Search results for: sensitivity

Authors: A. Arshad, M. Lehtonen. M. Humayun

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With the increasing Distributed Generation (DG) penetration, distribution systems are advancing towards the smart grid technology for least latency in tackling voltage control problem in a distributed manner. This paper proposes a Multi-agent based distributed voltage level control. In this method a flat architecture of agents is used and agents involved in the whole controlling procedure are On Load Tap Changer Agent (OLTCA), Static VAR Compensator Agent (SVCA), and the agents associated with DGs and loads at their locations. The objectives of the proposed voltage control model are to minimize network losses and DG curtailments while maintaining voltage value within statutory limits as close as possible to the nominal. The total loss cost is the sum of network losses cost, DG curtailment costs, and voltage damage cost (which is based on penalty function implementation). The total cost is iteratively calculated for various stricter limits by plotting voltage damage cost and losses cost against varying voltage limit band. The method provides the optimal limits closer to nominal value with minimum total loss cost. In order to achieve the objective of voltage control, the whole network is divided into multiple control regions; downstream from the controlling device. The OLTCA behaves as a supervisory agent and performs all the optimizations. At first, a token is generated by OLTCA on each time step and it transfers from node to node until the node with voltage violation is detected. Upon detection of such a node, the token grants permission to Load Agent (LA) for initiation of possible remedial actions. LA will contact the respective controlling devices dependent on the vicinity of the violated node. If the violated node does not lie in the vicinity of the controller or the controlling capabilities of all the downstream control devices are at their limits then OLTC is considered as a last resort. For a realistic study, simulations are performed for a typical Finnish residential medium-voltage distribution system using Matlab ®. These simulations are executed for two cases; simple Distributed Voltage Control (DVC) and DVC with optimized loss cost (DVC + Penalty Function). A sensitivity analysis is performed based on DG penetration. The results indicate that costs of losses and DG curtailments are directly proportional to the DG penetration, while in case 2 there is a significant reduction in total loss. For lower DG penetration, losses are reduced more or less 50%, while for higher DG penetration, loss reduction is not very significant. Another observation is that the newer stricter limits calculated by cost optimization moves towards the statutory limits of ±10% of the nominal with the increasing DG penetration as for 25, 45 and 65% limits calculated are ±5, ±6.25 and 8.75% respectively. Observed results conclude that the novel voltage control algorithm proposed in case 1 is able to deal with the voltage control problem instantly but with higher losses. In contrast, case 2 make sure to reduce the network losses through proposed iterative method of loss cost optimization by OLTCA, slowly with time.

Keywords: distributed voltage control, distribution system, multi-agent systems, smart grids

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Authors: Haftay Abraha Tadesse

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Background: Staphylococcus is a genus of worldwide distributed bacteria correlated to several infectious of different sites in humans and animals. They are among the most important causes of infection that are associated with the consumption of contaminated food. Objective: The objective of this study was to determine the isolates, antimicrobial susceptibility patterns and Public Health Significance of Staphylococcus aureus in raw meat from butchery and abattoir houses of Mekelle, Northern Ethiopia. Methodology: A cross-sectional study was conducted from April to October 2019. Socio-demographic data and Public Health Significance were collected using a predesigned questionnaire. The raw meat samples were collected aseptically in the butchery and abattoir houses and transported using an ice box to Mekelle University, College of Veterinary Sciences, for isolating and identification of Staphylococcus aureus. Antimicrobial susceptibility tests were determined by the disc diffusion method. Data obtained were cleaned and entered into STATA 22.0 and a logistic regression model with odds ratio was calculated to assess the association of risk factors with bacterial contamination. A P-value < 0.05 was considered statistically significant. Results: In the present study, 88 out of 250 (35.2%) were found to be contaminated with Staphylococcus aureus. Among the raw meat specimens, the positivity rate of Staphylococcus aureus was 37.6% (n=47) and (32.8% (n=41), butchery and abattoir houses, respectively. Among the associated risks, factories not using gloves reduces risk was found to (AOR=0.222; 95% CI: 0.104-0.473), Strict Separation b/n clean & dirty (AOR= 1.37; 95% CI: 0.66-2.86) and poor habit of hand washing (AOR=1.08; 95%CI: 0.35 3.35) was found to be statistically significant and have associated with Staphylococcus aureus contamination. All isolates of thirty-seven of Staphylococcus aureus were checked and displayed (100%) sensitive to doxycycline, trimethoprim, gentamicin, sulphamethoxazole, amikacin, CN, Co trimoxazole and nitrofurantoi. Whereas the showed resistance to cefotaxime (100%), ampicillin (87.5%), Penicillin (75%), B (75%), and nalidixic acid (50%) from butchery houses. On the other hand, all isolates of Staphylococcus aureus isolate 100% (n= 10) showed sensitive chloramphenicol, gentamicin and nitrofurantoin, whereas they showed 100% resistance of Penicillin, B, AMX, ceftriaxone, ampicillin and cefotaxime from abattoirs houses. The overall multi-drug resistance pattern for Staphylococcus aureus was 90% and 100% of butchery and abattoir houses, respectively. Conclusion: 35.3% Staphylococcus aureus isolated were recovered from the raw meat samples collected from the butchery and abattoirs houses. More has to be done in the development of hand washing behavior and availability of safe water in the butchery houses to reduce the burden of bacterial contamination. The results of the present finding highlight the need to implement protective measures against the levels of food contamination and alternative drug options. The development of antimicrobial resistance is nearly always a result of repeated therapeutic and/or indiscriminate use of them. Regular antimicrobial sensitivity testing helps to select effective antibiotics and to reduce the problems of drug resistance development towards commonly used antibiotics.

Keywords: abattoir house, AMR, butchery house, S. aureus

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Authors: Rodrigo Calili, Anna Carolina Sermarini, João Henrique Azevedo, Vanessa Cardoso de Albuquerque, Felipe Gonçalves, Gilberto Jannuzzi

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The diffusion of Distributed Energy Resources (DER) has caused structural changes in the relationship between consumers and electrical systems. The Photovoltaic Distributed Generation (PVDG), in particular, is an essential strategy for achieving the 2030 Agenda goals, especially SDG 7 and SDG 13. However, it is observed that most projects involving this technology in Brazil are restricted to the wealthiest classes of society, not yet reaching the low-income population, aligned with theories of energy justice. Considering the research for energy equality, one of the policies adopted by governments is the social electricity tariff (SET), which provides discounts on energy tariffs/bills. However, just granting this benefit may not be effective, and it is possible to merge it with DER technologies, such as the PVDG. Thus, this work aims to evaluate the economic viability of the policy to replace the social electricity tariff (the current policy aimed at the low-income population in Brazil) by PVDG projects. To this end, a proprietary methodology was developed that included: mapping the stakeholders, identifying critical variables, simulating policy options, and carrying out an analysis in the Brazilian context. The simulation answered two key questions: in which municipalities low-income consumers would have lower bills with PVDG compared to SET; which consumers in a given city would have increased subsidies, which are now provided for solar energy in Brazil and for the social tariff. An economic model was created for verifying the feasibility of the proposed policy in each municipality in the country, considering geographic issues (tariff of a particular distribution utility, radiation from a specific location, etc.). To validate these results, four sensitivity analyzes were performed: variation of the simultaneity factor between generation and consumption, variation of the tariff readjustment rate, zeroing CAPEX, and exemption from state tax. The behind-the-meter modality of generation proved to be more promising than the construction of a shared plant. However, although the behind-the-meter modality presents better results than the shared plant, there is a greater complexity in adopting this modality due to issues related to the infrastructure of the most vulnerable communities (e.g., precarious electrical networks, need to reinforce roofs). Considering the shared power plant modality, many opportunities are still envisaged since the risk of investing in such a policy can be mitigated. Furthermore, this modality can be an alternative due to the mitigation of the risk of default, as it allows greater control of users and facilitates the process of operation and maintenance. Finally, it was also found, that in some regions of Brazil, the continuity of the SET presents more economic benefits than its replacement by PVDG. However, the proposed policy offers many opportunities. For future works, the model may include other parameters, such as cost with low-income populations’ engagement, and business risk. In addition, other renewable sources of distributed generation can be studied for this purpose.

Keywords: low income, subsidy policy, distributed energy resources, energy justice

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Authors: Ha Phuong Tran, Feng Wang, Jo Dewulf, Hai Trung Huynh, Thomas Schaubroeck

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The fast increase and complex components have made waste of electrical and electronic equipment (or e-waste) one of the most problematic waste streams worldwide. Precise information on its size on national, regional and global level has therefore been highlighted as prerequisite to obtain a proper management system. However, this is a very challenging task, especially in developing countries where both formal e-waste management system and necessary statistical data for e-waste estimation, i.e. data on the production, sale and trade of electrical and electronic equipment (EEE), are often lacking. Moreover, there is an inflow of non-registered electronic and electric equipment, which ‘invisibly’ enters the EEE domestic market and then is used for domestic consumption. The non-registration/invisibility and (in most of the case) illicit nature of this flow make it difficult or even impossible to be captured in any statistical system. The e-waste generated from it is thus often uncounted in current e-waste estimation based on statistical market data. Therefore, this study focuses on enhancing e-waste estimation in developing countries and proposing a calculation pathway to quantify the magnitude of the non-registered EEE inflow. An advanced Input-Out Analysis model (i.e. the Sale–Stock–Lifespan model) has been integrated in the calculation procedure. In general, Sale-Stock-Lifespan model assists to improve the quality of input data for modeling (i.e. perform data consolidation to create more accurate lifespan profile, model dynamic lifespan to take into account its changes over time), via which the quality of e-waste estimation can be improved. To demonstrate the above objectives, a case study on televisions (TVs) in Vietnam has been employed. The results show that the amount of waste TVs in Vietnam has increased four times since 2000 till now. This upward trend is expected to continue in the future. In 2035, a total of 9.51 million TVs are predicted to be discarded. Moreover, estimation of non-registered TV inflow shows that it might on average contribute about 15% to the total TVs sold on the Vietnamese market during the whole period of 2002 to 2013. To tackle potential uncertainties associated with estimation models and input data, sensitivity analysis has been applied. The results show that both estimations of waste and non-registered inflow depend on two parameters i.e. number of TVs used in household and the lifespan. Particularly, with a 1% increase in the TV in-use rate, the average market share of non-register inflow in the period 2002-2013 increases 0.95%. However, it decreases from 27% to 15% when the constant unadjusted lifespan is replaced by the dynamic adjusted lifespan. The effect of these two parameters on the amount of waste TV generation for each year is more complex and non-linear over time. To conclude, despite of remaining uncertainty, this study is the first attempt to apply the Sale-Stock-Lifespan model to improve the e-waste estimation in developing countries and to quantify the non-registered EEE inflow to domestic consumption. It therefore can be further improved in future with more knowledge and data.

Keywords: e-waste, non-registered electrical and electronic equipment, TVs, Vietnam

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Authors: Tayebeh Sahraeibelverdi, Ahmad Shirazi Hadi Veladi, Mazdak Radmalekshah

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Optical sensors became attractive due to preciseness, low power consumption, and intrinsic electromagnetic interference-free characteristic. Among the waveguide optical sensors, cavity-based ones attended for the high Q-factor. Micro ring resonators as a potential platform have been investigated for various applications as biosensors to pressure sensors thanks to their sensitive ring structure responding to any small change in the refractive index. Furthermore, these small micron size structures can come in an array, bringing the opportunity to have any of the resonance in a specific wavelength and be addressed in this way. Another exciting application is applying a strain to the ring and making them an optical strain gauge where the traditional ones are based on the piezoelectric material. Making them in arrays needs electrical wiring and about fifty times bigger in size. Any physical element that impacts the waveguide cross-section, Waveguide elastic-optic property change, or ring circumference can play a role. In comparison, ring size change has a larger effect than others. Here an engineered ring structure is investigated to study the strain effect on the ring resonance wavelength shift and its potential for more sensitive strain devices. At the same time, these devices can measure any strain by mounting on the surface of interest. The idea is to change the" O" shape ring to a "C" shape ring with a small opening starting from 2π/360 or one degree. We used the Mode solution of Lumbrical software to investigate the effect of changing the ring's opening and the shift induced by applied strain. The designed ring radius is a three Micron silicon on isolator ring which can be fabricated by standard complementary metal-oxide-semiconductor (CMOS) micromachining. The measured wavelength shifts from1-degree opening of the ring to a 6-degree opening have been investigated. Opening the ring for 1-degree affects the ring's quality factor from 3000 to 300, showing an order of magnitude Q-factor reduction. Assuming a strain making the ring-opening from 1 degree to 6 degrees, our simulation results showing negligible Q-factor reduction from 300 to 280. A ring resonator quality factor can reach up to 108 where an order of magnitude reduction is negligible. The resonance wavelength shift showed a blue shift and was obtained to be 1581, 1579,1578,1575nm for 1-, 2-, 4- and 6-degree ring-opening, respectively. This design can find the direction of the strain-induced by applying the opening on different parts of the ring. Moreover, by addressing the specified wavelength, we can precisely find the direction. We can open a significant opportunity to find cracks and any surface mechanical property very specifically and precisely. This idea can be implemented on polymer ring resonators while they can come with a flexible substrate and can be very sensitive to any strain making the two ends of the ring in the slit part come closer or further.

Keywords: optical ring resonator, strain gauge, strain sensor, surface mechanical property analysis

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Authors: Dmitriy Babenko, Sergey Yegorov, Ilya Korshukov, Aidana Sultanbekova, Valentina Barkhanskaya, Tatiana Bashirova, Yerzhan Zhunusov, Yevgeniya Li, Viktoriya Parakhina, Svetlana Kolesnichenko, Yeldar Baiken, Aruzhan Pralieva, Zhibek Zhumadilova, Matthew S. Miller, Gonzalo H. Hortelano, Anar Turmuhambetova, Antonella E. Chesca, Irina Kadyrova

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Introduction: The rapidly evolving COVID-19 pandemic, along with the re-emergence of pathogens causing acute respiratory infections (ARI), has necessitated the development of novel diagnostic tools to differentiate various causes of ARI. MALDI-MS, due to its wide usage and affordability, has been proposed as a potential instrument for diagnosing SARS-CoV-2 versus non-SARS-CoV-2 ARI. The aim of this study was to investigate the potential of MALDI-MS in conjunction with a machine learning model to accurately distinguish between symptomatic infections caused by SARS-CoV-2 and non-SARS-CoV-2 during both the early and later phases of the pandemic. Furthermore, this study aimed to analyze mass spectrometry (MS) data obtained from nasal swabs of healthy individuals. Methods: We gathered mass spectra from 252 samples, comprising 108 SARS-CoV-2-positive samples obtained in 2020 (Covid 2020), 7 SARS-CoV- 2-positive samples obtained in 2023 (Covid 2023), 71 samples from symptomatic individuals without SARS-CoV-2 (Control non-Covid ARVI), and 66 samples from healthy individuals (Control healthy). All the samples were subjected to RT-PCR testing. For data analysis, we employed the caret R package to train and test seven machine-learning algorithms: C5.0, KNN, NB, RF, SVM-L, SVM-R, and XGBoost. We conducted a training process using a five-fold (outer) nested repeated (five times) ten-fold (inner) cross-validation with a randomized stratified splitting approach. Results: In this study, we utilized the Covid 2020 dataset as a case group and the non-Covid ARVI dataset as a control group to train and test various machine learning (ML) models. Among these models, XGBoost and SVM-R demonstrated the highest performance, with accuracy values of 0.97 [0.93, 0.97] and 0.95 [0.95; 0.97], specificity values of 0.86 [0.71; 0.93] and 0.86 [0.79; 0.87], and sensitivity values of 0.984 [0.984; 1.000] and 1.000 [0.968; 1.000], respectively. When examining the Covid 2023 dataset, the Naive Bayes model achieved the highest classification accuracy of 43%, while XGBoost and SVM-R achieved accuracies of 14%. For the healthy control dataset, the accuracy of the models ranged from 0.27 [0.24; 0.32] for k-nearest neighbors to 0.44 [0.41; 0.45] for the Support Vector Machine with a radial basis function kernel. Conclusion: Therefore, ML models trained on MALDI MS of nasopharyngeal swabs obtained from patients with Covid during the initial phase of the pandemic, as well as symptomatic non-Covid individuals, showed excellent classification performance, which aligns with the results of previous studies. However, when applied to swabs from healthy individuals and a limited sample of patients with Covid in the late phase of the pandemic, ML models exhibited lower classification accuracy.

Keywords: SARS-CoV-2, MALDI-TOF MS, ML models, nasopharyngeal swabs, classification

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Authors: Mercedes Bertotto, Marcelo Bello, Hector Goicoechea, Veronica Fusca

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The National Service of Agri-Food Health and Quality (SENASA), controls honey to detect contamination by synthetic or natural chemical substances and establishes and controls the traceability of the product. The utility of near-infrared spectroscopy for the detection of adulteration of honey with high fructose corn syrup (HFCS) was investigated. First of all, a mixture of different authentic artisanal Argentinian honey was prepared to cover as much heterogeneity as possible. Then, mixtures were prepared by adding different concentrations of high fructose corn syrup (HFCS) to samples of the honey pool. 237 samples were used, 108 of them were authentic honey and 129 samples corresponded to honey adulterated with HFCS between 1 and 10%. They were stored unrefrigerated from time of production until scanning and were not filtered after receipt in the laboratory. Immediately prior to spectral collection, honey was incubated at 40°C overnight to dissolve any crystalline material, manually stirred to achieve homogeneity and adjusted to a standard solids content (70° Brix) with distilled water. Adulterant solutions were also adjusted to 70° Brix. Samples were measured by NIR spectroscopy in the range of 650 to 7000 cm⁻¹. The technique of specular reflectance was used, with a lens aperture range of 150 mm. Pretreatment of the spectra was performed by Standard Normal Variate (SNV). The ant colony optimization genetic algorithm sample selection (ACOGASS) graphical interface was used, using MATLAB version 5.3, to select the variables with the greatest discriminating power. The data set was divided into a validation set and a calibration set, using the Kennard-Stone (KS) algorithm. A combined method of Potential Functions (PF) was chosen together with Partial Least Square Linear Discriminant Analysis (PLS-DA). Different estimators of the predictive capacity of the model were compared, which were obtained using a decreasing number of groups, which implies more demanding validation conditions. The optimal number of latent variables was selected as the number associated with the minimum error and the smallest number of unassigned samples. Once the optimal number of latent variables was defined, we proceeded to apply the model to the training samples. With the calibrated model for the training samples, we proceeded to study the validation samples. The calibrated model that combines the potential function methods and PLSDA can be considered reliable and stable since its performance in future samples is expected to be comparable to that achieved for the training samples. By use of Potential Functions (PF) and Partial Least Square Linear Discriminant Analysis (PLS-DA) classification, authentic honey and honey adulterated with HFCS could be identified with a correct classification rate of 97.9%. The results showed that NIR in combination with the PT and PLS-DS methods can be a simple, fast and low-cost technique for the detection of HFCS in honey with high sensitivity and power of discrimination.

Keywords: adulteration, multivariate analysis, potential functions, regression

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Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin

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Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.

Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis

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Authors: Tibor Ajtai, Noémi Utry, Máté Pintér, Tomi Smausz, Zoltán Kónya, Béla Hopp, Gábor Szabó, Zoltán Bozóki

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Characterization of spectral responses of light absorbing carbonaceous particulate matter (LAC) is of great importance in both modelling its climate effect and interpreting remote sensing measurement data. The residential or domestic combustion of coal is one of the dominant LAC constituent. According to some related assessments the residential coal burning account for roughly half of anthropogenic BC emitted from fossil fuel burning. Despite of its significance in climate the comprehensive investigation of optical properties of residential coal aerosol is really limited in the literature. There are many reason of that starting from the difficulties associated with the controlled burning conditions of the fuel, through the lack of detailed supplementary proximate and ultimate chemical analysis enforced, the interpretation of the measured optical data, ending with many analytical and methodological difficulties regarding the in-situ measurement of coal aerosol spectral responses. Since the gas matrix of ambient can significantly mask the physicochemical characteristics of the generated coal aerosol the accurate and controlled generation of residential coal particulates is one of the most actual issues in this research area. Most of the laboratory imitation of residential coal combustion is simply based on coal burning in stove with ambient air support allowing one to measure only the apparent spectral feature of the particulates. However, the recently introduced methodology based on a laser ablation of solid coal target opens up novel possibilities to model the real combustion procedure under well controlled laboratory conditions and makes the investigation of the inherent optical properties also possible. Most of the methodology for spectral characterization of LAC is based on transmission measurement made of filter accumulated aerosol or deduced indirectly from parallel measurements of scattering and extinction coefficient using free floating sampling. In the former one the accuracy while in the latter one the sensitivity are liming the applicability of this approaches. Although the scientific community are at the common platform that aerosol-phase PhotoAcoustic Spectroscopy (PAS) is the only method for precise and accurate determination of light absorption by LAC, the PAS based instrumentation for spectral characterization of absorption has only been recently introduced. In this study, the investigation of the inherent, spectral features of laser generated and chemically characterized residential coal aerosols are demonstrated. The experimental set-up and its characteristic for residential coal aerosol generation are introduced here. The optical absorption and the scattering coefficients as well as their wavelength dependency are determined by our state-of-the-art multi wavelength PAS instrument (4λ-PAS) and multi wavelength cosinus sensor (Aurora 3000). The quantified wavelength dependency (AAE and SAE) are deduced from the measured data. Finally, some correlation between the proximate and ultimate chemical as well as the measured or deduced optical parameters are also revealed.

Keywords: absorption, scattering, residential coal, aerosol generation by laser ablation

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Authors: Gopalasingam Daisan

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Landmines and ammunitions have been creating a significant threat to the people and animals, after the war, the landmines remain in the land and it plays a vital role in civilian’s security. Especially the Children are at the highest risk because they are curious. After all, an unexploded bomb can look like a tempting toy to an inquisitive child. The initial step of designing the UAS (Unmanned Aircraft Systems) for landmine detection is to choose an appropriate and effective sensor to locate the landmines and other unexploded ammunitions. The sensor weight and other components related to the sensor supporting device’s weight are taken as a payload weight. The mission requirement is to find the landmines in a particular area by making a proper path that will cover all the vicinity in the desired area. The weight estimation of the UAV (Unmanned Aerial Vehicle) can be estimated by various techniques discovered previously with good accuracy at the first phase of the design. The next crucial part of the design is to calculate the power requirement and the wing loading calculations. The matching plot techniques are used to determine the thrust-to-weight ratio, and this technique makes this process not only easiest but also precisely. The wing loading can be calculated easily from the stall equation. After these calculations, the wing area is determined from the wing loading equation and the required power is calculated from the thrust to weight ratio calculations. According to the power requirement, an appropriate engine can be selected from the available engine from the market. And the wing geometric parameter is chosen based on the conceptual sketch. The important steps in the wing design to choose proper aerofoil and which will ensure to create sufficient lift coefficient to satisfy the requirements. The next component is the tail; the tail area and other related parameters can be estimated or calculated to counteract the effect of the wing pitching moment. As the vertical tail design depends on many parameters, the initial sizing only can be done in this phase. The fuselage is another major component, which is selected based on the slenderness ratio, and also the shape is determined on the sensor size to fit it under the fuselage. The landing gear is one of the important components which is selected based on the controllability and stability requirements. The minimum and maximum wheel track and wheelbase can be determined based on the crosswind and overturn angle requirements. The minor components of the landing gear design and estimation are not the focus of this project. Another important task is to calculate the weight of the major components and it is going to be estimated using empirical relations and also the mass is added to each such component. The CG and moment of inertia are also determined to each component separately. The sensitivity of the weight calculation is taken into consideration to avoid extra material requirements and also reduce the cost of the design. Finally, the aircraft performance is calculated, especially the V-n (velocity and load factor) diagram for different flight conditions such as not disturbed and with gust velocity.

Keywords: landmine, UAS, matching plot, optimization

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Authors: Saiful Islam, Deuk Jong Bae

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The purpose of this study is to examine citizen satisfaction and competitiveness of a Public Private Partnership project. The study focuses on PPP in the transport sector and investigates the New Bundang Subway Line (NBL) in South Korea as the object of a case study. Most PPP studies are dominated by the study of public and private sector interests, which are classified in to three major areas comprising of policy, finance, and management. This study will explore the user perspective by assessing customer satisfaction upon NBL cost and service quality, also the competitiveness of NBL compared to other alternative transport modes which serve the Jeongja – Gangnam trip or vice versa. The regular Bundang Subway Line, New Bundang Subway Line, bus and private vehicle are selected as the alternative transport modes. The study analysed customer satisfaction of NBL and citizen’s preference of alternative transport modes based on a survey in Bundang district, South Korea. Respondents were residents and employees who live or work in Bundang city, and were divided into the following areas Pangyo, Jeongjae – Sunae, Migeun – Ori – Jukjeon, and Imae – Yatap – Songnam. The survey was conducted in January 2015 for two weeks, and 753 responses were gathered. By applying the Hedonic Utility approach, the factors which affect the frequency of using NBL were found to be overall customer satisfaction, convenience of access, and the socio economic demographic of the individual. In addition, by applying the Analytic Hierarchy Process (AHP) method, criteria factors influencing the decision to select alternative transport modes were identified. Those factors, along with the author judgement of alternative transport modes, and their associated criteria and sub-criteria produced a priority list of user preferences regarding their alternative transport mode options. The study found that overall the regular Bundang Subway Line (BL), which was built and operated under a conventional procurement method was selected as the most preferable transport mode due to its cost competitiveness. However, on the sub-criteria level analysis, the NBL has competitiveness on service quality, particularly on journey time. By conducting a sensitivity analysis, the NBL can become the first choice of transport by increasing the NBL’s degree of weight associated with cost by 0,05. This means the NBL would need to reduce either it’s fare cost or transfer fee, or combine those two cost components to reduce the total of the current cost by 25%. In addition, the competitiveness of NBL also could be obtained by increasing NBL convenience through escalating access convenience such as constructing an additional station or providing more access modes. Although these convenience improvements would require a few extra minutes of journey time, the user found this to be acceptable. The findings and policy suggestions can contribute to the next phase of NBL development, showing that consideration should be given to the citizen’s voice. The case study results also contribute to the literature of PPP projects specifically from a user side perspective.

Keywords: public private partnership, customer satisfaction, public transport, new Bundang subway line

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Authors: Adrien Chatel, Ehsan Askari Mahvelati, Laurent Fitschy

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Once-Through-Steam-Generators are commonly used in the oil-sand industry in the heavy fuel oil extraction process. They are composed of three main parts: the burner, the radiant and convective sections. Natural gas is burned through staged diffusive flames stabilized by the burner. The heat generated by the combustion is transferred to the water flowing through the piping system in the radiant and convective sections. The steam produced within the pipes is then directed to the ground to reduce the oil viscosity and allow its pumping. With the rapid development of the oil-sand industry, the number of OTSG in operation has increased as well as the associated emissions of environmental pollutants, especially the Nitrous Oxides (NOₓ). To limit the environmental degradation, various international environmental agencies have established regulations on the pollutant discharge and pushed to reduce the NOₓ release. To meet these constraints, OTSG constructors have to rely on more and more advanced tools to study and predict the NOₓ emission. With the increase of the computational resources, Computational Fluid Dynamics (CFD) has emerged as a flexible tool to analyze the combustion and pollutant formation process. Moreover, to optimize the burner operating condition regarding the NOx emission, field characterization and measurements are usually accomplished. However, these kinds of experimental campaigns are particularly time-consuming and sometimes even impossible for industrial plants with strict operation schedule constraints. Therefore, the application of CFD seems to be more adequate in order to provide guidelines on the NOₓ emission and reduction problem. In the present work, two different software are employed to simulate the combustion process in an OTSG, namely the commercial software ANSYS Fluent and the open source software OpenFOAM. RANS (Reynolds-Averaged Navier–Stokes) equations combined with the Eddy Dissipation Concept to model the combustion and closed by the k-epsilon model are solved. A mesh sensitivity analysis is performed to assess the independence of the solution on the mesh. In the first part, the results given by the two software are compared and confronted with experimental data as a mean to assess the numerical modelling. Flame temperatures and chemical composition are used as reference fields to perform this validation. Results show a fair agreement between experimental and numerical data. In the last part, OpenFOAM is employed to simulate several operating conditions, and an Emission Characteristic Map of the combustion system is generated. The sources of high NOₓ production inside the OTSG are pointed and correlated to the physics of the flow. CFD is, therefore, a useful tool for providing an insight into the NOₓ emission phenomena in OTSG. Sources of high NOₓ production can be identified, and operating conditions can be adjusted accordingly. With the help of RANS simulations, an Emission Characteristics Map can be produced and then be used as a guide for a field tune-up.

Keywords: combustion, computational fluid dynamics, nitrous oxides emission, once-through-steam-generators

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Authors: Megan L. Srinivas

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Individuals with underlying rheumatologic diseases such as dermatomyositis may not adequately respond to tuberculin (PPD) skin tests, creating false negative results. These illnesses are frequently treated with immunosuppressive therapy making proper identification of TB infection imperative. A 59-year-old Filipino man was diagnosed with dermatomyositis on the basis of rash, electromyography, and muscle biopsy. He was initially treated with IVIG infusions and transitioned to oral prednisone and mycophenolate. The patient’s symptoms improved on this regimen. Six months after starting mycophenolate, the patient began having fevers, night sweats, and productive cough without hemoptysis. He moved from the Philippines 5 years prior to dermatomyositis diagnosis, denied sick contacts, and was PPD negative both at immigration and immediately prior to starting mycophenolate treatment. A third PPD was negative following the onset of these new symptoms. He was treated for community-acquired pneumonia, but symptoms worsened over 10 days and he developed watery diarrhea and a growing non-tender, non-mobile mass on the left side of his neck. A chest x-ray demonstrated a cavitary lesion in right upper lobe suspicious for TB that had not been present one month earlier. Chest CT corroborated this finding also exhibiting necrotic hilar and paratracheal lymphadenopathy. Neck CT demonstrated the left-sided mass as cervical chain lymphadenopathy. Expectorated sputum and stool samples contained acid-fast bacilli (AFB), cultures showing TB bacteria. Fine-needle biopsy of the neck mass (scrofula) also exhibited AFB. An MRI brain showed nodular enhancement suspected to be a tuberculoma. Mycophenolate was discontinued and dermatomyositis treatment was switched to oral prednisone with a 3-day course of IVIG. The patient’s infection showed sensitivity to standard RIPE (rifampin, isoniazid, pyrazinamide, and ethambutol) treatment. Within a week of starting RIPE, the patient’s diarrhea subsided, scrofula diminished, and symptoms significantly improved. By the end of treatment week 3, the patient’s sputum no longer contained AFB; he was removed from isolation, and was discharged to continue RIPE at home. He was discharged on oral prednisone, which effectively addressed his dermatomyositis. This case illustrates the unreliability of PPD tests in patients with long-term inflammatory diseases such as dermatomyositis. Other immunosuppressive therapies (adalimumab, etanercept, and infliximab) have been affiliated with conversion of latent TB to disseminated TB. Mycophenolate is another immunosuppressive agent with similar mechanistic properties. Thus, it is imperative that patients with long-term inflammatory diseases and high-risk TB factors initiating immunosuppressive therapy receive a TB blood test (such as a quantiferon gold assay) prior to the initiation of therapy to ensure that latent TB is unmasked before it can evolve into a disseminated form of the disease.

Keywords: dermatomyositis, immunosuppressant medications, mycophenolate, disseminated tuberculosis

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Authors: Pola Goldberg Oppenheimer, Stephan Hofmann, Sumeet Mahajan

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Owing to its fingerprint molecular specificity and high sensitivity, surface-enhanced Raman scattering (SERS) is an established analytical tool for chemical and biological sensing capable of single-molecule detection. A strong Raman signal can be generated from SERS-active platforms given the analyte is within the enhanced plasmon field generated near a noble-metal nanostructured substrate. The key requirement for generating strong plasmon resonances to provide this electromagnetic enhancement is an appropriate metal surface roughness. Controlling nanoscale features for generating these regions of high electromagnetic enhancement, the so-called SERS ‘hot-spots’, is still a challenge. Significant advances have been made in SERS research, with wide-ranging techniques to generate substrates with tunable size and shape of the nanoscale roughness features. Nevertheless, the development and application of SERS has been inhibited by the irreproducibility and complexity of fabrication routes. The ability to generate straightforward, cost-effective, multiplex-able and addressable SERS substrates with high enhancements is of profound interest for miniaturised sensing devices. Carbon nanotubes (CNTs) have been concurrently, a topic of extensive research however, their applications for plasmonics has been only recently beginning to gain interest. CNTs can provide low-cost, large-active-area patternable substrates which, coupled with appropriate functionalization capable to provide advanced SERS-platforms. Herein, advanced methods to generate CNT-based SERS active detection platforms will be discussed. First, a novel electrohydrodynamic (EHD) lithographic technique will be introduced for patterning CNT-polymer composites, providing a straightforward, single-step approach for generating high-fidelity sub-micron-sized nanocomposite structures within which anisotropic CNTs are vertically aligned. The created structures are readily fine-tuned, which is an important requirement for optimizing SERS to obtain the highest enhancements with each of the EHD-CNTs individual structural units functioning as an isolated sensor. Further, gold-functionalized VACNTFs are fabricated as SERS micro-platforms. The dependence on the VACNTs’ diameters and density play an important role in the Raman signal strength, thus highlighting the importance of structural parameters, previously overlooked in designing and fabricating optimized CNTs-based SERS nanoprobes. VACNTs forests patterned into predesigned pillar structures are further utilized for multiplex detection of bio-analytes. Since CNTs exhibit electrical conductivity and unique adsorption properties, these are further harnessed in the development of novel chemical and bio-sensing platforms.

Keywords: carbon nanotubes (CNTs), EHD patterning, SERS, vertically aligned carbon nanotube forests (VACNTF)

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Authors: Haftay Abraha Tadesse

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Background: Staphylococcus is a genus of worldwide distributed bacteria correlated to several infectious of different sites in human and animals. They are among the most important causes of infection that are associated with the consumption of contaminated food. Objective: The objective of this study was to determine the isolates, antimicrobial susceptibility patterns and public health significance for Staphylococcus aureus in raw meat from butchery and abattoir houses of Mekelle, Northern Ethiopia. Methodology: A cross-sectional study was conducted from April to October 2019. Sociodemographic data and public health significance were collected using predesigned questionnaire. The raw meat samples were collected aseptically in the butchery and abattoir houses and transported using ice box to Mekelle University, College of Veterinary Sciences for isolating and identification of Staphylococcus aureus. Antimicrobial susceptibility tests were determined by disc diffusion method. Data obtained were cleaned and entered in to STATA 22.0 and logistic regression model with odds ratio were calculated to assess the association of risk factors with bacterial contamination. P-value < 0.05 was considered as statistically significant. Results: In present study, 88 out of 250 (35.2%) were found to be contamination with Staphylococcus aureus. Among the raw meat specimens to be positivity rate of Staphylococcus aureus were 37.6% (n=47) and (32.8% (n=41), butchery and abattoir houses, respectively. Among the associated risk factories not using gloves reduces risk was found to (AOR=0.222; 95% CI: 0.104-0.473), Strict Separation b/n clean & dirty (AOR= 1.37; 95% CI: 0.66-2.86) and poor habit of hand washing (AOR=1.08; 95%CI: 0.35-3.35) were found to be statistically significant and ha ve associated with Staphylococcus aureus contamination. All isolates thirty sevevn of Staphyloco ccus aureus were checked displayed (100%) sensitive to doxycycline, trimethoprim, gentamicin, sulphamethoxazole, amikacin, CN, Co trimoxazole and nitrofurantoi. whereas the showed resistance of cefotaxime (100%), ampicillin (87.5%), Penicillin (75%), B (75%), and nalidixic acid (50%) from butchery houses. On the other hand, all isolates of Staphylococcus aur eu isolate 100% (n= 10) showed sensitive chloramphenicol, gentamicin and nitrofurantoin whereas the showed 100% resistance of Penicillin, B, AMX, ceftriaxone, ampicillin and cefotaxime from abattoirs houses. The overall multi drug resistance pattern for Staphylococcus aureus were 90% and 100% of butchery and abattoirs houses, respectively. Conclusion: 35.3% Staphylococcus aureus isolated were recovered from the raw meat samples collected from the butchery and abattoirs houses. More has to be done in the developed of hand washing behavior, and availability of safe water in the butchery houses to reduce burden of bacterial contamination. The results of the present finding highlight the need to implement protective measures against the levels of food contamination and alternative drug options. The development of antimicrobial resistance is nearly always as a result of repeated therapeutic and/or indiscriminate use of them. Regular antimicrobial sensitivity testing helps to select effective antibiotics and to reduce the problems of drug resistance development towards commonly used antibiotics. Key words: abattoir houses, antimicrobial resistance, butchery houses, Ethiopia,

Keywords: abattoir houses, antimicrobial resistance, butchery houses, Ethiopia, staphylococcus aureuse, MDR

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Authors: Ali Kazemi

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The digital evolution of financial services, while offering unprecedented convenience and accessibility, has also escalated the vulnerabilities to fraudulent activities. In this study, we introduce a distinct approach to real-time anomaly detection in financial transactions, aiming to fortify the defenses of banking and financial institutions against such threats. Utilizing unsupervised machine learning algorithms, specifically autoencoders and isolation forests, our research focuses on identifying irregular patterns indicative of fraud within transactional data, thus enabling immediate action to prevent financial loss. The data we used in this study included the monetary value of each transaction. This is a crucial feature as fraudulent transactions may have distributions of different amounts than legitimate ones, such as timestamps indicating when transactions occurred. Analyzing transactions' temporal patterns can reveal anomalies (e.g., unusual activity in the middle of the night). Also, the sector or category of the merchant where the transaction occurred, such as retail, groceries, online services, etc. Specific categories may be more prone to fraud. Moreover, the type of payment used (e.g., credit, debit, online payment systems). Different payment methods have varying risk levels associated with fraud. This dataset, anonymized to ensure privacy, reflects a wide array of transactions typical of a global banking institution, ranging from small-scale retail purchases to large wire transfers, embodying the diverse nature of potentially fraudulent activities. By engineering features that capture the essence of transactions, including normalized amounts and encoded categorical variables, we tailor our data to enhance model sensitivity to anomalies. The autoencoder model leverages its reconstruction error mechanism to flag transactions that deviate significantly from the learned normal pattern, while the isolation forest identifies anomalies based on their susceptibility to isolation from the dataset's majority. Our experimental results, validated through techniques such as k-fold cross-validation, are evaluated using precision, recall, and the F1 score alongside the area under the receiver operating characteristic (ROC) curve. Our models achieved an F1 score of 0.85 and a ROC AUC of 0.93, indicating high accuracy in detecting fraudulent transactions without excessive false positives. This study contributes to the academic discourse on financial fraud detection and provides a practical framework for banking institutions seeking to implement real-time anomaly detection systems. By demonstrating the effectiveness of unsupervised learning techniques in a real-world context, our research offers a pathway to significantly reduce the incidence of financial fraud, thereby enhancing the security and trustworthiness of digital financial services.

Keywords: anomaly detection, financial fraud, machine learning, autoencoders, isolation forest, transactional data analysis

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Authors: A. Moghadasein, M. Ghasemi, S. Fazelifar

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Aim: Chemerin is a novel adipokine that play an important role in regulating lipid metabolism and abiogenesis. Chemerin is dependent on autocrine and paracrine signals for the differentiation and maturation of fat cells; it also regulates glucose uptake in fat cells and stimulates lipolysis. It has been reported that in adipocytes, chemerin enhances the insulin-stimulated glucose and causes the phosphorylation of tyrosine in Insulin receptor substrate. According to the studies, Chemerin may increase insulin sensitivity in adipose tissue and is largely associated with Body mass index, triglycerides, and blood pressure in those with normal glucose tolerance. There is limited information available regarding the effect of exercise training on serum chemerin concentrations. The purpose of this study was to investigate the effect of endurance training on serum chemerin levels and lipids of plasma in overweight women. Methodology: This study was a quasi-experimental research with a pre-post test design. After required examination and verification of high pressure by the physician, 22 obese subjects (age: 35.64±5.55 yr, weight: 75.62±9.30 kg, body mass index: 32.4±1.6 kg/m2) were randomly assigned to aerobic training (n= 12) and control (n= 12) groups. Participants completed a questionnaire indicating the lack of sports history during the past six months, the lack of anti-hypertension drugs use, hormone therapy, cardiovascular problems, and complete stoppage of menstrual cycle. Aerobic training was performed 3 times weekly for 8 weeks. Resting levels of chemerin plasma, metabolic parameters were measured prior to and after the intervention. The control group did not participate in any training program. In this study, ethical considerations included the complete description of the objectives to the study participants, ensuring the confidentiality of their information. Kolmogorov-Smirnov and Levin test were used for determining the normal distribution of data and homogeneity of variances, respectively. Analyze of variance with repeated measure were used to investigate the changes in the intra-group and the differences in inter-group of variables. Statistical operations were performed using SPSS 16 and the significance level of the tests was considered at P < 0.05. Results: After an 8 week aerobic training, levels of chemerin plasma were significantly decreased in aerobic trained group when compared with their control groups (p < 0.05).Concurrently, levels of HDL-c were significantly decreased (p < 0.05) whereas, levels of cholesterol, TG and LDL-c, showed no significant changes (p > 0.05). No significant correlations between chemerin levels and weight loss were observed in subjects with overweight women. Conclusion: The present study demonstrated, 8 weeks aerobic training, reduced serum chemerin concentrations in overweight women. Whereas, aerobic training exercise programmers affected the lipid profile response of obese subjects differently. However further research is warranted in order to unravel the molecular mechanism for the range of responses and the role of serum chemerin.

Keywords: chemerin, aerobic training, lipid profile, obese women

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Authors: Jiahui You, Kyung Jae Lee

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Hydraulic fracturing fluid (HFF) is widely used in shale reservoir productions. HFF contains diverse chemical additives, which result in the dissolution and precipitation of minerals through multiple chemical reactions. In this study, a new pore-scale Darcy–Brinkman–Stokes (DBS) model coupled with Level Set Method (LSM) is developed to address the microscopic phenomena occurring during the iron–HFF interaction, by numerically describing mass transport, chemical reactions, and pore structure evolution. The new model is developed based on OpenFOAM, which is an open-source platform for computational fluid dynamics. Here, the DBS momentum equation is used to solve for velocity by accounting for the fluid-solid mass transfer; an advection-diffusion equation is used to compute the distribution of injected HFF and iron. The reaction–induced pore evolution is captured by applying the LSM, where the solid-liquid interface is updated by solving the level set distance function and reinitialized to a signed distance function. Then, a smoothened Heaviside function gives a smoothed solid-liquid interface over a narrow band with a fixed thickness. The stated equations are discretized by the finite volume method, while the re-initialized equation is discretized by the central difference method. Gauss linear upwind scheme is used to solve the level set distance function, and the Pressure–Implicit with Splitting of Operators (PISO) method is used to solve the momentum equation. The numerical result is compared with 1–D analytical solution of fluid-solid interface for reaction-diffusion problems. Sensitivity analysis is conducted with various Damkohler number (DaII) and Peclet number (Pe). We categorize the Fe (III) precipitation into three patterns as a function of DaII and Pe: symmetrical smoothed growth, unsymmetrical growth, and dendritic growth. Pe and DaII significantly affect the location of precipitation, which is critical in determining the injection parameters of hydraulic fracturing. When DaII<1, the precipitation uniformly occurs on the solid surface both in upstream and downstream directions. When DaII>1, the precipitation mainly occurs on the solid surface in an upstream direction. When Pe>1, Fe (II) transported deeply into and precipitated inside the pores. When Pe<1, the precipitation of Fe (III) occurs mainly on the solid surface in an upstream direction, and they are easily precipitated inside the small pore structures. The porosity–permeability relationship is subsequently presented. This pore-scale model allows high confidence in the description of Fe (II) dissolution, transport, and Fe (III) precipitation. The model shows fast convergence and requires a low computational load. The results can provide reliable guidance for injecting HFF in shale reservoirs to avoid clogging and wellbore pollution. Understanding Fe (III) precipitation, and Fe (II) release and transport behaviors give rise to a highly efficient hydraulic fracture project.

Keywords: reactive-transport , Shale, Kerogen, precipitation

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Authors: Margarita Ivanova, Julia Dao, Andrew Friedman, Neil Kasaci, Rekha Gopal, Ozlem Goker-Alpan

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In Fabry disease (FD), α-galactosidase A (α-Gal A) deficiency leads to the accumulation of globotriaosylceramide (Lyso-Gb3 and Gb3), triggering a pathologic cascade that causes the severity of organs damage. The heart is one of the several organs with high sensitivity to the α-Gal A deficiency. A subgroup of patients with significant residual of α-Gal A activity with primary cardiac involvement is occasionally referred to as “cardiac variant.” The cardiovascular complications are most frequently encountered, contributing substantially to morbidity, and are the leading cause of premature death in male and female patients with FD. The deposition of Lyso-Gb-3 and Gb-3 within the myocardium affects cardiac function with resultant progressive cardiovascular pathology. Gb-3 and Lyso-Gb-3 accumulation at the cellular level trigger a cascade of events leading to end-stage fibrosis. In the cardiac tissue, Lyso-Gb-3 deposition is associated with the increased release of inflammatory factors and transforming growth factors. Infiltration of lymphocytes and macrophages into endomyocardial tissue indicates that inflammation plays a significant role in cardiac damage. Moreover, accumulated data suggest that chronic inflammation leads to multisystemic FD pathology even under enzyme replacement therapy (ERT). NF-κB activation plays a subsequent role in the inflammatory response to cardiac dysfunction and advanced heart failure in the general population. TNFalpha/NF-κB signaling protects the myocardial evoking by ischemic preconditioning; however, this protective effect depends on the concentration of TNF-α. Thus, we hypothesize that TNF-α is a critical factor in determining the grade of cardio-pathology. Cardiac hypertrophy corresponds to the expansion of the coronary vasculature to maintain a sufficient supply of nutrients and oxygen. Coronary activation of angiogenesis and fibrosis plays a vital role in cardiac vascularization, hypertrophy, and tissue remodeling. We suggest that the interaction between the inflammatory pathways and cardiac vascularization is a bi-directional process controlled by secreted cytokines and growth factors. The co-coordination of these two processes has never been explored in FD. In a cohort of 40 patients with FD, biomarkers associated with inflammation and cardio hypertrophic remodeling were studied. FD patients were categorized into three groups based on LVmass/DSA, LVEF, and ECG abnormalities: FD with no cardio complication, FD with moderate cardio complication, and severe cardio complication. Serum levels of NF-kB, TNFalpha, Il-6, Il-2, MCP1, ING-gamma, VEGF, IGF-1, TGFβ, and FGF2 were quantified by enzyme-linked immunosorbent assays (ELISA). Among the biomarkers, MCP-1, INF-gamma, VEGF, TNF-alpha, and TGF-beta were elevated in FD patients. Some of these biomarkers also have the potential to correlate with cardio pathology in FD. Conclusion: The study provides information about the role of inflammatory pathways and biomarkers of cardio hypertrophic remodeling in FD patients. This study will also reveal the mechanisms that link intracellular accumulation of Lyso-GB-3 and Gb3 to the development of cardiomyopathy with myocardial thickening and resultant fibrosis.

Keywords: biomarkers, Fabry disease, inflammation, growth factors

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Authors: Sarah Lister, Pauline Palmer

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Research findings presented within this paper form part of a larger scale collaboration between academics at Manchester Metropolitan University and a technology company. The overarching aims of this project focus on developing a series of game-based resources to promote the teaching of aspects of mathematics through a second language (L2) in primary schools. This study explores the potential of game-based learning (GBL) as a dynamic way to engage and motivate learners, making learning fun and purposeful. The research examines the capacity of GBL resources to provide a meaningful and purposeful context for CLIL. GBL is a powerful learning environment and acts as an effective vehicle to promote the learning of mathematics through an L2. The fun element of GBL can minimise stress and anxiety associated with mathematics and L2 learning that can create barriers. GBL provides one of the few safe domains where it is acceptable for learners to fail. Games can provide a life-enhancing experience for learners, revolutionizing the routinized ways of learning through fusing learning and play. This study argues that playing games requires learners to think creatively to solve mathematical problems, using the L2 in order to progress, which can be associated with the development of higher-order thinking skills and independent learning. GBL requires learners to engage appropriate cognitive processes with increased speed of processing, sensitivity to environmental inputs, or flexibility in allocating cognitive and perceptual resources. At surface level, GBL resources provide opportunities for learners to learn to do things. Games that fuse subject content and appropriate learning objectives have the potential to make learning academic subjects more learner-centered, promote learner autonomy, easier, more enjoyable, more stimulating and engaging and therefore, more effective. Data includes observations of the children playing the games and follow up group interviews. Given that learning as a cognitive event cannot be directly observed or measured. A Cognitive Discourse Functions (CDF) construct was used to frame the research, to map the development of learners’ conceptual understanding in an L2 context and as a framework to observe the discursive interactions that occur learner to learner and between learner and teacher. Cognitively, the children were required to engage with mathematical content, concepts and language to make decisions quickly, to engage with the gameplay to reason, solve and overcome problems and learn through experimentation. The visual elements of the games supported the learning of new concepts. Children recognised the value of the games to consolidate their mathematical thinking and develop their understanding of new ideas. The games afforded them time to think and reflect. The teachers affirmed that the games provided meaningful opportunities for the learners to practise the language. The findings of this research support the view that using the game-based resources supported children’s grasp of mathematical ideas and their confidence and ability to use the L2. Engaging with the content and language through the games led to deeper learning.

Keywords: CLIL, gaming, language, mathematics

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Authors: Justyna P. Majewska, Szymon M. Truskolaski

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The growing importance of digitalized services in the so-called new economy, including the e-sports industry, can be observed recently. Various demographic or technological changes lead consumers to modify their needs, not regarding the services themselves but the method of their application (attracting customers, forms of payment, new content, etc.). In the case of leisure-related to competitive spectating activities, there is a growing need to participate in events whose content is not sports competitions but computer games challenge – e-sport. The literature in this area so far focuses on determining the number of e-sport fans with elements of a simple statistical description (mainly concerning demographic characteristics such as age, gender, place of residence). Meanwhile, the development of the industry is influenced by a combination of many different, intertwined demographic, personality and psychosocial characteristics of customers, as well as the characteristics of their environment. Therefore, there is a need for a deeper recognition of the determinants of the behavioral patterns upon selecting digitalized services by customers, which, in the absence of available large data sets, can be achieved by using econometric simulations – multi-agent modeling. The cognitive aim of the study is to reveal internal and external determinants of behavioral patterns of customers taking into account various variants of economic development (the pace of digitization and technological development, socio-demographic changes, etc.). In the paper, an agent-based model with heterogeneous agents (characteristics of customers themselves and their environment) was developed, which allowed identifying a three-stage development scenario: i) initial interest, ii) standardization, and iii) full professionalization. The probabilities regarding the transition process were estimated using the Method of Simulated Moments. The estimation of the agent-based model parameters and sensitivity analysis reveals crucial factors that have driven a rising trend in e-sport spectating and, in a wider perspective, the development of digitalized services. Among the psychosocial characteristics of customers, they are the level of familiarization with the rules of games as well as sports disciplines, active and passive participation history and individual perception of challenging activities. Environmental factors include general reception of games, number and level of recognition of community builders and the level of technological development of streaming as well as community building platforms. However, the crucial factor underlying the good predictive power of the model is the level of professionalization. While in the initial interest phase, the entry barriers for new customers are high. They decrease during the phase of standardization and increase again in the phase of full professionalization when new customers perceive participation history inaccessible. In this case, they are prone to switch to new methods of service application – in the case of e-sport vs. sports to new content and more modern methods of its delivery. In a wider context, the findings in the paper support the idea of a life cycle of services regarding methods of their application from “traditional” to digitalized.

Keywords: agent-based modeling, digitalized services, e-sport, spectators motives

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Authors: David X. Dong, Qingming Zhang, Meng Lu

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Nitrites enter waterways as runoff from croplands and are discharged from many industrial sites. Excessive nitrite inputs to water bodies lead to eutrophication. On-site rapid detection of nitrite is of increasing interest for managing fertilizer application and monitoring water source quality. Existing methods for detecting nitrites use spectrophotometry, ion chromatography, electrochemical sensors, ion-selective electrodes, chemiluminescence, and colorimetric methods. However, these methods either suffer from high cost or provide low measurement accuracy due to their poor selectivity to nitrites. Therefore, it is desired to develop an accurate and economical method to monitor nitrites in environments. We report a low-cost optical sensor, in conjunction with a machine learning (ML) approach to enable high-accuracy detection of nitrites in water sources. The sensor works under the principle of measuring molecular absorptions of nitrites at three narrowband wavelengths (295 nm, 310 nm, and 357 nm) in the ultraviolet (UV) region. These wavelengths are chosen because they have relatively high sensitivity to nitrites; low-cost light-emitting devices (LEDs) and photodetectors are also available at these wavelengths. A regression model is built, trained, and utilized to minimize cross-sensitivities of these wavelengths to the same analyte, thus achieving precise and reliable measurements with various interference ions. The measured absorbance data is input to the trained model that can provide nitrite concentration prediction for the sample. The sensor is built with i) a miniature quartz cuvette as the test cell that contains a liquid sample under test, ii) three low-cost UV LEDs placed on one side of the cell as light sources, with each LED providing a narrowband light, and iii) a photodetector with a built-in amplifier and an analog-to-digital converter placed on the other side of the test cell to measure the power of transmitted light. This simple optical design allows measuring the absorbance data of the sample at the three wavelengths. To train the regression model, absorbances of nitrite ions and their combination with various interference ions are first obtained at the three UV wavelengths using a conventional spectrophotometer. Then, the spectrophotometric data are inputs to different regression algorithm models for training and evaluating high-accuracy nitrite concentration prediction. Our experimental results show that the proposed approach enables instantaneous nitrite detection within several seconds. The sensor hardware costs about one hundred dollars, which is much cheaper than a commercial spectrophotometer. The ML algorithm helps to reduce the average relative errors to below 3.5% over a concentration range from 0.1 ppm to 100 ppm of nitrites. The sensor has been validated to measure nitrites at three sites in Ames, Iowa, USA. This work demonstrates an economical and effective approach to the rapid, reagent-free determination of nitrites with high accuracy. The integration of the low-cost optical sensor and ML data processing can find a wide range of applications in environmental monitoring and management.

Keywords: optical sensor, regression model, nitrites, water quality

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Authors: Mohammad Hossein Pazandeh, Monir Doudi, Sona Rostampour Yasouri

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Irregular consumption of current antibiotic makes increases of antibiotic resistance between urin pathogens on all worlds. This study selected based on this great community problem. The aim of this study was the biosynthesis of silver nanoparticles from Zataria multiflora extract and then to investigate its antibacterial effect on gram-negative bacilli common in Urinary Tract Infections (UTI) and MDR. The plant used in the present research was Zataria multiflora whose extract was prepared through Soxhlet extraction method. Green synthesis condition of silver nanoparticles was investigated in terms of three parameters including the extract amount, concentration of silver nitrate salt, and temperature. The seizes of nanoparticles were determined by Zetasizer. In order to identify synthesized silver nanoparticles Transmission Electron Microscopy (TEM) and X-ray Diffraction (XRD) methods were used. For evaluating the antibacterial effects of nanoparticles synthesized through biological method different concentrations of silver nanoparticles were studied on 140 cases of Muliple Drug Resistance (MDR) bacteria strains Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Proteus vulgaris,Citrobacter freundii, Acinetobacter bumanii and Pseudomonas aeruginosa, (each genus of bacteria, 20 samples), which all were MDR and cause urinary tract infections , for identification of bacteria were used of Polymerase Chain Reaction (PCR) test and laboratory methods (Agar well diffusion and Microdilution methods) to assess their sensitivity to Nanoparticles. The data were analyzed using SPSS software by nonparametric Kruskal-Wallis and Mann-Whitney tests. Significant results were found about the effects of silver nitrate concentration, different amounts of Zataria multiflora extract, and temperature on nanoparticles; that is, by increasing the concentration of silver nitrate, extract amount, and temperature, the sizes of synthesized nanoparticles declined. However, the effect of above mentioned factors on particles diffusion index was not significant. Based on the TEM results, particles were mainly spherical shape with a diameter range of 25 to 50 nm. The results of XRD Analysis indicated the formation of Nanostructures and Nanocrystals of silver.. The obtained results of antibacterial effects of different concentrations of silver nanoparticles on according to agar well diffusion and microdilution method, biologically synthesized nanoparticles showed 1000 mg /ml highest and lowest mean inhibition zone diameter in E.coli , Acinetobacter bumanii 23 and 15mm, respectively. MIC was observed for all of bacteria 125mg/ml and for Acinetobacter bumanii 250mg/ml.Comparing the growth inhibitory effect of chemically synthesized Nanoparticles and biologically synthesized Nanoparticles showed that in the chemical method the highest growth inhibition belonged to the concentration of 62.5 mg /ml. The inhibitory effect on the growth all of bacteria causes of urine infection and MDR was observed and by increasing silver ion concentration in Nanoparticles, antibacterial activity increased. Generally, the biological synthesis can be considered an efficient way not only in making Nanoparticles but also for having anti-bacterial properties. It is more biocompatible and may be possess less toxicity than the Nanoparticles synthesized chemically.

Keywords: biosynthesis, MDR bacteria, silver nanoparticles, UTI

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Authors: Adriana Pereira Arteaga

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In many Latin American countries the transition towards legal pluralism - has developed as part of what is called Latin-American-Constitutionalism over the last thirty years. The aim of this paper is to discuss how legal pluralism in its current form in Bolivia may produce exclusion and violence. Legal sources and discourse analysis - as an approach to examine written language on discourse documentation- will be used to develop this paper. With the constitution of 2009, Bolivia was symbolically "re-founded" into a multi-nation state. This shift goes hand in hand with the "indigenista" and "decolonisation" ideologies developing since the early 20th century. Discourses based on these ideologies reflect the rejection of liberal and western premises on which the Bolivian republic was originally built after independence. According to the "indigenista" movements, the liberal nation-state generates institutions corresponding to a homogenous society. These liberal institutions not only ignore the Bolivian multi-nation reality, but also maintain the social structures originating form the colony times, based on prejudices against the indigenous. The described statements were elaborated through the image: the indigenous people humiliated by a cruel western system as highlighted by the constitution's preamble. This narrative had a considerable impact on the sensitivity of people and received great social support. Therefore the proposal for changing structures of the nation-state, is charged with an emancipatory message of restoring even the pre-Columbian order. An order at times romantically described as the perfect order. Legally this connotes a rejection of the positivistic national legal system based on individual rights and the promotion of constitutional recognition of indigenous justice administration. The pluralistic Constitution is supposed to promote tolerance and a peaceful coexistence among nations, so that the unity and integrity of the country could be maintained. In its current form, legal pluralism in Bolivia is justified on pre-existing rights contained for example in the International - Labour - Organization - Convention 169, but it is more developed on the described discursive constructions. Over time these discursive constructions created inconsistencies in terms of putting indigenous justice administration into practice: First, because legal pluralism has been more developed on level of political discourse, so a real interaction between the national and the indigenous jurisdiction cannot be observed. There are no clear coordination and cooperation mechanisms. Second, since the recently reformed constitution is based on deep sensitive experiences, little is said about the general legal principles on which a pluralistic administration of justice in Bolivia should be based. Third, basic rights, liberties, and constitutional guarantees are also affected by the antagonized image of the national justice administration. As a result, fundamental rights could be violated on a large scale because many indigenous justice administration practices run counter to these constitutional rules. These problems are not merely Bolivian but may also be encountered in other regional countries with similar backgrounds, like Ecuador.

Keywords: discourse, indigenous justice, legal pluralism, multi-nation

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Authors: Isaac Martin, Abigail Lark, Sandra Morales, Eric W. Alton, Jane C. Davies

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Objectives: The cystic fibrosis (CF) lung is a unique microbiological niche, wherein harmful bacteria persist for many years despite antibiotic therapy. Pseudomonas aeruginosa (Pa), the major culprit leading to lung decline and increased mortality, thrives in the lungs of patients with CF due to several factors that have been linked with poor antibiotic performance. Our group is investigating alternative therapies including bacteriophage cocktails with which we have previously demonstrated efficacy against planktonic organisms. In this study, we explored the effects of a 4-phage cocktail on Pa grown in two different conditions, intended to mirror the CF lung: a) alongside standard antibiotic treatment in pre-formed biofilms (structures formed by Pa-secreted exopolysaccharides which provide both physical and cell division barriers to antimicrobials and host defenses and b) in an acidic environment postulated to be present in the CF airway due both to the primary defect in bicarbonate secretion and secondary effects of inflammation. Methods: 16 Pa strains from CF patients at the Royal Brompton Hospital were selected based on sensitivity to a) ceftazidime/ tobramycin and b) the phage cocktail in a conventional plaque assay. To assess efficacy of phage in biofilms, 96 well plates with Pa (5x10⁷ CFU/ ml) were incubated in static conditions, allowing adherent bacterial colonies to form for 24 hr. Ceftazidime and tobramycin (both at 2 × MIC) were added, +/- bacteriophage (4x10⁸ PFU/mL) for a further 24 hr. Cell viability and biomass were estimated using fluorescent resazurin and crystal violet assays, respectively. To evaluate the effect of pH, strains were grown planktonically in shaking 96 well plates at pH 6.0, 6.6, 7.0 and 7.5 with tobramycin or phage, at varying concentrations. Cell viability was quantified by fluorescent resazurin assay. Results: For the biofilm assay, treatment groups were compared with untreated controls and expressed as percent reduction in cell viability and biomass. Addition of the 4-phage cocktail resulted in a 1.3-fold reduction in cell viability and 1.7-fold reduction in biomass (p < 0.001) when compared to standard antibiotic treatment alone. Notably, there was a 50 ± 15% reduction in cell viability and 60 ± 12% reduction in biomass (95% CI) for the 4 biofilms demonstrating the most resistance to antibiotic treatment. 83% of strains tested (n=6) showed decreased bacterial killing by tobramycin at acidic pHs (p < 0.01). However, 25% of strains (n=12) showed improved phage killing at acidic pHs (p < 0.05), with none showing the pattern of reduced efficacy at acidic pH demonstrated by tobramycin. Conclusion: The 4-phage anti-Pa cocktail tested against Pa performs well in pre-formed biofilms and in acidic environments; two conditions intended to mimic the CF lung. To our knowledge, these are the first data looking at the effects of subtle pH changes on phage-mediated bacterial killing in the context of Pa infection. These findings contribute to a growing body of evidence supporting the use of nebulised lytic bacteriophage as a treatment in the context of lung infection.

Keywords: biofilm, cystic fibrosis, pH, Pseudomonas aeruginosa, lytic bacteriophage

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Authors: Mary Ghobrial, Sahar Wefky

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Marine macroalgae have proven to be rich source of bioactive compounds with biomedical potential, not only for human but also for veterinary medicine. Emergence of microbial disease in aquaculture industries implies serious loses. Usage of commercial antibiotics for fish disease treatment produces undesirable side effects. Marine organisms are a rich source of structurally novel biologically active metabolites. Competition for space and nutrients led to the evolution of antimicrobial defense strategies in the aquatic environment. The interest in marine organisms as a potential and promising source of pharmaceutical agents has increased in the last years. Many bioactive and pharmacologically active substances have been isolated from microalgae. Compounds with antibacterial, antifungal and antiviral activities have been also detected in green, brown and red algae. Selected species of marine benthic algae belonging to the Phaeophyta and Rhodophyta, collected from different coastal areas of Alexandria (Egypt), were investigated for their antibacterial and antifungal, activities. Macroalgae samples were collected during low tide from the Alexandria Mediterranean coast. Samples were air dried under shade at room temperature. The dry algae were ground, using electric mixer grinder. They were soaked in 10 ml of each of the solvents acetone, ethanol, methanol and hexane. Antimicrobial activity was evaluated using well-cut diffusion technique In vitro screening of organic solvent extracts from the marine macroalgae Laurencia pinnatifida, Pterocladia capillaceae, Stepopodium zonale, Halopteris scoparia and Sargassum hystrix, showed specific activity in inhibiting the growth of five virulent strains of bacteria pathogenic to fish Pseudomonas fluorescens, Aeromonas hydrophila, Vibrio anguillarum, V. tandara, Escherichia coli and two fungi Aspergillus flavus and A. niger. Results showed that, acetone and ethanol extracts of all test macroalgae exhibited antibacterial activity, while acetone extract of the brown Sargassum hystrix displayed the highest antifungal activity. The extracts of seaweeds inhibited bacteria more strongly than fungi and species of the Rhodophyta showed the greatest activity against the bacteria rather than fungi tested. The gas liquid chromatography coupled with mass spectrometry detection technique allows good qualitative and quantitative analysis of the fractionated extracts with high sensitivity to the smaller amounts of components. Results indicated that, the main common component in the acetone extracts of L. pinnatifida and P. capillacea is 4-hydroxy-4-methyl2-pentanone representing 64.38 and 58.60%. Thus, the extracts derived from the red macroalgae were more efficient than those obtained from the brown macroalgae in combating bacterial pathogens rather than pathogenic fungi. The most preferred species over all was the red Laurencia pinnatifida. In conclusion, the present study provides the potential of red and brown macroalgae extracts for development of anti-pathogenic agents for use in fish aquaculture.

Keywords: bacteria, fungi, extracts, solvents

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Authors: Rupali Bhatia, Deepthi Nair, Geetika Khanna, Seema Singhal

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Introduction: Genital tract tuberculosis is a chronic disease (caused by reactivation of organisms from systemic distribution of Mycobacterium tuberculosis) that often presents with low grade symptoms and non-specific complaints. Patients with genital tuberculosis are usually young women seeking workup and treatment for infertility. Infertility is the commonest presentation due to involvement of the fallopian tubes, endometrium and ovarian damage with poor ovarian volume and reserve. The diagnosis of genital tuberculosis is difficult because of the fact that it is a silent invader of genital tract. Since tissue cannot be obtained from fallopian tubes, the diagnosis is made by isolation of bacilli from endometrial tissue obtained by endometrial biopsy curettage and/or aspiration. Problems are associated with sampling technique as well as diagnostic modality due to lack of adequate sample volumes and the segregation of the sample for various diagnostic tests resulting in non-uniform distribution of microorganisms. Moreover, lack of an efficient sampling technique universally applicable for all specific diagnostic tests contributes to the diagnostic challenges. Endometrial sampling plays a key role in accurate diagnosis of female genital tuberculosis. It may be done by 2 methods viz. endometrial curettage and endometrial aspiration. Both endometrial curettage and aspirate have their own limitations as curettage picks up strip of the endometrium from one of the walls of the uterine cavity including tubal osteal areas whereas aspirate obtains total tissue with exfoliated cells present in the secretory fluid of the endometrial cavity. Further, sparse and uneven distribution of the bacilli remains a major factor contributing to the limitations of the techniques. The sample that is obtained by either technique is subjected to histopathological examination, AFB staining, culture and PCR. Aim: Comparison of the sampling techniques viz. endometrial biopsy curettage and endometrial aspiration using different laboratory methods of histopathology, cytology, microbiology and molecular biology. Method: In a hospital based observational study, 75 Indian females suspected of genital tuberculosis were selected on the basis of inclusion criteria. The women underwent endometrial tissue sampling using Novaks biopsy curette and Karmans cannula. One part of the specimen obtained was sent in formalin solution for histopathological testing and another part was sent in normal saline for acid fast bacilli smear, culture and polymerase chain reaction. The results so obtained were correlated using coefficient of correlation and chi square test. Result: Concordance of results showed moderate agreement between both the sampling techniques. Among HPE, AFB and PCR, maximum sensitivity was observed for PCR, though the specificity was not as high as other techniques. Conclusion: Statistically no significant difference was observed between the results obtained by the two sampling techniques. Therefore, one may use either EA or EB to obtain endometrial samples and avoid multiple sampling as both the techniques are equally efficient in diagnosing genital tuberculosis by HPE, AFB, culture or PCR.

Keywords: acid fast bacilli (AFB), histopatholgy examination (HPE), polymerase chain reaction (PCR), endometrial biopsy curettage

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Authors: Sandra Hartl, Meena Chavan

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This paper presents the outcome of a four year Ph.D. research on cross-cultural conflict management in transnational business relationships. An important and complex problem about managing conflicts that arise across cultures in business relationships is investigated, and conflict resolution strategies are identified. This paper particularly focuses on transnational relationships within a Chinese, German and Middle Eastern framework. Unlike many papers on this issue which have been built on experiments with international MBA students, this research provides real-life cases of cross-cultural conflicts which are not easy to capture. Its uniqueness is underpinned as the real case data was gathered by interviewing top executives at management positions in large multinational corporations through a qualitative case study method approach. This paper makes a valuable contribution to the theory of cross-cultural conflicts, and despite the sensitivity, this research primarily presents real-time business data about breaches of contracts between two counterparties engaged in transnational operating organizations. The overarching aim of this research is to identify the degree of significance for the cultural factors and the communication factors embedded in cross-cultural business conflicts. It questions from a cultural perspective what factors lead to the conflicts in each of the cases, what the causes are and the role of culture in identifying effective strategies for resolving international disputes in an increasingly globalized business world. The results of 20 face to face interviews are outlined, which were conducted, recorded, transcribed and then analyzed using the NVIVO qualitative data analysis system. The outcomes make evident that the factors leading to conflicts are broadly organized under seven themes, which are communication, cultural difference, environmental issues, work structures, knowledge and skills, cultural anxiety and personal characteristics. When evaluating the causes of the conflict it is to notice that these are rather multidimensional. Irrespective of the conflict types (relationship or task-based conflict or due to individual personal differences), relationships are almost always an element of all conflicts. Cultural differences, which are a critical factor for conflicts, result from different cultures placing different levels of importance on relationships. Communication issues which are another cause of conflict also reflect different relationships styles favored by different cultures. In identifying effective strategies for solving cross-cultural business conflicts this research identifies that solutions need to consider the national cultures (country specific characteristics), organizational cultures and individual culture, of the persons engaged in the conflict and how these are interlinked to each other. Outcomes identify practical dispute resolution strategies to resolve cross-cultural business conflicts in reference to communication, empathy and training to improve cultural understanding and cultural competence, through the use of mediation. To conclude, the findings of this research will not only add value to academic knowledge of cross-cultural conflict management across transnational businesses but will also add value to numerous cross-border business relationships worldwide. Above all it identifies the influence of cultures and communication and cross-cultural competence in reducing cross-cultural business conflicts in transnational business.

Keywords: business conflict, conflict management, cross-cultural communication, dispute resolution

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Authors: Nicholas Mavrogiannis, Francesca Crivellari, Zachary Gagnon

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Development of low-cost, rapid, sensitive and portable biosensing systems are important for the detection and prevention of disease in developing countries, biowarfare/antiterrorism applications, environmental monitoring, point-of-care diagnostic testing and for basic biological research. Currently, the most established commercially available and widespread assays for portable point of care detection and disease testing are paper-based dipstick and lateral flow test strips. These paper-based devices are often small, cheap and simple to operate. The last three decades in particular have seen an emergence in these assays in diagnostic settings for detection of pregnancy, HIV/AIDS, blood glucose, Influenza, urinary protein, cardiovascular disease, respiratory infections and blood chemistries. Such assays are widely available largely because they are inexpensive, lightweight, and portable, are simple to operate, and a few platforms are capable of multiplexed detection for a small number of sample targets. However, there is a critical need for sensitive, quantitative and multiplexed detection capabilities for point-of-care diagnostics and for the detection and prevention of disease in the developing world that cannot be satisfied by current state-of-the-art paper-based assays. For example, applications including the detection of cardiac and cancer biomarkers and biothreat applications require sensitive multiplexed detection of analytes in the nM and pM range, and cannot currently be satisfied with current inexpensive portable platforms due to their lack of sensitivity, quantitative capabilities and often unreliable performance. In this talk, inexpensive label-free biomolecular detection at liquid interfaces using a newly discovered electrokinetic phenomenon known as fluidic dielectrophoresis (fDEP) is demonstrated. The electrokinetic approach involves exploiting the electrical mismatches between two aqueous liquid streams forced to flow side-by-side in a microfluidic T-channel. In this system, one fluid stream is engineered to have a higher conductivity relative to its neighbor which has a higher permittivity. When a “low” frequency (< 1 MHz) alternating current (AC) electrical field is applied normal to this fluidic electrical interface the fluid stream with high conductivity displaces into the low conductive stream. Conversely, when a “high” frequency (20MHz) AC electric field is applied, the high permittivity stream deflects across the microfluidic channel. There is, however, a critical frequency sensitive to the electrical differences between each fluid phase – the fDEP crossover frequency – between these two events where no fluid deflection is observed, and the interface remains fixed when exposed to an external field. To perform biomolecular detection, two streams flow side-by-side in a microfluidic T-channel: one fluid stream with an analyte of choice and an adjacent stream with a specific receptor to the chosen target. The two fluid streams merge and the fDEP crossover frequency is measured at different axial positions down the resulting liquid

Keywords: biodetection, fluidic dielectrophoresis, interfacial polarization, liquid interface

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Authors: Berengere Vire, Nicolas Salvetat, Yoann Lannay, Guillaume Marcellin, Siem Van Der Laan, Franck Molina, Dinah Weissmann

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Predicting suicidal behaviors is one of the most complex challenges of daily psychiatric practices. Today, suicide risk prediction using biological tools is not validated and is only based on subjective clinical reports of the at-risk individual. Therefore, there is a great need to identify biomarkers that would allow early identification of individuals at risk of suicide. Alterations of adenosine-to-inosine (A-to-I) RNA editing of neurotransmitter receptors and other proteins have been shown to be involved in etiology of different psychiatric disorders and linked to suicidal behavior. RNA editing is a co- or post-transcriptional process leading to a site-specific alteration in RNA sequences. It plays an important role in the epi transcriptomic regulation of RNA metabolism. On postmortem human brain tissue (prefrontal cortex) of depressed suicide victims, Alcediag found specific alterations of RNA editing activity on the mRNA coding for the serotonin 2C receptor (5-HT2cR). Additionally, an increase in expression levels of ADARs, the RNA editing enzymes, and modifications of RNA editing profiles of prime targets, such as phosphodiesterase 8A (PDE8A) mRNA, have also been observed. Interestingly, the PDE8A gene is located on chromosome 15q25.3, a genomic region that has recurrently been associated with the early-onset major depressive disorder (MDD). In the current study, we examined whether modifications in RNA editing profile of prime targets allow identifying disease-relevant blood biomarkers and evaluating suicide risk in patients. To address this question, we performed a clinical study to identify an RNA editing signature in blood of depressed patients with and without the history of suicide attempts. Patient’s samples were drawn in PAXgene tubes and analyzed on Alcediag’s proprietary RNA editing platform using next generation sequencing technology. In addition, gene expression analysis by quantitative PCR was performed. We generated a multivariate algorithm comprising various selected biomarkers to detect patients with a high risk to attempt suicide. We evaluated the diagnostic performance using the relative proportion of PDE8A mRNA editing at different sites and/or isoforms as well as the expression of PDE8A and the ADARs. The significance of these biomarkers for suicidality was evaluated using the area under the receiver-operating characteristic curve (AUC). The generated algorithm comprising the biomarkers was found to have strong diagnostic performances with high specificity and sensitivity. In conclusion, we developed tools to measure disease-specific biomarkers in blood samples of patients for identifying individuals at the greatest risk for future suicide attempts. This technology not only fosters patient management but is also suitable to predict the risk of drug-induced psychiatric side effects such as iatrogenic increase of suicidal ideas/behaviors.

Keywords: blood biomarker, next-generation-sequencing, RNA editing, suicide

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