Search results for: physiological shear

Authors: Hossein Bazmara, Kaamran Raahemifar, Mostafa Sefidgar, Madjid Soltani

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Angiogenesis is formation of new blood vessels from existing vessels. Due to flow of blood in vessels, during angiogenesis, blood flow plays an important role in regulating the angiogenesis process. Multiple mathematical models of angiogenesis have been proposed to simulate the formation of the complicated network of capillaries around a tumor. In this work, a multi-scale model of angiogenesis is developed to show the effect of blood flow on capillaries and network formation. This model spans multiple temporal and spatial scales, i.e. intracellular (molecular), cellular, and extracellular (tissue) scales. In intracellular or molecular scale, the signaling cascade of endothelial cells is obtained. Two main stages in development of a vessel are considered. In the first stage, single sprouts are extended toward the tumor. In this stage, the main regulator of endothelial cells behavior is the signals from extracellular matrix. After anastomosis and formation of closed loops, blood flow starts in the capillaries. In this stage, blood flow induced signals regulate endothelial cells behaviors. In cellular scale, growth and migration of endothelial cells is modeled with a discrete lattice Monte Carlo method called cellular Pott's model (CPM). In extracellular (tissue) scale, diffusion of tumor angiogenic factors in the extracellular matrix, formation of closed loops (anastomosis), and shear stress induced by blood flow is considered. The model is able to simulate the formation of a closed loop and its extension. The results are validated against experimental data. The results show that, without blood flow, the capillaries are not able to maintain their integrity.

Keywords: angiogenesis, endothelial cells, multi-scale model, cellular Pott's model, signaling cascade

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Authors: Arunas Emeljanovas, Brigita Mieziene, Tomas Venckunas

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Background statement: Level of aerobic capacity in school age children provides important information about the current and future cardiovascular, skeletal and mental health. It is widely recognised that risk factors for modern chronic diseases of the adults have their origins in childhood and adolescence. The aim of the study was to analyse the trends of aerobic capacity across decades within groups of gender and age. Methods. The research included data of participants from the three nationally representative cohort studies performed in Lithuania in the years 1992, 2002 and 2012 among 11 to 18-years-old school children. Total of 18,294 school children were recruited for testing. Only those who had their body weight and height measured and completed 20 m shuttle endurance test were included in the analysis. The total number of students included in the analyses was 15,213 (7608 boys and 7605 girls). The permission to conduct the study was obtained from the Lithuanian Bioethics Committee (permission number BE-2-45). Major findings: Results are performed across gender and age groups. The comparison of shuttle endurance test, controlling for body mass index, indicated that in general there is a constant decrease of aerobic capacity across decades in both genders and age groups. The deterioration in aerobic capacity in boys accounted for 17 to 43 percent across age groups within decades. The biggest decrease was in 14 years-old boys. The deterioration in girls accounted for 19 to 37 percent across age groups with the highest decrease in 11 years-old girls. Though, girls had lower levels of aerobic capacity through all age groups and across three decades. Body mass index, as a covariate, accounted for up to six percent in deterioration of aerobic capacity. Final statement: The detected relationships may reflect the level and pattern of engagement in physical activity and sports where increased activity associates with superior performance in the tests because of the upregulated physiological function and instigated competitive/motivational level. The significance of the decade indirectly supports the importance of the recently changed activity among schoolchildren for this relationship.

Keywords: aerobic capacity, cardiovascular health, endurance, school age children

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Authors: Solene Masloh, Anne Chevrel, Maxime Culot, Leonardo Scapozza, Magali Zeisser-Labouebe

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The limited stability of clinically proven therapeutic antibodies limits their administration by the parenteral route. However, oral administration remains the best alternative as it is the most convenient and less invasive one. Obtaining a targeted treatment based on biologics, which can be orally administered, would, therefore, be an ideal situation to improve patient adherence and compliance. Nevertheless, the delivery of macromolecules through the intestine remains challenging because of their sensitivity to the harsh conditions of the gastrointestinal tract and their low permeability across the intestinal mucosa. To address this challenge, this project aims to demonstrate that targeting receptor-mediated endocytosis followed by transcytosis could maximize the intestinal uptake and transport of large molecules, such as Nanofitins. These affinity proteins of 7 kDa with binding properties similar to antibodies have already demonstrated retained stability in the digestive tract and local efficiency. However, their size does not allow passive diffusion through the intestinal barrier. Nanofitins having a controlled affinity for membrane receptors involved in the transcytosis mechanism used naturally for the transport of large molecules in humans were generated. Proteins were expressed using ribosome display and selected based on affinity to the targeted receptor and other characteristics. Their uptake and transport ex vivo across viable porcine intestines were investigated using an Ussing chambers system. In this paper, we will report the results achieved while addressing the different challenges linked to this study. To validate the ex vivo model, first, we proved the presence of the receptors targeted in humans on the porcine intestine. Then, after the identification of an optimal way of detection of Nanofitins, transport experiments were performed on porcine intestines with viability followed during the time of the experiment. The results, showing that the physiological process of transcytosis is capable of being triggered by the binding of Nanofitins on their target, will be reported here. In conclusion, the results show that Nanofitins can be transported across the intestinal barrier by triggering the receptor-mediated transcytosis and that the ex vivo model is an interesting technique to assess biologics absorption through the intestine.

Keywords: ex-vivo, Nanofitins, oral administration, transcytosis

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Authors: Ishfaq A. Bukhari, Bassem Yousef Sheikh, Abdulrahman Almotrefi, Osama Yousaf, Amer Mahmood

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Olive oil is the primary source of fat in the Mediterranean diet which is associated with a low mortality for cardiovascular disease. Olive oil is rich in monounsaturated fatty acids, and has been reported for variety of beneficial cardiovascular effects including blood pressure lowering, anti-platelet, anti-diabetic and anti-inflammatory effects. Growing number evidences from preclinical and clinical studies have shown that olive oil improves insulin resistance, decrease vessels stiffness and prevent thromboembolism. We evaluated the effects of olive against streptozotocin-induced physiological disorders in the animal models of diabetes and ischemia and reperfusion (I/R)- induced cardiac arrhythmias. Diabetes was induced in male rats with a single intraperitoneal injection of streptozotocin (60 mg/kg), rats were treated for two months with olive oil (1 ml/kg p.o). Control animals received saline. Blood glucose, body weight were monitored every 14 days. At the end of the treatment rats were sacrificed hearts were isolated for mounting on langedorff’s apparatus. The blood glucose and body weight was not significantly different in the control and olive treated animals. The control diabetic animals exhibited 100% incidence of I/R –induced ventricular fibrillation which was reduced to 0% with olive oil, treatment. The duration of ventricular fibrillation reduced from 98.8± 2.3 (control) to 0 seconds in the olive oil treated group. Diltiazem, a calcium channel blocker (1 µm/L) showed similar results and protected the I/R-induced cardiac disorders. The biochemical analysis of the cardiac tissues showed that diabetes and I/R produce marked pathological changes in the cardiomyocytes including decreased glutathione (GSH) and increased oxidative stress (Malondialdehyde; MDA). Pretreatment of animals with olive oil (1 ml/kg p.o) increased GSH and MDA levels. Olive oil also improved the diabetic-induced histopathological changes in the cardiomyocytes. These finding indicates that olive possesses cardiac protective properties. Further studies are under way in our lab to explore the mechanism of the cardio-protective effect of olive oil.

Keywords: diabeties, ischemia-reperfusion, olive oil, rats heart

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Authors: Nafiseh Mirabdolhosseini, Jerry Zhou, Vincent Ho

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The dramatic global rise in acid reflux has also led to oesophageal adenocarcinoma (OAC) becoming the fastest-growing cancer in developed countries. While gastroscopy with biopsy is used to diagnose OAC patients, this labour-intensive and expensive process is not suitable for population screening. This study aims to design, develop, and implement a minimally invasive system to capture optical data of the distal oesophagus for rapid screening of potential abnormalities. To develop the system and understand user requirements, a user-centric approach was employed by utilising co-design strategies. Target users’ segments were identified, and 38 patients and 14 health providers were interviewed. Next, the technical requirements were developed based on consultations with the industry. A minimally invasive optical system was designed and developed considering patient comfort. This system consists of the sensing catheter, controller unit, and analysis program. Its procedure only takes 10 minutes to perform and does not require cleaning afterward since it has a single-use catheter. A prototype system was evaluated for safety and efficacy for both laboratory and clinical performance. This prototype performed successfully when submerged in simulated gastric fluid without showing evidence of erosion after 24 hours. The system effectively recorded a video of the mid-distal oesophagus of a healthy volunteer (34-year-old male). The recorded images were used to develop an automated program to identify abnormalities in the distal oesophagus. Further data from a larger clinical study will be used to train the automated program. This system allows for quick visual assessment of the lower oesophagus in primary care settings and can serve as a screening tool for oesophageal adenocarcinoma. In addition, this system is able to be coupled with 24hr ambulatory pH monitoring to better correlate oesophageal physiological changes with reflux symptoms. It also can provide additional information on lower oesophageal sphincter functions such as opening times and bolus retention.

Keywords: endoscopy, MedTech, oesophageal adenocarcinoma, optical system, screening tool

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Authors: Mahmoud Y. M. Ahmed, Ahmed Konsowa, Mostafa Sami, Ayman Mosallam

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Fukushima nuclear accident (Japan 2011) has drawn attention to the issue of gas leakage from hazardous facilities through building boundaries. The rapidly increasing investments in nuclear stations have made the ability to predict, and prevent, gas leakage a rather crucial issue both environmentally and economically. Leakage monitoring for underground facilities is rather complicated due to the combination of Reinforced Concrete Shear Wall (RCSW) and soil. In the framework of a recent research conducted by the authors, the gas insulation capabilities of RCSW-soil combination have been investigated via a lab-scale experimental work. Despite their accuracy, experimental investigations are expensive, time-consuming, hazardous, and lack for flexibility. Numerically simulating the gas leakage as a fluid flow problem based on Computational Fluid Dynamics (CFD) modeling approach can provide a potential alternative. This novel implementation of CFD approach is the topic of the present paper. The paper discusses the aspects of modeling the gas flow through porous media that resemble the RCSW both isolated and combined with the normal soil. A commercial CFD package is utilized in simulating this fluid flow problem. A fixed RCSW layer thickness is proposed, air is taken as the leaking gas, whereas the soil layer is represented as clean sand with variable properties. The variable sand properties include sand layer thickness, fine fraction ratio, and moisture content. The CFD simulation results almost demonstrate what has been found experimentally. A soil layer attached next to a cracked reinforced concrete section plays a significant role in reducing the gas leakage from that cracked section. This role is found to be strongly dependent on the soil specifications.

Keywords: RCSW, gas leakage, Pressure Decay Method, hazardous underground facilities, CFD

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Authors: Chaoge Wang, Xiquan Weng, Yan Meng, Wentao Lin

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Objective: Cold exposure and exercise serve as two physiological stimuli to glycolipid metabolism and insulin sensitivity. So far, it remains to be elucidated whether exercise plus cold exposure can produce an addictive effect on promoting glycolipid metabolism and insulin sensitivity. Methods: 64 SD rats were subjected to high-fat and high-sugar diets for 9-week and sucessfully to establish an obesity model. They were randomly divided into 8 groups: normal control group (NC), normal exercise group (NE), continuous cold control group (CC), continuous cold exercise group (CE), acute clod control group (AC), acute cold exercise group (AE), intermittent cold control group (IC) and intermittent cold exercise group (IE). For continuous cold exposure, the rats stayed in a cold environment all day; for acute cold exposure, the rats were exposed to cold for only 4h before the end of the experiment; for intermittent cold exposure, the rats were exposed to cold for 4h per day. The protocol for treadmill runnings were as follows: 25m/min (speed), 0°C (slope), 30 mins each time, an interval for 10 mins between two runnings, twice/two days, lasting for 5 weeks. Sampling were conducted on the 5th weekend. Blood lipids, free fatty acids, blood glucose (FBG), and serum insulin (FINS) were examined, and the insulin resistance index (HOMA-IR = FBG (mmol/L)×FINS(mIU/L)/22.5) was calculated. SPSS 22.0 was used for statistical analysis of the experimental results, and the ANOVA analysis was performed between groups (p < 0.05 was significant). Results: (1) Compared with the NC group, the FBG of the rats was significantly declined in the NE, CE, AC, AE, and IE groups (p < 0.05), the FINS of the rats was significantly declined in the AE group (p < 0.05), the HOMA-IR of the rats was significantly declined in the NE, CE, AC, AE and IE groups (p < 0.05). Compared with the NE group, the FBG of the rats was significantly declined in the CE, AE, and IE groups (p < 0.05), the FINS and HOMA-IR of the rats were significantly declined in the AE group (p < 0.05). (2) Compared with the NC group, the CHO, TG, LDL-C, and FFA of the rats were significantly declined in CE and IE groups (p < 0.05), the HDL-C of the rats was significantly higher in NE, CC, CE, AE, and IE groups (p < 0.05). Compared with the NE group, the HDL-C of the rats was significantly higher in the CE and IE groups (p < 0.05). Conclusions: Sedentariness or exercise in the acute cold doesn't make sense in the treatment of type 2 diabetes, which led to one-off increases of the body's insulin sensitivity. Exercise in the continuous and intermittent cold can effectively decline the FBG, TC, TG, LDL-C, and FFA levels and increase the HDL-C level and insulin sensitivity in obese rats. These results can impact the prevention and treatment of type 2 diabetes.

Keywords: cold, exercise, insulin sensitivity, obesity

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Authors: Fabio Marson, Revital Naor-Ziv, Patrizio Paoletti, Joseph Glicksohn, Filippo Carducci, Tal Dotan Ben-Soussan

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According to embodied cognition theories, higher-order cognitive functions and complex behaviors seems to be affected by bodily states. For example, the polyvagal theory suggests that the human autonomic nervous system evolved to support social interactions. Accordingly, integration and perception of information related to the physiological state arising from the peripherical nervous system (i.e., interoception) play a role in the regulation of social interaction by modulating emotional responses and prosocial behaviors. Moreover, recent studies showed that interoception is involved in the representations of conceptual knowledge, suggesting that the bodily information carried by the interoceptive system provides a perceptual basis for the embodiment of abstract concepts, especially those related to social and emotional domains. However, to the best of our knowledge, no studies explored the relationship between interoception, prosocial behaviors, and conceptual representations. Considering the privileged position of interoception in mediating higher-order cognition and social interaction, we designed a cross-cultural study to explore the relationship between interoception, the sensitivity of bodily functions, and empathy. We recruited Italian, English, and Hebrew participants, and we asked them to fill in a questionnaire about empathy (Empathy Quotient), a questionnaire about bodily perception (Body Perception Questionnaire), and to rate different concrete and abstract concepts for the extent such concepts can be experienced through vision, hearing, taste, smell, touch, and interoception. We observed that in all languages, interoception ratings for abstract concepts were greater than for concrete concepts. Importantly, interoception ratings for abstract concepts were positively correlated with empathy and sensitivity of bodily functions. Our results suggest that participants with higher empathy and sensitivity of bodily functions show also a greater embodiment of abstract concepts in interoception, providing further evidence for the importance of the interoceptive system in regulating prosocial behaviors and integrating conceptual representations.

Keywords: conceptual representations, embodiment, empathy, empathy quotient, interoception, prosocial behaviors

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Authors: Fanous Mohammadi, Majid H. Tangestani, Mohammad H. Tayebi

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This research aims to evaluate and compare Geographical Information Systems (GIS)-based fuzzy models for producing orogenic gold prospectivity maps in the Saqqez area, NW of Iran. Gold occurrences are hosted in sericite schist and mafic to felsic meta-volcanic rocks in this area and are associated with hydrothermal alterations that extend over ductile to brittle shear zones. The predictor maps, which represent the Pre-(Source/Trigger/Pathway), syn-(deposition/physical/chemical traps) and post-mineralization (preservation/distribution of indicator minerals) subsystems for gold mineralization, were generated using empirical understandings of the specifications of known orogenic gold deposits and gold mineral systems and were then pre-processed and integrated to produce mineral prospectivity maps. Five fuzzy logic operators, including AND, OR, Fuzzy Algebraic Product (FAP), Fuzzy Algebraic Sum (FAS), and GAMMA, were applied to the predictor maps in order to find the most efficient prediction model. Prediction-Area (P-A) plots and field observations were used to assess and evaluate the accuracy of prediction models. Mineral prospectivity maps generated by AND, OR, FAP, and FAS operators were inaccurate and, therefore, unable to pinpoint the exact location of discovered gold occurrences. The GAMMA operator, on the other hand, produced acceptable results and identified potentially economic target sites. The P-A plot revealed that 68 percent of known orogenic gold deposits are found in high and very high potential regions. The GAMMA operator was shown to be useful in predicting and defining cost-effective target sites for orogenic gold deposits, as well as optimizing mineral deposit exploitation.

Keywords: mineral prospectivity mapping, fuzzy logic, GIS, orogenic gold deposit, Saqqez, Iran

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Authors: Attef Kouadria, Yehya Bouteghrine, Amar Manaa, Tarek Mouats, Djalel Eddine Tria, Hamid Abdelhafid Ghouti

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Personal protection systems have been used in several forms for centuries. The need for light-weight composite structures has been in great demand due to their weight and high mechanical properties ratios in comparison to heavy and cumbersome steel plates. In this regard, lighter ceramic plates with a backing plate made of high strength polymeric fibers, mostly aramids, are widely used for protection against ballistic threats. This study aims to improve the ballistic performance of ceramic/composite plates subjected to ballistic impact by reducing the back face deformation (BFD) measured after each test. A new hybridization technique was developed in this investigation to increase the energy absorption capabilities of the backing plates. The hybridization consists of combining different types of aramid fabrics with different linear densities of aramid fibers (Dtex) and areal densities with an epoxy resin to form the backing plate. Therefore, several composite structures architectures were prepared and tested. For better understanding the effect of the hybridization, a serial of tensile, compression, and shear tests were conducted to determine the mechanical properties of the homogeneous composite materials prepared from different fabrics. It was found that the hybridization allows the backing plate to combine between the mechanical properties of the used fabrics. Aramid fabrics with higher Dtex were found to increase the mechanical strength of the backing plate, while those with lower Dtex found to enhance the lateral wave dispersion ratio due to their lower areal density. Therefore, the back face deformation was significantly reduced in comparison to a homogeneous composite plate.

Keywords: aramid fabric, ballistic impact, back face deformation, body armor, composite, mechanical testing

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Authors: Ameer A. Jebur, William Atherton, Rafid M. Alkhaddar, Edward Loffill

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Superstructures like offshore platforms, tall buildings, transition towers, skyscrapers and bridges are normally designed to resist compression, uplift and lateral forces from wind waves, negative skin friction, ship impact and other applied loads. Better understanding and the precise simulation of the response of batter piles under the action of independent uplift loads is a vital topic and an area of active research in the field of geotechnical engineering. This paper investigates the use of finite element code (FEC) to examine the behaviour of model batter piles penetrated in dense sand, subjected to pull-out pressure by means of numerical modelling. The concept of the Winkler Model (beam on elastic foundation) has been used in which the interaction between the pile embedded depth and adjacent soil in the bearing zone is simulated by nonlinear p-y curves. The analysis was conducted on different pile slenderness ratios (lc⁄d) ranging from 7.5, 15.22 and 30 respectively. In addition, the optimum batter angle for a model steel pile penetrated in dense sand has been chosen to be 20° as this is the best angle for this simulation as demonstrated by other researcher published in literature. In this numerical analysis, the soil response is idealized as elasto-plastic and the model piles are described as elastic materials for the purpose of simulation. The results revealed that the applied loads affect the pullout pile capacity as well as the lateral pile response for dense sand together with varying shear strength parameters linked to the pile critical depth. Furthermore, the pile pull-out capacity increases with increasing the pile aspect ratios.

Keywords: slenderness ratio, soil-pile interaction, winkler model (beam on elastic foundation), pull-out capacity

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Authors: María Teresa Baquero, Ester Higueras

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One of the challenges facing 21st century cities, is their adaptation to the phenomenon of an ageing population. International policies have been developed, such as the "Global Network for Age-friendly Cities and Communities". These cities must recognize the diversity of the elderly population, and facilitate an active, healthy, satisfied aging and promote inclusion. In order to promote active and healthy aging, older people should be encouraged to engage in physical activity, sunbathe, socialize and enjoy the public open spaces in the city. Some studies recognize thermal comfort as one of the factors that most influence the use of public open spaces. However, although some studies have shown vulnerability to thermal extremes and environmental conditions in older people, there is little research on thermal comfort for older adults, because it is usually analyzed based on the characteristics of the ¨average young person¨ without considering the physiological, physical and psychological differences that characterize the elderly. This study analyzes the relationship between the microclimate parameters as air temperature, relative humidity, wind speed and sky view factor (SVF) with the personal thermal perception of older adults in three public spaces in Madrid, through a mixed methodology that combines weather measurements with interviews, made during the year 2018. Statistical test like Chi-square, Spearman, and analysis of variance were used to analyze the relationship between preference votes and thermal sensation votes with environmental and personal parameters. The results show that there is a significant correlation between thermal sensation and thermal preference with the measured air temperature, age, level of clothing, the color of clothing, season, time of the day and kind of space while no influence of gender or other environmental variables was detected. These data would contribute to the design of comfortable public spaces that improve the welfare of the elderly contributing to "active and healthy aging" as one of the 21st century challenges cities face.

Keywords: healthy ageing, older adults, outdoor public space, thermal perception

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Authors: Younes El Khchine

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A parametric study has been conducted to analyse the flow around S809 airfoil of a wind turbine in order to better understand the characteristics and effects of laminar separation bubble (LSB) on aerodynamic design for maximizing wind turbine efficiency. Numerical simulations were performed at low Reynolds numbers by solving the Unsteady Reynolds Averaged Navier-Stokes (URANS) equations based on C-type structural mesh and using the γ-Reθt turbulence model. A two-dimensional study was conducted for the chord Reynolds number of 1×105 and angles of attack (AoA) between 0 and 20.15 degrees. The simulation results obtained for the aerodynamic coefficients at various angles of attack (AoA) were compared with XFoil results. A sensitivity study was performed to examine the effects of Reynolds number and free-stream turbulence intensity on the location and length of the laminar separation bubble and the aerodynamic performances of wind turbines. The results show that increasing the Reynolds number leads to a delay in the laminar separation on the upper surface of the airfoil. The increase in Reynolds number leads to an accelerated transition process, and the turbulent reattachment point moves closer to the leading edge owing to an earlier reattachment of the turbulent shear layer. This leads to a considerable reduction in the length of the separation bubble as the Reynolds number is increased. The increase in the level of free-stream turbulence intensity leads to a decrease in separation bubble length and an increase in the lift coefficient while having negligible effects on the stall angle. When the AoA increased, the bubble on the suction airfoil surface was found to move upstream to the leading edge of the airfoil, causing earlier laminar separation.

Keywords: laminar separation bubble, turbulence intensity, s809 airfoil, transition model, Reynolds number

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Authors: Spandan Sahu, Amiya Kumar Pati, Kishanjit Kumar Khatua

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Vegetation plays a major role in deciding the flow parameters in an open channel. It enhances the aesthetic view of the revetments. The major types of vegetation in river typically comprises of herbs, grasses, weeds, trees, etc. The vegetation in an open channel usually consists of aquatic plants with complete submergence, partial submergence, floating plants. The presence of vegetative plants can have both benefits and problems. The major benefits of aquatic plants are they reduce the soil erosion, which provides the water with a free surface to move on without hindrance. The obvious problems are they retard the flow of water and reduce the hydraulic capacity of the channel. The degree to which the flow parameters are affected depends upon the density of the vegetation, degree of submergence, pattern of vegetation, vegetation species. Vegetation in open channel tends to provide resistance to flow, which in turn provides a background to study the varying trends in flow parameters having vegetative growth in the channel surface. In this paper, an experiment has been conducted on a meandering channel having sinuosity of 1.33 with rigid vegetation cover to investigate the effect on flow parameters, variation of manning’s n with degree of the denseness of vegetation, vegetation pattern and submergence criteria. The measurements have been carried out in four different cross-sections two on trough portion of the meanders, two on the crest portion. In this study, the analytical solution of Shiono and knight (SKM) for lateral distributions of depth-averaged velocity and bed shear stress have been taken into account. Dimensionless eddy viscosity and bed friction have been incorporated to modify the SKM to provide more accurate results. A mathematical model has been formulated to have a comparative analysis with the results obtained from Shiono-Knight Method.

Keywords: bed friction, depth averaged velocity, eddy viscosity, SKM

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Authors: Ayman H. Amer Eissa, Abdul Rahman O. Alghannam

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The agricultural crop residuals are considered one of the most important problems faced by the environmental life and farmers in the world. A study was carried out to evaluate the physical characteristics of chopped date palm stalks (fronds and leaflets). These properties are necessary to apply normal design procedures such as pneumatic conveying, fluidization, drying, and combustion. The mechanical treatment by cutting, crushing or chopping and briquetting processes are the primary step and the suitable solution for solving this problem and recycling these residuals to be transformed into useful products. So the aim of the present work to get a high quality for agriculture residues such as date palm stalks (fronds), date palm leaflets briquettes. The results obtained from measuring the mechanical properties (average shear and compressive strength) for date palm stalks at different moisture content (12.63, 33.21 and 60.54%) was (6.4, 4.7 and 3.21MPa) and (3.8, 3.18 and 2.86MPa) respectively. The modulus of elasticity and toughness were evaluated as a function of moisture content. As the moisture content of the stalk regions increased the modulus of elasticity and toughness decreased indicating a reduction in the brittleness of the stalk regions. Chopped date palm stalks (palm fronds), date palm leaflets having moisture content of 8, 10 and 12% and 8, 10 and 12.8% w.b. were dandified into briquettes without binder and with binder (urea-formaldehyde) using a screw press machine. Quality properties for briquettes were durability, compression ratio hardness, bulk density, compression ratio, resiliency, water resistance and gases emission. The optimum quality properties found for briquettes at 8 % moisture content and without binder. Where the highest compression stress and durability were 8.95, 10.39 MPa and 97.06 %, 93.64 % for date palm stalks (palm fronds), date palm leaflets briquettes, respectively. The CO and CO2 emissions for date palm stalks (fronds), date palm leaflets briquettes were less than these for loose residuals.

Keywords: residues, date palm stalks, chopper, briquetting, quality properties

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Authors: Radyah Ivan, Khanferyan Roman

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Milk and dairy products are an important component of a balanced diet. Dairy products represent a heterogeneous food group of solid, semi-solid and liquid, fermented or non-fermented foods, each differing in nutrients such as fat and micronutrient content. Deficiency of milk and dairy products contributes a impact on the main health parameters of the various age groups of the population. The goal of this study was to analyze of the frequency of the consumption of milk and various groups of dairy products by students and its association with their body mass index (BMI), body composition and other physiological parameters. 388 full-time students of the Medical Institute of RUDN University (185 male and 203 female, average age was 20.4+2.2 and 21.9+1.7 y.o., respectively) took part in the cross-sectional study. Anthropometric measurements, estimation of BMI and body composition were analyzed by bioelectrical impedance analysis. The frequency of consumption of the milk and various groups of dairy products was studied using a modified questionnaire on the frequency of consumption of products. Due to the questionnaire data on the frequency of consumption of the diary products, it have been demonstrated that only 11% of respondents consume milk daily, 5% - cottage cheese, 4% and 1% - fermented natural and with fillers milk products, respectively, hard cheese -4%. The study demonstrated that about 16% of the respondents did not consume milk at all over the past month, about one third - cottage cheese, 22% - natural sour-milk products and 18% - sour-milk products with various fillers. hard cheeses and pickled cheeses didn’t consume 9% and 26% of respondents, respectively. We demonstrated the gender differences in the characteristics of consumer preferences were revealed. Thus female students are less likely to use cream, sour cream, soft cheese, milk comparing to male students. Among female students the prevalence of persons with overweight was higher (25%) than among male students (19%). A modest inverse relationship was demonstrated between daily milk intake, BMI, body composition parameters and diary products consumption (r=-0.61 and r=-0.65). The study showed daily insufficient milk and dairy products consumption by students and due to this it have been demonstrated the relationship between the low and rare consumption of diary products and main parameters of indicators of physical activity and health indicators.

Keywords: frequency of consumption, milk, dairy products, physical development, nutrition, body mass index.

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Authors: M. A. Rashed, A. S. Mansour, H. Faris, W. Afify

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The calcarenites carbonate rocks of the Quaternary ridges, which extend along the northwestern Mediterranean coastal plain of Egypt, represent an excellent model for the transformation of loose sediments to real sedimentary rocks by the different stages of meteoric diagenesis. The depositional and diagenetic fabrics of the rocks, in addition to the strata orientation, highly affect their ultimate compressive strength and other geotechnical properties. There is a marked increase in the compressive strength (UCS) from the first to the fourth ridge rock samples. The lowest values are related to the loose packing, weakly cemented aragonitic ooid sediments with high porosity, besides the irregularly distributed of cement, which result in decreasing the ability of these rocks to withstand crushing under direct pressure. The high (UCS) values are attributed to the low porosity, the presence of micritic cement, the reduction in grain size and the occurrence of micritization and calcretization processes. The strata orientation has a notable effect on the measured (UCS). The lowest values have been recorded for the samples cored in the inclined direction; whereas the highest values have been noticed in most samples cored in the vertical and parallel directions to bedding plane. In case of the inclined direction, the bedding planes were oriented close to the plane of maximum shear stress. The lowest and highest anisotropy values have been recorded for the first and the third ridges rock samples, respectively, which may attributed to the relatively homogeneity and well sorted grain-stone of the first ridge rock samples, and relatively heterogeneity in grain and pore size distribution and degree of cementation of the third ridge rock samples, besides, the abundance of shell fragments with intra-particle pore spaces, which may produce lines of weakness within the rock.

Keywords: compressive strength, anisotropy, calcarenites, Egypt

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Authors: Pawan Kumar, Dhananjoy Shaw

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Heart rate variability (HRV) is the physiological phenomenon of variation in the time interval between heartbeats and is alterable with fitness, age and different medical conditions including withdrawal/retirement from games/sports. Objectives of the study were to develop (a) percentile norms of heart rate variability (HRV) variables derived from time domain analysis of the Indian sportspersons withdrawn from competitive games/sports pertaining to sympathetic and parasympathetic activity (b) percentile norms of heart rate variability (HRV) variables derived from frequency domain analysis of the Indian sportspersons withdrawn from competitive games/sports pertaining to sympathetic and parasympathetic activity. The study was conducted on 430 males. Ages of the sample ranged from 30 to 35 years of same socio-economic status. Date was collected using ECG polygraphs. Data were processed and extracted using frequency domain analysis and time domain analysis. Collected data were computed with percentile from one to hundred. The finding showed that the percentile norms of heart rate variability (HRV) variables derived from time domain analysis of the Indian sportspersons withdrawn from competitive games/sports pertaining to sympathetic and parasympathetic activity namely, NN50 count (ranged from 1 to 189 score as percentile range). pNN50 count (ranged from .24 to 60.80 score as percentile range). SDNN (ranged from 17.34 to 167.29 score as percentile range). SDSD (ranged from 11.14 to 120.46 score as percentile range). RMMSD (ranged from 11.19 to 120.24 score as percentile range) and SDANN (ranged from 4.02 to 88.75 score as percentile range). The percentile norms of heart rate variability (HRV) variables derived from frequency domain analysis of the Indian sportspersons withdrawn from competitive games/sports pertaining to sympathetic and parasympathetic activity namely Low Frequency (Normalized Power) ranged from 20.68 to 90.49 score as percentile range. High Frequency (Normalized Power) ranged from 14.37 to 81.60 score as percentile range. LF/ HF ratio(ranged from 0.26 to 9.52 score as percentile range). LF (Absolute Power) ranged from 146.79 to 5669.33 score as percentile range. HF (Absolute Power) ranged from 102.85 to 10735.71 score as percentile range and Total Power (Absolute Power) ranged from 471.45 to 25879.23 score as percentile range. Conclusion: The analysis documented percentile norms for time domain analysis and frequency domain analysis for versatile use and evaluation.

Keywords: RMSSD, Percentile, SDANN, HF, LF

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Authors: Younes El Khchine, Mohammed Sriti

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A parametric study has been conducted to analyse the flow around S809 airfoil of wind turbine in order to better understand the characteristics and effects of laminar separation bubble (LSB) on aerodynamic design for maximizing wind turbine efficiency. Numerical simulations were performed at low Reynolds number by solving the Unsteady Reynolds Averaged Navier-Stokes (URANS) equations based on C-type structural mesh and using γ-Reθt turbulence model. Two-dimensional study was conducted for the chord Reynolds number of 1×105 and angles of attack (AoA) between 0 and 20.15 degrees. The simulation results obtained for the aerodynamic coefficients at various angles of attack (AoA) were compared with XFoil results. A sensitivity study was performed to examine the effects of Reynolds number and free-stream turbulence intensity on the location and length of laminar separation bubble and aerodynamic performances of wind turbine. The results show that increasing the Reynolds number leads to a delay in the laminar separation on the upper surface of the airfoil. The increase in Reynolds number leads to an accelerate transition process and the turbulent reattachment point move closer to the leading edge owing to an earlier reattachment of the turbulent shear layer. This leads to a considerable reduction in the length of the separation bubble as the Reynolds number is increased. The increase of the level of free-stream turbulence intensity leads to a decrease in separation bubble length and an increase the lift coefficient while having negligible effects on the stall angle. When the AoA increased, the bubble on the suction airfoil surface was found to moves upstream to leading edge of the airfoil that causes earlier laminar separation.

Keywords: laminar separation bubble, turbulence intensity, S809 airfoil, transition model, Reynolds number

Procedia PDF Downloads 73

Authors: Toumi Farah, Charallah Salima

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In the Algerian Sahara, goat farming is predominant, and it’s associated with other types of breeding, particularly camel and sheep; it also constitutes a significant proportion of breeding exclusively goat. This Saharan goat is a small ruminant with a black dress with white’s spots, hanging ears, and a coat more or less long. It is known for its hardiness and resistance to adverse conditions of arid zones and its perfect ecophysiological adaptation to harsh environmental conditions. However, pregnancy alterations, particularly abortion, degrade its productivity and cause economic losses, having both direct and indirect effects on animal production, like the costs of veterinary interventions and the reconstitution of livestock. The purpose of this work is to study the histological aspect of the liver of goats’ aborted living under nomadic herds in the region of Béni-Abbès (30° 7' N, 2° 10 'O). The organs were collected in physiological serum, rinsed, and then fixed with formaldehyde (37°, diluted at 10%). After that, these samples were processed for a topographic study. The morphometric study of the liver was performed by using an image analysis and processing software "Image J"; the various measurements obtained are intended to specify the supposed stage of development according to the body weight. The histological structure of the liver shows that the hepatic parenchyma consists of vascular conjunctive spaces surrounded by Glisson’s capsule. The sinusoids and hepatic portal vein are full of red blood cells, representing sinusoidal congestion and a thrombosed vein. At high magnification, the blood vessels show the presence of vascular thrombosis and haemorrhage in some areas of the hepatic parenchyma. Morphometric analysis shows that the number of liver parenchymal cells and the diameter of liver vessels vary according to the stage of development. The results obtained will provide details of the anatomical and cellular elements that can be used in the diagnosis of early or late abortion and late embryonic death. It would be interesting to find, by immunohistochemistry, some inflammatory markers useful for monitoring the progress of pregnancy and bioindicators of fetomaternal distress.

Keywords: aborting goat, arid zone, liver, histopathology

Procedia PDF Downloads 92

Authors: Mohammad Moridzadeh, Aaron Gallant

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The paper will present the design and construction of the underground excavations of a pump station forebay and its related components including connector tunnels, access shaft, riser shaft and well shafts. The underground openings include an 8 m-diameter riser shaft, an 8-m-diameter access shaft, 34 2.4-m-diameter well shafts, a 107-m-long forebay with a cross section having a height of 11 m and width of 10 m, and a 6 m by 6 m stub connector tunnel between the access shaft and a future forebay extension. The riser shaft extends down from the existing forebay connector tunnel at elevation 247 m to the crown of the forebay at elevation 770.0 feet. The access shaft will extend from the platform at the surface down to El. 223.5 m. The pump station will have the capacity to deliver 600 million gallons per day. The project is located on an uplifted horst consisting of a mass of Precambrian metamorphic rock trending in a north-south direction. The eastern slope of the area is very steep and pronounced and is likely the result of high-angle normal faulting. Toward the west, the area is bordered by a high angle normal fault and recent alluvial, lacustrine, and colluvial deposits. An evaluation of rock mass properties, fault and discontinuities, foliation and joints, and in situ stresses was performed. The response of the rock mass was evaluated in 3DEC using Discrete Element Method (DEM) by explicitly accounting for both major and minor discontinuities within the rock mass (i.e. joints, shear zones, faults). Moreover, the stability of the entire subsurface structure including the forebay, access and riser shafts, future forebay, well shafts, and connecting tunnels and their interactions with each other were evaluated using a 3D coupled hydromechanical Finite Element Analysis (FEA).

Keywords: coupled hydromechanical analysis, discontinuities, discrete element, finite element, pump station

Procedia PDF Downloads 259

Authors: F. Pottmeyer, M. Weispfenning, K. A. Weidenmann

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Continuous carbon fiber reinforced plastics (CFRP) exhibit a high application potential for lightweight structures due to their outstanding specific mechanical properties. Embedded metal elements, so-called inserts, can be used to join structural CFRP parts. Drilling of the components to be joined can be avoided using inserts. In consequence, no bearing stress is anticipated. This is a distinctive benefit of embedded inserts, since continuous CFRP have low shear and bearing strength. This paper aims at the investigation of the load bearing capacity after preinduced damages from impact tests and thermal-cycling. In addition, characterization of mechanical properties during dynamic high speed pull-out testing under different loading velocities was conducted. It has been shown that the load bearing capacity increases up to 100% for very high velocities (15 m/s) in comparison with quasi-static loading conditions (1.5 mm/min). Residual strength measurements identified the influence of thermal loading and preinduced mechanical damage. For both, the residual strength was evaluated afterwards by quasi-static pull-out tests. Taking into account the DIN EN 6038 a high decrease of force occurs at impact energy of 16 J with significant damage of the laminate. Lower impact energies of 6 J, 9 J, and 12 J do not decrease the measured residual strength, although the laminate is visibly damaged - distinguished by cracks on the rear side. To evaluate the influence of thermal loading, the specimens were placed in a climate chamber and were exposed to various numbers of temperature cycles. One cycle took 1.5 hours from -40 °C to +80 °C. It could be shown that already 10 temperature cycles decrease the load bearing capacity up to 20%. Further reduction of the residual strength with increasing number of thermal cycles was not observed. Thus, it implies that the maximum damage of the composite is already induced after 10 temperature cycles.

Keywords: composite, joining, inserts, dynamic loading, thermal loading, residual strength, impact

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Authors: Sherif D. El Wakil, John Rice

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The aim of the current work was to employ the finite element method to model a slab, with a small hole across its width, undergoing plastic plane strain deformation. The computational model had, however, to be validated by comparing its results with those obtained experimentally. Since they were in good agreement, the finite element method can therefore be considered a reliable tool that can help gain better understanding of the mechanism of ductile failure in structural members having stress raisers. The finite element software used was ANSYS, and the PLANE183 element was utilized. It is a higher order 2-D, 8-node or 6-node element with quadratic displacement behavior. A bilinear stress-strain relationship was used to define the material properties, with constants similar to those of the material used in the experimental study. The model was run for several tensile loads in order to observe the progression of the plastic deformation region, and the stress concentration factor was determined in each case. The experimental study involved employing the visioplasticity technique, where a circular mesh (each circle was 0.5 mm in diameter, with 0.05 mm line thickness) was initially printed on the side of an aluminum slab having a small hole across its width. Tensile loading was then applied to produce a small increment of plastic deformation. Circles in the plastic region became ellipses, where the directions of the principal strains and stresses coincided with the major and minor axes of the ellipses. Next, we were able to determine the directions of the maximum and minimum shear stresses at the center of each ellipse, and the slip-line field was then constructed. We were then able to determine the stress at any point in the plastic deformation zone, and hence the stress concentration factor. The experimental results were found to be in good agreement with the analytical ones.

Keywords: finite element method to model a slab, slab undergoing plastic deformation, stress distribution around a circular hole, visioplasticity

Procedia PDF Downloads 315

Authors: Harrys Purnama, Wardatul Jannah, Rizkia Nita Hawari

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In the development of the times, there are many materials used to plan a building structure. Steel became one of the most widely used materials in building construction that works as the main structure. Steel Castellated Beam is a type of innovation in the use of steel in building construction. Steel Castellated Beam is a beam that used for long span construction (more than 10 meters). The Castellated Beam is two steel profiles that unified into one to get the appropriate profile height (more than 10 meters). The profile is perforated to minimize the profile's weight, increase the rate, save costs, and have architectural value. The perforations shape in the Castellated Beam can be circular, elliptical, hexagonal, and rectangular. The Castellated beam has a height (h) almost 50% higher than the initial profile thus increasing the axial bending value and the moment of inertia (Iₓ). In this analysis, there are 3 specimens were used with 12.1 meters span of Castellated Beam as the sample with varied perforation, such us round, hexagon, and octagon. Castellated Beam testing system is done with computer-based applications that named Staad Pro V8i. It is to provide a central load in the middle of the steel beam span. It aims to determine the effect of perforation on bending behavior on the steel Castellated Beam by applying some form of perforations on the steel Castellated Beam with test specimen WF 200.100.5.5.8. From the analysis, results found the behavior of steel Castellated Beam when receiving such central load. From the results of the analysis will be obtained the amount of load, shear, strain, and Δ (deflection). The result of analysis by using Staad Pro V8i shows that with the different form of perforations on the profile of Castellated steel, then we get the different tendency of inertia moment. From the analysis, results obtained the moment of the greatest inertia can increase the stiffness of Castellated steel. By increasing the stiffness of the steel Castellated Beam the deflection will be smaller, so it can withstand the moment and a large strength. The results of the analysis show that the most effective and efficient perforations are the steel beam with a hexagon perforation shape.

Keywords: Castellated Beam, the moment of inertia, stress, deflection, bending test

Procedia PDF Downloads 163

Authors: E. Ormeno, C. Gutigny, J. Ruffault, J. Madrigal, M. Guijarro, C. Lecareux, C. Ballini

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Mediterranean plant species feature numerous metabolic and morpho-physiological responses crucial to survive under both, typical Mediterranean drought conditions and future aggravated drought expected by climate change. Whether these adaptive responses will, in turn, increase the ecosystem perturbation in terms of fire hazard, is an issue that needs to be addressed. The aim of this study was to test whether recurrent and aggravated drought in the Mediterranean area favors the accumulation of waxes in leaf litter, with an eventual increase of litter flammability. The study was conducted in 2017 in a garrigue in Southern France dominated by Quercus coccifera, where two drought treatments were used: a treatment with recurrent aggravated drought consisting of ten rain exclusion structures which withdraw part of the annual precipitation since January 2012, and a natural drought treatment where Q. coccifera stands are free of such structures and thus grow under natural precipitation. Waxes were extracted with organic solvent and analyzed by GC-MS and litter flammability was assessed through measurements of the ignition delay, flame residence time and flame intensity (flame height) using an epiradiator as well as the heat of combustion using an oxygen bomb calorimeter. Results show that after 5 years of rain restriction, wax content in the cuticle of leaf litter increases significantly compared to shrubs growing under natural precipitation, in accordance with the theoretical knowledge which expects increases of cuticle waxes in green leaves in order to limit water evapotranspiration. Wax concentrations were also linearly and positively correlated to litter flammability, a correlation that lies on the high flammability own to the long-chain alkanes (C25-C31) found in leaf litter waxes. This innovative investigation shows that climate change is likely to favor ecosystem fire hazard through accumulation of highly flammable waxes in litter. It also adds valuable information about the types of metabolites that are associated with increasing litter flammability, since so far, within the leaf metabolic profile, only terpene-like compounds had been related to plant flammability.

Keywords: cuticular waxes, drought, flammability, litter

Procedia PDF Downloads 167

Authors: B. S. Abdelwahed, B. B. Belkassem

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Beam-column joints are a critical part in reinforced concrete RC frames designed for inelastic response to several external loads. Investigating the behaviour of the exterior RC beam-column joints has attracted many researchers in the past decades due to its critical influence on the overall behaviour of RC moment-resisting frames subjected to lateral loads. One of the most critical zones in moment-resistant frames is the knee joints because of restraints associated with providing limited anchorage length to the beam and column longitudinal reinforcement in it and consequentially causes a lot of damage in such building frames. Previous numerical simulations focussed mainly on the exterior and interior joints, for knee joint further work is still needed to investigate its behaviour and discuss its affecting parameters. Structural response for an RC knee beam-column joint is performed in this study using LS-DYNA. Three-dimensional finite element (FE) models of an RC knee beam-column joint are described and verified with experimental results available in literature; this is followed by a parametric study to investigate the influence of the concrete compressive strength, the presence of lateral beams and increasing beam reinforcement ratio. It is shown that the concrete compressive strength has a significant effect on shear capacity, load-deflection characteristics and failure modes of an RC knee beam-column joints but to a certain limit, the presence of lateral beams increased the joint confinement and reduced the rate of concrete degradation in the joint after reaching ultimate joint capacity, added to that an increase in the maximum load resistance. Increasing beam reinforcement ratio is found to improve the flexural resistance of the anchored beam bars and increase the joint maximum load resistance.

Keywords: beam reinforcement ratio, joint confinement, numerical simulation, reinforced concrete beam-column joints, structural performance

Procedia PDF Downloads 457

Authors: Badreldein Mohamed, Song Jianguo

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Seismic inversion is the most efficient technique that yields critical information for fluid differentiation inside reservoir rocks. Conventional approaches depend extensively on unreliable stochastic techniques and necessitate considerable computational resources and effort. Deep learning is an economical and effective approach for extracting complex patterns from data to provide accurate predictions. The lack of borehole label data, essential for training precise models, impedes its application. Moreover, the utilization of synthetic data is inadequate for producing data that aligns with actual geological conditions and necessitates additional modification of the trained models for practical applications. This study commenced with poroelastic modelling to mimic the bulk and shear moduli of rock using various saturating fluids. Subsequently, we employed the acquired moduli in empirical equations to calculate the density and velocities of the saturated reservoir, then computed Vp/Vs, Poisson’s ratio, and acoustic impedance, which is critical for fluid analysis. This supplied essential labels for training multi-base inversion deep learning models with diverse topologies and hyperparameters. We integrated a prior knowledge component into the methodology to guarantee stability and compatibility with the local geological conditions. Subsequently, we assigned weights to individual models according to their accuracies and combined them to attain the most desirable outcome. The suggested method demonstrated superior performance compared to conventional inversion and popular deep learning approaches in a real-world application. This result is particularly crucial for understanding the reservoir’s potential for oil and gas production as well as for predicting its behaviour under different conditions.

Keywords: deep learning, reservoir rock characterization, rock-physics models, seismic inversion

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Authors: Noura El-Ahmady El-Naggar

Abstract:

L-asparaginase is an important enzyme as therapeutic agents used in combination therapy with other drugs in the treatment of acute lymphoblastic leukemia in children. L-asparaginase producing actinomycete strain, NEAE-K, was isolated from soil sample and identified on the basis of morphological, cultural, physiological and biochemical properties, together with 16S rDNA sequence as new subsp. Streptomyces rochei subsp. chromatogenes NEAE-K and sequencing product (1532 bp) was deposited in the GenBank database under accession number KJ200343. The study was conducted to screen parameters affecting the production of L-asparaginase by Streptomyces rochei subsp. chromatogenes NEAE-K on solid state fermentation using Plackett–Burman experimental design. Sixteen different independent variables including incubation time, moisture content, inoculum size, temperature, pH, soybean meal+ wheat bran, dextrose, fructose, L-asparagine, yeast extract, KNO3, K2HPO4, MgSO4.7H2O, NaCl, FeSO4. 7H2O, CaCl2, and three dummy variables were screened in Plackett–Burman experimental design of 20 trials. The most significant independent variables affecting enzyme production (dextrose, L-asparagine and K2HPO4) were further optimized by the central composite design. As a result, a medium of the following formula is the optimum for producing an extracellular L-asparaginase by Streptomyces rochei subsp. chromatogenes NEAE-K from solid state fermentation: g/L (soybean meal+ wheat bran 15, dextrose 3, fructose 4, L-asparagine 8, yeast extract 2, KNO3 1, K2HPO4 2, MgSO4.7H2O 0.5, NaCl 0.1, FeSO4. 7H2O 0.02, CaCl2 0.01), incubation time 7 days, moisture content 50%, inoculum size 3 mL, temperature 30°C, pH 8.5.

Keywords: streptomyces rochei subsp. chromatogenes neae-k, 16s rrna, identification, solid state fermentation, l-asparaginase production, plackett-burman design, central composite design

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Authors: Richa Dhingra, Monika, Manav Malhotra, Tilak Raj Bhardwaj, Neelima Dhingra

Abstract:

5-Alpha-reductases (5AR), a membrane bound, NADPH dependent enzyme and convert male hormone testosterone (T) into more potent androgen dihydrotestosterone (DHT). DHT is the required for the development and function of male sex organs, but its overproduction has been found to be associated with physiological conditions like Benign Prostatic Hyperplasia (BPH). Thus the inhibition of 5ARs could be a key target for the treatment of BPH. In present study, 2D and 3D Quantitative Structure Activity Relationship (QSAR) pharmacophore models have been generated for 5AR based on known inhibitory concentration (IC₅₀) values with extensive validations. The four featured 2D pharmacophore based PLS model correlated the topological interactions (–OH group connected with one single bond) (SsOHE-index); semi-empirical (Quadrupole2) and physicochemical descriptors (Mol. wt, Bromines Count, Chlorines Count) with 5AR inhibitory activity, and has the highest correlation coefficient (r² = 0.98, q² =0.84; F = 57.87, pred r² = 0.88). Internal and external validation was carried out using test and proposed set of compounds. The contribution plot of electrostatic field effects and steric interactions generated by 3D-QSAR showed interesting results in terms of internal and external predictability. The well validated 2D Partial Least Squares (PLS) and 3D k-nearest neighbour (kNN) models were used to search novel 5AR inhibitors with different chemical scaffold. To gain more insights into the molecular mechanism of action of these steroidal derivatives, molecular docking and in silico absorption, distribution, metabolism, and excretion (ADME) studies were also performed. Studies have revealed the hydrophobic and hydrogen bonding of the ligand with residues Alanine (ALA) 63A, Threonine (THR) 60A, and Arginine (ARG) 456A of 4AT0 protein at the hinge region. The results of QSAR, molecular docking, in silico ADME studies provide guideline and mechanistic scope for the identification of more potent 5-Alpha-reductase inhibitors (5ARI).

Keywords: 5α-reductase inhibitor, benign prostatic hyperplasia, ligands, molecular docking, QSAR

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Authors: Pavel Damborsky, Martina Zamorova, Jaroslav Katrlik

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Prostate cancer is annually the most common newly diagnosed cancer among men. An extensive number of evidence suggests that traditional serum Prostate-specific antigen (PSA) assay still suffers from a lack of sufficient specificity and sensitivity resulting in vast over-diagnosis and overtreatment. Thus, the early-stage detection of prostate cancer (PCa) plays undisputedly a critical role for successful treatment and improved quality of life. Over the last decade, particular altered glycans have been described that are associated with a range of chronic diseases, including cancer and inflammation. These glycans differences enable a distinction to be made between physiological and pathological state and suggest a valuable biosensing tool for diagnosis and follow-up purposes. Aberrant glycosylation is one of the major characteristics of disease progression. Consequently, the aim of this study was to develop a more reliable tool for early-stage PCa diagnosis employing lectins as glyco-recognition elements. Biosensor and biochip technology putting to use lectin-based glyco-profiling is one of the most promising strategies aimed at providing fast and efficient analysis of glycoproteins. The proof-of-concept experiments based on sandwich assay employing anti-PSA antibody and an aptamer as a capture molecules followed by lectin glycoprofiling were performed. We present a lectin-based biosensing assay for glycoprofiling of serum biomarker PSA using different biosensor and biochip platforms such as label-free surface plasmon resonance (SPR) and microarray with fluorescent label. The results suggest significant differences in interaction of particular lectins with PSA. The antibody-based assay is frequently associated with the sensitivity, reproducibility, and cross-reactivity issues. Aptamers provide remarkable advantages over antibodies due to the nucleic acid origin, stability and no glycosylation. All these data are further step for construction of highly selective, sensitive and reliable sensors for early-stage diagnosis. The experimental set-up also holds promise for the development of comparable assays with other glycosylated disease biomarkers.

Keywords: biomarker, glycosylation, lectin, prostate cancer

Procedia PDF Downloads 398