Search results for: fluid induced seismicity

Authors: Edda E. Falcone, Cinzia Federico, Sergio Bellomo, Lorenzo Brusca, Manfredi Longo, Walter D’Alessandro

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Although trace metals are an essential element for living beings, they can become toxic at high concentrations. Their potential toxicity is related not only to the total content in the environment but mostly upon their bioavailability. Volcanoes are important natural metal emitters and they can deeply affect the quality of air, water and soils, as well as the human health. Trace metals tend to accumulate in the tissues of living organisms, depending on the metal contents in food, air and water and on the exposure time. Birds are considered as bioindicators of interest, because their feathers directly reflects the metals uptake from the blood. Birds are exposed to the atmospheric pollution through the contact with rainfall, dust, and aerosol, and they accumulate metals over the whole life cycle. We report on the first data combining the rainfall metal content in three different areas of Mt Etna, variably fumigated by the volcanic plume, and the metal contents in the feathers of pigeons, collected in the same areas. Rainfall samples were collected from three rain gauges placed at different elevation on the Eastern flank of the volcano, the most exposed to airborne plume, filtered, treated with HNO₃ Suprapur-grade and analyzed for Fe, Cr, Co, Ni, Se, Zn, Cu, Sr, Ba, Cd and As by ICP-MS technique, and major ions by ion chromatography. Feathers were collected from single individuals, in the same areas where the rain gauges were installed. Additionally, some samples were collected in an urban area, poorly interested by the volcanic plume. The samples were rinsed in MilliQ water and acetone, dried at 50°C until constant weight and digested in a mixture of 2:1 HNO₃ (65%) - H₂O₂ (30%) Suprapur-grade for 25-50 mg of sample, in a bath at near-to-boiling temperature. The solutions were diluted up to 20 ml prior to be analyzed by ICP-MS. The rainfall samples most contaminated by the plume were collected at close distance from the summit craters (less than 6 km), and show lower pH values and higher concentrations for all analyzed metals relative to those from the sites at lower elevation. Analyzed samples are enriched in both metals directly emitted by the volcanic plume and transported by acidic gases (SO₂, HCl, HF), and metals leached from the airborne volcanic ash. Feathers show different patterns in the different sites related to the exposure to natural or anthropogenic pollutants. They show abundance ratios similar to rainfall for lithophile elements (Ba, Sr), whereas are enriched in Zn and Se, known for their antioxidant properties, probably as adaptive response to oxidative stress induced by toxic metal exposure. The pigeons revealed a clear heterogeneity of metal uptake in the different parts of the volcano, as an effect of volcanic plume impact. Additionally, some physiological processes can modify the fate of some metals after uptake and this offer some insights for translational studies.

Keywords: bioindicators, environmental pollution, feathers, trace metals, volcanic plume

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Authors: M. Grandcolas, N. Rival, H. Bu, S. Jahren, R. Schmid, H. Johnsen

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The concept of an autonomic self-healing material, where initiation of repair is integrated to the material, is now being considered for engineering applications and is a hot topic in the literature. Among several concepts/techniques, two are most interesting: i) Capsules: Integration of microcapsules in or at the surface of coatings or fibre-like structures has recently gained much attention. Upon damage-induced cracking, the microcapsules are broken by the propagating crack fronts resulting in a release of an active chemical (healing agent) by capillary action, subsequently repairing and avoiding further crack growth. ii) Self-healing polymers: Interestingly, the introduction of dynamic covalent bonds into polymer networks has also recently been used as a powerful approach towards the design of various intrinsically self-healing polymer systems. The idea behind this is to reconnect the chemical crosslinks which are broken when a material fractures, restoring the integrity of the material and thereby prolonging its lifetime. We propose here to integrate both self-healing concepts (capsules, self-healing polymers) in electrospun fibres and coatings. Different capsule preparation approaches have been investigated in SINTEF. The most advanced method to produce capsules is based on emulsification to create a water-in-oil emulsion before polymerisation. The healing agent is a polyurethane-based dispersion that was encapsulated in shell materials consisting of urea-benzaldehyde resins. Results showed the successful preparation of microcapsules and release of the agent when capsules break. Since capsules are produced in water-in-oil systems we mainly investigated organic solvent based coatings while a major challenge resides in the incorporation of capsules into water-based coatings. We also focused on developing more robust microcapsules to prevent premature rupture of the capsules. The capsules have been characterized in terms of size, and encapsulation and release might be visualized by incorporating fluorescent dyes and examine the capsules by microscopy techniques. Alternatively, electrospinning is an innovative technique that has attracted enormous attention due to unique properties of the produced nano-to-micro fibers, ease of fabrication and functionalization, and versatility in controlling parameters. Especially roll-to-roll electrospinning is a unique method which has been used in industry to produce nanofibers continuously. Electrospun nanofibers can usually reach a diameter down to 100 nm, depending on the polymer used, which is of interest for the concept with self-healing polymer systems. In this work, we proved the feasibility of fabrication of POSS-based (POSS: polyhedral oligomeric silsesquioxanes, tradename FunzioNano™) nanofibers via electrospinning. Two different formulations based on aqueous or organic solvents have shown nanofibres with a diameter between 200 – 450nm with low defects. The addition of FunzioNano™ in the polymer blend also showed enhanced properties in term of wettability, promising for e.g. membrane technology. The self-healing polymer systems developed are here POSS-based materials synthesized to develop dynamic soft brushes.

Keywords: capsules, coatings, electrospinning, fibers

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Authors: Sigal Portnoy, Jason Friedman, Eitan Raveh

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Introduction: Sensory substitution is possible due to the capacity of our brain to adapt to information transmitted by a synthetic receptor via an alternative sensory system. Practical sensory substitution systems are being developed in order to increase the functionality of individuals with sensory loss, e.g. amputees. For upper limb prosthetic-users the loss of tactile feedback compels them to allocate visual attention to their prosthesis. The effect of adding vibrotactile feedback (VTF) to the applied force has been studied, however its effect on the allocation if visual attention during dual-tasking and the response during misleading visual feedback have not been studied. We hypothesized that VTF will improve the performance and reduce visual attention during dual-task assignments in healthy individuals using a robotic hand and improve the performance in a standardized functional test, despite the presence of misleading visual feedback. Methods: For the dual-task paradigm, twenty healthy subjects were instructed to toggle two keyboard arrow keys with the left hand to retain a moving virtual car on a road on a screen. During the game, instructions for various activities, e.g. mix the sugar in the glass with a spoon, appeared on the screen. The subject performed these tasks with a robotic hand, attached to the right hand. The robotic hand was controlled by the activity of the flexors and extensors of the right wrist, recorded using surface EMG electrodes. Pressure sensors were attached at the tips of the robotic hand and induced VTF using vibrotactile actuators attached to the right arm of the subject. An eye-tracking system tracked to visual attention of the subject during the trials. The trials were repeated twice, with and without the VTF. Additionally, the subjects performed the modified box and blocks, hidden from eyesight, in a motion laboratory. A virtual presentation of a misleading visual feedback was be presented on a screen so that twice during the trial, the virtual block fell while the physical block was still held by the subject. Results: This is an ongoing study, which current results are detailed below. We are continuing these trials with transradial myoelectric prosthesis-users. In the healthy group, the VTF did not reduce the visual attention or improve performance during dual-tasking for the tasks that were typed transfer-to-target, e.g. place the eraser on the shelf. An improvement was observed for other tasks. For example, the average±standard deviation of time to complete the sugar-mixing task was 13.7±17.2s and 19.3±9.1s with and without the VTF, respectively. Also, the number of gaze shifts from the screen to the hand during this task were 15.5±23.7 and 20.0±11.6, with and without the VTF, respectively. The response of the subjects to the misleading visual feedback did not differ between the two conditions, i.e. with and without VTF. Conclusions: Our interim results suggest that the performance of certain activities of daily living may be improved by VTF. The substitution of visual sensory input by tactile feedback might require a long training period so that brain plasticity can occur and allow adaptation to the new condition.

Keywords: prosthetics, rehabilitation, sensory substitution, upper limb amputation

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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: Preeti Virkar, V. P. Uniyal, Vinod Kumar Bhatt

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With 50% decline in managed honey bee hives in the continents of Europe and America, farmers and landscape managers are turning to native wild bees for their essential ecosystem services of pollination. Wild bees population are too under danger due to the rapid land use changes from anthropogenic activities. With an escalating population reaching 9.0 billion by 2050, human-induced land use changes are predicted to further deteriorate the habitats of numerous species by the turn of this century. The status of bees are uncertain, especially in the tropical regions of the world, which also questions the crisis of global pollinator decline and their essential services to wild and managed flora. Our investigation collectively compares wild native bee diversity and their status in forests and agroecosystems in Doon Valley landscape, situated at the foothills of Himalayan ranges, Uttarakhand, India. We seek to ask whether (1) natural habitat are refuge to richer and rarer bees communities than the agroecosystems, (2) Are agroecosystems closer to natural habitats similar to them than agroecosystems farther away; hence support richer bee communities and hence, (3) Do polyculture farms support richer bee communities than monoculture. The data was collected using observation and pantrap sampling form February to May, 2012 to 2014. We recorded 43 species of bees in Doon Valley. They belonged to 5 families; Megachilidae, Apidae, Andrenidae, Halictidae and Collitidae. A multinomial model approach was used to classify the bees into 2 habitats, in which forests demonstrated to support greater number of specialist (26%, n= 11) species than agroecosystems (7%, n= 3). The valley had many species categorized as the rare (58%, n= 25) and very few generalists (9%, n=4). A linear regression model run on our data demonstrated higher bee diversity in agro-ecosystems in close proximity to forests (H’ for < 200 m = 1.60) compared to those further away (H’ for > 600 m = 0.56) (R2=0.782, SE=0.148, p value=0.004). Organic agriculture supported significantly greater species richness in comparison to conventional farms (Mann-Whitney U test, n1 = 33, n2 = 35; P = 0.001). Forests ecosystems are refuge to rare specialist groups and support bee communities in nearby agroecosystems. The findings of our investigation demonstrate the importance of natural habitats as a potential refuge for rare native wild bee pollinators. Polyculture in the valley behaves similar to natural habitats and supports diverse bee communities in comparison to conventional monocultures. Our study suggests that the farming communities adopt diverse organic agriculture systems to attract wild pollinators beneficial for better crop production. Forests are sanctuaries for bees to nest, forage, and breed. Therefore, our outcome also suggests landscape managers not only preserve protected areas but also enhance the floral diversity in semi-natural and urban areas.

Keywords: native bees, pollinators, polyculture, agroecosystem, natural habitat, diversity, monoculture, specialists, generalists

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Authors: Abirami Baleswaran, Christel Couderc, Loubnah Belahcen, Jean Dayde, Hélène Tormo, Gwénaëlle Jard

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Cheeses are often reported to be spoiled by Pseudomonas spp., responsible for defects in appearance, texture, taste, and smell, leading to their non-marketing and even their destruction. Despite preventive actions, problems linked to Pseudomonas spp. are difficult to control by the lack of knowledge and control of these contaminants during the cheese manufacturing. Lactic goat cheese producers are not spared by this problem and are looking for solutions to decrease the number of spoiled cheeses. To explore different hypotheses, experiments are needed. However, cheese-making experiments at the pilot scale are expensive and time consuming. Thus, there is a real need to develop a miniature cheeses model system under controlled conditions. In a previous study, several miniature cheese models corresponding to different type of commercial cheeses have been developed for different purposes. The models were, for example, used to study the influence of milk, starters cultures, pathogen inhibiting additives, enzymatic reactions, microflora, freezing process on cheese. Nevertheless, no miniature model was described on the lactic goat cheese. The aim of this work was to develop a miniature cheese model system under controlled laboratory conditions which resembles commercial lactic goat cheese to study Pseudomonas spp. spoilage during the manufacturing and ripening process. First, a protocol for the preparation of miniature cheeses (3.5 times smaller than a commercial one) was designed based on the cheese factorymanufacturing process. The process was adapted from “Rocamadour” technology and involves maturation of pasteurized milk, coagulation, removal of whey by centrifugation, moulding, and ripening in a little scale cellar. Microbiological (total bacterial count, yeast, molds) and physicochemical (pH, saltinmoisture, moisture in fat-free)analyses were performed on four key stages of the process (before salting, after salting, 1st day of ripening, and end of ripening). Factory and miniature cheeses volatilomewere also obtained after full scan Sift-MS cheese analysis. Then, Pseudomonas spp. strains isolated from contaminated cheeses were selected on their origin, their ability to produce pigments, and their enzymatic activities (proteolytic, lecithinasic, and lipolytic). Factory and miniature curds were inoculated by spotting selected strains on the cheese surface. The expression of cheese spoilage was evaluated by counting the level of Pseudomonas spp. during the ripening and by visual observation and under UVlamp. The physicochemical and microbiological compositions of miniature cheeses permitted to assess that miniature process resembles factory process. As expected, differences involatilomes were observed, probably due to the fact that miniature cheeses are made usingpasteurized milk to better control the microbiological conditions and also because the little format of cheese induced probably a difference during the ripening even if the humidity and temperature in the cellar were quite similar. The spoilage expression of Pseudomonas spp. was observed in miniature and factory cheeses. It confirms that the proposed model is suitable for the preparation of miniature cheese specimens in the spoilage study of Pseudomonas spp. in lactic cheeses. This kind of model could be deployed for other applications and other type of cheese.

Keywords: cheese, miniature, model, pseudomonas spp, spoilage

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Authors: De-Shin Liu, Po-Chun Wen, Zhen-Wei Zhuang, Hsueh-Chih Liu, Pei-Chen Huang

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Wafer probing tests play an important role in semiconductor manufacturing procedures in accordance with the yield and reliability requirement of the wafer after the backend-of-the-line process. Accordingly, the stable physical and electrical contact between the probe and the tested wafer during wafer probing is regarded as an essential issue in identifying the known good die. The probe card can be integrated with multiple probe needles, which are classified as vertical, cantilever and micro-electro-mechanical systems type probe selections. Among all potential probe types, the vertical probe has several advantages as compared with other probe types, including maintainability, high probe density and feasibility for high-speed wafer testing. In the present study, the mechanical response of the wafer probing test with the vertical cobra probe on 720 μm thick silicon (Si) substrate with a 1.4 μm thick aluminum (Al) pad is investigated by the experiment and transient dynamic simulation approach. Because the deformation mechanism of the vertical cobra probe is determined by both bending and buckling mechanisms, the stable correlation between contact forces and overdrive (OD) length must be carefully verified. Moreover, the decent OD length with corresponding contact force contributed to piercing the native oxide layer of the Al pad and preventing the probing test-induced damage on the interconnect system. Accordingly, the scratch depth of the Al pad under various OD lengths is estimated by the atomic force microscope (AFM) and simulation work. In the wafer probing test configuration, the contact phenomenon between the probe needle and the tested object introduced large deformation and twisting of mesh gridding, causing the subsequent numerical divergence issue. For this reason, the arbitrary Lagrangian-Eulerian method is utilized in the present simulation work to conquer the aforementioned issue. The analytic results revealed a slight difference when the OD is considered as 40 μm, and the simulated is almost identical to the measured scratch depths of the Al pad under higher OD lengths up to 70 μm. This phenomenon can be attributed to the unstable contact of the probe at low OD length with the scratch depth below 30% of Al pad thickness, and the contact status will be being stable when the scratch depth over 30% of pad thickness. The splash of the Al pad is observed by the AFM, and the splashed Al debris accumulates on a specific side; this phenomenon is successfully simulated in the transient dynamic simulation. Thus, the preferred testing OD lengths are found as 45 μm to 70 μm, and the corresponding scratch depths on the Al pad are represented as 31.4% and 47.1% of Al pad thickness, respectively. The investigation approach demonstrated in this study contributed to analyzing the mechanical response of wafer probing test configuration under large strain conditions and assessed the geometric designs and material selections of probe needles to meet the requirement of high resolution and high-speed wafer-level probing test for thinned wafer application.

Keywords: wafer probing test, vertical probe, probe mark, mechanical response, FEA simulation

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Authors: Fernanda Gonçalves, Karla Alcântara, Vanessa Moura, Patrícia Nolasco, Jorge Kalil, Maristela Hernandez

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Introduction: Atherosclerosis is a chronic disease where two striking features are observed: retention of lipids and inflammation. Understanding the interaction between immune cells and lipoproteins involved in atherogenesis are urgent challenges, since cardiovascular diseases are the leading cause of death worldwide. Macrophages are critical to the development of atherosclerotic plaques and in the perpetuation of inflammation in these lesions. These cells are also directly involved in unstable plaque rupture. Recently different populations of macrophages are being identified in atherosclerotic lesions. Although the presence of M2 macrophages (macrophages activated by the alternative pathway, eg. The IL-4) has been identified, the function of these cells in atherosclerosis is not yet defined. M2 macrophages have a high endocytic capacity, they promote remodeling of tissues and to have anti-inflammatory activity. However, in atherosclerosis, especially unstable plaques, severe inflammatory reaction, accumulation of cellular debris and intense degradation of the tissue is observed. Thus, it is possible that the M2 macrophages have altered function (phenotype) in atherosclerosis. Objective: Our aim is to evaluate if the presence of oxidized LDL alters the phenotype and function of M2 macrophages in vitro. Methods: For this, we will evaluate whether the addition of lipoprotein in M2 macrophages differentiated in vitro with IL -4 induces 1) a reduction in the secretion of anti-inflammatory cytokines (CBA and ELISA), 2) secretion of inflammatory cytokines (CBA and ELISA), 3) expression of cell activation markers (Flow cytometry), 4) alteration in gene expression of molecules adhesion and extracellular matrix (Real-Time PCR) and 5) Matrix degradation (confocal microscopy). Results: In oxLDL stimulated M2 macrophages cultures we did not find any differences in the expression of the cell surface markers tested, including: HLA-DR, CD80, CD86, CD206, CD163 and CD36. Also, cultures stimulated with oxLDL had similar phagocytic capacity when compared to unstimulated cells. However, in the supernatant of these cultures an increase in the secretion of the pro-inflammatory cytokine IL-8 was detected. No significant changes where observed in IL-6, IL-10, IL-12 and IL-1b levels. The culture supernatant also induced massive extracellular matrix (produced by mouse embryo fibroblast) filaments degradation. When evaluating the expression of 84 extracellular matrix and adhesion molecules genes, we observed that the stimulation of oxLDL in M2 macrophages decreased 47% of the genes and increased the expression of only 3% of the genes. In particular we noted that oxLDL inhibit the expression of 60% of the genes constituents of extracellular matrix and collagen expressed by these cells, including fibronectin1 and collagen VI. We also observed a decrease in the expression of matrix protease inhibitors, such as TIMP 2. On the opposite, the matricellular protein thrombospondin had a 12 fold increase in gene expression. In the presence of native LDL 90% of the genes had no altered expression. Conclusion: M2 macrophages stimulated with oxLDL secrete the pro-inflammatory cytokine IL-8, have an altered extracellular matrix constituents gene expression, and promote the degradation of extracellular matrix. M2 macrophages may contribute to the perpetuation of inflammation in atherosclerosis and to plaque rupture.

Keywords: atherosclerosis, LDL, macrophages, m2

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Authors: Elizabeth M. Annoni, Elena G. Tolkacheva

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Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia that is a known prognostic marker for stroke, heart failure and death. Reentrant mechanisms of rotor formation, which are stable electrical sources of cardiac excitation, are believed to cause AF. No existing commercial mapping systems have been demonstrated to consistently and accurately predict rotor locations outside of the pulmonary veins in patients with persistent AF. There is a clear need for robust spatio-temporal techniques that can consistently identify rotors using unique characteristics of the electrical recordings at the pivot point that can be applied to clinical intracardiac mapping. Recently, we have developed four new signal analysis approaches – Shannon entropy (SE), Kurtosis (Kt), multi-scale frequency (MSF), and multi-scale entropy (MSE) – to identify the pivot points of rotors. These proposed techniques utilize different cardiac signal characteristics (other than local activation) to uncover the intrinsic complexity of the electrical activity in the rotors, which are not taken into account in current mapping methods. We validated these techniques using high-resolution optical mapping experiments in which direct visualization and identification of rotors in ex-vivo Langendorff-perfused hearts were possible. Episodes of ventricular tachycardia (VT) were induced using burst pacing, and two examples of rotors were used showing 3-sec episodes of a single stationary rotor and figure-8 reentry with one rotor being stationary and one meandering. Movies were captured at a rate of 600 frames per second for 3 sec. with 64x64 pixel resolution. These optical mapping movies were used to evaluate the performance and robustness of SE, Kt, MSF and MSE techniques with respect to the following clinical limitations: different time of recordings, different spatial resolution, and the presence of meandering rotors. To quantitatively compare the results, SE, Kt, MSF and MSE techniques were compared to the “true” rotor(s) identified using the phase map. Accuracy was calculated for each approach as the duration of the time series and spatial resolution were reduced. The time series duration was decreased from its original length of 3 sec, down to 2, 1, and 0.5 sec. The spatial resolution of the original VT episodes was decreased from 64x64 pixels to 32x32, 16x16, and 8x8 pixels by uniformly removing pixels from the optical mapping video.. Our results demonstrate that Kt, MSF and MSE were able to accurately identify the pivot point of the rotor under all three clinical limitations. The MSE approach demonstrated the best overall performance, but Kt was the best in identifying the pivot point of the meandering rotor. Artifacts mildly affect the performance of Kt, MSF and MSE techniques, but had a strong negative impact of the performance of SE. The results of our study motivate further validation of SE, Kt, MSF and MSE techniques using intra-atrial electrograms from paroxysmal and persistent AF patients to see if these approaches can identify pivot points in a clinical setting. More accurate rotor localization could significantly increase the efficacy of catheter ablation to treat AF, resulting in a higher success rate for single procedures.

Keywords: Atrial Fibrillation, Optical Mapping, Signal Processing, Rotors

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Authors: Zohra Mhedhbi, Meheret Gaston, Sinda Haoues-Jouve, Julia Hidalgo, Pierre Mazzega

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In the current context of climate change, supporting national and local stakeholders to make climate-smart decisions is necessary but still underdeveloped in many countries. To overcome this problem, the Global Frameworks for Climate Services (GFCS), implemented under the aegis of the United Nations in 2012, has initiated many programs in different countries. The GFCS contributes to the development of Climate Services, an instrument based on the production and transfer of scientific climate knowledge for specific users such as citizens, urban planning actors, or agricultural professionals. As cities concentrate on economic, social and environmental issues that make them more vulnerable to climate change, the New Urban Agenda (NUA), adopted at Habitat III in October 2016, highlights the importance of paying particular attention to disaster risk management, climate and environmental sustainability and urban resilience. In order to support the implementation of the NUA, the World Meteorological Organization (WMO) has identified the urban dimension as one of its priorities and has proposed a new tool, the Integrated Urban Services (IUS), for more sustainable and resilient cities. In the southern countries, there’s a lack of development of climate services, which can be partially explained by problems related to their economic financing. In addition, it is often difficult to make climate change a priority in urban planning, given the more traditional urban challenges these countries face, such as massive poverty, high population growth, etc. Climate services and Integrated Urban Services, particularly in African cities, are expected to contribute to the sustainable development of cities. These tools will help promoting the acquisition of meteorological and socio-ecological data on their transformations, encouraging coordination between national or local institutions providing various sectoral urban services, and should contribute to the achievement of the objectives defined by the United Nations Framework Convention on Climate Change (UNFCCC) or the Paris Agreement, and the Sustainable Development Goals. To assess the state of the art on these various points, the Web of Science metadatabase is queried. With a query combining the keywords "climate*" and "urban*", more than 24,000 articles are identified, source of more than 40,000 distinct keywords (but including synonyms and acronyms) which finely mesh the conceptual field of research. The occurrence of one or more names of the 514 African cities of more than 100,000 inhabitants or countries, reduces this base to a smaller corpus of about 1410 articles (2990 keywords). 41 countries and 136 African cities are cited. The lexicometric analysis of the metadata of the articles and the analysis of the structural indicators (various centralities) of the networks induced by the co-occurrence of expressions related more specifically to climate services show the development potential of these services, identify the gaps which remain to be filled for their implementation and allow to compare the diversity of national and regional situations with regard to these services.

Keywords: African cities, climate change, climate services, integrated urban services, lexicometry, networks, urban planning, web of science

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Authors: Animesh Pan, Geoffrey D. Bothun

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With the development of nanotechnology, research in multifunctional delivery systems has a new pace and dimension. An incipient challenge is to design an all-in-one delivery system that can be used for multiple purposes, including tumor targeting therapy, radio-frequency (RF-), near-infrared (NIR-), light-, or pH-induced controlled release, photothermal therapy (PTT), photodynamic therapy (PDT), and medical diagnosis. In this regard, various inorganic nanoparticles (NPs) are known to show great potential as the 'functional components' because of their fascinating and tunable physicochemical properties and the possibility of multiple theranostic modalities from individual NPs. Magnetic, luminescent, and plasmonic properties are the three most extensively studied and, more importantly biomedically exploitable properties of inorganic NPs. Although successful attempts of combining any two of them above mentioned functionalities have been made, integrating them in one system has remained challenge. Keeping those in mind, controlled designs of complex colloidal nanoparticle system are one of the most significant challenges in nanoscience and nanotechnology. Therefore, systematic and planned studies providing better revelation are demanded. We report a multifunctional delivery platform-based liposome loaded with drug, iron-oxide magnetic nanoparticles (MNPs), and a gold shell on the surface of liposomes, were synthesized using a lipid with polyelectrolyte (layersomes) templating technique. MNPs and the anti-cancer drug doxorubicin (DOX) were co-encapsulated inside liposomes composed by zwitterionic phophatidylcholine and anionic phosphatidylglycerol using reverse phase evaporation (REV) method. The liposomes were coated with positively charge polyelectrolyte (poly-L-lysine) to enrich the interface with gold anion, exposed to a reducing agent to form a gold nanoshell, and then capped with thio-terminated polyethylene glycol (SH-PEG2000). The core-shell nanostructures were characterized by different techniques like; UV-Vis/NIR scanning spectrophotometer, dynamic light scattering (DLS), transmission electron microscope (TEM). This multifunctional system achieves a variety of functions, such as radiofrequency (RF)-triggered release, chemo-hyperthermia, and NIR laser-triggered for photothermal therapy. Herein, we highlight some of the remaining major design challenges in combination with preliminary studies assessing therapeutic objectives. We demonstrate an efficient loading and delivery system to significant cell death of human cancer cells (A549) with therapeutic capabilities. Coupled with RF and NIR excitation to the doxorubicin-loaded core-shell nanostructure helped in securing targeted and controlled drug release to the cancer cells. The present core-shell multifunctional system with their multimodal imaging and therapeutic capabilities would be eminent candidates for cancer theranostics.

Keywords: cancer thernostics, multifunctional nanostructure, photothermal therapy, radiofrequency targeting

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Authors: E. A. Krasikov

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As the service life of an operating nuclear power plant (NPP) increases, the potential misunderstanding of the degradation of aging components must receive more attention. Integrity assurance analysis contributes to the effective maintenance of adequate plant safety margins. In essence, the reactor pressure vessel (RPV) is the key structural component determining the NPP lifetime. Environmentally induced cracking in the stainless steel corrosion-preventing cladding of RPV’s has been recognized to be one of the technical problems in the maintenance and development of light-water reactors. Extensive cracking leading to failure of the cladding was found after 13000 net hours of operation in JPDR (Japan Power Demonstration Reactor). Some of the cracks have reached the base metal and further penetrated into the RPV in the form of localized corrosion. Failures of reactor internal components in both boiling water reactors and pressurized water reactors have increased after the accumulation of relatively high neutron fluences (5´1020 cm–2, E>0,5MeV). Therefore, in the case of cladding failure, the problem arises of hydrogen (as a corrosion product) embrittlement of irradiated RPV steel because of exposure to the coolant. At present when notable progress in plasma physics has been obtained practical energy utilization from fusion reactors (FR) is determined by the state of material science problems. The last includes not only the routine problems of nuclear engineering but also a number of entirely new problems connected with extreme conditions of materials operation – irradiation environment, hydrogenation, thermocycling, etc. Limiting data suggest that the combined effect of these factors is more severe than any one of them alone. To clarify the possible influence of the in-service synergistic phenomena on the FR structural materials properties we have studied hydrogen-irradiated steel interaction including alternating hydrogenation and heat treatment (annealing). Available information indicates that the life of the first wall could be expanded by means of periodic in-place annealing. The effects of neutron fluence and irradiation temperature on steel/hydrogen interactions (adsorption, desorption, diffusion, mechanical properties at different loading velocities, post-irradiation annealing) were studied. Experiments clearly reveal that the higher the neutron fluence and the lower the irradiation temperature, the more hydrogen-radiation defects occur, with corresponding effects on the steel mechanical properties. Hydrogen accumulation analyses and thermal desorption investigations were performed to prove the evidence of hydrogen trapping at irradiation defects. Extremely high susceptibility to hydrogen embrittlement was observed with specimens which had been irradiated at relatively low temperature. However, the susceptibility decreases with increasing irradiation temperature. To evaluate methods for the RPV’s residual lifetime evaluation and prediction, more work should be done on the irradiated metal–hydrogen interaction in order to monitor more reliably the status of irradiated materials.

Keywords: hydrogen, radiation, stability, structural steel

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Authors: Lucia Liu, Matthew Koziol

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Obsessive-compulsive disorder (OCD), a long-lasting anxiety disorder involving recurrent, intrusive thoughts, affects over 2 million adults in the United States. Transcranial magnetic stimulation (TMS) stands out as a noninvasive, cutting-edge therapy that has been shown to reduce symptoms in patients with treatment-resistant OCD. The Food and Drug Administration (FDA) approved protocol pairs TMS sessions with individualized symptom provocation, aiming to improve the susceptibility of brain circuits to stimulation. However, limited standardization or guidance exists on how to conduct symptom provocation and which methods are most effective. This study aims to compare the effect of internal versus external techniques to induce obsessional stress in a clinical setting during TMS therapy. Two symptom provocation methods, (i) Asking patients thought-provoking questions about their obsessions (internal) and (ii) Requesting patients to perform obsession-related tasks (external), were employed in a crossover design with repeated measurement. Thirty-six treatments of NeuroStar TMS were administered to each of two patients over 8 weeks in an outpatient clinic. Patient One received 18 sessions of internal provocation followed by 18 sessions of external provocation, while Patient Two received 18 sessions of external provocation followed by 18 sessions of internal provocation. The primary outcome was the level of self-reported obsessional stress on a visual analog scale from 1 to 10. The secondary outcome was self-reported OCD severity, collected biweekly in a four-level Likert-scale (1 to 4) of bad, fair, good and excellent. Outcomes were compared and tested between provocation arms through repeated measures ANOVA, accounting for intra-patient correlations. Ages were 42 for Patient One (male, White) and 57 for Patient Two (male, White). Both patients had similar moderate symptoms at baseline, as determined through the Yale-Brown Obsessive Compulsive Scale (YBOCS). When comparing obsessional stress induced across the two arms of internal and external provocation methods, the mean (SD) was 6.03 (1.18) for internal and 4.01 (1.28) for external strategies (P=0.0019); ranges were 3 to 8 for internal and 2 to 8 for external strategies. Internal provocation yielded 5 (31.25%) bad, 6 (33.33%) fair, 3 (18.75%) good, and 2 (12.5%) excellent responses for OCD status, while external provocation yielded 5 (31.25%) bad, 9 (56.25%) fair, 1 (6.25%) good, and 1 (6.25%) excellent responses (P=0.58). Internal symptom provocation tactics had a significantly stronger impact on inducing obsessional stress and led to better OCD status (non-significant). This could be attributed to the fact that answering questions may prompt patients to reflect more on their lived experiences and struggles with OCD. In the future, clinical trials with larger sample sizes are warranted to validate this finding. Results support the increased integration of internal methods into structured provocation protocols, potentially reducing the time required for provocation and achieving greater treatment response to TMS.

Keywords: obsessive-compulsive disorder, transcranial magnetic stimulation, mental health, symptom provocation

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Authors: Adil Murtaza, Muhammad Tahir Khan, Awais Ghani, Chao Zhou, Sen Yang, Xiaoping Song

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The morphotropic phase boundary (MPB); a boundary between two different crystallographic symmetries in the composition–temperature phase diagram has been widely studied in ferroelectrics and recently has drawn interest in ferromagnets for obtaining enhanced large field-induced strain. At MPB, the system gets a compressed free energy state, which allows the polarization to freely rotate and hence results in a high magnetoelastic response (e.g., high magnetization, low coercivity, and large magnetostriction). Based on the same mechanism, we designed MPB in a ferromagnetic Tb₁₋ₓNdₓCo₂ system. The temperature-dependent magnetization curves showed spin reorientation (SR); which can be explained by a two-sublattice model. Contrary to previously reported MPB involved ferromagnetic systems, the MPB composition of Tb₀.₃₅Nd₀.₆₅Co₂ exhibits a low saturation magnetization (MS), indicating a compensation of the Tb and Nd magnetic moments at MPB. The coercive field (HC) under a low magnetic field and first anisotropy constant (K₁) shows a minimum value at MPB composition of x=0.65. A detailed spin configuration diagram is provided for the Tb₁₋ₓNdₓCo₂ around the composition for the anisotropy compensation; this can guide the development of novel magnetostrictive materials. The anisotropic magnetostriction (λS) first decreased until x=0.8 and then continuously increased in the negative direction with further increase of Nd concentration. In addition, the large ratio between magnetostriction and the absolute values of the first anisotropy constant (λS/K₁) appears at MPB, indicating that Tb₀.₃₅Nd₀.₆₅Co₂ has good magnetostrictive properties. Present work shows an anomalous type of MPB in ferromagnetic materials, revealing that MPB can also lead to a weakening of magnetoelastic behavior as shown in the ferromagnetic Tb₁₋ₓNdₓCo₂ system. Our work shows the universal presence of MPB in ferromagnetic materials and suggests the differences between different ferromagnetic MPB systems that are important for substantial improvement of magnetic and magnetostrictive properties. Based on the results of this study, similar MPB effects might be achieved in other ferroic systems that can be used for technological applications. The finding of magnetic MPB in the ferromagnetic system leads to some important significances. First, it provides a better understanding of the fundamental concept of spin reorientation transitions (SRT) like ferro-ferro transitions are not only reorientation of magnetization but also crystal symmetry change upon magnetic ordering. Second, the flattened free energy corresponding to a low energy barrier for magnetization rotation and enhanced magnetoelastic response near MPB. Third, to attain large magnetostriction with MPB approach two terminal compounds have different easy magnetization directions below Curie temperature Tc in order to accomplish the weakening of magnetization anisotropy at MPB (as in ferroelectrics), thus easing the magnetic domain switching and the lattice distortion difference between two terminal compounds should be large enough, e.g., lattice distortion of R symmetry ˃˃ lattice distortion of T symmetry). So that the MPB composition agrees to a nearly isotropic state along with large ‘net’ lattice distortion, which is revealed in a higher value of magnetostriction.

Keywords: magnetization, magnetostriction, morphotropic phase boundary (MPB), phase transition

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Authors: Zainab Olabisi Tairu

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The human species is facing some of the most challenging issues encountered as civilization and development occurs. The most salient factors threatening all species globally are habitats loss and degradation, overexploitation, competition with unwanted invasive species, pollution, global climate and various individual lifestyles of indigenous species. In order to avoid or minimize the effect of our actions on the environment and to balance employee work life with their private life, Green Human Resource is important and must be practiced in every organization including Higher Learning Institutions. This study addressed Green HRM from an institutional perspective, University systems are involved in numerous and complex social, educational and extra-curricular activities. The University community must be challenged to rethink and re-construct their environmental policies and practices in order to contribute to sustainable development. Many institutions only look at sustainability from the technology improvement aspect and waste management. People are the principal actors for sustainability development at the institutional level. The aim of the study is to explore the concept of Green Human Resource Management at a case site. Divine Word University (DWU) an Institution of Higher Education that embraced the ‘Printing & Paper use Policy’, also commonly referred to as the ‘paperless policy’, the use of solar as an alternative source of energy, water conservation and improvement in internet technology (IT) with the aim of becoming a green institution in effort to help save the environment. This study used Participatory Action Research as the Overarching methodological framework and Egg of sustainability and Wellbeing as the theoretical perspective in analyzing the data, engaging Case study strategy and a mixed method design at DWU. Focus group interview were conducted with three departments at the University, semi-structure interviews with the senior managers, survey questionnaire administered to students and staff with a sample size of 176 participants, in addition, policy documents were also exploited as extra source of data. Waste management including e-waste appeared to be one of the main concerns at DWU. A vast majority of DWU staff and students expressed the need for their institution to do more on sustainability education. The findings revealed that members of the community are not fully integrated like the Egg of sustainability and wellbeing in order to achieve sustainable development goal. The concept of Green Human Resource Management in Universities lies with the idea that Universities must bear profound responsibilities to manage its stakeholders in an environmental friendly way. Human resource management can help local institutions to recognize the need for changes of lifestyle, production, consumption as well as the end product in order to combat or at least reduce human Induced which produce or aggravate it.

Keywords: sustainability, environmental management, higher education institutions, green human resource management

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Authors: Helen Potkin

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This paper presents a practice-based case study of a project in which the student group designed and planned the curriculum content, classroom activities and assessment briefs in collaboration with the tutor. It focuses on the co-creation of the curriculum within a history and theory module, Researching the Contemporary, which runs for BA (Hons) Fine Art and Art History and for BA (Hons) Art Design History Practice at Kingston University, London. The paper analyses the potential of collaborative approaches to engender students’ investment in their own learning and to encourage reflective and self-conscious understandings of themselves as learners. It also addresses some of the challenges of working in this way, attending to the risks involved and feelings of uncertainty produced in experimental, fluid and open situations of learning. Alongside this, it acknowledges the tensions inherent in adopting such practices within the framework of the institution and within the wider of context of the commodification of higher education in the United Kingdom. The concept underpinning the initiative was to test out co-creation as a creative process and to explore the possibilities of altering the traditional hierarchical relationship between teacher and student in a more active, participatory environment. In other words, the project asked about: what kind of learning could be imagined if we were all in it together? It considered co-creation as producing different ways of being, or becoming, as learners, involving us reconfiguring multiple relationships: to learning, to each other, to research, to the institution and to our emotions. The project provided the opportunity for students to bring their own research and wider interests into the classroom, take ownership of sessions, collaborate with each other and to define the criteria against which they would be assessed. Drawing on students’ reflections on their experience of co-creation alongside theoretical considerations engaging with the processual nature of learning, concepts of equality and the generative qualities of the interrelationships in the classroom, the paper suggests that the dynamic nature of collaborative and participatory modes of engagement have the potential to foster relevant and significant learning experiences. The findings as a result of the project could be quantified in terms of the high level of student engagement in the project, specifically investment in the assessment, alongside the ambition and high quality of the student work produced. However, reflection on the outcomes of the experiment prompts a further set of questions about the nature of positionality in connection to learning, the ways our identities as learners are formed in and through our relationships in the classroom and the potential and productive nature of creative practice in education. Overall, the paper interrogates questions of what it means to work with students to invent and assemble the curriculum and it assesses the benefits and challenges of co-creation. Underpinning it is the argument that, particularly in the current climate of higher education, it is increasingly important to ask what it means to teach and to envisage what kinds of learning can be possible.

Keywords: co-creation, collaboration, learning, participation, risk

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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: Qaisar Ali, Waqar A. Khan, Shafiq R. Qureshi

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Heat transfer in Power Law Fluids across cylindrical surfaces has copious engineering applications. These applications comprises of areas such as underwater pollution, bio medical engineering, filtration systems, chemical, petroleum, polymer, food processing, recovery of geothermal energy, crude oil extraction, pharmaceutical and thermal energy storage. The quantum of research work with diversified conditions to study the effects of combined heat transfer and fluid flow across porous media has increased considerably over last few decades. The most non-Newtonian fluids of practical interest are highly viscous and therefore are often processed in the laminar flow regime. Several studies have been performed to investigate the effects of free and mixed convection in Newtonian fluids along vertical and horizontal cylinder embedded in a saturated porous medium, whereas very few analysis have been performed on Power law fluids along wedge. In this study, boundary layer analysis under the effects of radiation-mixed convection in power law fluids along vertical wedge in porous medium have been investigated using an implicit finite difference method (Keller box method). Steady, 2-D laminar flow has been considered under prescribed surface heat flux condition. Darcy, Boussinesq and Roseland approximations are assumed to be valid. Neglecting viscous dissipation effects and the radiate heat flux in the flow direction, the boundary layer equations governing mixed convection flow over a vertical wedge are transformed into dimensionless form. The single mathematical model represents the case for vertical wedge, cone and plate by introducing the geometry parameter. Both similar and Non- similar solutions have been obtained and results for Non similar case have been presented/ plotted. Effects of radiation parameter, variable heat flux parameter, wedge angle parameter ‘m’ and mixed convection parameter have been studied for both Newtonian and Non-Newtonian fluids. The results are also compared with the available data for the analysis of heat transfer in the prescribed range of parameters and found in good agreement. Results for the details of dimensionless local Nusselt number, temperature and velocity fields have also been presented for both Newtonian and Non-Newtonian fluids. Analysis of data revealed that as the radiation parameter or wedge angle is increased, the Nusselt number decreases whereas it increases with increase in the value of heat flux parameter at a given value of mixed convection parameter. Also, it is observed that as viscosity increases, the skin friction co-efficient increases which tends to reduce the velocity. Moreover, pseudo plastic fluids are more heat conductive than Newtonian and dilatant fluids respectively. All fluids behave identically in pure forced convection domain.

Keywords: porous medium, power law fluids, surface heat flux, vertical wedge

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Authors: Lamia Bouzgarrou, Amira Omrane, Malika Azzouzi, Asma Kheder, Amira Saadallah, Ilhem Boussarsar, Kamel Rejeb

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Introduction: Increasing the women’s labor force participation is a political issue in countries with developed economies and those with low growth prospects. However, in the labor market, women continue to face several obstacles, either for the integration or for the maintenance at work. This study aims to assess the prevalence of premature withdrawal from working life -due to invalidity or medical justified early retirement- among active women in the Tunisian center and to identify its determinants. Material and methods: We conducted a cross-sectional study, over one year, focusing on the agreement for invalidity or early retirement for premature usury of the body- delivered by the medical commission of the National Health Insurance Fund (CNAM) in the central Tunisian district. We exhaustively selected women's files. Data related to Socio-demographic characteristics, professional and medical ones, were collected from the CNAM's administrative and medical files. Results: During the period of one year, 222 women have had an agreement for premature departure of their professional activity. Indeed, 149 women (67.11%) benefit of from invalidity agreement and 20,27% of them from favorable decision for early retirement. The average age was 50 ± 6 years with extremes of 23 and 62 years, and 18.9% of women were under 45 years. Married women accounted for 69.4% and 59.9% of them had at least one dependent child in charge. The average professional seniority in the sector was 23 ± 8 years. The textile-clothing sector was the most affected, with 70.7% of premature departure. Medical reasons for withdrawal from working life were mainly related to neuro-degenerative diseases in 46.8% of cases, rheumatic ones in 35.6% of cases and cardiovascular diseases in 22.1% of them. Psychiatric and endocrine disorders motivated respectively 17.1% and 13.5% of these departures. The evaluation of the sequels induced by these pathologies concluded to an average permanent partial disability equal to 61.4 ± 17.3%. The analytical study concluded that the agreement of disability or early retirement was correlated with the insured ‘age (p = 10-3), the professional seniority (p = 0.003) and the permanent partial incapacity (PPI) rate assessed by the expert physician (p = 0.04). No other social or professional factors were correlated with this decision. Conclusion: Despite many advances in labour law and Tunisian legal text on employability, women still exposed to several social and professional inequalities (payment inequality, precarious work ...). Indeed, women are often pushed to accept working in adverse conditions, thus they are more vulnerable to develop premature wear on the body and being forced to premature departures from the world of work. These premature withdrawals from active life are not only harmful to the concerned women themselves, but also associated with considerable costs for the insurance organism and the society. In order to ensure maintenance at work for women, a political commitment is imperative in the implementation of global prevention strategies and the improvement of working conditions, particularly in our socio-cultural context.

Keywords: Active Women , Early Retirement , Invalidity , Maintenance at Work

Procedia PDF Downloads 152

Authors: Mustaffa Kamal Bashar Mohd Fauzi, Puteri Shireen Jahn Kassim, Nurul Syala Abdul Latip

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It is increasingly realized that sustainability includes both a response to the climatic and cultural context of a place. To assess the cultural context, a morphological analysis of urban patterns from heritage legacies is necessary. While the climatic form is derived from an analysis of meteorological data, cultural patterns and forms must be abstracted from a typological and morphological study. This current study aims to analyzes morphological and formal elements of water-based architectural and urban design of past Islamic vernacular complexes in the hot arid regions and how a vast utilization of water was shaped and sited to act as cooling devices for an entire complex. Apart from its pleasant coolness, water can be used in an aesthetically way such as emphasizing visual axes, vividly enhancing the visual of the surrounding environment and symbolically portraying the act of purity in the design. By comparing 2 case studies based on the analysis of interactions of water features into the form, planning and morphology of 2 Islamic heritage complexes, Fatehpur Sikri (India) and Lahore Fort (Pakistan) with a focus on Shish Mahal of Lahore Fort in terms of their mass, architecture and urban planning, it is agreeable that water plays an integral role in their climatic amelioration via different methods of water conveyance system. Both sites are known for their substantial historical values and prominent for their sustainable vernacular buildings for example; the courtyard of Shish Mahal in Lahore fort are designed to provide continuous coolness by constructing various miniatures water channels that run underneath the paved courtyard. One of the most remarkable features of this system that all water is made dregs-free before it was inducted into these underneath channels. In Fatehpur Sikri, the method of conveyance seems differed from Lahore Fort as the need to supply water to the ridge where Fatehpur Sikri situated is become the major challenges. Thus, the achievement of supplying water to the palatial complexes is solved by placing inhabitable water buildings within the two supply system for raising water. The process of raising the water can be either mechanical or laborious inside the enclosed well and water rising houses. The studies analyzes and abstract the water supply forms, patterns and flows in 3-dimensional shapes through the actions of evaporative cooling and wind-induced ventilation under arid climates. Through the abstraction analytical and descriptive relational morphology of the spatial configurations, the studies can suggest the idealized spatial system that can be used in urban design and complexes which later became a methodological and abstraction tool of sustainability to suit the modern contemporary world.

Keywords: heritage site, Islamic vernacular architecture, water features, morphology, urban design

Procedia PDF Downloads 375

Authors: Ines Raies, Eric Kohler, Marc Fleury, Béatrice Ledésert

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In this work, the impact of clay minerals on the formation damage of sandstone reservoirs is studied to provide a better understanding of the problem of deep geothermal reservoir permeability reduction due to fine particle dispersion and migration. In some situations, despite the presence of filters in the geothermal loop at the surface, particles smaller than the filter size (<1 µm) may surprisingly generate significant permeability reduction affecting in the long term the overall performance of the geothermal system. Our study is carried out on cores from a Triassic reservoir in the Paris Basin (Feigneux, 60 km Northeast of Paris). Our goal is to first identify the clays responsible for clogging, a mineralogical characterization of these natural samples was carried out by coupling X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray Spectroscopy (EDS). The results show that the studied stratigraphic interval contains mostly illite and chlorite particles. Moreover, the spatial arrangement of the clays in the rocks as well as the morphology and size of the particles, suggest that illite is more easily mobilized than chlorite by the flow in the pore network. Thus, based on these results, illite particles were prepared and used in core flooding in order to better understand the factors leading to the aggregation and deposition of this type of clay particles in geothermal reservoirs under various physicochemical and hydrodynamic conditions. First, the stability of illite suspensions under geothermal conditions has been investigated using different characterization techniques, including Dynamic Light Scattering (DLS) and Scanning Transmission Electron Microscopy (STEM). Various parameters such as the hydrodynamic radius (around 100 nm), the morphology and surface area of aggregates were measured. Then, core-flooding experiments were carried out using sand columns to mimic the permeability decline due to the injection of illite-containing fluids in sandstone reservoirs. In particular, the effects of ionic strength, temperature, particle concentration and flow rate of the injected fluid were investigated. When the ionic strength increases, a permeability decline of more than a factor of 2 could be observed for pore velocities representative of in-situ conditions. Further details of the retention of particles in the columns were obtained from Magnetic Resonance Imaging and X-ray Tomography techniques, showing that the particle deposition is nonuniform along the column. It is clearly shown that very fine particles as small as 100 nm can generate significant permeability reduction under specific conditions in high permeability porous media representative of the Triassic reservoirs of the Paris basin. These retention mechanisms are explained in the general framework of the DLVO theory

Keywords: geothermal energy, reinjection, clays, colloids, retention, porosity, permeability decline, clogging, characterization, XRD, SEM-EDS, STEM, DLS, NMR, core flooding experiments

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Authors: Alastair Hales, Xi Jiang

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Numerical methods are used to evaluate the operation of confined face-to-face piezoelectric fan arrays as pitch, P, between the blades is varied. Both in-phase and counter-phase oscillation are considered. A piezoelectric fan consists of a fan blade, which is clamped at one end, and an extremely low powered actuator. This drives the blade tip’s oscillation at its first natural frequency. Sufficient blade tip speed, created by the high oscillation frequency and amplitude, is required to induce vortices and downstream volume flow in the surrounding air. A single piezoelectric fan may provide the ideal solution for low powered hot spot cooling in an electronic device, but is unable to induce sufficient downstream airflow to replace a conventional air mover, such as a convection fan, in power electronics. Piezoelectric fan arrays, which are assemblies including multiple fan blades usually in face-to-face orientation, must be developed to widen the field of feasible applications for the technology. The potential energy saving is significant, with a 50% power demand reduction compared to convection fans even in an unoptimised state. A numerical model of a typical piezoelectric fan blade is derived and validated against experimental data. Numerical error is found to be 5.4% and 9.8% using two data comparison methods. The model is used to explore the variation of pitch as a function of amplitude, A, for a confined two-blade piezoelectric fan array in face-to-face orientation, with the blades oscillating both in-phase and counter-phase. It has been reported that in-phase oscillation is optimal for generating maximum downstream velocity and flow rate in unconfined conditions, due at least in part to the beneficial coupling between the adjacent blades that leads to an increased oscillation amplitude. The present model demonstrates that confinement has a significant detrimental effect on in-phase oscillation. Even at low pitch, counter-phase oscillation produces enhanced downstream air velocities and flow rates. Downstream air velocity from counter-phase oscillation can be maximally enhanced, relative to that generated from a single blade, by 17.7% at P = 8A. Flow rate enhancement at the same pitch is found to be 18.6%. By comparison, in-phase oscillation at the same pitch outputs 23.9% and 24.8% reductions in peak downstream air velocity and flow rate, relative to that generated from a single blade. This optimal pitch, equivalent to those reported in the literature, suggests that counter-phase oscillation is less affected by confinement. The optimal pitch for generating bulk airflow from counter-phase oscillation is large, P > 16A, due to the small but significant downstream velocity across the span between adjacent blades. However, by considering design in a confined space, counterphase pitch should be minimised to maximise the bulk airflow generated from a certain cross-sectional area within a channel flow application. Quantitative values are found to deviate to a small degree as other geometric and operational parameters are varied, but the established relationships are maintained.

Keywords: piezoelectric fans, low energy cooling, power electronics, computational fluid dynamics

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Authors: Hanan M. Hassan, Laila Abouzeid, Lamya H. Al-Wahaibi, George S. G. Shehatou, Ali A. El-Emam

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Cancer is a major public health problem and the second leading cause of death worldwide. In 2020, cancer diagnosis and treatment have been negatively affected by the coronavirus 2019 (COVID-19) pandemic. During the quarantine, because of the limited access to healthcare and avoiding exposure to COVID-19 as a contagious disease; patients of cancer suffered deferments in follow-up and treatment regimens leading to substantial worsening of disease, death, and increased healthcare costs. Thus, this study is designed to investigate the molecular mechanisms by which adamantne derivatives attenuate hepatocllular carcinoma experimentally and theoretically. There is a close association between increased resistance to anticancer drugs and defective apoptosis that considered a causative factor for oncogenesis. Cancer cells use different molecular pathways to inhibit apoptosis, BAX and Bcl-2 proteins have essential roles in the progression or inhibition of intrinsic apoptotic pathways triggered by mitochondrial dysfunction. Therefore, their balance ratio can promote the cellular apoptotic fate. In this study, the in vitro cytotoxic effects of seven synthetic adamantyl isothiorea derivatives were evaluated against five human tumor cell lines by MTT assay. Compounds 5 and 6 showed the best results, mostly against hepatocellular carcinoma (HCC). Hence, in vivo studies were performed in male Sprague-Dawley (SD) rats in which experimental hepatocellular carcinoma was induced with thioacetamide (TAA) (200 mg/kg, i.p., twice weekly) for 16 weeks. The most promising compounds, 5 and 6, were administered to treat liver cancer rats at a dose of 10 mg/kg/day for an additional two weeks, and the effects were compared with doxorubicin (DR), the anticancer drug. Hepatocellular carcinoma was evidenced by a dramatic increase in liver indices, oxidative stress markers, and immunohistochemical studies that were accompanied by a plethora of inflammatory mediators and alterations in the apoptotic cascade. Our results showed that treatment with adamantane derivatives 5 and 6 significantly suppressed fibrosis, inflammation, and other histopathological insults resulting in the diminished formation of hepatocyte tumorigenesis. Moreover, administration of the tested compounds resulted in amelioration of EGFR protein expression, upregulation of BAX, and lessening down of Bcl-2 levels that prove their role as apoptosis inducers. Also, the docking simulations performed for adamantane showed good fit and binding to the EGFR protein through hydrogen bond formation with conservative amino acids, which gives a shred of strong evidence for its hepatoprotective effect. In most analyses, the effects of compound 6 were more comparable to DR than compound 5. Our findings suggest that adamantane derivatives 5 and 6 are shown to have cytotoxic activity against HCC in vitro and in vivo, by more than one mechanism, possibly by inhibiting the TLR4-MyD88-NF-κB pathway and targeting EGFR signaling.

Keywords: adamantane, EGFR, HCC, apoptosis

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Authors: O. Sauperl, L. Fras Zemljic

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The textile industry is gaining increasing importance in the field of medical materials. Therefore, presented research is focused on textile materials for external (out-of-body) use. Such materials could be various hygienic textile products (diapers, tampons, sanitary napkins, incontinence products, etc.), protective textiles and various hospital linens (surgical covers, masks, gowns, cloths, bed linens, etc.) wound pillows, bandages, orthopedic socks, etc. Function of tampons and sanitary napkins is not only to provide protection during the menstrual cycle, but their function can be also to take care of physiological or pathological vaginal discharge. In general, women's intimate areas are against infection protected by a low pH value of the vaginal flora. High pH inhibits the development of harmful microorganisms, as it is difficult to be reproduced in an acidic environment. The normal vaginal flora in healthy women is highly colonized by lactobacilli. The lactic acid produced by these organisms maintains the constant acidity of the vagina. If the balance of natural protection breaks, infections can occur. In the market, there exist probiotic tampons as a medical product supplying the vagina with beneficial probiotic lactobacilli. But, many users have concerns about the use of tampons due to the possible dry-out of the vagina as well as the possible toxic shock syndrome, which is the reason that they use mainly sanitary napkins during the menstrual cycle. Functionalization of sanitary napkins with probiotics is, therefore, interesting in regard to maintain a healthy vaginal flora and to offer to users added value of the sanitary napkins in the sense of health- and environmentally-friendly products. For this reason, the presented research is oriented in functionalization of the sanitary napkins with the probiotic paste in order to activate the lactic acid bacteria presented in the core of the functionalized sanitary napkin at the time of the contact with the menstrual fluid. In this way, lactobacilli could penetrate into vagina and by maintaining healthy vaginal flora to reduce the risk of vaginal disorders. In regard to the targeted research problem, the influence of probiotic paste applied onto cotton hygienic napkins on selected properties was studied. The aim of the research was to determine whether the sanitary napkins with the applied probiotic paste may assure suitable vaginal pH to maintain a healthy vaginal flora during the use of this product. Together with this, sorption properties of probiotic functionalized sanitary napkins were evaluated and compared to the untreated one. The research itself was carried out on the basis of tracking and controlling the input parameters, currently defined by Slovenian producer (Tosama d.o.o.) as the most important. Successful functionalization of sanitary pads with the probiotic paste was confirmed by ATR-FTIR spectroscopy. Results of the methods used within the presented research show that the absorption of the pads treated with probiotic paste deteriorates compared to non-treated ones. The coating shows a 6-month stability. Functionalization of sanitary pads with probiotic paste is believed to have a commercial potential for lowering the probability of infection during the menstrual cycle.

Keywords: functionalization, probiotic paste, sanitary pads, textile materials

Procedia PDF Downloads 191

Authors: W. S. Barber, S. L. King

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This paper is a qualitative case study analysis of the development of a fully online learning community of graduate students through arts-based community building activities. With increasing numbers and types of online learning spaces, it is incumbent upon educators to continue to push the edge of what best practices look like in digital learning environments. In digital learning spaces, instructors can no longer be seen as purveyors of content knowledge to be examined at the end of a set course by a final test or exam. The rapid and fluid dissemination of information via Web 3.0 demands that we reshape our approach to teaching and learning, from one that is content-focused to one that is process-driven. Rather than having instructors as formal leaders, today’s digital learning environments require us to share expertise, as it is the collective experiences and knowledge of all students together with the instructors that help to create a very different kind of learning community. This paper focuses on innovations pursued in a 36 hour 12 week graduate course in higher education entitled “Critical and Reflective Practice”. The authors chronicle their journey to developing a fully online learning community (FOLC) by emphasizing the elements of social, cognitive, emotional and digital spaces that form a moving interplay through the community. In this way, students embrace anywhere anytime learning and often take the learning, as well as the relationships they build and skills they acquire, beyond the digital class into real world situations. We argue that in order to increase student online engagement, pedagogical approaches need to stem from two primary elements, both creativity and critical reflection, that are essential pillars upon which instructors can co-design learning environments with students. The theoretical framework for the paper is based on the interaction and interdependence of Creativity, Intuition, Critical Reflection, Social Constructivism and FOLCs. By leveraging students’ embedded familiarity with a wide variety of technologies, this case study of a graduate level course on critical reflection in education, examines how relationships, quality of work produced, and student engagement can improve by using creative and imaginative pedagogical strategies. The authors examine their professional pedagogical strategies through the lens that the teacher acts as facilitator, guide and co-designer. In a world where students can easily search for and organize information as self-directed processes, creativity and connection can at times be lost in the digitized course environment. The paper concludes by posing further questions as to how institutions of higher education may be challenged to restructure their credit granting courses into more flexible modules, and how students need to be considered an important part of assessment and evaluation strategies. By introducing creativity and critical reflection as central features of the digital learning spaces, notions of best practices in digital teaching and learning emerge.

Keywords: online, pedagogy, learning, communities

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Authors: Hamed Movahedi, Nicolas Bovet, Henning Friis Poulsen

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Following the advent of the Industrial Revolution, there has been a significant increase in the extraction and utilization of hydrocarbon and fossil fuel resources. However, a new era has emerged, characterized by a shift towards sustainable practices, namely the reduction of carbon emissions and the promotion of renewable energy generation. Given the substantial number of mature oil and gas wells that have been developed inside the petroleum reservoir domain, it is imperative to establish an environmental strategy and adopt appropriate measures to effectively seal and decommission these wells. In general, the cement plug serves as a material for plugging purposes. Nevertheless, there exist some scenarios in which the durability of such a plug is compromised, leading to the potential escape of hydrocarbons via fissures and fractures within cement plugs. Furthermore, cement is often not considered a practical solution for temporary plugging, particularly in the case of well sites that have the potential for future gas storage or CO2 injection. The Danish oil and gas industry has promising potential as a prospective candidate for future carbon dioxide (CO2) injection, hence contributing to the implementation of carbon capture strategies within Europe. The primary reservoir component consists of chalk, a rock characterized by limited permeability. This work focuses on the development and characterization of a novel hydrogel variant. The hydrogel is designed to be injected via a low-permeability reservoir and afterward undergoes a transformation into a high-viscosity gel. The primary objective of this research is to explore the potential of this hydrogel as a new solution for effectively plugging well flow. Initially, the synthesis of polyacrylamide was carried out using radical polymerization inside the confines of the reaction flask. Subsequently, with the application of the Hoffman rearrangement, the polymer chain undergoes partial amination, facilitating its subsequent reaction with the crosslinker and enabling the formation of a hydrogel in the subsequent stage. The organic crosslinker, glutaraldehyde, was employed in the experiment to facilitate the formation of a gel. This gel formation occurred when the polymeric solution was subjected to heat within a specified range of reservoir temperatures. Additionally, a rheological survey and gel time measurements were conducted on several polymeric solutions to determine the optimal concentration. The findings indicate that the gel duration is contingent upon the starting concentration and exhibits a range of 4 to 20 hours, hence allowing for manipulation to accommodate diverse injection strategies. Moreover, the findings indicate that the gel may be generated in environments characterized by acidity and high salinity. This property ensures the suitability of this substance for application in challenging reservoir conditions. The rheological investigation indicates that the polymeric solution exhibits the characteristics of a Herschel-Bulkley fluid with somewhat elevated yield stress prior to solidification.

Keywords: polyacrylamide, hofmann rearrangement, rheology, gel time

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Authors: Shamsher Singh

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The Diaspora Literature involves a concept of native land, from where the displacement occurs and a record of harsh journeys undertaken on account of economic compulsions. Basically, Diaspora is a splintered community living in eviction. The scattering (initially) signifies the location of a fluid human autonomous space involving a complex set of negotiations and exchange between the nostalgia and desire for the native land and the making of a new home, adapting to the relationships between the minority and majority, being spokes persons for minority rights and their people back native place and significantly transacting the Contact Zone - a space changed with the possibility of multiple challenges. They write in the background of the sublime qualities of their homeland and, at the same time, try to fit themselves into the traditions and cultural values of other strange communities or land. It also serves as an interconnection of the various cultures involved, and it is used to understand the customs of different cultures and countries; it is also a source of inspiration globally. Although diasporic literature originated back in the 20th century, it spread to other countries like Britain, Canada, America, Denmark, Netherland, Australia, Kenya, Sweden, Kuwait and different parts of Europe. Meaning of Diaspora is the combination of two words which means the movement of people away from their own country or motherland. From a historical point of view, the ‘Diaspora’ is often associated with Jewish bigotry. At the moment, the Diaspora is used for the dispersal of social or cultural groups. This group will be living in two different streams of cultures at the same time. One who left behind his culture and the other has to adapt himself to new cultural situations. The diasporic mind hangs between his birth land and place of work at the same time. A person’s mental state, living in dual existence, gives birth to Dysphoria sensation. Litterateurs had different experiences in this type of sensation e.g., social, universal, political, economic and experiences from the strange land. The struggle of these experiences is seen in diasporic literature. When a person moves to different land or country to fulfill his dreams, the discrimination of language, work and other difficulties with strangers make his relationship more emotional and deeper into his past. These past memories and relations create more difficulties in settling in a foreign land. He lives there physically, but his mental state is in his past constantly, and he ends up his life in those background memories. A person living in Diaspora is actually a dual visionary man. Although this double vision expands his global consciousness, due to this vision, he gains judgemental qualities to understand others. At the same time, he weighs his respect for his native land and the situations of foreign land he experiences, and he finds it difficult to survive in those conditions. It can be said that diaspora literature indicates a person or social organization who lives dual life inquisition structure which becomes the cause of diasporic literature.

Keywords: homeland sickness, language problem, quest for identity, materialistic desire

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Authors: Marcel Verwey, Anna M. Joubert, Elsie M. Nolte, Wolfgang Dohle, Barry V. L. Potter, Anne E. Theron

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A tetrahydroisoquinolinone (THIQ) core can be used to mimic the A,B-ring of colchicine site-binding microtubule disruptors such as 2-methoxyestradiol in the design of anti-cancer agents. Steroidomimeric microtubule disruptors were synthesized by introducing C'2 and C'3 of the steroidal A-ring to C'6 and C'7 of the THIQ core and by introducing a decorated hydrogen bond acceptor motif projecting from the steroidal D-ring to N'2. For this in vitro study, four non-steroidal THIQ-based analogues were investigated and comparative studies were done between the non-sulphamoylated compound STX 3450 and the sulphamoylated compounds STX 2895, STX 3329 and STX 3451. The objective of this study was to investigate the modes of cell death induced by these four THIQ-based analogues in A549 lung carcinoma epithelial cells and metastatic breast adenocarcinoma MDA-MB-231 cells. Cytotoxicity studies to determine the half maximal growth inhibitory concentrations were done using spectrophotometric quantification via crystal violet staining and lactate dehydrogenase (LDH) assays. Microtubule integrity and morphologic changes of exposed cells were investigated using polarization-optical transmitted light differential interference contrast microscopy, transmission electron microscopy and confocal microscopy. Flow cytometric quantification was used to determine apoptosis induction and the effect that THIQ-based analogues have on cell cycle progression. Signal transduction pathways were elucidated by quantification of the mitochondrial membrane integrity, cytochrome c release and caspase 3, -6 and -8 activation. Induction of autophagic cell death by the THIQ-based analogues was investigated by morphological assessment of fluorescent monodansylcadaverine (MDC) staining of acidic vacuoles and by quantifying aggresome formation via flow cytometry. Results revealed that these non-steroidal microtubule disrupting analogues inhibited 50% of cell growth at nanomolar concentrations. Immunofluorescence microscopy indicated microtubule depolarization and the resultant mitotic arrest was further confirmed through cell cycle analysis. Apoptosis induction via the intrinsic pathway was observed due to depolarization of the mitochondrial membrane, induction of cytochrome c release as well as, caspase 3 activation. Potential involvement of programmed cell death type II was observed due to the presence of acidic vacuoles and aggresome formation. Necrotic cell death did not contribute significantly, indicated by stable LDH levels. This in vitro study revealed the induction of the intrinsic apoptotic pathway as well as possible involvement of autophagy after exposure to these THIQ-based analogues in both MDA-MB-231- and A549 cells. Further investigation of this series of anticancer drugs still needs to be conducted to elucidate the temporal, mechanistic and functional crosstalk mechanisms between the two observed programmed cell deaths pathways.

Keywords: apoptosis, autophagy, cancer, microtubule disruptor

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Authors: Brian J. Biroscak

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In the United States (US), “sex trafficking” is defined at the federal level in the Trafficking Victims Protection Act of 2000 as encompassing a number of processes such as recruitment, transportation, and provision of a person for the purpose of a commercial sex act. It involves the use of force, fraud, or coercion, or in which the person induced to perform such act has not attained 18 years of age. Accumulating evidence suggests that sex trafficking is exacerbated by social and environmental stressors (e.g., pandemics). Given that “provision” is a key part of the definition, “provisioning systems” may offer a useful lens through which to study sex trafficking dynamics. Provisioning systems are the social systems connecting individuals, small groups, entities, and embedded communities as they seek to satisfy their needs and wants for goods, services, experiences and ideas through value-based exchange in communities. This project presents a conceptual framework for understanding sex trafficking dynamics in the context of the COVID pandemic. The framework is developed as a system dynamics simulation model based on published evidence, social and behavioral science theory, and key informant interviews with stakeholders from the Protection, Prevention, Prosecution, and Partnership sectors in one US state. This “4 P Paradigm” has been described as fundamental to the US government’s anti-trafficking strategy. The present research question is: “How do sex trafficking systems (e.g., supply, demand and price) interact with other provisioning systems (e.g., networks of organizations that help sexually exploited persons) to influence trafficking over time vis-à-vis the COVID pandemic?” Semi-structured interviews with stakeholders (n = 19) were analyzed based on grounded theory and combined for computer simulation. The first step (Problem Definition) was completed by open coding video-recorded interviews, supplemented by a literature review. The model depicts provision of sex trafficking services for victims and survivors as declining in March 2020, coincidental with COVID, but eventually rebounding. The second modeling step (Dynamic Hypothesis Formulation) was completed by open- and axial coding of interview segments, as well as consulting peer-reviewed literature. Part of the hypothesized explanation for changes over time is that the sex trafficking system behaves somewhat like a commodities market, with each of the other subsystems exhibiting delayed responses but collectively keeping trafficking levels below what they would be otherwise. Next steps (Model Building & Testing) led to a ‘proof of concept’ model that can be used to conduct simulation experiments and test various action ideas, by taking model users outside the entire system and seeing it whole. If sex trafficking dynamics unfold as hypothesized, e.g., oscillated post-COVID, then one potential leverage point is to address the lack of information feedback loops between the actual occurrence and consequences of sex trafficking and those who seek to prevent its occurrence, prosecute the traffickers, protect the victims and survivors, and partner with the other anti-trafficking advocates. Implications for researchers, administrators, and other stakeholders are discussed.

Keywords: pandemics, provisioning systems, sex trafficking, system dynamics modeling

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Authors: Frederick Huie, Lauren Fusfeld, William Burchenal, Scott Howell, Alyssa McVey, Thomas F. Goss

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Alzheimer’s Disease (AD) is a degenerative brain disease characterized by memory loss and cognitive decline that presents a substantial economic burden for patients and health insurers in the US. This study evaluates the payer budget impact of the DISCERN™ test in the diagnosis and management of patients with symptoms of dementia evaluated for AD. DISCERN™ comprises three assays that assess critical factors related to AD that regulate memory, formation of synaptic connections among neurons, and levels of amyloid plaques and neurofibrillary tangles in the brain and can provide a quicker, more accurate diagnosis than tests in the current diagnostic pathway (CDP). An Excel-based model with a three-year horizon was developed to assess the budget impact of DISCERN™ compared with CDP in a Medicare Advantage plan with 1M beneficiaries. Model parameters were identified through a literature review and were verified through consultation with clinicians experienced in diagnosis and management of AD. The model assesses direct medical costs/savings for patients based on the following categories: •Diagnosis: costs of diagnosis using DISCERN™ and CDP. •False Negative (FN) diagnosis: incremental cost of care avoidable with a correct AD diagnosis and appropriately directed medication. •True Positive (TP) diagnosis: AD medication costs; cost from a later TP diagnosis with the CDP versus DISCERN™ in the year of diagnosis, and savings from the delay in AD progression due to appropriate AD medication in patients who are correctly diagnosed after a FN diagnosis.•False Positive (FP) diagnosis: cost of AD medication for patients who do not have AD. A one-way sensitivity analysis was conducted to assess the effect of varying key clinical and cost parameters ±10%. An additional scenario analysis was developed to evaluate the impact of individual inputs. In the base scenario, DISCERN™ is estimated to decrease costs by $4.75M over three years, equating to approximately $63.11 saved per test per year for a cohort followed over three years. While the diagnosis cost is higher with DISCERN™ than with CDP modalities, this cost is offset by the higher overall costs associated with CDP due to the longer time needed to receive a TP diagnosis and the larger number of patients who receive a FN diagnosis and progress more rapidly than if they had received appropriate AD medication. The sensitivity analysis shows that the three parameters with the greatest impact on savings are: reduced sensitivity of DISCERN™, improved sensitivity of the CDP, and a reduction in the percentage of disease progression that is avoided with appropriate AD medication. A scenario analysis in which DISCERN™ reduces the utilization for patients of computed tomography from 21% in the base case to 16%, magnetic resonance imaging from 37% to 27% and cerebrospinal fluid biomarker testing, positive emission tomography, electroencephalograms, and polysomnography testing from 4%, 5%, 10%, and 8%, respectively, in the base case to 0%, results in an overall three-year net savings of $14.5M. DISCERN™ improves the rate of accurate, definitive diagnosis of AD earlier in the disease and may generate savings for Medicare Advantage plans.

Keywords: Alzheimer’s disease, budget, dementia, diagnosis.

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