Search results for: gene delivery

Authors: Bonnie R. Brammall, Rhonda M. Garad, Helena J. Teede, Cheryce L. Harrison

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Introduction: Reproductive aged women are at high-risk for accelerated weight gain and obesity development, with pregnancy recognised as a critical contributory life phase. Healthy lifestyle interventions during the preconception and antenatal period improve maternal and infant health outcomes. Yet, interventions from preconception through to postpartum and translation and implementation into real-world healthcare settings remain limited. OptimalMe is a randomised, hybrid implementation effectiveness study of evidence-based healthy lifestyle intervention. Here, we report engagement, acceptability of the intervention during preconception, and self-reported behaviour change outcomes as a result of the preconception phase of the intervention. Methods: Reproductive aged women who upgraded their private health insurance to include pregnancy and birth cover, signalling a pregnancy intention, were invited to participate. Women received access to an online portal with preconception health and lifestyle modules, goal-setting and behaviour change tools, monthly SMS messages, and two coaching sessions (randomised to video or phone) prior to pregnancy. Results: Overall n=527 expressed interest in participating. Of these, n=33 did not meet inclusion criteria, n=8 were not contactable for eligibility screening, and n=177 failed to engage after the screening, leaving n=309 who were enrolled in OptimalMe and randomised to intervention delivery method. Engagement with coaching sessions dropped by 25% for session two, with no difference between intervention groups. Women had a mean (SD) age of 31.7 (4.3) years and, at baseline, a self-reported mean BMI of 25.7 (6.1) kg/m², with 55.8% (n=172) of a healthy BMI. Behaviour was sub-optimal with infrequent self-weighing (38.1%), alcohol consumption prevalent (57.1%), sub-optimal pre-pregnancy supplementation (61.5%), and incomplete medical screening. Post-intervention 73.2% of women reported engagement with a GP for preconception care and improved lifestyle behaviour (85.5%), since starting OptimalMe. Direct pre-and-post comparison of individual participant data showed that of 322 points of potential change (up-to-date cervical screening, elimination of high-risk behaviours [alcohol, drugs, smoking], uptake of preconception supplements and improved weighing habits) 158 (49.1%) points of change were achieved. Health coaching sessions were found to improve accountability and confidence, yet further personalisation and support were desired. Engagement with video and phone sessions was comparable, having similar impacts on behaviour change, and both methods were well accepted and increased women's accountability. Conclusion: A low-intensity digital health and lifestyle program with embedded health coaching can improve the uptake of preconception care and lead to self-reported behaviour change. This is the first program of its kind to reach an otherwise healthy population of women planning a pregnancy. Women who were otherwise healthy showed divergence from preconception health and lifestyle objectives and benefited from the intervention. OptimalMe shows promising results for population-based behaviour change interventions that can improve preconception lifestyle habits and increase engagement with clinical health care for pregnancy preparation.

Keywords: preconception, pregnancy, preventative health, weight gain prevention, self-management, behaviour change, digital health, telehealth, intervention, women's health

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Authors: Michelle C. S. Azevedo, Priscila M. Colavite, Carolina F. Francisconi, Ana P. Trombone, Gustavo P. Garlet

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VIP (vasoactive intestinal peptide) know as a potential protective factor in the view of its marked immunosuppressive properties. In this work, we investigated a possible association of VIP with the clinical status of experimental periapical granulomas and the association with expression markers in the lesions potentially associated with periapical lesions pathogenesis. C57BL/6WT mice were treated or not with recombinant VIP. Animals with active/progressive (N=40), inactive/stable (N=70) periapical granulomas and controls (N=50) were anesthetized and the right mandibular first molar was surgically opened, allowing exposure of dental pulp. Endodontic pathogenic bacterial strains were inoculated: Porphyromonas gingivalis, Prevotella nigrescens, Actinomyces viscosus, and Fusobacterium nucleatum subsp. polymorphum. The cavity was not sealed after bacterial inoculation. During lesion development, animals were treated or not with recombinant VIP 3 days post infection. Animals were killed after 3, 7, 14, and 21 days of infection and the jaws were dissected. The extraction of total RNA from periodontal tissues was performed and the integrity of samples was checked. qPCR reaction using TaqMan chemistry with inventoried primers were performed in ViiA7 equipment. The results, depicted as the relative levels of gene expression, were calculated in reference to GAPDH and β-actin expression. Periodontal tissues from upper molars were vested and incubated supplemented RPMI, followed by processing with 0.05% DNase. Cell viability and couting were determined by Neubauer chamber analysis. For flow cytometry analysis, after cell counting the cells were stained with the optimal dilution of each antibody; (PE)-conjugated and (FITC)-conjugated antibodies against CD4, CD25, FOXP3, IL-4, IL-17 and IFN-γ antibodies, as well their respective isotype controls. Cells were analyzed by FACScan and CellQuest software. Results are presented as the number of cells in the periodontal tissues or the number of positive cells for each marker in the CD4+FOXp3+, CD4+IL-4+, CD4+IFNg+ and CD4+IL-17+ subpopulations. The levels mRNA were measured by qPCR. The VIP expression was predominated in inactive lesions, as well part of the clusters of cytokine/Th markers identified as protective factors and a negative correlation between VIP expression and lesion evolution was observed. A quantitative analysis of IL1β, IL17, TNF, IFN, MMP2, RANKL, OPG, IL10, TGFβ, CTLA4, COL5A1, CTGF, CXCL11, FGF7, ITGA4, ITGA5, SERP1 and VTN expression was measured in experimental periapical lesions treated with VIP 7 and 14 days after lesion induction and healthy animals. After 7 days, all targets presented a significate increase in comparison to untreated animals. About migration kinetics, profile of chemokine receptors expression of TCD4+ subsets and phenotypic analysis of Tregs, Th1, Th2 and Th17 cells during the course of experimental periodontal disease evaluated by flow cytometry and depicted as the number of positive cells for each marker. CD4+IFNg+ and CD4+FOXp3+ cells migration were significate increased 7 days post VIP treatment. CD4+IL17+ cells migration were significate increased 7 and 14 days post VIP treatment, CD4+IL4+ cells migration were significate increased 14 and 21 days post VIP treatment compared to the control group. In conclusion, our experimental data support VIP involvement in determining the inactivity of periapical lesions. Financial support: FAPESP #2015/25618-2.

Keywords: chronic inflammation, cytokines, osteolytic lesions, VIP (Vasoactive Intestinal Peptide)

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Authors: Sini George

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Active learning pedagogies are valued for their success in increasing 21st-century learners’ engagement, developing transferable skills like critical thinking or quantitative reasoning, and creating deeper and more lasting educational gains. 'Blended learning' is an active learning pedagogical approach in which direct instruction moves from the group learning space to the individual learning space, and the resulting group space is transformed into a dynamic, interactive learning environment where the educator guides students as they apply concepts and engage creatively in the subject matter. This project aimed to develop a blended learning instructional approach to teaching concepts around pharmaceutical calculations to year 1 pharmacy students. The wrong dose, strength or frequency of a medication accounts for almost a third of medication errors in the NHS therefore, progression to year 2 requires a 70% pass in this calculation test, in addition to the standard progression requirements. Many students were struggling to achieve this requirement in the past. It was also challenging to teach these concepts to students of a large class (> 130) with mixed mathematical abilities, especially within a traditional didactic lecture format. Therefore, short screencasts with voice-over of the lecturer were provided in advance of a total of four teaching sessions (two hours/session), incorporating core content of each session and talking through how they approached the calculations to model metacognition. Links to the screencasts were posted on the learning management. Viewership counts were used to determine that the students were indeed accessing and watching the screencasts on schedule. In the classroom, students had to apply the knowledge learned beforehand to a series of increasingly difficult set of questions. Students were then asked to create a question in group settings (two students/group) and to discuss the questions created by their peers in their groups to promote deep conceptual learning. Students were also given time for question-and-answer period to seek clarifications on the concepts covered. Student response to this instructional approach and their test grades were collected. After collecting and organizing the data, statistical analysis was carried out to calculate binomial statistics for the two data sets: the test grade for students who received blended learning instruction and the test grades for students who received instruction in a standard lecture format in class, to compare the effectiveness of each type of instruction. Student response and their performance data on the assessment indicate that the learning of content in the blended learning instructional approach led to higher levels of student engagement, satisfaction, and more substantial learning gains. The blended learning approach enabled each student to learn how to do calculations at their own pace freeing class time for interactive application of this knowledge. Although time-consuming for an instructor to implement, the findings of this research demonstrate that the blended learning instructional approach improves student academic outcomes and represents a valuable method to incorporate active learning methodologies while still maintaining broad content coverage. Satisfaction with this approach was high, and we are currently developing more pharmacy content for delivery in this format.

Keywords: active learning, blended learning, deep conceptual learning, instructional approach, metacognition, pharmaceutical calculations

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Authors: Inna Kornienko, Svetlana Guryeva, Natalia Danilova, Elena Petersen

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Drug toxicity often goes undetected until clinical trials, the most expensive and dangerous phase of drug development. Both human cell culture and animal studies have limitations that cannot be overcome by improvements in drug testing protocols. Tissue engineering is an emerging alternative approach to creating models of human malignant tumors for experimental oncology, personalized medicine, and drug discovery studies. This new generation of bioengineered tumors provides an opportunity to control and explore the role of every component of the model system including cell populations, supportive scaffolds, and signaling molecules. An area that could greatly benefit from these models is cancer research. Recent advances in tissue engineering demonstrated that decellularized tissue is an excellent scaffold for tissue engineering. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. Decellularized Organs preserve organ microenvironment, which is critical for cancer metastasis. Utilizing 3D tumor models results greater proximity of cell culture morphological characteristics in a model to its in vivo counterpart, allows more accurate simulation of the processes within a functioning tumor and its pathogenesis. 3D models allow study of migration processes and cell proliferation with higher reliability as well. Moreover, cancer cells in a 3D model bear closer resemblance to living conditions in terms of gene expression, cell surface receptor expression, and signaling. 2D cell monolayers do not provide the geometrical and mechanical cues of tissues in vivo and are, therefore, not suitable to accurately predict the responses of living organisms. 3D models can provide several levels of complexity from simple monocultures of cancer cell lines in liquid environment comprised of oxygen and nutrient gradients and cell-cell interaction to more advanced models, which include co-culturing with other cell types, such as endothelial and immune cells. Following this reasoning, spheroids cultivated from one or multiple patient-derived cell lines can be utilized to seed the matrix rather than monolayer cells. This approach furthers the progress towards personalized medicine. As an initial step to create a new ex vivo tissue engineered model of a cancer tumor, optimized protocols have been designed to obtain organ-specific acellular matrices and evaluate their potential as tissue engineered scaffolds for cultures of normal and tumor cells. Decellularized biomatrix was prepared from animals’ kidneys, urethra, lungs, heart, and liver by two decellularization methods: perfusion in a bioreactor system and immersion-agitation on an orbital shaker with the use of various detergents (SDS, Triton X-100) in different concentrations and freezing. Acellular scaffolds and tissue engineered constructs have been characterized and compared using morphological methods. Models using decellularized matrix have certain advantages, such as maintaining native extracellular matrix properties and biomimetic microenvironment for cancer cells; compatibility with multiple cell types for cell culture and drug screening; utilization to culture patient-derived cells in vitro to evaluate different anticancer therapeutics for developing personalized medicines.

Keywords: 3D models, decellularization, drug discovery, drug toxicity, scaffolds, spheroids, tissue engineering

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Authors: Ipsita Pujari, Abitha Thomas, Vidhu S. Babu, K. Satyamoorthy

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Orchids are esteemed as celebrities in cut flower industry globally, due to their long-lasting fragrance and freshness. Apart from splendor, the unique metabolites endowed with pharmaceutical potency have made them one of the most hunted in plant kingdom. This had led to their trafficking, resulting in habitat loss, subsequently making them occupiers of IUCN red list as RET species. Many of the orchids especially wild varieties still remain undiscovered. In view to protect and conserve the wild germplasm, researchers have been inventing novel micropropagation protocols; thereby conserving Orchids. India is overflowing with exclusive wild cultivars of Orchids, whose pharmaceutical properties remain untapped and are not marketed owing to relatively small flowers. However, their germplasm is quite pertinent to be preserved for making unusual hybrids. Dendrobium genus is the second largest among Orchids exists in India and has highest demand attributable to enduring cut flowers and significant therapeutic uses in traditional medicinal system. Though the genus is quite endemic in Western Ghat regions of the country, many species are still anonymous with their unknown curative properties. A standard breeding cycle in Orchids usually takes five to seven years (Dendrobium hybrids taking a long juvenile phase of two to five years reaching maturity and flowering stage) and this extensive life cycle has always hindered the development of Dendrobium breeding. Dendrobium is reported with essential therapeutic plant bio-chemicals and ‘Moscatilin’ is one, found exclusive to this famous Dendrobium genus. Moscatilin is reported to have anti-mutagenic and anti-cancer properties, whose positive action has very recently been demonstrated against a range of cancers. Our preliminary study here established a simple and economic small-scale propagation protocol of Dendrobium ovatum describing in vitro production of Moscatilin. Subsequently for enhancing the content of Moscatilin, an efficient experimental related to the organization of transgenic (hairy) D. ovatum root cultures through infection of Agrobacterium rhizogenes 2364 strain on MS basal medium is being reported in the present study. Hairy roots generated on almost half of the explants used (spherules, in vitro plantlets and calli) maintained through suspension cultures, after 8 weeks of co-cultivation with Agrobacterium rhizogenes. GFP assay performed with isolated hairy roots has confirmed the integrative transformation which was further positively confirmed by PCR using rolB gene specific primers. Reverse phase-high performance liquid chromatography and mass spectrometry techniques were used for quantification and accurate identification of Moscatilin respectively from transgenic systems. A noticeable ~3 fold increase in contents were observed in transformed D. ovatum root cultures as compared to the simple in vitro culture, callus culture and callus regeneration plantlets. Role of elicitors e.g., Methyl jasmonate, Salicylic acid, Yeast extract and Chitosan were tested for elevating the Moscatilin content to obtain a comprehensive optimized protocol facilitating the in vitro production of valuable Moscatilin with larger yield. This study would provide evidence towards the in vitro assembly of Moscatilin within a short time-period through not a so-expensive technology for the first time. It also serves as an appropriate basis for bioreactor scale-up resulting in commercial bioproduction of Moscatilin.

Keywords: bioproduction, Dendrobium ovatum, hairy root culture, moscatilin

Procedia PDF Downloads 235

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

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

Keywords: cellular automata, fuzzy logic, landscape, spatiotemporal

Procedia PDF Downloads 77

Authors: Ma Chu Jui

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Culture plays a pivotal role in shaping societal responses to change and fostering adaptability. In the realm of healthcare provision, hospitals serve as dynamic settings molded by the cultural consciousness of healthcare professionals. This intricate interplay extends to their expectations of leadership, communication styles, and attitudes towards patient care. Recognizing the cultural inclinations of healthcare professionals becomes imperative in navigating this complex landscape. This study will utilize Hofstede's Value Survey Module 2013 (VSM 2013) as a comprehensive analytical tool. The targeted participants for this research are in-service nursing professionals with a tenure of at least three months, specifically employed in the nursing department of an Eastern hospital. This quantitative approach seeks to quantify diverse cultural tendencies among the targeted nursing professionals, elucidating not only abstract cultural concepts but also revealing their cultural inclinations across different dimensions. The study anticipates gathering between 400 to 500 responses, ensuring a robust dataset for a comprehensive analysis. The focused approach on nursing professionals within the Eastern hospital setting enhances the relevance and specificity of the cultural insights obtained. The research aims to contribute valuable knowledge to the understanding of cultural tendencies among in-service nursing personnel in the nursing department of this specific Eastern hospital. The VSM 2013 will be initially distributed to this specific group to collect responses, aiming to calculate scores on each of Hofstede's six cultural dimensions—Power Distance Index (PDI), Individualism vs. Collectivism (IDV), Uncertainty Avoidance Index (UAI), Masculinity vs. Femininity (MAS), Long-Term Orientation vs. Short-Term Normative Orientation (LTO), and Indulgence vs. Restraint (IVR). the study unveils a significant correlation between different cultural dimensions and healthcare professionals' tendencies in understanding leadership expectations through PDI, grasping behavioral patterns via IDV, acknowledging risk acceptance through UAI, and understanding their long-term and short-term behaviors through LTO. These tendencies extend to communication styles and attitudes towards patient care. These findings provide valuable insights into the nuanced interconnections between cultural factors and healthcare practices. Through a detailed analysis of the varying levels of these cultural dimensions, we gain a comprehensive understanding of the predominant inclinations among the majority of healthcare professionals. This nuanced perspective adds depth to our comprehension of how cultural values shape their approach to leadership, communication, and patient care, contributing to a more holistic understanding of the healthcare landscape. A profound comprehension of the cultural paradigms embraced by healthcare professionals holds transformative potential. Beyond a mere understanding, it acts as a catalyst for elevating the caliber of healthcare services. This heightened awareness fosters cohesive collaboration among healthcare teams, paving the way for the establishment of a unified healthcare ethos. By cultivating shared values, our study envisions a healthcare environment characterized by enhanced quality, improved teamwork, and ultimately, a more favorable and patient-centric healthcare landscape. In essence, our research underscores the critical role of cultural awareness in shaping the future of healthcare delivery.

Keywords: hofstede's cultural, cultural dimensions, cultural values in healthcare, cultural awareness in nursing

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Authors: Loyd R. Hook, Maryam Moharek

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With the envisioned future growth of low altitude urban aircraft operations for airborne delivery service and advanced air mobility, strategies to coordinate and deconflict aircraft flight paths must be prioritized. Autonomous coordination and planning of flight trajectories is the preferred approach to the future vision in order to increase safety, density, and efficiency over manual methods employed today. Difficulties arise because any conflict resolution must be constrained by all other aircraft, all airspace restrictions, and all ground-based obstacles in the vicinity. These considerations make pair-wise tactical deconfliction difficult at best and unlikely to find a suitable solution for the entire system of vehicles. In addition, more traditional methods which rely on long time scales and large protected zones will artificially limit vehicle density and drastically decrease efficiency. Instead, strategic planning, which is able to respond to highly dynamic conditions and still account for high density operations, will be required to coordinate multiple vehicles in the highly constrained low altitude urban environment. This paper develops and evaluates such a planning algorithm which can be implemented autonomously across multiple aircraft and situations. Data from this evaluation provide promising results with simulations showing up to 10 aircraft deconflicted through a relatively narrow low-altitude urban canyon without any vehicle to vehicle or obstacle conflict. The algorithm achieves this level of coordination beginning with the assumption that each vehicle is controlled to follow an independently constructed flight path, which is itself free of obstacle conflict and restricted airspace. Then, by preferencing speed change deconfliction maneuvers constrained by the vehicles flight envelope, vehicles can remain as close to the original planned path and prevent cascading vehicle to vehicle conflicts. Performing the search for a set of commands which can simultaneously ensure separation for each pair-wise aircraft interaction and optimize the total velocities of all the aircraft is further complicated by the fact that each aircraft's flight plan could contain multiple segments. This means that relative velocities will change when any aircraft achieves a waypoint and changes course. Additionally, the timing of when that aircraft will achieve a waypoint (or, more directly, the order upon which all of the aircraft will achieve their respective waypoints) will change with the commanded speed. Put all together, the continuous relative velocity of each vehicle pair and the discretized change in relative velocity at waypoints resembles a hybrid reachability problem - a form of control reachability. This paper proposes two methods for finding solutions to these multi-body problems. First, an analytical formulation of the continuous problem is developed with an exhaustive search of the combined state space. However, because of computational complexity, this technique is only computable for pairwise interactions. For more complicated scenarios, including the proposed 10 vehicle example, a discretized search space is used, and a depth-first search with early stopping is employed to find the first solution that solves the constraints.

Keywords: strategic planning, autonomous, aircraft, deconfliction

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Authors: Mingxin Li, Liya Ni

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Autonomous parking is a valuable feature applicable to many robotics applications such as tour guide robots, UV sanitizing robots, food delivery robots, and warehouse robots. With auto-parking, the robot will be able to park at the charging zone and charge itself without human intervention. As compared to self-driving vehicles, auto-parking is more challenging for a small-scale mobile robot only equipped with a front camera due to the camera view limited by the robot’s height and the narrow Field of View (FOV) of the inexpensive camera. In this research, auto-parking of a small-scale mobile robot with a front camera only was achieved in a four-step process: Firstly, transfer learning was performed on the AlexNet, a popular pre-trained convolutional neural network (CNN). It was trained with 150 pictures of empty parking slots and 150 pictures of occupied parking slots from the view angle of a small-scale robot. The dataset of images was divided into a group of 70% images for training and the remaining 30% images for validation. An average success rate of 95% was achieved. Secondly, the image of detected empty parking space was processed with edge detection followed by the computation of parametric representations of the boundary lines using the Hough Transform algorithm. Thirdly, the positions of the entrance point and center of available parking space were predicted based on the robot kinematic model as the robot was driving closer to the parking space because the boundary lines disappeared partially or completely from its camera view due to the height and FOV limitations. The robot used its wheel speeds to compute the positions of the parking space with respect to its changing local frame as it moved along, based on its kinematic model. Lastly, the predicted entrance point of the parking space was used as the reference for the motion control of the robot until it was replaced by the actual center when it became visible again by the robot. The linear and angular velocities of the robot chassis center were computed based on the error between the current chassis center and the reference point. Then the left and right wheel speeds were obtained using inverse kinematics and sent to the motor driver. The above-mentioned four subtasks were all successfully accomplished, with the transformed learning, image processing, and target prediction performed in MATLAB, while the motion control and image capture conducted on a self-built small scale differential drive mobile robot. The small-scale robot employs a Raspberry Pi board, a Pi camera, an L298N dual H-bridge motor driver, a USB power module, a power bank, four wheels, and a chassis. Future research includes three areas: the integration of all four subsystems into one hardware/software platform with the upgrade to an Nvidia Jetson Nano board that provides superior performance for deep learning and image processing; more testing and validation on the identification of available parking space and its boundary lines; improvement of performance after the hardware/software integration is completed.

Keywords: autonomous parking, convolutional neural network, image processing, kinematics-based prediction, transfer learning

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Authors: Alper T. Celebi, Ali Beskok

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Electroosmotic (EO) slip flows in nanochannels are investigated using non-equilibrium molecular dynamics (MD) simulations, and the results are compared with analytical solution of Poisson-Boltzmann and Stokes (PB-S) equations with slip contribution. The ultimate objective of this study is to show that well-known continuum flow model can accurately predict the EO velocity profiles in nanochannels using the slip lengths and apparent viscosities obtained from force-driven flow simulations performed at various liquid-wall interaction strengths. EO flow of aqueous NaCl solution in silicon nanochannels are simulated under realistic electrochemical conditions within the validity region of Poisson-Boltzmann theory. A physical surface charge density is determined for nanochannels based on dissociations of silanol functional groups on channel surfaces at known salt concentration, temperature and local pH. First, we present results of density profiles and ion distributions by equilibrium MD simulations, ensuring that the desired thermodynamic state and ionic conditions are satisfied. Next, force-driven nanochannel flow simulations are performed to predict the apparent viscosity of ionic solution between charged surfaces and slip lengths. Parabolic velocity profiles obtained from force-driven flow simulations are fitted to a second-order polynomial equation, where viscosity and slip lengths are quantified by comparing the coefficients of the fitted equation with continuum flow model. Presence of charged surface increases the viscosity of ionic solution while the velocity-slip at wall decreases. Afterwards, EO flow simulations are carried out under uniform electric field for different liquid-wall interaction strengths. Velocity profiles present finite slips near walls, followed with a conventional viscous flow profile in the electrical double layer that reaches a bulk flow region in the center of the channel. The EO flow enhances with increased slip at the walls, which depends on wall-liquid interaction strength and the surface charge. MD velocity profiles are compared with the predictions from analytical solutions of the slip modified PB-S equation, where the slip length and apparent viscosity values are obtained from force-driven flow simulations in charged silicon nano-channels. Our MD results show good agreements with the analytical solutions at various slip conditions, verifying the validity of PB-S equation in nanochannels as small as 3.5 nm. In addition, the continuum model normalizes slip length with the Debye length instead of the channel height, which implies that enhancement in EO flows is independent of the channel height. Further MD simulations performed at different channel heights also shows that the flow enhancement due to slip is independent of the channel height. This is important because slip enhanced EO flow is observable even in micro-channels experiments by using a hydrophobic channel with large slip and high conductivity solutions with small Debye length. The present study provides an advanced understanding of EO flows in nanochannels. Correct characterization of nanoscale EO slip flow is crucial to discover the extent of well-known continuum models, which is required for various applications spanning from ion separation to drug delivery and bio-fluidic analysis.

Keywords: electroosmotic flow, molecular dynamics, slip length, velocity-slip

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Authors: Malla Vijayeta, Y. Vijaya Kumar, N. Ramakrishna Raju, K. Satyanarayana

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Global AEC (architecture, engineering, and construction) industry has been coined as one of the most resistive domains in embracing technology. Although this digital era has been inundated with software tools like CAD, STADD, CANDY, Microsoft Project, Primavera etc. the key stakeholders have been working in siloes and processes remain fragmented. Unlike the yesteryears’ simpler project delivery methods, the current projects are of fast-track, complex, risky, multidisciplinary, stakeholder’s influential, statutorily regulative etc. pose extensive bottlenecks in preventing timely completion of projects. At this juncture, a paradigm shift surfaced in construction industry, and Building Information Modeling, aka BIM, has been a panacea to bolster the multidisciplinary teams’ cooperative and collaborative work leading to productive, sustainable and leaner project outcome. Building information modeling has been integrative, stakeholder engaging and centralized approach in providing a common platform of communication. A common misconception that BIM can be used for building/high rise projects in Indian Construction Industry, while this paper discusses of the implementation of BIM processes/methodologies in water and waste water industry. It elucidates about BIM 4D planning and constructability reviews of a Sewage Treatment Plant in India. Conventional construction planning and logistics management involves a blend of experience coupled with imagination. Even though the excerpts or judgments or lessons learnt gained from veterans might be predictive and helpful, but the uncertainty factor persists. This paper shall delve about the case study of real time implementation of BIM 4D planning protocols for one of the Sewage Treatment Plant of Dravyavati River Rejuvenation Project in India and develops a Time Liner to identify logistics planning and clash detection. With this BIM processes, we shall find that there will be significant reduction of duplication of tasks and reworks. Also another benefit achieved will be better visualization and workarounds during conception stage and enables for early involvement of the stakeholders in the Project Life cycle of Sewage Treatment Plant construction. Moreover, we have also taken an opinion poll of the benefits accrued utilizing BIM processes versus traditional paper based communication like 2D and 3D CAD tools. Thus this paper concludes with BIM framework for Sewage Treatment Plant construction which will achieve optimal construction co-ordination advantages like 4D construction sequencing, interference checking, clash detection checking and resolutions by primary engagement of all key stakeholders thereby identifying potential risks and subsequent creation of risk response strategies. However, certain hiccups like hesitancy in adoption of BIM technology by naïve users and availability of proficient BIM trainers in India poses a phenomenal impediment. Hence the nurture of BIM processes from conception, construction and till commissioning, operation and maintenance along with deconstruction of a project’s life cycle is highly essential for Indian Construction Industry in this digital era.

Keywords: integrated BIM workflow, 4D planning with BIM, building information modeling, clash detection and visualization, constructability reviews, project life cycle

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Authors: Maria Ledinskaya

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This paper examines the Morris Collection Conservation Project at the Sainsbury Centre for Visual Arts in the context of Agile, Lean, and Hybrid project management. It is part case study and part literature review. To date, relatively little has been written about non-traditional project management approaches in heritage conservation. This paper seeks to introduce Agile, Lean, and Hybrid project management concepts from business, software development, and manufacturing fields to museum conservation, by referencing their practical application on a recent museum-based conservation project. The Morris Collection Conservation Project was carried out in 2019-2021 in Norwich, UK, and concerned the remedial conservation of around 150 Abstract Constructivist artworks bequeathed to the Sainsbury Centre for Visual Arts by private collectors Michael and Joyce Morris. The first part introduces the chronological timeline and key elements of the project. It describes a medium-size conservation project of moderate complexity, which was planned and delivered in an environment with multiple known unknowns – unresearched collection, unknown condition and materials, unconfirmed budget. The project was also impacted by the unknown unknowns of the COVID-19 pandemic, such as indeterminate lockdowns, and the need to accommodate social distancing and remote communications. The author, a staff conservator at the Sainsbury Centre who acted as project manager on the Morris Collection Conservation Project, presents an incremental, iterative, and value-based approach to managing a conservation project in an uncertain environment. Subsequent sections examine the project from the point of view of Traditional, Agile, Lean, and Hybrid project management. The author argues that most academic writing on project management in conservation has focussed on a Traditional plan-driven approach – also known as Waterfall project management – which has significant drawbacks in today’s museum environment, due to its over-reliance on prediction-based planning and its low tolerance to change. In the last 20 years, alternative Agile, Lean and Hybrid approaches to project management have been widely adopted in software development, manufacturing, and other industries, although their recognition in the museum sector has been slow. Using examples from the Morris Collection Conservation Project, the author introduces key principles and tools of Agile, Lean, and Hybrid project management and presents a series of arguments on the effectiveness of these alternative methodologies in museum conservation, as well as the ethical and practical challenges to their implementation. These project management approaches are discussed in the context of consequentialist, relativist, and utilitarian developments in contemporary conservation ethics, particularly with respect to change management, bespoke ethics, shared decision-making, and value-based cost-benefit conservation strategy. The author concludes that the Morris Collection Conservation Project had multiple Agile and Lean features which were instrumental to the successful delivery of the project. These key features are identified as distributed decision making, a co-located cross-disciplinary team, servant leadership, focus on value-added work, flexible planning done in shorter sprint cycles, light documentation, and emphasis on reducing procedural, financial, and logistical waste. Overall, the author’s findings point largely in favour of a Hybrid model which combines traditional and alternative project processes and tools to suit the specific needs of the project.

Keywords: project management, conservation, waterfall, agile, lean, hybrid

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Authors: Paul J. McKay

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Large-scale genome-wide association studies (GWAS) investigating genetic contributions to sexual orientation and gender identity are largely lacking and may reduce stigma experienced in the LGBTQ+ community by providing an underlying biological explanation for queerness. While there is a growing consensus within the scientific community that genetic makeup contributes – at least in part – to sexual orientation and gender identity, there is a marked lack of genomics research exploring polygenic contributions to queerness. Based on recent (2019) findings from a large-scale GWAS investigating the genetic architecture of same-sex sexual behavior, and various additional peer-reviewed publications detailing novel insights into the molecular mechanisms of sexual orientation and gender identity, we hypothesize that sexual orientation and gender identity are complex, multifactorial, and polygenic; meaning that many genetic factors contribute to these phenomena, and environmental factors play a possible role through epigenetic modulation. In recent years, large-scale GWAS studies have been paramount to our modern understanding of many other complex human traits, such as in the case of autism spectrum disorder (ASD). Despite possible benefits of such research, including reduced stigma towards queer people, improved outcomes for LGBTQ+ in familial, socio-cultural, and political contexts, and improved access to healthcare (particularly for trans populations); important risks and considerations remain surrounding this type of research. To mitigate possibilities such as invalidation of the queer identities of existing LGBTQ+ individuals, genetic discrimination, or the possibility of euthanasia of embryos with a genetic predisposition to queerness (through reproductive technologies like IVF and/or gene-editing in utero), we propose a community-engaged research (CER) framework which emphasizes the privacy and confidentiality of research participants. Importantly, the historical legacy of scientific research attempting to pathologize queerness (in particular, falsely equating gender variance to mental illness) must be acknowledged to ensure any future research conducted in this realm does not propagate notions of homophobia, transphobia or stigma against queer people. Ultimately, in a world where same-sex sexual activity is criminalized in 69 UN member states, with 67 of these states imposing imprisonment, 8 imposing public flogging, 6 (Brunei, Iran, Mauritania, Nigeria, Saudi Arabia, Yemen) invoking the death penalty, and another 5 (Afghanistan, Pakistan, Qatar, Somalia, United Arab Emirates) possibly invoking the death penalty, the importance of this research cannot be understated, as finding a biological basis for queerness would directly oppose the harmful rhetoric that “being LGBTQ+ is a choice.” Anti-trans legislation is similarly widespread: In the United States in 2022 alone (as of Oct. 13), 155 anti-trans bills have been introduced preventing trans girls and women from playing on female sports teams, barring trans youth from using bathrooms and locker rooms that align with their gender identity, banning access to gender affirming medical care (e.g., hormone-replacement therapy, gender-affirming surgeries), and imposing legal restrictions on name changes. Understanding that a general lack of knowledge about the biological basis of queerness may be a contributing factor to the societal stigma faced by gender and sexual orientation minorities, we propose the initiation of large-scale GWAS studies investigating the genetic basis of gender identity and sexual orientation.

Keywords: genome-wide association studies (GWAS), sexual and gender minorities (SGM), polygenicity, community-engaged research (CER)

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Authors: Priyanka Yadav, Umesh Bnasal, Yashvinder Kumar

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The placenta is an important structure that provides oxygen and nutrients to the growing fetus in utero. It is usually thrown away after birth, but it has a therapeutic role in the regeneration of tissue. It is covered by the amniotic membrane, which can be easily separated into the amnion layer and the chorion layer—the amnion layer act as a biofilm for the healing of burn wound and non-healing ulcers. The freshly collected membrane has stem cells, cytokines, growth factors, and anti-inflammatory properties, which act as a biofilm for the healing of wounds. It functions as a barrier and prevents heat and water loss and also protects from bacterial contamination, thus supporting the healing process. The application of Amnion membranes has been successfully used for wound and reconstructive purposes for decades. It is a very cheap and easy process and has shown superior results to allograft and xenograft. However, there are very few case reports of amnion membrane grafting in newborns; we intend to highlight its therapeutic importance in burn injuries in newborns. We present a case of 9 days old male neonate who presented to the neonatal unit of Maulana Azad Medical College with a complaint of fluid-filled blisters and burns wound on the body for six days. He was born outside the hospital at 38 weeks of gestation to a 24-year-old primigravida mother by vaginal delivery. The presentation was cephalic and the amniotic fluid was clear. His birth weight was 2800 gm and APGAR scores were 7 and 8 at 1 and 5 minutes, respectively. His anthropometry was appropriate for gestational age. He developed respiratory distress after birth requiring oxygen support by nasal prongs for three days. On the day of life three, he developed blisters on his body, starting from than face then over the back and perineal region. At a presentation on the day of life nine, he had blisters and necrotic wound on the right side of the face, back, right shoulder and genitalia, affecting 60% of body surface area with full-thickness loss of skin. He was started on intravenous antibiotics and fluid therapy. Pus culture grew Pseudomonas aeuroginosa, for which culture-specific antibiotics were started. Plastic surgery reference was taken and regular wound dressing was done with antiseptics. He had a storming course during the hospital stay. On the day of life 35 when the baby was hemodynamically stable, amnion membrane grafting was done on the wound site; for the grafting, fresh amnion membrane was removed under sterile conditions from the placenta obtained by caesarean section. It was then transported to the plastic surgery unit in half an hour in a sterile fluid where the graft was applied over the infant’s wound. The amnion membrane grafting was done twice in two weeks for covering the whole wound area. After successful uptake of amnion membrane, skin from the thigh region was autografted over the whole wound area by Meek technique in a single setting. The uptake of autograft was excellent and most of the areas were healed. In some areas, there was patchy regeneration of skin so dressing was continued. The infant was discharged after three months of hospital stay and was later followed up in the plastic surgery unit of the hospital.

Keywords: amnion membrane grafting, autograft, meek technique, newborn, regeneration of skin

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Authors: Dagmara Malina, Katarzyna Bialik-Wąs, Klaudia Pluta

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The growing significance of transdermal systems, in which skin is a route for systemic drug delivery, has generated a considerable amount of data which has resulted in a deeper understanding of the mechanisms of transport across the skin in the context of the controlled and prolonged release of active substances. One of such solutions may be the use of carrier systems based on intelligent polymers with different physicochemical properties. In these systems, active substances, e.g. drugs, can be conjugated (attached), immobilized, or encapsulated in a polymer matrix that is sensitive to specific environmental conditions (e.g. pH or temperature changes). Intelligent polymers can be divided according to their sensitivity to specific environmental stimuli such as temperature, pH, light, electric, magnetic, sound, or electromagnetic fields. Materials & methods—The first stage of the presented research concerned the synthesis of pH-sensitive polymeric carriers by a radical polymerization reaction. Then, the selected active substance (hydrocortisone) was introduced into polymeric carriers. In a further stage, bio-hybrid sodium alginate/poly(vinyl alcohol) – SA/PVA-based hydrogel matrices modified with various carrier-drug systems were prepared with the chemical cross-linking method. The conducted research included the assessment of physicochemical properties of obtained materials i.e. degree of hydrogel swelling and degradation studies as a function of pH in distilled water and phosphate-buffered saline (PBS) at 37°C in time. The gel fraction represents the insoluble gel fraction as a result of inter-molecule cross-linking formation was also measured. Additionally, the chemical structure of obtained hydrogels was confirmed using FT-IR spectroscopic technique. The dynamic light scattering (DLS) technique was used for the analysis of the average particle size of polymer-carriers and carrier-drug systems. The nanocarriers morphology was observed using SEM microscopy. Results & Discussion—The analysis of the encapsulated polymeric carriers showed that it was possible to obtain the time-stable empty pH-sensitive carrier with an average size 479 nm and the encapsulated system containing hydrocortisone with an average 543 nm, which was introduced into hydrogel structure. Bio-hybrid hydrogel matrices are stable materials, and the presence of an additional component: pH-sensitive carrier – hydrocortisone system, does not reduce the degree of cross-linking of the matrix nor its swelling ability. Moreover, the results of swelling tests indicate that systems containing higher concentrations of the drug have a slightly higher sorption capacity in each of the media used. All analyzed materials show stable and statically changing swelling values in simulated body fluids - there is no sudden fluid uptake and no rapid release from the material. The analysis of FT-IR spectra confirms the chemical structure of the obtained bio-hybrid hydrogel matrices. In the case of modifications with a pH-sensitive carrier, a much more intense band can be observed in the 3200-3500 cm⁻¹ range, which most likely originates from the strong hydrogen interactions that occur between individual components.

Keywords: hydrogels, polymer nanocarriers, sodium alginate/poly(vinyl alcohol) matrices, wound dressings.

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Authors: Suman Chaudhary, Rupinder K. Kanwar, Jagat R. Kanwar

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Azadirachta indica, also known as Neem belonging to the mahogany family is actively gaining interest in the era of modern day medicine due to its extensive applications in homeopathic medicine such as Ayurveda and Unani. More than 140 phytochemicals have been extracted from neem leaves, seed, bark and flowers for agro-medicinal applications. Among the various components, neem leaf protein (NLP) is currently the most investigated active ingredient, due to its immunomodulatory activities against tumor growth. However, these therapeutic ingredients of neem are susceptible to degradation and cannot withstand the drastic pH changes under physiological environment, and therefore, there is an urgent need of an alternative strategy such as a nano-delivery system to exploit its medicinal benefits. This study hypothesizes that guar gum (GG) derived biodegradable nano-carrier based encapsulation of NLP will improve its stability, specificity and sensitivity, thus facilitating targeted anti-cancer therapeutics. GG is a galactomannan derived from the endosperm of the guar beans seeds. Synthesis of guar nanocapsules (NCs) was performed using nanoprecipitation technique where the GG was encapsulated with NLP. Preliminary experiments conducted to characterize the NCs confirmed spherical morphology with a narrow size distribution of 30-40 nm. Differential scanning colorimetric analysis (DSC) validated the stability of these NCs even at a temperature range of 50-60°C which was well within the physiological and storage conditions. Thermogravimetric (TGA) analysis indicated high decomposition temperature of these NCs ranging upto 350°C. Additionally, Fourier Transform Infrared spectroscopy (FTIR) and the SDS-PAGE data acquired confirmed the successful encapsulation of NLP in the NCs. The anti-cancerous therapeutic property of this NC was tested on colon cancer cells (caco-2) as they are one of the most prevalent form of cancer. These NCs (both NLP loaded and void) were also tested on human intestinal epithelial cells (FHs 74) cells to evaluate their effect on normal cells. Cytotoxicity evaluation of the NCs in the cell lines confirmed that the IC50 for NLP in FHs 74 cells was ~2 fold higher than in caco-2 cells, indicating that this nanoformulation system possessed biocompatible anti-cancerous properties Immunoconfocal microscopy analysis confirmed the time dependent internalization of the NCs within 6h. Recent findings performed using Annexin V and PI staining indicated a significant increase (p ≤ 0.001) in the early and late apoptotic cell population when treated with the NCs signifying the role of NLP in inducing apoptosis in caco-2 cells. This was further validated using Western blot, Polymerase chain reaction (PCR) and Fluorescence activated cell sorter (FACS) aided protein expressional analysis which presented a downregulation of survivin, an anti-apoptotic cell marker and upregulation of Bax/Bcl-2 ratio (pro-apoptotic indicator). Further, both the NLP NC and unencapsulated NLP treatment destabilized the mitochondrial membrane potential subsequently facilitating the release of the pro-apoptotic caspase cascade initiator, cytochrome-c. Future studies will be focused towards granting specificity to these NCs towards cancer cells, along with a comprehensive analysis of the anti-cancer potential of this naturally occurring compound in different cancer and in vivo animal models, will validate the clinical application of this unprecedented protein therapeutic.

Keywords: anti-tumor, guar gum, nanocapsules, neem leaf protein

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Authors: Wiseman Emmanuel Nkhomah, Chiyembekezo Kachimanga, Julia Huggins, Fabien Munyaneza

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Background: Partners In Health – Malawi introduced one of Operational Researches called Primary Health Care (PHC) Surveys in 2020, which seeks to assess progress of delivery of care in the district. The study consists of 5 long surveys, namely; Facility assessment, General Patient, Provider, Sick Child, Antenatal Care (ANC), primarily conducted in 4 health facilities in Neno district. These facilities include Neno district hospital, Dambe health centre, Chifunga and Matope. Usually, these annual surveys are conducted from January, and the target is to present final report by June. Once data is collected and analyzed, there are a series of reviews that take place before reaching final report. In the first place, the manual process took over 9 months to present final report. Initial findings reported about 76.9% of the data that added up when cross-checked with paper-based sources. Purpose: The aim of this approach is to run away from manually pulling the data, do fresh analysis, and reporting often associated not only with delays in reporting inconsistencies but also with poor quality of data if not done carefully. This automation approach was meant to utilize features of new technologies to create visualizations, reports, and dashboards in Power BI that are directly fished from the data source – CommCare hence only require a single click of a ‘refresh’ button to have the updated information populated in visualizations, reports, and dashboards at once. Methodology: We transformed paper-based questionnaires into electronic using CommCare mobile application. We further connected CommCare Mobile App directly to Power BI using Application Program Interface (API) connection as data pipeline. This provided chance to create visualizations, reports, and dashboards in Power BI. Contrary to the process of manually collecting data in paper-based questionnaires, entering them in ordinary spreadsheets, and conducting analysis every time when preparing for reporting, the team utilized CommCare and Microsoft Power BI technologies. We utilized validations and logics in CommCare to capture data with less errors. We utilized Power BI features to host the reports online by publishing them as cloud-computing process. We switched from sharing ordinary report files to sharing the link to potential recipients hence giving them freedom to dig deep into extra findings within Power BI dashboards and also freedom to export to any formats of their choice. Results: This data automation approach reduced research timelines from the initial 9 months’ duration to 5. It also improved the quality of the data findings from the original 76.9% to 98.9%. This brought confidence to draw conclusions from the findings that help in decision-making and gave opportunities for further researches. Conclusion: These results suggest that automating the research data process has the potential of reducing overall amount of time spent and improving the quality of the data. On this basis, the concept of data automation should be taken into serious consideration when conducting operational research for efficiency and decision-making.

Keywords: reporting, decision-making, power BI, commcare, data automation, visualizations, dashboards

Procedia PDF Downloads 116

Authors: Bandar Alkahlan

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The King Abdulaziz City for Science and Technology (KACST) created the Saudi Future Dwelling (SFD) initiative to identify, localize and commercialize a scalable home manufacturing technology suited to deployment across the Kingdom of Saudi Arabia (KSA). This paper outlines the journey, the creation of the international project delivery team, the product design, the selection of the process technologies, and the outcomes. A target was set to remove 85% of the construction and finishing processes from the building site as these activities could be more efficiently completed in a factory environment. Therefore, integral to the SFD initiative is the successful industrialization of the home building process using appropriate technologies, automation, robotics, and manufacturing logistics. The technologies proposed for the SFD housing system are designed to be energy efficient, economical, fit for purpose from a Saudi cultural perspective, and will minimize the use of concrete, relying mainly on locally available Saudi natural materials derived from the local resource industries. To this end, the building structure is comprised of a hybrid system of structural insulated panels (SIP), combined with a light gauge steel framework manufactured in a large format panel system. The paper traces the investigative process and steps completed by the project team during the selection process. As part of the SFD Project, a pathway was mapped out to include a proof-of-concept prototype housing module and the set-up and commissioning of a lab-factory complete with all production machinery and equipment necessary to simulate a full-scale production environment. The prototype housing module was used to validate and inform current and future product design as well as manufacturing process decisions. A description of the prototype design and manufacture is outlined along with valuable learning derived from the build and how these results were used to enhance the SFD project. The industrial engineering concepts and lab-factory detailed design and layout are described in the paper, along with the shop floor I.T. management strategy. Special attention was paid to showcase all technologies within the lab-factory as part of the engagement strategy with private investors to leverage the SFD project with large scale factories throughout the Kingdom. A detailed analysis is included in the process surrounding the design, specification, and procurement of the manufacturing machinery, equipment, and logistical manipulators required to produce the SFD housing modules. The manufacturing machinery was comprised of a combination of standardized and bespoke equipment from a wide range of international suppliers. The paper describes the selection process, pre-ordering trials and studies, and, in some cases, the requirement for additional research and development by the equipment suppliers in order to achieve the SFD objectives. A set of conclusions is drawn describing the results achieved thus far, along with a list of recommended ongoing operational tests, enhancements, research, and development aimed at achieving full-scale engagement with private sector investment and roll-out of the SFD project across the Kingdom.

Keywords: automation, dwelling, manufacturing, product design

Procedia PDF Downloads 120

Authors: Melissa de Zeeuw, Peter Smolianov, Arnold Bohl

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This study was designed to help and improve international performance as well increase swimming participation in the Netherlands. Over 200 sources of literature on sport delivery systems from 28 Australasian, North and South American, Western and Eastern European countries were analyzed to construct a globally applicable model of high performance swimming integrated with mass participation, comprising of the following seven elements and three levels: Micro level (operations, processes, and methodologies for development of individual athletes): 1. Talent search and development, 2. Advanced athlete support. Meso level (infrastructures, personnel, and services enabling sport programs): 3. Training centers, 4. Competition systems, 5. Intellectual services. Macro level (socio-economic, cultural, legislative, and organizational): 6. Partnerships with supporting agencies, 7. Balanced and integrated funding and structures of mass and elite sport. This model emerged from the integration of instruments that have been used to analyse and compare national sport systems. The model has received scholarly validation and showed to be a framework for program analysis that is not culturally bound. It has recently been accepted as a model for further understanding North American sport systems, including (in chronological order of publications) US rugby, tennis, soccer, swimming and volleyball. The above model was used to design a questionnaire of 42 statements reflecting desired practices. The statements were validated by 12 international experts, including executives from sport governing bodies, academics who published on high performance and sport development, and swimming coaches and administrators. In this study both a highly structured and open ended qualitative analysis tools were used. This included a survey of swim coaches where open responses accompanied structured questions. After collection of the surveys, semi-structured discussions with Federation coaches were conducted to add triangulation to the findings. Lastly, a content analysis of Dutch Swimming’s website and organizational documentation was conducted. A representative sample of 1,600 Dutch Swim coaches and administrators was collected via email addresses from Royal Dutch Swimming Federation' database. Fully completed questionnaires were returned by 122 coaches from all key country’s regions for a response rate of 7,63% - higher than the response rate of the previously mentioned US studies which used the same model and method. Results suggest possible enhancements at macro level (e.g., greater public and corporate support to prepare and hire more coaches and to address the lack of facilities, monies and publicity at mass participation level in order to make swimming affordable for all), at meso level (e.g., comprehensive education for all coaches and full spectrum of swimming pools particularly 50 meters long), and at micro level (e.g., better preparation of athletes for a future outside swimming and better use of swimmers to stimulate swimming development). Best Dutch swimming management practices (e.g., comprehensive support to most talented swimmers who win Olympic medals) as well as relevant international practices available for transfer to the Netherlands (e.g., high school competitions) are discussed.

Keywords: sport development, high performance, mass participation, swimming

Procedia PDF Downloads 204

Authors: Z. Zaman Asam, M. Ajmal, R. Saeed, H. Miraj, M. Muhammad Ahtisham, B. Hameed, A. -Sattar Nizami

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In Pakistan, environmental degradation and consequent human health deterioration has rapidly accelerated in the past decade due to solid waste mismanagement. As the situation worsens with time, establishment of proper waste management practices is urgently needed especially in semi urban and rural areas of Pakistan. This study uses a concept of Waste Bank, which involves a transfer station for collection of sorted waste fractions and its delivery to the targeted market such as recycling industries, biogas plants, composting facilities etc. The management efficiency and effectiveness of Waste Bank depend strongly on the proficient sorting and collection of solid waste fractions at household level. However, the social attitude towards such a solution in semi urban/rural areas of Pakistan demands certain prerequisites to make it workable. Considering these factors the objectives of this study are to: [A] Obtain reliable data about quantity and characteristics of generated waste to define feasibility of business and design factors, such as required storage area, retention time, transportation frequency of the system etc. [B] Analyze the effects of various social factors on waste generation to foresee future projections. [C] Quantify the improvement in waste sorting efficiency after awareness campaign. We selected Gujrat city of Central Punjab province of Pakistan as it is semi urban adjoined by rural areas. A total of 60 houses (20 from each of the three selected colonies), belonging to different social status were selected. Awareness sessions about waste segregation were given through brochures and individual lectures in each selected household. Sampling of waste, that households had attempted to sort, was then carried out in the three colored bags that were provided as part of the awareness campaign. Finally, refined waste sorting, weighing of various fractions and measurement of dry mass was performed in environmental laboratory using standard methods. It was calculated that sorting efficiency of waste improved from 0 to 52% as a result of the awareness campaign. The generation of waste (dry mass basis) on average from one household was 460 kg/year whereas per capita generation was 68 kg/year. Extrapolating these values for Gujrat Tehsil, the total waste generation per year is calculated to be 101921 tons dry mass (DM). Characteristics found in waste were (i) organic decomposable (29.2%, 29710 tons/year DM), (ii) recyclables (37.0%, 37726 tons/year DM) that included plastic, paper, metal and glass, and (iii) trash (33.8%, 34485 tons/year DM) that mainly comprised of polythene bags, medicine packaging, pampers and wrappers. Waste generation was more in colonies with comparatively higher income and better living standards. In future, data collection for all four seasons and improvements due to expansion of awareness campaign to educational institutes will be quantified. This waste management system can potentially fulfill vital sustainable development goals (e.g. clean water and sanitation), reduce the need to harvest fresh resources from the ecosystem, create business and job opportunities and consequently solve one of the most pressing environmental issues of the country.

Keywords: integrated solid waste management, waste segregation, waste bank, community development

Procedia PDF Downloads 141

Authors: Kasun P. Wijayaratna, Lauren Gardner, Taha Hossein Rashidi

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Undergraduate students entering university across the last 2 to 3 years tend to be born during the middle years of the 1990s. This generation of students has been exposed to the internet and the desire and dependency on technology since childhood. Brains develop based on environmental influences and technology has wired this generation of student to be attuned to sophisticated complex visual imagery, indicating visual forms of learning may be more effective than the traditional lecture or discussion formats. Furthermore, post-millennials perspectives on career are not focused solely on stability and income but are strongly driven by interest, entrepreneurship and innovation. Accordingly, it is important for educators to acknowledge the generational shift and tailor the delivery of learning material to meet the expectations of the students and the needs of industry. In the context of transport engineering, effectively teaching undergraduate students the basic principles of transport planning, traffic engineering and highway design is fundamental to the progression of the profession from a practice and research perspective. Recent developments in technology have transformed the discipline as practitioners and researchers move away from the traditional “pen and paper” approach to methods involving the use of computer programs and simulation. Further, enhanced accessibility of technology for students has changed the way they understand and learn material being delivered at tertiary education institutions. As a consequence, blended learning approaches, which aim to integrate face to face teaching with flexible self-paced learning resources, have become prevalent to provide scalable education that satisfies the expectations of students. This research study involved the development of a series of ‘Blended Learning’ initiatives implemented within an introductory transport planning and geometric design course, CVEN2401: Sustainable Transport and Highway Engineering, taught at the University of New South Wales, Australia. CVEN2401 was modified by conducting interactive polling exercises during lectures, including weekly online quizzes, offering a series of supplementary learning videos, and implementing a realistic design project that students needed to complete using modelling software that is widely used in practice. These activities and resources were aimed to improve the learning environment for a large class size in excess of 450 students and to ensure that practical industry valued skills were introduced. The case study compared the 2016 and 2017 student cohorts based on their performance across assessment tasks as well as their reception to the material revealed through student feedback surveys. The initiatives were well received with a number of students commenting on the ability to complete self-paced learning and an appreciation of the exposure to a realistic design project. From an educator’s perspective, blending the course made it feasible to interact and engage with students. Personalised learning opportunities were made available whilst delivering a considerable volume of complex content essential for all undergraduate Civil and Environmental Engineering students. Overall, this case study highlights the value of blended learning initiatives, especially in the context of large class size university courses.

Keywords: blended learning, highway design, teaching, transport planning

Procedia PDF Downloads 148

Authors: Niharika Kaushal, Minni Singh

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Citrus fruits fall into the category of those commercially grown fruits that constitute an excellent repository of phytochemicals with health-promoting properties. Fruits belonging to the citrus family, when processed by industries, produce tons of agriculture by-products in the form of peels, pulp, and seeds, which normally have no further usage and are commonly discarded. In spite of this, such residues are of paramount importance due to their richness in valuable compounds; therefore, agro-waste is considered a valuable bioresource for various purposes in the food sector. A range of biological properties, including anti-oxidative, anti-cancerous, anti-inflammatory, anti-allergenicity, and anti-aging activity, have been reported for these bioactive compounds. Taking advantage of these inexpensive residual sources requires special attention to extract bioactive compounds. Mandarin (Citrus nobilis X Citrus deliciosa) is a potential source of bioflavonoids with antioxidant properties, and it is increasingly regarded as a functional food. Despite these benefits, flavonoids suffer from a barrier of pre-systemic metabolism in gastric fluid, which impedes their effectiveness. Therefore, colloidal delivery systems can completely overcome the barrier in question. This study involved the extraction and identification of key flavonoids from mandarin biomass. Using a green chemistry approach, supercritical fluid extraction at 330 bar, temperature 40C, and co-solvent 10% ethanol was employed for extraction, and the identification of flavonoids was made by mass spectrometry. As flavonoids are concerned with a limitation, the obtained extract was encapsulated in polylactic-co-glycolic acid (PLGA) matrix using a solvent evaporation method. Additionally, the antioxidant potential was evaluated by the 2,2-diphenylpicrylhydrazyl (DPPH) assay. A release pattern of flavonoids was observed over time using simulated gastrointestinal fluids. From the results, it was observed that the total flavonoids extracted from the mandarin biomass were estimated to be 47.3 ±1.06 mg/ml rutin equivalents as total flavonoids. In the extract, significantly, polymethoxyflavones (PMFs), tangeretin and nobiletin were identified, followed by hesperetin and naringin. The designed flavonoid-PLGA nanoparticles exhibited a particle size between 200-250nm. In addition, the bioengineered nanoparticles had a high entrapment efficiency of nearly 80.0% and maintained stability for more than a year. Flavonoid nanoparticles showed excellent antioxidant activity with an IC50 of 0.55μg/ml. Morphological studies revealed the smooth and spherical shape of nanoparticles as visualized by Field emission scanning electron microscopy (FE-SEM). Simulated gastrointestinal studies of free extract and nanoencapsulation revealed the degradation of nearly half of the flavonoids under harsh acidic conditions in the case of free extract. After encapsulation, flavonoids exhibited sustained release properties, suggesting that polymeric encapsulates are efficient carriers of flavonoids. Thus, such technology-driven and biomass-derived products form the basis for their use in the development of functional foods with improved therapeutic potential and antioxidant properties. As a result, citrus processing waste can be considered a new resource that has high value and can be used for promoting its utilization.

Keywords: citrus, agrowaste, flavonoids, nanoparticles

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Authors: Ece A. Irmak, Amdulla O. Mekhrabov, M. Vedat Akdeniz

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There is a growing interest in the modeling and simulation of magnetic nanoalloys by various computational methods. Magnetic crystalline/amorphous nanoparticles (NP) are interesting materials from both the applied and fundamental points of view, as their properties differ from those of bulk materials and are essential for advanced applications such as high-performance permanent magnets, high-density magnetic recording media, drug carriers, sensors in biomedical technology, etc. As an important magnetic material, Fe-Ni based nanoalloys have promising applications in the chemical industry (catalysis, battery), aerospace and stealth industry (radar absorbing material, jet engine alloys), magnetic biomedical applications (drug delivery, magnetic resonance imaging, biosensor) and computer hardware industry (data storage). The physical and chemical properties of the nanoalloys depend not only on the particle or crystallite size but also on composition and atomic ordering. Therefore, computer modeling is an essential tool to predict structural, electronic, magnetic and optical behavior at atomistic levels and consequently reduce the time for designing and development of new materials with novel/enhanced properties. Although first-principles quantum mechanical methods provide the most accurate results, they require huge computational effort to solve the Schrodinger equation for only a few tens of atoms. On the other hand, molecular dynamics method with appropriate empirical or semi-empirical inter-atomic potentials can give accurate results for the static and dynamic properties of larger systems in a short span of time. In this study, structural evolutions, magnetic and electronic properties of Fe-Ni based nanoalloys have been studied by using molecular dynamics (MD) method in Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) and Density Functional Theory (DFT) in the Vienna Ab initio Simulation Package (VASP). The effects of particle size (in 2-10 nm particle size range) and temperature (300-1500 K) on stability and structural evolutions of amorphous and crystalline Fe-Ni bulk/nanoalloys have been investigated by combining molecular dynamic (MD) simulation method with Embedded Atom Model (EAM). EAM is applicable for the Fe-Ni based bimetallic systems because it considers both the pairwise interatomic interaction potentials and electron densities. Structural evolution of Fe-Ni bulk and nanoparticles (NPs) have been studied by calculation of radial distribution functions (RDF), interatomic distances, coordination number, core-to-surface concentration profiles as well as Voronoi analysis and surface energy dependences on temperature and particle size. Moreover, spin-polarized DFT calculations were performed by using a plane-wave basis set with generalized gradient approximation (GGA) exchange and correlation effects in the VASP-MedeA package to predict magnetic and electronic properties of the Fe-Ni based alloys in bulk and nanostructured phases. The result of theoretical modeling and simulations for the structural evolutions, magnetic and electronic properties of Fe-Ni based nanostructured alloys were compared with experimental and other theoretical results published in the literature.

Keywords: density functional theory, embedded atom model, Fe-Ni systems, molecular dynamics, nanoalloys

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Authors: Roshni Raha, Kavya P., Gayathri M.

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India, with a humongous population, remains the world's poorest developing nation in terms of nutritional status, with iron deficiency anaemia (IDA) affecting the population. Despite efforts over the past decades, India's anaemia prevalence has not been reduced. Researchers are interested in developing therapies that will minimize the typical side effects of oral iron and optimize iron salts-based treatment through delivery methods based on the physiology of hepcidin regulation. However, they need to come up with iron therapies that will prevent making the infection worse. This article explores using bio-nanotechnology as the alternative, promising substitution of providing iron supplements for the treatment of diarrhoea and gut inflammation in kids and pregnant women. This article is an exploratory study using a literature survey and secondary research from review papers. In the realm of biotechnology, nanoparticles have become extremely famous due to unexpected variations in surface characteristics caused by particle size. Particle size distribution and shape exhibit unusual, enhanced characteristics when reduced to nanoscale. The article attempts to develop a model for a nanotechnology based solution in iron fortification to combat the problems of diarrhoea and gut inflammation. Certain dimensions that have been considered in the model include the size, shape, source, and biosynthesis of the iron nanoparticles. Another area of investigation addressed in the article is the cost-effective biocompatible production of these iron nanoparticles. Studies have demonstrated that a substantial reduction of metal ions to form nanoparticles from the bulk metal occurs in plants because of the presence of a wide diversity of biomolecules. Using this concept, the paper investigates the effectiveness and impact of how similar sources can be used for the biological synthesis of iron nanoparticles. Results showed that iron particles, when prepared in nano-metre size, offer potential advantages. When the particle size of the iron compound decreases and attains nano configuration, its surface area increases, which further improves its solubility in the gastric acid, leading to higher absorption, higher bioavailability, and producing the least organoleptic changes in food. It has no negative effects and possesses a safe, effective profile to reduce IDA. Considering all the parameters, it has been concluded that iron particles in nano configuration serve as alternative iron supplements for the complete treatment of IDA. Nanoparticles of ferric phosphate, ferric pyrophosphate, and iron oxide are the choices of iron supplements. From a sourcing perspective, the paper concludes green sources are the primary sources for the biological synthesis of iron nanoparticles. It will also be a cost-effective strategy since our goal is to treat the target population in rural India. Bio-nanotechnology serves as an alternative and promising substitution for iron supplements due to its low cost, excellent bioavailability, and strong organoleptic properties. One area of future research can be to explore the type of size and shape of iron nanoparticles that would be suitable for the different age groups of pregnant women and children and whether it would be influenced based on the topography in certain areas.

Keywords: anemia, bio-nanotechnology, iron-fortification, nanoparticle

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Authors: Lily Ranjbar, Haori Yang

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Online education has been around for several decades, but the importance of online education became evident after the COVID-19 pandemic. Eventhough the online delivery approach works well for knowledge building through delivering content and oversight processes, it has limitations in developing hands-on laboratory skills, especially in the STEM field. During the pandemic, many education institutions faced numerous challenges in delivering lab-based courses, especially in the STEM field. Also, many students worldwide were unable to practice working with lab equipment due to social distancing or the significant cost of highly specialized equipment. The laboratory plays a crucial role in nuclear science and engineering education. It can engage students and improve their learning outcomes. In addition, online education and virtual labs have gained substantial popularity in engineering and science education. Therefore, developing virtual labs is vital for institutions to deliver high-class education to their students, including their online students. The School of Nuclear Science and Engineering (NSE) at Oregon State University, in partnership with SpectralLabs company, has developed an Advanced Virtual Radiation Detection and Measurement Lab (AVR-DML) to offer a fully online Master of Health Physics program. It was essential for us to use a system that could simulate nuclear modules that accurately replicate the underlying physics, the nature of radiation and radiation transport, and the mechanics of the instrumentations used in the real radiation detection lab. It was all accomplished using a Realistic, Adaptive, Interactive Learning System (RAILS). RAILS is a comprehensive software simulation-based learning system for use in training. It is comprised of a web-based learning management system that is located on a central server, as well as a 3D-simulation package that is downloaded locally to user machines. Users will find that the graphics, animations, and sounds in RAILS create a realistic, immersive environment to practice detecting different radiation sources. These features allow students to coexist, interact and engage with a real STEM lab in all its dimensions. It enables them to feel like they are in a real lab environment and to see the same system they would in a lab. Unique interactive interfaces were designed and developed by integrating all the tools and equipment needed to run each lab. These interfaces provide students full functionality for data collection, changing the experimental setup, and live data collection with real-time updates for each experiment. Students can manually do all experimental setups and parameter changes in this lab. Experimental results can then be tracked and analyzed in an oscilloscope, a multi-channel analyzer, or a single-channel analyzer (SCA). The advanced virtual radiation detection and measurement laboratory developed in this study enabled the NSE school to offer a fully online MHP program. This flexibility of course modality helped us to attract more non-traditional students, including international students. It is a valuable educational tool as students can walk around the virtual lab, make mistakes, and learn from them. They have an unlimited amount of time to repeat and engage in experiments. This lab will also help us speed up training in nuclear science and engineering.

Keywords: advanced radiation detection and measurement, virtual laboratory, realistic adaptive interactive learning system (rails), online education in stem fields, student engagement, stem online education, stem laboratory, online engineering education

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Authors: Leila Noori, Rosario Barone, Francesca Rappa, Antonella Marino Gammazza, Alessandra Maria Vitale, Giuseppe Donato Mangano, Giusy Sentiero, Filippo Macaluso, Kathryn H. Myburgh, Francesco Cappello, Federica Scalia

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The neuromuscular system controls, directs, and allows movement of the body through the action of neural circuits, which include motor neurons, sensory neurons, and skeletal muscle fibers. Protein homeostasis of the involved cytotypes appears crucial to maintain the correct and prolonged functions of the neuromuscular system, and both neuronal cells and skeletal muscle fibers express significant quantities of protein chaperones, the molecular machinery responsible to maintain the protein turnover. Genetic mutations or defective post-translational modifications of molecular chaperones (i.e., genetic or acquired chaperonopathies) may lead to neuromuscular disorders called as neurochaperonopathies. The limited knowledge of the effects of the defective chaperones on skeletal muscle fibers and neurons impedes the progression of therapeutic approaches. A distinct genetic variation of CCT5 gene encoding for the subunit 5 of the chaperonin CCT (Chaperonin Containing TCP1; also known as TRiC, TCP1 Ring Complex) was recently described associated with severe distal motor neuropathy by our team. In this study, we investigated the histopathological abnormalities of the skeletal muscle biopsy of the pediatric patient affected by the mutation Leu224Val in the CCT5 subunit. We provide molecular and structural features of the diseased skeletal muscle tissue that we believe may be useful to identify undiagnosed cases of this rare genetic disorder. We investigated the histological abnormalities of the affected tissue via hematoxylin and eosin staining. Then we used immunofluorescence and qPCR techniques to explore the expression and distribution of CCT5 in diseased and healthy skeletal muscle tissue. Immunofluorescence and immunohistochemistry assays were performed to study the sarcomeric and structural proteins of skeletal muscle, including actin, myosin, tubulin, troponin-T, telethonin, and titin. We performed Western blot to examine the protein expression of CCT5 and some heat shock proteins, Hsp90, Hsp60, Hsp27, and α-B crystallin, along with the main client proteins of the CCT5, actin, and tubulin. Our findings revealed muscular atrophy, abnormal morphology, and different sizes of muscle fibers in affected tissue. The swollen nuclei and wide interfiber spaces were seen. Expression of CCT5 had been decreased and showed a different distribution pattern in the affected tissue. Altered expression, distribution, and bandage pattern were detected by confocal microscopy for the interested muscular proteins in tissue from the patient compared to the healthy control. Protein levels of the studied Hsps normally located at the Z-disk were reduced. Western blot results showed increased levels of the actin and tubulin proteins in the diseased skeletal muscle biopsy compared to healthy tissue. Chaperones must be expressed at high levels in skeletal muscle to counteract various stressors such as mechanical, oxidative, and thermal crises; therefore, it seems relevant that defects of molecular chaperones may result in damaged skeletal muscle fibers. So far, several chaperones or cochaperones involved in neuromuscular disorders have been defined. Our study shows that alteration of the CCT5 subunit is associated with the damaged structure of skeletal muscle fibers and alterations of chaperone system components and paves the way to explore possible alternative substrates of chaperonin CCT. However, further studies are underway to investigate the CCT mechanisms of action to design applicable therapeutic strategies.

Keywords: molecular chaperones, neurochaperonopathy, neuromuscular system, protein homeostasis

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

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

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

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Authors: Kelsi Hagerty, Ami Rosen, Aaliyah Heyward, Nadia Ali, Emily Brown, Erin Demo, Yue Guan, Modele Ogunniyi, Brianna McDaniels, Alanna Morris, Kunal Bhatt

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Hereditary transthyretin amyloidosis (hATTR) is a progressive, multi-systemic, and life-threatening disease caused by a disruption in the TTR protein that delivers thyroxine and retinol to the liver. This disruption causes the protein to misfold into amyloid fibrils, leading to the accumulation of the amyloid fibrils in the heart, nerves, and GI tract. Over 130 variants in the TTR gene are known to cause hATTR. The Val122Ile variant is the most common in the United States and is seen almost exclusively in people of African descent. TTR variants are inherited in an autosomal dominant fashion and have incomplete penetrance and variable expressivity. Individuals with hATTR may exhibit symptoms from as early as 30 years to as late as 80 years of age. hATTR is characterized by a wide range of clinical symptoms such as cardiomyopathy, neuropathy, carpal tunnel syndrome, and GI complications. Without treatment, hATTR leads to progressive disease and can ultimately lead to heart failure. hATTR disproportionately affects individuals of African descent; the estimated prevalence of hATTR among Black individuals in the US is 3.4%. Unfortunately, hATTR is often underdiagnosed and misdiagnosed because many symptoms of the disease overlap with other cardiac conditions. Due to the progressive nature of the disease, multi-systemic manifestations that can lead to a shortened lifespan, and the availability of free genetic testing and promising FDA-approved therapies that enhance treatability, early identification of individuals with a pathogenic hATTR variant is important, as this can significantly impact medical management for patients and their relatives. Furthermore, recent literature suggests that TTR genetic testing should be performed in all patients with suspicion of TTR-related cardiomyopathy, regardless of age, and that follow-up with genetic counseling services is recommended. Relatives of patients with hATTR benefit from genetic testing because testing can identify carriers early and allow relatives to receive regular screening and management. Despite the striking prevalence of hATTR among Black individuals, hATTR remains underdiagnosed in this patient population, and germline genetic testing for hATTR in Black individuals seems to be underrepresented, though the reasons for this have not yet been brought to light. Historically, Black patients experience a number of barriers to seeking healthcare that has been hypothesized to perpetuate the underdiagnosis of hATTR, such as lack of access and mistrust of healthcare professionals. Prior research has described a myriad of factors that shape an individual’s decision about whether to pursue presymptomatic genetic testing for a familial pathogenic variant, such as family closeness and communication, family dynamics, and a desire to inform other family members about potential health risks. This study explores these factors through 10 in-depth interviews with patients with hATTR about what factors may be contributing to the underdiagnosis of hATTR in the Black population. Participants were selected from the Emory University Amyloidosis clinic based on having a molecular diagnosis of hATTR. Interviews were recorded and transcribed verbatim, then coded using MAXQDA software. Thematic analysis was completed to draw commonalities between participants. Upon preliminary analysis, several themes have emerged. Barriers identified include i) Misdiagnosis and a prolonged diagnostic odyssey, ii) Family communication and dynamics surrounding health issues, iii) Perceptions of healthcare and one’s own health risks, and iv) The need for more intimate provider-patient relationships and communication. Overall, this study gleaned valuable insight from members of the Black community about possible factors contributing to the underdiagnosis of hATTR, as well as potential solutions to go about resolving this issue.

Keywords: cardiac amyloidosis, heart failure, TTR, genetic testing

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Authors: Bassey O. Bassey

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Benchmarking has progressively become entrenched as a requisite activity for process improvement and enhancing service delivery at petroleum jetties and terminals, most especially during tanker discharge operations at the ship – shore interface, as avoidable delays result in extra operating costs, non-productive time, high demurrage payments and ultimate product scarcity. The jetty and terminal in focus had been operational for 3 and 8 years respectively, with proper operational and logistic records maintained to evaluate their progress over time in order to plan and implement modifications and review of procedures for greater technical and economic efficiency. Regular and emergency staff meetings were held on a team, departmental and company-wide basis to progressively address major challenges that were encountered during each operation. The process and outcome of the resultant collectively planned changes carried out within the past two years forms the basis of this paper, which mirrors the initiatives effected to enhance operational and maintenance excellence at the affected facilities. Operational modifications included a second cargo receipt line designated for gasoline, product loss control at jetty and shore ends, enhanced product recovery and quality control, and revival of terminal–jetty backloading operations. Logistic improvements were the incorporation of an internal logistics firm and shipping agency, fast tracking of discharge procedures for tankers, optimization of tank vessel selection process, and third party product receipt and throughput. Maintenance excellence was achieved through construction of two new lay barges and refurbishment of the existing one; revamping of existing booster pump and purchasing of a modern one as reserve capacity; extension of Phase 1 of the jetty to accommodate two vessels and construction of Phase 2 for two more vessels; regular inspection, draining, drying and replacement of cargo hoses; corrosion management program for all process facilities; and an improved, properly planned and documented maintenance culture. Safety, environmental and security compliance were enhanced by installing state-of-the-art fire fighting facilities and equipment, seawater intake line construction as backup for borehole at the terminal, remediation of the shoreline and marine structures, modern spill containment equipment, improved housekeeping and accident prevention practices, and installation of hi-technology security enhancements, among others. The end result has been observed over the past two years to include improved tanker turnaround time, higher turnover on product sales, consistent product availability, greater indigenous human capacity utilisation by way of direct hires and contracts, as well as customer loyalty. The lessons learnt from this exercise would, therefore, serve as a model to be adapted by other operators of similar facilities, contractors, academics and consultants in a bid to deliver greater sustainability and profitability of operations at the ship – shore interface to this strategic industry.

Keywords: benchmarking, optimisation, petroleum jetty, petroleum terminal

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Authors: Ajit Rai, Hamza Deroui, Blandine Vacher, Khwansiri Ninpan, Arthur Aumont, Francesco Vitillo, Robert Plana

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Large-scale critical industrial scheduling problems are based on Resource-Constrained Project Scheduling Problems (RCPSP), that necessitate integration with other optimization problems (e.g., vehicle routing, supply chain, or unique industrial ones), thus requiring practical solutions (i.e., modular, computationally efficient with feasible solutions). To the best of our knowledge, the current industrial state of the art is not addressing this holistic problem. We propose an original modular solution that answers the issues exhibited by the delivery of complex projects. With three interlinked entities (project, task, resources) having their constraints, it uses a greedy heuristic with a dynamic cost function for each task with a situational assessment at each time step. It handles large-scale data and can be easily integrated with other optimization problems, already existing industrial tools and unique constraints as required by the use case. The solution has been tested and validated by domain experts on three use cases: outage management in Nuclear Power Plants (NPPs), planning of future NPP maintenance operation, and application in the defense industry on supply chain and factory relocation. In the first use case, the solution, in addition to the resources’ availability and tasks’ logical relationships, also integrates several project-specific constraints for outage management, like, handling of resource incompatibility, updating of tasks priorities, pausing tasks in a specific circumstance, and adjusting dynamic unit of resources. With more than 20,000 tasks and multiple constraints, the solution provides a feasible schedule within 10-15 minutes on a standard computer device. This time-effective simulation corresponds with the nature of the problem and requirements of several scenarios (30-40 simulations) before finalizing the schedules. The second use case is a factory relocation project where production lines must be moved to a new site while ensuring the continuity of their production. This generates the challenge of merging job shop scheduling and the RCPSP with location constraints. Our solution allows the automation of the production tasks while considering the rate expectation. The simulation algorithm manages the use and movement of resources and products to respect a given relocation scenario. The last use case establishes a future maintenance operation in an NPP. The project contains complex and hard constraints, like on Finish-Start precedence relationship (i.e., successor tasks have to start immediately after predecessors while respecting all constraints), shareable coactivity for managing workspaces, and requirements of a specific state of "cyclic" resources (they can have multiple states possible with only one at a time) to perform tasks (can require unique combinations of several cyclic resources). Our solution satisfies the requirement of minimization of the state changes of cyclic resources coupled with the makespan minimization. It offers a solution of 80 cyclic resources with 50 incompatibilities between levels in less than a minute. Conclusively, we propose a fast and feasible modular approach to various industrial scheduling problems that were validated by domain experts and compatible with existing industrial tools. This approach can be further enhanced by the use of machine learning techniques on historically repeated tasks to gain further insights for delay risk mitigation measures.

Keywords: deterministic scheduling, optimization coupling, modular scheduling, RCPSP

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