivariate plots that the samples are mostly grouped, except for the Prince Albert samples that show scattered trend, which is due to the either mixture of two modes in equal proportion in bimodal sediments or good sorting in unimodal sediments. The linear discriminant function (LDF) analysis is dominantly indicative of turbidity current deposits under shallow marine environments for samples from the Prince Albert, Collingham and Ripon Formations, while those samples from the Fort Brown Formation are fluvial (deltaic) deposits. The graphic mean value shows the dominance of fine sand-size particles, which point to relatively low energy conditions of deposition. In addition, the LDF results point to low energy conditions during the deposition of the Prince Albert, Collingham and part of the Ripon Formation (Pluto Vale and Wonderfontein Shale Members), whereas the Trumpeters Member of the Ripon Formation and the overlying Fort Brown Formation accumulated under high energy conditions. The CM pattern shows a clustered distribution of sediments in the PQ and QR segments, indicating that the sediments were deposited mostly by suspension and rolling/saltation, and graded suspension. Furthermore, the plots also show that the sediments are mainly deposited by turbidity currents. Visher diagrams show the variability of hydraulic depositional conditions for the Permian Ecca Group sandstones. Saltation is the major process of transportation, although suspension and traction also played some role during deposition of the sediments. The sediments were mainly in saltation and suspension before being deposited.

Keywords: grain size analysis, hydrodynamic condition, depositional environment, Ecca Group, South Africa

Procedia PDF Downloads 460