Search results for: therapeutic simulations

Authors: Zachary Cooper-Baldock, Paulo E. Santos, Russell S. A. Brinkworth, Karl Sammut

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- In recent years, large unmanned underwater vehicles such as the Boeing Voyager and Anduril Ghost Shark have been developed. These vessels can be structured to contain onboard internal payload bays. These payload bays can serve a variety of purposes – including the launch and recovery (LAR) of smaller underwater vehicles. The LAR of smaller vessels is extremely important, as it enables transportation over greater distances, increased time on station, data transmission and operational safety. The larger vessel and its payload bay structure complicate the LAR of UUVs in contrast to static docks that are affixed to the seafloor, as they actively impact the local flow field. These flow field impacts require analysis to determine if UUV vessels can be safely launched and recovered inside the motherships. This research seeks to determine the hydrodynamic forces exerted on a vertically over-actuated, small, unmanned underwater vehicle (OUUV) during an internal LAR manoeuvre and compare this to an under-actuated vessel (UUUV). In this manoeuvre, the OUUV is navigated through the stern wake region of the larger vessel to a set point within the internal payload bay. The manoeuvre is simulated using ANSYS Fluent computational fluid dynamics models, covering the entire recovery of the OUUV and UUUV. The analysis of the OUUV is compared against the UUUV to determine the differences in the exerted forces. Of particular interest are the drag, pressure, turbulence and flow field effects exerted as the OUUV is driven inside the payload bay of the larger vessel. The hydrodynamic forces and flow field disturbances are used to determine the feasibility of making such an approach. From the simulations, it was determined that there was no significant detrimental physical forces, particularly with regard to turbulence. The flow field effects exerted by the OUUV are significant. The vertical thrusters exert significant wake structures, but their orientation ensures the wake effects are exerted below the UUV, minimising the impact. It was also seen that OUUV experiences higher drag forces compared to the UUUV, which will correlate to an increased energy expenditure. This investigation found no key indicators that recovery via a mothership payload bay was not feasible. The turbulence, drag and pressure phenomenon were of a similar magnitude to existing static and towed dock structures.

Keywords: underwater vehicles, submarine, autonomous underwater vehicles, auv, computational fluid dynamics, flow fields, pressure, turbulence, drag

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Authors: Elisabetta Cianfanelli, Paolo Pupparo, Maria Claudia Coppola

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The recent evolutions in the innovation processes and in the intrinsic tendencies of the product development process, lead to new considerations on the design flow. The instability and complexity that contemporary life describes, defines new problems in the production of products, stimulating at the same time the adoption of new solutions across the entire design process. The advent of Additive Manufacturing, but also of IOT and AI technologies, continuously puts us in front of new paradigms regarding design as a social activity. The totality of these technologies from the point of view of application describes a whole series of problems and considerations immanent to design thinking. Addressing these problems may require some initial intuition and the use of some provisional set of rules or plausible strategies, i.e., heuristic reasoning. At the same time, however, the evolution of digital technology and the computational speed of new design tools describe a new and contrary design framework in which to operate. It is therefore interesting to understand the opportunities and boundaries of the new man-algorithm relationship. The contribution investigates the man-algorithm relationship starting from the state of the art of the Made in Italy model, the most known fields of application are described and then focus on specific cases in which the mutual relationship between man and AI becomes a new driving force of innovation for entire production chains. On the other hand, the use of algorithms could engulf many design phases, such as the definition of shape, dimensions, proportions, materials, static verifications, and simulations. Operating in this context, therefore, becomes a strategic action, capable of defining fundamental choices for the design of product systems in the near future. If there is a human-algorithm combination within a new integrated system, quantitative values can be controlled in relation to qualitative and material values. The trajectory that is described therefore becomes a new design horizon in which to operate, where it is interesting to highlight the good practices that already exist. In this context, the designer developing new forms can experiment with ways still unexpressed in the project and can define a new synthesis and simplification of algorithms, so that each artifact has a signature in order to define in all its parts, emotional and structural. This signature of the designer, a combination of values and design culture, will be internal to the algorithms and able to relate to digital technologies, creating a generative dialogue for design purposes. The result that is envisaged indicates a new vision of digital technologies, no longer understood only as of the custodians of vast quantities of information, but also as a valid integrated tool in close relationship with the design culture.

Keywords: decision making, design euristics, product design, product design process, design paradigms

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Authors: Suruchi Saini, Hitender Kumar Tyagi

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With the rapid progress of the nanotechnology industry, it is becoming increasingly important to have compact semiconductor devices to function and offer the best results at various technology nodes. While performing the scaling of the device, several short-channel effects occur. To minimize these scaling limitations, some device architectures have been developed in the semiconductor industry. FinFET is one of the most promising structures. Also, the double-gate 2D Fin field effect transistor has the benefit of suppressing short channel effects (SCE) and functioning well for less than 14 nm technology nodes. In the present research, the MuGFET simulation tool is used to analyze and explain the electrical behaviour of a double-gate 2D Fin field effect transistor. The drift-diffusion and Poisson equations are solved self-consistently. Various models, such as Fermi-Dirac distribution, bandgap narrowing, carrier scattering, and concentration-dependent mobility models, are used for device simulation. The transfer and output characteristics of the double-gate 2D Fin field effect transistor are determined at 10 nm technology node. The performance parameters are extracted in terms of threshold voltage, trans-conductance, leakage current and current on-off ratio. In this paper, the device performance is analyzed at different structure parameters. The utilization of the Id-Vg curve is a robust technique that holds significant importance in the modeling of transistors, circuit design, optimization of performance, and quality control in electronic devices and integrated circuits for comprehending field-effect transistors. The FinFET structure is optimized to increase the current on-off ratio and transconductance. Through this analysis, the impact of different channel widths, source and drain lengths on the Id-Vg and transconductance is examined. Device performance was affected by the difficulty of maintaining effective gate control over the channel at decreasing feature sizes. For every set of simulations, the device's features are simulated at two different drain voltages, 50 mV and 0.7 V. In low-power and precision applications, the off-state current is a significant factor to consider. Therefore, it is crucial to minimize the off-state current to maximize circuit performance and efficiency. The findings demonstrate that the performance of the current on-off ratio is maximum with the channel width of 3 nm for a gate length of 10 nm, but there is no significant effect of source and drain length on the current on-off ratio. The transconductance value plays a pivotal role in various electronic applications and should be considered carefully. In this research, it is also concluded that the transconductance value of 340 S/m is achieved with the fin width of 3 nm at a gate length of 10 nm and 2380 S/m for the source and drain extension length of 5 nm, respectively.

Keywords: current on-off ratio, FinFET, short-channel effects, transconductance

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Authors: Aleksander Ejsmont, Aleksandra Galarda, Joanna Goscianska

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Smart porous carriers with defined structure and physicochemical properties are required for releasing the therapeutic drug with precise control of delivery time and location in the body. Due to their non-toxicity, ordered structure, chemical, and thermal stability, mesoporous carbons can be considered as modern carriers for active pharmaceutical ingredients (APIs) whose effectiveness needs frequent dosing algorithms. Such an API-carrier system, if programmed precisely, may stabilize the pharmaceutical and increase its dissolution leading to enhanced bioavailability. The substance conjugated with the material, through its prior adsorption, can later be successfully applied internally to the organism, as well as externally if the API release is feasible under these conditions. In the present study, ordered mesoporous carbons of different morphologies and structures, prepared by hard template method, were applied as carriers in the adsorption and controlled release of active pharmaceutical ingredients. In the first stage, the carbon materials were synthesized and functionalized with carboxylic groups by chemical oxidation using ammonium persulfate solution and then with amine groups. Materials obtained were thoroughly characterized with respect to morphology (scanning electron microscopy), structure (X-ray diffraction, transmission electron microscopy), characteristic functional groups (FT-IR spectroscopy), acid-base nature of surface groups (Boehm titration), parameters of the porous structure (low-temperature nitrogen adsorption) and thermal stability (TG analysis). This was followed by a series of tests of adsorption and release of paracetamol, benzocaine, and losartan potassium. Drug release experiments were performed in the simulated gastric fluid of pH 1.2 and phosphate buffer of pH 7.2 or 6.8 at 37.0 °C. The XRD patterns in the small-angle range and TEM images revealed that functionalization of mesoporous carbons with carboxylic or amine groups leads to the decreased ordering of their structure. Moreover, the modification caused a considerable reduction of the carbon-specific surface area and pore volume, but it simultaneously resulted in changing their acid-base properties. Mesoporous carbon materials exhibit different morphologies, which affect the host-guest interactions during the adsorption process of active pharmaceutical ingredients. All mesoporous carbons show high adsorption capacity towards drugs. The sorption capacity of materials is mainly affected by BET surface area and the structure/size matching between adsorbent and adsorbate. Selected APIs are linked to the surface of carbon materials mainly by hydrogen bonds, van der Waals forces, and electrostatic interactions. The release behavior of API is highly dependent on the physicochemical properties of mesoporous carbons. The release rate of APIs could be regulated by the introduction of functional groups and by changing the pH of the receptor medium. Acknowledgments—This research was supported by the National Science Centre, Poland (project SONATA-12 no: 2016/23/D/NZ7/01347).

Keywords: ordered mesoporous carbons, sorption capacity, drug delivery, carbon nanocarriers

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Authors: William C. Alexander

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The oscillating water column (OSC) wave energy converter (WEC) with deep water reactance (DWR) consists of a large hollow sphere filled with seawater at the base, referred to as the ‘stabilizer’, a hollow cylinder at the top of the device, with a said cylinder having a bottom open to the sea and a sealed top save for an orifice which leads to an air turbine, and a long, narrow rod connecting said stabilizer with said cylinder. A small amount of ballast at the bottom of the stabilizer and a small amount of floatation in the cylinder keeps the device upright in the sea. The floatation is set such that the mean water level is nominally halfway up the cylinder. The entire device is loosely moored to the seabed to keep it from drifting away. In the presence of ocean waves, seawater will move up and down within the cylinder, producing the ‘oscillating water column’. This gives rise to air pressure within the cylinder alternating between positive and negative gauge pressure, which in turn causes air to alternately leave and enter the cylinder through said top-cover situated orifice. An air turbine situated within or immediately adjacent to said orifice converts the oscillating airflow into electric power for transport to shore or elsewhere by electric power cable. Said oscillating air pressure produces large up and down forces on the cylinder. Said large forces are opposed through the rod to the large mass of water retained within the stabilizer, which is located deep enough to be mostly free of any wave influence and which provides the deepwater reactance. The cylinder and stabilizer form a spring-mass system which has a vertical (heave) resonant frequency. The diameter of the cylinder largely determines the power rating of the device, while the size (and water mass within) of the stabilizer determines said resonant frequency. Said frequency is chosen to be on the lower end of the wave frequency spectrum to maximize the average power output of the device over a large span of time (such as a year). The upper portion of the device (the cylinder) moves laterally (surge) with the waves. This motion is accommodated with minimal loading on the said rod by having the stabilizer shaped like a sphere, allowing the entire device to rotate about the center of the stabilizer without rotating the seawater within the stabilizer. A full-scale device of this type may have the following dimensions. The cylinder may be 16 meters in diameter and 30 meters high, the stabilizer 25 meters in diameter, and the rod 55 meters long. Simulations predict that this will produce 1,400 kW in waves of 3.5-meter height and 12 second period, with a relatively flat power curve between 5 and 16 second wave periods, as will be suitable for an open-ocean location. This is nominally 10 times higher power than similar-sized WEC spar buoys as reported in the literature, and the device is projected to have only 5% of the mass per unit power of other OWC converters.

Keywords: oscillating water column, wave energy converter, spar bouy, stabilizer

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Authors: Wanvipa Thongborisute, Punyaphat Sirithanabadeekul, Pichit Suvanprakorn, Anan Jiraviroon

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Background: Acne vulgaris is one of the most common dermatologic problems, and can have a significant psychological and physical effect on patients. Propionibacterium acnes' roles in acne vulgaris involve the activation of toll-like receptor 4 (TLR4), and toll-like receptor 2 (TLR2) pathways. By activating these pathways, inflammatory events of acne lesions, comedogenesis and sebaceous lipogenesis can occur. Currently, there are several topical agents commonly use in treating acne vulgaris that are known to have an effect on TLRs, such as retinoic acid and adapalene, but these drugs still have some irritating effects. At present, there is an alarming increase in rate of bacterial resistance due to irrational used of antibiotics both orally and topically. For this reason, acne treatments should contain bioactive molecules targeting at the site of action for the most effective therapeutic effect with the least side effects. Sparganium stoloniferumis a Chinese aquatic herb containing a compound called Sparstolonin B (SsnB), which has been reported to selectively blocks Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4)-mediated inflammatory signals. Therefore, this topical TLR2 and TLR4 antagonist, in a form of Sparganium stoloniferum-derived compound containing SsnB, should give a benefit in reducing inflammation of acne vulgaris lesions and providing an alternative treatments for patients with this condition. Materials and Methods: The objectives of this randomized double blinded split faced placebo controlled trial is to study the safety and efficacy of the Sparganium stoloniferum-derived compound. 32 volunteered patients with mild to moderate degree of acne vulgaris according to global acne grading system were included in the study. After being informed and consented the subjects were given 2 topical treatments for acne vulgaris, one being topical 2.40% Sparganium stoloniferum extraction (containing Sparstolonin B) and the other, placebo. The subjects were asked to apply each treatment to either half of the face daily morning and night by randomization for 8 weeks, and come in for a weekly follow up. For each visit, the patients went through a procedure of lesion counting, including comedones, papules, nodules, pustules, and cystic lesions. Results: During 8 weeks of experimentation, the result shows a reduction in total lesions number between the placebo and the treatment side show statistical significance starting at week 4, where the 95% confidence interval begin to no longer overlap, and shows a trend of continuing to be further apart. The decrease in the amount of total lesions between week 0 and week 8 of the placebo side shows no statistical significant at P value >0.05. While the decrease in the amount of total lesions of acne vulgaris of the treatment side comparing between week 0 and week 8 shows statistical significant at P value <0.001. Conclusion: The data demonstrates that 2.40% Sparganium stoloniferum extraction (containing Sparstolonin B) is more effective in treating acne vulgaris comparing to topical placebo in treating acne vulgaris, by showing significant reduction in the total numbers of acne lesions. Therefore, this topical Sparganium stoloniferum extraction could become a potential alternative treatment for acne vulgaris.

Keywords: acne vulgaris, sparganium stoloniferum, sparstolonin B, toll-like receptor 2, toll-like receptor 4

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Authors: Mohamed Gaafar, Evan Davies

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Many municipalities within Canada and abroad use chloramination to disinfect drinking water so as to avert the production of the disinfection by-products (DBPs) that result from conventional chlorination processes and their consequential public health risks. However, the long-lasting monochloramine disinfectant (NH2Cl) can pose a significant risk to the environment. As, it can be introduced into stormwater sewers, from different water uses, and thus freshwater sources. Little research has been undertaken to monitor and characterize the decay of NH2Cl and to study the parameters affecting its decomposition in stormwater networks. Therefore, the current study was intended to investigate this decay starting by building a stormwater model and validating its hydraulic and hydrologic computations, and then modelling water quality in the storm sewers and examining the effects of different parameters on chloramine decay. The presented work here is only the first stage of this study. The 30th Avenue basin in Southern Edmonton was chosen as a case study, because the well-developed basin has various land-use types including commercial, industrial, residential, parks and recreational. The City of Edmonton has already built a MIKE-URBAN stormwater model for modelling floods. Nevertheless, this model was built to the trunk level which means that only the main drainage features were presented. Additionally, this model was not calibrated and known to consistently compute pipe flows higher than the observed values; not to the benefit of studying water quality. So the first goal was to complete modelling and updating all stormwater network components. Then, available GIS Data was used to calculate different catchment properties such as slope, length and imperviousness. In order to calibrate and validate this model, data of two temporary pipe flow monitoring stations, collected during last summer, was used along with records of two other permanent stations available for eight consecutive summer seasons. The effect of various hydrological parameters on model results was investigated. It was found that model results were affected by the ratio of impervious areas. The catchment length was tested, however calculated, because it is approximate representation of the catchment shape. Surface roughness coefficients were calibrated using. Consequently, computed flows at the two temporary locations had correlation coefficients of values 0.846 and 0.815, where the lower value pertained to the larger attached catchment area. Other statistical measures, such as peak error of 0.65%, volume error of 5.6%, maximum positive and negative differences of 2.17 and -1.63 respectively, were all found in acceptable ranges.

Keywords: stormwater, urban drainage, simulation, validation, MIKE URBAN

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Authors: Almaz R. Gazizov, Sergey S. Kharintsev, Myakzyum Kh. Salakhov

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This work deals with background signal suppression in tip-enhanced near-field optical microscopy (TENOM). The background appears because an optical signal is detected not only from the subwavelength area beneath the tip but also from a wider diffraction-limited area of laser’s waist that might contain another substance. The background can be reduced by using a taper probe with a grating on its lateral surface where an external illumination causes surface plasmon excitation. It requires the grating with parameters perfectly matched with a given incident light for effective light coupling. This work is devoted to an analysis of the light-grating coupling and a quest of grating parameters to enhance a near-field light beneath the tip apex. The aim of this work is to find the figure of merit of plasmon excitation depending on grating period and location of grating in respect to the apex. In our consideration the metallic grating on the lateral surface of the tapered plasmonic probe is illuminated by a plane wave, the electric field is perpendicular to the sample surface. Theoretical model of efficiency of plasmon excitation and propagation toward the apex is tested by fdtd-based numerical simulation. An electric field of the incident light is enhanced on the grating by every single slit due to lightning rod effect. Hence, grating causes amplitude and phase modulation of the incident field in various ways depending on geometry and material of grating. The phase-modulating grating on the probe is a sort of metasurface that provides manipulation by spatial frequencies of the incident field. The spatial frequency-dependent electric field is found from the angular spectrum decomposition. If one of the components satisfies the phase-matching condition then one can readily calculate the figure of merit of plasmon excitation, defined as a ratio of the intensities of the surface mode and the incident light. During propagation towards the apex, surface wave undergoes losses in probe material, radiation losses, and mode compression. There is an optimal location of the grating in respect to the apex. One finds the value by matching quadratic law of mode compression and the exponential law of light extinction. Finally, performed theoretical analysis and numerical simulations of plasmon excitation demonstrate that various surface waves can be effectively excited by using the overtones of a period of the grating or by phase modulation of the incident field. The gratings with such periods are easy to fabricate. Tapered probe with the grating effectively enhances and localizes the incident field at the sample.

Keywords: angular spectrum decomposition, efficiency, grating, surface plasmon, taper nanoantenna

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Authors: Pratima Pokharel

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When sewer overflow due to rainfall in urban areas, this leads to public health risks when an individual is exposed to that contaminated floodwater. Nevertheless, it is still unclear the extent to which the infections pose a risk to public health. This study analyzed reported diarrheal cases by month and age in Bangkok, Thailand. The results showed that the cases are reported higher in the wet season than in the dry season. It was also found that in Bangkok, the probability of infection with diarrheal diseases in the wet season is higher for the age group between 15 to 44. However, the probability of infection is highest for kids under 5 years, but they are not influenced by wet weather. Further, this study introduced a vulnerability that leads to health risks from urban flooding. This study has found some vulnerability variables that contribute to health risks from flooding. Thus, for vulnerability analysis, the study has chosen two variables, economic status, and age, that contribute to health risk. Assuming that the people's economic status depends on the types of houses they are living in, the study shows the spatial distribution of economic status in the vulnerability maps. The vulnerability map result shows that people living in Sukhumvit have low vulnerability to health risks with respect to the types of houses they are living in. In addition, from age the probability of infection of diarrhea was analyzed. Moreover, a field survey was carried out to validate the vulnerability of people. It showed that health vulnerability depends on economic status, income level, and education. The result depicts that people with low income and poor living conditions are more vulnerable to health risks. Further, the study also carried out 1D Hydrodynamic Advection-Dispersion modelling with 2-year rainfall events to simulate the dispersion of fecal coliform concentration in the drainage network as well as 1D/2D Hydrodynamic model to simulate the overland flow. The 1D result represents higher concentrations for dry weather flows and a large dilution of concentration on the commencement of a rainfall event, resulting in a drop of the concentration due to runoff generated after rainfall, whereas the model produced flood depth, flood duration, and fecal coliform concentration maps, which were transferred to ArcGIS to produce hazard and risk maps. In addition, the study also simulates the 5-year and 10-year rainfall simulations to show the variation in health hazards and risks. It was found that even though the hazard coverage is very high with a 10-year rainfall events among three rainfall events, the risk was observed to be the same with a 5-year and 10-year rainfall events.

Keywords: urban flooding, risk, hazard, vulnerability, health risk, framework

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Authors: Mariyah Poonawala, Selvan Ravindran, Anuradha Vaidya

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Despite much progress in understanding the regulatory factors and cytokines that support the maturation of the various cell lineages of the hematopoietic system, factors that govern the self-renewal and proliferation of hematopoietic stem cells (HSCs) is still a grey area of research. Hematopoietic stem cell transplantation (HSCT) has evolved over the years and gained tremendous importance in the treatment of both malignant and non-malignant diseases. However, factors such as graft rejection and multiple organ failure have challenged HSCT from time to time, underscoring the urgent need for development of milder processes for successful hematopoietic transplantation. An emerging concept in the field of stem cell biology states that the interactions between the bone-marrow micro-environment and the hematopoietic stem and progenitor cells is essential for regulation, maintenance, commitment and proliferation of stem cells. Understanding the role of mesenchymal stromal cells in modulating the functionality of HSCs is, therefore, an important area of research. Trans-resveratrol has been extensively studied for its various properties to combat and prevent cancer, diabetes and cardiovascular diseases etc. The aim of the present study was to understand the effect of trans-resveratrol on HSCs using single and co-culture systems. We have used KG1a cells since it is a well accepted hematopoietic stem cell model system. Our preliminary experiments showed that low concentrations of trans-resveratrol stimulated the HSCs to undergo proliferation whereas high concentrations of trans-resveratrol did not stimulate the cells to proliferate. We used a murine fibroblast cell line, M210B4, as a stromal feeder layer. On culturing the KG1a cells with M210B4 cells, we observed that the stimulatory as well as inhibitory effects of trans-resveratrol at low and high concentrations respectively, were enhanced. Our further experiments showed that low concentration of trans-resveratrol reduced the generation of reactive oxygen species (ROS) and nitric oxide (NO) whereas high concentrations increased the oxidative stress in KG1a cells. We speculated that perhaps the oxidative stress was imposing inhibitory effects at high concentration and the same was confirmed by performing an apoptotic assay. Furthermore, cell cycle analysis and growth kinetic experiments provided evidence that low concentration of trans-resveratrol reduced the doubling time of the cells. Our hypothesis is that perhaps at low concentration of trans-resveratrol the cells get pushed into the G0/G1 phase and re-enter the cell cycle resulting in their proliferation, whereas at high concentration the cells are perhaps arrested at G2/M phase or at cytokinesis and therefore undergo apoptosis. Liquid Chromatography-Quantitative-Time of Flight–Mass Spectroscopy (LC-Q-TOF MS) analyses indicated the presence of trans-resveratrol and its metabolite(s) in the supernatant of the co-cultured cells incubated with high concentration of trans-resveratrol. We conjecture that perhaps the metabolites of trans-resveratrol are responsible for the apoptosis observed at the high concentration. Our findings may shed light on the unsolved problems in the in vitro expansion of stem cells and may have implications in the ex vivo manipulation of HSCs for therapeutic purposes.

Keywords: co-culture system, hematopoietic micro-environment, KG1a cell line, M210B4 cell line, trans-resveratrol

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Authors: J. Desbrieres, M. Popa, C. Peptu, S. Bacaita

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Because of their favorable properties (non-toxicity, biodegradability, mucoadhesivity etc.), polysaccharides were studied as biomaterials and as pharmaceutical excipients in drug formulations. These formulations may be produced in a wide variety of forms including hydrogels, hydrogel based particles (or capsules), films etc. In these formulations, the polysaccharide based materials are able to provide local delivery of loaded therapeutic agents but their delivery can be rapid and not easily time-controllable due to, particularly, the burst effect. This leads to a loss in drug efficiency and lifetime. To overcome the consequences of burst effect, systems involving liposomes incorporated into polysaccharide hydrogels may appear as a promising material in tissue engineering, regenerative medicine and drug loading systems. Liposomes are spherical self-closed structures, composed of curved lipid bilayers, which enclose part of the surrounding solvent into their structure. The simplicity of production, their biocompatibility, the size and similar composition of cells, the possibility of size adjustment for specific applications, the ability of hydrophilic or/and hydrophobic drug loading make them a revolutionary tool in nanomedicine and biomedical domain. Drug delivery systems were developed as hydrogels containing chitosan or carboxymethylcellulose (CMC) as polysaccharides and gelatin (GEL) as polypeptide, and phosphatidylcholine or phosphatidylcholine/cholesterol liposomes able to accurately control this delivery, without any burst effect. Hydrogels based on CMC were covalently crosslinked using glutaraldehyde, whereas chitosan based hydrogels were double crosslinked (ionically using sodium tripolyphosphate or sodium sulphate and covalently using glutaraldehyde). It has been proven that the liposome integrity is highly protected during the crosslinking procedure for the formation of the film network. Calcein was used as model active matter for delivery experiments. Multi-Lamellar vesicles (MLV) and Small Uni-Lamellar Vesicles (SUV) were prepared and compared. The liposomes are well distributed throughout the whole area of the film, and the vesicle distribution is equivalent (for both types of liposomes evaluated) on the film surface as well as deeper (100 microns) in the film matrix. An obvious decrease of the burst effect was observed in presence of liposomes as well as a uniform increase of calcein release that continues even at large time scales. Liposomes act as an extra barrier for calcein release. Systems containing MLVs release higher amounts of calcein compared to systems containing SUVs, although these liposomes are more stable in the matrix and diffuse with difficulty. This difference comes from the higher quantity of calcein present within the MLV in relation with their size. Modeling of release kinetics curves was performed and the release of hydrophilic drugs may be described by a multi-scale mechanism characterized by four distinct phases, each of them being characterized by a different kinetics model (Higuchi equation, Korsmeyer-Peppas model etc.). Knowledge of such models will be a very interesting tool for designing new formulations for tissue engineering, regenerative medicine and drug delivery systems.

Keywords: controlled and delayed release, hydrogels, liposomes, polysaccharides

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Authors: M. Bahari Mehrabani, Hua-Peng Chen

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Management and maintenance of coastal defence structures during the expected life cycle have become a real challenge for decision makers and engineers. Accurate evaluation of the current condition and future performance of flood defence structures is essential for effective practical maintenance strategies on the basis of available field inspection data. Moreover, as coastal defence structures age, it becomes more challenging to implement maintenance and management plans to avoid structural failure. Therefore, condition inspection data are essential for assessing damage and forecasting deterioration of ageing flood defence structures in order to keep the structures in an acceptable condition. The inspection data for flood defence structures are often collected using discrete visual condition rating schemes. In order to evaluate future condition of the structure, a probabilistic deterioration model needs to be utilised. However, existing deterioration models may not provide a reliable prediction of performance deterioration for a long period due to uncertainties. To tackle the limitation, a time-dependent condition-based model associated with a transition probability needs to be developed on the basis of condition grade scheme for flood defences. This paper presents a probabilistic method for predicting future performance deterioration of coastal flood defence structures based on condition grading inspection data and deterioration curves estimated by expert judgement. In condition-based deterioration modelling, the main task is to estimate transition probability matrices. The deterioration process of the structure related to the transition states is modelled according to Markov chain process, and a reliability-based approach is used to estimate the probability of structural failure. Visual inspection data according to the United Kingdom Condition Assessment Manual are used to obtain the initial condition grade curve of the coastal flood defences. The initial curves then modified in order to develop transition probabilities through non-linear regression based optimisation algorithms. The Monte Carlo simulations are then used to evaluate the future performance of the structure on the basis of the estimated transition probabilities. Finally, a case study is given to demonstrate the applicability of the proposed method under no-maintenance and medium-maintenance scenarios. Results show that the proposed method can provide an effective predictive model for various situations in terms of available condition grading data. The proposed model also provides useful information on time-dependent probability of failure in coastal flood defences.

Keywords: condition grading, flood defense, performance assessment, stochastic deterioration modelling

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Authors: Anna Mucha, Ewa Wojtyna, Anita Pollak

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The environment in which an individual resides and observes may play a meaningful role in well-being and related constructs. Contact with nature may have a positive influence of natural environments on individuals, impacting mood and psychophysical sensations, such as pain relief. Conversely, urban settings, dominated by concrete elements, might lead to mood decline and heightened stress levels. Similarly, the situation may appear in the case of the perception of virtual environments. However, this is a topic that requires further exploration, especially in the context of relationships with pain. The aforementioned matters served as the basis for formulating and executing the outlined experimental research within the realm of environmental psychology, leveraging new technologies, notably virtual reality (VR), which is progressively gaining prominence in the domain of mental health. The primary objective was to investigate the impact of a simulated virtual environment, mirroring a natural setting abundant in greenery, on the perception of acute pain induced by thermal stimuli (high temperature) – encompassing intensity, unpleasantness, and pain tolerance. Comparative analyses were conducted between the virtual natural environment (intentionally constructed in the likeness of a therapeutic garden), virtual urban environment, and a control group devoid of virtual projections. Secondary objectives aimed to determine the mutual relationships among variables such as positive and negative emotions, preferences regarding virtual environments, sense of presence, and restorative experience in the context of the perception of presented virtual environments and induced thermal pain. The study encompassed 126 physically healthy Polish adults, distributing 42 individuals across each of the three comparative groups. Oculus Rift VR technology and the TSA-II neurosensory analyzer facilitated the experiment. Alongside demographic data, participants' subjective feelings concerning virtual reality and pain were evaluated using the Visual Analogue Scale (VAS), the original Restorative Experience in the Virtual World questionnaire (Doświadczenie Regeneracji w Wirtualnym Świecie), and an adapted Slater-Usoh-Steed (SUS) questionnaire. Results of statistical and psychometric analyses, such as Kruskal-Wallis tests, Wilcoxon tests, and contrast analyses, underscored the positive impact of the virtual natural environment on individual pain perception and mood. The virtual natural environment outperformed the virtual urban environment and the control group without virtual projection, particularly in subjective pain components like intensity and unpleasantness. Variables such as restorative experience, sense of presence and virtual environment preference also proved pivotal in pain perception and pain tolerance threshold alterations, contingent on specific conditions. This implies considerable application potential for virtual natural environments across diverse realms of psychology and related fields, among others as a supportive analgesic approach and a form of relaxation following psychotherapeutic sessions.

Keywords: environmental psychology, nature, acute pain, emotions, vitrual reality, virtual environments

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Authors: Muhammad Shahzad Hussain

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Two major problems are facing generally by conventional poultry farming that is disease outbreaks and poor performance, which results due to improper management. To enhance the growth performance and efficiency of feed and reduce disease outbreaks, antibiotic growth promoters (AGPs) which are antibiotics at sub-therapeutic levels, are extensively used in the poultry industry. European Union has banned the use of antibiotics due to their presence in poultry products, development of antibiotic-resistant pathogens, and disturbance of normal gut microbial ecology. These residues cause serious health concerns and produce antibiotic resistance in pathogenic microbes in human beings. These issues strengthen the need for the withdrawal of AGPs from poultry feed. Nowadays, global warming is a major issue, and it is more critical in tropical areas like Pakistan, where heat stress is already a major problem. Heat stress leads to poor production performance, high mortality, immuno-suppression, and concomitant diseases outbreak. The poultry feed industry in Pakistan, like other countries of the world, has been facing shortages and high prices of local as well as imported feed ingredients. Prebiotics are potential replacer for AGP as prebiotics has properties to enhance the production potential and reduce the growth of harmful bacteria as well as stimulate the growth/activity of beneficial bacteria. The most commonly used prebiotics in poultry includes mannan oligosaccharide (MOS). MOS is an essential component of the yeast cell wall (YCW) (Saccharomyces cerevisiae); therefore, the YCW wall possesses prebiotic properties. The use of distillery yeast wall (YCW) has the potential to replace conventional AGPs and to reduce mortality due to heat stress as well as to bind toxins in the feed. The dietary addition of YCW has not only positive effects on production performance in poultry during normal conditions but during stressful conditions. A total of 168-day-old broilers were divided into 6 groups, each of which has 28 birds with 4 replicates (n=7).Yeast cell wall (YCW) supplementation @ 0%, 1%, 1.5%, 2%, 2.5%, 3% from day 0 to 35. Heat stress was exposed from day 21 to 35 at 30±1.1ᵒC with relative humidity 65±5%. Zootechnical parameters like body weight, FCR, Organ development, and histomorphometric parameters were studied. A significant weight gain was observed at group C supplemented @ 1.5% YCW during the fifth week. Significant organ weight gain of Gizzard, spleen, small intestine, and cecum was observed at group C supplemented @ 1.5% YCW. According to morphometric indices Duodenum, Jejunum, and Ileum has significant villus height, while Jejunum and Ileum have also significant villus surface area in the group supplemented with 1.5% YCW. IEL count was only decreased in 1.5% YCW-fed group in jejunum and ileum, not in duodenum, that was less in 2% YCW-supplemented group. Dietary yeast cell wall of saccharomyces cerevisiae partially reduced the effects of high ambient temperature in terms of better growth and modified gut histology and components of mucosal immune response to better withstand heat stress in broilers.

Keywords: antibiotics, AGPs, broilers, MOS, prebiotics, YCW

Procedia PDF Downloads 66

Authors: Sandeep Kumar Agrawal, Aditi Bhattacharya, Janvie Manhas, Krushna Bhatt, Yatin Kholakiya, Nupur Khera, Ajoy Roychoudhury, Sudip Sen

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Autologous cultured explants of human oral mucosal epithelial cells (OMEC) are a potential therapeutic modality for limbal stem cell deficiency (LSCD). Injury or inflammation of the ocular surface in the form of burns, chemicals, Stevens Johnson syndrome, ocular cicatricial pemphigoid etc. can lead to destruction and deficiency of limbal stem cells. LSCD manifests in the form of severe ocular surface diseases (OSD) characterized by persistent and recurrent epithelial defects, conjuntivalisation and neovascularisation of the corneal surface, scarring and ultimately opacity and blindness. Most of the cases of OSD are associated with severe dry eye pertaining to diminished mucin and aqueous secretion. Mycophenolate mofetil (MMF) has been shown to upregulate the mucin expression in conjunctival goblet cells in vitro. The aim of this study was to evaluate the effects of MMF on mucin expression in primary cultures of oral mucosal epithelial cells. With institutional ethics committee approval and written informed consent, thirty oral mucosal epithelial tissue samples were obtained from patients undergoing oral surgery for non-malignant conditions. OMEC were grown on human amniotic membrane (HAM, obtained from expecting mothers undergoing elective caesarean section) scaffold for 2 weeks in growth media containing DMEM & Ham’s F12 (1:1) with 10% FBS and growth factors. In vitro dosage of MMF was standardised by MTT assay. Analysis of stem cell markers was done using RT-PCR while mucin mRNA expression was quantified using RT-PCR and q-PCR before and after treating cultured OMEC with graded concentrations of MMF for 24 hours. Protein expression was validated using immunocytochemistry. Morphological studies revealed a confluent sheet of proliferating, stratified oral mucosal epithelial cells growing over the surface of HAM scaffold. The presence of progenitor stem cell markers (p63, p75, β1-Integrin and ABCG2) and cell surface associated mucins (MUC1, MUC15 and MUC16) were elucidated by RT-PCR. The mucin mRNA expression was found to be upregulated in MMF treated primary cultures of OMEC, compared to untreated controls as quantified by q-PCR with β-actin as internal reference gene. Increased MUC1 protein expression was validated by immunocytochemistry on representative samples. Our findings conclude that OMEC have the ability to form a multi-layered confluent sheet on the surface of HAM similar to a cornea, which is important for the reconstruction of the damaged ocular surface. Cultured OMEC has stem cell properties as demonstrated by stem cell markers. MMF can be a novel enhancer of mucin production in OMEC. It has the potential to improve dry eye in patients undergoing OMEC transplantation for bilateral OSD. Further clinical trials are required to establish the role of MMF in patients undergoing OMEC transplantation.

Keywords: limbal stem cell deficiency, mycophenolate mofetil, mucin, ocular surface disease

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Authors: Sahar Nasr, Lin Li, Edwin Wang

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Bladder cancer (BLCA) is known as the 13th cause of death among cancer patients worldwide, and ~575,000 new BLCA cases are diagnosed each year. Urothelial carcinoma (UC) is the most prevalent subtype among BLCA patients, which can be categorized into muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Currently, various therapeutic options are available for UC patients, including (1) transurethral resection followed by intravesical instillation of chemotherapeutics or Bacillus Calmette-Guérin for NMIBC patients, (2) neoadjuvant platinum-based chemotherapy (NAC) plus radical cystectomy is the standard of care for localized MIBC patients, and (3) systematic chemotherapy for metastatic UC. However, conventional treatments may lead to several challenges for treating patients. As an illustration, some patients may suffer from recurrence of the disease after the first line of treatment. Recently, immune checkpoint therapy (ICT) has been introduced as an alternative treatment strategy for the first or second line of treatment in advanced or metastatic BLCA patients. Although ICT showed lucrative results for a fraction of BLCA patients, ~80% of patients were not responsive to it. Therefore, novel treatment methods are required to augment the ICI response rate within BLCA patients. It has been shown that the infiltration of T-cells into the tumor microenvironment (TME) is positively correlated with the response to ICT within cancerous patients. Therefore, the goal of this study is to enhance the infiltration of cytotoxic T-cells into TME through the identification of target genes within the tumor that are responsible for the non-T-cell inflamed TME and their inhibition. BLCA bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and immune score for TCGA samples were used to determine the Pearson correlation score between the expression of different genes and immune score for each sample. The genes with strong negative correlations were selected (r < -0.2). Thereafter, the correlation between the expression of each gene and survival in BLCA patients was calculated using the TCGA data and Cox regression method. The genes that are common in both selected gene lists were chosen for further analysis. Afterward, BLCA bulk and single-cell RNA-sequencing data were ranked based on the expression of each selected gene and the top and bottom 25% samples were used for pathway enrichment analysis. If the pathways related to the T-cell infiltration (e.g., antigen presentation, interferon, or chemokine pathways) were enriched within the low-expression group, the gene was included for downstream analysis. Finally, the selected genes will be used to calculate the correlation between their expression and the infiltration rate of the activated CD+8 T-cells, natural killer cells and the activated dendric cells. A list of potential target genes has been identified and ranked based on the above-mentioned analysis and criteria. SUN-1 got the highest score within the gene list and other identified genes in the literature as benchmarks. In conclusion, inhibition of SUN1 may increase the tumor-infiltrating lymphocytes and the efficacy of ICI in BLCA patients. BLCA tumor cells with and without SUN-1 CRISPR/Cas9 knockout will be injected into the syngeneic mouse model to validate the predicted SUN-1 effect on increasing tumor-infiltrating lymphocytes.

Keywords: data analysis, gene expression analysis, gene identification, immunoinformatic, functional genomics, transcriptomics

Procedia PDF Downloads 135

Authors: Qian Yi Ooi

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At present, airfoil parameters are still designed and optimized according to the scale of conventional aircraft, and there are still some slight deviations in terms of scale differences. However, insufficient parameters or poor surface mesh quality is likely to occur if these small deviations are embedded in a future civil aircraft with a size that is quite different from conventional aircraft, such as a blended-wing-body (BWB) aircraft with future potential, resulting in large deviations in geometric similarity in computational fluid dynamics (CFD) simulations. To avoid this situation, the study on the CFD calculation on the geometric similarity of airfoil parameters and the quality of the surface mesh is conducted to obtain the ability of different parameterization methods applied on different airfoil scales. The research objects are three airfoil scales, including the wing root and wingtip of conventional civil aircraft and the wing root of the giant hybrid wing, used by three parameterization methods to compare the calculation differences between different sizes of airfoils. In this study, the constants including NACA 0012, a Reynolds number of 10 million, an angle of attack of zero, a C-grid for meshing, and the k-epsilon (k-ε) turbulence model are used. The experimental variables include three airfoil parameterization methods: point cloud method, B-spline curve method, and class function/shape function transformation (CST) method. The airfoil dimensions are set to 3.98 meters, 17.67 meters, and 48 meters, respectively. In addition, this study also uses different numbers of edge meshing and the same bias factor in the CFD simulation. Studies have shown that with the change of airfoil scales, different parameterization methods, the number of control points, and the meshing number of divisions should be used to improve the accuracy of the aerodynamic performance of the wing. When the airfoil ratio increases, the most basic point cloud parameterization method will require more and larger data to support the accuracy of the airfoil’s aerodynamic performance, which will face the severe test of insufficient computer capacity. On the other hand, when using the B-spline curve method, average number of control points and meshing number of divisions should be set appropriately to obtain higher accuracy; however, the quantitative balance cannot be directly defined, but the decisions should be made repeatedly by adding and subtracting. Lastly, when using the CST method, it is found that limited control points are enough to accurately parameterize the larger-sized wing; a higher degree of accuracy and stability can be obtained by using a lower-performance computer.

Keywords: airfoil, computational fluid dynamics, geometric similarity, surface mesh quality

Procedia PDF Downloads 196

Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Shohei Koide, Christopher Park, Dimitris Placantonakis

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Background: Glioblastoma (GBM) is the most common and deadly primary brain malignancy in adults. Tumor propagation, brain invasion, and resistance to therapy critically depend on GBM stem-like cells (GSCs); however, the mechanisms that regulate GSC self-renewal are incompletely understood. Given the aggressiveness and poor prognosis of GBM, it is imperative to find biomarkers that could also translate into novel drug targets. Along these lines, we have identified a cell surface antigen, CD97 (ADGRE5), an adhesion G protein-coupled receptor (GPCR), that is expressed on GBM cells but is absent from non-neoplastic brain tissue. CD97 has been shown to promote invasiveness, angiogenesis, and migration in several human cancers, but its frequency of expression and functional role in regulating GBM growth and survival, and its potential as a therapeutic target has not been investigated. Design: We assessed CD97 mRNA and protein expression in patient derived GBM samples and cell lines using publicly available RNA-sequencing datasets and flow cytometry, respectively. To assess CD97 function, we generated shRNA lentiviral constructs that target a sequence in the CD97 extracellular domain (ECD). A scrambled shRNA (scr) with no predicted targets in the genome was used as a control. We evaluated CD97 shRNA lentivirally transduced GBM cells for Ki67, Annexin V, and DAPI. We also tested CD97 KD cells for their ability to self-renew using clonogenic tumorsphere formation assays. Further, we utilized synthetic Abs (sAbs) generated against the ECD of CD97 to test for potential antitumor effects using patient-derived GBM cell lines. Results: CD97 mRNA expression was expressed at high levels in all GBM samples available in the TCGA cohort. We found high levels of surface CD97 protein expression in 6/6 patient-derived GBM cell cultures, but not human neural stem cells. Flow cytometry confirmed downregulation of CD97 in CD97 shRNA lentivirally transduced cells. CD97 KD induced a significant reduction in cell growth in 3 independent GBM cell lines representing mesenchymal and proneural subtypes, which was accompanied by reduced (~20%) Ki67 staining and increased (~30%) apoptosis. Incubation of GBM cells with sAbs (20 ug/ ml) against the ECD of CD97 for 3 days induced GSC differentiation, as determined by the expression of GFAP and Tubulin. Using three unique GBM patient derived cultures, we found that CD97 KD attenuated the ability of GBM cells to initiate sphere formation by over 300 fold, consistent with an impairment in GSC self-renewal. Conclusion: Loss of CD97 expression in patient-derived GBM cells markedly decreases proliferation, induces cell death, and reduces tumorsphere formation. sAbs against the ECD of CD97 reduce tumorsphere formation, recapitulating the phenotype of CD97 KD, suggesting that sAbs that inhibit CD97 function exhibit anti-tumor activity. Collectively, these findings indicate that CD97 is necessary for the proliferation and survival of human GBM cells and identify CD97 as a promising therapeutically targetable vulnerability in GBM.

Keywords: adhesion GPCR, CD97, GBM stem cell, glioblastoma

Procedia PDF Downloads 107

Authors: Maari Sugawara

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This arts-based research is about "self-torture": the interplay of seemingly opposing elements of pain, pleasure, submission, and power. It asserts that "self-torture" can be considered a nontrivial mediation between the aesthetic and the sociopolitical. It explores what the author calls queered self-torture; "self-torture" marked by an ambivalence that allows the oppressed to resist, and their counter-valorization occasionally functions as therapeutic solutions to the problems they highlight and condense. The research goal is to deconstruct normative self-torture and propose queered self-torture as a fertile ground for considering the complexities of desire that allow the oppressed to practice freedom. While “self-torture” manifests in many societies, this research focuses on cultural and national identity in post-WWII Japan using this lens of self-torture, as masochism functions as the very basis for Japanese cultural and national identity to ensure self-preservation. This masochism is defined as an impulse to realize a sense of pride and construct an identity through the acceptance of subordination, shame, and humiliation in the face of an all-powerful Other; the dominant Euro-America. It could be argued that this self-torture is a result of Japanese cultural annihilation and the trauma of the nation's defeat to the US. This is the definition of "self-torturous thresholds," the author’s post-WWII Japan psycho-historical diagnosis; when this threshold is crossed, the oppressed begin to torture themselves; the oppressors no longer need to do anything to maintain their power. The oppressed are already oppressing themselves. The term "oppressed" here refers to Japanese individuals and residents of Japan who are subjected to oppressive “white” heteropatriarchal supremacist structures and values that serve colonialist interests. There are three stages in "self-torturous thresholds": (1) the oppressors no longer need to oppress because the oppressed voluntarily commit to self-torture; (2) the oppressed find pleasure in self-torture; and (3) the oppressed achieve queered self-torture, to achieve alternative futures. Using the conceptualization of "self-torture," this research examines and critiques pleasure, desire, capital, and power in postwar Japan, which enables the discussion of the data-colonizing “Moonshot Research and Development program”. If the oppressed want to divest from the habits of normative self-torture, which shape what is possible in both our present and future, we need methods to feel and know that the alternative results of self-torture are possible. Phase three will be enacted using Sarah Ahmed's queer methodology to reorient national and cultural identity away from heteronormativity. Through theoretical analysis, textual analysis, archival research, ethnographic interviews, and digital art projects, including experimental documentary as a method to capture the realities of the individuals who are practicing self-torture, this research seeks to reveal how self-torture may become not just a vehicle of pleasure but also a mode of critiquing power and achieving freedom. It seeks to encourage the imaginings of queer Japanese futures, where the marginalized survive Japan’s natural and man-made disasters and Japan’s Imperialist past and present rather than submitting to the country’s continued violence.

Keywords: arts-based research, Japanese studies, interdisciplinary arts, queer studies, cultural studies, popular culture, BDSM, sadomasochism, sexuality, VR, AR, digital art, visual arts, speculative fiction

Procedia PDF Downloads 41

Authors: Dino Carpentras, Alejandro Dinkelberg, Michael Quayle

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Within agent-based modeling, opinion dynamics is the field that focuses on modeling people's opinions. In this prolific field, most of the literature is dedicated to the exploration of the two 'degrees of freedom' and how they impact the model’s properties (e.g., the average final opinion, the number of final clusters, etc.). These degrees of freedom are (1) the interaction rule, which determines how agents update their own opinion, and (2) the network topology, which defines the possible interaction among agents. In this work, we show that the third degree of freedom exists. This can be used to change a model's output up to 100% of its initial value or to transform two models (both from the literature) into each other. Since opinion dynamics models are representations of the real world, it is fundamental to understand how people’s opinions can be measured. Even for abstract models (i.e., not intended for the fitting of real-world data), it is important to understand if the way of numerically representing opinions is unique; and, if this is not the case, how the model dynamics would change by using different representations. The process of measuring opinions is non-trivial as it requires transforming real-world opinion (e.g., supporting most of the liberal ideals) to a number. Such a process is usually not discussed in opinion dynamics literature, but it has been intensively studied in a subfield of psychology called psychometrics. In psychometrics, opinion scales can be converted into each other, similarly to how meters can be converted to feet. Indeed, psychometrics routinely uses both linear and non-linear transformations of opinion scales. Here, we analyze how this transformation affects opinion dynamics models. We analyze this effect by using mathematical modeling and then validating our analysis with agent-based simulations. Firstly, we study the case of perfect scales. In this way, we show that scale transformations affect the model’s dynamics up to a qualitative level. This means that if two researchers use the same opinion dynamics model and even the same dataset, they could make totally different predictions just because they followed different renormalization processes. A similar situation appears if two different scales are used to measure opinions even on the same population. This effect may be as strong as providing an uncertainty of 100% on the simulation’s output (i.e., all results are possible). Still, by using perfect scales, we show that scales transformations can be used to perfectly transform one model to another. We test this using two models from the standard literature. Finally, we test the effect of scale transformation in the case of finite precision using a 7-points Likert scale. In this way, we show how a relatively small-scale transformation introduces both changes at the qualitative level (i.e., the most shared opinion at the end of the simulation) and in the number of opinion clusters. Thus, scale transformation appears to be a third degree of freedom of opinion dynamics models. This result deeply impacts both theoretical research on models' properties and on the application of models on real-world data.

Keywords: degrees of freedom, empirical validation, opinion scale, opinion dynamics

Procedia PDF Downloads 104

Authors: Lorena Blasco-Arcas, Francesca Pucciarelli

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Business contexts have become globalised and digitalised, which requires that managers develop a strong sense of cross-cultural intelligence while working in geographically distant teams by means of digital technologies. How to better equip future managers on these kinds of skills has been put forward as a critical issue in Business Schools. In pursuing these goals, higher education is shifting from a passive lecture approach, to more active and experiential learning approaches that are more suitable to learn skills. For example, through the use of case studies, proposing plausible business problem to be solved by students (or teams of students), these institutions have focused for long in fostering learning by doing. Though, case studies are no longer enough as a tool to promote active teamwork and experiential learning. Moreover, digital advancements applied to educational settings have enabled augmented classrooms, expanding the learning experience beyond the class, which increase students’ engagement and experiential learning. Different authors have highlighted the benefits of digital engagement in order to achieve a deeper and longer-lasting learning and comprehension of core marketing concepts. Clickers, computer-based simulations and business games have become fairly popular between instructors, but still are limited by the fact that are fictional experiences. Further exploration of real digital platforms to implement real, live projects in the classroom seem relevant for marketing and business education. Building on this, this paper describes the development of an experiential learning activity in class, in which students developed a communication campaign in teams using the BuzzFeed platform, and subsequently implementing the campaign by using other social media platforms (e.g. Facebook, Instagram, Twitter…). The article details the procedure of using the project for a marketing module in a Bachelor program with students located in France, Italy and Spain campuses working on multi-campus groups. Further, this paper describes the project outcomes in terms of students’ engagement and analytics (i.e. visits achieved). the project included a survey in order to analyze and identify main aspects related to how the learning experience is influenced by the cultural competence developed through working in geographically distant and culturally diverse teamwork. Finally, some recommendations to use project-based social media tools while working with virtual teamwork in the classroom are provided.

Keywords: cultural competences, experiential learning, social media, teamwork, virtual group work

Procedia PDF Downloads 156

Authors: Lacramioara Ochiuz, Manuela Hortolomei, Aurelia Vasile, Iulian Stoleriu, Marcel Popa, Cristian Peptu

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Local antibiotherapy is one of the most effective acne therapies. Erythromycin (ER) is a macrolide antibiotic topically administered for over 30 years in the form of gel, ointment or hydroalcoholic solution for the acne therapy. The use of ER as a base for topical dosage forms raises some technological challenges due to the physicochemical properties of this substance. The main disadvantage of ER is the poor water solubility (2 mg/mL) that limits both formulation using hydrophilic bases and skin permeability. Cyclodextrins (CDs) are biocompatible cyclic oligomers of glucose, with hydrophobic core and hydrophilic exterior. CDs are used to improve the bioavailability of drugs by increasing their solubility and/or their rate of dissolution after including the poorly water soluble substances (such as ER) in the hydrophobic cavity of CDs. Adding CDs leads to the increase of solubility and improved stability of the drug substance, increased permeability of substances of low water solubility, decreased toxicity and even to active dose reduction as a result of increased bioavailability. CDs increase skin tolerability by reducing the irritant effect of certain substances. We have included ER to lactide modified β-cyclodextrin, in order to improve the therapeutic effect of topically administered ER. The aims of the present study were to synthesise and describe a new complex with prolonged release of ER with lactide modified β-cyclodextrin (CD-LA_E), to investigate the CD-LA_E complex by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), to analyse the effect of semisolid base on the in vitro and ex vivo release characteristics of ER in the CD-LA_E complex by assessing the permeability coefficient and the release kinetics by fitting on mathematical models. SEM showed that, by complexation, ER changes its crystal structure and enters the amorphous phase. FTIR analysis has shown that certain specific bands of some groups in the ER structure move during the incapsulation process. The structure of the CD-LA_E complex has a molar ratio of 2.12 to 1 between lactide modified β-cyclodextrin and ER. The three semisolid bases (2% Carbopol, 13% Lutrol 127 and organogel based on Lutrol and isopropyl myristate) show a good capacity for incorporating the CD-LA_E complex, having a content of active ingredient ranging from 98.3% to 101.5% as compared to the declared value of 2% ER. The results of the in vitro dissolution test showed that the ER solubility was significantly increased by CDs incapsulation. The amount of ER released from the CD-LA_E gels was in the range of 76.23% to 89.01%, whereas gels based on ER released a maximum percentage of 26.01% ER. The ex vivo dissolution test confirms the increased ER solubility achieved by complexation, and supports the assumption that the use of this process might increase ER permeability. The highest permeability coefficient was obtained in ER released from gel based on 2% Carbopol: in vitro 33.33 μg/cm2/h, and ex vivo 26.82 μg/cm2/h, respectively. The release kinetics of complexed ER is performed by Fickian diffusion, according to the results obtained by fitting the data in the Korsmeyer-Peppas model.

Keywords: erythromycin, acne, lactide, cyclodextrin

Procedia PDF Downloads 236

Authors: Funda Erdem Şahnali, Ş. Özgür Atayılmaz, Tolga N. Aynur

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Almost all of the domestic refrigerators operate on the principle of the vapor compression refrigeration cycle and removal of heat from the refrigerator cabinets is done via one of the two methods: natural convection or forced convection. In this study, airflow and temperature distributions inside a 375L no-frost type larder cabinet, in which cooling is provided by forced convection, are evaluated both experimentally and numerically. Airflow rate, compressor capacity and temperature distribution in the cooling chamber are known to be some of the most important factors that affect the cooling performance and energy consumption of a refrigerator. The objective of this study is to evaluate the original temperature distribution in the larder cabinet, and investigate for better temperature distribution solutions throughout the refrigerator domain via system optimizations that could provide uniform temperature distribution. The flow visualization and airflow velocity measurements inside the original refrigerator are performed via Stereoscopic Particle Image Velocimetry (SPIV). In addition, airflow and temperature distributions are investigated numerically with Ansys Fluent. In order to study the heat transfer inside the aforementioned refrigerator, forced convection theories covering the following cases are applied: closed rectangular cavity representing heat transfer inside the refrigerating compartment. The cavity volume has been represented with finite volume elements and is solved computationally with appropriate momentum and energy equations (Navier-Stokes equations). The 3D model is analyzed as transient, with k-ε turbulence model and SIMPLE pressure-velocity coupling for turbulent flow situation. The results obtained with the 3D numerical simulations are in quite good agreement with the experimental airflow measurements using the SPIV technique. After Computational Fluid Dynamics (CFD) analysis of the baseline case, the effects of three parameters: compressor capacity, fan rotational speed and type of shelf (glass or wire) are studied on the energy consumption; pull down time, temperature distributions in the cabinet. For each case, energy consumption based on experimental results is calculated. After the analysis, the main effective parameters for temperature distribution inside a cabin and energy consumption based on CFD simulation are determined and simulation results are supplied for Design of Experiments (DOE) as input data for optimization. The best configuration with minimum energy consumption that provides minimum temperature difference between the shelves inside the cabinet is determined.

Keywords: air distribution, CFD, DOE, energy consumption, experimental, larder cabinet, refrigeration, uniform temperature

Procedia PDF Downloads 82

Authors: Ram V. Mohan, John Rivas-Murillo, Ahmed Mohamed, Wayne D. Hodo

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Cementitious materials, an excellent example of highly complex, heterogeneous material systems, are cement-based systems that include cement paste, mortar, and concrete that are heavily used in civil infrastructure; though commonly used are one of the most complex in terms of the material morphology and structure than most materials, for example, crystalline metals. Processes and features occurring at the nanometer sized morphological structures affect the performance, deformation/failure behavior at larger length scales. In addition, cementitious materials undergo chemical and morphological changes gaining strength during the transient hydration process. Hydration in cement is a very complex process creating complex microstructures and the associated molecular structures that vary with hydration. A fundamental understanding can be gained through multi-scale level modeling for the behavior and properties of cementitious materials starting from the material chemistry level atomistic scale to further explore their role and the manifested effects at larger length and engineering scales. This predictive modeling enables the understanding, and studying the influence of material chemistry level changes and nanomaterial additives on the expected resultant material characteristics and deformation behavior. Atomistic-molecular dynamic level modeling is required to couple material science to engineering mechanics. Starting at the molecular level a comprehensive description of the material’s chemistry is required to understand the fundamental properties that govern behavior occurring across each relevant length scale. Material chemistry level models and molecular dynamics modeling and simulations are employed in our work to describe the molecular-level chemistry features of calcium-silicate-hydrate (CSH), one of the key hydrated constituents of cement paste, their associated deformation and failure. The molecular level atomic structure for CSH can be represented by Jennite mineral structure. Jennite has been widely accepted by researchers and is typically used to represent the molecular structure of the CSH gel formed during the hydration of cement clinkers. This paper will focus on our recent work on the shear and compressive deformation and failure behavior of CSH represented by Jennite mineral structure that has been widely accepted by researchers and is typically used to represent the molecular structure of CSH formed during the hydration of cement clinkers. The deformation and failure behavior under shear and compression loading deformation in traditional hydrated CSH; effect of material chemistry changes on the predicted stress-strain behavior, transition from linear to non-linear behavior and identify the on-set of failure based on material chemistry structures of CSH Jennite and changes in its chemistry structure will be discussed.

Keywords: cementitious materials, deformation, failure, material chemistry modeling

Procedia PDF Downloads 265

Authors: E. Mosiniewicz-Szablewska, P. Suchocki, P. C. Morais

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Despite the significant progress in cancer treatment, there is a need to search for new therapeutic methods in order to minimize side effects. Chemotherapy, the main current method of treating cancer, is non-selective and has a number of limitations. Toxicity to healthy cells is undoubtedly the biggest problem limiting the use of many anticancer drugs. The problem of how to kill cancer without harming a patient can be solved by using organic selenium (IV) compounds. Organic selenium (IV) compounds are a new class of materials showing a strong anticancer activity. They are first organic compounds containing selenium at the +4 oxidation level and therefore they eliminate the multidrug-resistance for all tumor cell lines tested so far. These materials are capable of selectively killing cancer cells without damaging the healthy ones. They are obtained by the incorporation of selenous acid (H2SeO3) into molecules of fatty acids of sunflower oil and therefore, they are inexpensive to manufacture. Attaching these compounds to magnetic carriers enables their precise delivery directly to the tumor area and the simultaneous application of the magnetic hyperthermia, thus creating a huge opportunity to effectively get rid of the tumor without any side effects. Polylactic-co-glicolic acid (PLGA) nanocapsules loaded with maghemite (-Fe2O3) nanoparticles and organic selenium (IV) compounds are successfully prepared by nanoprecipitation method. In vitro antitumor activity of the nanocapsules were evidenced using murine melanoma (B16-F10), oral squamos carcinoma (OSCC) and murine (4T1) and human (MCF-7) breast lines. Further exposure of these cells to an alternating magnetic field increased the antitumor effect of nanocapsules. Moreover, the nanocapsules presented antitumor effect while not affecting normal cells. Magnetic properties of the nanocapsules were investigated by means of dc magnetization, ac susceptibility and electron spin resonance (ESR) measurements. The nanocapsules presented a typical superparamagnetic behavior around room temperature manifested itself by the split between zero field-cooled/field-cooled (ZFC/FC) magnetization curves and the absence of hysteresis on the field-dependent magnetization curve above the blocking temperature. Moreover, the blocking temperature decreased with increasing applied magnetic field. The superparamagnetic character of the nanocapsules was also confirmed by the occurrence of a maximum in temperature dependences of both real ′(T) and imaginary ′′ (T) components of the ac magnetic susceptibility, which shifted towards higher temperatures with increasing frequency. Additionally, upon decreasing the temperature the ESR signal shifted to lower fields and gradually broadened following closely the predictions for the ESR of superparamagnetoc nanoparticles. The observed superparamagnetic properties of nanocapsules enable their simple manipulation by means of magnetic field gradient, after introduction into the blood stream, which is a necessary condition for their use as magnetic drug carriers. The observed anticancer and superparamgnetic properties show that the magnetic nanocapsules loaded with organic selenium (IV) compounds should be considered as an effective material system for magnetic drug delivery and magnetohyperthermia inductor in antitumor therapy.

Keywords: cancer treatment, magnetic drug delivery system, nanomaterials, nanotechnology

Procedia PDF Downloads 180

Authors: B. S. Premalatha, Mereen Rose Babu, Vaishali Prabhu

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Background: Dysphagia must be assessed, either subjectively or objectively, in order to properly address the swallowing difficulty. Providing therapeutic care to patients with dysphagia via tele mode was one approach for providing clinical services during the COVID-19 epidemic. As a result, the teleassessment of dysphagia has increased in India. Aim: This study aimed to identify challenges faced by Indian SLPs while providing teleassessment to individuals with dysphagia during the outbreak of COVID-19 from 2020 to 2021. Method: After receiving approval from the institute's institutional review board and ethics committee, the current study was carried out. The study was cross-sectional in nature and lasted from 2020 to 2021. The study enrolled participants who met the inclusion and exclusion criteria of the study. It was decided to recruit roughly 246 people based on the sample size calculations. The research was done in three stages: questionnaire development and content validation, questionnaire administration. Five speech and hearing professionals' content verified the questionnaire for faults and clarity. Participants received questionnaires via various social media platforms such as e-mail and WhatsApp, which were written in Microsoft Word and then converted to Google Forms. SPSS software was used to examine the data. Results: In light of the obstacles that Indian SLPs encounter, the study's findings were examined. Only 135 people responded. During the COVID-19 lockdowns, 38% of participants said they did not deal with dysphagia patients. After the lockout, 70.4% of SLPs kept working with dysphagia patients, while 29.6% did not. From the beginning of the oromotor examination, the main problems in completing tele evaluation of dysphagia have been highlighted. Around 37.5% of SLPs said they don't undertake the OPME online because of difficulties doing the evaluation, such as the need for repeated instructions from patients and family members and trouble visualizing structures in various positions. The majority of SLPs' online assessments were inefficient and time-consuming. A bigger percentage of SLPs stated that they will not advocate tele evaluation in dysphagia to their colleagues. SLPs' use of dysphagia assessment has decreased as a result of the epidemic. When it came to the amount of food, the majority of people proposed a small amount. Apart from placing the patient for assessment and gaining less cooperation from the family, most SLPs found that Internet speed was a source of concern and a barrier. Hearing impairment and the presence of a tracheostomy in patients with dysphagia proved to be the most difficult conditions to treat online. For patients with NPO, the majority of SLPs did not advise tele-evaluation. In the anterior region of the oral cavity, oral meal residue was more visible. The majority of SLPs reported more anterior than posterior leakage. Even while the majority of SLPs could detect aspiration by coughing, many found it difficult to discern the gurgling tone of speech after swallowing. Conclusion: The current study sheds light on the difficulties that Indian SLPs experience when assessing dysphagia via tele mode, indicating that tele-assessment of dysphagia is still to gain importance in India.

Keywords: dysphagia, teleassessment, challenges, Indian SLP

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Authors: Felipe M. de Freitas, Icaro V. Soares, Lucas L. L. Fortes, Sandro T. M. Gonçalves, Úrsula D. C. Resende

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The SPICE-based simulators are quite robust and widely used for simulation of electronic circuits, their algorithms support linear and non-linear lumped components and they can manipulate an expressive amount of encapsulated elements. Despite the great potential of these simulators based on SPICE in the analysis of quasi-static electromagnetic field interaction, that is, at low frequency, these simulators are limited when applied to microwave hybrid circuits in which there are both lumped and distributed elements. Usually the spatial discretization of the FDTD (Finite-Difference Time-Domain) method is done according to the actual size of the element under analysis. After spatial discretization, the Courant Stability Criterion calculates the maximum temporal discretization accepted for such spatial discretization and for the propagation velocity of the wave. This criterion guarantees the stability conditions for the leapfrogging of the Yee algorithm; however, it is known that for the field update, the stability of the complete FDTD procedure depends on factors other than just the stability of the Yee algorithm, because the FDTD program needs other algorithms in order to be useful in engineering problems. Examples of these algorithms are Absorbent Boundary Conditions (ABCs), excitation sources, subcellular techniques, grouped elements, and non-uniform or non-orthogonal meshes. In this work, the influence of the stability of the FDTD method in the modeling of concentrated elements such as resistive sources, resistors, capacitors, inductors and diode will be evaluated. In this paper is proposed, therefore, the electromagnetic modeling of electronic components in order to create models that satisfy the needs for simulations of circuits in ultra-wide frequencies. The models of the resistive source, the resistor, the capacitor, the inductor, and the diode will be evaluated, among the mathematical models for lumped components in the LE-FDTD method (Lumped-Element Finite-Difference Time-Domain), through the parametric analysis of Yee cells size which discretizes the lumped components. In this way, it is sought to find an ideal cell size so that the analysis in FDTD environment is in greater agreement with the expected circuit behavior, maintaining the stability conditions of this method. Based on the mathematical models and the theoretical basis of the required extensions of the FDTD method, the computational implementation of the models in Matlab® environment is carried out. The boundary condition Mur is used as the absorbing boundary of the FDTD method. The validation of the model is done through the comparison between the obtained results by the FDTD method through the electric field values and the currents in the components, and the analytical results using circuit parameters.

Keywords: hybrid circuits, LE-FDTD, lumped element, parametric analysis

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Authors: Neha Adsul, Rohit Shah

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Background: The global history of nursing is exclusively a history of deep contradictions as it seeks to negotiate inclusion in an already gendered world. Although a powerful 'clinical gaze exists, nurses have toiled to re-negotiate and subvert the 'medical gaze' by practicing the 'therapeutic gaze' to tether back 'care into nursing practice.' This helps address the duality of the 'body' and 'mind' wherein the patient is not just limited to being an object of medical inquiry. Nevertheless, there has been a consistent effort to fit 'nursing' into being an art or an emerging science over the years. Especially with advances in hospital-based techno-centric medical practices, the boundaries between technology and nursing practices are becoming more blurred as the technical process becomes synonymous with nursing, eroding the essence of nursing care. Aim: This paper examines the history of nursing and offers insights into how gendered relations and the ideological belief of 'nursing as gendered work' have propagated to the subjugation of the nursing profession. It further aims to provide insights into the patriarchally imbibed techno-centrism that negates the gendered caregiving which lies at the crux of a nurse's work. Method: A literature search was carried out using Google Scholar, Web of Science and PubMed databases. Search words included: technology and nursing, medical technology and nursing, history of nursing, sociology and nursing and nursing care. The history of nursing is presented in a discussion that weaves together the historical events of the 'Birth of the Clinic' and the shift from 'bed-side medicine' to 'hospital-based medicine' that legitimizes exploitation of the bodies of patients to the 'medical gaze while the emergence of nursing as acquiescent to instrumental, technical, positivist and dominant views of medicine. The resultant power asymmetries, wherein in contemporary nursing, the constant struggle of nurses to juggle between being the physicians "operational right arm" to harboring that subjective understanding of the patients to refrain from de-humanizing nursing-care. Findings: The nursing profession suffers from being rendered invisible due to gendered relations having patrifocal societal roots. This perpetuates a notion rooted in the idea that emphasizes empiricism and has resulted in theoretical and epistemological fragmentation of the understanding of body and mind as separate entities. Nurses operate within this structure while constantly being at the brink of being pushed beyond the legitimate professional boundaries while being labeled as being 'unscientific' as the work does not always corroborate and align with the existing dominant positivist lines of inquiries. Conclusion: When understood in this broader context of how nursing as a practice has evolved over the years, it provides a particularly crucial testbed for understanding contemporary gender relations. Not because nurses like to live in a gendered work trap but because the gendered relations at work are written in a covert narcissistic patriarchal milieu that fails to recognize the value of intangible yet utmost necessary 'caring work in nursing. This research urges and calls for preserving and revering the humane aspect of nursing care alongside the emerging tech-savvy expectations from nursing work.

Keywords: nursing history, technocentric, power relations, scientific duality

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Authors: Asma Ben Hmidene, Mizuho Hanaki, Kazuma Murakami, Kazuhiro Irie, Hiroko Isoda, Hideyuki Shigemori

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Type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) are characterized as a peripheral metabolic disorder and a degenerative disease of the central nervous system, respectively. It is now widely recognized that T2DM and AD share many pathophysiological features including glucose metabolism, increased oxidative stress and amyloid aggregation. Amyloid beta (Aβ) is the components of the amyloid deposits in the AD brain and while the component of the amyloidogenic peptide deposit in the pancreatic islets of Langerhans is identified as human islet amyloid polypeptide (hIAPP). These two proteins are originated from the amyloid precursor protein and have a high sequence similarity. Although the amino acid sequences of amyloidogenic proteins are diverse, they all adopt a similar structure in aggregates called cross-beta-spine. Add at that, extensive studies in the past years have found that like Aβ1-42, IAPP forms early intermediate assemblies as spherical oligomers, implicating that these oligomers possess a common folding pattern or conformation. These similarities can be used in the search for effective pharmacotherapy for DM, since potent therapeutic agents such as antioxidants with a catechol moiety, proved to inhibit Aβ aggregation, may play a key role in the inhibit the aggregation of hIAPP treatment of patients with DM. Tamarix gallica is one of the halophyte species having a powerful antioxidant system. Although it was traditionally used for the treatment of various liver metabolic disorders, there is no report about the use of this plant for the treatment or prevention of T2DM and AD. Therefore, the aim of this work is to investigate their protective effect towards T2DM and AD by isolation and identification of α-glucosidase inhibitors, with antioxidant potential, that play an important role in the glucose metabolism in diabetic patient, as well as, the polymerization of hIAPP and Aβ aggregation inhibitors. Structure-activity relationship study was conducted for both assays. And as for α-glucosidase inhibitors, their mechanism of action and their synergistic potential when applied with a very low concentration of acarbose were also suggesting that they can be used not only as α-glucosidase inhibitors but also be combined with established α-glucosidase inhibitors to reduce their adverse effect. The antioxidant potential of the purified substances was evaluated by DPPH and SOD assays. Th-T assay using 42-mer amyloid β-protein (Aβ42) for AD and hIAPP which is a 37-residue peptide secreted by the pancreatic β –cells for T2DM and Transmission electronic microscopy (TEM) were conducted to evaluate the amyloid aggragation of the actives substances. For α-glucosidase, p-NPG and glucose oxidase assays were performed for determining the inhibition potential and structure-activity relationship study. The Enzyme kinetic protocol was used to study the mechanism of action. From this research, it was concluded that polyphenols playing a role in the glucose metabolism and oxidative stress can also inhibit the amyloid aggregation, and that substances with a catechol and glucuronide moieties inhibiting amyloid-β aggregation, might be used to inhibit the aggregation of hIAPP.

Keywords: α-glucosidase inhibitors, amyloid aggregation inhibition, mechanism of action, polyphenols, structure activity relationship, synergistic potential, tamarix gallica

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Authors: Maryam Hajrezaie, Mahmood Ameen Abdulla, Nazia Abdul Majid, Hapipa Mohd Ali, Pouya Hassandarvish, Maryam Zahedi Fard

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Background: Colon cancer is one of the most prevalent cancers in the world and is the third leading cause of death among cancers in both males and females. The incidence of colon cancer is ranked fourth among all cancers but varies in different parts of the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. Andrographolide is the major labdane diterpenoidal constituent of the plant Andrographis paniculata (family Acanthaceae), used extensively in the traditional medicine. Extracts of the plant and their constituents are reported to exhibit a wide spectrum of biological activities of therapeutic importance. Laboratory animal model studies have provided evidence that Andrographolide play a role in inhibiting the risk of certain cancers. Objective: Our aim was to evaluate the chemopreventive efficacy of the Andrographolide in the AOM induced rat model. Methods: To evaluate inhibitory properties of andrographolide on colonic aberrant crypt foci (ACF), five groups of 7-week-old male rats were used. Group 1 (control group) were fed with 10% Tween 20 once a day, Group 2 (cancer control) rats were intra-peritoneally injected with 15 mg/kg Azoxymethan, Gropu 3 (drug control) rats were injected with 15 mg/kg azoxymethan and 5-Flourouracil, Group 4 and 5 (experimental groups) were fed with 10 and 20 mg/kg andrographolide each once a day. After 1 week, the treatment group rats received subcutaneous injections of azoxymethane, 15 mg/kg body weight, once weekly for 2 weeks. Control rats were continued on Tween 20 feeding once a day and experimental groups 10 and 20 mg/kg andrographolide feeding once a day for 8 weeks. All rats were sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated grossly and histopathologically for ACF. Results: Administration of 10 mg/kg and 20 mg/kg andrographolide were found to be effectively chemoprotective, as evidenced microscopily and biochemically. Andrographolide suppressed total colonic ACF formation up to 40% to 60%, respectively, when compared with control group. Pre-treatment with andrographolide, significantly reduced the impact of AOM toxicity on plasma protein and urea levels as well as on plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GGT) activities. Grossly, colorectal specimens revealed that andrographolide treatments decreased the mean score of number of crypts in AOM-treated rats. Importantly, rats fed andrographolide showed 75% inhibition of foci containing four or more aberrant crypts. The results also showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE2) activities and a decrease in malondialdehyde (MDA) level. Histologically all treatment groups showed a significant decrease of dysplasia as compared to control group. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. Conclusion: The current study demonstrated that Andrographolide reduce the number of ACF. According to these data, Andrographolide might be a promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, andrographolide, colon cancer, aberrant crypt foci (ACF)

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