Search results for: assembling

Authors: S. Behnia, S. Fathizadeh, A. Akhshani

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In the recent decades, DNA has increasingly interested in the potential technological applications that not directly related to the coding for functional proteins that is the expressed in form of genetic information. One of the most interesting applications of DNA is related to the construction of nanostructures of high complexity, design of functional nanostructures in nanoelectronical devices, nanosensors and nanocercuits. In this field, DNA is of fundamental interest to the development of DNA-based molecular technologies, as it possesses ideal structural and molecular recognition properties for use in self-assembling nanodevices with a definite molecular architecture. Also, the robust, one-dimensional flexible structure of DNA can be used to design electronic devices, serving as a wire, transistor switch, or rectifier depending on its electronic properties. In order to understand the mechanism of the charge transport along DNA sequences, numerous studies have been carried out. In this regard, conductivity properties of DNA molecule could be investigated in a simple, but chemically specific approach that is intimately related to the Su-Schrieffer-Heeger (SSH) model. In SSH model, the non-diagonal matrix element dependence on intersite displacements is considered. In this approach, the coupling between the charge and lattice deformation is along the helix. This model is a tight-binding linear nanoscale chain established to describe conductivity phenomena in doped polyethylene. It is based on the assumption of a classical harmonic interaction between sites, which is linearly coupled to a tight-binding Hamiltonian. In this work, the Hamiltonian and corresponding motion equations are nonlinear and have high sensitivity to initial conditions. Then, we have tried to move toward the nonlinear dynamics and phase space analysis. Nonlinear dynamics and chaos theory, regardless of any approximation, could open new horizons to understand the conductivity mechanism in DNA. For a detailed study, we have tried to study the current flowing in DNA and investigated the characteristic I-V diagram. As a result, It is shown that there are the (quasi-) ohmic areas in I-V diagram. On the other hand, the regions with a negative differential resistance (NDR) are detectable in diagram.

Keywords: DNA conductivity, Landauer resistance, negative dierential resistance, Chaos theory, mean Lyapunov exponent

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Authors: Tomasz Dubiel, Tadeusz Balawender, Miroslaw Osetek

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The paper presents the influence of non-metallic inclusions on the multi-stage forging process and the mechanical properties of the dodecagon socket bolt used in the automotive industry. The detected metallurgical defect was so large that it directly influenced the mechanical properties of the bolt and resulted in failure to meet the requirements of the mechanical property class. In order to assess the defect, an X-ray examination and metallographic examination of the defective bolt were performed, showing exogenous non-metallic inclusion. The size of the defect on the cross-section was 0.531 [mm] in width and 1.523 [mm] in length; the defect was continuous along the entire axis of the bolt. In analysis, a FEM simulation of the multi-stage forging process was designed, taking into account a non-metallic inclusion parallel to the sample axis, reflecting the studied case. The process of defect propagation due to material upset in the head area was analyzed. The final forging stage in shaping the dodecagonal socket and filling the flange area was particularly studied. The effect of the defect was observed to significantly reduce the effective cross-section as a result of the expansion of the defect perpendicular to the axis of the bolt. The mechanical properties of products with and without the defect were analyzed. In the first step, the hardness test confirmed that the required value for the mechanical class 8.8 of both bolt types was obtained. In the second step, the bolts were subjected to a static tensile test. The bolts without the defect gave a positive result, while all 10 bolts with the defect gave a negative result, achieving a tensile strength below the requirements. Tensile strength tests were confirmed by metallographic tests and FEM simulation with perpendicular inclusion spread in the area of the head. The bolts were damaged directly under the bolt head, which is inconsistent with the requirements of ISO 898-1. It has been shown that non-metallic inclusions with orientation in accordance with the axis of the bolt can directly cause loss of functionality and these defects should be detected even before assembling in the machine element.

Keywords: continuous casting, multi-stage forging, non-metallic inclusion, upset bolt head

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Authors: Massimiliano Condotta, Paolo Ruggeri, Chiara Scanagatta, Giovanni Borga

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Architects and urban planners, when designing and renewing cities, have to face a complex set of problems, including the issues of noise and air pollution which are considered as hot topics (i.e., the Clean Air Act of London and the Soundscape definition). It is usually taken for granted that these problems go by together because the noise pollution present in cities is often linked to traffic and industries, and these produce air pollutants as well. Traffic congestion can create both noise pollution and air pollution, because NO₂ is mostly created from the oxidation of NO, and these two are notoriously produced by processes of combustion at high temperatures (i.e., car engines or thermal power stations). We can see the same process for industrial plants as well. What have to be investigated – and is the topic of this paper – is whether or not there really is a correlation between noise pollution and air pollution (taking into account NO₂) in urban areas. To evaluate if there is a correlation, some low-cost methodologies will be used. For noise measurements, the OpeNoise App will be installed on an Android phone. The smartphone will be positioned inside a waterproof box, to stay outdoor, with an external battery to allow it to collect data continuously. The box will have a small hole to install an external microphone, connected to the smartphone, which will be calibrated to collect the most accurate data. For air, pollution measurements will be used the AirMonitor device, an Arduino board to which the sensors, and all the other components, are plugged. After assembling the sensors, they will be coupled (one noise and one air sensor) and placed in different critical locations in the area of Mestre (Venice) to map the existing situation. The sensors will collect data for a fixed period of time to have an input for both week and weekend days, in this way it will be possible to see the changes of the situation during the week. The novelty is that data will be compared to check if there is a correlation between the two pollutants using graphs that should show the percentage of pollution instead of the values obtained with the sensors. To do so, the data will be converted to fit on a scale that goes up to 100% and will be shown thru a mapping of the measurement using GIS methods. Another relevant aspect is that this comparison can help to choose which are the right mitigation solutions to be applied in the area of the analysis because it will make it possible to solve both the noise and the air pollution problem making only one intervention. The mitigation solutions must consider not only the health aspect but also how to create a more livable space for citizens. The paper will describe in detail the methodology and the technical solution adopted for the realization of the sensors, the data collection, noise and pollution mapping and analysis.

Keywords: air quality, data analysis, data collection, NO₂, noise mapping, noise pollution, particulate matter

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Authors: Rizwan Ahmed Bhutto, Noor ul ain Hira Bhutto, Mingwei Wang, Shahid Iqbal, Jiang Yi

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Curcumin, a natural polyphenolic compound, boasts numerous health benefits; however, its industrial applications are hindered by instabilities and poor solubility. Encapsulating curcumin in Pickering emulsion presents a promising strategy to enhance its bioavailability. Yet, the development of an efficient and straightforward method to fabricate a natural emulsifier for Pickering emulsion poses a significant challenge. Chitosan has garnered attention due to its non-toxicity and excellent emulsifying properties. This study aimed to prepare four distinct types of self-aggregated chitosan particles using a pH-responsive self-assembling approach. The properties of the aggregated particles were adjusted by pH, degree of deacetylation (DDA), and molecular weight (MW), thereby controlling surface charge, size (ranging from nano to micro and floc), and contact angle. Pickering emulsions were then formulated using these various aggregated particles. As MW and pH increased and DDA decreased, the networked structures of the aggregated particles formed, resulting in highly elastic gels that were more resistant to the breakdown of Pickering emulsion at ambient temperature. With elevated temperatures, the kinetic energy of the aggregated particles increased, disrupting hydrogen bonds and potentially transforming the systems from fluids to gels. The Pickering emulsion based on aggregated particles served as a carrier for curcumin encapsulation. It was observed that DDA and MW played crucial roles in regulating drug loading, encapsulation efficiency, and release profile. This research sheds light on selecting suitable chitosan for controlling the release of bioactive compounds in Pickering emulsions, considering factors such as adjustable rheological properties, microstructure, and macrostructure. Furthermore, this study introduces an environmentally friendly and cost-effective synthesis of pH-responsive aggregate particles without the need for high-pressure homogenizers. It underscores the potential of aggregate particles with various MWs and DDAs for encapsulating other bioactive compounds, offering valuable applications in industries including food, flavor/fragrance, cosmetics, and medicine.

Keywords: chitosan, molecular weight, rheological properties, curcumin encapsulation

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Authors: Navid P Roodaki, Rochelle Abila, Daisy Evangeline Garcia

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Background and Objective: Respiratory Distress Syndrome (RDS) among premature infants is a major causes of neonatal death. The use of Continuous Positive Airway Pressure (CPAP) has become a standard of care for preterm newborns with RDS hence cost-effective innovations are needed. This study compared a novel low-cost Bubble CPAP (bCPAP) device to ventilator driven CPAP in the treatment of RDS. Methods: This is a single-blind, randomized controlled trial done on May 2022 to October 2022 in a Level III Neonatal Intensive Care Unit in the Philippines. Preterm newborns (<36 weeks) with RDS were randomized to receive Vayu bCPAP device or Ventilator-derived CPAP. Arterial Blood Gases, Oxygen Saturation, administration of surfactant, and CPAP failure rates were measured. Results: Seventy preterm newborns were included. No differences were observed between the Ventilator driven CPAP and Vayu bCPAP on the PaO2 (97.51mmHg vs 97.37mmHg), So2 (97.08% vs 95.60%) levels, amount of surfactant administered between groups. There were no observed differences in CPAP failure rates between Vayu bPCAP (x̄ 3.23 days) and ventilator-driven CPAP (x̄ 2.98 days). However, a significant difference was noted on the CO2 level (40.32mmHg vs 50.70mmHg), which was higher among those hooked to Ventilator-driven CPAP (p 0.004). Conclusion: This study has shown that the novel low-cost bubble CPAP (Vayu bCPAP) can be used as an efficacious alternate non invasive oxygen therapy among preterm neonates with RDS, although the CO2 levels were higher among those hooked to ventilator driven CPAP, other outcome parameters measured showed that both devices are comparable. Recommendation: A multi-center or national study to account for geographic region, which may alter the outcomes of patients connected to different ventilatory support. Cost comparison between devices is also suggested. A mixed-method research assessing the experiences of health care professionals in assembling and utilizing the gadget is a second consideration.

Keywords: bubble CPAP, ventilator-derived CPAP; infant, premature, respiratory distress syndrome

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Authors: Lee Cahaner, Nissim Leon

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The segregation of populations is one of the main axes in the research of urban geography, which refers to the spatial and functional relationships between settlements. In Israel, this phenomenon has its unique expression in the spatial processes concerning the ultra-orthodox population. This population holds a set of interactions within itself as well as with the non-orthodox surrounding population because of historical and contemporary motivations on its which strength depends on its homogeneousness and separation. Its demographic growth rate and the internal social processes that the ultra-orthodox society undergoes create a new image of the ultra-orthodox concentration and its location in the Israeli space. The goals of the present study have also been defined with the express intention of filling the scholarly vacuum noted above: firstly, to discuss the development of the Israeli ultra-Orthodox sector’s hierarchical and spatial structure as of 2015, in light of the principles and mechanisms that guide it and vis-à-vis the general population’s hierarchical locality system; secondly, to map Israel’s ultra-Orthodox population, with attention to its physical boundaries, its subdivisions (Hassidic, Lithuanian, Sephardic) and the geographical and demographic processes that have characterized it in recent years; and thirdly, to shed light on the interactions between ultra-Orthodox localities via several different parameters, e.g. migration, education, transportation, employment, consumerism and community services. In order to understand the changes in ultra-Orthodox geographic distribution and the social processes that these changes have generated, a number of research activities were conducted during the course of this study− notably, gathering and assembling material from earlier academic studies, newspaper advertisements, state and private archives; in-depth interviews with major figures in the ultra-Orthodox community and others who come into contact with it; tours of the core areas of ultra-Orthodox settlement; and gathering quantitative and qualitative data from the statistical reports of governmental and other bodies. In addition, a multi-participant (2400-respondent) quantitative survey was conducted among residents of the new ultra-Orthodox cities, designed to elucidate the attributes and spatial attitudes of the residents− as a means of tracing and understanding this new settlement pattern within ultra-Orthodox space. A major portion of the quantitative and qualitative material was processed to form a system of maps that visually describe the distribution of Israel’s ultra-Orthodox population.

Keywords: migration, new cities, segregation, ultra-orthodox

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Authors: Pisut Boonkaew, Jatuporn Thongsri

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In hard disk drive manufacturing industry, the process of reducing an unnecessary part and qualifying the quality of part before assembling is important. Thus, clamp was designed and fabricated as a fixture for holding in testing process. Basically, testing by trial and error consumes a long time to improve. Consequently, the simulation was brought to improve the part and reduce the time taken. The problem is the present clamp has a low life expectancy because of the critical stress that occurred. Hence, the simulation was brought to study the behavior of stress and compressive force to improve the clamp expectancy with all probability of designs which are present up to 27 designs, which excluding the repeated designs. The probability was calculated followed by the full fractional rules of six sigma methodology which was provided correctly. The six sigma methodology is a well-structured method for improving quality level by detecting and reducing the variability of the process. Therefore, the defective will be decreased while the process capability increasing. This research focuses on the methodology of stress and fatigue reduction while compressive force still remains in the acceptable range that has been set by the company. In the simulation, ANSYS simulates the 3D CAD with the same condition during the experiment. Then the force at each distance started from 0.01 to 0.1 mm will be recorded. The setting in ANSYS was verified by mesh convergence methodology and compared the percentage error with the experimental result; the error must not exceed the acceptable range. Therefore, the improved process focuses on degree, radius, and length that will reduce stress and still remain in the acceptable force number. Therefore, the fatigue analysis will be brought as the next process in order to guarantee that the lifetime will be extended by simulating through ANSYS simulation program. Not only to simulate it, but also to confirm the setting by comparing with the actual clamp in order to observe the different of fatigue between both designs. This brings the life time improvement up to 57% compared with the actual clamp in the manufacturing. This study provides a precise and trustable setting enough to be set as a reference methodology for the future design. Because of the combination and adaptation from the six sigma method, finite element, fatigue and linear regressive analysis that lead to accurate calculation, this project will able to save up to 60 million dollars annually.

Keywords: clamp, finite element analysis, structural, six sigma, linear regressive analysis, fatigue analysis, probability

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Authors: Robson da Cunha Santos, Caio Cezar R. Bonifacio, Diego Mureb Quesada, Gerson Gomes Cunha

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The paper is related to the safety of oil wells and environmental preservation on the planet, because they require great attention and commitment from oil companies and people who work with these equipments. This must occur from drilling the well until it is abandoned in order to safeguard the environment and prevent possible damage. The project had as main objective the constitution resulting from comparatives made among books, articles and publications with information gathered in technical visits to operational bases of Petrobras. After the visits, the information from methods of utilization and present managements, which were not available before, became available to the general audience. As a result, it is observed a huge flux of incorrect and out-of-date information that comprehends not only bibliographic archives, but also academic resources and materials. During the gathering of more in-depth information on the manufacturing, assembling, and use aspects of DHSVs, several issues that were previously known as correct, customary issues were discovered to be uncertain and outdated. Information of great importance resulted in affirmations about subjects as the depth of the valve installation that was before installed to 30 meters from the seabed (mud line). Despite this, the installation should vary in conformity to the ideal depth to escape from area with the biggest tendency to hydrates formation according to the temperature and pressure. Regarding to valves with nitrogen chamber, in accordance with books, they have their utilization linked to water line ≥ 700 meters, but in Brazilian exploratory fields, their use occurs from 600 meters of water line. The valves used in Brazilian fields are able to be inserted to the production column and self-equalizing, but the use of screwed valve in the column of production and equalizing is predominant. Although these valves are more expensive to acquire, they are more reliable, efficient, with a bigger shelf life and they do not cause restriction to the fluid flux. It follows that based on researches and theoretical information confronted to usual forms used in fields, the present project is important and relevant. This project will be used as source of actualization and information equalization that connects academic environment and real situations in exploratory situations and also taking into consideration the enrichment of precise and easy to understand information to future researches and academic upgrading.

Keywords: down hole safety valve, security devices, installation, oil-wells

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Authors: S. Srinivasan, E. Cretu

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The information flow (e.g. block-diagram or signal flow graph) paradigm for the design and simulation of Microelectromechanical (MEMS)-based systems allows to model MEMS devices using causal transfer functions easily, and interface them with electronic subsystems for fast system-level explorations of design alternatives and optimization. Nevertheless, the physical bi-directional coupling between different energy domains is not easily captured in causal signal flow modeling. Moreover, models of fundamental components acting as building blocks (e.g. gap-varying MEMS capacitor structures) depend not only on the component, but also on the specific excitation mode (e.g. voltage or charge-actuation). In contrast, the energy flow modeling paradigm in terms of generalized across-through variables offers an acausal perspective, separating clearly the physical model from the boundary conditions. This promotes reusability and the use of primitive physical models for assembling MEMS devices from primitive structures, based on the interconnection topology in generalized circuits. The physical modeling capabilities of Simscape have been used in the present work in order to develop a MEMS library containing parameterized fundamental building blocks (area and gap-varying MEMS capacitors, nonlinear springs, displacement stoppers, etc.) for the design, simulation and optimization of MEMS inertial sensors. The models capture both the nonlinear electromechanical interactions and geometrical nonlinearities and can be used for both small and large signal analyses, including the numerical computation of pull-in voltages (stability loss). Simscape behavioral modeling language was used for the implementation of reduced-order macro models, that present the advantage of a seamless interface with Simulink blocks, for creating hybrid information/energy flow system models. Test bench simulations of the library models compare favorably with both analytical results and with more in-depth finite element simulations performed in ANSYS. Separate MEMS-electronic integration tests were done on closed-loop MEMS accelerometers, where Simscape was used for modeling the MEMS device and Simulink for the electronic subsystem.

Keywords: across-through variables, electromechanical coupling, energy flow, information flow, Matlab/Simulink, MEMS, nonlinear, pull-in instability, reduced order macro models, Simscape

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Authors: Wei Wang, Yuan Hu

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Epoxy resins (EP), one of the most important thermosetting polymers, is widely applied in various fields due to its desirable properties, such as excellent electrical insulation, low shrinkage, outstanding mechanical stiffness, satisfactory adhesion and solvent resistance. However, like most of the polymeric materials, EP has the fatal drawbacks including inherent flammability and high yield of toxic smoke, which restricts its application in the fields requiring fire safety. So, it is still a challenge and an interesting subject to develop new flame retardants which can not only remarkably improve the flame retardancy, but also render modified resins low toxic gases generation. In recent work, polymer nanocomposites based on nanohybrids that contain two or more kinds of nanofillers have drawn intensive interest, which can realize performance enhancements. The realization of previous hybrids of carbon nanotubes (CNTs) and molybdenum disulfide provides us a novel route to decorate layered double hydroxide (LDH) nanosheets on the surface of β-FeOOH nanorods; the deposited LDH nanosheets can fill the network and promote the work efficiency of β-FeOOH nanorods. Moreover, the synergistic effects between LDH and β-FeOOH can be anticipated to have potential applications in reducing fire hazards of EP composites for the combination of condense-phase and gas-phase mechanism. As reported, β-FeOOH nanorods can act as a core to prepare hybrid nanostructures combining with other nanoparticles through electrostatic attraction through layer-by-layer assembly technique. In this work, LDH nanosheets wrapped β-FeOOH nanorods (LDH-β-FeOOH) hybrids was synthesized by a facile method, with the purpose of combining the characteristics of one dimension (1D) and two dimension (2D), to improve the fire resistance of epoxy resin. The hybrids showed a well dispersion in EP matrix and had no obvious aggregation. Thermogravimetric analysis and cone calorimeter tests confirmed that LDH-β-FeOOH hybrids into EP matrix with a loading of 3% could obviously improve the fire safety of EP composites. The plausible flame retardancy mechanism was explored by thermogravimetric infrared (TG-IR) and X-ray photoelectron spectroscopy. The reasons were concluded: condense-phase and gas-phase. Nanofillers were transferred to the surface of matrix during combustion, which could not only shield EP matrix from external radiation and heat feedback from the fire zone, but also efficiently retard transport of oxygen and flammable pyrolysis.

Keywords: fire hazards, toxic gases, self-assembly, epoxy

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Authors: Guohong Wang, Hao Huang, Rui Xing, Liyan Tang, Yu Wang

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Start-ups are consistently under pressure to overcome liabilities of newness and smallness. They must focus on assembling resource and engaging constant renewal and repeated entrepreneurial activities to survive and grow. As an important form of resource, knowledge is constantly vital to start-ups, which will help start-ups with developing new product in hence forming competitive advantage. However, significant knowledge is usually needed to be identified and exploited from external entities, which makes it difficult to achieve knowledge transfer; with limited resources, it can be quite challenging for start-ups balancing the exploration and exploitation of knowledge. The research on knowledge transfer has become a relatively well-developed domain by indicating that knowledge transfer can be achieved through plenty of patterns, yet it is still under-explored that what processes and organizational practices help start-ups facilitating knowledge transfer for new product in the context portfolio entrepreneurship. Resource orchestration theory emphasizes the initiative and active management of company or the manager to explain the fulfillment of resource utility, which will help understand the process of managing knowledge as a certain kind of resource in start-ups. Drawing on the resource orchestration theory, this research aims to explore how knowledge transfer can be facilitated through resource orchestration. A qualitative single-case study of a sodium-ion battery new venture was conducted. The case company is sampled deliberately from representative industrial agglomeration areas in Liaoning Province, China. It is found that distinctive resource orchestration sub-processes are leveraged to facilitate knowledge transfer: (i) resource structuring makes knowledge available across the portfolio; (ii) resource bundling makes combines internal and external knowledge to form new knowledge; and (iii) resource harmonizing balances specific knowledge configurations across the portfolio. Meanwhile, by purposefully reallocating knowledge configurations to new product development in a certain new venture (exploration) and gradually adjusting knowledge configurations to being applied to existing products across the portfolio (exploitation), resource orchestration processes as a whole make exploration and exploitation of knowledge balanced. This study contributes to the knowledge management literature through proposing a resource orchestration view and depicting how knowledge transfer can be facilitated through different resource orchestration processes and mechanisms. In addition, by revealing the balancing process of exploration and exploitation of knowledge, and laying stress on the significance of the idea of making exploration and exploitation of knowledge balanced in the context of portfolio entrepreneurship, this study also adds specific efforts to entrepreneurship and strategy management literature.

Keywords: exploration and exploitation, knowledge transfer, new product development, portfolio entrepreneur, resource orchestration

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Authors: Ludmila Vucolova

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The thought is a process that underlies consciousness and cognition and understanding its origin and processes is a longstanding goal of many academic disciplines. By integrating over twenty novel ideas and hypotheses of this theoretical proposal, we can speculate that thought is an emergent property of coded neural events, translating the electro-chemical interactions of the body with its environment—the objects of sensory stimulation, X, and Y. The latter is a self- generated feedback entity, resulting from the arbitrary pattern of the motion of a body’s motor repertory (M). A culmination of these neural events gives rise to a thought: a state of identity between an observed object X and a symbol Y. It manifests as a “state of awareness” or “state of knowing” and forms our perception of the physical world. The values of the variables of a construct—X (object), S1 (sense for the perception of X), Y (object), S2 (sense for perception of Y), and M (motor repertory that produces Y)—will specify the particular conscious percept at any given time. The proposed principle of interaction between the elements of a construct (X, Y, S1, S2, M) is universal and applies for all modes of communication (normal, deaf, blind, deaf and blind people) and for various language systems (Chinese, Italian, English, etc.). The particular arrangement of modalities of each of the three modules S1 (5 of 5), S2 (1 of 3), and M (3 of 3) defines a specific mode of communication. This multifaceted paradigm demonstrates a predetermined pattern of relationships between X, Y, and M that passes from generation to generation. The presented analysis of a cognitive experience encompasses the key elements of embodied cognition theories and unequivocally accords with the scientific interpretation of cognition as the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses, and cognition means thinking and awareness. By assembling the novel ideas presented in twelve sections, we can reveal that in the invisible “chaos”, there is an order, a structure with landmarks and principles of operations and mental processes (thoughts) are physical and have a biological basis. This innovative proposal explains the phenomenon of mental imagery; give the first insight into the relationship between mental states and brain states, and support the notion that mind and body are inseparably connected. The findings of this theoretical proposal are supported by the current scientific data and are substantiated by the records of the evolution of language and human intelligence.

Keywords: agent, awareness, cognitive, element, experience, feedback, first person, imagery, language, mental, motor, object, sensory, symbol, thought

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Authors: Michael N. O'Sullivan, Con Sheahan

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Researchers have spent decades developing tools and techniques to aid teams in the new product development (NPD) process. Despite this, it is evident that there is a huge gap between their academic prevalence and their industry adoption. For the fuzzy front-end, in particular, there is a wide range of tools to choose from, including the Kano Model, the House of Quality, and many others. In fact, there are so many tools that it can often be difficult for teams to know which ones to use and how they interact with one another. Moreover, while the benefits of using these tools are obvious to industrialists, they are rarely used as they carry a learning curve that is too steep and they become too complex to manage over time. In essence, it is commonly believed that they are simply not worth the effort required to learn and use them. This research explores a streamlined process for the fuzzy front-end, assembling the most effective tools and making them accessible to everyone. The process was developed iteratively over the course of 3 years, following over 80 final year NPD teams from engineering, design, technology, and construction as they carried a product from concept through to production specification. Questionnaires, focus groups, and observations were used to understand the usability issues with the tools involved, and a human-centred design approach was adopted to produce a solution to these issues. The solution takes the form of physical toolkit, similar to a board game, which allows the team to play through an example of a new product development in order to understand the process and the tools, before using it for their own product development efforts. A complimentary website is used to enhance the physical toolkit, and it provides more examples of the tools being used, as well as deeper discussions on each of the topics, allowing teams to adapt the process to their skills, preferences and product type. Teams found the solution very useful and intuitive and experienced significantly less confusion and mistakes with the process than teams who did not use it. Those with a design background found it especially useful for the engineering principles like Quality Function Deployment, while those with an engineering or technology background found it especially useful for design and customer requirements acquisition principles, like Voice of the Customer. Products developed using the toolkit are added to the website as more examples of how it can be used, creating a loop which helps future teams understand how the toolkit can be adapted to their project, whether it be a small consumer product or a large B2B service. The toolkit unlocks the potential of these beneficial tools to those in industry, both for large, experienced teams and for inexperienced start-ups. It allows users to assess the market potential of their product concept faster and more effectively, arriving at the product design stage with technical requirements prioritized according to their customers’ needs and wants.

Keywords: new product development, fuzzy front-end, usability, Kano model, quality function deployment, voice of customer

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Authors: Rio Hirakawa, Christian Gundlach, Sven Hartwig

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In recent years, the use of aluminium has further expanded and is expected to replace steel in the future as vehicles become lighter and more recyclable in order to reduce greenhouse gas (GHG) emissions and improve fuel economy. In line with this, structures and components are becoming increasingly multi-material, with different materials, including aluminium, being used in combination to improve mechanical utility and performance. A common method of assembling dissimilar materials is mechanical fastening, but it has several drawbacks, such as increased manufacturing processes and the influence of substrate-specific mechanical properties. Adhesive bonding and fusion bonding are methods that overcome the above disadvantages. In these two joining methods, surface pre-treatment of the substrate is always necessary to ensure the strength and durability of the joint. Previous studies have shown that laser surface treatment improves the strength and durability of the joint. Yan et al. showed that laser surface treatment of aluminium alloys changes α-Al2O3 in the oxide layer to γ-Al2O3. As γ-Al2O3 has a large specific surface area, is very porous and chemically active, laser-treated aluminium surfaces are expected to undergo physico-chemical changes over time and adsorb moisture and organic substances from the air or storage atmosphere. The impurities accumulated on the laser-treated surface may be released at the adhesive and bonding interface by the heat input to the bonding system during the joining phase, affecting the strength and durability of the joint. However, only a few studies have discussed the effect of such storage periods on laser-treated surfaces. This paper, therefore, investigates the ageing of laser-treated aluminium alloy surfaces through thermal analysis, electrochemical analysis and microstructural observations.AlMg3 of 0.5 mm and 1.5 mm thickness was cut using a water-jet cutting machine, cleaned and degreased with isopropanol and surface pre-treated with a pulsed fibre laser at 1060 nm wavelength, 70 W maximum power and 55 kHz repetition frequency. The aluminium surface was then analysed using SEM, thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR) and cyclic voltammetry (CV) after storage in air for various periods ranging from one day to several months TGA and FTIR analysed impurities adsorbed on the aluminium surface, while CV revealed changes in the true electrochemically active surface area. SEM also revealed visual changes on the treated surface. In summary, the changes in the laser-treated aluminium surface with storage time were investigated, and the final results were used to determine the appropriate storage period.

Keywords: laser surface treatment, pre-treatment, adhesion, bonding, corrosion, durability, dissimilar material interface, automotive, aluminium alloys

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Authors: Rio Hirakawa, Christian Gundlach, Sven Hartwig

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Aluminium has been used in a wide range of industrial applications due to its numerous advantages, including excellent specific strength, thermal conductivity, corrosion resistance, workability and recyclability. The automotive industry is increasingly adopting multi-materials, including aluminium in structures and components to improve the mechanical usability and performance of individual components. A common method for assembling dissimilar materials is mechanical joining, but mechanical joining requires multiple manufacturing steps, affects the mechanical properties of the base material and increases the weight due to additional metal parts. Fusion bonding is being used in more and more industries as a way of avoiding the above drawbacks. Infusion bonding, and surface pre-treatment of the base material is essential to ensure the long-life durability of the joint. Laser surface treatment of aluminium has been shown to improve the durability of the joint by forming a passive oxide film and roughening the substrate surface. Infusion bonding, the polymer bonds directly to the metal instead of the adhesive, but the sensitivity to interfacial contamination is higher due to the chemical activity and molecular size of the polymer. Laser-treated surfaces are expected to absorb impurities from the storage atmosphere over time, but the effect of such changes in the treated surface over time on the durability of fusion-bonded joints has not yet been fully investigated. In this paper, the effect of the ageing of laser-treated surfaces of aluminum alloys on the corrosion resistance of fusion-bonded joints is therefore investigated. AlMg3 of 1.5 mm thickness was cut using a water-jet cutting machine, cleaned and degreased with isopropanol and surface pre-treated with a pulsed fiber laser at a wavelength of 1060 nm, maximum power of 70 W and repetition rate of 55 kHz. The aluminum surfaces were then stored in air for various periods of time and their corrosion resistance was assessed by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). For the aluminum joints, induction heating was employed as the fusion bonding method and single-lap shear specimens were prepared. The corrosion resistance of the joints was assessed by measuring the lap shear strength before and after neutral salt spray. Cross-sectional observations by scanning electron microscopy (SEM) were also carried out to investigate changes in the microstructure of the bonded interface. Finally, the corrosion resistance of the surface and the joint were compared and the differences in the mechanisms of corrosion resistance enhancement between the two were discussed.

Keywords: laser surface treatment, pre-treatment, bonding, corrosion, durability, interface, automotive, aluminium alloys, joint, fusion bonding

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Authors: Debjit Ray

Abstract:

Horizontal gene transfer (HGT) and recombination leads to the emergence of bacterial antibiotic resistance and pathogenic traits. HGT events can be identified by comparing a large number of fully sequenced genomes across a species or genus, define the phylogenetic range of HGT, and find potential sources of new resistance genes. In-depth comparative phylogenomics can also identify subtle genome or plasmid structural changes or mutations associated with phenotypic changes. Comparative phylogenomics requires that accurately sequenced, complete and properly annotated genomes of the organism. Assembling closed genomes requires additional mate-pair reads or “long read” sequencing data to accompany short-read paired-end data. To bring down the cost and time required of producing assembled genomes and annotating genome features that inform drug resistance and pathogenicity, we are analyzing the performance for genome assembly of data from the Illumina NextSeq, which has faster throughput than the Illumina HiSeq (~1-2 days versus ~1 week), and shorter reads (150bp paired-end versus 300bp paired end) but higher capacity (150-400M reads per run versus ~5-15M) compared to the Illumina MiSeq. Bioinformatics improvements are also needed to make rapid, routine production of complete genomes a reality. Modern assemblers such as SPAdes 3.6.0 running on a standard Linux blade are capable in a few hours of converting mixes of reads from different library preps into high-quality assemblies with only a few gaps. Remaining breaks in scaffolds are generally due to repeats (e.g., rRNA genes) are addressed by our software for gap closure techniques, that avoid custom PCR or targeted sequencing. Our goal is to improve the understanding of emergence of pathogenesis using sequencing, comparative genomics, and machine learning analysis of ~1000 pathogen genomes. Machine learning algorithms will be used to digest the diverse features (change in virulence genes, recombination, horizontal gene transfer, patient diagnostics). Temporal data and evolutionary models can thus determine whether the origin of a particular isolate is likely to have been from the environment (could it have evolved from previous isolates). It can be useful for comparing differences in virulence along or across the tree. More intriguing, it can test whether there is a direction to virulence strength. This would open new avenues in the prediction of uncharacterized clinical bugs and multidrug resistance evolution and pathogen emergence.

Keywords: genomics, pathogens, genome assembly, superbugs

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Authors: Abubakar Rashid, Muhammad Saad, Faheem Ahmed

Abstract:

This paper provides a comprehensive study pertaining to diagnosis of intermittent high vibrations on an industrial gas turbine using detailed vibrations analysis, followed by its rectification. Engro Polymer & Chemicals Limited, a Chlor-Vinyl complex located in Pakistan has a captive combined cycle power plant having two 28 MW gas turbines (make Hitachi) & one 15 MW steam turbine. In 2018, the organization faced an issue of high vibrations on one of the gas turbines. These high vibration peaks appeared intermittently on both compressor’s drive end (DE) & turbine’s non-drive end (NDE) bearing. The amplitude of high vibration peaks was between 150-170% on the DE bearing & 200-300% on the NDE bearing from baseline values. In one of these episodes, the gas turbine got tripped on “High Vibrations Trip” logic actuated at 155µm. Limited instrumentation is available on the machine, which is monitored with GE Bently Nevada 3300 system having two proximity probes installed at Turbine NDE, Compressor DE &at Generator DE & NDE bearings. Machine’s transient ramp-up & steady state data was collected using ADRE SXP & DSPI 408. Since only 01 key phasor is installed at Turbine high speed shaft, a derived drive key phasor was configured in ADRE to obtain low speed shaft rpm required for data analysis. By analyzing the Bode plots, Shaft center line plot, Polar plot & orbit plots; rubbing was evident on Turbine’s NDE along with increased bearing clearance of Turbine’s NDE radial bearing. The subject bearing was then inspected & heavy deposition of carbonized coke was found on the labyrinth seals of bearing housing with clear rubbing marks on shaft & housing covering at 20-25 degrees on the inner radius of labyrinth seals. The collected coke sample was tested in laboratory & found to be the residue of lube oil in the bearing housing. After detailed inspection & cleaning of shaft journal area & bearing housing, new radial bearing was installed. Before assembling the bearing housing, cleaning of bearing cooling & sealing air lines was also carried out as inadequate flow of cooling & sealing air can accelerate coke formation in bearing housing. The machine was then taken back online & data was collected again using ADRE SXP & DSPI 408 for health analysis. The vibrations were found in acceptable zone as per ISO standard 7919-3 while all other parameters were also within vendor defined range. As a learning from subject case, revised operating & maintenance regime has also been proposed to enhance machine’s reliability.

Keywords: ADRE, bearing, gas turbine, GE Bently Nevada, Hitachi, vibration

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Authors: Nguyen J. M., Lucas G., Ruan S., Digonnet H., Antonioli D.

Abstract:

Introduction: Deep Learning (DL) is a very powerful tool for analyzing image data. But for tabular data, it cannot compete with machine learning methods like XGBoost. The research question becomes: can tabular data be transformed into images that can be analyzed by simple CNNs (Convolutional Neuron Networks)? Will DL be the absolute tool for data classification? All current solutions consist in repositioning the variables in a 2x2 matrix using their correlation proximity. In doing so, it obtains an image whose pixels are the variables. We implement a technology, DeepNIC, that offers the possibility of obtaining an image for each variable, which can be analyzed by simple CNNs. Material and method: The 'ROP' (Regression OPtimized) model is a binary and atypical decision tree whose nodes are managed by a new artificial neuron, the Neurop. By positioning an artificial neuron in each node of the decision trees, it is possible to make an adjustment on a theoretically infinite number of variables at each node. From this new decision tree whose nodes are artificial neurons, we created the concept of a 'Random Forest of Perfect Trees' (RFPT), which disobeys Breiman's concepts by assembling very large numbers of small trees with no classification errors. From the results of the RFPT, we developed a family of 10 statistical information criteria, Nguyen Information Criterion (NICs), which evaluates in 3 dimensions the predictive quality of a variable: Performance, Complexity and Multiplicity of solution. A NIC is a probability that can be transformed into a grey level. The value of a NIC depends essentially on 2 super parameters used in Neurops. By varying these 2 super parameters, we obtain a 2x2 matrix of probabilities for each NIC. We can combine these 10 NICs with the functions AND, OR, and XOR. The total number of combinations is greater than 100,000. In total, we obtain for each variable an image of at least 1166x1167 pixels. The intensity of the pixels is proportional to the probability of the associated NIC. The color depends on the associated NIC. This image actually contains considerable information about the ability of the variable to make the prediction of Y, depending on the presence or absence of other variables. A basic CNNs model was trained for supervised classification. Results: The first results are impressive. Using the GSE22513 public data (Omic data set of markers of Taxane Sensitivity in Breast Cancer), DEEPNic outperformed other statistical methods, including XGBoost. We still need to generalize the comparison on several databases. Conclusion: The ability to transform any tabular variable into an image offers the possibility of merging image and tabular information in the same format. This opens up great perspectives in the analysis of metadata.

Keywords: tabular data, CNNs, NICs, DeepNICs, random forest of perfect trees, classification

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Authors: M. Marín-Ferrer, M. A. Hernández, T. Tollefsen, S. Vanzo, E. Nweke, P. V. Tognoli, M. De Cort

Abstract:

Under the terms of Article 36 of the Euratom Treaty, European Union Member States (MSs) shall periodically communicate to the European Commission (EC) information on environmental radioactivity levels. Compilations of the information received have been published by the EC as a series of reports beginning in the early 1960s. The environmental radioactivity results received from the MSs have been introduced into the Radioactivity Environmental Monitoring database (REMdb) of the Institute for Transuranium Elements of the EC Joint Research Centre (JRC) sited in Ispra (Italy) as part of its Directorate General for Energy (DG ENER) support programme. The REMdb brings to the scientific community dealing with environmental radioactivity topics endless of research opportunities to exploit the near 200 millions of records received from MSs containing information of radioactivity levels in milk, water, air and mixed diet. The REM action was created shortly after Chernobyl crisis to support the EC in its responsibilities in providing qualified information to the European Parliament and the MSs on the levels of radioactive contamination of the various compartments of the environment (air, water, soil). Hence, the main line of REM’s activities concerns the improvement of procedures for the collection of environmental radioactivity concentrations for routine and emergency conditions, as well as making this information available to the general public. In this way, REM ensures the availability of tools for the inter-communication and access of users from the Member States and the other European countries to this information. Specific attention is given to further integrate the new MSs with the existing information exchange systems and to assist Candidate Countries in fulfilling these obligations in view of their membership of the EU. Article 36 of the EURATOM treaty requires the competent authorities of each MS to provide regularly the environmental radioactivity monitoring data resulting from their Article 35 obligations to the EC in order to keep EC informed on the levels of radioactivity in the environment (air, water, milk and mixed diet) which could affect population. The REMdb has mainly two objectives: to keep a historical record of the radiological accidents for further scientific study, and to collect the environmental radioactivity data gathered through the national environmental monitoring programs of the MSs to prepare the comprehensive annual monitoring reports (MR). The JRC continues his activity of collecting, assembling, analyzing and providing this information to public and MSs even during emergency situations. In addition, there is a growing concern with the general public about the radioactivity levels in the terrestrial and marine environment, as well about the potential risk of future nuclear accidents. To this context, a clear and transparent communication with the public is needed. EURDEP (European Radiological Data Exchange Platform) is both a standard format for radiological data and a network for the exchange of automatic monitoring data. The latest release of the format is version 2.0, which is in use since the beginning of 2002.

Keywords: environmental radioactivity, Euratom, monitoring report, REMdb

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Authors: D. Pugazhenthi, B. Sree Vidya

Abstract:

Cloud computing is one of the emerging technologies that enables end users to use the services of cloud on ‘pay per usage’ strategy. This technology grows in a fast pace and so is its security threat. One among the various services provided by cloud is storage. In this service, security plays a vital factor for both authenticating legitimate users and protection of information. This paper brings in efficient ways of authenticating users as well as securing information on the cloud. Initial phase proposed in this paper deals with an authentication technique using multi-factor and multi-dimensional authentication system with multi-level security. Unique identification and slow intrusive formulates an advanced reliability on user-behaviour based biometrics than conventional means of password authentication. By biometric systems, the accounts are accessed only by a legitimate user and not by a nonentity. The biometric templates employed here do not include single trait but multiple, viz., iris and finger prints. The coordinating stage of the authentication system functions on Ensemble Support Vector Machine (SVM) and optimization by assembling weights of base SVMs for SVM ensemble after individual SVM of ensemble is trained by the Artificial Fish Swarm Algorithm (AFSA). Thus it helps in generating a user-specific secure cryptographic key of the multimodal biometric template by fusion process. Data security problem is averted and enhanced security architecture is proposed using encryption and decryption system with double key cryptography based on Fuzzy Neural Network (FNN) for data storing and retrieval in cloud computing . The proposing scheme aims to protect the records from hackers by arresting the breaking of cipher text to original text. This improves the authentication performance that the proposed double cryptographic key scheme is capable of providing better user authentication and better security which distinguish between the genuine and fake users. Thus, there are three important modules in this proposed work such as 1) Feature extraction, 2) Multimodal biometric template generation and 3) Cryptographic key generation. The extraction of the feature and texture properties from the respective fingerprint and iris images has been done initially. Finally, with the help of fuzzy neural network and symmetric cryptography algorithm, the technique of double key encryption technique has been developed. As the proposed approach is based on neural networks, it has the advantage of not being decrypted by the hacker even though the data were hacked already. The results prove that authentication process is optimal and stored information is secured.

Keywords: artificial fish swarm algorithm (AFSA), biometric authentication, decryption, encryption, fingerprint, fusion, fuzzy neural network (FNN), iris, multi-modal, support vector machine classification

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Authors: Rumbidzai Sipiwe Zimvumi

Abstract:

The study aimed to identify the top management team attributes for ambidexterity in small and medium-sized enterprises by utilizing the upper echelons theory. The conventional opinion holds that an organization's ability to pursue both exploitative and explorative innovation methods at the same time is reflected in its ambidexterity. Top-level managers are critical to this matrix because they forecast and explain strategic choices that guarantee success by improving organizational performance. Since the focus of the study was on the unique characteristics of TMTs that can facilitate ambidexterity, the primary goal was to comprehend how TMTs in SMEs can better manage ambidexterity. The study used document analysis to collect information on ambidexterity and TMT traits. Finding, choosing, assessing, and synthesizing data from peer-reviewed publications allowed for the review and evaluation of papers. The fact that SMEs will perform better if they can achieve a balance between exploration and exploitation cannot be overstated. Unfortunately, exploitation is the main priority for most SMEs. The results showed that some of the noteworthy TMT traits that support ambidexterity in SMEs are age diversity, shared responsibility, leadership impact, psychological safety, and self-confidence. It has been shown that most SMEs confront significant obstacles in recruiting people, including formalizing their management and assembling executive teams with seniority. Small and medium-sized enterprises (SMEs) are often held by families or people who neglect to keep their personal lives apart from the firm, which eliminates the opportunity for management and staff to take the initiative. This helps to explain why exploitative strategies, which preserve present success, are used rather than explorative strategies, which open new economic opportunities and dimensions. It is evident that psychological safety deteriorates, and creativity is hindered in the process. The study makes the case that TMTs who are motivated to become ambidextrous can exist. According to the report, small- and medium-sized business owners should value the opinions of all parties involved and provide their managers and regular staff the freedom to think creatively and in a safe environment. TMTs who experience psychological safety are more likely to be inventive, creative, and productive. A team's collective perception that it is acceptable to take chances, voice opinions and concerns, ask questions, and own up to mistakes without fear of unfavorable outcomes is known as team psychological safety. Thus, traits like age diversity, leadership influence, learning agility, psychological safety, and self-assurance are critical to the success of SMEs. As a solution to ensuring ambidexterity is attained, the study suggests a clear separation of ownership and control, the adoption of technology to stimulate creativity, team spirit and excitement, shared accountability, and good management of diversity. Among the suggestions for the SME's success are resource allocation and important collaborations.

Keywords: navigating, ambidexterity, top management team, small and medium enterprises

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Authors: Matthias Haenisch, Marc Godau, Julia Barreiro, Dominik Maxelon

Abstract:

In times of ubiquitous digitalization and the increasing entanglement of humans and technologies in musical practices in the 21st century, it is to be asked, how popular musicians learn in the (post)digital Age. Against the backdrop of the increasing interest in transferring informal learning practices into formal settings of music education the interdisciplinary research association »MusCoDA – Musical Communities in the (Post)Digital Age« (University of Erfurt/University of Applied Sciences Clara Hoffbauer Potsdam, funded by the German Ministry of Education and Research, pursues the goal to derive an empirical model of collective songwriting practices from the study of informal lelearningf songwriters and bands that can be translated into pedagogical concepts for music education in schools. Drawing on concepts from Community of Musical Practice and Actor Network Theory, lelearnings considered not only as social practice and as participation in online and offline communities, but also as an effect of heterogeneous networks composed of human and non-human actors. Learning is not seen as an individual, cognitive process, but as the formation and transformation of actor networks, i.e., as a practice of assembling and mediating humans and technologies. Based on video stimulated recall interviews and videography of online and offline activities, songwriting practices are followed from the initial idea to different forms of performance and distribution. The data evaluation combines coding and mapping methods of Grounded Theory Methodology and Situational Analysis. This results in network maps in which both the temporality of creative practices and the material and spatial relations of human and technological actors are reconstructed. In addition, positional analyses document the power relations between the participants that structure the learning process of the field. In the area of online informal lelearninginitial key research findings reveal a transformation of the learning subject through the specific technological affordances of TikTok and Instagram and the accompanying changes in the learning practices of the corresponding online communities. Learning is explicitly shaped by the material agency of online tools and features and the social practices entangled with these technologies. Thus, any human online community member can be invited to directly intervene in creative decisions that contribute to the further compositional and structural development of songs. At the same time, participants can provide each other with intimate insights into songwriting processes in progress and have the opportunity to perform together with strangers and idols. Online Lelearnings characterized by an increase in social proximity, distribution of creative agency and informational exchange between participants. While it seems obvious that traditional notions not only of lelearningut also of the learning subject cannot be maintained, the question arises, how exactly the observed informal learning practices and the subject that emerges from the use of social media as online learning technologies can be transferred into contexts of formal learning

Keywords: informal learning, postdigitality, songwriting, actor-network theory, community of musical practice, social media, TikTok, Instagram, apps

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Authors: Monica Racha, Siva Chandrasekaran, Alex Stojcevski

Abstract:

The engineering programs focus on promoting students' personal and professional development by ensuring that students acquire technical and professional competencies during four-year studies. The traditional engineering laboratory provides an opportunity for students to "practice by doing," and laboratory facilities aid them in obtaining insight and understanding of their discipline. Due to rapid technological advancements and the current COVID-19 outbreak, the traditional labs were transforming into virtual learning environments. Aim: To better understand the limitations of the physical laboratory, this research study aims to use a Machine Learning (ML) algorithm that interfaces with the Augmented Reality HoloLens and predicts the image behavior to classify and detect the electronic components. The automated electronic components error classification and detection automatically detect and classify the position of all components on a breadboard by using the ML algorithm. This research will assist first-year undergraduate engineering students in conducting laboratory practices without any supervision. With the help of HoloLens, and ML algorithm, students will reduce component placement error on a breadboard and increase the efficiency of simple laboratory practices virtually. Method: The images of breadboards, resistors, capacitors, transistors, and other electrical components will be collected using HoloLens 2 and stored in a database. The collected image dataset will then be used for training a machine learning model. The raw images will be cleaned, processed, and labeled to facilitate further analysis of components error classification and detection. For instance, when students conduct laboratory experiments, the HoloLens captures images of students placing different components on a breadboard. The images are forwarded to the server for detection in the background. A hybrid Convolutional Neural Networks (CNNs) and Support Vector Machines (SVMs) algorithm will be used to train the dataset for object recognition and classification. The convolution layer extracts image features, which are then classified using Support Vector Machine (SVM). By adequately labeling the training data and classifying, the model will predict, categorize, and assess students in placing components correctly. As a result, the data acquired through HoloLens includes images of students assembling electronic components. It constantly checks to see if students appropriately position components in the breadboard and connect the components to function. When students misplace any components, the HoloLens predicts the error before the user places the components in the incorrect proportion and fosters students to correct their mistakes. This hybrid Convolutional Neural Networks (CNNs) and Support Vector Machines (SVMs) algorithm automating electronic component error classification and detection approach eliminates component connection problems and minimizes the risk of component damage. Conclusion: These augmented reality smart glasses powered by machine learning provide a wide range of benefits to supervisors, professionals, and students. It helps customize the learning experience, which is particularly beneficial in large classes with limited time. It determines the accuracy with which machine learning algorithms can forecast whether students are making the correct decisions and completing their laboratory tasks.

Keywords: augmented reality, machine learning, object recognition, virtual laboratories

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Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs, followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology

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Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation

Procedia PDF Downloads 72