Search results for: 2006 inflation targeting regime

Authors: Brigitta Bodnár, Lajos Kovács, Zoltán Kupihár

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The cancer cells require higher amount of nucleoside building blocks for their proliferation, therefore they have significantly higher uptake of nucleosides by the different nucleoside transporters. Therefore, the conjugation with nucleosides may significantly increase the efficiency and selectivity of potential active pharmaceutical ingredients. On the other hand, the advantage of using a nucleoside could be either the higher activity on targeted enzymes overrepresented in cancer cells or an enhanced cellular uptake of the bioconjugates in these cells compared to the healthy ones. This fact can be used to make the nucleosides, as targeting moieties covalently bound to anti-cancer drug molecules which can selectively accumulate in cancer cells. However, in order to form the nucleoside-drug conjugates, such nucleoside building blocks are needed, which can selectively be coupled to the drug molecules containing even a high number of diverse functional groups. One of the most selective conjugation techniques is the copper-catalyzed azide-alkyne click reaction that requires the presence of an alkyl group on one of the conjugated molecules and an azide group on the other. In case of nucleosides, the development of azide group is simpler for which the replacement of the 5'-hydroxy group is the most suitable. This transformation generally involves many side reactions and result in very low yields. In addition, during our experiments, the transformation of the 2'-deoxyguanosine to the corresponding 5'-deoxy-5’-azido-2’-deoxyguanosine could not be performed with any of the methods described in the literature. Therefore, we have tried to overcome these difficulties with not only using the traditional process based on the 2 step exchange of tosyl to azide, but also using the Mitsunobu reaction which requires only one step. However, this path proved to be unsuccessful in spite of the optimizing the reaction conditions. Finally, a method has been developed whereby the azide groups were incorporated into the 5’-position resulting in significantly better yields compared to all other previous methods, and we were able to produce all the four nucleoside derivatives.

Keywords: 5'-azidonucleosides, bioconjugate, click reaction, proliferation

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Authors: Abul B. M. M. K. Islam, Mandar Dave, Roderick V. Jensen, Ashok R. Amin

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A systems approach was applied to characterize differentially expressed transcripts, bioinformatics pathways, and proteins and prostaglandins (PGs) from lung fibroblasts procured from wild-type (WT), COX-1-/- and COX-2-/- mice to understand system level control mechanism. Bioinformatics analysis of COX-2 and COX-1 ablated cells induced COX-1 and COX-2 specific signature respectively, which significantly overlapped with an 'IL-1β induced inflammatory signature'. This defined novel cross-talk signals that orchestrated coordinated activation of pathways of sterile inflammation sensed by cellular stress. The overlapping signals showed significant over-representation of shared pathways for interferon y and immune responses, T cell functions, NOD, and toll-like receptor signaling. Gene Ontology Biological Process (GOBP) and pathway enrichment analysis specifically showed an increase in mRNA expression associated with: (a) organ development and homeostasis in COX-1-/- cells and (b) oxidative stress and response, spliceosomes and proteasomes activity, mTOR and p53 signaling in COX-2-/- cells. COX-1 and COX-2 showed signs of functional pathways committed to cell cycle and DNA replication at the genomics level. As compared to WT, metabolomics analysis revealed a significant increase in COX-1 mRNA and synthesis of basal levels of eicosanoids (PGE2, PGD2, TXB2, LTB4, PGF1α, and PGF2α) in COX-2 ablated cells and increase in synthesis of PGE2, and PGF1α in COX-1 null cells. There was a compensation of PGE2 and PGF1α in COX-1-/- and COX-2-/- cells. Collectively, these results support a broader, differential and collaborative regulation of both COX-1 and COX-2 pathways at the metabolic, signaling, and genomics levels in cellular homeostasis and sterile inflammation induced by cellular stress.

Keywords: cyclooxygenases, inflammation, lung fibroblasts, systemic

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Authors: Gurbanova Lamiya

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The Republic of Azerbaijan is considered a region with limited water resources, as up to 70% of surface water is formed outside the country's borders, and most of its territory is an arid (dry) climate zone. It is located at the lower limit of transboundary flows, which is the weakest source of natural water resources in the South Caucasus. It is essential to correctly assess the quality of natural, collector-drainage and groundwater of the area and their suitability for irrigation in order to properly carry out land reclamation measures, provide the normal water-salt regime, and prevent repeated salinization. Through the 141-km-long main Mil-Mugan collector, groundwater, household waste, and floodwaters generated during floods and landslides are poured into the Caspian Sea. The hydrochemical composition of the samples taken from the Sabir irrigation canal passing through the center of the Kura-Araz plain, the Main Mil-Mugan Collector, and the groundwater of the region, which we chose as our research object, were studied and the obtained results were compared by periods. A model is proposed that allows for a complete visualization of the primary materials collected for the study area. The practical use of the established digital model provides all possibilities. The practical use of the established digital model provides all possibilities. An extensive database was created with the ArcGis 10.8 package, using publicly available LandSat satellite images as primary data in addition to ground surveys to build the model. The principles of the construction of the geographic information system of modern GIS technology were developed, the boundary and initial condition of the research area were evaluated, and forecasts and recommendations were given.

Keywords: irrigation channel, groundwater, collector, meliorative measures

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Authors: Jiarong Zhang

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Digitizing intangible cultural heritage is a complex and comprehensive process from which sorts of intellectual property rights may be generated. Digitizing may be a repacking process of cultural heritage, which creates copyrights; recording folk songs and indigenous performances can create 'related rights'. At the same time, digitizing intangible cultural heritage may infringe the intellectual property rights of others unintentionally. Recording religious rituals of indigenous communities without authorization can violate the moral right of the ceremony participants of the community; making digital copies of rock paintings may infringe the right of reproduction. In addition, several parties are involved in the digitization process: indigenous peoples, museums, and archives can be holders of cultural heritage; companies and research institutions can be technology providers; internet platforms can be promoters and sellers; the public and groups above can be beneficiaries. When diverse intellectual property rights versus various parties, problems and disputes can arise easily. What are the types of intellectual property rights generated in the digitization process? What is the essence of these rights? Who should these rights belong to? How to use intellectual property to protect the digitalization of cultural heritage? How to avoid infringing on the intellectual property rights of others? While the digitization has been regarded as an effective approach to preserve intangible cultural heritage, related intellectual property issues have not received the attention and full discussion. Thus, parties involving in the digitization process may face intellectual property infringement lawsuits. The article will explore those problems from the intersection perspective of intellectual property law and cultural heritage. From a comparative approach, the paper will analysis related legal documents and cases, and shed some lights of those questions listed. The findings show, although there are no intellectual property laws targeting the cultural heritage in most countries, the involved stakeholders can seek protection from existing intellectual property rights following the suggestions of the article. The research will contribute to the digitization of intangible cultural heritage from a legal and policy aspect.

Keywords: copyright, digitization, intangible cultural heritage, intellectual property, Internet platforms

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Authors: Okuyade Ighoroje Wilson Ata

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Magneto-hydrodynamic mixed convective chemically reacting fluid flow through two parallel vertical plates channel with Hall, radiation, and chemical reaction effects are examined. The fluid is assumed to be chemically reactive, electrically conducting, magnetically susceptible, viscous, incompressible, and Newtonian; the plates are porous, electrically conductive, and heated to a high-temperature regime to generate thermal rays. The flow system is highly interactive, such that cross/double diffusion is present. The governing equations are partial differential equations transformed into ordinary differential equations using similarity transformation and solved by the method of Homotopy Perturbation. Expressions for the concentration, temperature, velocity, Nusselt number, Sherwood number, and Wall shear stress are obtained, computed, and presented graphically and tabularly. The analysis of results shows, amongst others, that an increase in the Raleigh number increases the main velocity and temperature but decreases the concentration. More so, an increase in chemical reaction rate increases the main velocity, temperature, rate of heat transfer from the terminal plate, the rate of mass transfer from the induced plate, and Wall shear stress on both the induced and terminal plates, decreasing the concentration, and the mass transfer rate from the terminal plate. Some of the obtained results are benchmarked with those of existing literature and are in consonance.

Keywords: chemical reaction, hall effect, magneto-hydrodynamic, radiation, vertical plates channel

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Authors: Shasline Gedeon, Tiffany W. Ardley, Ying Wang, Nathan J. Gesmundo, Katarina A. Sarris, Ana L. Aguirre

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Drug discovery and delivery involve drug targeting, an approach that helps find a drug against a chosen target through high throughput screening and other methods by way of identifying the physical properties of the potential lead compound. Physical properties of potential drug candidates have been an imperative focus since the unveiling of Lipinski's Rule of 5 for oral drugs. Throughout a compound's journey from discovery, clinical phase trials, then becoming a classified drug on the market, the desirable properties are optimized while minimizing/eliminating toxicity and undesirable properties. In the pharmaceutical industry, the ability to generate molecules in parallel with maximum efficiency is a substantial factor achieved through sp²-sp² carbon coupling reactions, e.g., Suzuki Coupling reactions. These reaction types allow for the increase of aromatic fragments onto a compound. More recent literature has found benefits to decreasing aromaticity, calling for more sp³-sp² carbon coupling reactions instead. The objective of this project is to provide a comparison between various sp³-sp² carbon coupling methods and reaction conditions, collecting data on production of the desired product. There were four different coupling methods being tested amongst three cores and 4-5 installation groups per method; each method ran under three distinct reaction conditions. The tested methods include the Photoredox Decarboxylative Coupling, the Photoredox Potassium Alkyl Trifluoroborate (BF3K) Coupling, the Photoredox Cross-Electrophile (PCE) Coupling, and the Weix Cross-Electrophile (WCE) Coupling. The results concluded that the Decarboxylative method was very difficult in yielding product despite the several literature conditions chosen. The BF3K and PCE methods produced competitive results. Amongst the two Cross-Electrophile coupling methods, the Photoredox method surpassed the Weix method on numerous accounts. The results will be used to build future libraries.

Keywords: drug discovery, high throughput chemistry, photoredox chemistry, sp³-sp² carbon coupling methods

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Authors: Manon Giraud, Francois-Damien Delapierre, Guenaelle Jasmin-Lebras, Cecile Feraudet-Tarisse, Stephanie Simon, Claude Fermon

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Early diagnosis or detection of harmful substances at low level is a growing field of high interest. The ideal test should be cheap, easy to use, quick, reliable, specific, and with very low detection limit. Combining the high specificity of antibodies-functionalized magnetic beads used to immune-capture biologic objects and the high sensitivity of a GMR-based sensors, it is possible to even detect these biologic objects one by one, such as a cancerous cell, a bacteria or a disease biomarker. The simplicity of the detection process makes its use possible even for untrained staff. Giant Magneto Resistance (GMR) is a recently discovered effect consisting in the electrical resistance modification of some conductive layers when exposed to a magnetic field. This effect allows the detection of very low variations of magnetic field (typically a few tens of nanoTesla). Magnetic nanobeads coated with antibodies targeting the analytes are mixed with a biological sample (blood, saliva) and incubated for 45 min. Then the mixture is injected in a very simple microfluidic chip and circulates above a GMR sensor that detects changes in the surrounding magnetic field. Magnetic particles do not create a field sufficient to be detected. Therefore, only the biological objects surrounded by several antibodies-functionalized magnetic beads (that have been captured by the complementary antigens) are detected when they move above the sensor. Proof of concept has been carried out on NS1 mouse cancerous cells diluted in PBS which have been bonded to magnetic 200nm particles. Signals were detected in cells-containing samples while none were recorded for negative controls. Binary response was hence assessed for this first biological model. The precise quantification of the analytes and its detection in highly diluted solution is the step now in progress.

Keywords: early diagnosis, giant magnetoresistance, lab-on-a-chip, submicron particle

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Authors: Patrice Conner

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Nanotechnologies have enormous potential to contribute to human flourishing in responsible and sustainable ways. They are rapidly developing field of science, technology and innovation. As enabling technologies, their full scope of applications is potentially very wide. Major implications are expected in many areas, e.g. healthcare, information and communication technologies, energy production and storage, materials science/chemical engineering, manufacturing, environmental protection, consumer products, etc. However, nanotechnologies are unlikely to realize their full potential unless their associated societal and ethical issues are adequately attended. Namely nanotechnologies and nanoparticles may expose humans and the environment to new health risks, possibly involving quite different mechanisms of interference with the physiology of human and environmental species. One of the building blocks of the ‘safe, integrated and responsible’ approach is standardization. Both the Economic and Social Committee and the European Parliament have highlighted the importance to be attached to standardization as a means to accompany the introduction on the market of nanotechnologies and nanomaterials, and a means to facilitate the implementation of regulation. ISO and CEN have respectively started in 2005 and 2006 to deal with selected topics related to this emerging and enabling technology. In the beginning of 2010, EC DG ‘Enterprise and Industry’ addressed the mandate M/461 to CEN, CENELEC and ETSI for standardization activities regarding nanotechnologies and nanomaterials. Thus CEN/TC 352 ‘Nanotechnologies’ has been asked to take the leadership for the coordination in the execution of M/461 (46 topics to be standardized) and to contact relevant European and International Technical committees and interested stakeholders as appropriate (56 structures have been identified). Prior requests from M/461 deal with characterization and exposure of nanomaterials and any matters related to Health, Safety and Environment. Answers will be given to: - What are the structures and how they work? - Where are we right now and how work is going from now onwards? - How CEN’s work and targets deal with and interact with global matters in this field?

Keywords: characterization, environmental protection, exposure, health risks, nanotechnologies, responsible and sustainable ways, safety

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Authors: Corlia van der Walt, Michele K. Havenga

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The study considers corporate governance regulation and practice in South African higher education institutions and makes recommendations for the improvement of current governance practices in this sector. The development of corporate governance principles and practices in South Africa, culminating in the King IV Report on Corporate Governance which was launched in November 2016, is discussed. King IV enjoys international recognition as a progressive corporate governance instrument. It was necessitated by the fundamental changes in business and society nationally and globally, as well as by the significant changes to South African company law introduced by new legislation. Corporate governance and the corporate form are narrowly associated, but there is general recognition that the principles of ethical and effective leadership are not restricted to corporations. Thus King IV was drafted with the express aim that it should apply to all organisations, regardless of their form of incorporation, and the report includes specific sector supplements in support of this aspiration. The South African higher education sector has of late been under intense scrutiny, and a few universities have been placed under administration because of poor governance practices. Universities have also been severely impacted by the consequences of what is generally known as ‘#FeesmustFall’, a student led protest movement initially aimed against the increase of fees at public universities, but which rapidly expanded to also include other concerns. It was clearly necessary to revisit corporate governance policy and practice in the sector. The review of the current higher education governance regime in light of the King IV recommendations, lessons from company law regarding the entrenchment and enforcement of corporate governance principles, and a comparison of higher education governance practices in selected other jurisdictions led to recommendations for the improvement of governance practices in South African higher education. It is further suggested that a sector supplement for higher education institutions may provide additional clarity. Some of the recommendations may be of comparative value for international higher education governance.

Keywords: committees, corporate governance, ethical leadership, higher education institutions, integrated reporting, King IV, sector supplements, sustainability

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Authors: Zhipeng Yan, Janice Wing-Tung Kwong, Ching-Lung Lai

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Background: Advanced melanoma accounts for the majority of skin cancer death due to its poor prognosis. Nivolumab and ipilimumab are monoclonal antibodies targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocytes antigen 4 (CTLA-4). Nivolumab and ipilimumab combination therapy has been proven to be effective for advanced melanoma. This systematic review and meta-analysis are to evaluate its clinical efficacy and adverse events. Method: A systematic search was done on databases (Pubmed, Embase, Medline, Cochrane) on 21 June 2020. Search keywords were nivolumab, ipilimumab, melanoma, and randomised controlled trials. Clinical trials fulfilling the inclusion criteria were selected to evaluate the efficacy of combination therapy in terms of prolongation of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The odd ratios and distributions of grade 3 or above adverse events were documented. Subgroup analysis was performed based on PD-L1 expression-status and BRAF-mutation status. Results: Compared with nivolumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR in combination therapy were 0.64 (95% CI, 0.48-0.85; p=0.002), 0.84 (95% CI, 0.74-0.95; p=0.007) and 1.76 (95% CI, 1.51-2.06; p < 0.001), respectively. Compared with ipilimumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR were 0.46 (95% CI, 0.37-0.57; p < 0.001), 0.54 (95% CI, 0.48-0.61; p < 0.001) and 6.18 (95% CI, 5.19-7.36; p < 0.001), respectively. In combination therapy, the odds ratios of grade 3 or above adverse events were 4.71 (95% CI, 3.57-6.22; p < 0.001) compared with nivolumab monotherapy, and 3.44 (95% CI, 2.49-4.74; p < 0.001) compared with ipilimumab monotherapy, respectively. High PD-L1 expression level and BRAF mutation were associated with better clinical outcomes in patients receiving combination therapy. Conclusion: Combination therapy is effective for the treatment of advanced melanoma. Adverse events were common but manageable. Better clinical outcomes were observed in patients with high PD-L1 expression levels and positive BRAF-mutation.

Keywords: nivolumab, ipilimumab, advanced melanoma, systematic review, meta-analysis

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Authors: Hala M. El-hanbuli, Mohammed F. Darweesh

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The incidence rates of any tumor vary hugely with geographical location. Basal Cell Carcinoma (BCC) is one of the most common skin cancer that has many histopathologic subtypes. Objective: The aim was to study the histopathological features of BCC cases that were received in the Pathology Department, Kasr El-Aini hospital, Cairo University, Egypt during the period from Jan 2004 to Dec 2013 and to evaluate the clinical characters through the patient data available in the request sheets. Methods: Slides and data of BCC cases were collected from the archives of the pathology department, Kasr El-Aini hospital. Revision of all available slides and histological classification of BCC according to WHO (2006) was done. Results: A total number of 310 cases of BCC representing about 65% from the total number of malignant skin tumors examined during the 10-years duration in the department. The age ranged from 8 to 84 years, the mean age was (55.7 ± 15.5). Most of the patients (85%) were above the age of 40 years. There was a slight male predominance (55%). Ulcerated BCC was the most common gross picture (60%), followed by nodular lesion (30%) and finally the ulcerated nodule (10%). Most of the lesions situated in the high-risk sites (77%) where the nose was the most common site (35%) followed by the periocular area (22%), then periauricular (15%) and finally perioral (5%). No lesion was reported outside the head. The tumor size was less than 2 centimeters in 65% of cases, and from 2-5 centimeters in the lesions' greatest dimension in the rest of cases. Histopathological reclassification revealed that the nodular BCC was the most common (68%) followed by the pigmented nodular (18.75%). The histologic high-risk groups represented (7.5%) about half of them (3.75%) being basosquamous carcinoma. The total incidence for multiple BCC and 2nd primary was 12%. Recurrent BCC represented 8%. All of the recurrent lesions of BCC belonged to the histologic high-risk group. Conclusion: Basal Cell Carcinoma is the most common skin cancer in the 10-year survey. Histopathological diagnosis and classification of BCC cases are essential for the determination of the tumor type and its biological behavior.

Keywords: basal cell carcinoma, high risk, histopathological features, statistical analysis

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Authors: Bengan Simbarashe Manwere

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The entire African continent, comprising 55 countries, holds a 2% share of the global carbon market. The World Bank attributes the continent’s insignificant share and participation in the carbon market to the limited access to electricity. Approximately 800 million people spread across 47 African countries generate as much power as Spain, with a population of 45million. Only South Africa and North Africa have carbon-reduction investment opportunities on the continent and dominate the 2% market share of the global carbon market. On the back of the 2015 Paris Agreement, South Africa signed into law the Carbon Tax Act 15 of 2019 and the Customs and Excise Amendment Act 13 of 2019 (Gazette No. 4280) on 1 June 2019. By these laws, South Africa was ushered into the league of active global carbon market players. By increasing the cost of production by the rate of R120/tCO2e, the tax intentionally compels the internalization of pollution as a cost of production and, relatedly, stimulate investment in clean technologies. The first phase covered the 1 June 2019 – 31 December 2022 period during which the tax was meant to escalate at CPI + 2% for Scope 1 emitters. However, in the second phase, which stretches from 2023 to 2030, the tax will escalate at the inflation rate only as measured by the consumer price index (CPI). The Carbon Tax Act provides for carbon allowances as mitigation strategies to limit agents’ carbon tax liability by up to 95% for fugitive and process emissions. Although the June 2019 Carbon Tax Act explicitly makes provision for a carbon trading scheme (CTS), the carbon trading regulations thereof were only finalised in December 2020. This points to a delay in the establishment of a carbon trading scheme (CTS). Relatedly, emitters in South Africa are not able to benefit from the 95% reduction in effective carbon tax rate from R120/tCO2e to R6/tCO2e as the Johannesburg Stock Exchange (JSE) has not yet finalized the establishment of the market for trading carbon credits. Whereas most carbon trading schemes have been designed and constructed from the beginning as new tailor-made systems in countries the likes of France, Australia, Romania which treat carbon as a financial product, South Africa intends, on the contrary, to leverage existing trading infrastructure of the Johannesburg Stock Exchange (JSE) and the Clearing and Settlement platforms of Strate, among others, in the interest of the Paris Agreement timelines. Therefore the carbon trading scheme will not be constructed from scratch. At the same time, carbon will be treated as a commodity in order to align with the existing institutional and infrastructural capacity. This explains why the Carbon Tax Act is silent about the involvement of the Financial Sector Conduct Authority (FSCA).For South Africa, there is need to establish they equilibrium stability of the CTS. This is important as South Africa is an innovator in carbon trading and the successful trading of carbon credits on the JSE will lead to imitation by early adopters first, followed by the middle majority thereafter.

Keywords: carbon trading scheme (CTS), Johannesburg stock exchange (JSE), carbon tax act 15 of 2019, South Africa

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Authors: M. G. Murtaza, E. E. Tzirtzilakis, M. Ferdows

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Biomagnetic fluid dynamics is an interdisciplinary field comprising engineering, medicine, and biology. Bio fluid dynamics is directed towards finding and developing the solutions to some of the human body related diseases and disorders. This article describes the flow and heat transfer of two dimensional, steady, laminar, viscous and incompressible biomagnetic fluid over a non-linear stretching sheet in the presence of magnetic dipole. Our model is consistent with blood fluid namely biomagnetic fluid dynamics (BFD). This model based on the principles of ferrohydrodynamic (FHD). The temperature at the stretching surface is assumed to follow a power law variation, and stretching velocity is assumed to have a nonlinear form with signum function or sign function. The governing boundary layer equations with boundary conditions are simplified to couple higher order equations using usual transformations. Numerical solutions for the governing momentum and energy equations are obtained by efficient numerical techniques based on the common finite difference method with central differencing, on a tridiagonal matrix manipulation and on an iterative procedure. Computations are performed for a wide range of the governing parameters such as magnetic field parameter, power law exponent temperature parameter, and other involved parameters and the effect of these parameters on the velocity and temperature field is presented. It is observed that for different values of the magnetic parameter, the velocity distribution decreases while temperature distribution increases. Besides, the finite difference solutions results for skin-friction coefficient and rate of heat transfer are discussed. This study will have an important bearing on a high targeting efficiency, a high magnetic field is required in the targeted body compartment.

Keywords: biomagnetic fluid, FHD, MHD, nonlinear stretching sheet

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Authors: Alessandro Suardi, Rodolfo Picchio, Domenico Coaloa, Maria Bonaventura Forleo, Nadia Palmieri, Luigi Pari

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The reconversion process of the Italian sugar supply chain to bio-energy supply chains, as a result of the 2006 Sugar CMO reform, have involved research to define the best logistics, the most adapted energy crops for the Italian territory and their sustainability. Rapeseed (Brassica napus L.), Giant reed (Arundo donax L.) and Poplar (Poplar ssp.) are energy crops considered strategic for the development of Italian energy supply-chains. This study analyzed the environmental and the economic impacts on the farm level of these three energy crops. The environmental assessment included six farming units, two per crop, which were extracted from a sample of 251 rapeseed farm units (2751 ha), 7 giant reed farm units (7.8 ha), and 91 poplar farm units (440 ha) using a statistical multivariate analysis. Life Cycle Assessment (LCA) research method has been used to evaluate and compare the sustainability of the agricultural phases of the crops studied. The impact analyses have been performed at mid-point and end-point levels. The results of the analysis shown that the fertilization, is the major source of environmental impact of the agricultural phase due to the production of the fertilizers and the soil emissions of GHG following the treatment. The perennial energy crops studied (Arundo donax L., Poplar ssp.) were environmentally more sustainable if compared with the annual crop (Brassica napus L.) for all the impact categories at mid-point and end-point levels analyzed. The most relevant impact category influenced by the agricultural process result the fossil depletion, mainly due to the fossil fuels consumed during the mineral fertilizers production (urea). Human health was the most affected damage category at the end point level. Poplar result the energy crop with the best environmental performance for the Italian territory, in the distribution areas most suitable for its cultivation.

Keywords: LCA, energy crops, rapeseed, giant reed, poplar

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Authors: Tissa Ravinda Perera

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An open economic policy was introduced by Sri Lanka in 1977, before many other countries in Asia to align her economy to world economic trends and it was affected indigenous businesses since they had to compete with foreign products, processes, technology, innovations and businesses. The year 2010 was a milestone in Sri Lankan history to achieve the developmental goals when Foxbuisness rated Sri Lanka as the best performing global economy. However, Sri Lanka missed her chances of achieving development with the political and social chaos, consequent the regime change in 2015. This paper argues that to support the development of the country, Sri Lanka must develop an entrepreneurial culture. In this endeavor, creativity and innovation will play a pivotal role to achieve the desired level of development. In this study, it was used secondary data from various local and international sources to understand and explore the existing scenario of Sri Lankan economy, state of entrepreneurial culture and innovation, and challenges and competencies for the development of an entrepreneurial culture in Sri Lanka. The data was collected from secondary sources were depicted in tables in this paper in a meaningful manner. Based on the tables many findings were aroused and conclusions were made to support the argument in this paper. This paper revealed that the development of an entrepreneurial culture has to be associated with creativity and innovation to gain a competitive advantage over the development strategies of other countries. It is exposed that an entrepreneurial culture will help minorities, women and underprivileged societies to empower themselves. This product will help to confront and manage youth unrest which has created anarchy in the country from time to time. Throughout this paper, it was highlighted the past, present and future scenario of Sri Lankan economy along with modification to be done to it through the development of an entrepreneur culture in light of innovation and creativity to achieve the desired level of development.

Keywords: economy, industry, creativity, innovation, entrepreneurship, entrepreneurial culture

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Authors: Khawaja A. Wahaj Wani, Aykut Erkal

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Pakistan's construction industry, a key player in economic development, has experienced remarkable growth. However, the surge in activities has been accompanied by dangerous working conditions, attributed to legislative gaps and flaws. Unhealthy construction practices, uncertain site conditions, and hazardous environments contribute to a concerning rate of injuries and fatalities. The principal aim of this research study is to undertake a thorough evaluation based on the assessment of the current situation of Health & Safety policies and the surveys performed by stakeholders of Pakistan with the aim of providing solution-centric methodologies for the enforcement of health and safety regulations within construction companies operating on project sites. Recognizing the pivotal role that the construction industry plays in bolstering a nation's economy, it is imperative to address the pressing need for heightened awareness among site engineers and laborers. The study adopts a robust approach, utilizing questionnaire surveys and interviews. As an exclusive investigative study, it encompasses all stakeholders: clients, consultants, contractors, and subcontractors. Targeting PEC-registered companies. Safety performance was assessed through the examination of sixty safety procedures using SPSS-18. A high Cronbach's alpha value of 0.958 ensures data reliability, and non-parametric tests were employed due to the non-normal distribution of data. The safety performance evaluation revealed significant insights. "Using Hoists and Cranes" and "Precautionary Measures (Shoring and Excavation)" exhibited commendable safety levels. Conversely, "Trainings on Safety" displayed a lower safety performance, alongside areas such as "Safety in Contract Documentation," "Meetings for Safety," and "Worker Participation," indicating room for improvement. These findings provide stakeholders with a detailed understanding of current safety measures within Pakistan's construction industry.

Keywords: construction industry, health and safety regulations, Pakistan, risk management

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Authors: Mohamed Abdalla Saleem

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Around one hundred wells were drilled in the Cyrenaica platform north-east Libya, and almost all of them were dry. Although the drilled samples reveal good oil shows and good source rock maturity. Most of the upper Cretaceous age and the above deposit successions are outcrops in different places. We have a thorough understanding and mapping of the structures related to the Cretaceous and above Cenozoic Era. But the subsurface beneath these outcrops still needs more investigation and delineation. This study aims to give answers to some questions about the tectonic history and the types of structures that are distributed in the area using gravity, magnetic, and well data. According to the information that has been obtained from groups of wells drilled in concessions 31, 35, and 37, one can note that the depositional sections become ticker and deeper southward. The topography map of the study area shows that the area is highly elevated at the north, about 300 m above the sea level, while the minimum elevation (16–18 m) exists nearly in the middle (lat. 30°). South to this latitude, the area is started elevated again (more than 100 m). The third-order residual gravity map, which was constructed from the Bouguer gravity map, reveals that the area is dominated by a large negative anomaly working as a sub-basin (245 km x 220 km), which means a very thick depositional section, and the basement is very deep. The mentioned depocenter is surrounded by four high gravity anomalies (12-37 mGal), which means a shallow basement and a relative thinner succession of sediments. The highest gravity values are located beside the coast line. The total horizontal gradient (THG) map reveals various systems of structures, the first system where the structures are oriented NE-SW, which is crosscut by the second regime extending NW-SE. This second system is distributed through the whole area, but it is very strong and shallow near the coast line and at the south part, while it is relatively deep at the middle depocenter area.

Keywords: cyrenaica platform, gravity, structures, basement, tectonic history

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Authors: Eduardo Jorge Cabral dos Santos Fernandes

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Over the last sixty-seven years, Portuguese architect Álvaro Siza Vieira designed several interventions for the Leça da Palmeira waterfront. With this paper, we aim to analyze the history of this set of projects in a chronological approach, seeking to understand the connections that can be established between them. Born in Matosinhos, a fishing and industrial village located near Porto, Álvaro Siza built a remarkable relationship with Leça da Palmeira (a neighboring village located to the north) from a personal and professional point of view throughout his life: it was there that he got married (in the small chapel located next to the Boa Nova lighthouse) and it was there that he designed his first works of great impact, the Boa Nova Tea House and the Ocean Swimming Pool, today classified as national monuments. These two works were the subject of several projects spaced over time, including recent restoration interventions designed by the same author. However, the marks of Siza's intervention in this territory are not limited to these two cases; there were other projects designed for this territory, which we also intend to analyze: the monument to the poet António Nobre (1967-80), the unbuilt project for a restaurant next to Piscina das Marés (presented in 1966 and redesigned in 1993), the reorganization of the Avenida da Liberdade (with a first project, not carried out, in 1965-74, and a reformulation carried out between 1998 and 2006) and, finally, the project for the new APDL facilities, which completes Avenida da Liberdade to the south (1995). Altogether, these interventions are so striking in this territory, from a landscape, formal, functional, and tectonic point of view, that it is difficult to imagine this waterfront without their presence. In all cases, the relationship with the site explains many of the design options. Time after time, the conditions of the pre-existing territory (also affected by the previous interventions of Siza) were considered, so each project created a new circumstance, conditioning the following interventions. This paper is part of a more comprehensive project, which aims to analyze the work of Álvaro Siza in its fundamental relationship with the site.

Keywords: Álvaro Siza, contextualism, Leça da Palmeira, landscape

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Authors: Barry Aifesehi Aiworo, Henry Oriakhi

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This paper, examines the analysis of access pattern to school and travel risks among school children in Benin City, Edo State, Nigeria. The risk includes accident, molestation (sexually) and kidnapping. The objective of this paper are to examine the various means (modes) of transport to school; determine the type and incidences of risk experienced by school children in the study area; examine the risk incidences and ages of school children in the study area. Hypothesis which states that the types of risks encountered by school children are independent of means of transport was tested using the chi-square test (X2). A sampling ratio of twelve percent (12%) was taken from 396 schools in Benin City. By implication, 49 schools were randomly selected in Benin City for this research. A total of 42,053 students in the 49 schools constitute the sample frame for the research. Two percent (2%), 841 students were taken as the sample size. The use of stratified sampling method was applied by stratifying the study area (Benin City) into local governments- Egor, Ikpoba-Okha and Oredo. Thereafter, the lists of schools in the various local governments were obtained from the Ministry of Education before the schools for research were randomly chosen from each local government area. The analysis revealed that 6.7% of the total students interviewed have been involved in road accidents. 1.04% of the total respondents said at one time or the other that they have been kidnapped. Finally, the research found that travel is comparatively safe and believes this may be partly attributable to safer route to schools and school children being more familiar with the school journey. The research indicates that children aged between eleven and fifteen are most at risk of hit or knocked down on Benin City’s roads. These findings may help in planning and targeting road safety initiative (education, campaigns) in Benin City.

Keywords: accident, molestation (sexually), kidnapping, pedophile, pedestrian

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Authors: Rajkumar Ghosh

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Out-of-sequence thrusts (OOST) are reported at different geographic locations with various local names along Siwalik Himalaya (SH), Lesser Himalaya (LH), Higher Himalaya (HH) from Bhutan, India, Nepal, and Pakistan Himalayan range. Most of OOSTs have been identified within the upper LH, and the lower HH based on geochronological age jump across. These thrusts activated from Late Miocene to recent. The Chaura Thrust (CT) was deciphered from age jump of Apatite Fission Track (AFT) and considered as blind thrust base on variable exhumation rates in Chaura region, Satluj river valley, Himachal Pradesh. CT is located north of Jhakri Thrust (JhT) and is also differently identified as Sarahan thrust (ST). Structural documentation from the rocks near the OOST in Chaura was not so far done. Detail structural study of the Jeori Group of rocks was carried out in this study to understand the manifestation of the Chaura thrust and associated structures in meso- to micro-scale. Box fold, scar fold, kink fold, crenulation cleavages, and boudins are developed in the Chaura region. These structures usually do not indicate shear sense. When studied under an optical microscope, the Chaura samples reveal that the mica fish are usually lenticular with aspect ratio (R) varying from 6–11 and inclination angle (α) from 15–40°. According to ‘R’ and ‘α’, elongated sigmoid shaped mica fish and parallelogram shaped mica fish were also documented. Asymmetric mica fish demonstrate top-to-S/SW ductile shear, which is similar as that of Chaura thrust. Grain boundary migration (GBM) structures in quartzo-feldspathic grains from Jeori Group of rocks indicate deformation temperature ranging from 400 to 650°C. This can indicate that the OOST at Chaura, i.e., the Chaura Thrust, underwent thrusting in the ductile regime.

Keywords: out-of-sequence thrust, chaura thrust, sarahan thrust, jakhri thrust, higher himalaya, s/c- fabric

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Authors: Khaled Hesham Hyari, Amjad Almani

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Construction projects in the public sector are commonly awarded through competitive bidding. In the last decade, the Construction projects environment in the Middle East went through many changes. These changes have been caused by different factors including the economic crisis, delays in monthly payments, international competition and reduced number of projects. These factors had a great impact on the bidding behaviors of contractors and their pricing strategies. This paper examines the competition characteristics in public construction projects through an analysis of bidding results of contractors in public construction projects over a period of 6 years (2006-2011) in Jordan. The analyzed projects include all categories of projects such as infrastructure, buildings, transportation and engineering services (design and supervision contracts). Data for the projects were obtained from the General Tender’s Directorate in Jordan and includes 462 projects. The analysis performed in this projects includes, studying the bid spread in all projects as it is an indication of the level of competition in the analyzed bids. The analysis studied the factors that affect bid spread such as number of bidders, Value of the project, Project category and years. It also studying the “Signal to Noise Ratio” in all projects as it is an indication of the accuracy of cost estimating performed by competing bidders and bidder´s evaluation of project risks. The analysis performed includes the relationship between signal to noise ratio and different parameters such as project category, number of bidders and changes over years. Moreover, the analysis includes determining the bidder´s aggressiveness in bidding as it is an indication of competition level in such projects. This was performed by determining the pack price which can be considered as the true value of the project and comparing it with the lowest bid submitted for each project to determine the level of aggressiveness in submitted bids. The analysis performed in this project should prove to be useful to owners in understanding bidding behaviors of contractors and pointing out areas that needs improvement in preparing bidding documents. Also the project should be useful to contractors in understanding the competitive bidding environment and should help them to improve their bidding strategies to maximize the success rate in obtaining contracts.

Keywords: construction projects, competitive bidding, public construction, competition

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Authors: Ricardo Pinto Mario Covele, Patricio V. Langa, Patrick Swanzy

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The English language has been recognized as a universal medium of instruction in academia, especially in Higher Education Institutions (HEIs) hence exerting enormous influence within the context of research and publication. By extension, the English Language has been embraced by scholars from non-English speaking countries. The purpose of this review was to synthesize the discussions using four databases. Discussion in the English language in the career development of academics, particularly in non-English speaking universities, is largely less visible. This paper seeks to fill this gap and to improve the visibility of the English language in the career development of academics focusing on non-English language speaking universities by undertaking a systematic literature review. More specifically, the paper addresses the language policy, English language learning model as a second language, sociolinguistic field and career development, methods, as well as its main findings. This review analyzed 75 relevant resources sourced from Western Cape’s Library, Scopus, Google scholar, and web of science databases from November 2020 to July 2021 using the PQRS framework as an analytical lens. The paper’s findings demonstrate that, while higher education continues to be under-challenges of English language usage, literature targeting non-English speaking universities remains less discussed than it is often described. The findings also demonstrate the dominance of English language policy, both for knowledge production and dissemination of literature challenging emerging scholars from non-English speaking HEIs. Hence, the paper argues for the need to reconsider the context of non-English language speakers in the English language in the career development of academics’ research, both as empirical fields and as emerging knowledge producers. More importantly, the study reveals two bodies of literature: (1) the instrumentalist approach to English Language learning and (2) Intercultural approach to the English Language for career opportunities, classified as the appropriate to explain the English language learning process and how is it perceived towards scholars’ academic careers in HEIs.

Keywords: English language, public and private universities, language policy, career development, non-English speaking countries

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Authors: Mudassir Ghafoor, Irsalan Arif, Shuaib Salamat

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This paper presents modeling and analysis of different intake bump (compression surface) configurations and comparison with an existing supersonic aircraft having bump intake configuration. Many successful aircraft models have shown that Diverter less Supersonic Inlet (DSI) as compared to conventional intake can reduce weight, complexity and also maintenance cost. The research is divided into two parts. In the first part, four different intake bumps are modeled for comparative analysis keeping in view the consistency of outer perimeter dimensions of fighter aircraft and various characteristics such as flow behavior, boundary layer diversion and pressure recovery are analyzed. In the second part, modeled bumps are integrated with intake duct for performance analysis and comparison with existing supersonic aircraft data is carried out. The bumps are named as uniform large (Config 1), uniform small (Config 2), uniform sharp (Config 3), non-uniform (Config 4) based on their geometric features. Analysis is carried out at different Mach Numbers to analyze flow behavior in subsonic and supersonic regime. Flow behavior, boundary layer diversion and Pressure recovery are examined for each bump characteristics, and comparative study is carried out. The analysis reveals that at subsonic speed, Config 1 and Config 2 give similar pressure recoveries as diverterless supersonic intake, but difference in pressure recoveries becomes significant at supersonic speed. It was concluded from research that Config 1 gives better results as compared to Config 3. Also, higher amplitude (Config 1) is preferred over lower (Config 2 and 4). It was observed that maximum height of bump is preferred to be placed near cowl lip of intake duct.

Keywords: bump intake, boundary layer, computational fluid dynamics, diverter-less supersonic inlet

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Authors: Melchor C. Morandarte

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Entrepreneurship education if well-designed, supported, and true to its sense in its implementation, can play a pivotal role in the development of Micro, small and Medium Enterprises (MSMEs) of the country. As its foundation, there is no amount of economic shocks that can prevent the country’s economic development and sustainability. Likewise, if properly developed, entrepreneurship education is the only kind of academic activity that rains employment opportunities propel and sustain economic growth. The study will try to find the contributions of the entrepreneurship education in the Philippines. Provide possible solutions that will solve academic heads and educators of entrepreneurship dilemma in making graduates of the program to engage or pursue a business after their graduation. Transforming BS in Entrepreneurship graduates from employment to an entrepreneurial minded individuals to establish and manage their owned businesses (as designed) whether micro, small or medium enterprises justifies the purpose within which it was created. Formally started in academic year 2006-2007, the program suffers in a very low enrollment in the first three academic years when it was first offered in the different HEIs all over the country. It started to experience only some increase in enrollment as a result of the moratorium in the Bachelor of Science in Business Administration (BSBA) in academic year 2011-2012 till today. The number of enrollees resulted in a substantial number of graduates. Considering the number of Bachelor of Science in Entrepreneurship graduates as of today, there would have been an additional number of business establishments from since the program started to be offered in the different HEIs throughout the country. In conclusion, coming up with a well-designed curriculum, relevant curricular, co-curricular and extra-curricular activities couple with much needed support from concerned government agencies, the institutions, other government and non-governmental institutions, private organizations, entrepreneurship practitioners can make the difference in terms of the mindset of the students of entrepreneurship.

Keywords: economic shocks, educators dilemma, rains employment opportunities, co-curricular

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Authors: Daniela Lamaison Sepulveda

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Critical media literacy teaches people to think analytically about the information they receive through the media. It is heavily influenced by Paulo Freire’s critical pedagogy and the necessity of becoming conscious of one’s reality in order to transform it. This qualitative research examines the case of Bolivia, which experienced dramatic political change after the first indigenous president, Evo Morales, was elected in 2006. In 2010, the government passed an education reform — the Avelino Siñani Elizardo Pérez (ASEP) —that draws heavily on decolonial thought and the Freirean notion of critical consciousness. The extent to which these theories were implemented in practice is evaluated in context of a media literacy project, run by an NGO, that trains secondary school teachers from public schools across Bolivia through yearly workshops ranging from producing media to identifying fake news. This context is examined against the backdrop of the highly contested general elections in October 2019. While there is plenty of literature that outlines the benefits of teaching media literacy in the classroom and different ways to apply it, little research has been done analysing implementation at an institutional level and how to best enable teachers who are motivated to teach the subject. Through semi-structured interviews, document analysis and naturalistic observations, this study aims to identify the struggles faced by teachers who are dedicated to teaching critical media literacy in their classrooms and how they navigate educational spaces while being subject to a demanding national curriculum that supposedly also seeks to promote critical thinking. The interplay between the aspirations of teachers and NGOs in contrast to the top-down discourse and policy of governmental institutions provides for a very enlightening case. By exploring these institutional, cultural, sociopolitical and economic barriers the teachers face, this research attempts to contribute to the debate in media literacy theories concerned with implementing the practice in schools.

Keywords: media literacy, critical pedagogy, teacher agency, misinformation, education reform, Bolivia

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Authors: Mitra Assadi, Md. Faan

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Background: Autism Spectrum Disorder (ASD) in a common neurodevelopmental disorder with limited pharmacological interventions. Transcranial Magnetic Stimulation (rTMS) has produced promising results in ASD, although there is no consensus regarding optimal targets or stimulation paradigms. A prevailing theory in ASD attributes the core deficits to dysfunction of the mirror neurons located in the inferior parietal lobule (IPL) and inferior frontal gyrus (IFG). Methods: Thus far, 11 subjects with ASD, 10 boys and 1 girl with the mean age of 13.36 years have completed the study by receiving 10 session of high frequency rTMS to the IPL. The subjects were randomized to receive stimulation on the left or right IPL and sham stimulation to the opposite side. The outcome measures included the Social Responsiveness Scale – Second Edition (SRS-2) and Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency task. Results: None of the 11 subjects experienced any adverse effects. The rTMS did not produce any improvement in verbal fluency, nor there was any statistically significant difference between the right versus left sided stimulation. Analysis of social awareness on SRS-2 (SRS-AWR) indicated a close to significant effect of the treatment with a small to medium effect size. After removing a single subject with Level 3 ASD, we demonstrated a close to significant improvement on SRS-AWR with a large effect size. The analysis of the data 3-month post TMS demonstrated return of the SRS-AWR values to baseline. Conclusion: This preliminary analysis of the 11 subjects who have completed our study thus far shows a favorable response to high frequency rTMS stimulation of the mirror neurons/IPL on social awareness. While the decay of the response noted during the 3-month follow-up may be considered a limitation of rTMS, the presence of the improvement, especially the effect size despite the small sample size, is indicative of the efficacy of this technique.

Keywords: rTMS, autism, scoial cognition, mirror neurons

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Authors: Kalkidan Worku, Eniyew Tegegne, Menichil Amsalu, Samuel Derbie Habtegiorgis

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Introduction: Because of the seasonal nature of the work, day laborers are exposed to risky sexual practices. Since the majority of them are living far away from their birthplace and family, they engage in unplanned and multiple sexual practices. These unplanned and unprotected sexual experiences are a risk for different types of sexual-related health crises. This study aimed to assess the pooled prevalence of risky sexual practices and its determinants among day laborers in Ethiopia. Methods: Online databases, including PubMed, Google Scholar, Science Direct, African Journal of Online, Academia Edu, Semantic Scholar, and university repository sites, were searched from database inception until March 2023. PRISMA 2020 guideline was used to conduct the review. Among 851 extracted studies, ten articles were retained for the final quantitative analysis. To identify the source of heterogeneity, a sub-group analysis and I² test were performed. Publication bias was assessed by using a funnel plot and the Egger and Beg test. The pooled prevalence of risky sexual practices was calculated. Besides, the association between determinant factors and risky sexual practice was determined using a pooled odds ratio (OR) with a 95% confidence interval. Result: The pooled prevalence of risky sexual practices among day laborers was 46.00% (95% CI: 32.96, 59.03). Being single (OR: 2.49; 95% CI: 1.29 to 4.83), substance use (OR: 1.79; 95% CI: 1.40 to 2.29), alcohol intake (OR: 4.19; 95% CI: 2.19 to 8.04), watching pornographic (OR: 5.49; 95% CI: 2.99 to 10.09), discussion about SRH (OR: 4.21; 95% CI: 1.34 to 13.21), visiting night clubs (OR: 2.86 95% CI: 1.79 to 4.57) and risk perception (OR: 0.37 95% CI: 0.20 to 0.70) were the possible factors for risky sexual practice of day laborers in Ethiopia. Conclusions: A large proportion of day laborers engaged in risky sexual practices. Interventions targeting creating awareness of sexual and reproductive health for day laborers should be implemented. Continuous peer education on sexual health should be given to day laborers. Sexual and reproductive health services should be accessible in their workplaces to maximize condom utilization and to facilitate sexual health education for all day laborers.

Keywords: day laborers, sexual health, risky sexual practice, unsafe sex, multiple sexual partners

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Authors: Martin Botz, Michael Kraus, Geralt Siebert

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The use of laminated glass gains increasing importance in structural engineering. For safety reasons, at least two glass panes are laminated together with a polymeric interlayer. In case of breakage of one or all of the glass panes, the glass fragments are still connected to the interlayer due to adhesion forces and a certain residual load-bearing capacity is left in the system. Polymer interlayers used in the laminated glass show a viscoelastic material behavior, e.g. stresses and strains in the interlayer are dependent on load duration and temperature. In the intact stage only small strains appear in the interlayer, thus the material can be described in a linear way. In the broken stage, large strains can appear and a non-linear viscoelasticity material theory is necessary. Relaxation tests on two different types of polymeric interlayers are performed at different temperatures and strain amplitudes to determine the border to the non-linear material regime. Based on the small-scale specimen results further tests on broken laminated glass panes are conducted. So-called ‘through-crack-bending’ (TCB) tests are performed, in which the laminated glass has a defined crack pattern. The test set-up is realized in a way that one glass layer is still able to transfer compressive stresses but tensile stresses have to be transferred by the interlayer solely. The TCB-tests are also conducted under different temperatures but constant force (creep test). Aims of these experiments are to elaborate if the results of small-scale tests on the interlayer are transferable to a laminated glass system in the broken stage. In this study, limits of the applicability of linear-viscoelasticity are established in the context of two commercially available polymer-interlayers. Furthermore, it is shown that the results of small-scale tests agree to a certain degree to the results of the TCB large-scale experiments. In a future step, the results can be used to develop material models for the post breakage performance of laminated glass.

Keywords: glass breakage, laminated glass, relaxation test, viscoelasticity

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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: Saman Khan, Imrana Naseem

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Copper is an essential trace element required for pro-angiogenic co-factors including vascular endothelial growth factor (VEGF). Elevated levels of copper are found in various types of cancer including prostrate, colon, breast, lung and liver for angiogensis and metastasis. Therefore, targeting copper via copper-specific chelators in cancer cells can be developed as effective anticancer treatment strategy. In continuation of our pursuit to design and synthesize copper chelators, herein we opted for a reaction to incorporate di-(2-picolyl) amine in 3-(bromoacetyl) coumarin (parent backbone) for the synthesis of complex 1. We evaluated lipid peroxidation, protein carbonylation, ROS generation, DNA damage and consequent apoptosis by complex 1 in exogenously added Cu(II) in human peripheral lymphocytes (simulate malignancy condition). Results showed that Cu(II)-complex 1 interaction leads to cell proliferation inhibition, apoptosis, ROS generation and DNA damage in human lymphocytes, and these effects were abrogated by cuprous chelator neocuproine and ROS scavengers (thiourea, catalase, SOD). This indicates that complex 1 cytotoxicity is due to redox cycling of copper to generate ROS which leads to pro-oxidant cell death in cancer cells. To further confirm our hypothesis, using the rat model of diethylnitrosamine (DEN) induced hepatocellular carcinoma; we showed that complex 1 mediates DNA breakage and cell death in isolated carcinoma cells. Membrane permeant copper chelator, neocuproine, and ROS scavengers inhibited the complex 1-mediated cellular DNA degradation and apoptosis. In summary, complex 1 anticancer activity is due to its copper chelation capability. These results will provide copper chelation as an effective targeted cancer treatment strategy for selective cytotoxic action against malignant cells without affecting normal cells.

Keywords: cancer treatment, copper chelation, ROS generation, DNA damage, redox cycling, apoptosis

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