Search results for: acidification and C limitation

Authors: Pawel Martynowicz

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Vibrations are a crucial problem for slender structures such as towers, masts, chimneys, wind turbines, bridges, high buildings, etc., that is why most of them are equipped with vibration attenuation or fatigue reduction solutions. In this work, a slender structure (i.e., wind turbine tower-nacelle model) equipped with nonlinear, semiactive tuned vibration absorber(s) is analyzed. For this study purposes, magnetorheological (MR) dampers are used as semiactive actuators. Several optimal-based approaches to structural vibration attenuation are investigated against the standard ‘ground-hook’ law and passive tuned vibration absorber(s) implementations. The common approach to optimal control of nonlinear systems is offline computation of the optimal solution, however, so determined open loop control suffers from lack of robustness to uncertainties (e.g., unmodelled dynamics, perturbations of external forces or initial conditions), and thus perturbation control techniques are often used. However, proper linearization may be an issue for highly nonlinear systems with implicit relations between state, co-state, and control. The main contribution of the author is the development as well as numerical and experimental verification of the Pontriagin maximum-principle-based vibration control concepts that produce directly actuator control input (not the demanded force), thus force tracking algorithm that results in control inaccuracy is entirely omitted. These concepts, including one-step optimal control, quasi-optimal control, and optimal-based modified ‘ground-hook’ law, can be directly implemented in online and real-time feedback control for periodic (or semi-periodic) disturbances with invariant or time-varying parameters, as well as for non-periodic, transient or random disturbances, what is a limitation for some other known solutions. No offline calculation, excitations/disturbances assumption or vibration frequency determination is necessary, moreover, all of the nonlinear actuator (MR damper) force constraints, i.e., no active forces, lower and upper saturation limits, hysteresis-type dynamics, etc., are embedded in the control technique, thus the solution is optimal or suboptimal for the assumed actuator, respecting its limitations. Depending on the selected method variant, a moderate or decisive reduction in the computational load is possible compared to other methods of nonlinear optimal control, while assuring the quality and robustness of the vibration reduction system, as well as considering multi-pronged operational aspects, such as possible minimization of the amplitude of the deflection and acceleration of the vibrating structure, its potential and/or kinetic energy, required actuator force, control input (e.g. electric current in the MR damper coil) and/or stroke amplitude. The developed solutions are characterized by high vibration reduction efficiency – the obtained maximum values of the dynamic amplification factor are close to 2.0, while for the best of the passive systems, these values exceed 3.5.

Keywords: magnetorheological damper, nonlinear tuned vibration absorber, optimal control, real-time structural vibration attenuation, wind turbines

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Authors: Atefeh Omidkhah Kharashtomi, Rasoul Hedayat Nejad, Saeed Bakhtiyari

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Circulation paths and indoor connection network of the building play an important role both in the daily operation of the building and during evacuation in emergency situations. The degree of legibility of the paths for navigation inside the building has a deep connection with the perceptive and cognitive system of human, and the way the surrounding environment is being perceived. Human perception of the space is based on the sensory systems in a three-dimensional environment, and non-linearly, so it is necessary to avoid reducing its representations in architectural design as a two-dimensional and linear issue. Today, the advances in the field of virtual reality (VR) technology have led to various applications, and architecture and building science can benefit greatly from these capabilities. Especially in cases where the design solution requires a detailed and complete understanding of the human perception of the environment and the behavioral response, special attention to VR technologies could be a priority. Way-finding in the indoor circulation network is a proper example for such application. Success in way-finding could be achieved if human perception of the route and the behavioral reaction have been considered in advance and reflected in the architectural design. This paper discusses the VR technology applications for the way-finding improvements in indoor engineering of the building. In a systematic review, with a database consisting of numerous studies, firstly, four categories for VR applications for circulation way-finding have been identified: 1) data collection of key parameters, 2) comparison of the effect of each parameter in virtual environment versus real world (in order to improve the design), 3) comparing experiment results in the application of different VR devices/ methods with each other or with the results of building simulation, and 4) training and planning. Since the costs of technical equipment and knowledge required to use VR tools lead to the limitation of its use for all design projects, priority buildings for the use of VR during design are introduced based on case-studies analysis. The results indicate that VR technology provides opportunities for designers to solve complex buildings design challenges in an effective and efficient manner. Then environmental parameters and the architecture of the circulation routes (indicators such as route configuration, topology, signs, structural and non-structural components, etc.) and the characteristics of each (metrics such as dimensions, proportions, color, transparency, texture, etc.) are classified for the VR way-finding experiments. Then, according to human behavior and reaction in the movement-related issues, the necessity of scenario-based and experiment design for using VR technology to improve the design and receive feedback from the test participants has been described. The parameters related to the scenario design are presented in a flowchart in the form of test design, data determination and interpretation, recording results, analysis, errors, validation and reporting. Also, the experiment environment design is discussed for equipment selection according to the scenario, parameters under study as well as creating the sense of illusion in the terms of place illusion, plausibility and illusion of body ownership.

Keywords: virtual reality (VR), way-finding, indoor, circulation, design

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Authors: Oibar Martinez, Clara Oliver, Jose Miguel Miranda

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In this paper, we discuss the standard improvements which can be made to reduce the earth resistance in difficult terrains for optimum lightning protection, what are the practical limitations, and how the modeling can be refined for accurate diagnostics and ground resistance minimization. Ground resistance minimization can be made via three different approaches: burying vertical electrodes connected in parallel, burying horizontal conductive plates or meshes, or modifying the own terrain, either by changing the entire terrain material in a large volume or by adding earth-enhancing compounds. The use of vertical electrodes connected in parallel pose several practical limitations. In order to prevent loss of effectiveness, it is necessary to keep a minimum distance between each electrode, which is typically around five times larger than the electrode length. Otherwise, the overlapping of the local equipotential lines around each electrode reduces the efficiency of the configuration. The addition of parallel electrodes reduces the resistance and facilitates the measurement, but the basic parallel resistor formula of circuit theory will always underestimate the final resistance. Numerical simulation of equipotential lines around the electrodes overcomes this limitation. The resistance of a single electrode will always be proportional to the soil resistivity. The electrodes are usually installed with a backfilling material of high conductivity, which increases the effective diameter. However, the improvement is marginal, since the electrode diameter counts in the estimation of the ground resistance via a logarithmic function. Substances that are used for efficient chemical treatment must be environmentally friendly and must feature stability, high hygroscopicity, low corrosivity, and high electrical conductivity. A number of earth enhancement materials are commercially available. Many are comprised of carbon-based materials or clays like bentonite. These materials can also be used as backfilling materials to reduce the resistance of an electrode. Chemical treatment of soil has environmental issues. Some products contain copper sulfate or other copper-based compounds, which may not be environmentally friendly. Carbon-based compounds are relatively inexpensive and they do have very low resistivities, but they also feature corrosion issues. Typically, the carbon can corrode and destroy a copper electrode in around five years. These compounds also have potential environmental concerns. Some earthing enhancement materials contain cement, which, after installation acquire properties that are very close to concrete. This prevents the earthing enhancement material from leaching into the soil. After analyzing different configurations, we conclude that a buried conductive ring with vertical electrodes connected periodically should be the optimum baseline solution for the grounding of a large size structure installed on a large resistivity terrain. In order to show this, a practical example is explained here where we simulate the ground resistance of a conductive ring buried in a terrain with a resistivity in the range of 1 kOhm·m.

Keywords: grounding improvements, large scale scientific instrument, lightning risk assessment, lightning standards

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Authors: William Ho, Agus Wicaksana

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Anecdotal evidence in the last decade shows that the occurrence of disruptive events and uncertainties in the supply chain is increasing. The coupling of these events with the nature of an increasingly complex and interdependent business environment leads to devastating impacts that quickly propagate within and across organizations. For example, the recent COVID-19 pandemic increased the global supply chain disruption frequency by at least 20% in 2020 and is projected to have an accumulative cost of $13.8 trillion by 2024. This crisis raises attention to organizational resilience to weather business uncertainty. However, the concept has been criticized for being vague and lacking a consistent definition, thus reducing the significance of the concept for practice and research. This study is intended to solve that issue by providing a comprehensive review of the conceptualization, measurement, and antecedents of operational resilience that have been discussed in the supply chain risk management literature (SCRM). We performed a Scholarly Network Analysis, combining citation-based and text-based approaches, on 252 articles published from 2000 to 2021 in top-tier journals based on three parameters: AJG ranking and ABS ranking, UT Dallas and FT50 list, and editorial board review. We utilized a hybrid scholarly network analysis by combining citation-based and text-based approaches to understand the conceptualization, measurement, and antecedents of operational resilience in the SCRM literature. Specifically, we employed a Bibliographic Coupling Analysis in the research cluster formation stage and a Co-words Analysis in the research cluster interpretation and analysis stage. Our analysis reveals three major research clusters of resilience research in the SCRM literature, namely (1) supply chain network design and optimization, (2) organizational capabilities, and (3) digital technologies. We portray the research process in the last two decades in terms of the exemplar studies, problems studied, commonly used approaches and theories, and solutions provided in each cluster. We then provide a conceptual framework on the conceptualization and antecedents of resilience based on studies in these clusters and highlight potential areas that need to be studied further. Finally, we leverage the concept of abnormal operating performance to propose a new measurement strategy for resilience. This measurement overcomes the limitation of most current measurements that are event-dependent and focus on the resistance or recovery stage - without capturing the growth stage. In conclusion, this study provides a robust literature review through a scholarly network analysis that increases the completeness and accuracy of research cluster identification and analysis to understand conceptualization, antecedents, and measurement of resilience. It also enables us to perform a comprehensive review of resilience research in SCRM literature by including research articles published during the pandemic and connects this development with a plethora of articles published in the last two decades. From the managerial perspective, this study provides practitioners with clarity on the conceptualization and critical success factors of firm resilience from the SCRM perspective.

Keywords: supply chain risk management, organizational resilience, scholarly network analysis, systematic literature review

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Authors: Drew Commandeur, Ryan Brodie, Sandra Hundza, Marc Klimstra

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The amplitude of raw electromyography (EMG) is affected by recording conditions and often requires normalization to make meaningful comparisons. Bioelectric methods normalize with an EMG signal recorded during a standardized task or from the experimental protocol itself, while biomechanical methods often involve measurements with an additional sensor such as a force transducer. Common bioelectric normalization techniques for treadmill walking include maximum voluntary isometric contraction (MVIC), dynamic EMG peak (EMGPeak) or dynamic EMG mean (EMGMean). There are several concerns with using MVICs to normalize EMG, including poor reliability and potential discomfort. A limitation of bioelectric normalization techniques is that they could result in a misrepresentation of the absolute magnitude of force generated by the muscle and impact the interpretation of EMG between functionally disparate groups. Additionally, methods that normalize to EMG recorded during the task may eliminate some real inter-individual variability due to biological variation. This study compared biomechanical and bioelectric EMG normalization techniques during treadmill walking to assess the impact of the normalization method on the functional interpretation of EMG data. For the biomechanical method, we normalized EMG to a target torque (EMGTS) and the bioelectric methods used were normalization to the mean and peak of the signal during the walking task (EMGMean and EMGPeak). The effect of normalization on muscle activation pattern, EMG amplitude, and inter-individual variability were compared between disparate cohorts of OLD (76.6 yrs N=11) and YOUNG (26.6 yrs N=11) adults. Participants walked on a treadmill at a self-selected pace while EMG was recorded from the right lower limb. EMG data from the soleus (SOL), medial gastrocnemius (MG), tibialis anterior (TA), vastus lateralis (VL), and biceps femoris (BF) were phase averaged into 16 bins (phases) representing the gait cycle with bins 1-10 associated with right stance and bins 11-16 with right swing. Pearson’s correlations showed that activation patterns across the gait cycle were similar between all methods, ranging from r =0.86 to r=1.00 with p<0.05. This indicates that each method can characterize the muscle activation pattern during walking. Repeated measures ANOVA showed a main effect for age in MG for EMGPeak but no other main effects were observed. Interactions between age*phase of EMG amplitude between YOUNG and OLD with each method resulted in different statistical interpretation between methods. EMGTS normalization characterized the fewest differences (four phases across all 5 muscles) while EMGMean (11 phases) and EMGPeak (19 phases) showed considerably more differences between cohorts. The second notable finding was that coefficient of variation, the representation of inter-individual variability, was greatest for EMGTS and lowest for EMGMean while EMGPeak was slightly higher than EMGMean for all muscles. This finding supports our expectation that EMGTS normalization would retain inter-individual variability which may be desirable, however, it also suggests that even when large differences are expected, a larger sample size may be required to observe the differences. Our findings clearly indicate that interpretation of EMG is highly dependent on the normalization method used, and it is essential to consider the strengths and limitations of each method when drawing conclusions.

Keywords: electromyography, EMG normalization, functional EMG, older adults

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Authors: Abdou Elhendy

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Numerous study have shown the efficacy of the percutaneous intervention (PCI) and coronary stenting in improving left ventricular function and relieving exertional angina. Furthermore, PCI remains the main line of therapy in acute myocardial infarction. Improvement of procedural techniques and new devices have resulted in an increased number of PCI in those with difficult and extensive lesions, multivessel disease as well as total occlusion. Immediate and late outcome may be compromised by acute thrombosis or the development of fibro-intimal hyperplasia. In addition, progression of coronary artery disease proximal or distal to the stent as well as in non-stented arteries is not uncommon. As a result, complications can occur, such as acute myocardial infarction, worsened heart failure or recurrence of angina. In a stent, restenosis can occur without symptoms or with atypical complaints rendering the clinical diagnosis difficult. Routine invasive angiography is not appropriate as a follow up tool due to associated risk and cost and the limited functional assessment. Exercise and pharmacologic stress testing are increasingly used to evaluate the myocardial function, perfusion and adequacy of revascularization. Information obtained by these techniques provide important clues regarding presence and severity of compromise in myocardial blood flow. Stress echocardiography can be performed in conjunction with exercise or dobutamine infusion. The diagnostic accuracy has been moderate, but the results provide excellent prognostic stratification. Adding myocardial contrast agents can improve imaging quality and allows assessment of both function and perfusion. Stress radionuclide myocardial perfusion imaging is an alternative to evaluate these patients. The extent and severity of wall motion and perfusion abnormalities observed during exercise or pharmacologic stress are predictors of survival and risk of cardiac events. According to current guidelines, stress echocardiography and radionuclide imaging are considered to have appropriate indication among patients after PCI who have cardiac symptoms and those who underwent incomplete revascularization. Stress testing is not recommended in asymptomatic patients, particularly early after revascularization, Coronary CT angiography is increasingly used and provides high sensitive for the diagnosis of coronary artery stenosis. Average sensitivity and specificity for the diagnosis of in stent stenosis in pooled data are 79% and 81%, respectively. Limitations include blooming artifacts and low feasibility in patients with small stents or thick struts. Anatomical and functional cardiac imaging modalities are corner stone for the assessment of patients after PCI and provide salient diagnostic and prognostic information. Current imaging techniques cans serve as gate keeper for coronary angiography, thus limiting the risk of invasive procedures to those who are likely to benefit from subsequent revascularization. The determination of which modality to apply requires careful identification of merits and limitation of each technique as well as the unique characteristic of each individual patient.

Keywords: coronary artery disease, stress testing, cardiac imaging, restenosis

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Authors: Bernice Jeanne Lottering, Yi-Wen Lin

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Introduction: Chronic pain has a definitive lack of objective parameters in the measurement and treatment efficacy of diseases such as Fibromyalgia (FM). Persistent widespread pain and generalized tenderness are the characteristic symptoms affecting a large majority of the global population, particularly females. This disease has indicated a refractory tendency to conventional treatment ventures, largely resultant from a lack of etiological and pathogenic understanding of the disease development. Emerging evidence indicates that the central nervous system (CNS) plays a critical role in the amplification of pain signals and the neurotransmitters associated therewith. Various stimuli have been found to activate the channels existent on nociceptor terminals, thereby actuating nociceptive impulses along the pain pathways. The transient receptor potential vanalloid 1 (TRPV1) channel functions as a molecular integrator for numerous sensory inputs, such as nociception, and was explored in the current study. Current intervention approaches face a multitude challenges, ranging from effective therapeutic interventions to the limitation of pathognomonic criteria resultant from incomplete understanding and partial evidence on the mechanisms of action of FM. It remains unclear whether electroacupuncture (EA) plays an integral role in the functioning of the TRPV1 pathway, and whether or not it can reduce the chronic pain induced by FM. Aims: The aim of this study was to explore the mechanisms underlying the activation and modulation of the TRPV1 channel pathway in a cold stress model of FM applied to a murine model. Furthermore, the effect of EA in the treatment of mechanical and thermal pain, as expressed in FM was also to be investigated. Methods: 18 C57BL/6 wild type and 6 TRPV1 knockout (KO) mice, aged 8-12 weeks, were exposed to an intermittent cold stress-induced fibromyalgia-like pain model, with or without EA treatment at ZusanLi ST36 (2Hz/20min) on day 3 to 5. Von Frey and Hargreaves behaviour tests were implemented in order to analyze the mechanical and thermal pain thresholds on day 0, 3 and 5 in control group (C), FM group (FM), FM mice with EA treated group (FM + EA) and FM in KO group. Results: An increase in mechanical and thermal hyperalgesia was observed in the FM, EA and KO groups when compared to the control group. This initial increase was reduced in the EA group, which directs focus at the treatment efficacy of EA in nociceptive sensitization, and the analgesic effect EA has attenuating FM associated pain. Discussion: An increase in the nociceptive sensitization was observed through higher withdrawal thresholds in the von Frey mechanical test and the Hargreaves thermal test. TRPV1 function in mice has been scientifically associated with these nociceptive conduits, and the increased behaviour test results suggest that TRPV1 upregulation is central to the FM induced hyperalgesia. This data was supported by the decrease in sensitivity observed in results of the TRPV1 KO group. Moreover, the treatment of EA showed a decrease in this FM induced nociceptive sensitization, suggesting TRPV1 upregulation and overexpression can be attenuated by EA at bilateral ST36. This evidence compellingly implies that the analgesic effect of EA is associated with TRPV1 downregulation.

Keywords: fibromyalgia, electroacupuncture, TRPV1, nociception

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Authors: Eric Bang

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Interactions between receptors and ligands are crucial for many essential biological processes, including neurotransmission and metabolism. Ligand-receptor analyses that examine cell behavior and interactions often utilize cell type-specific RNA expressions from single-cell RNA sequencing (scRNA-seq) data. Using CellPhoneDB, a public repository consisting of ligands, receptors, and ligand-receptor interactions, the cell-cell interactions were explored in a specific scRNA-seq dataset from kidney tissue and portrayed the results with dot plots and heat maps. Depending on the type of cell, each ligand-receptor pair was aligned with the interacting cell type and calculated the positori probabilities of these associations, with corresponding P values reflecting average expression values between the triads and their significance. Using single-cell data (sample kidney cell references), genes in the dataset were cross-referenced with ones in the existing CellPhoneDB dataset. For example, a gene such as Pleiotrophin (PTN) present in the single-cell data also needed to be present in the CellPhoneDB dataset. Using the single-cell transcriptomics data via slide-seq and reference data, the CellPhoneDB program defines cell types and plots them in different formats, with the two main ones being dot plots and heat map plots. The dot plot displays derived measures of the cell to cell interaction scores and p values. For the dot plot, each row shows a ligand-receptor pair, and each column shows the two interacting cell types. CellPhoneDB defines interactions and interaction levels from the gene expression level, so since the p-value is on a -log10 scale, the larger dots represent more significant interactions. By performing an interaction analysis, a significant interaction was discovered for myeloid and T-cell ligand-receptor pairs, including those between Secreted Phosphoprotein 1 (SPP1) and Fibronectin 1 (FN1), which is consistent with previous findings. It was proposed that an effective protocol would involve a filtration step where cell types would be filtered out, depending on which ligand-receptor pair is activated in that part of the tissue, as well as the incorporation of the CellPhoneDB data in a streamlined workflow pipeline. The filtration step would be in the form of a Python script that expedites the manual process necessary for dataset filtration. Being in Python allows it to be integrated with the CellPhoneDB dataset for future workflow analysis. The manual process involves filtering cell types based on what ligand/receptor pair is activated in kidney cells. One limitation of this would be the fact that some pairings are activated in multiple cells at a time, so the manual manipulation of the data is reflected prior to analysis. Using the filtration script, accurate sorting is incorporated into the CellPhoneDB database rather than waiting until the output is produced and then subsequently applying spatial data. It was envisioned that this would reveal wherein the cell various ligands and receptors are interacting with different cell types, allowing for easier identification of which cells are being impacted and why, for the purpose of disease treatment. The hope is this new computational method utilizing spatially explicit ligand-receptor association data can be used to uncover previously unknown specific interactions within kidney tissue.

Keywords: bioinformatics, Ligands, kidney tissue, receptors, spatial transcriptome

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Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

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Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

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Authors: Nisha Sharma, Mili Kaur, Ashutosh Halder, Seema Kaushal, Manoj Kumar, Manish Jain

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Purpose: To investigate microRNAs (miRNA) as an epigenomic etiological factor in idiopathic non-obstructive azoospermia (NOA). In order to achieve the same, an association was seen between occupational exposure to radiation, thermal, and chemical factors and idiopathic cases of non-obstructive azoospermia, and later, testicular differential miRNA expression profiling was done in exposure group NOA cases. Method: It is a prospective study in which 200 apparent idiopathic male factor infertility cases, who have been advised to undergo testicular fine needle aspiration (FNA) evaluation, are recruited. A detailed occupational history was taken to understand the possible type of exposure due to the nature and duration of work. A total of 26 patients were excluded upon XY-FISH and Yq microdeletion tests due to the presence of genetic causes of infertility, 6 hypospermatogeneis (HS), six Sertoli cell-only syndrome (SCOS), and six normospermatogeneis patients testicular FNA samples were used for RNA isolation followed by small RNA sequencing and nCounter miRNA expression analysis. Differential miRNA expression profile of HS and SCOS patients was done. A web-based tool, miRNet, was used to predict the interacting compounds or chemicals using the shortlisted miRNAs with high fold change. The major limitation encountered in this study was the insufficient quantity of testicular FNA sample used for total RNA isolation, which resulted in a low yield and RNA integrity number (RIN) value. Therefore, the number of RNA samples admissible for differential miRNA expression analysis was very small in comparison to the total number of patients recruited. Results: Differential expression analysis revealed 69 down-regulated and 40 up-regulated miRNAs in HS and 66 down-regulated and 33 up-regulated miRNAs in SCOS in comparison to normospermatogenesis controls. The miRNA interaction analysis using the miRNet tool showed that the differential expression profiles of HS and SCOS patients were associated with arsenic trioxide, bisphenol-A, calcium sulphate, lithium, and cadmium. These compounds are reproductive toxins and might be responsible for miRNA-mediated epigenetic deregulation leading to NOA. The association between occupational risk factor exposure and the non-exposure group of NOA patients was not statistically significant, with ꭓ2 (3, N= 178) = 6.70, p= 0.082. The association between individual exposure groups (radiation, thermal, and chemical) and various sub-types of NOA is also not significant, with ꭓ2 (9, N= 178) = 15.06, p= 0.089. Functional analysis of HS and SCOS patients' miRNA profiles revealed some important miR-family members in terms of male fertility. The miR-181 family plays a role in the differentiation of spermatogonia and spermatocytes, as well as the transcriptional regulation of haploid germ cells. The miR-34 family is expressed in spermatocytes and round spermatids and is involved in the regulation of SSCs differentiation. Conclusion: The reproductive toxins might adopt the miRNA-mediated mechanism of disease development in idiopathic cases of NOA. Chemical compound induced; miRNA-mediated epigenetic deregulation can give a future perspective on the etiopathogenesis of the disease.

Keywords: microRNA, non-obstructive azoospermia (NOA), occupational exposure, hypospermatogenesis (HS), Sertoli cell only syndrome (SCOS)

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Authors: Sharon Harel, Rachel Kizony, Yoram Feldman, Gabi Zeilig, Mordechai Shani

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Multiple Sclerosis (MS) is a neurological disease that may cause restriction in participation in daily activities of young adults. Main symptoms include fatigue, weakness and cognitive decline. The appearance of symptoms, their severity and deterioration rate, change between patients. The challenge of health services is to provide long-term rehabilitation services to people with MS. The objective of this presentation is to describe a course of tele-rehabilitation service of a woman with MS. Methods; R is a 48 years-old woman, diagnosed with MS when she was 22. She started to suffer from weakness of her non-dominant left upper extremity about ten years after the diagnosis. She was referred to the tele-rehabilitation service by her rehabilitation team, 16 years after diagnosis. Her goals were to improve ability to use her affected upper extremity in daily activities. On admission her score in the Mini-Mental State Exam was 30/30. Her Fugl-Meyer Assessment (FMA) score of the left upper extremity was 48/60, indicating mild weakness and she had a limitation of her shoulder abduction (90 degrees). In addition, she reported little use of her arm in daily activities as shown in her responses to the Motor Activity Log (MAL) that were equal to 1.25/5 in amount and 1.37 in quality of use. R. received two 30 minutes on-line sessions per week in the tele-rehabilitation service, with the CogniMotion system. These were complemented by self-practice with the system. The CogniMotion system provides a hybrid (synchronous-asynchronous), the home-based tele-rehabilitation program to improve the motor, cognitive and functional status of people with neurological deficits. The system consists of a computer, large monitor, and the Microsoft’s Kinect 3D sensor. This equipment is located in the client’s home and connected to a clinician’s computer setup in a remote clinic via WiFi. The client sits in front of the monitor and uses his body movements to interact with games and tasks presented on the monitor. The system provides feedback in the form of ‘knowledge of results’ (e.g., the success of a game) and ‘knowledge of performance’ (e.g., alerts for compensatory movements) to enhance motor learning. The games and tasks were adapted for R. motor abilities and level of difficulty was gradually increased according to her abilities. The results of her second assessment (after 35 on-line sessions) showed improvement in her FMA score to 52 and shoulder abduction to 140 degrees. Moreover, her responses to the MAL indicated an increased amount (2.4) and quality (2.2) of use of her left upper extremity in daily activities. She reported high level of enjoyment from the treatments (5/5), specifically the combination of cognitive challenges while moving her body. In addition, she found the system easy to use as reflected by her responses to the System Usability Scale (85/100). To-date, R. continues to receive treatments in the tele-rehabilitation service. To conclude, this case report shows the potential of using tele-rehabilitation for people with MS to provide strategies to enhance the use of the upper extremity in daily activities as well as for maintaining motor function.

Keywords: motor function, multiple-sclerosis, tele-rehabilitation, daily activities

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Authors: Andy Alubaidy

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In this work, a robotic additive manufacturing system (RAMS) that is capable of three-dimensional (3D) printing in six degrees of freedom (DOF) with very high accuracy and virtually on any surface has been designed and built. One of the major shortcomings in existing 3D printer technology is the limitation to three DOF, which results in prolonged fabrication time. Depending on the techniques used, it usually takes at least two hours to print small objects and several hours for larger objects. Another drawback is the size of the printed objects, which is constrained by the physical dimensions of most low-cost 3D printers, which are typically small. In such cases, large objects are produced by dividing them into smaller components that fit the printer’s workable area. They are then glued, bonded or otherwise attached to create the required object. Another shortcoming is material constraints and the need to fabricate a single part using different materials. With the flexibility of a six-DOF robot, the RAMS has been designed to overcome these problems. A feeding mechanism using an adaptive Proportional-Integral-Derivative (PID) controller is utilized along with a national instrument compactRIO (NI cRIO), an ABB robot, and off-the-shelf sensors. The RAMS have the ability to 3D print virtually anywhere in six degrees of freedom with very high accuracy. It is equipped with an ABB IRB 120 robot to achieve this level of accuracy. In order to convert computer-aided design (CAD) files to digital format that is acceptable to the robot, Hypertherm Robotic Software Inc.’s state-of-the-art slicing software called “ADDMAN” is used. ADDMAN is capable of converting any CAD file into RAPID code (the programing language for ABB robots). The robot uses the generated code to perform the 3D printing. To control the entire process, National Instrument (NI) compactRIO (cRio 9074), is connected and communicated with the robot and a feeding mechanism that is designed and fabricated. The feeding mechanism consists of two major parts, cold-end and hot-end. The cold-end consists of what is conventionally known as an extruder. Typically, a stepper-motor is used to control the push on the material, however, for optimum control, a DC motor is used instead. The hot-end consists of a melt-zone, nozzle, and heat-brake. The melt zone ensures a thorough melting effect and consistent output from the nozzle. Nozzles are made of brass for thermo-conductivity while the melt-zone is comprised of a heating block and a ceramic heating cartridge to transfer heat to the block. The heat-brake ensures that there is no heat creep-up effect as this would swell the material and prevent consistent extrusion. A control system embedded in the cRio is developed using NI Labview which utilizes adaptive PID to govern the heating cartridge in conjunction with a thermistor. The thermistor sends temperature feedback to the cRio, which will issue heat increase or decrease based on the system output. Since different materials have different melting points, our system will allow us to adjust the temperature and vary the material.

Keywords: robotic, additive manufacturing, PID controller, cRIO, 3D printing

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Authors: Ewelina Wisnik, Zsolt Regdon, Kinga Chmielewska, Laszlo Virag, Agnieszka Robaszkiewicz

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Apart from protecting genome, PARP1 has been documented to regulate many intracellular processes inter alia gene transcription by physically interacting with chromatin bound proteins and by their ADP-ribosylation. Our recent findings indicate that expression of PARP1 decreases during the differentiation of human CD34+ hematopoietic stem cells to monocytes as a consequence of differentiation-associated cell growth arrest and formation of E2F4-RBL2-HDAC1-SWI/SNF repressive complex at the promoter of this gene. Since the RBL2 complexes repress genes in a E2F-dependent manner and are widespread in the genome in G0 arrested cells, we asked (a) if RBL2 directly contributes to defining monocyte phenotype and function by targeting gene promoters and (b) if RBL2 controls gene transcription indirectly by repressing PARP1. For identification of genes controlled by RBL2 and/or PARP1,we used primer libraries for surface receptors and TLR signaling mediators, genes were silenced by siRNA or shRNA, analysis of gene promoter occupation by selected proteins was carried out by ChIP-qPCR, while statistical analysis in GraphPad Prism 5 and STATISTICA, ChIP-Seq data were analysed in Galaxy 2.5.0.0. On the list of 28 genes regulated by RBL2, we identified only four solely repressed by RBL2-E2F4-HDAC1-BRM complex. Surprisingly, 24 out of 28 emerged genes controlled by RBL2 were co-regulated by PARP1 in six different manners. In one mode of RBL2/PARP1 co-operation, represented by MAP2K6 and MAPK3, PARP1 was found to associate with gene promoters upon RBL2 silencing, which was previously shown to restore PARP1 expression in monocytes. PARP1 effect on gene transcription was observed only in the presence of active EP300, which acetylated gene promoters and activated transcription. Further analysis revealed that PARP1 binding to MA2K6 and MAPK3 promoters enabled recruitment of EP300 in monocytes, while in proliferating cancer cell lines, which actively transcribe PARP1, this protein maintained EP300 at the promoters of MA2K6 and MAPK3. Genome-wide analysis revealed a similar distribution of PARP1 and EP300 around transcription start sites and the co-occupancy of some gene promoters by PARP1 and EP300 in cancer cells. Here, we described a new RBL2/PARP1/EP300 axis which controls gene transcription regardless of the cell type. In this model cell, cycle-dependent transcription of PARP1 regulates expression of some genes repressed by RBL2 upon cell cycle limitation. Thus, RBL2 may indirectly regulate transcription of some genes by controlling the expression of EP300-recruiting PARP1. Acknowledgement: This work was financed by Polish National Science Centre grants nr DEC-2013/11/D/NZ2/00033 and DEC-2015/19/N/NZ2/01735. L.V. is funded by the National Research, Development and Innovation Office grants GINOP-2.3.2-15-2016-00020 TUMORDNS, GINOP-2.3.2-15-2016-00048-STAYALIVE and OTKA K112336. AR is supported by Polish Ministry of Science and Higher Education 776/STYP/11/2016.

Keywords: retinoblastoma transcriptional co-repressor like 2 (RBL2), poly(ADP-ribose) polymerase 1 (PARP1), E1A binding protein p300 (EP300), monocytes

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Authors: Nils Haglund, Svenolof Dahlgren, Maria Rastam, Peik Gustafsson, Karin Kalien

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In Sweden, like in most developed countries, there is a substantial increase of children diagnosed with autism and other conditions within the autism spectrum (ASD). The rapid increase of ASD rates stresses the importance of developing care programs to provide support and comprehensive interventions for affected families. The current observational study was conducted in order to evaluate an ongoing Comprehensive Intensive Early Intervention (CIEI) program for children with autism in southern Sweden. The change in autism symptoms among children participating in CIEI (intervention group, n=67) was compared with children who received traditional habilitation services only (comparison group, n=27). Children of parents who accepted the offered CIEI-program, constituted the intervention group, whereas children, whose parents (for some reason) were not interested in the offered CIEI-program, constituted the comparison group. The CIEI-program was individualized to each child by experienced applied behavior analysis (ABA) specialists with different backgrounds as psychologists, speech pathologists or special education teachers, in cooperation with parents and preschool staff. Due to the individualization, the intervention could vary in intensity and techniques. The intensity was calculated to 15-25 hours each week at home and the preschool altogether. Each child was assigned one 'trainer', who was often employed as a preschool teacher but could have another educational background. An agreement between supervisor- parents and preschool staff was reached to confirm the intensity and content of the CIEI- program over an approximately two-year intervention period. Symptom changes were measured as evaluation-ADOS-2-scores, total- and severity-scores, minus the corresponding baseline-scores, divided by the time between baseline and evaluation. The difference between the study-groups regarding change of ADOS-2-scores was estimated using ANCOVA. In the current study, children in the CIEI-group improved their ADOS-2-total scores between baseline and evaluation (-0.8 scores per year; 95%CI: -1.2 to -0.4), whereas no such improvement was detected in the comparison group (+0.1 scores per year; 95%CI: -0.7 to +0.9). The change difference (change in the CIEI-group vs. change in the comparison group) was statistically significant, both crude and after adjusting for possible confounders (-1.1; 95%CI -1.9 to -0.4). Children in the CIEI-group also significantly improved their ADOS-calibrated severity scores, but not significantly differently so from the comparison group. The results from the current study indicate that the CIEI program significantly improves social and communicative skills among children with autism and that children with developmental delay could benefit to a similar degree as other children. The results support earlier studies reporting on the improvement of autism symptoms after early intensive interventions. The results from observational studies are difficult to interpret, but it is nevertheless of uttermost importance to evaluate costly autism intervention programs. Such results may be of immediate importance to healthcare organizations when allocating the already strained resources to different patient groups. Albeit the obvious limitation of the current naturalistic study, the results support previous positive studies and indicate that children with autism benefit from participating in early comprehensive, intensive programs and that investments in these programs may be highly justifiable.

Keywords: autism symptoms, ADOS-scores, evaluation, intervention program

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Authors: Maisam Rafiee, Chikashi Deguchi, Akio Odake, Minoru Matsui, Takanori Sata

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Cities in Afghanistan have been rapidly urbanized; however, many parts of these cities have been developed with no detailed land use plan or infrastructure. In other words, they have been informally developed without any government leadership. The new government started the In-situ Upgrading Project in Kabul to upgrade roads, the water supply network system, and the surface water drainage system on the existing street layout in 2002, with the financial support of international agencies. This project is an appropriate emergency improvement for living life, but not an essential improvement of living conditions and infrastructure problems because the life expectancies of the improved facilities are as short as 10–15 years, and residents cannot obtain land tenure in the unplanned areas. The Land Readjustment System (LRS) conducted in Japan has good advantages that rearrange irregularly shaped land lots and develop the infrastructure effectively. This study investigates the effects of the In-situ Upgrading Project on private investment, land prices, and residents’ satisfaction with projects in Kart-e-Char, where properties are registered, and in Afshar-e-Silo Lot 1, where properties are unregistered. These projects are located 5 km and 7 km from the CBD area of Kabul, respectively. This study discusses whether LRS should be applied to the unplanned area based on the questionnaire and interview responses of experts experienced in the In-situ Upgrading Project who have knowledge of LRS. The analysis results reveal that, in Kart-e-Char, a lot of private investment has been made in the construction of medium-rise (five- to nine-story) buildings for commercial and residential purposes. Land values have also incrementally increased since the project, and residents are commonly satisfied with the road pavement, drainage systems, and water supplies, but dissatisfied with the poor delivery of electricity as well as the lack of public facilities (e.g., parks and sport facilities). In Afshar-e-Silo Lot 1, basic infrastructures like paved roads and surface water drainage systems have improved from the project. After the project, a few four- and five-story residential buildings were built with very low-level private investments, but significant increases in land prices were not evident. The residents are satisfied with the contribution ratio, drainage system, and small increase in land price, but there is still no drinking water supply system or tenure security; moreover, there are substandard paved roads and a lack of public facilities, such as parks, sport facilities, mosques, and schools. The results of the questionnaire and interviews with the four engineers highlight the problems that remain to be solved in the unplanned areas if LRS is applied—namely, land use differences, types and conditions of the infrastructure still to be installed by the project, and time spent for positive consensus building among the residents, given the project’s budget limitation.

Keywords: in-situ upgrading, Kabul city, land readjustment, land value, planned area, private investment, residents' satisfaction, unplanned area

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

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

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

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Authors: Huan Peng, Chenye Zeng, Zhao Wang

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Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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Authors: Naghmeh M. Bandari, Javad Dargahi, Muthukumaran Packirisamy

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Robot-assisted minimally invasive surgery (RMIS) has been widely performed around the world during the last two decades. RMIS demonstrates significant advantages over conventional surgery, e.g., improving the accuracy and dexterity of a surgeon, providing 3D vision, motion scaling, hand-eye coordination, decreasing tremor, and reducing x-ray exposure for surgeons. Despite benefits, surgeons cannot touch the surgical site and perceive tactile information. This happens due to the remote control of robots. The literature survey identified the lack of force feedback as the riskiest limitation in the existing technology. Without the perception of tool-tissue contact force, the surgeon might apply an excessive force causing tissue laceration or insufficient force causing tissue slippage. The primary use of force sensors has been to measure the tool-tissue interaction force in real-time in-situ. Design of a tactile sensor is subjected to a set of design requirements, e.g., biocompatibility, electrical-passivity, MRI-compatibility, miniaturization, ability to measure static and dynamic force. In this study, a planar optical fiber-based sensor was proposed to mount at the surgical grasper. It was developed based on the light intensity modulation principle. The deflectable part of the sensor was a beam modeled as a cantilever Euler-Bernoulli beam on rigid substrates. A semi-cylindrical indenter was attached to the bottom surface the beam at the mid-span. An optical fiber was secured at both ends on the same rigid substrates. The indenter was in contact with the fiber. External force on the sensor caused deflection in the beam and optical fiber simultaneously. The micro-bending of the optical fiber would consequently result in light power loss. The sensor was simulated and studied using finite element methods. A laser light beam with 800nm wavelength and 5mW power was used as the input to the optical fiber. The output power was measured using a photodetector. The voltage from photodetector was calibrated to the external force for a chirp input (0.1-5Hz). The range, resolution, and hysteresis of the sensor were studied under monotonic and harmonic external forces of 0-2.0N with 0 and 5Hz, respectively. The results confirmed the validity of proposed sensing principle. Also, the sensor demonstrated an acceptable linearity (R2 > 0.9). A minimum external force was observed below which no power loss was detectable. It is postulated that this phenomenon is attributed to the critical angle of the optical fiber to observe total internal reflection. The experimental results were of negligible hysteresis (R2 > 0.9) and in fair agreement with the simulations. In conclusion, the suggested planar sensor is assessed to be a cost-effective solution, feasible, and easy to use the sensor for being miniaturized and integrated at the tip of robotic graspers. Geometrical and optical factors affecting the minimum sensible force and the working range of the sensor should be studied and optimized. This design is intrinsically scalable and meets all the design requirements. Therefore, it has a significant potential of industrialization and mass production.

Keywords: force sensor, minimally invasive surgery, optical sensor, robotic surgery, tactile sensor

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Authors: Michael Josef Schwerer, Oliver Peschel

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Background: The sense and purpose of forensic postmortem examinations are undoubtedly the same in Institutes of Legal Medicine all over the world. Cause and manner of death must be determined, persons responsible for unnatural death must be brought to justice, and accidents demand changes in the respective scenarios to avoid future mishaps. The latter particularly concerns aircraft accidents, not only regarding consequences from criminal or civil law but also in pursuance of the International Civil Aviation Authority’s regulations, which demand lessons from mishap investigations to improve flight safety. Irrespective of the distinct circumstances of a given casualty or the respective questions in subsequent death investigations, a forensic autopsy is the basis for all further casework, the clue to otherwise hidden solutions, and the crucial limitation for final success when not all possible findings have been properly collected. This also implies that the targeted work of police forces and expert witnesses strongly depends on the quality of forensic pathology practice. Deadly events in foreign countries, which lead to investigations not only abroad but also in Germany, can be challenging in this context. Frequently, second-look autopsies after the repatriation of the deceased to Germany are requested by the legal authorities to ensure proper and profound documentation of all relevant findings. Aims and Methods: To validate forensic postmortem practice abroad, a retrospective study using the findings in the corresponding second-look autopsies in the Institute of Legal Medicine Munich over the last 20 years was carried out. New findings unreported in the previous autopsy were recorded and judged for their relevance to solving the respective case. Further, the condition of the corpse at the time of the second autopsy was rated to discuss artifacts mimicking evidence or the possibility of lost findings resulting from, e.g., decomposition. Recommendations for future handling of death cases abroad and efficient autopsy practice were pursued. Results and Discussion: Our re-evaluation confirmed a high quality of autopsy practice abroad in the vast majority of cases. However, in some casework, incomplete documentation of pathology findings was revealed along with either insufficient or misconducted dissection of organs. Further, some of the bodies showed missing parts of some organs, most probably resulting from sampling for histology studies during the first postmortem. For the aeromedical evaluation of a decedent’s health status prior to an aviation mishap, particularly lost or obscured findings in the heart, lungs, and brain impeded expert testimony. Moreover, incomplete fixation of the body or body parts for repatriation was seen in several cases. This particularly involved previously dissected organs deposited back into the body cavities at the end of the first autopsy. Conclusions and Recommendations: Detailed preparation in the first forensic autopsy avoids the necessity of a second-look postmortem in the majority of cases. To limit decomposition changes during repatriation from abroad, special care must be taken to include pre-dissected organs in the chemical fixation process, particularly when they are separated from the blood vessels and just deposited back into the body cavities.

Keywords: autopsy practice, second-look autopsy, retrospective study, quality standards, decomposition changes, repatriation

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Authors: Sara Scolari, Davide Mombelli, Gianluca Dall'Osto, Jasna Kastivnik, Gašper Tavčar, Carlo Mapelli

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The EIT Raw Materials RIS-DustRec-II project aims to transform Electric Arc Furnace Dust (EAFD) into a valuable resource by overcoming the challenges associated with traditional recycling approaches. EAFD, a zinc-rich industrial by-product typically recycled by the Waelz process, contains complex oxides such as franklinite (ZnFe₂O₄), which hinder the efficient extraction of zinc, by also introducing other valuable elements (Fe, Ni, Cr, Cu, …) in the slag. The project aims to develop a multistage multidisciplinary approach to separate EAFD into two streams: a magnetic and non-magnetic one. In this paper the production of self-reducing briquettes from the magnetic stream of EAFD with a reducing agent, aiming to drive carbothermic reduction and recover iron as a usable alloy, was investigated. Research was focused on optimizing the magnetic and subsequent gravimetric separation (MGS) processes, followed by high-temperature smelting to evaluate reduction efficiency and phase separation. The characterization of selected two different raw EAFD samples and their magnetic-gravitational separation to isolate zinc- and iron-rich fractions was performed by X-ray diffraction and scanning electron microscope. The iron-enriched concentrates were then agglomerated into self-reducing briquettes by mixing them with either biochar (olive pomace pyrolyzed at 350 and 750°C and wood chips pyrolyzed at 750 °C) and a Cupola Furnace dust as reducing agents, combined with gelatinized corn starch as a binder. Cylindrical briquettes were produced and cured for 14 days to ensure structural integrity during subsequent thermal treatments. Smelting tests were carried out at 1400 °C in an inert argon atmosphere to assess the metallization efficiency and the separation between metal and slag phases. A carbon/oxides mass ratio of 0.262 (C/(ZnO+Fe₂O₃)) was used in these tests to maintain continuity with previous studies and to standardize reduction conditions. The magnetic and gravimetric separations effectively isolated zinc- and iron-enriched fractions, particularly for one of the two EAFD, where the concentration of Zn in the concentration fraction was reduced by 8 wt.% while Fe reached 45 wt.%. The reduction tests conducted at 1400 °C showed that the chosen carbon/oxides ratio was sufficient for the smelting of the reducible oxides within the briquettes. However, an important limitation became apparent: the amount of carbon, exceeding the stochiometric value, proved to be excessive for the effective coalescence of metal droplets, preventing clear metal-slag separation. To address this, further smelting tests were carried out in an air atmosphere rather than inert conditions to burn off excess carbon. This paper demonstrates the potential of controlled carbothermic reduction for EAFD recycling. By carefully optimizing the C/(ZnO+Fe₂O₃) ratio, the process can maximize metal recovery while achieving better separation of the metal and slag phases. This approach offers a promising alternative to traditional EAFD recycling methods, with further studies recommended to refine the parameters for industrial application.

Keywords: biochars, electrical arc furnace dust, metallization, smelting

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Authors: Maddalena Arigoni, Maria Luisa Ratto, Raffaele A. Calogero, Luca Alessandri

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The presence of tumor heterogeneity, where distinct cancer cells exhibit diverse morphological and phenotypic profiles, including gene expression, metabolism, and proliferation, poses challenges for molecular prognostic markers and patient classification for targeted therapies. Understanding the causes and progression of cancer requires research efforts aimed at characterizing heterogeneity, which can be facilitated by evolving single-cell sequencing technologies. However, analyzing single-cell data necessitates computational methods that often lack objective validation. Therefore, the establishment of benchmarking datasets is necessary to provide a controlled environment for validating bioinformatics tools in the field of single-cell oncology. Benchmarking bioinformatics tools for single-cell experiments can be costly due to the high expense involved. Therefore, datasets used for benchmarking are typically sourced from publicly available experiments, which often lack a comprehensive cell annotation. This limitation can affect the accuracy and effectiveness of such experiments as benchmarking tools. To address this issue, we introduce omics benchmark experiments designed to evaluate bioinformatics tools to depict the heterogeneity in single-cell tumor experiments. We conducted single-cell RNA sequencing on six lung cancer tumor cell lines that display resistant clones upon treatment of EGFR mutated tumors and are characterized by driver genes, namely ROS1, ALK, HER2, MET, KRAS, and BRAF. These driver genes are associated with downstream networks controlled by EGFR mutations, such as JAK-STAT, PI3K-AKT-mTOR, and MEK-ERK. The experiment also featured an EGFR-mutated cell line. Using 10XGenomics platform with cellplex technology, we analyzed the seven cell lines together with a pseudo-immunological microenvironment consisting of PBMC cells labeled with the Biolegend TotalSeq™-B Human Universal Cocktail (CITEseq). This technology allowed for independent labeling of each cell line and single-cell analysis of the pooled seven cell lines and the pseudo-microenvironment. The data generated from the aforementioned experiments are available as part of an online tool, which allows users to define cell heterogeneity and generates count tables as an output. The tool provides the cell line derivation for each cell and cell annotations for the pseudo-microenvironment based on CITEseq data by an experienced immunologist. Additionally, we created a range of pseudo-tumor tissues using different ratios of the aforementioned cells embedded in matrigel. These tissues were analyzed using 10XGenomics (FFPE samples) and Curio Bioscience (fresh frozen samples) platforms for spatial transcriptomics, further expanding the scope of our benchmark experiments. The benchmark experiments we conducted provide a unique opportunity to evaluate the performance of bioinformatics tools for detecting and characterizing tumor heterogeneity at the single-cell level. Overall, our experiments provide a controlled and standardized environment for assessing the accuracy and robustness of bioinformatics tools for studying tumor heterogeneity at the single-cell level, which can ultimately lead to more precise and effective cancer diagnosis and treatment.

Keywords: single cell omics, benchmark, spatial transcriptomics, CITEseq

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Authors: Shanna Swart, Caryn Fenner, Athanasios Kotsiopoulos, Susan Harrison

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Linear alkanes are produced as by-products from the increasing use of gas-to-liquid fuel technologies for synthetic fuel production and offer great potential for value addition. Their current use as low-value fuels and solvents do not maximize this potential. Therefore, attention has been drawn towards direct activation of these aliphatic alkanes to more useful products such as alcohols, aldehydes, carboxylic acids and derivatives. Cytochrome P450 monooxygenases (P450s) can be used for activation of these aliphatic alkanes using whole-cells or cell-free systems. Some limitations of whole-cell systems include reduced mass transfer, stability and possible side reactions. Since the P450 systems are little studied as cell-free systems, they form the focus of this study. Challenges of a cell-free system include co-factor regeneration, substrate availability and enzyme stability. Enzyme immobilization offers a positive outlook on this dilemma, as it may enhance stability of the enzyme. In the present study, 2 different P450s (CYP153A6 and CYP102A1) as well as the relevant accessory enzymes required for electron transfer (ferredoxin and ferredoxin reductase) and co-factor regeneration (glucose dehydrogenase) have been expressed in E. coli and purified by metal affinity chromatography. Glucose dehydrogenase (GDH), was used as a model enzyme to assess the potential of various enzyme immobilization strategies including; surface attachment on MagReSyn® microspheres with various functionalities and on electrospun nanofibers, using self-assembly based methods forming Cross Linked Enzymes (CLE), Cross Linked Enzyme Aggregates (CLEAs) and spherezymes as well as in a sol gel. The nanofibers were synthesized by electrospinning, which required the building of an electrospinning machine. The nanofiber morphology has been analyzed by SEM and binding will be further verified by FT-IR. Covalent attachment based methods showed limitations where only ferredoxin reductase and GDH retained activity after immobilization which were largely attributed to insufficient electron transfer and inactivation caused by the crosslinkers (60% and 90% relative activity loss for the free enzyme when using 0.5% glutaraldehyde and glutaraldehyde/ethylenediamine (1:1 v/v), respectively). So far, initial experiments with GDH have shown the most potential when immobilized via their His-tag onto the surface of MagReSyn® microspheres functionalized with Ni-NTA. It was found that Crude GDH could be simultaneously purified and immobilized with sufficient activity retention. Immobilized pure and crude GDH could be recycled 9 and 10 times, respectively, with approximately 10% activity remaining. The immobilized GDH was also more stable than the free enzyme after storage for 14 days at 4˚C. This immobilization strategy will also be applied to the P450s and optimized with regards to enzyme loading and immobilization time, as well as characterized and compared with the free enzymes. It is anticipated that the proposed immobilization set-up will offer enhanced enzyme stability (as well as reusability and easy recovery), minimal mass transfer limitation, with continuous co-factor regeneration and minimal enzyme leaching. All of which provide a positive outlook on this robust multi-enzyme system for efficient activation of linear alkanes as well as the potential for immobilization of various multiple enzymes, including multimeric enzymes for different bio-catalytic applications beyond alkane activation.

Keywords: alkane activation, cytochrome P450 monooxygenase, enzyme catalysis, enzyme immobilization

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Authors: Bensaid A., Mostephaoui T., Nedjai R.

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Nowadays, wetlands are the subject of contradictory debates opposing scientific, political and administrative meanings. Indeed, given their multiple services (drinking water, irrigation, hydrological regulation, mineral, plant and animal resources...), wetlands concentrate many socio-economic and biodiversity issues. In some regions, they can cover vast areas (>100 thousand ha) of the landscape, such as the Camargue area in the south of France, inside the Rhone delta. The high biological productivity of wetlands, the strong natural selection pressures and the diversity of aquatic environments have produced many species of plants and animals that are found nowhere else. These environments are tremendous carbon sinks and biodiversity reserves depending on their age, composition and surrounding environmental conditions, wetlands play an important role in global climate projections. Covering more than 3% of the earth's surface, wetlands have experienced since the beginning of the 1990s a tremendous revival of interest, which has resulted in the multiplication of inventories, scientific studies and management experiments. The geographical and physical characteristics of the wetlands of the central region conceal a large number of natural habitats that harbour a great biological diversity. These wetlands, one of the natural habitats, are still influenced by human activities, especially agriculture, which affects its layout and functioning. In this perspective, decision-makers need to delimit spatial objects (natural habitats) in a certain way to be able to take action. Thus, wetlands are no exception to this rule even if it seems to be a difficult exercise to delimit a type of environment as whose main characteristic is often to occupy the transition between aquatic and terrestrial environment. However, it is possible to map wetlands with databases, derived from the interpretation of photos and satellite images, such as the European database Corine Land cover, which allows quantifying and characterizing for each place the characteristic wetland types. Scientific studies have shown limitations when using high spatial resolution images (SPOT, Landsat, ASTER) for the identification and characterization of small wetlands (1 hectare). To address this limitation, it is important to note that these wetlands generally represent spatially complex features. Indeed, the use of very high spatial resolution images (>3m) is necessary to map small and large areas. However, with the recent evolution of artificial intelligence (AI) and deep learning methods for satellite image processing have shown a much better performance compared to traditional processing based only on pixel structures. Our research work is also based on spectral and textural analysis on THR images (Spot and IRC orthoimage) using two object-oriented approaches, the nearest neighbour approach (k-NN) and the Super Vector Machine approach (SVM). The k-NN approach gave good results for the delineation of wetlands (wet marshes and moors, ponds, artificial wetlands water body edges, ponds, mountain wetlands, river edges and brackish marshes) with a kappa index higher than 85%.

Keywords: land development, GIS, sand dunes, segmentation, remote sensing

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Authors: Muhammad Hanif Amiri, Edris Sadeqy, Ahmad Freed Osman

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International Conference on Architectural Engineering and Skyscraper (ICAES 2016) on January 18 - 19, 2016 is aimed to exchange new ideas and application experiences face to face, to establish business or research relations and to find global partners for future collaboration. Therefore, we are very keen to participate and share our issues in order to get valuable feedbacks of the conference participants. Urbanization is a controversial issue all around the world. Substandard and unplanned urbanization has many implications on a social, cultural and economic situation of population life. Unplanned and illegal construction has become a critical issue in Afghanistan particularly Kabul city. In addition, lack of municipal bylaws, poor municipal governance, lack of development policies and strategies, budget limitation, low professional capacity of ainvolved private sector in development and poor coordination among stakeholders are the other factors which made the problem more complicated. The main purpose of this research paper is to review urbanization pattern of Kabul city and find out the improvement solutions and to evaluate the increasing of population density which caused vast illegal and unplanned development which finally converts the Kabul city to a slam area as the whole. The Kabul city Master Plan was reviewed in the year 1978 and revised for the planned 2million population. In 2001, the interim administration took place and the city became influx of returnees from neighbor countries and other provinces of Afghanistan mostly for the purpose of employment opportunities, security and better quality of life, therefore, Kabul faced with strange population growth. According to Central Statistics Organization of Afghanistan population of Kabul has been estimated approx. 5 million (2015), however a new Master Plan has been prepared in 2009, but the existing challenges have not been dissolved yet. On the other hand, 70% of Kabul population is living in unplanned (slam) area and facing the shortage of drinking water, inexistence of sewerage and drainage network, inexistence of proper management system for solid waste collection, lack of public transportation and traffic management, environmental degradation and the shortage of social infrastructure. Although there are many problems in Kabul city, but still the development of 22 townships are in progress which caused the great attraction of population. The research is completed with a detailed analysis on four main issues such as elimination of duplicated administrations, Development of regions, Rehabilitation and improvement of infrastructure, and prevention of new townships establishment in Kabul Central Core in order to mitigate the problems and constraints which are the foundation and principal to find the point of departure for an objective based future development of Kabul city. The closure has been defined to reflect the stage-wise development in light of prepared policy and strategies, development of a procedure for the improvement of infrastructure, conducting a preliminary EIA, defining scope of stakeholder’s contribution and preparation of project list for initial development. In conclusion this paper will help the transformation of Kabul city.

Keywords: development of regions, illegal construction, population density, urbanization pattern

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Authors: Rachana Tank, Donald. M. Lyall, Kristin Flegal, Joey Ward, Jonathan Cavanagh

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Alzheimer’s research UK estimates by 2050, 2 million individuals will be living with Late Onset Alzheimer’s disease (LOAD). However, individuals experience considerable cognitive deficits and brain pathology over decades before reaching clinically diagnosable LOAD and studies have utilised gene candidate studies such as genome wide association studies (GWAS) and polygenic risk (PGR) scores to identify high risk individuals and potential pathways. This investigation aims to determine whether high genetic risk of LOAD is associated with worse brain MRI and cognitive performance in healthy older adults within the UK Biobank cohort. Previous studies investigating associations of PGR for LOAD and measures of MRI or cognitive functioning have focused on specific aspects of hippocampal structure, in relatively small sample sizes and with poor ‘controlling’ for confounders such as smoking. Both the sample size of this study and the discovery GWAS sample are bigger than previous studies to our knowledge. Genetic interaction between loci showing largest effects in GWAS have not been extensively studied and it is known that APOE e4 poses the largest genetic risk of LOAD with potential gene-gene and gene-environment interactions of e4, for this reason we  also analyse genetic interactions of PGR with the APOE e4 genotype. High genetic loading based on a polygenic risk score of 21 SNPs for LOAD is associated with worse brain MRI and cognitive outcomes in healthy individuals within the UK Biobank cohort. Summary statistics from Kunkle et al., GWAS meta-analyses (case: n=30,344, control: n=52,427) will be used to create polygenic risk scores based on 21 SNPs and analyses will be carried out in N=37,000 participants in the UK Biobank. This will be the largest study to date investigating PGR of LOAD in relation to MRI. MRI outcome measures include WM tracts, structural volumes. Cognitive function measures include reaction time, pairs matching, trail making, digit symbol substitution and prospective memory. Interaction of the APOE e4 alleles and PGR will be analysed by including APOE status as an interaction term coded as either 0, 1 or 2 e4 alleles. Models will be adjusted partially for adjusted for age, BMI, sex, genotyping chip, smoking, depression and social deprivation. Preliminary results suggest PGR score for LOAD is associated with decreased hippocampal volumes including hippocampal body (standardised beta = -0.04, P = 0.022) and tail (standardised beta = -0.037, P = 0.030), but not with hippocampal head. There were also associations of genetic risk with decreased cognitive performance including fluid intelligence (standardised beta = -0.08, P<0.01) and reaction time (standardised beta = 2.04, P<0.01). No genetic interactions were found between APOE e4 dose and PGR score for MRI or cognitive measures. The generalisability of these results is limited by selection bias within the UK Biobank as participants are less likely to be obese, smoke, be socioeconomically deprived and have fewer self-reported health conditions when compared to the general population. Lack of a unified approach or standardised method for calculating genetic risk scores may also be a limitation of these analyses. Further discussion and results are pending.

Keywords: Alzheimer's dementia, cognition, polygenic risk, MRI

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Authors: Adrian W. Egger, Savvas P. Triantafyllou, Eleni N. Chatzi

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The scaled boundary finite element method (SBFEM) is a semi-analytical numerical method, which introduces a scaling center in each element’s domain, thus transitioning from a Cartesian reference frame to one resembling polar coordinates. Consequently, an analytical solution is achieved in radial direction, implying that only the boundary need be discretized. The only limitation imposed on the resulting polygonal elements is that they remain star-convex. Further arbitrary p- or h-refinement may be applied locally in a mesh. The polygonal nature of SBFEM elements has been exploited in quadtree meshes to alleviate all issues conventionally associated with hanging nodes. Furthermore, since in 2D this results in only 16 possible cell configurations, these are precomputed in order to accelerate the forward analysis significantly. Any cells, which are clipped to accommodate the domain geometry, must be computed conventionally. However, since SBFEM permits polygonal elements, significantly coarser meshes at comparable accuracy levels are obtained when compared with conventional quadtree analysis, further increasing the computational efficiency of this scheme. The generalized stress intensity factors (gSIFs) are computed by exploiting the semi-analytical solution in radial direction. This is initiated by placing the scaling center of the element containing the crack at the crack tip. Taking an analytical limit of this element’s stress field as it approaches the crack tip, delivers an expression for the singular stress field. By applying the problem specific boundary conditions, the geometry correction factor is obtained, and the gSIFs are then evaluated based on their formal definition. Since the SBFEM solution is constructed as a power series, not unlike mode superposition in FEM, the two modes contributing to the singular response of the element can be easily identified in post-processing. Compared to the extended finite element method (XFEM) this approach is highly convenient, since neither enrichment terms nor a priori knowledge of the singularity is required. Computation of the gSIFs by SBFEM permits exceptional accuracy, however, when combined with hybrid quadtrees employing linear elements, this does not always hold. Nevertheless, it has been shown that crack propagation schemes are highly effective even given very coarse discretization since they only rely on the ratio of mode one to mode two gSIFs. The absolute values of the gSIFs may still be subject to large errors. Hence, we propose a post-processing scheme, which minimizes the error resulting from the approximation space of the cracked element, thus limiting the error in the gSIFs to the discretization error of the quadtree mesh. This is achieved by h- and/or p-refinement of the cracked element, which elevates the amount of modes present in the solution. The resulting numerical description of the element is highly accurate, with the main error source now stemming from its boundary displacement solution. Numerical examples show that this post-processing procedure can significantly improve the accuracy of the computed gSIFs with negligible computational cost even on coarse meshes resulting from hybrid quadtrees.

Keywords: linear elastic fracture mechanics, generalized stress intensity factors, scaled finite element method, hybrid quadtrees

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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: Mohammad R. Aghakashkooli, Milutin G. Jovanovic

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The brushless doubly-fed reluctance generator (BDFRG) is an emerging, medium-speed alternative to a conventional wound rotor slip-ring doubly-fed induction generator (DFIG) in wind energy conversion systems (WECS). It can provide competitive overall performance and similar low failure rates of a typically 30% rated back-to-back power electronics converter in 2:1 speed ranges but with the following important reliability and cost advantages over DFIG: the maintenance-free operation afforded by its brushless structure, 50% synchronous speed with the same number of rotor poles (allowing the use of a more compact, and more efficient two-stage gearbox instead of a vulnerable three-stage one), and superior grid integration properties including simpler protection for the low voltage ride through compliance of the fractional converter due to the comparatively higher leakage inductances and lower fault currents. Vector controlled pulse-width-modulated converters generally feature a much lower total harmonic distortion relative to hysteresis counterparts with variable switching rates and as such have been a predominant choice for BDFRG (and DFIG) wind turbines. Eliminating a shaft position sensor, which is often required for control implementation in this case, would be desirable to address the associated reliability issues. This fact has largely motivated the recent growing research of sensorless methods and developments of various rotor position and/or speed estimation techniques for this purpose. The main limitation of all the observer-based control approaches for grid-connected wind power applications of the BDFRG reported in the open literature is the requirement for pre-commissioning procedures and prior knowledge of the machine inductances, which are usually difficult to accurately identify by off-line testing. A model reference adaptive system (MRAS) based sensor-less vector control scheme to be presented will overcome this shortcoming. The true machine parameter independence of the proposed field-oriented algorithm, offering robust, inherently decoupled real and reactive power control of the grid-connected winding, is achieved by on-line estimation of the inductance ratio, the underlying rotor angular velocity and position MRAS observer being reliant upon. Such an observer configuration will be more practical to implement and clearly preferable to the existing machine parameter dependent solutions, and especially bearing in mind that with very little modifications it can be adapted for commercial DFIGs with immediately obvious further industrial benefits and prospects of this work. The excellent encoder-less controller performance with maximum power point tracking in the base speed region will be demonstrated by realistic simulation studies using large-scale BDFRG design data and verified by experimental results on a small laboratory prototype of the WECS emulation facility.

Keywords: brushless doubly fed reluctance generator, model reference adaptive system, sensorless vector control, wind energy conversion

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Authors: Ainura Tursunalieva, Irene Hudson

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Continuous improvement of both the quality and safety of health care is an important goal in Australia and internationally. The intensive care unit (ICU) receives patients with a wide variety of and severity of illnesses. Accurately identifying patients at risk of developing complications or dying is crucial to increasing healthcare efficiency. Thus, it is essential for clinicians and researchers to have a robust framework capable of evaluating the risk profile of a patient. ICU scoring systems provide such a framework. The Acute Physiology and Chronic Health Evaluation III and the Simplified Acute Physiology Score II are ICU scoring systems frequently used for assessing the severity of acute illness. These scoring systems collect multiple risk factors for each patient including physiological measurements then render the assessment outcomes of individual risk factors into a single numerical value. A higher score is related to a more severe patient condition. Furthermore, the Mortality Probability Model II uses logistic regression based on independent risk factors to predict a patient’s probability of mortality. An important overlooked limitation of SAPS II and MPM II is that they do not, to date, include interaction terms between a patient’s vital signs. This is a prominent oversight as it is likely there is an interplay among vital signs. The co-existence of certain conditions may pose a greater health risk than when these conditions exist independently. One barrier to including such interaction terms in predictive models is the dimensionality issue as it becomes difficult to use variable selection. We propose an innovative scoring system which takes into account a dependence structure among patient’s vital signs, such as systolic and diastolic blood pressures, heart rate, pulse interval, and peripheral oxygen saturation. Copulas will capture the dependence among normally distributed and skewed variables as some of the vital sign distributions are skewed. The estimated dependence parameter will then be incorporated into the traditional scoring systems to adjust the points allocated for the individual vital sign measurements. The same dependence parameter will also be used to create an alternative copula-based model for predicting a patient’s probability of mortality. The new copula-based approach will accommodate not only a patient’s trajectories of vital signs but also the joint dependence probabilities among the vital signs. We hypothesise that this approach will produce more stable assessments and lead to more time efficient and accurate predictions. We will use two data sets: (1) 250 ICU patients admitted once to the Chui Regional Hospital (Kyrgyzstan) and (2) 37 ICU patients’ agitation-sedation profiles collected by the Hunter Medical Research Institute (Australia). Both the traditional scoring approach and our copula-based approach will be evaluated using the Brier score to indicate overall model performance, the concordance (or c) statistic to indicate the discriminative ability (or area under the receiver operating characteristic (ROC) curve), and goodness-of-fit statistics for calibration. We will also report discrimination and calibration values and establish visualization of the copulas and high dimensional regions of risk interrelating two or three vital signs in so-called higher dimensional ROCs.

Keywords: copula, intensive unit scoring system, ROC curves, vital sign dependence

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Authors: Saleh Gorji, Sahil Gulati, Ana Pakzad

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Continuous electron diffraction tomography, also known as microcrystal electron diffraction (MicroED) or three-dimensional electron diffraction (3DED), is a powerful technique, which in combination with cryo-electron microscopy (cryo-ED), can provide atomic-scale 3D information about the crystal structure and composition of different classes of crystalline materials such as proteins, peptides, and small molecules. Unlike the well-established X-ray crystallography method, 3DED does not require large single crystals and can collect accurate electron diffraction data from crystals as small as 50 – 100 nm. This is a critical advantage as growing larger crystals, as required by X-ray crystallography methods, is often very difficult, time-consuming, and expensive. In most cases, specimens studied via 3DED method are electron beam sensitive, which means there is a limitation on the maximum amount of electron dose one can use to collect the required data for a high-resolution structure determination. Therefore, collecting data using a conventional scintillator-based fiber coupled camera brings additional challenges. This is because of the inherent noise introduced during the electron-to-photon conversion in the scintillator and transfer of light via the fibers to the sensor, which results in a poor signal-to-noise ratio and requires a relatively higher and commonly specimen-damaging electron dose rates, especially for protein crystals. As in other cryo-EM techniques, damage to the specimen can be mitigated if a direct detection camera is used which provides a high signal-to-noise ratio at low electron doses. In this work, we have used two classes of such detectors from Gatan, namely the K3® camera (a monolithic active pixel sensor) and Stela™ (that utilizes DECTRIS hybrid-pixel technology), to address this problem. The K3 is an electron counting detector optimized for low-dose applications (like structural biology cryo-EM), and Stela is also a counting electron detector but optimized for diffraction applications with high speed and high dynamic range. Lastly, data collection workflows, including crystal screening, microscope optics setup (for imaging and diffraction), stage height adjustment at each crystal position, and tomogram acquisition, can be one of the other challenges of the 3DED technique. Traditionally this has been all done manually or in a partly automated fashion using open-source software and scripting, requiring long hours on the microscope (extra cost) and extensive user interaction with the system. We have recently introduced Latitude® D in DigitalMicrograph® software, which is compatible with all pre- and post-energy-filter Gatan cameras and enables 3DED data acquisition in an automated and optimized fashion. Higher quality 3DED data enables structure determination with higher confidence, while automated workflows allow these to be completed considerably faster than before. Using multiple examples, this work will demonstrate how to direct detection electron counting cameras enhance 3DED results (3 to better than 1 Angstrom) for protein and small molecule structure determination. We will also show how Latitude D software facilitates collecting such data in an integrated and fully automated user interface.

Keywords: continuous electron diffraction tomography, direct detection, diffraction, Latitude D, Digitalmicrograph, proteins, small molecules

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