Search results for: human rights in Islam

Authors: Saima Saleem, Zubair Abbasi, Abdul Hameed, Mansoor Ahmed Khan, Navid Rashid Qureshi, Abid Azhar

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Oral Squamous Cell Carcinoma (OSCC) is the leading cause of death in the developing countries like Pakistan. This problem aggravates because of the excessive use of available chewing products. In spite of widespread information on their use and purported legislations against their use the Pakistani markets are classical examples of selling chewable carcinogenic mutagens. Reported studies indicated that these products are rich in reactive oxygen species (ROS) and polyphenols. TP53 gene is involved in the suppression of tumor. It has been reported that somatic mutations caused by TP53 gene are the foundation of the cancer. This study aims to find the loss of TP53 functions due to mutation/polymorphism caused by genomic alteration and interaction with tobacco and its related ingredients. Total 260 tissues and blood specimens were collected from OSCC patients and compared with age and sex matched controls. Mutations in exons 2-11 of TP53 were examined by PCR-SSCP. Samples showing mobility shift were directly sequenced. Two mutations were found in exon 4 at nucleotide position 108 and 215 and one in exon 7 at nucleotide position 719 of the coding sequences in patient’s tumor samples. These results show that substitution of proline with arginine at codon 72 and serine with threonine at codon 240 of p53 protein. These polymorphic changes, found in tumor samples of OSCC, could be involved in loss of heterozygocity and apoptotic activity in the binding domain of TP53. The model of the mutated TP53 gene elaborated a nonfunctional unfolded p53 protein, suggesting an important role of these mutations in p53 protein inactivation and malfunction. This nonfunctional 3D model also indicates that exogenous tobacco related carcinogens may act as DNA-damaging agents affecting the structure of DNA. The interpretations could be helpful in establishing the pathways responsible for tumor formation in OSCC patients.

Keywords: TP53 mutation/polymorphism, OSCC, PCR-SSCP, direct DNA sequencing, 3D structure

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Authors: Mei-Ling Chan, Jin-Ming Wu, Konstantin V. Kudryavtsev, Jih-Hwa Guh

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Prostate cancer is one of the most common malignant disease in men. KUD983 is an enantiomerically pure β-dipeptide derivative, which may have anti-cancer effects. In the present study, KUD983 exhibits powerful activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells. The IC50 values of KUD983 in PC-3 and DU145 cells are 0.56±0.07M and 0.50±0.04 M respectively. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with the down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB. The protein expressions of nuclear and total c-Myc protein, which was able to regulate the expression of both cyclin D1 and cyclin E, were significantly suppressed by KUD983. Phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is an important signaling pathway that influences the energy metabolism, cell cycle, proliferation, survival and apoptosis of cells, and is associated with numerous other signaling pathways. The Western Blot data revealed that KUD983 inhibited PI3K/Akt and mTOR/p70S6K/4E-BP1 pathways. The transient transfection of constitutively active myristylated Akt (myr-Akt) cDNA significantly reversed KUD983-induced caspase activation but did not abolish the suppression of mTOR/p70S6K/4E-BP1 signaling cascade indicating the presence of both Akt-dependent and -independent pathways. Moreover, KUD983-induced effect was collaborated with the down-regulation of anti-apoptotic Bcl-2 members (e.g., Bcl-2, and Mcl-1) and IAP family members (e.g., survivin). Furthermore, KUD983 induced autophagic cell death using confocal microscopic examination, investigating the level of conversion of LC3-I to LC3-II and flow cytometric detection of AVO-positive cells. Taken together, the data suggest that KUD983 is an anticancer β-dipeptide against HRPCs through the inhibition of cell proliferation and induction of apoptotic and autophagic cell death. The suppression of signaling pathways mediated by c-Myc, PI3K/Akt and mTOR/p70S6K/4E-BP1 and the collaboration with down-regulation of Mcl-1 and survivin may indicate the mechanism of KUD983 against HRPC.

Keywords: β-dipeptide, hormone-refractory prostate cancer, mTOR, PI3K/Akt

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Authors: Zehra Aybike Kılıç, Alpin Köknel Yener

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Daylight is a powerful driver in terms of improving human health, enhancing productivity and creating sustainable solutions by minimizing energy demand. A proper daylighting system allows not only a pleasant and attractive visual and thermal environment, but also reduces lighting energy consumption and heating/cooling energy load with the optimization of aperture size, glazing type and solar control strategy, which are the major design parameters of daylighting system design. Particularly, in high-rise buildings where large openings that allow maximum daylight and view out are preferred, evaluation of daylight performance by considering the major parameters of the building envelope design becomes crucial in terms of ensuring occupants’ comfort and improving energy efficiency. Moreover, it is increasingly necessary to examine the daylighting design of high-rise residential buildings, considering the share of residential buildings in the construction sector, the duration of occupation and the changing space requirements. This study aims to identify a proper daylighting design solution considering window area, glazing type and solar control strategy for a high-residential building in terms of visual comfort and lighting energy efficiency. The dynamic simulations are carried out/conducted by DIVA for Rhino version 4.1.0.12. The results are evaluated with Daylight Autonomy (DA) to demonstrate daylight availability in the space and Daylight Glare Probability (DGP) to describe the visual comfort conditions related to glare. Furthermore, it is also analyzed that the lighting energy consumption occurred in each scenario to determine the optimum solution reducing lighting energy consumption by optimizing daylight performance. The results revealed that it is only possible that reduction in lighting energy consumption as well as providing visual comfort conditions in buildings with the proper daylighting design decision regarding glazing type, transparency ratio and solar control device.

Keywords: daylighting , glazing type, lighting energy efficiency, residential building, solar control strategy, visual comfort

Procedia PDF Downloads 176

Authors: Bui Phuong Linh, Yuki Sakakibara, Ryuto Tanaka, Elizabeth H. Pigney, Taishi Hashiguchi

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NASH is an increasingly prevalent chronic liver disease that can progress to hepatocellular carcinoma and now is attracting interest worldwide. The STAM™ model is a clinically-correlated murine NASH model which shows the same pathological progression as NASH patients and has been widely used for pharmacological and basic research. The multiple parallel hits hypothesis suggests abnormalities in adipocytokines, intestinal microflora, and endotoxins are intertwined and could contribute to the development of NASH. In fact, NASH patients often exhibit gut dysbiosis and dysfunction in adipose tissue and metabolism. However, the analysis of the STAM™ model has only focused on the liver. To clarify whether the STAM™ model can also mimic multiple pathways of NASH progression, we analyzed the organ crosstalk interactions between the liver and the gut and the phenotype of adipose tissue in the STAM™ model. NASH was induced in male mice by a single subcutaneous injection of 200 µg streptozotocin 2 days after birth and feeding with high-fat diet after 4 weeks of age. The mice were sacrificed at NASH stage. Colon samples were snap-frozen in liquid nitrogen and stored at -80˚C for tight junction-related protein analysis. Adipose tissue was prepared into paraffin blocks for HE staining. Blood adiponectin was analyzed to confirm changes in the adipocytokine profile. Tight junction-related proteins in the intestine showed that expression of ZO-1 decreased with the progression of the disease. Increased expression of endotoxin in the blood and decreased expression of Adiponectin were also observed. HE staining revealed hypertrophy of adipocytes. Decreased expression of ZO-1 in the intestine of STAM™ mice suggests the occurrence of leaky gut, and abnormalities in adipocytokine secretion were also observed. Together with the liver, phenotypes in these organs are highly similar to human NASH patients and might be involved in the pathogenesis of NASH.

Keywords: Non-alcoholic steatohepatitis, hepatocellular carcinoma, fibrosis, organ crosstalk, leaky gut

Procedia PDF Downloads 159

Authors: Nelson F. F. Ebecken, Gilberto C. Pereira, Lucio P. de Andrade

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Bays, estuaries and coastal ecosystems are some of the most used and threatened natural systems globally. Its deterioration is due to intense and increasing human activities. This paper aims to monitor the socio-ecological in Brazil, model and simulate it through a multilayer network representing a DPSIR structure (Drivers, Pressures, States-Impacts-Responses) considering the concept of Management based on Ecosystems to support decision-making under the National/State/Municipal Coastal Management policy. This approach considers several interferences and can represent a significant advance in several scientific aspects. The main objective of this paper is the coupling of three different types of complex networks, the first being an ecological network, the second a social network, and the third a network of economic activities, in order to model the marine ecosystem. Multilayer networks comprise two or more "layers", which may represent different types of interactions, different communities, different points in time, and so on. The dependency between layers results from processes that affect the various layers. For example, the dispersion of individuals between two patches affects the network structure of both samples. A multilayer network consists of (i) a set of physical nodes representing entities (e.g., species, people, companies); (ii) a set of layers, which may include multiple layering aspects (e.g., time dependency and multiple types of relationships); (iii) a set of state nodes, each of which corresponds to the manifestation of a given physical node in a layer-specific; and (iv) a set of edges (weighted or not) to connect the state nodes among themselves. The edge set includes the intralayer edges familiar and interlayer ones, which connect state nodes between layers. The applied methodology in an existent case uses the Flow cytometry process and the modeling of ecological relationships (trophic and non-trophic) following fuzzy theory concepts and graph visualization. The identification of subnetworks in the fuzzy graphs is carried out using a specific computational method. This methodology allows considering the influence of different factors and helps their contributions to the decision-making process.

Keywords: marine ecosystems, complex systems, multilayer network, ecosystems management

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Authors: Joy Debski

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Due to the varying degrees of the problem posed by global warming, environmental sustainability dominates international discourse. International initiatives' aims and expectations have proven particularly challenging to put into practice in developing nations. To reduce human exploitation of the environment, stricter measures are urgently needed. However, putting them into practice has proven more difficult. Relatively recent information from the Climate Accountability Institute and academic researchers shows that fossil fuel companies are major contributors to the climate crisis. Host communities in oil and gas-producing areas, particularly in developing nations, have grown hostile toward both oil and gas companies and government policies. It is now essential that the three main stakeholders—government, the oil and gas sector, and host communities—cooperate to achieve the shared objective of environmental sustainability. This research, therefore, advocates a governance system for Nigeria that facilitates the achieving the goal of environmental sustainability. This objective is achieved by the research's examination of the main institutional framework for environmental sustainability, evaluation of the strategies used by major oil companies to increase stakeholder engagement in environmental sustainability, and examination of the involvement of host communities in environmental sustainability. The study reveals that while environmental sustainability is important to the identified stakeholders, it's challenging to accomplish without an informed synergy. Hence the research advocates the centralisation of CSR through a CSR commission for environmental sustainability. The commission’s mandate is to facilitate, partner with, and endorse companies. The commission is strongly advised to incorporate host community liaison offices into the process of negotiating contracts with oil and gas firms, as well as to play a facilitative role in helping firms adhere to both domestic and international regulations. The recommendations can benefit Nigerian policymakers in enhancing their unsuccessful efforts to pass CSR legislation. Through the research-proposed CSR department, which has competent training and stakeholder engagement strategies, oil and gas companies can enhance and centralise their goals for environmental sustainability. Finally, the CSR Commission's expertise would give host communities more leverage when negotiating their memorandum of understanding with oil and gas companies.

Keywords: environmental sustainability, corporate social responsibility, CSR, oil and gas, nigeria

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Authors: M. Achemo, O. Saito

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Jefoure land use system is one of the traditional landscape human settlement patterns, and it is a cultural design and peculiar art of the people of Gurage in Ethiopia via which houses and trees flank roads left and right. Assessment of the multiple benefits of the traditional road that benefit society and development could enhance the understanding of the land use planners and decision makers to pay attention while planning and managing the land use system. Recent trend shows that the Jefoure land use is on the threshold of change as a result of flourishing road networks, overgrazing, and agricultural expansion. This study aimed to evaluate the multiple ecosystem services provided by the Jefoure land use system after characterization of the socio-ecological landscape. Information was compiled from existing data sources such as ordnance survey maps, aerial photographs, recent high resolution satellite imageries, designated questionnaires and interviews, and local authority contacts. The result generated scientific data on the characteristics, ecosystem services provision, and drivers of changes. The cultural landscape has novel characteristics and providing multiple ecosystem services to the community for long period of time. It is serving as road for humans, livestock and vehicles, habitat for plant species, regulating local temperature, climate, runoff and infiltration, and place for meeting, conducting religious and spiritual activities, holding social events such as marriage and mourning, playing station for children and court for football and other traditional games. As a result of its aesthetic quality and scenic beauty, it is considered as recreational place for improving mental and physical health. The study draws relevant land use planning and management solution in the improvement of socio-ecological resilience in the Jefoure land use system. The study suggests the landscape needs to be registrar as heritage site for recognizing the wisdom of the community and enhancing the conservation mechanisms.

Keywords: cultural landscape, ecosystem services, Gurage, Jefoure

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Authors: Catia S. A. Sima, K. Bousson

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Congestion in the Terminal Maneuvering Areas (TMAs) of larger airports impacts all aspects of air traffic flow, not only at national level but may also induce arrival delays at international level. Hence, there is a need to monitor appropriately the air traffic flow in TMAs so that efficient decisions may be taken to manage their occupancy rates. It would be desirable to physically increase the existing airspace to accommodate all existing demands, but this question is entirely utopian and, given this possibility, several studies and analyses have been developed over the past decades to meet the challenges that have arisen due to the dizzying expansion of the aeronautical industry. The main objective of the present paper is to propose concepts to manage and reduce the degree of uncertainty in the air traffic operations, maximizing the interest of all involved, ensuring a balance between demand and supply, and developing and/or adapting resources that enable a rapid and effective adaptation of measures to the current context and the consequent changes perceived in the aeronautical industry. A central task is to emphasize the increase in air traffic flow management capacity to the present day, taking into account not only a wide range of methodologies but also equipment and/or tools already available in the aeronautical industry. The efficient use of these resources is crucial as the human capacity for work is limited and the actors involved in all processes related to air traffic flow management are increasingly overloaded and, as a result, operational safety could be compromised. The methodology used to answer and/or develop the issues listed above is based on the advantages promoted by the application of Markov Chain principles that enable the construction of a simplified model of a dynamic network that describes the air traffic flow behavior anticipating their changes and eventual measures that could better address the impact of increased demand. Through this model, the proposed concepts are shown to have potentials to optimize the air traffic flow management combined with the operation of the existing resources at each moment and the circumstances found in each TMA, using historical data from the air traffic operations and specificities found in the aeronautical industry, namely in the Portuguese context.

Keywords: air traffic flow, terminal maneuvering area, TMA, air traffic management, ATM, Markov chains

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Authors: Madifedile Thasi, Azola Mayeza

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In South Africa, provision of housing to the growing population has been described as one of the greatest challenges facing the government. Between 1994 to 2015, more than 2.5 million housing units were provided by the government for the poorest households and the low-income earners under the Reconstruction and Development Programme (RDP). Yet, the latest census figure revealed that about 2.1 million households still live in shacks and informal dwellings. Human settlements patterns remain dysfunctional across in South Africa because of rapid urbanisation. The housing backlog is growing at a rate of 178 000 units a year. The aforementioned predicament calls the need for innovative approaches to address the issue in a sustainable way and this need not be overemphasized. Aside from the issue of cost, the delivery of more housing units comes with environmental and sustainability issues. The prefabrication building technology has resulted into accelerated housing delivery to a satisfactory level in some countries such as Nigeria and Malaysia that are facing similar issue. It is therefore expected to be a foremost option to address the social housing backlog in South Africa and within the country housing sustainability agenda. This paper appraises the factors responsible for the limited implementation of prefabrication technology in South African housing projects. The objective is to recommend the method and materials that can be best sustained in the country in terms of local availability, cost effectiveness and environmental friendliness. It presents empirical data to support the hypothesis that a wider implementation of prefabrication technology in the social housing projects will be of significant benefit, by providing fast turnaround, cost-effective and sustainable solution that will dent the housing backlog, as well as improving the quality of the social housings. It was found that only 17 000 units of the RDP housings provided were constructed using alternative building technologies. Furthermore, there are variety of prefabricated technologies in the market but mostly have limited production capacity, minimal manufacturing capacity and most materials are imported, which leads to unavailability of the technology for large scale delivery and utilization despite its obvious advantages.

Keywords: prefabrication technology, sustainable social housings, South Africa, housing delivery

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Authors: Shimhanda M. N., Mogomotsi P. K., Thakadu O. T., Rutina L. P.

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Wildlife tourism (WT) in communal conservancies has the potential to contribute significantly to sustainable rural development. However, understanding local perceptions, promoting participation, and addressing stakeholder concerns are all required for sustainability. This study looks at stakeholder perceptions of WT in conservancies near protected areas in Namibia's Zambezi region, specifically the Mudumu North Complex. A mixed-methods approach was employed to collect data from 356 households using stratified sampling. Qualitative data was gathered through six focus group discussions and 22 key informant interviews. Quantitative analysis, using descriptive statistics and Spearman correlation, investigated socio-demographic influences on WT perceptions, while qualitative data were subjected to thematic analysis to identify key themes. Results revealed high awareness and generally positive perceptions of WT, particularly in Mashi Conservancy, which benefits from diverse tourism activities and joint ventures with lodges. Kwandu and Kyaramacan, which rely heavily on consumptive tourism, had lower awareness and perceived benefits. Human-wildlife conflict emerged as a persistent issue, especially in Kwandu and Mashi, where crop damage and wildlife interference undermined community support for WT. Younger, more educated, and employed individuals held more positive attitudes towards WT. The study highlights the importance of recognising community heterogeneity and tailoring WT strategies to meet diverse needs, including HWC mitigation. Policy implications include increasing community engagement, ensuring equitable benefit distribution, and implementing inclusive tourism strategies that promote long-term sustainability. These findings are critical for developing long-term WT models that address local challenges, encourage community participation, and contribute to socioeconomic development and conservation goals.

Keywords: sustainable tourism, stakeholder perceptions, community involvement, socio-economic development

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Authors: Loonibha Manandhar, Rajendra Bhandari, Kumud Raj Kafle

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Nepal’s Terai region is a part of the Ganges river basin which is one of the most disaster-prone areas of the world, with recurrent monsoon flooding causing millions in damage and the death and displacement of hundreds of people and households every year. The vulnerability of human settlements to natural disasters such as floods is increasing, and mapping changes in land use practices and hydro-geological parameters is essential in developing resilient communities and strong disaster management policies. The objective of this study was to develop a flood hazard zonation map of Orai Khola watershed and map the decadal land use/land cover dynamics of the watershed. The watershed area was delineated using SRTM DEM, and LANDSAT images were classified into five land use classes (forest, grassland, sediment and bare land, settlement area and cropland, and water body) using pixel-based semi-automated supervised maximum likelihood classification. Decadal changes in each class were then quantified using spatial modelling. Flood hazard mapping was performed by assigning weights to factors slope, rainfall distribution, distance from the river and land use/land cover on the basis of their estimated influence in causing flood hazard and performing weighed overlay analysis to identify areas that are highly vulnerable. The forest and grassland coverage increased by 11.53 km² (3.8%) and 1.43 km² (0.47%) from 1996 to 2016. The sediment and bare land areas decreased by 12.45 km² (4.12%) from 1996 to 2016 whereas settlement and cropland areas showed a consistent increase to 14.22 km² (4.7%). Waterbody coverage also increased to 0.3 km² (0.09%) from 1996-2016. 1.27% (3.65 km²) of total watershed area was categorized into very low hazard zone, 20.94% (60.31 km²) area into low hazard zone, 37.59% (108.3 km²) area into moderate hazard zone, 29.25% (84.27 km²) area into high hazard zone and 31 villages which comprised 10.95% (31.55 km²) were categorized into high hazard zone area.

Keywords: flood hazard, land use/land cover, Orai river, supervised maximum likelihood classification, weighed overlay analysis

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Authors: Soumita Mitra, Santosh Kumar Sarkar

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Hooghly river estuary (HRE), situated at the north eastern part of Bay of Bengal has global significance due to its holiness. It is of immense importance to the local population as it gives perpetual water supply for various activities such as transportation, fishing, boating, bathing etc. to the local people who settled on both the banks of this estuary. This study was done to assess the dissolved and particulate trace metal in the estuary covering a stretch of about 175 Km. The water samples were collected from the surface (0-5 cm) along the salinity gradient and metal concentration were studied both in dissolved and particulate phase using Graphite Furnace Atomic Absorption Spectrophotometer (GF-AAS) along some physical characteristics such as water temperature, salinity, pH, turbidity and total dissolved solids. Although much significant spatial variation was noticed but little enrichment was found along the downstream of the estuary. The mean concentration of the metals in the dissolved and particulate phase followed the same trend and as follows: Fe>Mn>Cr>Zn>Cu>Ni>Pb. The concentration of the metals in the particulate phase were much greater than that in dissolved phase which was also depicted from the values of the partition coefficient (Kd)(ml mg-1). The Kdvalues ranged from 1.5x105 (in case of Pb) to 4.29x106 (in case of Cr). The high value of Kd for Cr denoted that the metal Cr is mostly bounded with the suspended particulate matter while the least value for Pb signified it presence more in dissolved phase. Moreover, the concentrations of all the studied metals in the dissolved phase were many folds higher than their respective permissible limits assested by WHO 2008, 2009 and 2011. On the other hand, according to Sediment Quality Guidelines (SQGs), Zn, Cu and Ni in the particulate phase lied between ERL and ERM values but Cr exceeded ERM values at all the stations confirming that the estuary is mostly contaminated with the particulate Cr and it might cause frequent adverse effects on the aquatic life. Multivariate statistics Cluster analysis was also performed which separated the stations according to the level of contamination from several point and nonpoint sources. Thus, it is found that the estuarine system is much polluted by the toxic metals and further investigation, toxicological studies should be implemented for full risk assessment of this system, better management and restoration of the water quality of this globally significant aquatic system.

Keywords: dissolved and particulate phase, Hooghly river estuary, partition coefficient, surface water, toxic metals

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Authors: Ritvik Chauhan, Vijay Kumar Baraik

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Crime is a rare event on earth surface. It is not simple but a complex event occurring in a spatio- temporal environment. Crime is one of the most serious security threats to human environments as it may result in harm to the individuals through the loss of property, physical and psychological injuries. The conventional studies done on different nature crime was mostly related to laws, psychological, social and political themes. The geographical areas are heterogeneous in their environmental conditions, associations between structural conditions, social organization which contributing specific crimes. The crime pattern analysis is made through theories in which criminal events occurs in persistent, identifiable patterns in a particular space and time. It will be the combined analysis of spatial factors and rational factors to the crime. In this study, we are analyzing the combined factors for the origin of crime against children. Children have always been vulnerable to victimization more because they are silent victims both physically and mentally to crimes and they even not realize what is happening with them. Their trusting nature and innocence always misused by criminals to perform crimes. The nature of crime against children is changed in past years like child rape, kidnapping &abduction, selling & buying of girls, foeticide, infanticide, prostitution, child marriage etc turned to more cruel and inhuman. This study will focus on understanding the space-time pattern of crime against children during the period 2001-2012. It also makes an attempt to explore and ascertain the association of crimes categorised against children, its rates with various geographical and socio-demographic factors through causal analysis using selected indicators (child sex-ratio, education, literacy rate, employment, income, etc.) obtained from the Census of India and other government sources. The outcome of study will help identifying the high crime regions with specified nature of crimes. It will also review the existing efforts and exploring the new plausible measure for tracking, monitoring and minimization of crime rate to meet the end goal of protecting the children from crimes committed against them.

Keywords: crime against children, geographic profiling, spatio-temporal analysis, hotspot

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Authors: Samart Homthong, Wutthipong Moungnoi

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Critical success factors (CSFs) and the criteria to measure project success have received much attention over the decades and are among the most widely researched topics in the context of project management. However, although there have been extensive studies on the subject by different researchers, to date, there has been little agreement on the CSFs. The aim of this study is to identify the CSFs that influence the performance of construction projects, and determine their relative importance for different objectives across five stages in the project life cycle. A considerable literature review was conducted that resulted in the identification of 179 individual factors. These factors were then grouped into nine major categories. A questionnaire survey was used to collect data from three groups of respondents: client representatives, consultants, and contractors. Out of 164 questionnaires distributed, 93 were returned, yielding a response rate of 56.7%. Using the mean score, relative importance index, and weighted average method, the top 10 critical factors for each category were identified. The agreement of survey respondents on those categorised factors were analysed using Spearman’s rank correlation. A one-way analysis of variance was then performed to determine whether the mean scores among the various groups of respondents were statistically significant. The findings indicate the most CSFs in each category in procurement phase are: proper procurement programming of materials (time), stability in the price of materials (cost), and determining quality in the construction (quality). They are then followed by safety equipment acquisition and maintenance (health and safety), budgeting allowed in a contractual arrangement for implementing environmental management activities (environment), completeness of drawing documents (productivity), accurate measurement and pricing of bill of quantities (risk management), adequate communication among the project team (human resource), and adequate cost control measures (client satisfaction). An understanding of CSFs would help all interested parties in the construction industry to improve project performance. Furthermore, the results of this study would help construction professionals and practitioners take proactive measures for effective project management.

Keywords: critical success factors, procurement phase, project life cycle, project performance

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Authors: Mary Edokpa Fadal, Frances Agweda

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Considering the volatile and evolving nature of the political environment in the developing countries, it is important that the subject of effective leadership practices that focus on transformational and systematic political development and values be reviewed. If the attitude towards partisan politics and the played politics by political parties is relatively deviated from expected adherence to acceptance, safe, efficient and practical standard, the political parties will continue to struggle endlessly in an effort to maintain a system that works. The analysis is situated in the context of political parties and partisan political behavior in contemporary societies and developing nations. Recent research of empirical evidence shows that most of the political parties are more or less, not too active in playing their instrumental role in the political system, such as unifying, simplifying and stabilizing the political process. This is however traced to the problem of ethnic politics that have been dominated by tribalism. The rising clamor for political development needs re-structuring and correcting the abnormalities in the center of the polity to address the flaws in our political system. The paper argues that political parties and political actors are some of the vital instrument of attaining societal goals of democratic principles for peace and durability. Issues of ethnic and partisan politics are also discussed, as it relates to question pertaining to political ideologies. It is in the findings that this paper examines some of the issues that have been seen revolving the true practice of political parties and its activities towards the democratic trend of a society, that help to resolve questions surrounding the issues of politics and governance in developing countries. These issues are seen as an aberration that have characterized politics and political behavior especially in the aspect of transparency and fulfilling its purpose of existence. The paper argues that the transition of the developing nature of states largely depends on the political structures and party politics and the nature of constitutionalism following the democratic awakening. The paper concludes that politics and political behavior are all human factors that play a vital role in the development of contemporary societies. They drive the wheel of nations towards its goal attainment. This paper relies on documentary, primary sources of data collection and empirical analysis.

Keywords: development, ethnicity, partisan politics, political behavior, political parties

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Authors: Goodness Thandi Ntuli

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As one of the sub-Saharan African countries, South Africa has a majority of women living at the receiving end of all ferocious atrocities, afflictions and social ills such as utter poverty, unemployment, morbidity, sexual exploitation and abuse, gender-based and domestic violence. The response to these social ills that permeate the South African context like wildfire requires postcolonial feminism as a lens which needs to directly address this particular context. In the empirical study that was conducted among the Zulu people about Zulu young women in the South African context, it was found that a postcolonial young woman has a lot of social challenges that militate against her. In her struggle to liberate herself, there are layers of oppression that she has to deal with before attaining emancipation of any kind. These layers of oppression emanate from postcolonial effects on cultural norms that come with patriarchal issues, racial issues as the woman of colour and socio-economic issues as the poverty-stricken marginalised woman. Such layers also render marginalized women voiceless on many occasions, and hence the kind of feminism that needs to be applied in this context has to give them a voice, worth and human dignity that they deserve. From the postcolonial feminist perspective, this paper examines the condition of women from the margins and seeks the ways in which the layers of oppression could be disengaged. In the process of the severed layers of oppression, these women can be uplifted to becoming the women of worth, restored to life-giving dignity from the inferiority complex of racial discrimination and liberation from all forms of patriarchy and its upshots that keep them bound by gender inequality. This requires, in particular, postcolonial feminism that would find profound ways of reaching into the deep-seated socialization and internalization of every kind of prejudice against women. It is the kind of feminism that questions the status core even among those who consider themselves feminists. With the ruination of all postcolonial layers of oppression, women in the margins could find real emancipation that they have always longed for through feminism that will take into consideration their context. This calls for the rethinking of feminism in different contexts because the conditions of the oppressed woman of the South cannot be the same as the conditions of the woman who considers herself oppressed in the North.

Keywords: exploration, feminism, postcolonial, margins, South African, women

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Authors: Kremena Ivanona, Bistra Kunovska, Jana Djunova, Desislava Djunakova, Zdenka Stojanovska

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In recent decades, the general public has become increasingly interested in the impact of air pollutions on their health. Currently, numerous studies are aimed at identifying pollutants in the indoor environment where they carry out daily activities. Internal pollutants can be of both natural and artificial origin. With regard to natural pollutants, special attention is paid to natural radioactivity. In recent years, radon has been one of the most studied indoor pollutants because it has the greatest contribution to human exposure to natural radionuclides. It is a known fact that lung cancer can be caused by radon radiation and it is the second risk factor after smoking for the onset of the disease. The main objective of the study under the National Science Fund of Bulgaria, in the framework of grant No КП-06-Н23/1/07.12.2018 is to evaluate the indoor radon as an important air pollutant in school buildings in order to reduce the exposure to children. The measurements were performed in 48 schools located in 55 buildings in one Bulgarian administrative district (Kardjaly). The nuclear track detectors (CR-39) were used for measurements. The arithmetic and geometric means of radon concentrations are AM = 140 Bq/m3, and GM = 117 Bq/m3 respectively. In 51 school rooms, the radon levels were greater than 200 Bq/m3, and in 28 rooms, located in 17 school buildings, it exceeded the national reference level of 300 Bq/m3, defined in the Bulgarian ordinance on radiation protection (or 30% of the investigated buildings). The statistically significant difference in the values of radon concentration by municipalities (KW, р < 0.001) obtained showed that the most likely reason for the differences between the groups is the geographical location of the buildings and the possible influence of the geological composition. The combined effect of the year of construction (technical condition of the buildings) and the energy efficiency measures was considered. The values of the radon concentration in the buildings where energy efficiency measures have been implemented are higher than those in buildings where they have not been performed. This result confirms the need for investigation of radon levels before conducting the energy efficiency measures in buildings. Corrective measures for reducing the radon levels have been recommended in school buildings with high radon levels in order to decrease the children's exposure.

Keywords: air pollution, indoor radon, children exposure, schools

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Authors: Christopher Meyer, Laima Gerlitz

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European ports are facing high political pressure through the implementation of initiatives such as the European Green Deal or IMO's 2030 targets (Fit for 55). However, small and medium-sized ports face even higher challenges compared to bigger ones due to lower capacities in various fields such as investments, infra-structure, Human Resources, and funding opportunities. Small and Medium-Sized Ports (SMPs) roles in economic systems are various depending on their specific functionality in maritime ecosystems. Depending on their different situations, being an actor in multiport gateways, aligned to core ports, regional nodes in peripheries for the hinterland, specialized cluster members, or logistical nodes, different strategic business models may be applied to increase SMPs' competitiveness among other bigger ports. Additionally, SMPs are facing more challenges for future development in terms of digital and green transition of their operations. Thus, it is necessary to evaluate the own strategical position and apply management strategies alongside the regional growth and innovation strategies for diversification or specialisation of own port businesses. The research uses inductive perspectives to set up a transferable framework based on case studies to be analysed. In line with particular research and document analysis, qualitative approaches were considered. The research is based on a deep literature review on SMPs as well as theories on diversification and specialisation. Existing theories from different fields are evaluated on their application for the port sector and these specific maritime actors, paying respect to enabling innovation incorporation to enhance digital and environmental transition with fu-ture perspectives for SMPs. The paper aims to provide a decision-making matrix for the strategic positioning of SMPs in Europe, including opportunities to get access to particular EU funds for future development alongside the Regional In-novation Strategies on Smart Specialisation.

Keywords: strategic planning, sustainability transition, competitiveness portfolio, EU green deal

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Authors: Yuqiao Zhou

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The Sapir-Whorf hypothesis (SWH) emphasizes the effect produced by language on people’s minds. According to linguistic relativity, language has evolved over the course of human life on earth, and, in turn, the acquisition of language shapes learners’ thoughts. Despite much attention drawn by SWH, few scholars have attempted to analyse people’s thoughts via their literary works. And yet, the linguistic choices that create a narrative can enable us to examine its writer’s thoughts. Still, less work has been done on the impact of language on the minds of bilingual people. Internationalization has resulted in an increasing number of bilingual and multilingual individuals. In China, where more than one hundred languages are used for communication, most people are bilingual in Mandarin Chinese (the official language of China) and their own dialect. Taking as its corpus the ethnic minority myth of Ge Sa-er Wang by Alai and its English translation by Goldblatt and Lin, this paper aims to analyse the effects of culture on bilingual people’s minds. It will first analyse Alai’s thoughts on using the original version of Ge Sa-er Wang; next, it will examine the thoughts of the two translators by looking at translation choices made in the English version; finally, it will compare the cultural influences evident in the thoughts of Alai, and Goldblatt and Lin. Whereas Alai can speak two Sino-Tibetan languages – Mandarin Chinese and Tibetan – Goldblatt and Lin can speak two languages from different families – Mandarin Chinese (a Sino-Tibetan language) and English (an Indo-European language). The results reveal two systems of thought existing in the translators’ minds; Alai’s text, on the other hand, does not reveal a significant influence from North China, where Mandarin Chinese originated. The findings reveal the inconsistency of a second language’s influence on people’s minds. Notably, they suggest that the more different the two languages are, the greater the influence produced by the second language culture on people’s thoughts. It is hoped that this research will expand the scope of SWH as well as shed light on future translation studies on ethnic minority literature.

Keywords: Sapir-Whorf hypothesis, cultural translation, cultural-specific items, Ge Sa-er Wang, ethnic minority literature, Tibet

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Authors: Anamika Sahu

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The Himalayas, like many mountainous regions, is susceptible to multiple hazards. In recent times, the frequency of such disasters is continuously increasing due to extreme weather phenomena. These natural hazards are responsible for irreparable human and economic loss. The Indian Himalayas has repeatedly been ruptured by great earthquakes in the past and has the potential for a future large seismic event as it falls under the seismic gap. Damages caused by earthquakes are different in different localities. It is well known that, during earthquakes, damage to the structure is associated with the subsurface conditions and the quality of construction materials. So, for sustainable mountain development, prior estimation of site characterization will be valuable for designing and constructing the space area and for efficient mitigation of the seismic risk. Both geotechnical and geophysical investigation of the subsurface is required to describe the subsurface complexity. In mountainous regions, geophysical methods are gaining popularity as areas can be studied without disturbing the ground surface, and also these methods are time and cost-effective. The MASW method is used to calculate the Vs30. Vs30 is the average shear wave velocity for the top 30m of soil. Shear wave velocity is considered the best stiffness indicator, and the average of shear wave velocity up to 30 m is used in National Earthquake Hazards Reduction Program (NEHRP) provisions (BSSC,1994) and Uniform Building Code (UBC), 1997 classification. Parameters obtained through geotechnical investigation have been integrated with findings obtained through the subsurface geophysical survey. Joint interpretation has been used to establish inter-relationships among mineral constituents, various textural parameters, and unconfined compressive strength (UCS) with shear wave velocity. It is found that results obtained through the MASW method fitted well with the laboratory test. In both conditions, mineral constituents and textural parameters (grain size, grain shape, grain orientation, and degree of interlocking) control the petrophysical and mechanical properties of rocks and the behavior of shear wave velocity.

Keywords: MASW, mechanical, petrophysical, site characterization

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Authors: Monika Haanpää

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Well-functioning workplaces are often characterized by good co-operation, adequate flow of information, open interaction between workers and a supportive work environment. The workplace is a mosaic of human personalities and the influx of people, who speak different languages and who are from different cultural backgrounds, may bring about new challenges and enrich this environment. However, this influx of people could also pose a problem as the adaptation of immigrant people to new terms of work may depend heavily on the level of language skills, the stage of culture shock, professional identity, and personality. Migration is not a rare phenomenon in Finland anymore; nobody is surprised to see people from different countries and different backgrounds in the schools, on the streets or in shops. However, this does not mean that immigration is an easy process for people coming from other countries. The experience of workers, with diverse language and backgrounds, has rarely been researched, particularly from the superior's point of view. In addition, the vast majority of researchers have paid more attention to multicultural kindergartens in terms of immigrant children and their families. Hence, there is a need to show the problem which exists in the recruitment of the increasing number of workers who come from different countries. Opinions about kindergartens, as multicultural workplaces, have been gathered through interviews with immigrant workers responsible for education. In addition, a questionnaire for native Finnish workers and superiors in kindergartens was carried out. The collected material has been analyzed qualitatively, focusing on topics such as: the kindergarten as a multicultural workplace, factors influencing career success of workers with diverse language and cultural backgrounds, the social relations in the multicultural workplaces and teachers’ changing professional identity. The results of the research provided a novel aspect of the multicultural workplace and emphasized a dependency of immigrant workers’ on language skills in Finnish; affecting professional success. In addition, they showed the good relations between other native Finnish co-workers and superiors. The results also illustrate why writing skills in Finnish are so important in kindergartens. Part of the investigation also questions some results of the research i.e. which is more important in the kindergarten as a multicultural workplace: personality, good professional skills or good language skills.

Keywords: kindergarten, multicultural workplace, social relations at work, work satisfaction

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Authors: Khemakhem Nahed, Hammami Fatma, Trabelsi Houaida, Neji Sourour, Sellami Hayet, Makni Fattouma, Turki Hamida, Ayadi Ali

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Dermatophytoses are considered a public health problem and represent 10% of dermatological consultations in our region. Their epidemiology is influenced by various factors, such as lifestyle, human migration patterns, changes in the environment and the host relationship. The understanding of epidemiology has a major impact on their prevention and treatment. The aim of the study is to determine the prevalence pattern of aetiological agents and to describe the clinical characteristics of dermatophytoses between 1999 and 2019. Out of 65 059 subjects suspected to have superficial mycoses, 36 220 (55.67%) were affected with dermatophytoses. The mean age was 40.1 years (range: 10 days to 99 years). The sex ratio was 0.8. Our patients were from urban regions in 80.9% of cases. The most common type of infection was onychomycosis (42.64%), followed by tinea pedis (20.8%), intertrigo (18.3%), tinea corporis (8.48%) and tinea capitis (7.87%). The most isolated dermatophyte was Trichophyton rubrum (76.5%), followed by T. mentagrophytes complex (6.3%), Microsporum canis (5.8%), T. violaceum (5.3%), T. verrucosum (0.83%) and Epidermophyton floccosum (0.3%). Zoophilic agents have become more prevalent and their frequency has been increased from 6.46% in 1999 to 13% in 2019. It is interesting to note that M. canis has been on the rise since 2010 and it was the first etiological agent of tinea capitis (48%), while infections caused by T. violaceum continued to decrease from 1999 (16.2%) to 2019 (4.7%). Other dermatophytes have been rarely isolated: T. tonsurans (9 cases), T. schoenleinii (3 cases), T. soudanense (2 cases), M. fulvum (1 case), M. audouinii (1 case) and M. ferrugineum (2 cases).T. mentagrophytes var. quinckeanum was isolated from an inflammatory tinea capitis lesion in an a-3-year-old girl. T. mentagrophytes var. erinacei was isolated from the first case of tinea manuum, in-a-10-year-old girl. The same fungus was isolated from the hair and scales of the hedgehog. Our study showed significant changes in the dermatophytes spectrum in our region. The prevalence of zoophilic species increased in recent years due to people's behavioral changes with the adoption of pets and animal husbandry in urban settings. Molecular methods are often crucial that help us to refine the identification strains of dermatophytes and to identify their origin of the contamination.

Keywords: dermatophytoses, PCR-sequencing, spectrum, Sfax, Tunisia

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Authors: Laura Amato, Paolo Mulatti, Fabrizio Montarsi, Matteo Mazzucato, Laura Gagliazzo, Michele Brichese, Manlio Palei, Gioia Capelli, Lebana Bonfanti

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West Nile virus (WNV) re-emerged in north-eastern Italy in 2008, after ten years from its first appearance in Tuscany. In 2009, a national surveillance programme was implemented, and re-modulated in north-eastern Italy in 2011. Hereby, we present the results of surveillance activities in 2008-2016 in the north-eastern Italian regions, with inferences on WNV epidemiological trend in the area. The re-modulated surveillance programmes aimed at early detecting WNV seasonal reactivation by searching IgM antibodies in horses. In 2013, the surveillance plans were further modified including a risk-based approach. Spatial analysis techniques, including Bernoulli space-time scan-statistics, were applied to the results of 2010–2012 surveillance on mosquitoes, equines, and humans to identify areas where WNV reactivation was more likely to occur. From 2008 to 2016, residential horses tested positive for anti-WNV antibodies on a yearly basis (503 cases), also in areas where WNV circulation was not detected in mosquito populations. Surveillance activities detected 26 syndromic cases in horses, 102 infected mosquito pools and WNV in 18 dead wild birds. Human cases were also recurrently detected in the study area during the surveillance period (68 cases of West Nile neuroinvasive disease). The recurrent identification of WNV in animals, mosquitoes, and humans indicates the virus has likely become endemic in the area. In 2016, findings of WNV positives in horses or mosquitoes were included as triggers for enhancing screening activities in humans. The evolution of the epidemiological situation prompts for continuous and accurate surveillance measures. The results of the 2013-2016 surveillance indicate that the risk-based approach was effective in early detecting seasonal reactivation of WNV, key factor of the integrated surveillance strategy in endemic areas.

Keywords: arboviruses, horses, Italy, surveillance, west nile virus, zoonoses

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Authors: Mehri Sadat Alavinasab Ashgezari, Gholam Reza Nabi Bidhendi, Fatemeh Sadat Alavinasab Ashkezari

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Atmospheric aerosol loading (AAL) from anthropogenic sources is an evidence in industrial development. The accelerated trends in material consumption at the global scale in recent years demonstrate consumption paradigms sensible to the planetary boundaries (PB). This paper is a statistical approach on recognizing the path of climate-relevant bulk materials production (CBMP) of steel, cement and plastics to AAL via an updated and validated spatiotemporal distribution. The methodology of statistical analysis used the most updated regional or global databases or instrumental technologies. This corresponded to a selection of processes and areas capable for tracking AAL within the last decade, analyzing the most validated data while leading to explore the behavior functions or models. The results also represented a correlation within socio economic metabolism idea between the materials specified as macronutrients of society and AAL as a PB with an unknown threshold. The selected country contributors of China, India, US and the sample country of Iran show comparable cumulative AAL values vs to the bulk materials domestic extraction and production rate in the study period of 2012 to 2022. Generally, there is a tendency towards gradual descend in the worldwide and regional aerosol concentration after 2015. As of our evaluation, a considerable share of human role, equivalent 20% from CBMP, is for the main anthropogenic species of aerosols, including sulfate, black carbon and organic particulate matters too. This study, in an innovative approach, also explores the potential role of AAL control mechanisms from the economy sectors where ordered and smoothing loading trends are accredited through the disordered phenomena of CBMP and aerosol precursor emissions. The equilibrium states envisioned is an approval to the well-established theory of Spin Glasses applicable in physical system like the Earth and here to AAL.

Keywords: atmospheric aeroso loading, material flows, climate bulk materials, industrial ecology

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Authors: Fatma Mohamed Magdy Badr El Dine, Amr Mohamed Abd Allah

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Introduction: Age estimation of individuals is one of the crucial steps in forensic practice. Different traditional methods rely on the length of the diaphysis of long bones of limbs, epiphyseal-diaphyseal union, fusion of the primary ossification centers as well as dental eruption. However, there is a growing need for the development of precise and reliable methods to estimate age, especially in cases where dismembered corpses, burnt bodies, purified or fragmented parts are recovered. Teeth are the hardest and indestructible structure in the human body. In recent years, assessment of pulp/tooth area ratio, as an indirect quantification of secondary dentine deposition has received a considerable attention. However, scanty work has been done in Egypt in terms of applicability of pulp/tooth ratio for age estimation. Aim of the Work: The present work was designed to assess the Cameriere’s method for age estimation from pulp/tooth ratio of maxillary canines, central and lateral incisors among a sample from Egyptian population. In addition, to formulate regression equations to be used as population-based standards for age determination. Material and Methods: The present study was conducted on 270 peri-apical X-rays of maxillary canines, central and lateral incisors (collected from 131 males and 139 females aged between 19 and 52 years). The pulp and tooth areas were measured using the Adobe Photoshop software program and the pulp/tooth area ratio was computed. Linear regression equations were determined separately for canines, central and lateral incisors. Results: A significant correlation was recorded between the pulp/tooth area ratio and the chronological age. The linear regression analysis revealed a coefficient of determination (R² = 0.824 for canine, 0.588 for central incisor and 0.737 for lateral incisor teeth). Three regression equations were derived. Conclusion: As a conclusion, the pulp/tooth ratio is a useful technique for estimating age among Egyptians. Additionally, the regression equation derived from canines gave better result than the incisors.

Keywords: age determination, canines, central incisors, Egypt, lateral incisors, pulp/tooth ratio

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Authors: Mathodzi Nditsheni, Olawole Emmanuel Aina, Joshua Oluwole Olowoyo

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The ever-increasing world population is putting extreme pressure on the already limited agricultural resources for food production. Different soil enhancers were introduced by famers to meet the need of the ever-increasing population demand for food. One of the soil enhancers is the municipal waste sludge. This research investigated the differences in the concentrations of trace metals and levels of phytochemicals in four different tomato varieties cultivated on soil treated with municipal waste sludge in Pretoria, South Africa. Fruits were harvested at maturity and analyzed for trace metals and phytochemicals contents using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES) and a High-Performance Liquid Chromatography (HPLC) respectively. A one-way analysis of variance (ANOVA) was used to determine the differences in the concentrations of trace metals and phytochemical from different tomato varieties were significant. From the study, Rodade tomato bioaccumulated the highest concentrations of Mn, Cr, Cu and Ni, Roma bioaccumulated the highest concentrations of, Cd, Fe and Pb while Heinz bioaccumulated the highest concentrations of As and Zn. Cherry tomato on the other hand, recorded the lowest concentrations for most metals, Cd, Cr, Cu, Mn, Ni, Pb and Zn. The results of the study further showed that phenolic and flavonoids content were higher in the Solanum lycopersicum fruit grown in soils treated with municipal waste sludge. The study also showed that there was an inverse relationship between the levels of trace metals and phytochemicals. The calculated contamination factor values of trace metals like Cr, Cu, Pb and Zn were above the safe value of 1 which indicated that the tomato fruits may be unsafe for human consumption. However, the contamination factor values for the remaining trace metals were well below the safe value of 1. From the results obtained either for the control group or the treatment, the tomato varieties used in the study, bioaccumulated the toxic trace metals in their fruits and some of the values obtained were higher than the acceptable limit, which may then imply that the varieties of tomato used in this study bio accumulated the toxic trace metals from the soil, hence care should be taken when these tomato varieties are either cultivated or harvested from polluted areas

Keywords: trace metals, flavonoids, phenolics, waste sludge, tomato, contamination factors

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Authors: Banu Hatice Gürcüm, Pınar Arslan, Mahmut Yalçın

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Fashion designers create lots of dresses, suits, shoes, and other clothing and accessories, which are purchased every year by consumers. Fashion trends, sketches of designs, accessories affect the apparel goods, but colors make the finishing touches to an outfit. In all fields of apparel men's, women's, and children's wear, including casual wear, suits, sportswear, formal wear, outerwear, maternity, and intimate apparel, color sells. Thus, specialization in color in apparel is a basic concern each season. The perception of color is the key to sales for every sector in textile business. Mechanism of color perception, cognition in brain and color emotion are unique subjects, which scientists have been investigating for many years. The parameters of color may not be corresponding to visual scales since human emotions induced by color are completely subjective. However, with a very few exception each manufacturer concern their top selling colors for each season through seasonal sales reports of apparel companies. This paper examines sensory and instrumental methods for quantifying color of fabrics and investigates the relationship between fabric color and sale numbers. 5 top selling colors for each season from 10 leading apparel companies in the same segment are taken. The compilation is based according to the sales of the companies for 5 to 10 years. The research’s main concern is the corelation with the magnitude of seasonal color selling figures and the CIE chromaticity coordinates. The colors are chosen from the globally accepted Pantone Textile Color System and the three-dimentional measurement system CIE L*a*b* (CIELAB) is used, L* representing the degree of lightness of color, a* the degree of color ranging from magenta to green, and b* the degree of color ranging from blue to yellow. The objective of this paper is to demonstrate the feasibility of relating color perceptance to a laboratory instrument yielding measurements in the CIELAB system. Our approach is to obtain a total of a hundred reference fabrics to be measured on a laboratory spectrophotometer calibrated to the CIELAB color system. Relationships between the CIE tristimulus (X, Y, Z) and CIELAB (L*, a*, b*) are examined and are reported herein.

Keywords: CIELAB, CIE tristimulus, color preference, fashion

Procedia PDF Downloads 335

Authors: Valeria Arcucci, Musarat Ishaq, Steven A. Stacker, Greg J. Goodall, Marc G. Achen

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Metastasis is the lethal aspect of cancer for most patients. Remodelling of lymphatic vessels associated with a tumour is a key initial step in metastasis because it facilitates the entry of cancer cells into the lymphatic vasculature and their spread to lymph nodes and distant organs. Although it is clear that vascular endothelial growth factors (VEGFs), such as VEGF-C and VEGF-D, are key drivers of lymphatic remodelling, the means by which many signaling pathways in endothelial cells are coordinately regulated to drive growth and remodelling of lymphatics in cancer is not understood. We seek to understand the broader molecular mechanisms that control cancer metastasis, and are focusing on microRNAs, which coordinately regulate signaling pathways involved in complex biological responses in health and disease. Here, using small RNA sequencing, we found that a specific microRNA, miR-132, is upregulated in expression in lymphatic endothelial cells (LECs) in response to the lymphangiogenic growth factors. Interestingly, ectopic expression of miR-132 in LECs in vitro stimulated proliferation and tube formation of these cells. Moreover, miR-132 is expressed in lymphatic vessels of a subset of human breast tumours which were previously found to express high levels of VEGF-D by immunohistochemical analysis on tumour tissue microarrays. In order to dissect the complexity of regulation by miR-132 in lymphatic biology, we performed Argonaute HITS-CLIP, which led us to identify the miR-132-mRNA interactome in LECs. We found that this microRNA in LECs is involved in the control of many different pathways mainly involved in cell proliferation and regulation of the extracellular matrix and cell-cell junctions. We are now exploring the functional significance of miR-132 targets in the biology of LECs using biochemical techniques, functional in vitro cell assays and in vivo lymphangiogenesis assays. This project will ultimately define the molecular regulation of lymphatic remodelling by miR-132, and thereby identify potential therapeutic targets for drugs designed to restrict the growth and remodelling of tumour lymphatics resulting in metastatic spread.

Keywords: argonaute HITS-CLIP, cancer, lymphatic remodelling, miR-132, VEGF

Procedia PDF Downloads 128

Authors: Chiara Della Rocca, Gavino Piras, Andrea Berti, Alessandro Mameli

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DNA identification of human skeletal remains plays a valuable role in the forensic field, especially in missing persons and mass disaster investigations. Hard tissues, such as bones and teeth, represent a very common kind of samples analyzed in forensic laboratories because they are often the only biological materials remaining. However, the major limitation of using these compact samples relies on the extremely time–consuming and labor–intensive treatment of grinding them into powder before proceeding with the conventional DNA purification and extraction step. In this context, a DNA extraction assay called the TBone Ex kit (DNA Chip Research Inc.) was developed to digest bone chips without powdering. Here, we simultaneously analyzed bone and tooth samples that arrived at our police laboratory and belonged to 15 different forensic casework that occurred in Sardinia (Italy). A total of 27 samples were recovered from different scenarios and were exposed to extreme environmental factors, including sunlight, seawater, soil, fauna, vegetation, and high temperature and humidity. The TBone Ex kit was used prior to the EZ2 DNA extraction kit on the EZ2 Connect Fx instrument (Qiagen), and high-quality autosomal and Y-chromosome STRs profiles were obtained for the 80% of the caseworks in an extremely short time frame. This study provides additional support for the use of the TBone Ex kit for digesting bone fragments/whole teeth as an effective alternative to pulverization protocols. We empirically demonstrated the effectiveness of the kit in processing multiple bone samples simultaneously, largely simplifying the DNA extraction procedure and the good yield of recovered DNA for downstream genetic typing in highly compromised forensic real specimens. In conclusion, this study turns out to be extremely useful for forensic laboratories, to which the various actors of the criminal justice system – such as potential jury members, judges, defense attorneys, and prosecutors – required immediate feedback.

Keywords: DNA, skeletal remains, bones, tbone ex kit, extreme conditions

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Authors: Yutong Wan, John N. Wood

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Introduction: SCN9A encoded Nav1.7 is an ideal therapeutic target with minimal side effects for the pharmaceutical industry because SCN9A variants can cause both human gains of function pain-related mutations and loss of function pain-free mutations. This study reviews the clinical effectiveness of existing Nav1.7 inhibitors, which theoretically should be powerful analgesics. Methods: A systematic review is conducted on the effectiveness of current Nav1.7 blockers undergoing clinical trials. Studies were mainly extracted from PubMed, U.S. National Library of Medicine Clinical Trials, World Health Organization International Clinical Trials Registry, ISRCTN registry platform, and Integrated Research Approval System by NHS. Only studies with full text available and those conducted using double-blinded, placebo controlled, and randomised designs and reporting at least one analgesic measurement were included. Results: Overall, 61 trials were screened, and eight studies covering PF 05089771 (Pfizer), TV 45070 (Teva & Xenon), and BIIB074 (Biogen) met the inclusion criteria. Most studies were excluded because results were not published. All three compounds demonstrated insignificant analgesic effects, and the comparison between PF 05089771 and pregabalin/ibuprofen showed that PF 05089771 was a much weaker analgesic. All three drug candidates only have mild side effects, indicating the potentials for further investigation of Nav1.7 antagonists. Discussion: The failure of current Nav1.7 small molecule inhibitors might attribute to ignorance of the key role of endogenous systems in Nav1.7 null mutants, the lack of selectivity and blocking potency, and central impermeability. The synergistic combination of analgesic drugs, a recent UCL patent, combining a small dose of Nav1.7 blockers and opioids or enkephalinase inhibitors dramatically enhanced the analgesic effects. Conclusion: The current clinical testing Nav1.7 blockers are generally disappointing. However, the newer generation of Nav1.7 targeting analgesics has overcome the major constraints of its predecessors.

Keywords: chronic pain, Nav1.7 blockers, SCN9A, systematic review

Procedia PDF Downloads 131