Search results for: perpendicular to grain stress

Authors: Mengjie Qu, Yi Wang, Jiawei Ding, Siyu Chen, Yanan Di

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Marine ecosystem is facing intensified multiple stresses caused by environmental contaminants from human activities. Xenobiotics, such as benzo(α)pyrene (BaP) have been discharged into marine environment and cause hazardous impacts on both marine organisms and human beings. As a filter-feeder, marine mussels, Mytilus spp., has been extensively used to monitor the marine environment. However, their genomic alterations induced by such xenobiotics are still kept unknown. In the present study, gills, as the first defense barrier in mussels, were selected to evaluate the genetic instability alterations induced by the exposure to BaP both in vivo and in vitro. Both random amplified polymorphic DNA (RAPD) assay and comet assay were applied as the rapid tools to assess the environmental stresses due to their low money- and time-consumption. All mussels were identified to be the single species of Mytilus coruscus before used in BaP exposure at the concentration of 56 μg/l for 1 & 3 days (in vivo exposure) or 1 & 3 hours (in vitro). Both RAPD and comet assay results were showed significantly increased genomic instability with time-specific altering pattern. After the recovery period in 'in vivo' exposure, the genomic status was as same as control condition. However, the relative higher genomic instabilities were still observed in gill cells after the recovery from in vitro exposure condition. Different repair mechanisms or signaling pathway might be involved in the isolated gill cells in the comparison with intact tissues. The study provides the robust and rapid techniques to exam the genomic stability in marine organisms in response to marine environmental changes and provide basic information for further mechanism research in stress responses in marine organisms.

Keywords: genotoxic impacts, in vivo/vitro exposure, marine mussels, RAPD and comet assay

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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: D. Dannehl, Z. Taylor, J. Suhl, L. Miranda, R., Ulrichs, C., Salazar, E. Fitz-Rodriguez, I. Lopez-Cruz, A. Rojano-Aguilar, G. Navas-Gomez, U. Schmidt

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Growing environmental and sustainability concerns have driven continual modernization of horticultural practices, especially for urban farming. Controlled environment and soilless production methods are increasing in popularity because of their efficient resource use and intensive cropping capabilities. However, some popular substrates used for hydroponic cultivation, particularly rock wool, represent a large environmental burden in regard to their manufacture and disposal. Substrate-less hydroponic systems are effective in producing short cropping cycle plants such as lettuce or herbs, but less information is available for the production of plants with larger root-systems and longer cropping times. Here, we investigated the viability of a hybrid aeroponic/nutrient film technique (AP/NFT) system for the cultivation of greenhouse tomatoes (Solanum lycopersicum ‘Panovy’). The plants grown in the AP/NFT system had a more compact phenotype, accumulated more Na⁺ and less P and S than the rock wool grown counterparts. Due to forced irrigation interruptions, we propose that the differences observed were cofounded by the differing severity of water-stress for plants with and without substrate. They may also be caused by a higher root zone temperature predominant in plants exposed to AP/NFT. However, leaf area, stem diameter, and number of trusses did not differ significantly. The same was found for leaf pigments and plant photosynthetic efficiency. Overall, the AP/NFT system appears to be viable for the production of greenhouse tomato, enabling the environment to be relieved by way of lessening rock wool usage.

Keywords: closed aeroponic systems, fruit quality, nutrient dynamics, substrate waste reduction, urban farming systems, water savings

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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: Mohammed S. Mohammed, Asmaa M. S. Mohammed

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Background: To achieve the quality of cancer care, the oncologic academic programs should be continuously developed with establishing new ones. We highlighted three disciplines, Clinical nutrition, medical biophysics and radiobiology and Psycho-oncology programs; without a doubt, the Egyptian National Cancer Institute, in ‎the accreditation era, will be establishing them ‎ due to their importance in improving the skills of cancer practitioners. Methods: The first suggested program in Clinical Nutrition that is dealing with the assessment of the patient's well-being before, during and after treatment to avoid the defects in the metabolism resulting from the cancer disease and its treatment by giving the supplements in the patient's diet. The second program is Medical Biophysics and Radiobiology, which there's no denying that it ‎is ‎provided ‎in Cairo University as a good program in the faculty of science but lacks the clinical ‎practice. Hence, it is probably better to establish this program in our institute to ‎improve the ‎practitioner skills and introduce a tailored radiation therapy regimen for every patient according to ‎their characteristic profile.‎ While patients are receiving their treatment, the risk of post-traumatic stress disorder arises, so the importance of the third program, Psycho-Oncology, is clearly obtained. This program is concerned with the psychological, social, behavioral, and ethical aspects of cancer. The area of multi-disciplinary interest has boundaries with the major specialties in oncology: the clinical disciplines (surgery, medicine, pediatrics, and radiotherapy), epidemiology, immunology, endocrinology, biology, pathology, bioethics, palliative care, rehabilitation medicine, clinical trials research and decision making, as well as psychiatry and psychology. Results: It is a prospective academic plan which is compatible with the institutional vision and its strategic plan. Conclusion: In this context, evaluating and understanding the suggested academic programs has become a mandatory part of cancer care. And it is essential to be provided by the NCI.

Keywords: clinical nutrition, psycho-oncology, medical biophysics and radiobiology, medical education

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Authors: Mehrak Zargaryaeghoubi, Masood Hajali

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Drilled shafts are the most popular of deep foundations, because they have the capability that one single shaft can easily carry the entire load of a large column from a bridge or tall building. Drilled shaft may be an economical alternative to pile foundations because a pile cap is not needed, which not only reduces that expense, but also provides a rough surface in the border of soil and concrete to carry a more axial load. Due to the larger construction sizes of drilled shafts, they have an excellent axial load carrying capacity. Part of the axial load carrying capacity of the drilled shaft is resisted by the soil below the tip of the shaft which is tip resistance and the other part is resisted by the friction developed around the drilled shaft which is side resistance. The condition at the bottom of the excavation can affect the end bearing capacity of the drilled shaft. Also, type of the soil and size of the drilled shaft can affect the frictional resistance. The main loads applied on the drilled shafts are axial compressive loads. It is important to know how many percent of the maximum applied load will be shed inside friction and how much will be transferred to the base. The axial capacity of the drilled shaft foundation is influenced by the size of the drilled shaft, and soil characteristics. In this study, the effect of the size and soil characteristic will be investigated on the contribution of side resistance and end-bearing capacity. Also, the study presents a three-dimensional finite element modeling of a drilled shaft subjected to axial load using ANSYS. The top displacement and settlement of the drilled shaft are verified with analytical results. The soil profile is considered as Table 1 and for a drilled shaft with 7 ft diameter and 95 ft length the stresses in z-direction are calculated through the length of the shaft. From the stresses in z-direction through the length of the shaft the side resistance can be calculated and with the z-direction stress at the tip, the tip resistance can be calculated. The result of the side and tip resistance for this drilled shaft are compared with the analytical results.

Keywords: Drilled Shaft Foundation, size and soil characteristic, axial load capacity, Finite Element

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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: 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

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Authors: Sima Saadi, Carolyn Johns

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The concept of a "Smart Water City" is emerging as a framework to address critical urban water challenges, integrating technology, data, and sustainable management practices to enhance water quality, conservation, and accessibility. This paper explores the definition of a Smart Water City, examines the pressing need for such cities in Canada, and proposes policy pathways for their development. Smart Water Cities utilize advanced monitoring systems, data analytics, and integrated water resources management to optimize water usage, anticipate and mitigate environmental impacts, and engage citizens in sustainable practices. Global examples from regions such as Europe, Asia, and Australia illustrate how Smart Water City models can transform urban water systems by enhancing resilience, improving resource efficiency, and driving economic development through job creation in environmental technology sectors. For Canada, adopting Smart Water City principles could address pressing challenges, including climate-induced water stress, aging infrastructure, and the need for equitable water access across diverse urban and rural communities. Building on Canada's existing water policies and technological expertise, it propose strategic investments in digital water infrastructure, data-driven governance, and community partnerships. Through case studies, this paper offers insights into how Canadian cities could benefit from cross-sector collaboration, policy development, and funding for smart water technology. By aligning national policy with smart urban water solutions, Canada has the potential to lead globally in sustainable water management, ensuring long-term water security and environmental stewardship for its cities and communities.

Keywords: smart water city, urban water resilience, water management technology, sustainable water infrastructure, canada water policy, smart city initiatives

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Authors: Zewdneh Zana Zate

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The study focuses on the evolutionary and ecological genomics of both wild and cultivated Coffea arabica L. at its center of origin, Ethiopia, aiming to uncover how this vital species may withstand future climate changes. Utilizing bioclimatic models, we project the future distribution of Arabica under varied climate scenarios for 2050 and 2080, identifying potential conservation zones and immediate risk areas. Through whole-genome resequencing of accessions from Ethiopian gene banks, this research assesses genetic diversity and divergence between wild and cultivated populations. It explores relationships, demographic histories, and potential hybridization events among Coffea arabica accessions to better understand the species' origins and its connection to parental species. This genomic analysis also seeks to detect signs of natural or artificial selection across populations. Integrating these genomic discoveries with ecological data, the study evaluates the current and future ecological and genomic vulnerabilities of wild Coffea arabica, emphasizing necessary adaptations for survival. We have identified key genomic regions linked to environmental stress tolerance, which could be crucial for breeding more resilient Arabica varieties. Additionally, our ecological modeling predicted a contraction of suitable habitats, urging immediate conservation actions in identified key areas. This research not only elucidates the evolutionary history and adaptive strategies of Arabica but also informs conservation priorities and breeding strategies to enhance resilience to climate change. By synthesizing genomic and ecological insights, we provide a robust framework for developing effective management strategies aimed at sustaining Coffea arabica, a species of profound global importance, in its native habitat under evolving climatic conditions.

Keywords: coffea arabica, climate change adaptation, conservation strategies, genomic resilience

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Authors: Preethy Mary Donald, Renjith George

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Oral tori are localized non-neoplastic protuberances of maxilla and mandible. Torus palatinus (TP) is found on the midline of the roof of mouth existing as single growth or in clusters. Torus mandibularis(TM) is located on the lingual aspect of the mandible commonly between canine and premolar region. Etiology of their presence was not clear and was found to be multifactorial. Their variations in relation to age, gender, ethnicity and also the characteristics of TP and TM have become the interest of multiple studies. The objectives of this study were to determine the prevalence of torus palatinus (TP) and torus mandibularis (TM) among patients who have visited outpatient department, Faculty of Dentistry, Melaka Manipal Medical College. 108 patients were examined for the presence of oral tori at the outpatient department, Faculty of Dentistry, Melaka-Manipal Medical College. Factors such as age, gender, ethnicity of the patients and size, shape, location of the oral tori were studied. For TP, Malays (62.96%) have been found to have the highest prevalence than Chinese (43.3%) and Indians (35.71%). For TM, Chinese (7.46%) had predominated compared to Malays (7.41%) and Indians (0%). There is no significant association between occurrence of TP and TM with age, gender and ethnicity. For Torus palatinus, the most common size was Grade 1(1-3mm), most common location was molar region, and the most common shape was spindle. For Torus mandibularis, the most frequent location was canine premolar region and exists in unilateral single or bilateral single fashion. The overall prevalence rates were 47.2% for TP and 6.48% for TM. However, there is no significant association between occurrence of TP and TM with age, gender and ethnicity. The results showed variations in clinical characteristics and support the findings that occurrence of tori is a dynamic phenomenon which is multifactorial owing to the environmental factors such as stress from occlusion and dietary habits. It could be due to the genetic make-up of the individual.

Keywords: torus palatinus, torus mandibularis, age, gender

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Authors: Soheil Heydari, Ailar Hajimohammadi, Nasser Khalili

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The application of plastic waste for asphalt modification is a sustainable strategy to deal with the enormous plastic waste generated each year and enhance the properties of asphalt. The modification is either practiced by the dry process or the wet process. In the dry process, plastics are added straight into the asphalt mixture, and in the wet process, they are mixed and digested into bitumen. In this article, the effects of plastic inclusion in asphalt mixture, through the dry process, on the permanent deformation of the asphalt are investigated. The main waste plastics that are usually used in asphalt modification are taken into account, which is linear, low-density polyethylene, low-density polyethylene, high-density polyethylene, and polypropylene. Also, to simulate a plastic waste stream, different grades of each virgin plastic are mixed and used. For instance, four different grades of polypropylene are mixed and used as representative of polypropylene. A precisely designed mixing condition is considered to dry-mix the plastics into the mixture such that the polymer was melted and modified by the later introduced binder. In this mixing process, plastics are first added to the hot aggregates and mixed three times in different time intervals, then bitumen is introduced, and the whole mixture is mixed three times in fifteen minutes intervals. Marshall specimens were manufactured, and dynamic creep tests were conducted to evaluate the effects of modification on the permanent deformation of the asphalt mixture. Dynamic creep is a common repeated loading test conducted at different stress levels and temperatures. Loading cycles are applied to the AC specimen until failure occurs; with the amount of deformation constantly recorded, the cumulative, permanent strain is determined and reported as a function of the number of cycles. The results of this study showed that the dry inclusion of the waste plastics is very effective in enhancing the resistance against permanent deformation of the mixture. However, the mixing process must be precisely engineered to melt the plastics, and a homogenous mixture is achieved.

Keywords: permanent deformation, waste plastics, low-density polyethene, high-density polyethene, polypropylene, linear low-density polyethene, dry process

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Authors: Kunal K. S., Shwetashri K. R., Keerthan G., Ajinkya R.

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Background: Normal pressure hydrocephalus is a condition caused by abnormal accumulation of cerebrospinal fluid (CSF) within the brain resulting in enlarged cerebral ventricles due to a disruption of CSF formation, absorption, or flow. Over the course of time, ventriculoperitoneal shunt under general anesthesia has become a standard of care. Yet only a finite number of centers have started the inclusion of regional anesthesia techniques for the such patient cohort. Stem Case: We report a case of a 75-year-old male with underlying aortic sclerosis and cardiomyopathy who presented with complaints of confusion, forgetfulness, and difficulty in walking. Neuro-imaging studies revealed disproportionally enlarged subarachnoid space hydrocephalus (DESH). The baseline blood pressure was 116/67 mmHg with a heart rate of 106 beats/min and SpO2 of 96% on room air. The patient underwent smooth induction followed by sonographically guided superficial cervical plexus block and transverse abdominis plane block. Intraoperative pain indices were monitored with Analgesia nociceptive index monitor (ANI, MdolorisTM) and surgical plethysmographic index (SPI, GE Healthcare, Helsinki, FinlandTM). These remained stable during the application of the block and the entire surgical duration. No significant hemodynamic response was observed during the tunneling of the skin by the surgeon. The patient underwent a smooth recovery and emergence. Conclusion: Our decision to incorporate peripheral nerve blockade in conjunction with general anesthesia resulted in opioid-sparing anesthesia and decreased post-operative analgesic requirement by the patient. This blockade was successful in suppressing intraoperative stress responses. Our patient recovered adequately and underwent an uncomplicated post-operative stay.

Keywords: desh, NPH, VP shunt, cervical plexus block, transversus abdominis plane block

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Authors: Musawira Iftikhar

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The field of membrane materials is the most dynamic due to the constantly evolving requirements advancement of materials, to address challenges such as biocompatibility, protein-bound uremic toxins, blood coagulation, auto-immune responses, oxidative stress, and poor clearance of uremic toxins. Hemodialysis is a membrane filtration processes that is currently necessary for daily living of the patients with ESRD. Tens of millions of people with ESRD have benefited from hemodialysis over the past 60–70 years, both in terms of safeguarding life and a longer lifespan. Beyond challenges associated with the efficiency and separative properties of the membranes, ensuring hemocompatibility, or the safe circulation of blood outside the body for four hours every two days, remains a persistent challenge. This review explores the ongoing field of metal–Organic Frameworks (MOFs) and their applications in hemodialysis, offering a comprehensive examination of various MOFs employed to address challenges inherent in traditional hemodialysis methodologies. this This review included includes the experimental work done with various MOFs as a filler such as UiO-66, HKUST-1, MIL-101, and ZIF-8, which together lead to improved adsorption capacities for a range of uremic toxins and proteins. Furthermore, this review highlights how effectively MOF-based hemodialysis membranes remove a variety of uremic toxins, including p-cresol, urea, creatinine, and indoxyl sulfate and potential filler choices for the future. Future research efforts should focus on refining synthesis techniques, enhancing toxin selectivity, and investigating the long-term durability of MOF-based membranes. With these considerations, MOFs emerge as transformative materials in the quest to develop advanced and efficient hemodialysis technologies, holding the promise to significantly enhance patient outcomes and redefine the landscape of renal therapy.

Keywords: membrane, hemodailysis, metal organic frameworks, seperation, protein adsorbtion

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Authors: Ammara Khan

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Sepsis is characterized by an overwhelming surge of cytokines and oxidative stress to one of many factors, gram-negative bacteria commonly implicated. Despite major expansion and elaboration of sepsis pathophysiology and therapeutic approach; death rate remains very high in septic patients due to multiple organ damages including hepatotoxicity.The present study was aimed to ascertain the adequacy of three different drugs delivered separately and collectively- low dose steroid-dexamethasone (3mg/kg i.p) ,antioxidant-melatonin(10 mg/kg i.p) ,and phosphodiesterases inhibitor - pentoxifylline (75 mg/kg i.p)in endotoxin-induced hepatotoxicity in mice. Endotoxin/lipopolysaccharides induced hepatotoxicity was reproduced in mice by giving lipopolysaccharide of serotype E.Coli intraperitoneally. The preventive role was questioned by giving the experimental agent half an hour prior to LPS injection whereas the therapeutic potential of the experimental agent was searched out via post-LPS delivering. The extent of liver damage was adjudged via serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with a histopathological examination of liver tissue. Dexamethasone is given before (Group 3) and after LPS (group 4) significantly attenuated LPS generated liver injury.Pentoxifylline generated similar results and serum ALT; AST histological alteration abated considerably (p≤ 0.05) both in animals subjected to pentoxifylline pre (Group 5) and post-treatment(Group 6). Melatonin was also prosperous in aversion (Group 7) and curation (Group 8) of LPS invoked hepatotoxicity as evident by lessening of augmented ALT (≤0.01) and AST (≤0.01) along with restoration of pathological changes in liver sections (p≤0.05). Combination therapies with dexamethasone in conjunction with melatonin (Group 9), dexamethasone together with pentoxifylline (Group 10), and pentoxifylline along with melatonin (Group 11) after LPS administration tapered LPS evoked hepatic dysfunction statistically considerably. In conclusion, both melatonin and pentoxifylline set up promising results in endotoxin-induced hepatotoxicity and can be used therapeutic adjuncts to conventional treatment strategies in sepsis-induced liver failure.

Keywords: endotoxin/lipopolysacchride, dexamethasone, hepatotoxicity, melatonin, pentoxifylline

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Authors: Natalia Uribe Corrales, Carolina Cano Arroyave, Santiago Henao Villegas

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Introduction: Stunning is an important stage in the meat industry due to the repercussions on the characteristics of the carcass. It has been demonstrated that inadequate stun can lead to hematomas, fractures and promote the appearance of pale, soft and exudative meat due to the stress caused in animals. In Colombia, gas narcosis and electrical stunning are the two authorized methods in pigs. Objective: To describe the practices of stunning in the Valle de Aburrá and its relation with animal welfare. Methods: A descriptive cross - sectional study was carried out in Valle de Aburrá slaughterhouses, which were authorized by National Institute for Food and Medicine Surveillance (INVIMA). Variables such as stunning method, presence of vocalization, falls, slips, rhythmic breathing, corneal reflex and attempts to incorporate after stunning, stun time and time between stun and bleeding were analyzed. Results: 225 pigs were analyzed, finding that 50.2% had electrical stun, whose amperage and voltage were 1.23 (A) and 120 (V) respectively; 49.8% of the animals were stunned with CO2 chamber whose concentration was always above 95%, the mean desensitization time was 16.8 seconds (d.e.5.37); the mean time of stunning - bleeding was 47.9 seconds (d.e.13.9); similarly, it was found that 27.1% had vocalizations after stunning; 12% had falls; 10.7% showed rhythmic breathing; 33.3% exhibited corneal reflex; and 10.7% had reincorporation attempts. Conclusions: The methods of stunning used in the Valle de Aburrá, although performed with those permitted by law, are shortcomings in relation to the amperage and voltage used for each type of pig, as well, it is found that welfare animal is being violated to find signology of an inadequate desensitization. It is necessary to promote compliance with the principles of stunning according to Animal Welfare, and keep in mind that in electrical desensitization, the calibration of the equipment must be guaranteed (pressure according to the type of animal or current applied and the position where the electrodes are) and in the narcosis the equipment should be calibrated to ensure proper gas concentration and exposure time.

Keywords: animal welfare, pigs, quality of meat, stun methods

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Authors: Abd El-Aziz Khairy Abd El-Aal, Yuji Yagi, Heba Kamal

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In this study, an integrated multi-channel analysis of Surface Waves (MASW) technique is applied to explore the geotechnical parameters of subsurface layers at the Zafarana wind farm. Moreover, a seismic hazard procedure based on the extended deterministic technique is used to estimate the seismic hazard load for the investigated area. The study area includes many active fault systems along the Gulf of Suez that cause many moderate and large earthquakes. Overall, the seismic activity of the area has recently become better understood following the use of new waveform inversion methods and software to develop accurate focal mechanism solutions for recent recorded earthquakes around the studied area. These earthquakes resulted in major stress-drops in the Eastern desert and the Gulf of Suez area. These findings have helped to reshape the understanding of the seismotectonic environment of the Gulf of Suez area, which is a perplexing tectonic domain. Based on the collected new information and data, this study uses an extended deterministic approach to re-examine the seismic hazard for the Gulf of Suez region, particularly the wind turbine towers at Zafarana Wind Farm and its vicinity. Alternate seismic source and magnitude-frequency relationships were combined with various indigenous attenuation relationships, adapted within a logic tree formulation, to quantify and project the regional exposure on a set of hazard maps. We select two desired exceedance probabilities (10 and 20%) that any of the applied scenarios may exceed the largest median ground acceleration. The ground motion was calculated at 50th, 84th percentile levels.

Keywords: MASW, seismic hazard, wind turbine towers, Zafarana wind farm

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Authors: Hesti Ghassani, Tessa Septiadi

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In the world we live on today, young generation highly influences the future of a nation. We have to concern that the condition of the country in 20 years later depending by the character of young adults these days. Therefore, it is important that we have to support and control the teenagers especially in one of developing countries in which I live in: Indonesia. Indonesia is a home to 240 million people. It diverse in languages, cultures, as well as attitudes. The differences among each individual lead us to think that there is something we have to take care of. It is necessary to pay attention to the nutrition consumed by the nation. We initiate to control the food consumed by young generation as early as a primary students. Nutrition affects the immune of the body, neuron system, and, most importantly brain. One of the nutrition that has to be fulfilled is milk. However, most of the population in Indonesia isn’t aware of the importance of consuming milk as their daily basis. We’ve formed an innovation called the Brilliant Candy which is affordable and rich in nutrition. So that is why the paper made by literature study to solve the problem with effective ways using available resources, practice and cheap. Brilliant Candy consists of Centella asiatica extract mixed with Soy milk. Centella asiatica contains of alkaloid which give the energy to brain and circulate oxygen. Based on the research of Sathya and Ganga, Centella asiatica can increase the intelligence. Indeed, Centella asiatica can relieve stress, and help us in staying focus. Soy milk is a kind of milk which come from extracted soybean. Soybean is rich in flafonoid. It has various advantages for our body. Which can also support child nutrition consumed. Soybean boosts immune system, helps digestive system, and in terms of food, soy bean exists as a source of nutrition. A method to get extraction of Centella asiatica is namely maserasi using ethanol. While making soybean milk with got the pollen of soybean. Both materials get mixed processed into hard candy with congelation of.

Keywords: Indonesia, Centella asiatica, Soy milk, alkaloid, flafonoid

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Authors: Ehsan Mehryaar, Seyed Armin Motahari Tabari

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Coarse-grained soils are known and commonly used in a wide range of geotechnical projects, including high earth dams or embankments for their high shear strength. The most important engineering property of these soils is friction angle which represents the interlocking between soil particles and can be applied widely in designing and constructing these earth structures. Friction angle and dilative behavior of coarse-grained soils can be estimated from empirical correlations with in-situ testing and physical properties of the soil or measured directly in the laboratory performing direct shear or triaxial tests. Unfortunately, large-scale testing is difficult, challenging, and expensive and is not possible in most soil mechanic laboratories. So, it is common to remove the large particles and do the tests, which cannot be counted as an exact estimation of the parameters and behavior of the original soil. This paper describes a new methodology to simulate particles grading distribution of a well-graded gravel sample to a smaller scale sample as it can be tested in an ordinary direct shear apparatus to estimate the stress-strain behavior, friction angle, and dilative behavior of the original coarse-grained soil considering its confining pressure, and relative density using a machine learning method. A total number of 72 direct shear tests are performed in 6 different sizes, 3 different confining pressures, and 4 different relative densities. Multivariate Adaptive Regression Spline (MARS) technique was used to develop an equation in order to predict shear strength and dilative behavior based on the size distribution of coarse-grained soil particles. Also, an uncertainty analysis was performed in order to examine the reliability of the proposed equation.

Keywords: MARS, coarse-grained soil, shear strength, uncertainty analysis

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Authors: Gurli Olsen, Ida Bruheim Jensen

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Internationally, many young adults not in education, employment, or training (NEET) remain in temporary solutions such as labour market measures or other forms of welfare arrangements. These trends have been associated with ineffective labour market measures, an underfunded theoretical foundation for activation work, limited competence among social workers and labour market employees in using ordinary workplaces as job inclusion measures, and an overemphasis on young adults’ personal limitations such as health challenges and lack of motivation. Two competing models have been prominent in activation work: Place‐Then‐Train and Train‐Then‐Place. A traditional strategy for labour market measures has been to first motivate NEETs to sheltered work and training and then to the regular labour market (train then place). Measures such as Supported Employment (SE) and Individual Placement and Support (IPS) advocate for rapid entry into paid work at the regular labour market with close supervision and training from social workers, employees, and others (place then train). None of these models demonstrate unquestionable results. In this web of working life measures, young adults (NEETs) experience a lack of confidence in their own capabilities and coping strategies vis-á-vis labour market- and educational demands. Drawing on young adults’ own experiences, we argue that the Job Demands-Resources (JD-R) Theory can contribute to the theoretical and practical dimensions of activation work. This presentation will focus on what the JD-R theory entails and how it can be fruitful in activation work with NEETs (what and how). The overarching rationale of the JD-R theory is that an enduring balance between demands (e.g., deadlines, working hours) and resources (e.g., social support, enjoyable work tasks) is important for job performance for people in any job and potentially in other meaningful activities. Extensive research has demonstrated that a balance between demands and resources increases motivation and decreases stress. Nevertheless, we have not identified literature on the JD-R theory in activation work with young adults.

Keywords: activation work, job demands-resources theory, social work, theory development

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Authors: Betsy Hannam

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Background: Staff nurses felt overwhelmed to learn new skills or complete competencies during their shift. Med/Surg units need to provide dedicated, uninterrupted time to complete training and mandatory competencies and practice skills. Purpose: To improve nurse satisfaction and competence by creating a Skills Day with uninterrupted time to complete competencies, brush up on skills, and evaluate skills learned through pre- and post-tests. Methods: The USL and CNL interviewed nurses to obtain input regarding skills needing reinforcement and included mandatory competencies relevant to Med/Surg to create the Skills Day agenda. Content experts from multiple disciplines were invited to educate staff to help address knowledge gaps. To increase attendance, multiple class days were offered. Results: 2018 Skills Day was held for an inpatient unit with 95% participation (n=35 out of 37RNs). The average pretest score, comprised of content questions from topics discussed, was 57%, and post test scoresaveraged 80%. 94% of test scores improved or remained the same. RNs were given an evaluation at the end of the day, where100% of staff noted Skills Day as beneficial, and 97% requested to repeat next year. Another Med/Surg unit asked to join Skills Day in 2019. In 2019, with 89% participation (n=57 out 64 RNs), the average pretest score was 68%, and the average post test score was 85%. 97% of scores improved or remained the same. 98% reported the class as beneficial, and 96% requested to repeat next year. Skills Day 2020-2022 on hold due to COVID. Looking forward to Skills Day 2023. Conclusion: Skills Day allows nurses to maintain competencies and improve knowledge in areas of interest without the stress of a patient assignment. Having unit leaders organize Skills Day, with the involvement of content experts from multiple disciplines, showed to be a successful and innovative team approach to support professional development.

Keywords: education, competency, skills day, medical/surgical

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Authors: L. Meksem Amara, M. Ferfar, N. Meksem, M. R. Djebar

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The wheat is the cereal the most consumed in the world. In Algeria, the production of this cereal covers only 20 in 25 % of the needs for the country, the rest being imported. To improve the efficiency and the productivity of the durum wheat, the farmers turn to the use of pesticides: weed-killers, fungicides and insecticides. However this use often entrains losses of products more at least important contaminating the environment and all the food chain. Weed-killers are substances developed to control or destroy plants considered unwanted. That they are natural or produced by the human being (molecule of synthesis), the absorption and the metabolization of weed-killers by plants cause the death of these plants. In this work, we set as goal the evaluation of the effect of a weed-killer sulfonylurea, the CossackOD with various concentrations (0, 2, 4 and 9 µg) on variety of Triticum durum: Cirta. We evaluated the plant growth by measuring the leaves and root length, compared with the witness as well as the content of proline and analyze the level of one of the antioxydative enzymes: catalase, after 14 days of treatment. Sulfonylurea is foliar and root weed-killers inhibiting the acetolactate synthase: a vegetable enzyme essential to the development of the plant. This inhibition causes the ruling of the growth then the death. The obtained results show a diminution of the average length of leaves and roots this can be explained by the fact that the ALS inhibitors are more active in the young and increasing regions of the plant, what inhibits the cellular division and talks a limitation of the foliar and root’s growth. We also recorded a highly significant increase in the proline levels and a stimulation of the catalase activity. As a response to increasing the herbicide concentrations a particular increases in antioxidative mechanisms in wheat cultivar Cirta suggest that the high sensitivity of Cirta to this sulfonylurea herbicide is related to the enhanced production and oxidative damage of reactive oxygen species.

Keywords: sulfonylurea, triticum durum, oxydative stress, toxicity

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Authors: Wen-Ting Wang, Wei-An Tsai, Rong-Hong Hsieh

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Long term taking high fat diet can lead to over production of energy, result in accumulation of body fat, dyslipidemia and increased lipid metabolism in the body. Over metabolism of lipid results in excessive reactive oxygen species and oxidative stress, may also cause mitochondrial dysfunction and cell death. Krill oil, fish oil and linseed oil are good sources of n-3 polyunsaturated fatty acids (PUFA). The present study investigated the effect of high fat diet and various oil rich of n-3 fatty acids on mitochondrial function and cell membrane composition. Six-weeks old male Spraque-Dawley rats were randomly divided into 8 groups including: control group, high fat diet group, low dosage and high dosage krill oil group, low dosage and high dosage fish oil group, and low dosage and high dosage linseed oil group. After 12 weeks of experimental period, the low dosage krill oil, fish oil group and linseed oil group with different dosage prevented mitochondrial dysfunction caused by high fat diet. The supplementation of different oils increased plasma, erythrocyte and mitochondrial n-3/n-6 ratio and further increased the proportion of PUFA in erythrocyte and mitochondrial membrane. It also decreased serum triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) concentration. However, there was no significant change in serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), biomarker of liver function, glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR) and plasma malonadialdehyde (MDA) concentration when compared with high fat diet group. The supplementation of different sources of n-3 PUFA can maintain mitochondrial function and modulate cell membrane fatty acid composition in high fat diet conditions, and there is a positive relationship between mitochondrial function and mitochondrial membrane composition.

Keywords: fish oil, linseed oil, mitochondria, n-3 PUFA

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Authors: Ritu Karwasra, Surender Singh

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Inflammation is an important physiological response of the body’s self-defense system that helps in eliminating and protecting organism from harmful stimuli and in tissue repair. It is a highly regulated protective response which helps in eliminating the initial cause of cell injury, and initiates the process of repair. The present study was designed to evaluate the ameliorative effect of pomegranate rind extract on pain and inflammation. Hydroalcoholic standardized rind extract of pomegranate at doses 50, 100 and 200 mg/kg and indomethacin (3 mg/kg) was tested against eddy’s hot plate induced thermal algesia, carrageenan (acute inflammation) and Complete Freund’s Adjuvant (chronic inflammation) induced models in Wistar rats. Parameters analyzed were inhibition of paw edema, measurement of joint diameter, levels of GSH, TBARS, SOD, TNF-α, radiographic imaging, tissue histology and synovial expression of pro-inflammatory cytokine receptor (TNF-R1). Radiological and light microscopical analysis were carried out to find out the bone damage in CFA-induced chronic inflammatory model. Findings of the present study revealed that pomegranate rind extract at a dose of 200 mg/kg caused a significant (p<0.05) reduction in paw swelling in both the inflammatory models. Nociceptive threshold was also significantly (p<0.05) improved. Immunohistochemical analysis of TNF-R1 in CFA-induced group showed elevated level, whereas reduction in level of TNF-R1 was observed in pomegranate (200 mg/kg). Henceforth, we might say that pomegranate produced a dose-dependent reduction in inflammation and pain along with the reduction in levels of oxidative stress markers and tissue histology, and the effect was found to be comparable to that of indomethacin. Thus, it can be concluded that pomegranate is a potential therapeutic target in the pathogenesis of inflammation and pain, and punicalagin is the major constituents found in rind extract might be responsible for the activity.

Keywords: carrageenan, inflammation, nociceptive-threshold, pomegranate, histopathology

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Authors: Arturo Daag

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The Philippine Institute of Volcanology and Seismology (PHIVOLCS) is enhancing its liquefaction hazard map towards a detailed probabilistic approach using SDS and geophysical data. Target sites for liquefaction assessment are public schools in Metro Manila. Since target sites are in highly urbanized-setting, the objective of the project is to conduct both non-destructive geotechnical studies using Screw Driving Testing (SDFS) combined with geophysical data such as refraction microtremor array (ReMi), 3 component microtremor Horizontal to Vertical Spectral Ratio (HVSR), and ground penetrating RADAR (GPR). Initial test data was conducted in liquefaction impacted areas from the Mw 6.1 earthquake in Central Luzon last April 22, 2019 Province of Pampanga. Numerous accounts of liquefaction events were documented areas underlain by quaternary alluvium and mostly covered by recent lahar deposits. SDS estimated values showed a good correlation to actual SPT values obtained from available borehole data. Thus, confirming that SDS can be an alternative tool for liquefaction assessment and more efficient in terms of cost and time compared to SPT and CPT. Conducting borehole may limit its access in highly urbanized areas. In order to extend or extrapolate the SPT borehole data, non-destructive geophysical equipment was used. A 3-component microtremor obtains a subsurface velocity model in 1-D seismic shear wave velocity of the upper 30 meters of the profile (Vs30). For the ReMi, 12 geophone array with 6 to 8-meter spacing surveys were conducted. Microtremor data were computed through the Factor of Safety, which is the quotient of Cyclic Resistance Ratio (CRR) and Cyclic Stress Ratio (CSR). Complementary GPR was used to study the subsurface structure and used to inferred subsurface structures and groundwater conditions.

Keywords: screw drive testing, microtremor, ground penetrating RADAR, liquefaction

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Authors: Ali Karimi, Shabnam Karimifam, Amirhosein Karimi, Farahnaz Pournavvab

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Researches have emphasis on the important role of psychosocial support and appropriate interventions for individuals that involved in serious physical and psychological problems . Patients with AIDS are often discussed in studies, but sometimes the psychological conditions of the people who live with them are ignored. In the present study, while paying attention to the spouses of AIDS patients, the role of supportive interventions has been investigated. the other word , Researchers Show that life skills training causes significant improvement in the mean scores of mothers physical health , mental health, social relationship and ultimately quality of life in the experimental group . The purpose of this study is determine of mental health of Twenty-one wives of patients with HIV+ In Shiraz ( city in sought of Iran) and effects of life skills on promotion of their mental health . Sampling was systematic randomize . These women were selected and invited to the training program based on their husbands' file numbers, who were selected to the counseling center for people with AIDS. first , they filled out GHQ questionnaires . Then , the life skills training for 8 sessions were taught for these women . Results indicated that Psychological condition of wife of patients with HIV+ was not appropriate . Scores of most them were above of cut of point of questionnaires .T test was done . worse scores were Assigned to anxiety and weakness in social functions . In the other hand , life skills have been effective significantly only in social functions of women . Scores of research’s participants in anxiety , depression and total test score were enhanced , but have not been significant . In the main of article , researchers have discussed why life skills training does not have much effect on some emotional problems .Despite the fact that life skills training had a positive effect on these spouses, but due to the stress of women with AIDS spouses, life skills training did not show much effectiveness, and for outstanding effects, there is a need for individual psychological treatments and broader social support.

Keywords: Hiv, aids, social suport, life skills

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Authors: Liana Gomide, Juliana Rodrigues

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The morphology of the foot defines its mode of operation and a biomechanical reform indispensable for a symmetrical distribution of plantar pressures in order not to overload some of its components in isolation. High plantar pressures at specific points in the foot may be a causal factor in several orthopedic disorders that affect the feet such as pain and stress fracture. With digital baro-podometry equipment one can observe an intensity of pressures along the entire foot and quantify some of the movements, such as a subtalar pronation present in the midfoot region. Although, they are involved in microtraumas. In clinical practice, excessive movement has been limited with the use of different taping techniques applied on the plantar arch. Thus, the objective of the present study was to analyze and compare the influence of the inelastic and elastic taping on the distribution of plantar pressure of runners pronators. This is a randomized clinical trial and blind-crossover. Twenty (20) male subjects, mean age 33 ± 7 years old, mean body mass of 71 ± 7 kg, mean height of 174 ± 6 cm, were included in the study. A data collection was carried out by a single research through barop-odometry equipment - Tekscan, model F-scan mobile. The tests were performed at three different times. In the first, an initial barop-odometric evaluation was performed, without a bandage application, with edges at a speed of 9.0 km/h. In the second and third moments, the inelastic or elastic taping was applied consecutively, according to the definition defined in the randomization. As results, it was observed that both as inelastic and elastic taping, provided significant reductions in contact pressure and peak pressure values when compared to the moment without a taping. However, an elastic taping was more effective in decreasing contact pressure (no bandage = 714 ± 201, elastic taping = 690 ± 210 and inelastic taping = 716 ± 180) and no peak pressure in the midfoot region (no bandage = 1490 ± 42, elastic taping = 1273 ± 323 and inelastic taping = 1487 ± 437). It is possible to conclude that it is an elastic taping provided by pressure in the middle region, thereby reducing the subtalar pronunciation event during the run.

Keywords: elastic taping, inelastic taping, running, subtalar pronation

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Authors: Mohammad Altaf Hossain

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A growing body of literature in urban studies has presented that urban precarity has been a lived experience for low-income groups of people in the cities of the Global South. It does not necessarily mean that cities in the Global North, where advanced capitalist economies exist, avoided the adverse realities of urban precarity. As a multifaceted condition, it creates other associated precariousness in lives -for example, economic deprivation, mental stress, and housing precarity. The interrelations between urbanity and precarity have been ubiquitous regardless of the developed and developing countries. People, mainly manual labourers with low incomes, go through uncertainties in every aspect of life. By analysing qualitative data and embracing structure-agency interaction, this paper intends to present how Bangladeshi migrants experience housing precarity in Dublin. Continued population growth and political economy factors such as labour market inequality, financialisation of the private rental sector, and the impact of cuts to government funding for social housing provision are combined to produce a housing supply crisis, affordability, and access in the city. As a result, low-income people practice informality in securing jobs and housing. The macro-structural components of this analysis include the Irish housing policy, the European labour market, the immigration policy, and the financialised housing market. The micro-structural components of South Asian communities’ experiences include social networks and social class. Access to social networks and practices of informality play a significant role in enabling them to negotiate urban precarity, including housing crises and income insecurity. In some cases, the collective agency of ethnic diaspora communities plays a vital role in negotiating with structural constraints.

Keywords: housing precarity, housing pathways, migration, agency, Dublin

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Authors: Ozlem Oral, Seval Kilic, Ozlem Yedier, Serap Dokmeci, Devrim Gozuacik

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Autophagy is a degradation pathway, activating under stress conditions. It digests macromolecules, such as abnormal proteins and long-lived organelles by engulfing them and by subsequent delivery of the cargo to lysosomes. The members of the phospholipid-dependent serine/threonine kinases, involved in many signaling pathways, which are necessary for the regulation of cellular metabolic activation. Previous studies implicate that, serine/threonine kinases have crucial roles in the mechanism of many diseases depend on the activated and/or inactivated signaling pathway. Data indicates, the signaling pathways activated by serine/threonine kinases are also involved in activation of autophagy mechanism. However, the information about the effect of serine/threonine kinases on autophagy mechanism and the roles of these effects in disease formation is limited. In this study, we investigated the effect of activated serine/threonine kinases on autophagic pathway. We performed a commonly used autophagy technique, GFP-LC3 dot formation and by using microscopy analyses, we evaluated promotion and/or inhibition of autophagy in serine/threonine kinase-overexpressed fibroblasts as well as cancer cells. In addition, we carried out confocal microscopy analyses and examined autophagic flux by utilizing the differential pH sensitivities of RFP and GFP in mRFP-GFP-LC3 probe. Based on the shRNA-library based screening, we identified autophagy-related proteins affected by serine/threonine kinases. We further studied the involvement of serine/threonine kinases on the molecular mechanism of newly identified autophagy proteins and found that, autophagic pathway is indirectly controlled by serine/threonine kinases via specific autophagic proteins. Our data indicate the molecular connection between two critical cellular mechanisms, which have important roles in the formation of many disease pathologies, particularly cancer. This project is supported by TUBITAK-1001-Scientific and Technological Research Projects Funding Program, Project No: 114Z836.

Keywords: autophagy, GFP-LC3 dot formation assay, serine/threonine kinases, shRNA-library screening

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Authors: Sajeli A. Begum, Ameer Basha, Kirti Hira, Rukaiyya Khan

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Cyclic dipeptides are simple diketopiperazine derivatives being investigated by several scientists for their biological effects which include anticancer, antimicrobial, haematological, anticonvulsant, immunomodulatory effect, etc. They are potentially active microbial metabolites having been synthesized too, for developing into drug candidates. Cultures of Pseudomonas species have earlier been reported to produce cyclic dipeptides, helping in quorum sensing signals and bacterial–host colonization phenomena during infections, causing cell anti-proliferation and immunosuppression. Fluorescing Pseudomonas species have been identified to secrete lipid derivatives, peptides, pyrroles, phenazines, indoles, aminoacids, pterines, pseudomonic acids and some antibiotics. In the present work, results of investigation on the cyclic dipeptide metabolites secreted by the culture broth of Pseudomonas species as potent pro-inflammatory cytokine inhibitors are discussed. The bacterial strain was isolated from the rhizospheric soil of groundnut crop and identified as Pseudomonas aeruginosa by 16S rDNA sequence (GenBank Accession No. KT625586). Culture broth of this strain was prepared by inoculating into King’s B broth and incubating at 30 ºC for 7 days. The ethyl acetate extract of culture broth was prepared and lyophilized to get a dry residue (EEPA). Lipopolysaccharide (LPS)-induced ELISA assay proved the inhibition of tumor necrosis factor-alpha (TNF-α) secretion in culture supernatant of RAW 264.7 cells by EEPA (IC50 38.8 μg/mL). The effect of oral administration of EEPA on plasma TNF-α level in rats was tested by ELISA kit. The LPS mediated plasma TNF-α level was reduced to 45% with 125 mg/kg dose of EEPA. Isolation of the chemical constituents of EEPA through column chromatography yielded ten cyclic dipeptides, which were characterized using nuclear magnetic resonance and mass spectroscopic techniques. These cyclic dipeptides are biosynthesized in microorganisms by multifunctional assembly of non-ribosomal peptide synthases and cyclic dipeptide synthase. Cyclo (Gly-L-Pro) was found to be more potentially (IC50 value 4.5 μg/mL) inhibiting TNF-α production followed by cyclo (trans-4-hydroxy-L-Pro-L-Phe) (IC50 value 14.2 μg/mL) and the effect was equal to that of standard immunosuppressant drug, prednisolone. Further, the effect was analyzed by determining mRNA expression of TNF-α in LPS-stimulated RAW 264.7 macrophages using quantitative real-time reverse transcription polymerase chain reaction. EEPA and isolated cyclic dipeptides demonstrated diminution of TNF-α mRNA expression levels in a dose-dependent manner under the tested conditions. Also, they were found to control the expression of other pro-inflammatory cytokines like IL-1β and IL-6, when tested through their mRNA expression levels in LPS-stimulated RAW 264.7 macrophages under LPS-stimulated conditions. In addition, significant inhibition effect was found on Nitric oxide production. Further all the compounds exhibited weak toxicity to LPS-induced RAW 264.7 cells. Thus the outcome of the study disclosed the effectiveness of EEPA and the isolated cyclic dipeptides in down-regulating key cytokines involved in pathophysiology of autoimmune diseases.In another study led by the investigators, microbial cyclic dipeptides were found to exhibit excellent antimicrobial effect against Fusarium moniliforme which is an important causative agent of Sorghum grain mold disease. Thus, cyclic dipeptides are emerging small molecular drug candidates for various autoimmune diseases.

Keywords: cyclic dipeptides, cytokines, Fusarium moniliforme, Pseudomonas, TNF-alpha

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