Search results for: gradient descent strategy

Authors: Sukwoong Kang

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Background: The application of light-emitting diode (LED)-dependent photobiomodulation (PBM) in promoting post-tendon injury healing has been recently reported. Despite the establishment of a theoretical basis for ligament restoration through PBM, the lack of any empirical evidence deems this therapeutic strategy contentious. Therefore, the aim of this study was to investigate the potency of LED-based PBM in facilitating tendon healing in a murine model. Methods: Migration kinetics were analyzed at two specific wavelengths: 630 and 880 nm. The Achilles tendon in the hind limbs of Balb/c mice was severed via Achilles tendon transection. Subsequently, the mice were randomized into LED non-irradiation and LED irradiation groups. Mice with intact tendons were employed as healthy controls. The wounds were LED-irradiated for 20 min daily for two days. Histological properties, tendon healing mediators, and inflammatory mediators were screened on day 14. Results: The roundness of the nuclei and fiber structure, indicating the degree of infiltrated inflammatory cells and severity of fiber fragmentation, respectively, were considerably lower in the LED irradiation group than in the LED non-irradiation group. Immunohistochemical analysis depicted an increase in tenocytes (SCX+ cells) and a recovery of wounds with reduced fibrosis (lower collagen 3 and TGF-β1) in the LED irradiation group during healing; conversely, the LED non-irradiation group exhibited tissue fibrosis. The ratio of M2 macrophages to total macrophages was higher in the LED irradiation group than in the injured group. Conclusion: LED-based PBM in the Achilles tendon rupture murine model effectuated a rapid restoration of histological and immunochemical outcomes. The aforementioned findings suggest that LED-based PBM presents remarkable potential as an adjunct therapeutic for tendon healing and warrants further research to standardize various parameters to advance and establish it as a reliable treatment regime.

Keywords: photobiomodulation, light-emitting diode, tendon, regeneration

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Authors: Saleh Alkarri, Dimple Sharma, Teresa M. Bergholz, Muhammad Rabnawaz

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Aims: Develop a methodology for the fabrication of anti-microbial polypropylene (PP) surfaces with (i) leachable copper, (II) chloride dihydrate (CuCl₂·₂H₂O) and (ii) non-leachable magnesium hydroxide (Mg(OH)₂) biocides. Methods and Results: Two methodologies are used to develop anti-microbial PP surfaces. One method involves melt-blending and subsequent injection molding, where the biocide additives were compounded with PP and subsequently injection-molded. The other method involves the thermal embossing of anti-microbial agents on the surface of a PP substrate. The obtained biocide-bearing PP surfaces were evaluated against E. coli K-12 MG1655 for 0, 4, and 24 h to evaluate their anti-microbial properties. The injection-molded PP bearing 5% CuCl2·₂H₂O showed a 6-log reduction of E. coli K-12 MG1655 after 24 h, while only 1 log reduction was observed for PP bearing 5% Mg(OH)2. The thermally embossed PP surfaces bearing CuCl2·2H2O and Mg(OH)₂ particles (at a concentration of 10 mg/mL) showed 3 log and 4 log reduction, respectively, against E.coli K-12 MG1655 after 24 h. Conclusion: The results clearly demonstrate that CuCl₂·2H₂O conferred anti-microbial properties to PP surfaces that were prepared by both injection molding as well as thermal embossing approaches owing to the presence of leachable copper ions. In contrast, the non-leachable Mg(OH)₂ imparted anti-microbial properties only to the surface prepared via the thermal embossing technique. Significance and Impact of The Study: Plastics with leachable biocides are effective anti-microbial surfaces, but their toxicity is a major concern. This study provides a fabrication methodology for non-leachable PP-based anti-microbial surfaces that are potentially safer. In addition, this strategy can be extended to many other plastics substrates.

Keywords: anti-microbial activity, E. coli K-12 MG1655, copper (II) chloride dihydrate, magnesium hydroxide, leachable, non-leachable, compounding, thermal embossing

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Authors: Saleh Alkarri, Dimple Sharma, Teresa M. Bergholz, Muhammad Rabnawa

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Aims: Develop a methodology for the fabrication of anti-microbial polypropylene (PP) surfaces with (i) leachable copper (II) chloride dihydrate (CuCl2·2H2O) and (ii) non-leachable magnesium hydroxide (Mg(OH)2) biocides. Methods and Results: Two methodologies are used to develop anti-microbial PP surfaces. One method involves melt-blending and subsequent injection molding, where the biocide additives were compounded with PP and subsequently injection-molded. The other method involves the thermal embossing of anti-microbial agents on the surface of a PP substrate. The obtained biocide-bearing PP surfaces were evaluated against E. coli K-12 MG1655 for 0, 4, and 24 h to evaluate their anti-microbial properties. The injection-molded PP bearing 5% CuCl2·2H2O showed a 6-log reduction of E. coli K-12 MG1655 after 24 h, while only 1 log reduction was observed for PP bearing 5% Mg(OH)2. The thermally embossed PP surfaces bearing CuCl2·2H2O and Mg(OH)2 particles (at a concentration of 10 mg/mL) showed 3 log and 4 log reduction, respectively, against E.coli K-12 MG1655 after 24 h. Conclusion: The results clearly demonstrate that CuCl2·2H2O conferred anti-microbial properties to PP surfaces that were prepared by both injection molding as well as thermal embossing approaches owing to the presence of leachable copper ions. In contrast, the non-leachable Mg(OH)2 imparted anti-microbial properties only to the surface prepared via the thermal embossing technique. Significance and Impact of The Study: Plastics with leachable biocides are effective anti-microbial surfaces, but their toxicity is a major concern. This study provides a fabrication methodology for non-leachable PP-based anti-microbial surfaces that are potentially safer. In addition, this strategy can be extended to many other plastics substrates.

Keywords: anti-microbial activity, E. coli K-12 MG1655, copper (II) chloride dihydrate, magnesium hydroxide, leachable, non-leachable, compounding, thermal embossing

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Authors: Calvin A. Omolo, Rahul S. Kalhapure, Mahantesh Jadhav, Sanjeev Rambharose, Chunderika Mocktar, Thirumala Govender

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Treatment of infections is compromised by limitations of conventional dosage forms and drug resistance. Nanocarrier system is a strategy to overcome these challenges and improve therapy. Thus, the development of novel materials for drug delivery via nanocarriers is essential. The aim of the study was to synthesize a multi-arm polymer (6-mPEPEA) for enhanced activity of vancomycin (VM) against susceptible and resistant Staphylococcus aureus (MRSA). The synthesis steps of the star polymer followed reported procedures. The synthesized 6-mPEPEA was characterized by FTIR, ¹H and ¹³CNMR and MTT assays. VM loaded micelles were prepared from 6-mPEPEA and characterized for size, polydispersity index (PI) and surface charge (ZP) (Dynamic Light Scattering), morphology by TEM, drug loading (UV Spectrophotometry), drug release (dialysis bag), in vitro and in vivo efficacy against sensitive and resistant S. aureus. 6-mPEPEA was synthesized, and its structure was confirmed. MTT assays confirmed its nontoxic nature with a high cell viability (77%-85%). Unimolecular spherical micelles were prepared. Size, PI, and ZP was 52.48 ± 2.6 nm, 0.103 ± 0.047, -7.3 ± 1.3 mV, respectively and drug loading was 62.24 ± 3.8%. There was a 91% drug release from VCM-6-mPEPEA after 72 hours. In vitro antibacterial test revealed that VM-6-mPEPEA had 8 and 16-fold greater activity against S. aureus and MRSA when compared to bare VM. Further investigations using flow cytometry showed that VM-6-mPEPEA had 99.5% killing rate of MRSA at the MIC concentration. In vivo antibacterial activity revealed that treatment with VM-6-mPEPEA had a 190 and a 15-fold reduction in the MRSA load in untreated and VM treated respectively. These findings confirmed the potential of 6-mPEPEA as a promising bio-degradable nanocarrier for antibiotic delivery to improve treatment of bacterial infections.

Keywords: biosafe, MRSA, nanocarrier, resistance, unimolecular-micelles

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Authors: Khaled Klib, Yousri Azzam, Ibrahim Maarouf

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Tourism is one of the most important and fastest growing economic activities in the world, which has a prominent role in the growth and development of countries and has become increasingly important as business and trade after the World War II. The tourism development is one of the most important aspects of urban development, which aims to plan and develop tourist attractions and improve the urban environment within cities. Tourism development has become a priority for the urban development policy of cities, particularly those which have many tourist potentials. Complementary services, such as infrastructure, roads’ networks, transportation, and communications are needed for these potentials to function properly. In order to achieve these functionalities, also a new planning for the new areas as an expansion is required, or developing and renovating the existing urban areas according to pre-prepared plans to avoid random expansion of the urban structure of the city. This paper aims to determine the tourist attractions of Al-Khomse city, by reviewing the most important tourist attractions such as the Roman city (Leptis Magna), the geographical location on the Mediterranean coast, the temperate climate and diversity of the natural environment. The paper also examines the reality of the infrastructure and tourist services in the city and its suitability to serve the tourism sector. The paper also includes a proposed for tourism development in the city as one of the city's urban expansion trends, which can guide the development strategy in the future. The paper concludes with a vision for the tourism development areas as one of the trends for urban expansion in the future. The paper also concludes tourism development will have an effective role in the growth and development of urban, economic and social, in addition to preserving the natural environment. The paper recommended the need to emphasize the role of tourism development as one of the pillars and trends for the development policy and expansion of Al-Khomse city, preservation of tourist attractions and natural resources and developing infrastructure and tourist services such as accommodation, entertainment, mobility, and accessibility.

Keywords: tourism, tourist attractions, tourism development, urban expansion

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Authors: Hassen Mohammed, Michelle Clarke, Helen Marshall

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Maternal immunization is an effective strategy to protect pregnant women and their offspring from vaccine-preventable diseases. Despite the recommendation of maternal influenza and more recently pertussis immunization in Australia, uptake of these vaccines has been suboptimal. Monitoring the impact of the current funded vaccine programs for pregnant women is limited. The study aimed to assess the impact of the funded program and determine factors associated with vaccine uptake in pregnant women. This observational prospective study was undertaken between November 2014 and July 2016 at the Women’s and Children’s Hospital in South Australia (WCH). Demographic details and vaccination history from South Australian pregnant women who attended the WCH were reviewed. A standardized self-reported survey was conducted in antenatal care with a follow up telephone interview at 8-10 weeks post-delivery. A midwife delivered immunization program for pregnant women in antenatal clinic commenced in April 2015. Of the 180 pregnant women who completed the survey questionnaire, 75.5% and 80.5 % received maternal influenza and pertussis vaccines respectively. First-time mothers had twice the odds of having received influenza vaccine during pregnancy than multiparous women (OR 2.4; CI 1.14 - 4.94; p= 0.021). The proportion of women who received pertussis vaccine during pregnancy, following the introduction of the midwife delivered pertussis vaccination program (140/155, 90.3%) was significantly higher compared with women who received maternal pertussis vaccination prior to the introduction of the program (5/22, 23.7%, p < 0.001). The odds of women receiving maternal pertussis vaccine following the implementation of the midwife delivered program were 31 times higher than women who delivered babies prior to the program (OR 31.7, CI 10.24- 98.27; p < 0.001). High uptake of influenza and pertussis vaccines during pregnancy can be attained with health care provider recommendation and inclusion of maternal immunization as part of standard antenatal care.

Keywords: influenza, maternal immunization, pertussis, provider recommendation

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Authors: Dawit Abay Tesfamariam

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Ethiopia’s Climate- Resilient Green Economy (ECRGE) strategy focuses mainly on generating and proper utilization of renewable energy (RE). Nonetheless, the current electricity generation of the country is dominated by hydropower. The data collected in 2016 by Ethiopian Electric Power (EEP) indicates that the intermittent RE sources from solar and wind energy were only 8 %. On the other hand, the EEP electricity generation plan in 2030 indicates that 36.1 % of the energy generation share will be covered by solar and wind sources. Thus, a case study was initiated to model and compute the balance and consumption of electricity in three different scenarios: 2016, 2025, and 2030 using the EnergyPLAN Model (EPM). Initially, the model was validated using the 2016 annual power-generated data to conduct the EnergyPLAN (EP) analysis for two predictive scenarios. The EP simulation analysis using EPM for 2016 showed that there was no significant excess power generated. Thus, the EPM was applied to analyze the role of energy storage in RE in Ethiopian grid systems. The results of the EP simulation analysis showed there will be excess production of 402 /7963 MW average and maximum, respectively, in 2025. The excess power was in the three rainy months of the year (June, July, and August). The outcome of the model also showed that in the dry seasons of the year, there would be excess power production in the country. Consequently, based on the validated outcomes of EP indicates, there is a good reason to think about other alternatives for the utilization of excess energy and storage of RE. Thus, from the scenarios and model results obtained, it is realistic to infer that if the excess power is utilized with a storage system, it can stabilize the grid system and be exported to support the economy. Therefore, researchers must continue to upgrade the current and upcoming storage system to synchronize with potentials that can be generated from renewable energy.

Keywords: renewable energy, power, storage, wind, energy plan

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Authors: Anusha Atmakuri, R. D. Tyagi, Patrick Drogui

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Landfilling is the most familiar and easy way to dispose solid waste. Landfill is generally received via wastes from municipal near to a landfill. The waste collected is from commercial, industrial, and residential areas and many more. Landfill leachate (LFL) is formed when rainwater passes through the waste placed in landfills and consists of several dissolved organic materials, for instance, aquatic humic substances (AHS), volatile fatty acids (VFAs), heavy metals, inorganic macro components, and xenobiotic organic matters, highly toxic to the environment. These components of LFL put a load on it, hence it necessitates the treatment of LFL prior to its discharge into the environment. Various methods have been used to treat LFL over the years, such as physical, chemical, biological, physicochemical, electrical, and advanced oxidation methods. This study focuses on the combination of biological and electrochemical methods- extracellular polymeric substances and electrocoagulation(EC). The coupling of electro-coagulation process with extracellular polymeric substances (EPS) (as flocculant) as pre and\or post treatment strategy provides efficient and economical process for the decontamination of landfill leachate contaminated with suspended matter, metals (e.g., Fe, Mn) and ammonical nitrogen. Electro-coagulation and EPS mediated coagulation approach could be an economically viable for the treatment of landfill leachate, along with possessing several other advantages over several other methods. This study utilised waste substrates such as activated sludge, crude glycerol and waste cooking oil for the production of EPS using fermentation technology. A comparison of different scenarios for the treatment of landfill leachate is presented- such as using EPS alone as bioflocculant, EPS and EC with EPS being the 1st stage, and EPS and EC with EC being the 1st stage. The work establishes the use of crude EPS as a bioflocculant for the treatment of landfill leachate and wastewater from a site near a landfill, along with EC being successful in removal of some major pollutants such as COD, turbidity, total suspended solids. A combination of these two methods is to be explored more for the complete removal of all pollutants from landfill leachate.

Keywords: landfill leachate, extracellular polymeric substances, electrocoagulation, bioflocculant.

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Authors: Nkrumak Micheal Atta Ofori

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The Vocational System is a decentralized Studies System implemented in Ghana as vocation studies strategy for grassroot that focuses on providing individuals with the specific skills, knowledge, and training necessary for a particular trade, craft, profession, or occupation. This article asks how devolution of vocational studies to local level authorities produces responsive and accountable representation and sustainable vocational learning under the vocational Studies System. It focuses on two case studies: Asokore Mampong and Atwima kwanwoma Municipal. Then, the paper asks how senior high school are developing new material and social practices around the vocational studies System to rebuild their livelihoods and socio-economic wellbeing. Here, the article focusses on Kumasi District, drawing lessons for the two other cases. The article shows how the creation of representative groups under the Vocational Studies System provides the democratic space necessary for effective representation of community aspirations. However, due to elite capture, the interests of privilege few people are promoted. The state vocational training fails to devolve relevant and discretionary resources to local teachers and do not follow the prescribed policy processes of the Vocational Studies System. Hence, local teachers are unable to promote responsive and accountable representation. Rural communities continue to show great interest in the Vocational Studies System, but the interest is bias towards gaining access to vocational training schools for advancing studies. There is no active engagement of the locals in vocational training, and hence, the Vocational Studies System exists only to promote individual interest of communities. This article shows how ‘failed’ interventions can gain popular support for rhetoric and individual gains.

Keywords: vocational studies system, devolution of vocational studies, local-level authorities, senior high schools and vocational learning, community aspirations and representation

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Authors: Sharda Kumari, Saiman Shetty

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Autonomous trucking is just one of the numerous significant shifts impacting fleet management services. The Society of Automotive Engineers (SAE) has defined six levels of vehicle automation that have been adopted internationally, including by the United States Department of Transportation. On public highways in the United States, organizations are testing driverless vehicles with at least Level 4 automation which indicates that a human is present in the vehicle and can disable automation, which is usually done while the trucks are not engaged in highway driving. However, completely driverless vehicles are presently being tested in the state of California. While autonomous trucking can increase safety, decrease trucking costs, provide solutions to trucker shortages, and improve efficiencies, logistics, too, requires advancements to keep up with trucking innovations. Given that artificial intelligence, machine learning, and automated procedures enable people to do their duties in other sectors with fewer resources, CRM (Customer Relationship Management) can be applied to the autonomous trucking business to provide the same level of efficiency. In a society witnessing significant digital disruptions, fleet management is likewise being transformed by technology. Utilizing strategic alliances to enhance core services is an effective technique for capitalizing on innovations and delivering enhanced services. Utilizing analytics on CRM systems improves cost control of fuel strategy, fleet maintenance, driver behavior, route planning, road safety compliance, and capacity utilization. Integration of autonomous trucks with automated fleet management, yard/terminal management, and customer service is possible, thus having significant power to redraw the lines between the public and private spheres in autonomous trucking logistics.

Keywords: autonomous vehicles, customer relationship management, customer experience, autonomous trucking, digital transformation

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Authors: Jamil Hijazi, Stirling Howieson

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Reducing energy consumption and CO₂ emissions are probably the greatest challenge now facing mankind. From considerations surrounding global warming and CO₂ production, it has to be recognized that oil is a finite resource and the KSA like many other oil-rich countries will have to start to consider a horizon where hydro-carbons are not the dominant energy resource. The employment of hybrid ground-cooling pipes in combination with the black body solar collection and radiant night cooling systems may have the potential to displace a significant proportion of oil currently used to run conventional air conditioning plant. This paper presents an investigation into the viability of such hybrid systems with the specific aim of reducing cooling load and carbon emissions while providing all year-round thermal comfort in a typical Saudi Arabian urban housing block. Soil temperatures were measured in the city of Jeddah. A parametric study then was carried out by computational simulation software (DesignBuilder) that utilized the field measurements and predicted the cooling energy consumption of both a base case and an ideal scenario (typical block retro-fitted with insulation, solar shading, ground pipes integrated with hypocaust floor slabs/stack ventilation and radiant cooling pipes embed in floor). Initial simulation results suggest that careful ‘ecological design’ combined with hybrid radiant and ground pipe cooling techniques can displace air conditioning systems, producing significant cost and carbon savings (both capital and running) without appreciable deprivation of amenity.

Keywords: cooling load, energy efficiency, ground pipe cooling, hybrid cooling strategy, hydronic radiant systems, low carbon emission, passive designs, thermal comfort

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Authors: Avinash Vellore Sunder, Shikha Shah, Pramod P. Wangikar

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The enzymatic conversion of nitriles to carboxylic acids by nitrilases has gained significance in the green synthesis of several pharmaceutical precursors and fine chemicals. While nitrilases have been characterized from different sources, the industrial application requires the identification of nitrilases that possess higher substrate tolerance, wider specificity and better thermostability, along with the development of an efficient bioprocess for producing large amounts of nitrilase. To produce large amounts of nitrilase, we developed a fed-batch fermentation process on defined media for the high cell density cultivation of E. coli cells expressing the well-studied nitrilase from Alcaligenes fecalis. A DO-stat feeding approach was employed combined with an optimized post-induction strategy to achieve nitrilase titer of 2.5*105 U/l and 78 g/l dry cell weight. We also identified 16 novel nitrilase sequences from genome mining and analysis of substrate binding residues. The nitrilases were expressed in E. coli and their biocatalytic potential was evaluated on a panel of 22 industrially relevant nitrile substrates using high-throughput screening and HPLC analysis. Nine nitrilases were identified to exhibit high activity on structurally diverse nitriles including aliphatic and aromatic dinitriles, heterocyclic, -hydroxy and -keto nitriles. With fed-batch biotransformation, whole-cell Zobelia galactanivorans nitrilase achieved yields of 2.4 M nicotinic acid and 1.8 M isonicotinic acid from 3-cyanopyridine and 4-cyanopyridine respectively within 5 h, while Cupravidus necator nitrilase enantioselectively converted 740 mM mandelonitrile to (R)–mandelic acid. The nitrilase from Achromobacter insolitus could hydrolyze 542 mM iminodiacetonitrile in 1 h. The availability of highly active nitrilases along with bioprocesses for enzyme production expands the toolbox for industrial biocatalysis.

Keywords: biocatalysis, isonicotinic acid, iminodiacetic acid, mandelic acid, nitrilase

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Authors: Kashif Habib, Zeeshan Ayyub

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ZnO voltage dependent resistor was widely used as components of the electrical system for over-voltage protection. It has a wide application prospect in superconducting energy-removal, generator de-excitation, overvoltage protection of electrical & electronics equipment. At present, the research for the application of ZnO voltage dependent resistor stop, it uses just in the field of its nonlinear voltage current characteristic and overvoltage protection areas. There is no further study over the over-voltage breakdown characteristics, such as the combustion phenomena and the measure of the voltage/current when it breakdown, and the affect to its surrounding equipment. It is also a blind spot in its application. So, when we do the feature test of ZnO voltage dependent resistor, we need to design a reasonable test power supply, making the terminal voltage keep for sine wave, simulating the real use of PF voltage in power supply conditions. We put forward the solutions of using inverter to generate a controllable power. The paper mainly focuses on the breakdown characteristic test power supply of nonlinear ZnO voltage dependent resistor. According to the current mature switching power supply technology, we proposed power control system using the inverter as the core. The power mainly realize the sin-voltage output on the condition of three-phase PF-AC input, and 3 control modes (RMS, Peak, Average) of the current output. We choose TMS320F2812M as the control part of the hardware platform. It is used to convert the power from three-phase to a controlled single-phase sin-voltage through a rectifier, filter, and inverter. Design controller produce SPWM, to get the controlled voltage source via appropriate multi-loop control strategy, while execute data acquisition and display, system protection, start logic control, etc. The TMS320F2812M is able to complete the multi-loop control quickly and can be a good completion of the inverter output control.

Keywords: ZnO, multi-loop control, SPWM, non-linear load

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Authors: Karen Armstrong

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This study is a narrative inquiry into the use of simulated person methodology (SPM) in teacher education classes. This methodology -often used in medical schools- has tremendous benefits in terms of enhancing experiential education in teacher education classes. Literacy education is a major focus in elementary schools. New teachers must work with parents to ensure that children learn to read and expand their literacy horizons. The classes used in this narrative inquiry research consist of one graduate class on family literacy and two pre-service teacher education classes: literacy and culture and early and family literacy. Two scenarios were devised, both of which simulated a parent-teacher interview. In the first scenario, the parent is a reluctant father who is ashamed of his lack of reading ability and does not understand why literacy is important. His seven-year-old son, wanting to emulate his father, has suddenly transformed from an eager student to one who rejects the value of reading in loyalty to his father who cannot read. In the second scenario, a father is called in by the teacher because his son has started acting out in class. The mother in this scenario is temporarily absent from the home, and the father is now the sole caregiver. In each of the scenarios, students are the teachers who are problem-solving these dilemmas in a safe environment with the 'parent' who is a specially trained simulated person. Teacher candidates enact, with the trained simulated person, their strategies for encouraging parents to engage in the literacy development of their children. Teacher candidates attempt to offer support and encouragement to parents. This simulation strategy offers both beginning and more experienced teachers the opportunity to practice an interview with two distinct and contrasting family situations with regard to the literacy of young children. The paper discusses the details of the scenarios enacted in class and the reflective discussion through which students learn from the simulation.

Keywords: experiential education, literacy, simulated person methodology, teacher education

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Authors: I. Boroňová, J.Bernasovská, J. Kľoc, Z. Tomková, E. Petrejčíková, D. Gabriková, S. Mačeková

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Osteoporosis is a complex health disease characterized by low bone mineral density, which is determined by an interaction of genetics with metabolic and environmental factors. Current research in genetics of osteoporosis is focused on identification of responsible genes and polymorphisms. TNFRSF11B gene plays a key role in bone remodeling. The aim of this study was to investigate the genotype and allele distribution of A163G (rs3102735) osteoprotegerin gene promoter and G1181C (rs2073618) osteoprotegerin first exon polymorphisms in the group of 180 unrelated postmenopausal women with diagnosed osteoporosis and 180 normal controls. Genomic DNA was isolated from peripheral blood leukocytes using standard methodology. Genotyping for presence of different polymorphisms was performed using the Custom Taqman®SNP Genotyping assays. Hardy-Weinberg equilibrium was tested for each SNP in the groups of participants using the chi-square (χ2) test. The distribution of investigated genotypes in the group of patients with osteoporosis were as follows: AA (66.7%), AG (32.2%), GG (1.1%) for A163G polymorphism; GG (19.4%), CG (44.4%), CC (36.1%) for G1181C polymorphism. The distribution of genotypes in normal controls were follows: AA (71.1%), AG (26.1%), GG (2.8%) for A163G polymorphism; GG (22.2%), CG (48.9%), CC (28.9%) for G1181C polymorphism. In A163G polymorphism the variant G allele was more common among patients with osteoporosis: 17.2% versus 15.8% in normal controls. Also, in G1181C polymorphism the phenomenon of more frequent occurrence of C allele in the group of patients with osteoporosis was observed (58.3% versus 53.3%). Genotype and allele distributions showed no significant differences (A163G: χ2=0.270, p=0.605; χ2=0.250, p=0.616; G1181C: χ2= 1.730, p=0.188; χ2=1.820, p=0.177). Our results represents an initial study, further studies of more numerous file and associations studies will be carried out. Knowing the distribution of genotypes is important for assessing the impact of these polymorphisms on various parameters associated with osteoporosis. Screening for identification of “at-risk” women likely to develop osteoporosis and initiating subsequent early intervention appears to be most effective strategy to substantially reduce the risks of osteoporosis.

Keywords: osteoporosis, real-time PCR method, SNP polymorphisms

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Authors: Beatriz Lafuente Alcázar, Yash Wani, Amit J. Nimunkar

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Cardiovascular Diseases (CVDs) are the leading cause of death globally, and around 80% of sudden cardiac deaths are due to arrhythmias or irregular heartbeats. The majority of these pathologies are revealed by either short-term or long-term alterations in the electrocardiogram (ECG) morphology. The ECG is the main diagnostic tool in cardiology. It is a non-invasive, pain free procedure that measures the heart’s electrical activity and that allows the detecting of abnormal rhythms and underlying conditions. A cardiologist can diagnose a wide range of pathologies based on ECG’s form alterations, but the human interpretation is subjective and it is contingent to error. Moreover, ECG records can be quite prolonged in time, which can further complicate visual diagnosis, and deeply retard disease detection. In this context, deep learning methods have risen as a promising strategy to extract relevant features and eliminate individual subjectivity in ECG analysis. They facilitate the computation of large sets of data and can provide early and precise diagnoses. Therefore, the cardiology field is one of the areas that can most benefit from the implementation of deep learning algorithms. In the present study, a deep learning algorithm is trained following a novel approach, using a combination of different databases as the training set. The goal of the algorithm is to achieve the detection of R-peaks in ECG signals. Its performance is further evaluated in ECG signals with different origins and features to test the model’s ability to generalize its outcomes. Performance of the model for detection of R-peaks for clean and noisy ECGs is presented. The model is able to detect R-peaks in the presence of various types of noise, and when presented with data, it has not been trained. It is expected that this approach will increase the effectiveness and capacity of cardiologists to detect divergences in the normal cardiac activity of their patients.

Keywords: arrhythmia, deep learning, electrocardiogram, machine learning, R-peaks

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Authors: Benoit Landi, Hervé Pingaud, Jean-Benoit Culie, Michel Galaup

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Serious games have been widely disseminated in the field of digital learning. They have proved their utility in improving skills through virtual environments that simulate the field where new competencies have to be improved and assessed. This paper describes how we created CLONE, a serious game whose purpose is to help nurses create an efficient work plan in a hospital care unit. In CLONE, the number of patients to take care of is similar to the reality of their job, going far beyond what is currently practiced in nurse school classrooms. This similarity with the operational field increases proportionally the number of activities to be scheduled. Moreover, very often, the team of nurses is composed of regular nurses and nurse assistants that must share the work with respect to the regulatory obligations. Therefore, on the one hand, building a short-term planning is a complex task with a large amount of data to deal with, and on the other, good clinical practices have to be systematically applied. We present how reference planning has been defined by addressing an optimization problem formulation using the expertise of teachers. This formulation ensures the gameplay feasibility for the scenario that has been produced and enhanced throughout the game design process. It was also crucial to steer a player toward a specific gaming strategy. As one of our most important learning outcomes is a clear understanding of the workload concept, its factual calculation for each caregiver along time and its inclusion in the nurse reasoning during planning elaboration are focal points. We will demonstrate how to modify the game scenario to create a digital environment in which these somewhat abstract principles can be understood and applied. Finally, we give input on an experience we had on a pilot of a thousand undergraduate nursing students.

Keywords: care planning, workload, game design, hospital nurse, organizational skills, digital learning, serious game

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Authors: Pavitra Sharma, A. K. Singh

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The establishment of pest population in a habitat is greatly influenced by abiotic factors, such as temperature, photoperiod, and humidity. These factors influence the biology and behavior of insects and their pest status. Nezara viridula (Heteroptera: Pentatomidae), commonly known as southern green stink bug, is economically important pest of legumes. Both nymphs and adult suck the sap from different part of the plant and deteriorate the standing crop. Present study involves effects of temperature on incubation, hatching success and nymphal duration of N. viridula. The results indicated that the development of eggs requires optimal temperature range. Temperature conditions above and below the optimum range affect the incubation period as well as the percent hatchability of eggs. At 19°C, the egg incubation period was longest whereas it was shortest at 27°C. The change in temperature from the optimum condition also affected the hatchability of eggs in N. viridula. Decrease in the hatchability was observed with the decrease in temperature. However, the results were not statistically significant. Decrease in temperature from the optimum temperature to 19°C, also resulted in an increase in nymphal duration of N. viridula. However, no such effect of temperature within the studied range was observed on the morphology of nymphs or adults. Variation in temperature also had no adverse effects on the survival of laboratory bred population of Nezara nymphs. The feeding activity of the bug in relation to photoperiod was assessed by counting the number of punctures on the food surface. The results indicated that day-night regime did not affect the feeding activity of the bug significantly. The present study enhances our knowledge about the effect of environmental factors on the biology of insects and developing the strategy for ‘Integrated Pest Management’ of hemipteran insects by management of the physical factors.

Keywords: development, feeding, hatchability, Nezara viridula

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Authors: Diego Romero, Fabio Rojas, J. Alejandro Urrego

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The sounding rockets are aerospace vehicles that were developed in the mid-20th century, and Colombia has been involved in research that was carried out with the aim of innovating with this technology. The rockets are university research programs with the collaboration of the local government, with a simple strategy, develop and reduce the greatest costs associated with the production of a kind type of technology. In this way, in this document presents the failure analysis of a solid rocket motor, with the real compatibly to reach the thermosphere with a low-cost fuel. This solid rocket motor is the latest development of the Uniandes Aerospace Project (PUA for its Spanish acronym), an undergraduate and postgraduate research group at Universidad de los Andes (Bogotá, Colombia), dedicated to incurring in this type of technology. This motor has been carried out on Candy-type solid fuel, which is a compound of potassium nitrate and sorbitol, and the investigation has allowed the production of solid motors powerful enough to reach space, and which represents a unique technological advance in Latin America and an important development in experimental rocketry.To outline the main points the explosion in a static test is an important to explore and demonstrate the ways to develop technology, methodologies, production and manufacturing, being a solid rocket motor with 30 kN of thrust. In conclusion, this analysis explores different fields such as: design, manufacture, materials, production, first fire and more, with different engineering tools with principal objective find root failure. Following the engineering analysis methodology, was possible to design a new version of motor, with learned lessons new manufacturing specification, therefore, when publishing this project, it is intended to be a reference for future research in this field and benefit the industry.

Keywords: candy propellant, candy rockets, explosion, failure analysis, static test, solid rocket motor

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Authors: Opara Monica Onyinyechi, Ahmad Iqmer Nashriq Mohd Nazan, Suriani Ismail

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Introduction: Global estimates of malaria indicate that at least 3.3 billion people are at risk of being infected with malaria and 1.2 billion are at high risk. The review investigates the effectiveness of health education strategies to increase the level of malaria knowledge and ITN ownership among the populations of sub-Sahara African countries. Methods: A literature search was conducted using Science direct, CINAHL, PubMed, Prisma, Pico, Cochrane library and PsycINFO databases to retrieve articles published between 2000 until 2020. Eleven studies that reported on malaria prevention and intervention using health education strategies conducted in sub-Saharan Africa were included in the final review. Results: Four studies used educational interventions to teach appropriate ITN strategies and promote ITN usage. Two others focused on improving knowledge of malaria transmission, prevention, treatment, and its signs and symptoms. The remaining five studies assessed both ITN use and malaria knowledge. Of these, 10 were eligible for meta-analysis. On average, health education interventions significantly increase the odds of a person in the intervention group to report better malaria knowledge (odds ratio 1.30, 95% CI: 1.00 to 1.70, P= 0.05) and higher ITN ownership (odds ratio 1.53, 95% CI: 1.02 to 2.29, P= 0.004) compared to those in the control group. The odds of ITN ownership also substantially increases when the intervention was based on a theory or model (odds ratio 5.27, 95% CI: 3.24 to 8.58, P= 0.05). Conclusion: Our review highlights the various health education strategies used in sub-Saharan Africa to curb malaria over the past two decades. Meta-analysis findings show that health education intervention is moderately effective in improving malaria knowledge and ITN ownership and has contributed to the effort of global malaria strategy.

Keywords: malaria, health education, insecticide treated nets, sub-Saharan Africa, meta-analysis

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Authors: Wen Hsin Hsu, Pin Lin

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Objective: Thirst discomfort is the most common yet often overlooked symptom in patients in the intensive care unit (ICU), with an incidence rate of 69.8%. If not properly cared for, it can easily lead to irritability, affect sleep quality, and increase the incidence of delirium, thereby extending the length of hospital stay. Research points out that the sensation of coldness is an effective strategy to alleviate thirst. Using a combined care approach for thirst can prolong the sensation of coldness in the mouth and reduce thirst discomfort. Therefore, it needs to be further analyzed and its effectiveness reviewed. Methods: This study uses systematic literature review and meta-analysis methodologies and searched databases including PubMed, MEDLINE, EMBASE, Cochrane, CINAHL, and two Chinese databases (CEPS and CJTD) based on keywords. JBI was used to appraise the quality of the literature. RevMen 5.4 software package was used, and Fix Effect Model was applied for data analysis. We selected experimental articles, including those in English and Chinese, that met the inclusion and exclusion criteria. Three research articles were included in total, with a sample size of 416 people. Two were randomized controlled trials, and one was a quasi-experimental design. Results: The results show that the combined care for thirst, which includes ice water spray or oral swab wipes, menthol mouthwash, and lip balm, can significantly relieve thirst intensity MD=-1.36 (3 studies, 95% CI (-1.77, -0.95), p <0.001) and thirst distress MD=-0.71 (2 studies, 95% CI (-1.32, -0.10), p =0.02). Therefore, it is recommended that medical staff identify high-risk groups for thirst early on. Implications for Practice: For patients who cannot eat orally, providing combined care for thirst can increase oral comfort and improve the quality of care.

Keywords: thirst bundle care, intensive care units, meta-analysis, ice water spray, menthol

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Authors: Mustafa Eruyar, Ersoy Pehlivan, Fatih Kafalı, Fatih Gundogan

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All megacities are not only under the pressure of common urbanization and growth problems but also dealing with different challenges according to their specific circumstances. However, the majority of cities focuses mainly on popular smart city projects, which are usually driven by strong private sector, regardless of their characteristics, each city needs to develop customized projects within a tailor-made smart city roadmap to be able to solve its own challenges. Smart city manifest, helps citizens to feel the action better than good reading smart city vision statements, which consists of five elements; namely purpose, values, mission, vision, and strategy. This study designs a methodology for smart city roadmap based on a top-down approach, breaking down of smart city manifest to feasible projects for a systematic smart city transformation. This methodology was implemented in Istanbul smart city transformation program which includes smart city literature review, current state analysis, roadmap, and architecture projects, respectively. Istanbul smart city roadmap project followed an extensive literature review of certain leading smart cities around the world and benchmarking of the city’s current state using well known smart city indices. In the project, needs of citizens and service providers of the city were identified via stakeholder, persona and social media analysis. The project aimed to develop smart city projects targeting fulfilling related needs by implementing a gap analysis between current state and foreseen plans. As a result, in 11 smart city domains and enablers; 24 strategic objectives, 50 programs, and 101 projects were developed with the support of 183 smart city stakeholder entities and based on 125 citizen persona profiles and last one-year social media analysis. In conclusion, the followed methodology helps cities to identify and prioritize their needs and plan for long-term sustainable development, despite limited resources.

Keywords: needs-based, manifest, roadmap, smart city, top-down approach

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Authors: Miguel A. Jimenez Barros, Elyn L. Solano Charris, Luis E. Ramirez, Lauren Castro Bolano, Carlos Torres Barreto, Juliana Morales Cubillo

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This project sought to mitigate the high levels of water consumption in industrial processes in accordance with the water-rationing plan promoted at national and international level due to the water consumption projections published by the United Nations. Water consumption has three main uses, municipal (common use), agricultural and industrial where the latter consumes a minimum percentage (around 20% of the total consumption). Awareness on world water scarcity, a Colombian company responsible for generation of massive consumption products, decided to implement politics and techniques for water treatment, recycling, and reuse. The project consisted in a business technology program that permits a better use of wastewater caused by production operations. This approach reduces the potable water consumption, generates better conditions of water in the sewage dumps, generates a positive environmental impact for the region, and is a reference model in national and international levels. In order to achieve the objective, a process flow diagram was used in order to define the industrial processes that required potable water. This strategy allowed the industry to determine a water reuse plan at the operational level without affecting the requirements associated with the manufacturing process and even more, to support the activities developed in administrative buildings. Afterwards, the company made an evaluation and selection of the chemical and biological processes required for water reuse, in compliance with the Colombian Law. The implementation of the business technology program optimized the water use and recirculation rate up to 70%, accomplishing an important reduction of the regional environmental impact.

Keywords: bio-reactor, potable water, reverse osmosis, water treatment

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Authors: Keyao Li, Sai On Cheung

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Incorporation of alternative dispute resolution (ADR) mechanism has been the main feature of current trend of construction project dispute resolution (CPDR). ADR approaches have been identified as efficient mechanisms and are suitable alternatives to litigation and arbitration. Moreover, the use of ADR in this multi-tiered dispute resolution process often leads to repeated evaluations of a same dispute. Multi-tiered CPDR may become a breeding ground for cognitive biases. When completed knowledge is not available at the early tier of construction dispute resolution, disputing parties may form preconception of the dispute matter or the counterpart. This preconception would influence their information processing in the subsequent tier. Disputing parties tend to search and interpret further information in a self-defensive way to confirm their early positions. Their imbalanced information collection would boost their confidence in the held assessments. Their attitudes would be hardened and difficult to compromise. The occurrence of cognitive bias, therefore, impedes efficient dispute settlement. This study aims to explore ways to minimize bias in CPDR. Based on a comprehensive literature review, three types of bias minimizing approaches were collected: strategy-based, attitude-based and process-based. These approaches were further operationalized into bias minimizing measures. To verify the usefulness and practicability of these bias minimizing measures, semi-structured interviews were conducted with ten CPDR third party neutral professionals. All of the interviewees have at least twenty years of experience in facilitating settlement of construction dispute. The usefulness, as well as the implications of the bias minimizing measures, were validated and suggested by these experts. There are few studies on cognitive bias in construction management in general and in CPDR in particular. This study would be the first of its type to enhance the efficiency of construction dispute resolution by highlighting strategies to minimize the biases therein.

Keywords: bias, construction project dispute resolution, minimization, multi-tiered, semi-structured interview

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Authors: Camilo A. Guerrero-Martin, Erik Montes Paez, Marcia C. K. Oliveira, Jonathan Campos, Elizabete F. Lucas

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Asphaltenes precipitation is considered as a formation damage problem, which can reduce the oil recovery factor. It fouls piping and surface installations, as well as cause serious flow assurance complications and decline oil well production. Therefore, researchers have shown an interest in chemical treatments to control this phenomenon. The aim of this paper is to assess the asphaltenes precipitation onset of crude oils in the presence of cardanol, by titrating the crude with n-heptane. Moreover, based on this results obtained at atmosphere pressure, the asphaltenes precipitation onset pressure were calculated to predict asphaltenes precipitation in the reservoir, by using differential liberation and refractive index data of the oils. The influence of cardanol concentrations in the asphaltenes stabilization of three Brazilian crude oils samples (with similar API densities) was studied. Therefore, four formulations of cardanol in toluene were prepared: 0, 3, 5, 10 and 15 m/m%. The formulations were added to the crude at 2:98 ratio. The petroleum samples were characterized by API density, elemental analysis and differential liberation test. The asphaltenes precipitation onset (APO) was determined by titrating with n-heptane and monitoring with near-infrared (NIR). UV-Vis spectroscopy experiments were also done to assess the precipitate asphaltenes content. The asphaltenes precipitation envelopes (APE) were also determined by numerical simulation (Multiflash). In addition, the adequate artificial lift systems (ALS) for the oils were selected. It was based on the downhole well profile and a screening methodology. Finally, the oil flowrates were modelling by NODAL analysis production system in the PIPESIM software. The results of this study show that the asphaltenes precipitation onset of the crude oils were 2.2, 2.3 and 6.0 mL of n-heptane/g of oil. The cardanol was an effective inhibitor of asphaltenes precipitation for the crude oils used in this study, since it displaces the precipitation pressure of the oil to lower values. This indicates that cardanol can increase the oil wells productivity.

Keywords: asphaltenes, NODAL analysis production system, precipitation pressure onset, inhibitory molecule

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Authors: Ahmed Bux Jamali

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The purpose of this study is to examine and evaluate the overall counterterrorism cooperation during Obama Administration towards Pakistan. It aims and focuses on the performances and measures taken by United States of America during President Obama in office in order to eradicate terrorism from Pakistan. Being a grave national security threat, terrorism played a disastrous role in the domestic peace and stability of both countries. For the sake of curbing this menace in South Asia in general and Pakistan in particular, the role of Obama Administration is viable and results-oriented despite major ups and downs in Pakistan U.S Relations during that period of time. Obama administration formulated policies when he comes to office in 2009 by looking at the already efforts done by Bush Administration to counterterrorism from Pakistan. Obama’s foreign policy was revolving around defense and diplomacy when it comes to dealing with Pakistan. The concept of smart power was indeed a core principle of Obama’s administration to gain the strategic objectives in Pakistan. Obama’s strategies in terms of providing military aid packages and various assistance programs, working on institutional building and strengthening the economy helped Pakistan in strengthening the military capabilities to go for militant operation in the safe havens area in the tribal areas of Pakistan. It further helped building institutional mechanism in the governmental policies to counter terrorism and militancy. The training of combat forces, artillery, and equipment provided by US proved fatal for the militant terrorist organizations seeking hideouts in the tribal areas of Pakistan. Resultantly, many top leaders of al Qaeda and many affiliated militant groups were captured and given to US as well. Despite many ups and downs in the bilateral relations on various domestic and international issues, both countries didn’t compromise the elimination of terrorist phenomena from Pakistan which was indeed a great success of the Obama administration’s counterterrorism and counterinsurgency strategies in the long run.

Keywords: counterterrorism cooperation, national security strategy, Obama administration, Pakistan-US relations

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Authors: David Ahiamadia, Ramilan Thiagarajah, Peter Tozer

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In Sub Saharan Africa, farm typologies have been used as a practical way to address heterogeneity among farming systems which is mostly done by grouping farms into subsets with similar characteristics. Due to the complexity in farming systems among farm households, it is not possible to formulate policy recommendations for individual farmers. As a result, this study employs a multivariate statistical approach using Principal Component Analysis (PCA) coupled with cluster analysis to reduce heterogeneity in a 615-household data set from the Africa Rising Baseline Evaluation Survey for 25 farming communities in Northern Ghana. Variables selected for the study were mostly socio-economic, production potential, production intensity, production orientation, crop diversity, food security, resource endowments, and climate risk variables. To avoid making some individuals in the subpopulation worse off when aclimate risk intervention is broadly implemented, the findings of the study also account for diversity in climate risk perception among the different farm types identified and their response strategies towards climate risk. The climate risk variables used in this study involve the most severeclimate shock types perceived by the household, household response to climate shock type, and reason for crop failure (i.e., maize, rice, and groundnut). Eventually, four farm types, each with an adequate level of homogeneity in climate risk perception and response strategies, were identified. Farm type 1 and 3 were wealthy with a lower degree of climate risk perception compared to farm type 2 and 4. Also, relatively wealthy farmers used asset liquidation as a climate risk management strategy, whereas poor farmers resorted to engaging in spiritual activities such as prayers, sacrifices, and divine consultations.

Keywords: smallholder, households, climate risk, variables, typologies

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Authors: Amir Sattari, Mac Panah, Naeim Rashidfarokhi

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To enhance the mixing of fluid in a rectangular enclosure with a circular inlet and outlet, an energy-efficient approach is further investigated through computational fluid dynamics (CFD). Particle image velocimetry (PIV) measurements help confirm that the pulsation of the inflow velocity improves the mixing performance inside the enclosure considerably without increasing energy consumption. In this study, multiple CFD simulations with different turbulent models were performed. The results obtained were compared with experimental PIV results. This study investigates small-scale representations of flow patterns in a ventilated rectangular room. The objective is to validate the concept of an energy-efficient ventilation strategy with improved thermal comfort and reduction of stagnant air inside the room. Experimental and simulated results confirm that through pulsation of the inflow velocity, strong secondary vortices are generated downstream of the entrance wall-jet. The pulsatile inflow profile promotes a periodic generation of vortices with stronger eddies despite a relatively low inlet velocity, which leads to a larger boundary layer with increased kinetic energy in the occupied zone. A real-scale study was not conducted; however, it can be concluded that a constant velocity inflow profile can be replaced with a lower pulsated flow rate profile while preserving the mixing efficiency. Among the turbulent CFD models demonstrated in this study, SST-kω is most advantageous, exhibiting a similar global airflow pattern as in the experiments. The detailed near-wall velocity profile is utilized to identify the wall-jet instabilities that consist of mixing and boundary layers. The SAS method was later applied to predict the turbulent parameters in the center of the domain. In both cases, the predictions are in good agreement with the measured results.

Keywords: CFD, PIV, pulsatile inflow, ventilation, wall-jet

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Authors: Nitin Kumar

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Purpose: The current research work focuses mainly on evolving a delivery system for ginseng extract (GE), which in turn will ameliorate the neuroprotective potential by means of enhancing the ginsenoside (Rb1) bio-availability (BA). For more noteworthy enhancement in oral bioavailability (OBA) along with pharmacological properties, the drug carriers’ performance can be strengthened by utilizing phytosomes-loaded microspheres (PM) delivery system. Methods: For preparing the disparate phytosome complexes (F1, F2, and F3), an aqueous extract of ginseng roots (GR) along with phospholipids were reacted in disparate ratio. Considering the outcomes, F3 formulation (spray-dried) was chosen for preparing the phytosomes powder (PP), PM, and extract microspheres (EM). PM was made by means of loading of F3 into Gum Arabic (GA) in addition to maltodextrin polymer mixture, whereas EM was prepared by means of the addition of extract directly into the same polymer mixture. For investigating the neuroprotective effect (NPE) in addition to their pharmacokinetic (PK) properties, PP, PM, and EM formulations were assessed. Results: F3 formulation gave enhanced entrapment efficiency (EE) (i.e., 50.61%) along with good homogeneity of spherical shaped particle size (PS) (42.58 ± 1.4 nm) with least polydispersity index (PDI) (i.e., 0.193 ± 0.01). The sustained release (up to 24 h) of ginsenoside Rb1 (GRb1) is revealed by the dissolution study of PM. A significantly (p < 0.05) greater anti-oxidant (AO) potential of PM can well be perceived as of the diminution in the lipid peroxidase level in addition to the rise in the glutathione superoxide dismutase (SOD) in addition to catalase levels. It also showed a greater neuroprotective potential exhibiting significant (p < 0.05) augmentation in the nociceptive threshold together with the diminution in damage to nerves. A noteworthy enhancement in the relative BA (157.94%) of GRb1 through the PM formulation can well be seen in the PK studies. Conclusion: It is exhibited that the PM system is an optimistic and feasible strategy to enhance the delivery of GE for the effectual treatment of neuropathic pain.

Keywords: ginseng, neuropathic, phytosome, pain

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Authors: Achraf Al Faraj, Asma Sultana Shaik, Baraa Al Sayed

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Specific and effective targeting of drug delivery systems (DDS) to cancerous sites remains a major challenge for a better diagnostic and therapy. Recently, SWCNTs with their unique physicochemical properties and the ability to cross the cell membrane show promising in the biomedical field. The purpose of this study was first to develop a biocompatible iron oxide tagged SWCNTs as diagnostic nanoprobes to allow their noninvasive detection using MRI and their preferential targeting in a breast cancer murine model by placing an optimized flexible magnet over the tumor site. Magnetic targeting was associated to specific antibody-conjugated SWCNTs active targeting. The therapeutic efficacy of doxorubicin-conjugated SWCNTs was assessed, and the superiority of diffusion-weighted (DW-) MRI as sensitive imaging biomarker was investigated. Short Polyvinylpyrrolidone (PVP) stabilized water soluble SWCNTs were first developed, tagged with iron oxide nanoparticles and conjugated with Endoglin/CD105 monoclonal antibodies. They were then conjugated with doxorubicin drugs. SWCNTs conjugates were extensively characterized using TEM, UV-Vis spectrophotometer, dynamic light scattering (DLS) zeta potential analysis and electron spin resonance (ESR) spectroscopy. Their MR relaxivities (i.e. r1 and r2*) were measured at 4.7T and their iron content and metal impurities quantified using ICP-MS. SWCNTs biocompatibility and drug efficacy were then evaluated both in vitro and in vivo using a set of immunological assays. Luciferase enhanced bioluminescence 4T1 mouse mammary tumor cells (4T1-Luc2) were injected into the right inguinal mammary fat pad of Balb/c mice. Tumor bearing mice received either free doxorubicin (DOX) drug or SWCNTs with or without either DOX or iron oxide nanoparticles. A multi-pole 10x10mm high-energy flexible magnet was maintained over the tumor site during 2 hours post-injections and their properties and polarity were optimized to allow enhanced magnetic targeting of SWCNTs toward the primary tumor site. Tumor volume was quantified during the follow-up investigation study using a fast spin echo MRI sequence. In order to detect the homing of SWCNTs to the main tumor site, susceptibility-weighted multi-gradient echo (MGE) sequence was used to generate T2* maps. Apparent diffusion coefficient (ADC) measurements were also performed as a sensitive imaging biomarker providing early and better assessment of disease treatment. At several times post-SWCNT injection, histological analysis were performed on tumor extracts and iron-loaded SWCNT were quantified using ICP-MS in tumor sites, liver, spleen, kidneys, and lung. The optimized multi-poles magnet revealed an enhanced targeting of magnetic SWCNTs to the primary tumor site, which was found to be much higher than the active targeting achieved using antibody-conjugated SWCNTs. Iron-loading allowed their sensitive noninvasive tracking after intravenous administration using MRI. The active targeting of doxorubicin through magnetic antibody-conjugated SWCNTs nanoprobes was found to considerably decrease the primary tumor site and may have inhibited the development of metastasis in the tumor-bearing mice lung. ADC measurements in DW-MRI were found to significantly increase in a time-dependent manner after the injection of DOX-conjugated SWCNTs complexes.

Keywords: single-walled carbon nanotubes, nanomedicine, magnetic resonance imaging, cancer diagnosis and therapy

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