Search results for: response characteristic

Authors: Lyndsee Baumann-Birkbeck, Sohil A. Khan, Shailendra Anoopkumar-Dukie, Gary D. Grant

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Technology-enhanced education tools are being rapidly integrated into health programs globally. These tools provide an interactive platform for students and can be used to deliver topics in various modes including games and simulations. Simulations are of particular interest to healthcare education, where they are employed to enhance clinical knowledge and help to bridge the gap between theory and practice. Simulations will often assess competencies for practical tasks, yet limited research examines the effects of simulation on student perceptions of their learning. The aim of this study was to determine the effects of an interactive virtual patient simulation for pharmacology education and clinical practice on student knowledge, skills and confidence. Ethics approval for the study was obtained from Griffith University Research Ethics Committee (PHM/11/14/HREC). The simulation was intended to replicate the pharmacy environment and patient interaction. The content was designed to enhance knowledge of proton-pump inhibitor pharmacology, role in therapeutics and safe supply to patients. The tool was deployed into a third-year clinical pharmacology and therapeutics course. A number of core practice areas were examined including the competency domains of questioning, counselling, referral and product provision. Baseline measures of student self-reported knowledge, skills and confidence were taken prior to the simulation using a specifically designed questionnaire. A more extensive questionnaire was deployed following the virtual patient simulation, which also included measures of student engagement with the activity. A quiz assessing student factual and conceptual knowledge of proton-pump inhibitor pharmacology and related counselling information was also included in both questionnaires. Sixty-one students (response rate >95%) from two cohorts (2014 and 2015) participated in the study. Chi-square analyses were performed and data analysed using Fishers exact test. Results demonstrate that student knowledge, skills and confidence within the competency domains of questioning, counselling, referral and product provision, show improvement following the implementation of the virtual patient simulation. Statistically significant (p<0.05) improvement occurred in ten of the possible twelve self-reported measurement areas. Greatest magnitude of improvement occurred in the area of counselling (student confidence p<0.0001). Student confidence in all domains (questioning, counselling, referral and product provision) showed a marked increase. Student performance in the quiz also improved, demonstrating a 10% improvement overall for pharmacology knowledge and clinical practice following the simulation. Overall, 85% of students reported the simulation to be engaging and 93% of students felt the virtual patient simulation enhanced learning. The data suggests that the interactive virtual patient simulation developed for clinical pharmacology and therapeutics education enhanced students knowledge, skill and confidence, with respect to the competency domains of questioning, counselling, referral and product provision. These self-reported measures appear to translate to learning outcomes, as demonstrated by the improved student performance in the quiz assessment item. Future research of education using virtual simulation should seek to incorporate modern quantitative measures of student learning and engagement, such as eye tracking.

Keywords: clinical simulation, education, pharmacology, simulation, virtual learning

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Authors: Naomi Grigoryan, Alexandros Loutsioli Daskalakis, Anna Elisse Uy, Yihe Huang, Aude Laurent (Webanck)

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In response to the building and construction sectors accounting for a third of all energy demand and emissions, the European Union has placed new laws and regulations in the construction sector that emphasize material circularity, energy efficiency, biodiversity, and social impact. Existing design tools assess sustainability in early-stage design for products or buildings; however, there is no standardized methodology for measuring the circularity performance of building components. Existing assessment methods for building components focus primarily on carbon footprint but lack the comprehensive analysis required to design for circularity. The research conducted in this paper covers the parameters needed to assess sustainability in the design process of architectural products such as doors, windows, and facades. It maps a framework for a tool that assists designers with real-time sustainability metrics. Considering the life cycle of building components such as façades, windows, and doors involves the life cycle stages applied to product design and many of the methods used in the life cycle analysis of buildings. The current industry standards of sustainability assessment for metal building components follow cradle-to-grave life cycle assessment (LCA), track Global Warming Potential (GWP), and document the parameters used for an Environmental Product Declaration (EPD). Developed by the Ellen Macarthur Foundation, the Material Circularity Indicator (MCI) is a methodology utilizing the data from LCA and EPDs to rate circularity, with a "value between 0 and 1 where higher values indicate a higher circularity+". Expanding on the MCI with additional indicators such as the Water Circularity Index (WCI), the Energy Circularity Index (ECI), the Social Circularity Index (SCI), Life Cycle Economic Value (EV), and calculating biodiversity risk and uncertainty, the assessment methodology of an architectural product's impact can be targeted more specifically based on product requirements, performance, and lifespan. Broadening the scope of LCA calculation for products to incorporate aspects of building design allows product designers to account for the disassembly of architectural components. For example, the Material Circularity Indicator for architectural products such as windows and facades is typically low due to the impact of glass, as 70% of glass ends up in landfills due to damage in the disassembly process. The low MCI can be combatted by expanding beyond cradle-to-grave assessment and focusing the design process on disassembly, recycling, and repurposing with the help of real-time assessment tools. Design for Disassembly and Urban Mining has been integrated within the construction field on small scales as project-based exercises, not addressing the entire supply chain of architectural products. By adopting more comprehensive sustainability metrics and incorporating uncertainty calculations, the sustainability assessment of building components can be more accurately assessed with decarbonization and disassembly in mind, addressing the large-scale commercial markets within construction, some of the most significant contributors to climate change.

Keywords: architectural products, early-stage design, life cycle assessment, material circularity indicator

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Authors: Paola Clerici Maestosi

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Positive Energy District (PED) is a rather recent concept whose aim is to contribute to the main objectives of the Energy Union strategy. It is based on an integrated multi-sectoral approach in response to Europe's most complex challenges. PED integrates energy efficiency, renewable energy production, and energy flexibility in an integrated, multi-sectoral approach at the city level. The core idea behind Positive Energy Districts (PEDs) is to establish an urban area that can generate more energy than it consumes. Additionally, it should be flexible enough to adapt to changes in the energy market. This is crucial because a PED's goal is not just to achieve an annual surplus of net energy but also to help reduce the impact on the interconnected centralized energy networks. It achieves this by providing options to increase on-site load matching and self-consumption, employing technologies for short- and long-term energy storage, and offering energy flexibility through smart control. Thus, it seems that PEDs can encompass all types of buildings in the city environment. Given this which is the added value of having green buildings being constitutive part of PEDS? The paper will present a systematic literature review identifying the role of green building in Positive Energy District to provide answer to following questions: (RQ1) the state of the art of PEDs implementation; (RQ2) penetration of green building in Positive Energy District selected case studies. Methodological approach is based on a broad holistic study of bibliographic sources according to Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) further data will be analysed, mapped and text mining through VOSviewer. Main contribution of research is a cognitive framework on Positive Energy District in Europe and a selection of case studies where green building supported the transition to PED. The inclusion of green buildings within Positive Energy Districts (PEDs) adds significant value for several reasons. Firstly, green buildings are designed and constructed with a focus on environmental sustainability, incorporating energy-efficient technologies, materials, and design principles. As integral components of PEDs, these structures contribute directly to the district's overall ability to generate more energy than it consumes. Secondly, green buildings typically incorporate renewable energy sources, such as solar panels or wind turbines, further boosting the district's capacity for energy generation. This aligns with the PED objective of achieving a surplus of net energy. Moreover, green buildings often feature advanced systems for on-site energy management, load-matching, and self-consumption. This enhances the PED's capability to respond to variations in the energy market, making the district more agile and flexible in optimizing energy use. Additionally, the environmental considerations embedded in green buildings align with the broader sustainability goals of PEDs. By reducing the ecological footprint of individual structures, PEDs with green buildings contribute to minimizing the overall impact on centralized energy networks and promote a more sustainable urban environment. In summary, the incorporation of green buildings within PEDs not only aligns with the district's energy objectives but also enhances environmental sustainability, energy efficiency, and the overall resilience of the urban environment.

Keywords: positive energy district, renewables energy production, energy flexibility, energy efficiency

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Authors: Pedro A. Marques, Francisco Monteiro, Alessandra Zumbo, Alessia Simonini, Miguel A. Mendez

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Cryogenic fuels such as Liquid Hydrogen (LH₂) must be transported and stored at extremely low temperatures. Without expensive active cooling solutions, preventing fuel boil-off over time is impossible. Hence, one must resort to venting systems at the cost of significant energy and fuel mass loss. These losses increase significantly in propellant tanks installed on vehicles, as the presence of external accelerations induces sloshing. Sloshing increases heat and mass transfer rates and leads to significant pressure oscillations, which might further trigger propellant venting. To make LH₂ economically viable, it is essential to minimize these factors by using advanced control techniques. However, these require accurate modelling and a full understanding of the tank's thermodynamics. The present research aims to implement a simple thermodynamic model capable of predicting the state of a cryogenic fuel tank under different operating conditions (i.e., filling, pressurization, fuel extraction, long-term storage, and sloshing). Since this model relies on a set of closure parameters to drive the system's transient response, it must be calibrated using experimental or numerical data. This work focuses on the former approach, wherein the model is calibrated through an experimental campaign carried out on a reduced-scale model of a cryogenic tank. The thermodynamic model of the system is composed of three control volumes: the ullage, the liquid, and the insulating walls. Under this lumped formulation, the governing equations are derived from energy and mass balances in each region, with mass-averaged properties assigned to each of them. The gas-liquid interface is treated as an infinitesimally thin region across which both phases can exchange mass and heat. This results in a coupled system of ordinary differential equations, which must be closed with heat and mass transfer coefficients between each control volume. These parameters are linked to the system evolution via empirical relations derived from different operating regimes of the tank. The derivation of these relations is carried out using an inverse method to find the optimal relations that allow the model to reproduce the available data. This approach extends classic system identification methods beyond linear dynamical systems via a nonlinear optimization step. Thanks to the data-driven assimilation of the closure problem, the resulting model accurately predicts the evolution of the tank's thermodynamics at a negligible computational cost. The lumped model can thus be easily integrated with other submodels to perform complete system simulations in real time. Moreover, by setting the model in a dimensionless form, a scaling analysis allowed us to relate the tested configurations to a representative full-size tank for naval applications. It was thus possible to compare the relative importance of different transport phenomena between the laboratory model and the full-size prototype among the different operating regimes.

Keywords: destratification, hydrogen, modeling, pressure-drop, pressurization, sloshing, thermodynamics

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Authors: Dario Milani, Guido Morgenthal

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Fluid dynamic computation of wind caused forces on bluff bodies e.g light flexible civil structures or high incidence of ground approaching airplane wings, is one of the major criteria governing their design. For such structures a significant dynamic response may result, requiring the usage of small scale devices as guide-vanes in bridge design to control these effects. The focus of this paper is on the numerical simulation of the bluff body problem involving multiscale phenomena induced by small scale devices. One of the solution methods for the CFD simulation that is relatively successful in this class of applications is the Vortex Particle Method (VPM). The method is based on a grid free Lagrangian formulation of the Navier-Stokes equations, where the velocity field is modeled by particles representing local vorticity. These vortices are being convected due to the free stream velocity as well as diffused. This representation yields the main advantages of low numerical diffusion, compact discretization as the vorticity is strongly localized, implicitly accounting for the free-space boundary conditions typical for this class of FSI problems, and a natural representation of the vortex creation process inherent in bluff body flows. When the particle resolution reaches the Kolmogorov dissipation length, the method becomes a Direct Numerical Simulation (DNS). However, it is crucial to note that any solution method aims at balancing the computational cost against the accuracy achievable. In the classical VPM method, if the fluid domain is discretized by Np particles, the computational cost is O(Np2). For the coupled FSI problem of interest, for example large structures such as long-span bridges, the aerodynamic behavior may be influenced or even dominated by small structural details such as barriers, handrails or fairings. For such geometrically complex and dimensionally large structures, resolving the complete domain with the conventional VPM particle discretization might become prohibitively expensive to compute even for moderate numbers of particles. It is possible to reduce this cost either by reducing the number of particles or by controlling its local distribution. It is also possible to increase the accuracy of the solution without increasing substantially the global computational cost by computing a correction of the particle-particle interaction in some regions of interest. In this paper different strategies are presented in order to extend the conventional VPM method to reduce the computational cost whilst resolving the required details of the flow. The methods include temporal sub stepping to increase the accuracy of the particles convection in certain regions as well as dynamically re-discretizing the particle map to locally control the global and the local amount of particles. Finally, these methods will be applied on a test case and the improvements in the efficiency as well as the accuracy of the proposed extension to the method are presented. The important benefits in terms of accuracy and computational cost of the combination of these methods will be thus presented as long as their relevant applications.

Keywords: adaptation, fluid dynamic, remeshing, substepping, vortex particle method

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Authors: Jessica J. Gillies

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Awareness of the tragedy that is human trafficking has increased exponentially over the past two decades. The four pillars widely recognised as global solutions to the problem are prevention, prosecution, protection, and partnership between government and non-government organisations. While ‘sex-trafficking’ initially received major attention, this focus has shifted to other industries that conceal broader experiences of exploitation. However, within the regions of focus for this study, namely Australia and Thailand, trafficking for the purpose of sexual exploitation remains the commonly uncovered narrative of criminal justice investigations. In these regions anti-trafficking action is characterised by government-led prevention and prosecution efforts; whereas protection and reintegration practices have received criticism. Typically, non-government organisations straddle the critical chasm between policy and practice; therefore, they are perfectly positioned to contribute valuable experiential knowledge toward understanding how both sectors can support survivors in the post-trafficking experience. The aim of this research is to inform improved partnerships throughout government and non-government post-trafficking services by illuminating gaps in protection and reintegration initiatives. This research will explore government and non-government responses to human trafficking in Thailand and Australia, in order to understand how meaning is constructed in this context and how the construction of meaning effects survivors in the post-trafficking experience. A qualitative, three-stage methodology was adopted for this study. The initial stage of enquiry consisted of a discursive analysis, in order to deconstruct the broader discourses surrounding human trafficking. The data included empirical papers, grey literature such as publicly available government and non-government reports, and anti-trafficking policy documents. The second and third stages of enquiry will attempt to further explore the findings of the discourse analysis and will focus more specifically on protection and reintegration in Australia and Thailand. Stages two and three will incorporate process observations in government and non-government survivor support services, and semi-structured interviews with employees and volunteers within these settings. Two key findings emerged from the discursive analysis. The first exposed conflicting feminist arguments embedded throughout anti-trafficking discourse. Informed by conflicting feminist discourses on sex-work, a discursive relationship has been constructed between sex-industry policy and anti-trafficking policy. In response to this finding, data emerging from the process observations and semi-structured interviews will be interpreted using a feminist theoretical framework. The second finding progresses from the construction in the first. The discursive construction of sex-trafficking appears to have had influence over perceptions of the legitimacy of survivors, and therefore the support they receive in the post-trafficking experience. For example; women who willingly migrate for employment in the sex-industry, and on arrival are faced with exploitative conditions, are not perceived to be deserving of the same support as a woman who is not coerced, but rather physically forced, into such circumstances, yet both meet the criteria for a victim of human trafficking. The forthcoming study is intended to contribute toward building knowledge and understanding around the implications of the construction of legitimacy; and contextualise this in reference to government led protection and reintegration support services for survivors in the post-trafficking experience.

Keywords: Australia, government, human trafficking, non-government, reintegration, Thailand

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Authors: Prabhjot Kaur, B.K. Kang, Balwinder Singh

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The tobacco caterpillar, Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae) is an agricultural important pest species. S. litura has a wide host range of approximately recorded 150 plant species worldwide. In Punjab, this pest attains sporadic status primarily on cauliflower, Brassica oleracea (L.). This pest destroys vegetable crop and particularly prefers the cruciferae family. However, it is also observed feeding on other crops such as arbi, Colocasia esculenta (L.), mung bean, Vigna radiata (L.), sunflower, Helianthus annuus (L.), cotton, Gossypium hirsutum (L.), castor, Ricinus communis (L.), etc. Larvae of this pest completely devour the leaves of infested plant resulting in huge crop losses which ranges from 50 to 70 per cent. Indiscriminate and continuous use of insecticides has contributed in development of insecticide resistance in insects and caused the environmental degradation as well. Moreover, a base line data regarding the toxicity of the newer insecticides would help in understanding the level of resistance developed in this pest and any possible cross-resistance there in, which could be assessed in advance. Therefore, present studies on development of resistance in S. litura against four new chemistry insecticides (emamectin benzoate, chlorantraniliprole, indoxacarb and spinosad) were carried out in the Toxicology laboratory, Department of Entomology, Punjab Agricultural University, Ludhiana, Punjab, India during the year 2011-12. Various stages of S. litura (eggs, larvae) were collected from four different locations (Malerkotla, Hoshiarpur, Amritsar and Samrala) of Punjab. Resistance is developed in third instars of lepidopterous pests. Therefore, larval bioassays were conducted to estimate the response of field populations of thirty third-instar larvae of S. litura under laboratory conditions at 25±2°C and 65±5 per cent relative humidity. Leaf dip bioassay technique with diluted insecticide formulations recommended by Insecticide Resistance Action Committee (IRAC) was performed in the laboratory with seven to ten treatments depending on the insecticide class, respectively. LC50 values were estimated by probit analysis after correction to record control mortality data which was used to calculate the resistance ratios (RR). The LC50 values worked out for emamectin benzoate, chlorantraniliprole, indoxacarb, spinosad are 0.081, 0.088, 0.380, 4.00 parts per million (ppm) against pest populations collected from Malerkotla; 0.051, 0.060, 0.250, 3.00 (ppm) of Amritsar; 0.002, 0.001, 0.0076, 0.10 ppm for Samrala and 0.000014, 0.00001, 0.00056, 0.003 ppm against pest population of Hoshiarpur, respectively. The LC50 values for populations collected from these four locations were in the order Malerkotla>Amritsar>Samrala>Hoshiarpur for the insecticides (emamectin benzoate, chlorantraniliprole, indoxacarb and spinosad) tested. Based on LC50 values obtained, emamectin benzoate (0.000014 ppm) was found to be the most toxic among all the tested populations, followed by chlorantraniliprole (0.00001 ppm), indoxacarb (0.00056 ppm) and spinosad (0.003 ppm), respectively. The pairwise correlation coefficients of LC50 values indicated that there was lack of cross resistance for emamectin benzoate, chlorantraniliprole, spinosad, indoxacarb in populations of S. litura from Punjab. These insecticides may prove to be promising substitutes for the effective control of insecticide resistant populations of S. litura in Punjab state, India.

Keywords: Spodoptera litura, insecticides, toxicity, resistance

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Authors: Ahmad Ali, Muhammad Imran Ghani, Haiyan Ding, Zhihui Cheng, Muhammad Iqbal

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Background and Aims: In recent years, protected cultivation trend, especially in the northern parts of China, spread dynamically where production area, structure, and crops diversity have expanded gradually under plastic greenhouse vegetable cropping (PGVC) system. Under this growing system, continuous monoculture with excessive synthetic fertilizers inputs are common cultivation practices frequently adopted by commercial producers. Such long-term cumulative wild exercise year after year sponsor the continuous cropping obstacles in PGVC soil, which have greatly threatened the regional soil eco-sustainability and further impose the continuous assault on soil ecological diversity leading to the exhaustion of agriculture productivity. The aim of this study was to develop new allelopathic insights by exploiting available biological resources in the favor of sustainable PGVC to illuminate the continuous obstacle factors in plastic greenhouse. Method: A greenhouse study was executed under plastic tunnel located at the Horticulture Experimental Station of the College of Horticulture, Northwest A&F University, Yangling, Shaanxi Province, one of the prominent regions for intensive commercial PGVC in China. Post-harvest garlic residues (stalk, leaves) mechanically smashed, homogenized into powder size and incorporated at the ratio of 1:100; 3:100; 5:100 as a soil amendment in a replanted soil that have been used for continuous cucumber monoculture for 7 years (annually double cropping system in a greenhouse). Results: Incorporated C-rich garlic stalk significantly influenced the soil condition through various ways; organic matter decomposition and mineralization, moderately adjusted the soil pH, enhanced the soil nutrient availability, increased enzymatic activities, and promoted 20% more cucumber yield in short-time. Using Illumina MiSeq sequencing analysis of bacterial 16S rRNA and fungal 18S rDNA genes, the current study revealed that addition of garlic stalk/residue could also improve the microbial abundance and community composition in extensively exploited soil, and contributed in soil functionality, caused prosper changes in soil characteristics, reinforced to good crop yield. Conclusion: Our study provided evidence that addition of garlic stalk as soil fertility amendment is a feasible, cost-effective and efficient resource utilization way for renovation of degraded soil health, ameliorate soil quality components and improve ecological environment in short duration. Our study may provide a better scientific understanding for efficient crop residue management typically from allelopathic source.

Keywords: garlic stalk, microbial community dynamics, plant growth, soil amendment, soil-plant system

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Authors: Aleksandra Bylinska, Samantha Slight-Webb, Kevin Thomas, Miles Smith, Susan Macwana, Nicolas Dominguez, Eliza Chakravarty, Joan T. Merrill, Judith A. James, Joel M. Guthridge

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Background: Systemic Lupus Erythematosus (SLE) is an interferon-related autoimmune disease characterized by B cell dysfunction. One of the main hallmarks is a loss of tolerance to self-antigens leading to increased levels of autoantibodies against nuclear components (ANAs). However, up to 20% of healthy ANA+ individuals will not develop clinical illness. SLE is more prevalent among women and minority populations (African, Asian American and Hispanics). Moreover, African Americans have a stronger interferon (IFN) signature and develop more severe symptoms. The exact mechanisms involved in ethnicity-dependent B cell dysregulation and the progression of autoimmune disease from ANA+ healthy individuals to clinical disease remains unclear. Methods: Peripheral blood mononuclear cells (PBMCs) from African (AA) and European American (EA) ANA- (n=12), ANA+ (n=12) and SLE (n=12) individuals were assessed by multimodal scRNA-Seq/CITE-Seq methods to examine differential gene signatures in specific B cell subsets. Library preparation was done with a 10X Genomics Chromium according to established protocols and sequenced on Illumina NextSeq. The data were further analyzed for distinct cluster identification and differential gene signatures in the Seurat package in R and pathways analysis was performed using Ingenuity Pathways Analysis (IPA). Results: Comparing all subjects, 14 distinct B cell clusters were identified using a community detection algorithm and visualized with Uniform Manifold Approximation Projection (UMAP). The proportion of each of those clusters varied by disease status and ethnicity. Transitional B cells trended higher in ANA+ healthy individuals, especially in AA. Ribonucleoprotein high population (HNRNPH1 elevated, heterogeneous nuclear ribonucleoprotein, RNP-Hi) of proliferating Naïve B cells were more prevalent in SLE patients, specifically in EA. Interferon-induced protein high population (IFIT-Hi) of Naive B cells are increased in EA ANA- individuals. The proportion of memory B cells and plasma cells clusters tend to be expanded in SLE patients. As anticipated, we observed a higher signature of cytokine-related pathways, especially interferon, in SLE individuals. Pathway analysis among AA individuals revealed an NRF2-mediated Oxidative Stress response signature in the transitional B cell cluster, not seen in EA individuals. TNFR1/2 and Sirtuin Signaling pathway genes were higher in AA IFIT-Hi Naive B cells, whereas they were not detected in EA individuals. Interferon signaling was observed in B cells in both ethnicities. Oxidative phosphorylation was found in age-related B cells (ABCs) for both ethnicities, whereas Death Receptor Signaling was found only in EA patients in these cells. Interferon-related transcription factors were elevated in ABCs and IFIT-Hi Naive B cells in SLE subjects of both ethnicities. Conclusions: ANA+ healthy individuals have altered gene expression pathways in B cells that might drive apoptosis and subsequent clinical autoimmune pathogenesis. Increases in certain regulatory pathways may delay progression to SLE. Further, AA individuals have more elevated activation pathways that may make them more susceptible to SLE.

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Authors: Mohamed Emran, Giovanni Pardini, Maria Gispert, Mohamed Rashad

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Land use and abandonment in semi-arid degraded ecosystems may cause regressive dynamics in vegetation cover affecting organic matter contents, soil nutrients and structural stability, thus reducing soil resistance to erosion. Mediterranean areas are generally subjected to climatic fluctuations, which modify soil conditions and hydrological processes, such as runoff and water infiltration within the upper soil horizons. Low erosion rates occur in very fragile and shallow soils with minor clay content progressively decrease organic carbon C and nitrogen N pools in the upper soil horizons. Seven soils were selected representing variant context of land use and abandonment at the Cap de Creus Peninsula, Catalonia, NE Spain, from recent cultivated vines and olive groves, mid abandoned forests standing under cork and pine trees, pasture to late abandoned Cistus and Erica scrubs. The aim of this work was to study the effect of changes in land use and abandonment on the depletion of soil organic carbon and nitrogen transported by runoff water in shallow soils after natural rainfall events during two years with different rainfall patterns (1st year with low rainfall and 2nd year with high rainfall) by i) monitoring the most significant soil erosion parameters at recorded rainfall events, ii) studying the most relevant soil physical and chemical characteristics on seasonal basis and iii) analysing the seasonal trends of depleted carbon and nitrogen and their interaction with soil surface compaction parameters. Significant seasonal variability was observed in the relevant soil physical and chemical parameters and soil erosion parameters in all soils to establish their evolution under land use and abandonment during two years of different rainfall patterns (214 and 487 mm per year), giving important indications on soil response to rainfall impacts. Erosion rates decreased significantly with the increasing of soil C and N under low and high rainfall. In cultivated soils, C and N depletion increased by 144% and 115%, respectively by 13% increase in erosion rates during the 1st year with respect to the 2nd year. Depleted C and N were proportionally higher in soils under vines and olive with vulnerable soil structure and low soil resilience leading to degradation, altering nutrients cycles and causing adverse impact on environmental quality. Statistical analysis underlined that, during the 1st year, soil surface was less effective in preserving stocks of organic resources leading to higher susceptibility to erosion with consequent C and N depletion. During the 2nd year, higher organic reserve and water storage occurred despite the increasing of C and N loss with an effective contribution from soil surface compaction parameters. The overall estimation during the two years indicated clear differences among soils under vines, olive, cork and pines, suggesting on the one hand, that current cultivation practices are inappropriate and that reforestation with pines may delay the achievement of better soil conditions. On the other hand, the natural succession of vegetation under Cistus, pasture and Erica suggests the recovery of good soil conditions.

Keywords: land abandonment, land use, nutrient's depletion, soil erosion

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Authors: Jae Won Lee, Kyung Hyun Min, Hong Jae Lee, Sang Cheon Lee

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To date, imaging techniques have attracted much attention in medicine because the detection of diseases at an early stage provides greater opportunities for successful treatment. Consequently, over the past few decades, diverse imaging modalities including magnetic resonance (MR), positron emission tomography, computed tomography, and ultrasound (US) have been developed and applied widely in the field of clinical diagnosis. However, each of the above-mentioned imaging modalities possesses unique strengths and intrinsic weaknesses, which limit their abilities to provide accurate information. Therefore, multimodal imaging systems may be a solution that can provide improved diagnostic performance. Among the current medical imaging modalities, US is a widely available real-time imaging modality. It has many advantages including safety, low cost and easy access for patients. However, its low spatial resolution precludes accurate discrimination of diseased region such as cancer sites. In contrast, MR has no tissue-penetrating limit and can provide images possessing exquisite soft tissue contrast and high spatial resolution. However, it cannot offer real-time images and needs a comparatively long imaging time. The characteristics of these imaging modalities may be considered complementary, and the modalities have been frequently combined for the clinical diagnostic process. Biominerals such as calcium carbonate (CaCO3) and calcium phosphate (CaP) exhibit pH-dependent dissolution behavior. They demonstrate pH-controlled drug release due to the dissolution of minerals in acidic pH conditions. In particular, the application of this mineralization technique to a US contrast agent has been reported recently. The CaCO3 mineral reacts with acids and decomposes to generate calcium dioxide (CO2) gas in an acidic environment. These gas-generating mineralized nanoparticles generated CO2 bubbles in the acidic environment of the tumor, thereby allowing for strong echogenic US imaging of tumor tissues. On the basis of this previous work, it was hypothesized that the loading of MR contrast agents into the CaCO3 mineralized nanoparticles may be a novel strategy in designing a contrast agent for dual imaging. Herein, CaCO3 mineralized nanoparticles that were capable of generating CO2 bubbles to trigger the release of entrapped MR contrast agents in response to tumoral acidic pH were developed for the purposes of US and MR dual-modality imaging of tumors. Gd2O3 nanoparticles were selected as an MR contrast agent. A key strategy employed in this study was to prepare Gd2O3 nanoparticle-loaded mineralized nanoparticles (Gd2O3-MNPs) using block copolymer-templated CaCO3 mineralization in the presence of calcium cations (Ca2+), carbonate anions (CO32-) and positively charged Gd2O3 nanoparticles. The CaCO3 core was considered suitable because it may effectively shield Gd2O3 nanoparticles from water molecules in the blood (pH 7.4) before decomposing to generate CO2 gas, triggering the release of Gd2O3 nanoparticles in tumor tissues (pH 6.4~7.4). The kinetics of CaCO3 dissolution and CO2 generation from the Gd2O3-MNPs were examined as a function of pH and pH-dependent in vitro magnetic relaxation; additionally, the echogenic properties were estimated to demonstrate the potential of the particles for the tumor-specific US and MR imaging.

Keywords: calcium carbonate, mineralization, ultrasound imaging, magnetic resonance imaging

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Authors: Rijnbout-St.James Willem, Lindner Volkhard, Scholand Mary Beth, Ashton M. Tillett, Di Gennaro Michael Jude, Smith Silvia Enrica

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Introduction: Fibrosing lung diseases are characterized by changes in the lung interstitium and are classified based on etiology: 1) environmental/exposure-related, 2) autoimmune-related, 3) sarcoidosis, 4) interstitial pneumonia, and 4) idiopathic. Among interstitial lung diseases (ILD) idiopathic forms, idiopathic pulmonary fibrosis (IPF) is the most severe. Pathogenesis of IPF is characterized by an increased presence of proinflammatory mediators, resulting in alveolar injury, where injury to alveolar epithelium precipitates an increase in collagen deposition, subsequently thickening the alveolar septum and decreasing gas exchange. Identifying biomarkers implicated in the pathogenesis of lung fibrosis is key to developing new therapies and improving the efficacy of existing therapies. The transforming growth factor-beta (TGF-B1), a mediator of tissue repair associated with WNT5A signaling, is partially responsible for fibroblast proliferation in ILD and is the target of Pirfenidone, one of the antifibrotic therapies used for patients with IPF. Canonical TGF-B signaling is mediated by the proteins SMAD 2/3, which are, in turn, indirectly regulated by Collagen Triple Helix Repeat Containing 1 (CTHRC1). In this study, we tested the following hypotheses: 1) CTHRC1 is more elevated in the ILD cohort compared to unaffected controls, and 2) CTHRC1 is differently expressed among ILD types. Material and Methods: CTHRC1 levels were measured by ELISA in 171 plasma samples from the deidentified University of Utah ILD cohort. Data represent a cohort of 131 ILD-affected participants and 40 unaffected controls. CTHRC1 samples were categorized by a pulmonologist based on affectation status and disease subtypes: IPF (n = 45), sarcoidosis (4), nonspecific interstitial pneumonia (16), hypersensitivity pneumonitis (n = 7), interstitial pneumonia (n=13), autoimmune (n = 15), other ILD - a category that includes undifferentiated ILD diagnoses (n = 31), and unaffected controls (n = 40). We conducted a single-factor ANOVA of plasma CTHRC1 levels to test whether CTHRC1 variance among affected and non-affected participants is statistically significantly different. In-silico analysis was performed with Ingenuity Pathway Analysis® to characterize the role of CTHRC1 in the pathway of lung fibrosis. Results: Statistical analyses of CTHRC1 in plasma samples indicate that the average CTHRC1 level is significantly higher in ILD-affected participants than controls, with the autoimmune ILD being higher than other ILD types, thus supporting our hypotheses. In-silico analyses show that CTHRC1 indirectly activates and phosphorylates SMAD3, which in turn cross-regulates TGF-B1. CTHRC1 also may regulate the expression and transcription of TGFB-1 via WNT5A and its regulatory relationship with CTNNB1. Conclusion: In-silico pathway analyses demonstrate that CTHRC1 may be an important biomarker in ILD. Analysis of plasma samples indicates that CTHRC1 expression is positively associated with ILD affectation, with autoimmune ILD having the highest average CTHRC1 values. While characterizing CTHRC1 levels in plasma can help to differentiate among ILD types and predict response to Pirfenidone, the extent to which plasma CTHRC1 level is a function of ILD severity or chronicity is unknown.

Keywords: interstitial lung disease, CTHRC1, idiopathic pulmonary fibrosis, pathway analyses

Procedia PDF Downloads 165

Authors: Suikinai Nobre Santos, Ranko Gacesa, Paul F. Long, Itamar Soares de Melo

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Extremophilic microorganism are adapted to biotopes combining several stress factors (temperature, pressure, radiation, salinity and pH), which indicate the richness valuable resource for the exploitation of novel biotechnological processes and constitute unique models for investigations their biomolecules (1, 2). The above information encourages us investigate bioprospecting synthesized compounds by a noval actinomycete, designated thermotolerant Streptomyces caatingaensis CMAA 1322, isolated from sample soil tropical dry forest (Caatinga) in the Brazilian semiarid region (3-17°S and 35-45°W). This set of constrating physical and climatic factores provide the unique conditions and a diversity of well adapted species, interesting site for biotechnological purposes. Preliminary studies have shown the great potential in the production of cytotoxic, pesticidal and antimicrobial molecules (3). Thus, to extend knowledge of the genes clusters responsible for producing biosynthetic pathways of natural products in strain CMAA1322, whole-genome shotgun (WGS) DNA sequencing was performed using paired-end long sequencing with PacBio RS (Pacific Biosciences). Genomic DNA was extracted from a pure culture grown overnight on LB medium using the PureLink genomic DNA kit (Life Technologies). An approximately 3- to 20-kb-insert PacBio library was constructed and sequenced on an 8 single-molecule real-time (SMRT) cell, yielding 116,269 reads (average length, 7,446 bp), which were allocated into 18 contigs, with 142.11x coverage and N50 value of 20.548 bp (BioProject number PRJNA288757). The assembled data were analyzed by Rapid Annotations using Subsystems Technology (RAST) (4) the genome size was found to be 7.055.077 bp, comprising 6167 open reading frames (ORFs) and 413 subsystems. The G+C content was estimated to be 72 mol%. The closest-neighbors tool, available in RAST through functional comparison of the genome, revealed that strain CMAA1322 is more closely related to Streptomyces hygroscopicus ATCC 53653 (similarity score value, 537), S. violaceusniger Tu 4113 (score value, 483), S. avermitilis MA-4680 (score value, 475), S. albus J1074 (score value, 447). The Streptomyces sp. CMAA1322 genome contains 98 tRNA genes and 135 genes copies related to stress response, mainly osmotic stress (14), heat shock (16), oxidative stress (49). Functional annotation by antiSMASH version 3.0 (5) identified 41 clusters for secondary metabolites (including two clusters for lanthipeptides, ten clusters for nonribosomal peptide synthetases [NRPS], three clusters for siderophores, fourteen for polyketide synthetase [PKS], six clusters encoding a terpene, two clusters encoding a bacteriocin, and one cluster encoding a phenazine). Our work provide in comparative analyse of genome and extract produced (data no published) by lineage CMAA1322, revealing the potential of microorganisms accessed from extreme environments as Caatinga” to produce a wide range of biotechnological relevant compounds.

Keywords: caatinga, streptomyces, environmental stresses, biosynthetic pathways

Procedia PDF Downloads 213

Authors: Natalie Riley, Anita Quigley, Robert M. I. Kapsa, George W. Greene

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As the fields of medicine and bionics grow rapidly in technological advancement, the future and success of it depends on the ability to effectively interface between the artificial and the biological worlds. The biggest obstacle when it comes to implantable, electronic medical devices, is maintaining a ‘clean’, low noise electrical connection that allows for efficient sharing of electrical information between the artificial and biological systems. Implant fouling occurs with the adhesion and accumulation of proteins and various cell types as a result of the immune response to protect itself from the foreign object, essentially forming an electrical insulation barrier that often leads to implant failure over time. Lubricin (LUB) functions as a major boundary lubricant in articular joints, a unique glycoprotein with impressive anti-adhesive properties that self-assembles to virtually any substrate to form a highly ordered, ‘telechelic’ polymer brush. LUB does not passivate electroactive surfaces which makes it ideal, along with its innate biocompatibility, as a coating for implantable bionic electrodes. It is the aim of the study to investigate LUB’s anti-fouling properties and its potential as a safe, bioinspired material for coating applications to enhance the performance and longevity of implantable medical devices as well as reducing the frequency of implant replacement surgeries. Native, bovine-derived LUB (N-LUB) and recombinant LUB (R-LUB) were applied to gold-coated mylar surfaces. Fibroblast, chondrocyte and neural cell types were cultured and grown on the coatings under both passive and electrically stimulated conditions to test the stability and anti-adhesive property of the LUB coating in the presence of an electric field. Lactate dehydrogenase (LDH) assays were conducted as a directly proportional cell population count on each surface along with immunofluorescent microscopy to visualize cells. One-way analysis of variance (ANOVA) with post-hoc Tukey’s test was used to test for statistical significance. Under both passive and electrically stimulated conditions, LUB significantly reduced cell attachment compared to bare gold. Comparing the two coating types, R-LUB reduced cell attachment significantly compared to its native counterpart. Immunofluorescent micrographs visually confirmed LUB’s antiadhesive property, R-LUB consistently demonstrating significantly less attached cells for both fibroblasts and chondrocytes. Preliminary results investigating neural cells have so far demonstrated that R-LUB has little effect on reducing neural cell attachment; the study is ongoing. Recombinant LUB coatings demonstrated impressive anti-adhesive properties, reducing cell attachment in fibroblasts and chondrocytes. These findings and the availability of recombinant LUB brings into question the results of previous experiments conducted using native-derived LUB, its potential not adequately represented nor realized due to unknown factors and impurities that warrant further study. R-LUB is stable and maintains its anti-fouling property under electrical stimulation, making it suitable for electroactive surfaces.

Keywords: anti-fouling, bioinspired, cell attachment, lubricin

Procedia PDF Downloads 101

Authors: Juliane Toce, Steven Holochwost

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A substantial and growing literature has demonstrated that arts education benefits young children’s socioemotional and cognitive development. Less is known about the capacity of arts-integrated instruction to yield benefits to similar domains, particularly among demographically and socioeconomically diverse groups of young children. However, the small literature on this topic suggests that arts-integrated instruction may foster young children’s socioemotional and cognitive development by presenting opportunities to 1) engage in instructional content in diverse ways, 2) experience and regulate strong emotions, 3) experience growth-oriented feedback, and 4) engage in collaborative work with peers. Start with the Art is a new program of arts-integrated instruction currently being implemented in four schools in a school district that serves students from a diverse range of backgrounds. The program employs a co-teaching model in which teaching artists and classroom teachers engage in collaborative lesson planning and instruction over the course of the academic year and is currently the focus of an impact study featuring a randomized-control design, as well as an implementation study, both of which are funded through an Educational Innovation and Research grant from the United States Department of Education. The paper will present the early results from the Start with the Art implementation study. These results will provide an overview of the extent to which the program was implemented in accordance with design, with a particular emphasis on the degree to which the four opportunities enumerated above (e.g., opportunities to engage in instructional content in diverse ways) were presented to students. There will be a review key factors that may influence the fidelity of implementation, including classroom teachers’ reception of the program and the extent to which extant conditions in the classroom (e.g., the overall level of classroom organization) may have impacted implementation fidelity. With the explicit purpose of creating a program that values and meets the needs of the teachers and students, Start with the Art incorporates the feedback from individuals participating in the intervention. Tracing its trajectory from inception to ongoing development and examining the adaptive changes made in response to teachers' transformative experiences in the post-pandemic classroom, Start with the Art continues to solicit input from experts in integrating artistic content into core curricula within educational settings catering to students from under-represented backgrounds in the arts. Leveraging the input from this rich consortium of experts has allowed for a comprehensive evaluation of the program’s implementation. The early findings derived from the implementation study emphasize the potential of arts-integrated instruction to incorporate restorative practices. Such practices serve as a crucial support system for both students and educators, providing avenues for children to express themselves, heal emotionally, and foster social development, while empowering teachers to create more empathetic, inclusive, and supportive learning environments. This all-encompassing analysis spotlights Start with the Art’s adaptability to any learning environment through the program’s effectiveness, resilience, and its capacity to transform - through art - the classroom experience within the ever-evolving landscape of education.

Keywords: arts-integration, social emotional learning, diverse learners, co-teaching, teaching artists, post-pandemic teaching

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Authors: Tracey Woods

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In the ever-evolving landscape of academia, the traditional role of the librarian has undergone a remarkable transformation. Once considered as custodians of books and gatekeepers of information, librarians have the potential to take on the vital role of facilitators of cross and inter-disciplinary projects. This shift is driven by the growing recognition of the value of interdisciplinary collaboration in addressing complex research questions in pursuit of novel solutions to real-world problems. This paper shall explore the potential of the academic librarian’s role in facilitating innovative, multi-disciplinary projects, both recognising and validating the vital role that the librarian plays in a somewhat underplayed profession. Academic libraries support teaching, the strengthening of knowledge discourse, and, potentially, the development of innovative practices. As the role of the library gradually morphs from a quiet repository of books to a community-based information hub, a potential opportunity arises. The academic librarian’s role is to build knowledge across a wide span of topics, from the advancement of AI to subject-specific information, and, whilst librarians are generally not offered the research opportunities and funding that the traditional academic disciplines enjoy, they are often invited to help build research in support of the academic. This identifies that one of the primary skills of any 21st-century librarian must be the ability to collaborate and facilitate multi-disciplinary projects. In universities seeking to develop research diversity and academic performance, there is an increasing awareness of the need for collaboration between faculties to enable novel directions and advancements. This idea has been documented and discussed by several researchers; however, there is not a great deal of literature available from recent studies. Having a team based in the library that is adept at creating effective collaborative partnerships is valuable for any academic institution. This paper outlines the development of such a project, initiated within and around an identified library-specific need: the replication of fragile special collections for object-based learning. The research was developed as a multi-disciplinary project involving the faculties of engineering (digital twins lab), architecture, design, and education. Centred around methods for developing a fragile archive into a series of tactile objects furthers knowledge and understanding in both the role of the library as a facilitator of projects, chairing and supporting, alongside contributing to the research process and innovating ideas through the bank of knowledge found amongst the staff and their liaising capabilities. This paper shall present the method of project development from the initiation of ideas to the development of prototypes and dissemination of the objects to teaching departments for analysis. The exact replication of artefacts is also balanced with the adaptation and evolutionary speculations initiated by the design team when adapted as a teaching studio method. The dynamic response required from the library to generate and facilitate these multi-disciplinary projects highlights the information expertise and liaison skills that the librarian possesses. As academia embraces this evolution, the potential for groundbreaking discoveries and innovative solutions across disciplines becomes increasingly attainable.

Keywords: Liaison librarian, multi-disciplinary collaborations, library innovations, librarian stakeholders

Procedia PDF Downloads 34

Authors: Beatriz González-rodrigo, Diego Hidalgo-leiva, Omar Flores, Claudia Germoso, Maribel Jiménez-martínez, Laura Navas-sánchez, Belén Orta, Nicola Tarque, Orlando Hernández- Rubio, Miguel Marchamalo, Juan Gregorio Rejas, Belén Benito-oterino

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Cities facing seismic hazard necessitate detailed risk assessments for effective urban planning and vulnerability identification, ensuring the safety and sustainability of urban infrastructure. Comprehensive studies involving seismic hazard, vulnerability, and exposure evaluations are pivotal for estimating potential losses and guiding proactive measures against seismic events. However, broad-scale traditional risk studies limit consideration of specific local threats and identify vulnerable housing within a structural typology. Achieving precise results at neighbourhood levels demands higher resolution seismic hazard exposure, and vulnerability studies. This research aims to bolster sustainability and safety against seismic disasters in three Central American and Caribbean capitals. It integrates geospatial techniques and artificial intelligence into seismic risk studies, proposing cost-effective methods for exposure data collection and damage prediction. The methodology relies on prior seismic threat studies in pilot zones, utilizing existing exposure and vulnerability data in the region. Emphasizing detailed building attributes enables the consideration of behaviour modifiers affecting seismic response. The approach aims to generate detailed risk scenarios, facilitating prioritization of preventive actions pre-, during, and post-seismic events, enhancing decision-making certainty. Detailed risk scenarios necessitate substantial investment in fieldwork, training, research, and methodology development. Regional cooperation becomes crucial given similar seismic threats, urban planning, and construction systems among involved countries. The outcomes hold significance for emergency planning and national and regional construction regulations. The success of this methodology depends on cooperation, investment, and innovative approaches, offering insights and lessons applicable to regions facing moderate seismic threats with vulnerable constructions. Thus, this framework aims to fortify resilience in seismic-prone areas and serves as a reference for global urban planning and disaster management strategies. In conclusion, this research proposes a comprehensive framework for seismic risk assessment in high-risk urban areas, emphasizing detailed studies at finer resolutions for precise vulnerability evaluations. The approach integrates regional cooperation, geospatial technologies, and adaptive fragility curve adjustments to enhance risk assessment accuracy, guiding effective mitigation strategies and emergency management plans.

Keywords: assessment, behaviour modifiers, emergency management, mitigation strategies, resilience, vulnerability

Procedia PDF Downloads 41

Authors: Anitha Kandasamy, Thirumurugan Ramaiah

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Interestingly, organic materials exhibit large optical nonlinearity with quick responses and having the flexibility of molecular tailoring using computational modelling and favourable synthetic methodologies. Pyridine based organic compounds and carboxylic acid contained aromatic compounds play a crucial role in crystal engineering of NCS complexes that displays admirable optical nonlinearity with fast response and favourable physicochemical properties such as low dielectric constant, wide optical transparency and large laser damage threshold value requires for optoelectronics device applications. Based on these facts, it was projected to form an acentric molecule of π-conjugated system interaction with appropriately replaced electron donor and acceptor groups for achieving higher SHG activity in which quinoline-2-carboyxlic acid is chosen as an electron acceptor and capable of acting as an acid as well as a base molecule, while 2-amino-4-methylpyridine is used as an electron donor and previously employed in numerous proton transfer complexes for synthesis of NLO materials for optoelectronic applications. 2-amino-4-mehtylpyridinium quinoline-2-carboxylate molecular complex (2AQ) is having π-donor-acceptor groups in which 2-amino-4-methylpyridine donates one of its electron to quinoline -2-carboxylic acid thereby forming a protonated 2-amino-4-methyl pyridinium moiety and mono ionized quinoline-2-carboxylate moiety which are connected via N-H…O intermolecular interactions with non-centrosymmetric crystal packing arrangement at microscopic scale is accountable to the enhancement of macroscopic second order NLO activity. The 2AQ crystal was successfully grown by a slow evaporation solution growth technique and its structure was determined in orthorhombic crystal system with acentric, P212121, space group. Hirshfeld surface analysis reveals that O…H intermolecular interactions primarily contributed with 31.0 % to the structural stabilization of 2AQ. The molecular structure of title compound has been confirmed by 1H and 13C NMR spectral studies. The vibrational modes of functional groups present in 2AQ have been assigned by using FTIR and FT-Raman spectroscopy. The grown 2AQ crystal exhibits high optical transparency with lower cut-off wavelength (275 nm) within the region of 275-1500 nm. The laser study confirmed that 2AQ exhibits high SHG efficiency of 12.6 times greater than that of KDP. TGA-DTA analysis revealed that 2AQ crystal had a thermal stability of 223 °C. The low dielectric constant and low dielectric loss at higher frequencies confirmed good crystalline nature with fewer defects of grown 2AQ crystal. The grown crystal exhibits soft material and positive photoconduction behaviour. Mulliken atomic distribution and FMOs analysis suggested that the strong intermolecular hydrogen bonding which lead to the enhancement of NLO activity. These properties suggest that 2AQ crystal is a suitable material for optoelectronic and laser frequency conversion applications.

Keywords: crystal growth, NLO activity, proton transfer complex, quantum chemical investigation

Procedia PDF Downloads 97

Authors: Stanislav Babaev, Vladimir Cuk, Sjef Cobben, Jan Desmet

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The procedures for performing harmonic studies for medium-voltage distribution feeders have become relatively mature topics since the early 1980s. The efforts of various electric power engineers and researchers were mainly focused on handling large harmonic non-linear loads connected scarcely at several buses of medium-voltage feeders. In order to assess the impact of these loads on the voltage quality of the distribution system, specific modeling and simulation strategies were proposed. These methodologies could deliver a reasonable estimation accuracy given the requirements of least computational efforts and reduced complexity. To uphold these requirements, certain analysis assumptions have been made, which became de facto standards for establishing guidelines for harmonic analysis. Among others, typical assumptions include balanced conditions of the study and the negligible impact of impedance frequency characteristics of various power system components. In latter, skin and proximity effects are usually omitted, and resistance and reactance values are modeled based on the theoretical equations. Further, the simplifications of the modelling routine have led to the commonly accepted practice of neglecting phase angle diversity effects. This is mainly associated with developed load models, which only in a handful of cases are representing the complete harmonic behavior of a certain device as well as accounting on the harmonic interaction between grid harmonic voltages and harmonic currents. While these modelling practices were proven to be reasonably effective for medium-voltage levels, similar approaches have been adopted for low-voltage distribution systems. Given modern conditions and massive increase in usage of residential electronic devices, recent and ongoing boom of electric vehicles, and large-scale installing of distributed solar power, the harmonics in current low-voltage grids are characterized by high degree of variability and demonstrate sufficient diversity leading to a certain level of cancellation effects. It is obvious, that new modelling algorithms overcoming previously made assumptions have to be accepted. In this work, a simulation approach aimed to deal with some of the typical assumptions is proposed. A practical low-voltage feeder is modeled in PowerFactory. In order to demonstrate the importance of diversity effect and harmonic interaction, previously developed measurement-based models of photovoltaic inverter and battery charger are used as loads. The Python-based script aiming to supply varying voltage background distortion profile and the associated current harmonic response of loads is used as the core of unbalanced simulation. Furthermore, the impact of uncertainty of feeder frequency-impedance characteristics on total harmonic distortion levels is shown along with scenarios involving linear resistive loads, which further alter the impedance of the system. The comparative analysis demonstrates sufficient differences with cases when all the assumptions are in place, and results indicate that new modelling and simulation procedures need to be adopted for low-voltage distribution systems with high penetration of non-linear loads and renewable generation.

Keywords: electric power system, harmonic distortion, power quality, public low-voltage network, harmonic modelling

Procedia PDF Downloads 132

Authors: Nurkhairul Bariyah Baharun, Afzan Adam, Reena Rahayu Md Zin

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Tumor microenvironment (TME) in breast cancer is mainly composed of cancer cells, immune cells, and stromal cells. The interaction between cancer cells and their microenvironment plays an important role in tumor development, progression, and treatment response. The TME in breast cancer includes tumor-infiltrating lymphocytes (TILs) that are implicated in killing tumor cells. TILs can be found in tumor stroma (sTILs) and within the tumor (iTILs). TILs in triple negative breast cancer (TNBC) have been demonstrated to have prognostic and potentially predictive value. The international Immune-Oncology Biomarker Working Group (TIL-WG) had developed a guideline focus on the assessment of sTILs using hematoxylin and eosin (H&E)-stained slides. According to the guideline, the pathologists use “eye balling” method on the H&E stained- slide for sTILs assessment. This method has low precision, poor interobserver reproducibility, and is time-consuming for a comprehensive evaluation, besides only counted sTILs in their assessment. The TIL-WG has therefore recommended that any algorithm for computational assessment of TILs utilizing the guidelines provided to overcome the limitations of manual assessment, thus providing highly accurate and reliable TILs detection and classification for reproducible and quantitative measurement. This study is carried out to develop a TNBC digital whole slide image (WSI) dataset from H&E-stained slides and IHC (CD4+ and CD8+) stained slides. TNBC cases were retrieved from the database of the Department of Pathology, Hospital Canselor Tuanku Muhriz (HCTM). TNBC cases diagnosed between the year 2010 and 2021 with no history of other cancer and available block tissue were included in the study (n=58). Tissue blocks were sectioned approximately 4 µm for H&E and IHC stain. The H&E staining was performed according to a well-established protocol. Indirect IHC stain was also performed on the tissue sections using protocol from Diagnostic BioSystems PolyVue™ Plus Kit, USA. The slides were stained with rabbit monoclonal, CD8 antibody (SP16) and Rabbit monoclonal, CD4 antibody (EP204). The selected and quality-checked slides were then scanned using a high-resolution whole slide scanner (Pannoramic DESK II DW- slide scanner) to digitalize the tissue image with a pixel resolution of 20x magnification. A manual TILs (sTILs and iTILs) assessment was then carried out by the appointed pathologist (2 pathologists) for manual TILs scoring from the digital WSIs following the guideline developed by TIL-WG 2014, and the result displayed as the percentage of sTILs and iTILs per mm² stromal and tumour area on the tissue. Following this, we aimed to develop an automated digital image scoring framework that incorporates key elements of manual guidelines (including both sTILs and iTILs) using manually annotated data for robust and objective quantification of TILs in TNBC. From the study, we have developed a digital dataset of TNBC H&E and IHC (CD4+ and CD8+) stained slides. We hope that an automated based scoring method can provide quantitative and interpretable TILs scoring, which correlates with the manual pathologist-derived sTILs and iTILs scoring and thus has potential prognostic implications.

Keywords: automated quantification, digital pathology, triple negative breast cancer, tumour infiltrating lymphocytes

Procedia PDF Downloads 81

Authors: Leah Li Echiverri, Haoyu Shang, Yue Li

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Wenzhou-Kean University (WKU) is a Sino-US Cooperative University in China. It practices the English Immersion Program (EIP), where all the courses are taught in English. Class discussions and presentations are pervasively interwoven in designing students’ learning experiences. This WKU model has brought positive influences on students and is in some way ahead of traditional college English majors. However, literature to support the perceptions on the positive outcomes of this teaching and learning model remain scarce. The distinctive profile of Chinese-ESL students in an English Medium of Instruction (EMI) environment contributes further to the scarcity of literature compared to existing studies conducted among ESL learners in Western educational settings. Hence, the study investigated the students’ perceptions towards the English Immersion Program and determine how it influences Chinese-ESL students’ academic performance (AP). This research can provide empirical data that would be helpful to educators, teaching practitioners, university administrators, and other researchers in making informed decisions when developing curricular reforms, instructional and pedagogical methods, and university-wide support programs using this educational model. The purpose of the study was to establish the relationship between the English Immersion Program and Academic Performance among Chinese-ESL students enrolled at WKU for the academic year 2020-2021. Course length, immersion location, course type, and instructional design were the constructs of the English immersion program. English language learning, learning efficiency, and class participation were used to measure academic performance. Descriptive-correlational design was used in this cross-sectional research project. A quantitative approach for data analysis was applied to determine the relationship between the English immersion program and Chinese-ESL students’ academic performance. The research was conducted at WKU; a Chinese-American jointly established higher educational institution located in Wenzhou, Zhejiang province. Convenience, random, and snowball sampling of 283 students, a response rate of 10.5%, were applied to represent the WKU student population. The questionnaire was posted through the survey website named Wenjuanxing and shared to QQ or WeChat. Cronbach’s alpha was used to test the reliability of the research instrument. Findings revealed that when professors integrate technology (PowerPoint, videos, and audios) in teaching, students pay more attention. This contributes to the acquisition of more professional knowledge in their major courses. As to course immersion, students perceive WKU as a good place to study, providing them a high degree of confidence to talk with their professors in English. This also contributes to their English fluency and better pronunciation in their communication. In the construct of designing instruction, the use of pictures, video clips, and professors’ non-verbal communication, and demonstration of concern for students encouraged students to be more active in-class participation. Findings on course length and academic performance indicated that students’ perception regarding taking courses during fall and spring terms can moderately contribute to their academic performance. In conclusion, the findings revealed a significantly strong positive relationship between course type, immersion location, instructional design, and academic performance.

Keywords: class participation, English immersion program, English language learning, learning efficiency

Procedia PDF Downloads 146

Authors: Fadi Al Khatib, Raouf Mbarki, Malek Adouni

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In various sport and recreational activities, the patellofemoral joint undergoes large forces and moments while accommodating the significant knee joint movement. In doing so, this joint is commonly the source of anterior knee pain related to instability in normal patellar tracking and excessive pressure syndrome. One well-observed explanation of the instability of the normal patellar tracking is the patellofemoral ligaments and patellar tendon damage. Improved knowledge of the damage mechanism mediating ligaments and tendon injuries can be a great help not only in rehabilitation and prevention procedures but also in the design of better reconstruction systems in the management of knee joint disorders. This damage mechanism, specifically due to excessive mechanical loading, has been linked to the micro level of the fibred structure precisely to the tropocollagen molecules and their connection density. We argue defining a clear frame starting from the bottom (micro level) to up (macro level) in the hierarchies of the soft tissue may elucidate the essential underpinning on the state of the ligaments damage. To do so, in this study a multiscale fibril reinforced hyper elastoplastic Finite Element model that accounts for the synergy between molecular and continuum syntheses was developed to determine the short-term stresses/strains patellofemoral ligaments and tendon response. The plasticity of the proposed model is associated only with the uniaxial deformation of the collagen fibril. The yield strength of the fibril is a function of the cross-link density between tropocollagen molecules, defined here by a density function. This function obtained through a Coarse-graining procedure linking nanoscale collagen features and the tissue level materials properties using molecular dynamics simulations. The hierarchies of the soft tissues were implemented using the rule of mixtures. Thereafter, the model was calibrated using a statistical calibration procedure. The model then implemented into a real structure of patellofemoral ligaments and patellar tendon (OpenKnee) and simulated under realistic loading conditions. With the calibrated material parameters the calculated axial stress lies well with the experimental measurement with a coefficient of determination (R2) equal to 0.91 and 0.92 for the patellofemoral ligaments and the patellar tendon respectively. The ‘best’ prediction of the yielding strength and strain as compared with the reported experimental data yielded when the cross-link density between the tropocollagen molecule of the fibril equal to 5.5 ± 0.5 (patellofemoral ligaments) and 12 (patellar tendon). Damage initiation of the patellofemoral ligaments was located at the femoral insertions while the damage of the patellar tendon happened in the middle of the structure. These predicted finding showed a meaningful correlation between the cross-link density of the tropocollagen molecules and the stiffness of the connective tissues of the extensor mechanism. Also, damage initiation and propagation were documented with this model, which were in satisfactory agreement with earlier observation. To the best of our knowledge, this is the first attempt to model ligaments from the bottom up, predicted depending to the tropocollagen cross-link density. This approach appears more meaningful towards a realistic simulation of a damaging process or repair attempt compared with certain published studies.

Keywords: tropocollagen, multiscale model, fibrils, knee ligaments

Procedia PDF Downloads 102

Authors: Pomozova Kseniia, Gorlachev Gennadiy, Chernyaev Aleksandr, Golanov Andrey

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In clinical practice, and especially in stereotactic radiosurgery planning, the significance of diffusion-weighted imaging (DWI) is growing. This makes the existence of software capable of quickly processing and reliably visualizing diffusion data, as well as equipped with tools for their analysis in terms of different tasks. We are developing the «MRDiffusionImaging» software on the standard C++ language. The subject part has been moved to separate class libraries and can be used on various platforms. The user interface is Windows WPF (Windows Presentation Foundation), which is a technology for managing Windows applications with access to all components of the .NET 5 or .NET Framework platform ecosystem. One of the important features is the use of a declarative markup language, XAML (eXtensible Application Markup Language), with which you can conveniently create, initialize and set properties of objects with hierarchical relationships. Graphics are generated using the DirectX environment. The MRDiffusionImaging software package has been implemented for processing diffusion magnetic resonance imaging (dMRI), which allows loading and viewing images sorted by series. An algorithm for "masking" dMRI series based on T2-weighted images was developed using a deformable surface model to exclude tissues that are not related to the area of interest from the analysis. An algorithm of distortion correction using deformable image registration based on autocorrelation of local structure has been developed. Maximum voxel dimension was 1,03 ± 0,12 mm. In an elementary brain's volume, the diffusion tensor is geometrically interpreted using an ellipsoid, which is an isosurface of the probability density of a molecule's diffusion. For the first time, non-parametric intensity distributions, neighborhood correlations, and inhomogeneities are combined in one segmentation of white matter (WM), grey matter (GM), and cerebrospinal fluid (CSF) algorithm. A tool for calculating the coefficient of average diffusion and fractional anisotropy has been created, on the basis of which it is possible to build quantitative maps for solving various clinical problems. Functionality has been created that allows clustering and segmenting images to individualize the clinical volume of radiation treatment and further assess the response (Median Dice Score = 0.963 ± 0,137). White matter tracts of the brain were visualized using two algorithms: deterministic (fiber assignment by continuous tracking) and probabilistic using the Hough transform. The proposed algorithms test candidate curves in the voxel, assigning to each one a score computed from the diffusion data, and then selects the curves with the highest scores as the potential anatomical connections. White matter fibers were visualized using a Hough transform tractography algorithm. In the context of functional radiosurgery, it is possible to reduce the irradiation volume of the internal capsule receiving 12 Gy from 0,402 cc to 0,254 cc. The «MRDiffusionImaging» will improve the efficiency and accuracy of diagnostics and stereotactic radiotherapy of intracranial pathology. We develop software with integrated, intuitive support for processing, analysis, and inclusion in the process of radiotherapy planning and evaluating its results.

Keywords: diffusion-weighted imaging, medical imaging, stereotactic radiosurgery, tractography

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Authors: Carina Emminger, Umut D. Cakmak, Evrim Burkut, Rene Preuer, Ingrid Graz, Zoltan Major

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Damping accompanies us daily in everyday life and is used to protect (e.g., in shoes) and make our life more comfortable (damping of unwanted motion) and calm (noise reduction). In general, damping is the absorption of energy which is either stored in the material (vibration isolation systems) or changed into heat (vibration absorbers). In case of the last, the damping mechanism can be split in active, passive, as well as semi-active (a combination of active and passive). Active damping is required to enable an almost perfect damping over the whole application range and is used, for instance, in sport cars. In contrast, passive damping is a response of the material due to external loading. Consequently, the material composition has a huge influence on the damping behavior. For elastomers, the material behavior is inherent viscoelastic, temperature, and frequency dependent. However, passive damping is not adjustable during application. Therefore, it is of importance to understand the fundamental viscoelastic behavior and the dissipation capability due to external loading. The objective of this work is to assess the limitation and applicability of viscoelastic material damping for applications in which currently coil-over shock absorbers are utilized. Coil-over shock absorbers are usually made of various mechanical parts and incorporate fluids within the damper. These shock absorbers are well-known and studied in the industry, and when needed, they can be easily adjusted during their product lifetime. In contrary, dampers made of – ideally – a single material are more resource efficient, have an easier serviceability, and are easier manufactured. However, they lack of adaptability and adjustability in service. Therefore, a case study with a remote-controlled sport car was conducted. The original shock absorbers were redesigned, and the spring-dashpot system was replaced by both an elastomer and a thermoplastic-elastomer, respectively. Here, five different formulations of elastomers were used, including a pure and an iron-particle filled thermoplastic poly(urethan) (TPU) and blends of two different poly(dimethyl siloxane) (PDMS). In addition, the TPUs were investigated as full and hollow dampers to investigate the difference between solid and structured material. To get comparative results each material formulation was comprehensively characterized, by monotonic uniaxial compression tests, dynamic thermomechanical analysis (DTMA), and rebound resilience. Moreover, the new material-based shock absorbers were compared with spring-dashpot shock absorbers. The shock absorbers were analyzed under monotonic and cyclic loading. In addition, an impact loading was applied on the remote-controlled car to measure the damping properties in operation. A servo-hydraulic high-speed linear actuator was utilized to apply the loads. The acceleration of the car and the displacement of specific measurement points were recorded while testing by a sensor and high-speed camera, respectively. The results prove that elastomers are suitable in damping applications, but they are temperature and frequency dependent. This is a limitation in applicability of viscous material damper. Feasible fields of application may be in the case of micromobility, like bicycles, e-scooters, and e-skateboards. Furthermore, the viscous material damping could be used to increase the inherent damping of a whole structure, e.g., in bicycle-frames.

Keywords: damper structures, material damping, PDMS, TPU

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Authors: A. Newman-Tancredi, R. Depoortère, P. Gruca, E. Litwa, M. Lason, M. Papp

Abstract:

The N-methyl-D-aspartic acid (NMDA) receptor antagonist, ketamine, can elicit rapid-acting antidepressant (RAAD) effects in treatment-resistant patients, but it requires parenteral co-administration with a classical antidepressant under medical supervision. In addition, ketamine can also produce serious side effects that limit its long-term use, and there is much interest in identifying RAADs based on ketamine’s mechanism of action but with safer profiles. Ketamine elicits GABAergic interneuron inhibition, glutamatergic neuron stimulation, and, notably, activation of serotonin 5-HT1A receptors in the prefrontal cortex (PFC). Direct activation of the latter receptor subpopulation with selective ‘biased agonists’ may therefore be a promising strategy to identify novel RAADs and, consistent with this hypothesis, the prototypical cortical biased agonist, NLX-101, exhibited robust RAAD-like activity in the chronic mild stress model of depression (CMS). The present study compared the effects of a novel, selective 5-HT1A receptor-biased agonist, NLX-204, with those of ketamine and NLX-101. Materials and methods: CMS procedure was conducted on Wistar rats; drugs were administered either intraperitoneally (i.p.) or by bilateral intracortical microinjection. Ketamine: 10 mg/kg i.p. or 10 µg/side in PFC; NLX-204 and NLX-101: 0.08 and 0.16 mg/kg i.p. or 16 µg/side in PFC. In addition, interaction studies were carried out with systemic NLX-204 or NLX-101 (each at 0.16 mg/kg i.p.) in combination with intracortical WAY-100635 (selective 5-HT1A receptor antagonist; 2 µg/side) or muscimol (GABA-A receptor agonist, 12.5 ng/side). Anhedonia was assessed by CMS-induced decrease in sucrose solution consumption; anxiety-like behavior was assessed using the Elevated Plus Maze (EPM), and cognitive impairment was assessed by the Novel Object Recognition (NOR) test. Results: A single administration of NLX-204 was sufficient to reverse the CMS-induced deficit in sucrose consumption, similarly to ketamine and NLX-101. NLX-204 also reduced CMS-induced anxiety in the EPM and abolished CMS-induced NOR deficits. These effects were maintained (EPM and NOR) or enhanced (sucrose consumption) over a subsequent 2-week period of treatment. The anti-anhedonic response of the drugs was also maintained for several weeks Following treatment discontinuation, suggesting that they had sustained effects on neuronal networks. A single PFC administration of NLX-204 reversed deficient sucrose consumption, similarly to ketamine and NLX-101. Moreover, the anti-anhedonic activities of systemic NLX-204 and NLX 101 were abolished by coadministration with intracortical WAY-100635 or muscimol. Conclusions: (i) The antidepressant-like activity of NLX-204 in the rat CMS model was as rapid as that of ketamine or NLX-101, supporting targeting cortical 5-HT1A receptors with selective, biased agonists to achieve RAAD effects. (ii)The anti-anhedonic activity of systemic NLX-204 was mimicked by local administration of the compound in the PFC, confirming the involvement of cortical circuits in its RAAD-like effects. (iii) Notably, the effects of systemic NLX-204 and NLX-101 were abolished by PFC administration of muscimol, indicating that they act by (indirectly) eliciting a reduction in cortical GABAergic neurotransmission. This is consistent with ketamine’s mechanism of action and suggests that there are converging NMDA and 5-HT1A receptor signaling cascades in PFC underlying the RAAD-like activities of ketamine and NLX-204. Acknowledgements: The study was financially supported by NCN grant no. 2019/35/B/NZ7/00787.

Keywords: depression, ketamine, serotonin, 5-HT1A receptor, chronic mild stress

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Authors: John Lachapelle

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Introduction: Neural stimulation is increasingly targeted toward treatment of back pain, PTSD, Parkinson’s disease, and for sensory perception. Sensory recording during stimulation is important in order to examine neural response to stimulation. Most neural amplifiers (headstages) focus on noise efficiency factor (NEF). Conversely, neural headstages need to handle artifacts from several sources including power lines, movement (EMG), and neural stimulation itself. In this work a layered approach to artifact rejection is used to reduce corruption of the neural ENG signal by 60dBv, resulting in recovery of sensory signals in rats and primates that would previously not be possible. Methods: The approach combines analog techniques to reduce and handle unwanted signal amplitudes. The methods include optimized (1) sensory electrode placement, (2) amplifier configuration, and (3) artifact blanking when necessary. The techniques together are like concentric moats protecting a castle; only the wanted neural signal can penetrate. There are two conditions in which the headstage operates: unwanted artifact < 50mV, linear operation, and artifact > 50mV, fast-settle gain reduction signal limiting (covered in more detail in a separate paper). Unwanted Signals at the headstage input: Consider: (a) EMG signals are by nature < 10mV. (b) 60 Hz power line signals may be > 50mV with poor electrode cable conditions; with careful routing much of the signal is common to both reference and active electrode and rejected in the differential amplifier with <50mV remaining. (c) An unwanted (to the neural recorder) stimulation signal is attenuated from stimulation to sensory electrode. The voltage seen at the sensory electrode can be modeled Φ_m=I_o/4πσr. For a 1 mA stimulation signal, with 1 cm spacing between electrodes, the signal is <20mV at the headstage. Headstage ASIC design: The front end ASIC design is designed to produce < 1% THD at 50mV input; 50 times higher than typical headstage ASICs, with no increase in noise floor. This requires careful balance of amplifier stages in the headstage ASIC, as well as consideration of the electrodes effect on noise. The ASIC is designed to allow extremely small signal extraction on low impedance (< 10kohm) electrodes with configuration of the headstage ASIC noise floor to < 700nV/rt-Hz. Smaller high impedance electrodes (> 100kohm) are typically located closer to neural sources and transduce higher amplitude signals (> 10uV); the ASIC low-power mode conserves power with 2uV/rt-Hz noise. Findings: The enhanced neural processing ASIC has been compared with a commercial neural recording amplifier IC. Chronically implanted primates at MGH demonstrated the presence of commercial neural amplifier saturation as a result of large environmental artifacts. The enhanced artifact suppression headstage ASIC, in the same setup, was able to recover and process the wanted neural signal separately from the suppressed unwanted artifacts. Separately, the enhanced artifact suppression headstage ASIC was able to separate sensory neural signals from unwanted artifacts in mouse-implanted peripheral intrafascicular electrodes. Conclusion: Optimizing headstage ASICs allow observation of neural signals in the presence of large artifacts that will be present in real-life implanted applications, and are targeted toward human implantation in the DARPA HAPTIX program.

Keywords: ASIC, biosensors, biomedical signal processing, biomedical sensors

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Authors: Maria Lazari, Lorenzo Sanavia

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Mechanics of unsaturated soils has been an active field of research in the last decades. Efficient constitutive models that take into account the partial saturation of soil are necessary to solve a number of engineering problems e.g. instability of slopes and cuts due to heavy rainfalls. A large number of constitutive models can now be found in the literature that considers fundamental issues associated with the unsaturated soil behaviour, like the volume change and shear strength behaviour with suction or saturation changes. Partially saturated soils may either expand or collapse upon wetting depending on the stress level, and it is also possible that a soil might experience a reversal in the volumetric behaviour during wetting. Shear strength of soils also changes dramatically with changes in the degree of saturation, and a related engineering problem is slope failures caused by rainfall. There are several states of the art reviews over the last years for studying the topic, usually providing a thorough discussion of the stress state, the advantages, and disadvantages of specific constitutive models as well as the latest developments in the area of unsaturated soil modelling. However, only a few studies focused on the coupling between partial saturation states and time effects on the behaviour of geomaterials. Rate dependency is experimentally observed in the mechanical response of granular materials, and a viscoplastic constitutive model is capable of reproducing creep and relaxation processes. Therefore, in this work an elasto-viscoplastic constitutive model for unsaturated soils is proposed and validated on the basis of experimental data. The model constitutes an extension of an existing elastoplastic strain-hardening constitutive model capable of capturing the behaviour of variably saturated soils, based on energy conjugated stress variables in the framework of superposed continua. The purpose was to develop a model able to deal with possible mechanical instabilities within a consistent energy framework. The model shares the same conceptual structure of the elastoplastic laws proposed to deal with bonded geomaterials subject to weathering or diagenesis and is capable of modelling several kinds of instabilities induced by the loss of hydraulic bonding contributions. The novelty of the proposed formulation is enhanced with the incorporation of density dependent stiffness and hardening coefficients in order to allow the modeling of the pycnotropy behaviour of granular materials with a single set of material constants. The model has been implemented in the commercial FE platform PLAXIS, widely used in Europe for advanced geotechnical design. The algorithmic strategies adopted for the stress-point algorithm had to be revised to take into account the different approach adopted by PLAXIS developers in the solution of the discrete non-linear equilibrium equations. An extensive comparison between models with a series of experimental data reported by different authors is presented to validate the model and illustrate the capability of the newly developed model. After the validation, the effectiveness of the viscoplastic model is displayed by numerical simulations of a partially saturated slope failure of the laboratory scale and the effect of viscosity and degree of saturation on slope’s stability is discussed.

Keywords: PLAXIS software, slope, unsaturated soils, Viscoplasticity

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Authors: Adenike Adesanya, Nonthaphat Wong, Xiang-Yun Lan, Shea Ping Yip, Chien-Ling Huang

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Background: The most challenging mutation of the oncokinase BCR-ABL protein T315I, which is commonly known as the “gatekeeper” mutation and is notorious for its strong resistance to almost all tyrosine kinase inhibitors (TKIs), especially imatinib. Therefore, this study aims to identify T315I-dependent downstream microRNA (miRNA) pathways associated with drug resistance in chronic myeloid leukemia (CML) for prognostic and therapeutic purposes. Methods: T315I-carrying K562 cell clones (K562-T315I) were generated by the CRISPR-Cas9 system. Imatinib-treated K562-T315I cells were subjected to small RNA library preparation and next-generation sequencing. Putative lncRNA-miRNA-mRNA networks were analyzed with (i) DESeq2 to extract differentially expressed miRNAs, using Padj value of 0.05 as cut-off, (ii) STarMir to obtain potential miRNA response element (MRE) binding sites of selected miRNAs on lncRNA H19, (iii) miRDB, miRTarbase, and TargetScan to predict mRNA targets of selected miRNAs, (iv) IntaRNA to obtain putative interactions between H19 and the predicted mRNAs, (v) Cytoscape to visualize putative networks, and (vi) several pathway analysis platforms – Enrichr, PANTHER and ShinyGO for pathway enrichment analysis. Moreover, mitochondria isolation and transcript quantification were adopted to determine the new mechanism involved in T315I-mediated resistance of CML treatment. Results: Verification of the CRISPR-mediated mutagenesis with digital droplet PCR detected the mutation abundance of ≥80%. Further validation showed the viability of ≥90% by cell viability assay, and intense phosphorylated CRKL protein band being detected with no observable change for BCR-ABL and c-ABL protein expressions by Western blot. As reported by several investigations into hematological malignancies, we determined a 7-fold increase of H19 expression in K562-T315I cells. After imatinib treatment, a 9-fold increment was observed. DESeq2 revealed 171 miRNAs were differentially expressed K562-T315I, 112 out of these miRNAs were identified to have MRE binding regions on H19, and 26 out of the 112 miRNAs were significantly downregulated. Adopting the seed-sequence analysis of these identified miRNAs, we obtained 167 mRNAs. 6 hub miRNAs (hsa-let-7b-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-129-5p, and hsa-miR-372-3p) and 25 predicted genes were identified after constructing hub miRNA-target gene network. These targets demonstrated putative interactions with H19 lncRNA and were mostly enriched in pathways related to cell proliferation, senescence, gene silencing, and pluripotency of stem cells. Further experimental findings have also shown the up-regulation of mitochondrial transcript and lncRNA MALAT1 contributing to the lncRNA-miRNA-mRNA networks induced by BCR-ABL T315I mutation. Conclusions: Our results have indicated that lncRNA-miRNA regulators play a crucial role not only in leukemogenesis but also in drug resistance, considering the significant dysregulation and interactions in the K562-T315I cell model generated by CRISPR-Cas9. In silico analysis has further shown that lncRNAs H19 and MALAT1 bear several complementary miRNA sites. This implies that they could serve as a sponge, hence sequestering the activity of the target miRNAs.

Keywords: chronic myeloid leukemia, imatinib resistance, lncRNA-miRNA-mRNA, T315I mutation

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Authors: Palak V. Patel, Jessica Pixley, Steven R. Feldman

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Introduction: Basal cell carcinoma (BCC) is the most common skin cancer worldwide and requires substantial resources to treat. When choosing between indicated therapies, providers consider their associated adverse effects, efficacy, cosmesis, and function preservation. The patient’s tumor burden, infiltrative risk, and risk of tumor recurrence are also considered. Treatment cost is often left out of these discussions. This can lead to financial toxicity, which describes the harm and quality of life reductions inflicted by high care costs. Methods: We studied the guidelines set forth by the American Academy of Dermatology for the treatment of BCC. A PubMed literature search was conducted to identify the costs of each recommended therapy. We discuss costs alongside treatment efficacy and side-effect profile. Results: Surgical treatment for BCC can be cost-effective if the appropriate treatment is selected for the presenting tumor. Curettage and electrodesiccation can be used in low-grade, low-recurrence tumors in aesthetically unimportant areas. The benefits of cost-conscious care are not likely to be outweighed by the risks of poor cosmesis or tumor return ($471 BCC of the cheek). When tumor burden is limited, MMS offers better cure rates and lower recurrence rates than surgical excision, and with comparable costs (MMS $1263; SE $949). Surgical excision with permanent sections may be indicated when tumor burden is more extensive or if molecular testing is necessary. The utility of surgical excision with frozen sections, which costs substantially more than MMS without comparable outcomes, is less clear (SE with frozen sections $2334-$3085). Less data exists on non-surgical treatments for BCC. These techniques cost less, but recurrence-risk is high. Side-effects of nonsurgical treatment are limited to local skin reactions, and cosmesis is good. Cryotherapy, 5-FU, and MAL-PDT are all more affordable than surgery, but high recurrence rates increase risk of secondary financial and psychosocial burden (recurrence rates 21-39%; cost $100-270). Radiation therapy offers better clearance rates than other nonsurgical treatments but is associated with similar recurrence rates and a significantly larger financial burden ($2591-$3460 BCC of the cheek). Treatments for advanced or metastatic BCC are extremely costly, but few patients require their use, and the societal cost burden remains low. Vismodegib and sonidegib have good response rates but substantial side effects, and therapy should be combined with multidisciplinary care and palliative measures. Expert-review has found sonidegib to be the less expensive and more efficacious option (vismodegib $128,358; sonidegib $122,579). Platinum therapy, while not FDA-approved, is also effective but expensive (~91,435). Immunotherapy offers a new line of treatment in patients intolerant of hedgehog inhibitors ($683,061). Conclusion: Dermatologists working within resource-compressed practices and with resource-limited patients must prudently manage the healthcare dollar. Surgical therapies for BCC offer the lowest risk of recurrence at the most reasonable cost. Non-surgical therapies are more affordable, but high recurrence rates increase the risk of secondary financial and psychosocial burdens. Treatments for advanced BCC are incredibly costly, but the low incidence means the overall cost to the system is low.

Keywords: nonmelanoma skin cancer, basal cell skin cancer, squamous cell skin cancer, cost of care

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Authors: Ponchang Apollos Wuyep, Alice Njolke Mafe, Longchi Satkat Zacheaus, Dogun Ojochogu, Dabot Ayuba Yakubu

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Fungi causes huge losses when infections occur both in plants and animals. Synthetic Antifungal drugs are mostly very expensive and highly cytotoxic when taken. This study was aimed at determining the in vitro and in vivo antifungal activities of the leaves and stem extracts of Terminalia mantaly (Umbrella tree)H. Perrier on Aspergillus species in a bid to identify potential sources of cheap starting materials for the synthesis of new drugs to address the growing antimicrobial resistance. T. mantaly leave and stem powdered plant was extracted by fractionation using the method of solvent partition co-efficient in their graded form in the order n-hexane, Ethyl acetate, methanol and distilled water and phytochemical screening of each fraction revealed the presence of alkaloids, saponins, Tannins, flavonoids, carbohydrates, steroids, anthraquinones, cardiac glycosides and terpenoids in varying degrees. The Agar well diffusion technique was used to screen for antifungal activity of the fractions on clinical isolates of Aspergillus species (Aspergillus flavus and Aspergillus fumigatus). Minimum inhibitory concentration (MIC50) of the most active extracts was determined by the broth dilution method. The fractions test indicated a high antifungal activity with zones of inhibition ranging from 6 to 26 mm and 8 to 30mm (leave fractions) and 10mm to 34mm and 14mm to36mm (stem fractions) on A. flavus and A. fumigatus respectively. All the fractions indicated antifungal activity in a dose response relationship at concentrations of 62.5mg/ml, 125mg/ml, 250mg/ml and 500mg/ml. Better antifungal efficacy was shown by the Ethyl acetate, Hexane and Methanol fractions in the in vitro as the most potent fraction with MIC ranging from 62.5 to 125mg/ml. There was no statistically significant difference (P>0.05) in the potency of the Eight fractions from leave and stem (Hexane, Ethyl acetate, methanol and distilled water, antifungal (fluconazole), which served as positive control and 10% DMSO(Dimethyl Sulfoxide)which served as negative control. In the in vivo investigations, the ingestion technique was used for the infectious studies Female Drosophilla melanogaster(UAS-Diptericin)normal flies(positive control),infected and not treated flies (negative control) and infected flies with A. fumigatus and placed on normal diet, diet containing fractions(MSM and HSM each at concentrations of 10mg/ml 20mg/ml, 30mg/ml, 40mg/ml, 50mg/ml, 60mg/ml, 70mg/ml, 80mg/ml, 90mg/ml and 100mg/ml), diet containing control drugs(fluconazole as positive control)and infected flies on normal diet(negative control), the flies were observed for fifteen(15) days. Then the total mortality of flies was recorded each day. The results of the study reveals that the flies were susceptible to infection with A. fumigatus and responded to treatment with more effectiveness at 50mg/ml, 60mg/ml and 70mg/ml for both the Methanol and Hexane stem fractions. Therefore, the Methanol and Hexane stem fractions of T. mantaly contain therapeutically useful compounds, justifying the traditional use of this plant for the treatment of fungal infections.

Keywords: Terminalia mantaly, Aspergillus fumigatus, cytotoxic, Drosophila melanogaster, antifungal

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