Search results for: human papilloma virus

Authors: Olumuyiwa Ojo, Masengo Ilunga

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Artificial neural network (ANN) has broken the bounds of the convention programming, which is actually a function of garbage in garbage out by its ability to mimic the human brain. Its ability to adopt, adapt, adjust, evaluate, learn and recognize the relationship, behavior, and pattern of a series of data set administered to it, is tailored after the human reasoning and learning mechanism. Thus, the study aimed at modeling wastewater treatment process in order to accurately diagnose water control problems for effective treatment. For this study, a stage ANN model development and evaluation methodology were employed. The source data analysis stage involved a statistical analysis of the data used in modeling in the model development stage, candidate ANN architecture development and then evaluated using a historical data set. The model was developed using historical data obtained from Daspoort Wastewater Treatment plant South Africa. The resultant designed dimensions and model for wastewater treatment plant provided good results. Parameters considered were temperature, pH value, colour, turbidity, amount of solids and acidity. Others are total hardness, Ca hardness, Mg hardness, and chloride. This enables the ANN to handle and represent more complex problems that conventional programming is incapable of performing.

Keywords: ANN, artificial neural network, wastewater treatment, model, development

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Authors: Julia Ive, Lucia Specia

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Understanding and detecting toxicity is an important problem to support safer human interactions online. Our work focuses on the important problem of contextual toxicity detection, where automated classifiers are tasked with determining whether a short textual segment (usually a sentence) is toxic within its conversational context. We use “toxicity” as an umbrella term to denote a number of variants commonly named in the literature, including hate, abuse, offence, among others. Detecting toxicity in context is a non-trivial problem and has been addressed by very few previous studies. These previous studies have analysed the influence of conversational context in human perception of toxicity in controlled experiments and concluded that humans rarely change their judgements in the presence of context. They have also evaluated contextual detection models based on state-of-the-art Deep Learning and Natural Language Processing (NLP) techniques. Counterintuitively, they reached the general conclusion that computational models tend to suffer performance degradation in the presence of context. We challenge these empirical observations by devising better contextual predictive models that also rely on NLP data augmentation techniques to create larger and better data. In our study, we start by further analysing the human perception of toxicity in conversational data (i.e., tweets), in the absence versus presence of context, in this case, previous tweets in the same conversational thread. We observed that the conclusions of previous work on human perception are mainly due to data issues: The contextual data available does not provide sufficient evidence that context is indeed important (even for humans). The data problem is common in current toxicity datasets: cases labelled as toxic are either obviously toxic (i.e., overt toxicity with swear, racist, etc. words), and thus context does is not needed for a decision, or are ambiguous, vague or unclear even in the presence of context; in addition, the data contains labeling inconsistencies. To address this problem, we propose to automatically generate contextual samples where toxicity is not obvious (i.e., covert cases) without context or where different contexts can lead to different toxicity judgements for the same tweet. We generate toxic and non-toxic utterances conditioned on the context or on target tweets using a range of techniques for controlled text generation(e.g., Generative Adversarial Networks and steering techniques). On the contextual detection models, we posit that their poor performance is due to limitations on both of the data they are trained on (same problems stated above) and the architectures they use, which are not able to leverage context in effective ways. To improve on that, we propose text classification architectures that take the hierarchy of conversational utterances into account. In experiments benchmarking ours against previous models on existing and automatically generated data, we show that both data and architectural choices are very important. Our model achieves substantial performance improvements as compared to the baselines that are non-contextual or contextual but agnostic of the conversation structure.

Keywords: contextual toxicity detection, data augmentation, hierarchical text classification models, natural language processing

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Authors: Chinmayee Choudhury

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Human Melanocortin 4 Receptor (HMC4R) is one of the most potential drug targets for the treatment of obesity which controls the appetite. A deletion of the residues 88-92 in HMC4R is sometimes the cause of severe obesity in the humans. In this study, two homology models are constructed for the normal as well as mutated HMC4Rs and some phytochemicals present in Green Tea, Honey and Cinnamon have been docked to them to study their differential binding to the normal and mutated HMC4R as compared to the natural agonist α- MSH. Two homology models have been constructed for the normal as well as mutated HMC4Rs using the Modeller9v7. Some of the phytochemicals present in Green Tea, Honey, and Cinnamon, which have appetite suppressant activities are constructed, minimized and docked to these normal and mutated HMC4R models using ArgusLab 4.0.1. The mode of binding of the phytochemicals with the Normal and Mutated HMC4Rs have been compared. Further, the mode of binding of these phytochemicals with that of the natural agonist α- Melanocyte Stimulating Hormone(α-MSH) to both normal and mutated HMC4Rs have also been studied. It is observed that the phytochemicals Kaempherol, Epigallocatechin-3-gallate (EGCG) present in Green Tea and Honey, Isorhamnetin, Chlorogenic acid, Chrysin, Galangin, Pinocambrin present in Honey, Cinnamaldehyde, Cinnamyl acetate and Cinnamyl alcohol present in Cinnamon have capacity to form more stable complexes with the Mutated HMC4R as compared to α- MSH. So they may be potential agonists of HMC4R to suppress the appetite.

Keywords: HMC4R, α-MSH, docking, photochemical, appetite suppressant, homology modelling

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Authors: Deddi Nordiawan

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Effective public policy creation required a strong budget system, both in terms of design and implementation. Performance-based Budget is an evolutionary approach with two substantial characteristics; first, the strong integration between budgeting and planning, and second, its existence as guidance so that all activities and expenditures refer to measurable performance targets. There are four processes in the government that should be followed in order to make the budget become performance-based. These four processes consist of the preparation of a vision according to the bold aspiration, the formulation of outcome, the determination of output based on the analysis of organizational resources, and the formulation of Value Creation Map that contains a series of programs and activities. This is consistent with the concept of logic model which revealed that the budget performance should be placed within a relational framework of resources, activities, outputs, outcomes and impacts. Through the issuance of Law 17/2003 regarding State Finance, local governments in Indonesia have to implement performance-based budget. Central Government then issued Government Regulation 58/2005 which contains the detail guidelines how to prepare local governments budget. After a decade, implementation of performance budgeting in local government is still not fully meet expectations, though the guidance is completed, socialization routinely performed, and trainings have also been carried out at all levels. Accordingly, this study views the practice of performance-based budget at local governments as a problematic situation. This condition must be approached with a system approach that allows the solutions from many point of views. Based on the fact that the infrastructure of budgeting has already settled, the study then considering the situation as complexity. Therefore, the intervention needs to be done in the area of human activity system. Using Soft Systems Methodology, this research will reconstruct the process of performance-based budget at local governments is area of human activity system. Through conceptual models, this study will invite all actors (central government, local government, and the parliament) for dialogue and formulate interventions in human activity systems that systematically desirable and culturally feasible. The result will direct central government in revise the guidance to local government budgeting process as well as a reference to build the capacity building strategy.

Keywords: soft systems methodology, performance-based budgeting, Indonesia, public policy

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Authors: Chethan Purushothama

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Coronary artery disease is one of the major causes of death in developing countries. The coronary arteries show wide range of variations and these variations have not been dealt with different population groups. The present study aims to focus on the pattern and variations of coronary artery in south Indian population. The study was performed to analyze the coronary artery dominance and divisions of main trunk of left coronary artery in 81 isolated adult human cadaveric hearts of South Indian population. The specimens were fixed in 10% formalin and were dissected manually. In our specimens, 74.1% of the hearts were right dominant, 11.1% were left dominant, and 14.8% were co-dominant. Bifurcation, trifurcation, and quadrifurcation of main trunk of left coronary artery were seen in 49.4%, 48.1%, and 2.5% cases respectively. The right dominant hearts had bifurcation, trifurcation and quadrifurcation of main trunk of left coronary artery in 46.7%, 50% and 3.3% hearts respectively. The left dominant hearts had bifurcation and trifurcation of main trunk of left coronary artery in 55.6% and 44.4% cases respectively. The co-dominant hearts had bifurcation and trifurcation of main trunk of left coronary artery in 58.3% and 41.7% respectively. Quadrifurcation of main trunk of left coronary artery were seen only in right dominant hearts. We believe that the data obtained from the present study are important to the interventional cardiologists and radiologists. The details obtained will also be helpful for the clinical anatomists.

Keywords: bifurcation, coronary artery, trifurcation, quadrifurcation

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Authors: Aniruddha Hore, Saptarshi Mitra, Sandip Ghosh, Sujoy Bose, Avijit Ghosh

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The Indian rupee is the official currency of India. With time, science and technology got advanced, and our society is slowly making its way to a cashless mode of transaction. But as India is still a developing country, a large part of our society still depends on transaction through cash. During times of pandemics, we came to understand that everything that we touch is not safe from microbial contamination. The Indian currency is also not an exception. The Indian currency is the modern-day medium of harmful bacterial as well as other microbial contaminations resulting in diseases in human bodies. Therefore, the need came to make the currency disinfectant to give our people a healthier lifestyle. The main focus of the study is to develop a solution that, when applied to the currency notes, will kill the persisting bacteria or microbes present in the notes. So various natural edible products were used in order to prepare the solution, which is highly effective against the presence of harmful bacteria such as E. coli and S. aureus. The antibacterial activity of these natural ingredients is not unknown to us, so extracts from those products were mixed together to form a solution which was made the Indian currency notes antibacterial for 20min approx. The solution was creating a layer on the surface of currency notes, therefore, making it antibacterial for a given duration of time, i.e., no bacterial growth was seen during the time period of 20 minutes, therefore, making it safe for the usage of human hands.

Keywords: Indian currency, antibacterial property of Indian currency, surface coating, currency disinfectant

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Authors: Ming-Tzu Tsai, Jui-Ting Hsu, Chia-Chieh Lin, Feng-Tsai Chiang, Cheng-Chin Huang

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Far infrared (FIR), an invisible and short electromagnetic waves ranges from 6-14 μm also defines as the “growth ray.” Although the mechanism of FIR is still unknown, most data have suggested that FIR could accelerate the skin microcirculation by elevating the blood flow and nitric-oxide (NO) synthesis. In this present work, the effect of FIR irradiation and endothelial cell growth supplement (ECGS) on human umbilical vascular endothelial cells (HUVECs) was evaluated. To understand whether the cell viability and NO production of HUVECs affected by NO, cells with/without ECGS were treated in the presence or absence of L-NAME, an eNOS inhibitor. For FIR exposure, FIR-emitted ceramic powders consisted of a variety of well-mixed metal oxides were developed. The results showed that L-NAME did had a strong effect on the inhibition of NO production, especially in the ECGS-treated group. However, the cell viability of each group was rarely affected in the presence of L-NAME. Cells with the incubation of ECGS showed much higher cell viability compared to the control. Moreover, NO production of HUVECs exposed to FIR irradiation was significantly inhibited in the presence of L-NAME. It suggested that NO could play a role modulating the downstream signals of HUVECs during FIR exposure.

Keywords: far-infrared irradiation (FIR), nitric oxide (NO), endothelial nitric oxide synthase (eNOS), endothelial cell growth supplement (ECGS)

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Authors: Ananya Das, Arun Kumar, Gazala Habib, Vivekanandan Perumal

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Regulatory bodies has proposed limits on Particulate Matter (PM) concentration in air; however, it does not explicitly indicate the incorporation of effects of toxicities of constituents of PM in developing regulatory limits. This study aimed to provide a structured approach to incorporate toxic effects of components in developing regulatory limits on PM. A four-step human health risk assessment framework consists of - (1) hazard identification (parameters: PM and its constituents and their associated toxic effects on health), (2) exposure assessment (parameters: concentrations of PM and constituents, information on size and shape of PM; fate and transport of PM and constituents in respiratory system), (3) dose-response assessment (parameters: reference dose or target toxicity dose of PM and its constituents), and (4) risk estimation (metric: hazard quotient and/or lifetime incremental risk of cancer as applicable). Then parameters required at every step were obtained from literature. Using this information, an attempt has been made to determine limits on PM using component-specific information. An example calculation was conducted for exposures of PM_2.5 and its metal constituents from Indian ambient environment to determine limit on PM values. Identified data gaps were: (1) concentrations of PM and its constituents and their relationship with sampling regions, (2) relationship of toxicity of PM with its components.

Keywords: air, component-specific toxicity, human health risks, particulate matter

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Authors: Geetakshi Arora, Danish Malhotra

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Diabetic wounds are serious health issues and often fail to heal, leading to limb amputation that makes the life of the patient miserable. Delayed wound healing has been characterized by an increase in matrix metalloproteinase-9 (MMP-9). Thus research throughout the world has been going on to develop selective MMP-9 inhibitors for aiding diabetic wound healing. Bioactive constituents from natural sources always served as potential leads in drug development with high rates of success. Considering the need for novel selective MMP-9 inhibitors and the importance of natural bioactive compounds in drug development, we have screened a library of bioactive constituents from plant sources that were effective in diabetic wound healing on human MMP-9 (hMMP-9) using molecular docking studies. Screened constituents are ranked according to their dock score, ∆G value (binding affinity), and Ligand efficiency evaluated from FleXX docking and Hyde scoring modules available with drug designing platform LeadIT. Rhamnocitrin showed the highest correlation between dock score, ∆G value (binding affinity), and Ligand efficiency was further explored for binding interactions with hMMP-9. The overall study suggest that Rhamnocitrin is sufficiently decorated with both hydrophilic and hydrophobic substitutions that perfectly block hMMP-9 and act as a potential lead in the design and development of selective hMMP-9 inhibitors.

Keywords: MMP-9, diabetic wound, molecular docking, phytoconstituents

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Authors: Manal M. Kame, Zeinab A. Demerdash, Hanan G. El-Baz, Salwa M. Hassan, Faten M. Salah, Wafaa Mansour, Olfat Hammam

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Cord blood (CB) derived Unrestricted Somatic Stem Cells (USSCs) with their multipotentiality hold great promise in liver regeneration. This work aims at evaluation of the therapeutic potentiality of USSCs in two experimental models of chronic liver injury induced either by S. mansoni infection in balb/c mice or CCL4 injection in hamsters. Isolation, propagation, and characterization of USSCs from CB samples were performed. USSCs were induced to differentiate into osteoblasts, adipocytes and hepatocyte-like cells. Cells of the third passage were transplanted in two models of liver fibrosis: (1) Twenty hamsters were induced to liver fibrosis by repeated i. p. injection of 100 μl CCl4 /hamster for 8 weeks. This model was designed as; 10 hamsters with liver fibrosis and treated with i.h. injection of 3x106 USSCs (USSCs transplanted group), 10 hamsters with liver fibrosis (pathological control group), and 10 hamsters with healthy livers (normal control group). (2) Murine chronics S.mansoni model: twenty mice were induced to liver fibrosis with S. mansoni ceracariae (60 cercariae/ mouse) using the tail immersion method and left for 12 weeks. This model was designed as; 10 mice with liver fibrosis were transplanted with i. v. injection of 1×106 USCCs (USSCs transplanted group). Other 2 groups were designed as in hamsters model. Animals were sacrificed 12 weeks after USSCs transplantation, and their liver sections were examined for detection of human hepatocyte-like cells by immunohistochemistry staining. Moreover, liver sections were examined for fibrosis level, and fibrotic indices were calculated. Sera of sacrificed animals were tested for liver functions. CB USSCs, with fibroblast-like morphology, expressed high levels of CD44, CD90, CD73 and CD105 and were negative for CD34, CD45, and HLA-DR. USSCs showed high expression of transcripts for Oct4 and Sox2 and were in vitro differentiated into osteoblasts, adipocytes. In both animal models, in vitro induced hepatocyte-like cells were confirmed by cytoplasmic expression of glycogen, alpha-fetoprotein, and cytokeratin18. Livers of USSCs transplanted group showed engraftment with human hepatocyte-like cells as proved by cytoplasmic expression of human alpha-fetoprotein, cytokeratin18, and OV6. In addition, livers of this group showed less fibrosis than the pathological control group. Liver functions in the form of serum AST & ALT level and serum total bilirubin level were significantly lowered in USSCs transplanted group than pathological control group (p < 0.001). Moreover, the fibrotic index was significantly lower (p< 0.001) in USSCs transplanted group than pathological control group. In addition liver sections, of i. v. injection of 1×106 USCCs of mice, stained with either H&E or sirius red showed diminished granuloma size and a relative decrease in hepatic fibrosis. Our experimental liver fibrosis models transplanted with CB-USSCs showed liver engraftment with human hepatocyte-like cells as well as signs of liver regeneration in the form of improvement in liver function assays and fibrosis level. These data provide hope that human CB- derived USSCs are introduced as multipotent stem cells with great potentiality in regenerative medicine & strengthens the concept of cellular therapy for the treatment of liver fibrosis.

Keywords: cord blood, liver fibrosis, stem cells, transplantation

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Authors: David Abrahams

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In October 2016 South Africa deposited its ‘instrument of withdrawal’ from the Rome Statute of the International Criminal Court, with the Secretary-General of the United Nations. The Rome Statute is the founding document of the treaty-based International Criminal Court (ICC). The ICC has jurisdiction to hear cases where crimes against humanity, war crimes and genocide have been committed, on the basis of individual criminal responsibility. It is therefore not surprising that one of the ICCs mandates is to ensure that the sufferings, due to gross human rights violations towards the civilian population is, in principle, brought to an end by punishing those individuals responsible, thus providing justice to the victims. The ICC is unable to effectively fulfill its mandate and thus depends, in part on the willingness of states to assist the Court in its functions. This requires states to ratify the Statute and to domesticate its provisions, depending on whether it is a monist or dualist state. South Africa ratified the Statute in November 2000, and domesticated the Statute in 2002 by virtue of the Implementation of the Rome Statute of the International Criminal Court Act 27 of 2002. South Africa thus remains under an obligation to cooperate with the ICC until the final date of withdrawal, which is October 2017. An AU Summit was hosted by South Africa during June 2015. Omar Al-Bashir, whom the prosecutor of the ICC has indicted on two separate occasions, was invited to the summit. South Africa made an agreement with the AU that it will honour its obligations in terms of its Diplomatic and Immunities Privileges Act of 2001, by granting immunity to all heads of state, including that of Sudan. This decision by South Africa has raised a plethora of questions regarding the status and hierarchy of international laws versus regional laws versus domestic laws. In particular, this paper explores whether a state’s international law treaty obligations may be suspended in favour of, firstly, regional peace (thus safeguarding the security of the civilian population against further atrocities and other gross violations of human rights), and secondly, head of state immunity. This paper also reflects on the effectiveness of the trias politca in South Africa in relation the manner in which South African courts have confirmed South Africa’s failure in fulfilling its obligations in terms of the Rome Statute. A secondary question which will also be explored, is whether the Rome Statute is currently an effective tool in dealing with gross violations of human rights, particularly in a regional African context, given the desire by a number of African states currently party to the Statute, to engage in a mass exodus from the Statute. Finally, the paper concludes with a proposal that there can be no justice for victims of gross human rights violations unless states are serious in playing an instrumental role in bringing an end to impunity in Africa, and that withdrawing from the ICC without an alternative, effective system in place, will simply perpetuate impunity.

Keywords: African Union, diplomatic immunity, impunity, international criminal court, South Africa

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Authors: Sepideh Hassanpour Khodaei

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Background/Objectives: The purpose of this study is to evaluate the effect of mummy substances on two issues of proliferation and production of matrix protein synthesis in wound healing. Methods: The methodology used for this aim involves isolating mesenchymal stem cells and human fibroblasts procured at Pastor Institute, Iran. The cells were treated with mummy substances separately and co-cultured between ASCs and WJSCs, and fibroblasts. Proliferation was assessed by Ki67 method in monolayer conditions. Synthesis of components of extracellular matrix (ECM) such as collagen type I, type III, and fibronectin 1 (FN1) was determined by qPCR. Results: The effects of adipocyte stem cells (ASCs), Wharton Jelly Stem Cells (WJSCs), and Mummy material on fibroblast proliferation and migration were evaluated. The present finding underlined the importance of Mummy material, ASCs, and WJSCs in the proliferation and migration of fibroblast cells. Furthermore, the expression of collagen I, III, and FN1 was increased in the presence of the above material and cells. Conclusion: This study presented an effective in vitro method for the healing process. Hence, the prospect of utilizing Mummy material and stem cell-based therapies in wound healing as a therapeutic approach is promising.

Keywords: mummy material, wound healing, adipose tissue, Wharton’s jelly

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Authors: Gehan ElAkabawy

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Background: Diabetes mellitus causes severe deteriorations of almost all the organs and systems of the body, as well as significant damage to the oral cavity. The oral changes are mainly related to salivary glands dysfunction characterized by hyposalivation and xerostomia, which significantly reduce diabetic patients’ quality of life. Human dental pulp stem cells represent a promising source for cell-based therapies, owing to their easy, minimally invasive surgical access, and high proliferative capacity. It was reported that the trophic support mediated by dental pulp stem cells can rescue the functional and structural alterations of damaged salivary glands. However, potential differentiation and paracrine effects of human dental pulp stem cells in diabetic-induced parotid gland damage have not been previously investigated. Our study aimed to investigate the therapeutic effects of intravenous transplantation of human dental pulp stem cells (hDPSCs) on parotid gland injury in a rat model of streptozotocin (STZ)-induced type 1 diabetes. Methods: Thirty Sprague-Dawley male rats were randomly categorised into three groups: control, diabetic (STZ), and transplanted (STZ+hDPSCs). hDPSCs or vehicle was injected into the tail vein 7 days after STZ injection. The fasting blood glucose levels were monitored weekly. A glucose tolerance test was performed, and the parotid gland weight, salivary flow rate, oxidative stress indices, parotid gland histology, and caspase-3, vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen (PCNA) expression in parotid tissues were assessed 28 days post-transplantation. Results: Transplantation of hDPSCs downregulated blood glucose, improved the salivary flow rate, and reduced oxidative stress. The cells migrated to, survived, and differentiated into acinar, ductal, and myoepithelial cells in the STZ-injured parotid gland. Moreover, they downregulated the expression of caspase-3 and upregulated the expression of VEGF and PCNA, likely exerting pro-angiogenetic and antiapoptotic effects and promoting endogenous regeneration. In addition, the transplanted cells enhanced the parotid nitric oxide (NO) -tetrahydrobiopterin (BH4) pathway. Conclusions: Our results show that hDPSCs can migrate to and survive within the STZ-injured parotid gland, where they prevent its functional and morphological damage by restoring normal glucose levels, differentiating into parotid cell populations, and stimulating paracrine-mediated regeneration. Thus, hDPSCs may have therapeutic potential in the treatment of diabetes-induced parotid gland injury.

Keywords: dental pulp stem cells, diabetes, streptozotocin, parotid gland

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Authors: Nikhil Kewalkrishna Mehta

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In the past researchers have questioned the effectiveness of ethics training in higher education. Also, there are observations that support the view that ethical behaviour (range of actions)/ethical decision making models used in the past make use of vignettes to explain ethical behaviour. The understanding remains in the perspective that these vignettes play a limited role in determining individual intentions and not actions. Some authors have also agreed that there are possibilities of differences in one’s intentions and actions. This paper makes an attempt to fill those gaps by evaluating real actions rather than intentions. In a way this study suggests the use of an experiential methodology to explore Berlo’s model of communication as an action along with orchestration of various principles. To this endeavor, an attempt was made to use conversational analysis in the pursuance of evaluating ethical decision making behaviour among students and middle level managers. The process was repeated six times with the set of an average of 15 participants. Similarities have been observed in the behaviour of students and middle level managers that calls for understanding that both the groups of individuals have no cognizance of their actual actions. The deliberations derived out of conversation were taken a step forward for meta-ethical evaluations to portray a clear picture of ethical behaviour among participants. This study provides insights for understanding demonstrated unconscious human behaviour which may fortuitously be termed both ethical and unethical.

Keywords: ethical behaviour, unethical behavior, ethical decision making, intentions and actions, conversational analysis, human actions, sensitivity

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Authors: Kassaye Bewketu Zellelew

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The Main Ethiopian Rift Valley lakes suffer from water level fluctuations due to several natural and anthropocentric factors. Lakes located at terminal positions are highly affected by the fluctuations. These fluctuations are disturbing the stability of ecosystems, putting very serious impacts on the lives of many animals and plants around the lakes. Hence, studying the hydrodynamics of the lakes was found to be very essential. The main purpose of this study is to find the most significant factors that contribute to the water level fluctuations and also to quantify the fluctuations so as to identify lakes that need special attention. The research method included correlations, least squares regressions, multi-temporal satellite image analysis and land use change assessment. The results of the study revealed that much of the fluctuations, specially, in Central Ethiopian Rift are caused by human activities. Lakes Abiyata, Chamo, Ziway and Langano are declining while Abaya and Hawassa are rising. Among the studied lakes, Abiyata is drastically reduced in size (about 28% of its area in 1986) due to both human activities (most dominant ones) and natural factors. The other seriously affected lake is Chamo with about 11% reduction in its area between 1986 and 2010. Lake Abaya was found to be relatively stable during this period (showed only a 0.8% increase in its area). Concerned bodies should pay special attention to and take appropriate measures on lakes Abiyata, Chamo and Hawassa.

Keywords: correlations, hydrodynamics, lake level fluctuation, landsat satellite images

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Authors: Jou-An Chen, Julio Castillo, Errol Duncan Cason, Gabre Kemp, Leana Esterhuizen, Angel Valverde Portal, Esta Van Heerden

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Emerging contaminants (EC) such as pharmaceutical and personal care products have been accumulating for years in water bodies all over the world. However, very little is known about the occurrences, levels, and effects of ECs in South African water resources. This study provides an initial assessment of the distribution of eight ECs (Acetaminophen, Atrazine, Terbuthlyazine, Carbamazepine, Phenyton, Sulfmethoxazole, Nevirapine and Fluconozole) in fifteen water sources from the Free State and Easter Cape provinces of South Africa. Overall, the physiochemical conditions were different in surface and groundwater samples, with concentrations of several elements such as B, Ca, Mg, Na, NO3, and TDS been statistically higher in groundwater. In contrast, ECs levels, quantified at ng/mL using the LC/MS/ESI, were much lower in groundwater samples. The ECs with higher contamination levels were Carbamazepine, Sulfmethoxazole, Nevirapine, and Terbuthlyazine, while the most widespread were Sulfmethoxazole and Fluconozole, detected in all surface and groundwater samples. Fecal and E. coli tests indicated that surface water was more contaminated than groundwater. Microbial communities, assessed using NGS, were dominated by the phyla Proteobacteria and Bacteroidetes, in both surface and groundwater. Actinobacteria, Planctomycetes, and Cyanobacteria, were more dominant in surface water, while Verrucomicrobia were overrepresented in groundwater. In conclusion, ECs contamination is closely associated with human activities (human wastes). The microbial diversity identified can suggest possible biodegradation processes.

Keywords: emerging contaminants, EC, personal care products, pharmaceuticals, natural attenuation process

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Authors: O. R. Razanakoto, L. Temple

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Living in a least developed country, the Malagasy society has a weak capacity to internalize progress, including health concerns. Since the arrival in the fifteenth century of Arabic script, called Sorabe, that was mainly dedicated to the aristocracy, until the colonial era beginning at the end of the nineteenth century and that has popularized the current usual script of the occidental civilization, the upcoming manuscripts that deal with apparent scientific or at least academic issue have been slowly established. So that, the Malagasy communities’ way of life is not well documented yet to allow a precise understanding of the major concerns, reason, and purpose of the existence of the farmers that compose them. A question arises, according to literature, how does Malagasy community that is dominated by agrarian society conceive the conservation of its wellbeing? This study aims to emphasize the scope and the limits of the « One Health » concept or of the Health Integrated Approach (HIA) that evolves at global scale, with regard to the specific context of local Malagasy smallholder farms. It is expected to identify how this society represents linked risks and the mechanisms between human health, animal health, plant health, and ecosystem health within the last 100 years. To do so, the framework to conduct systematic review for agricultural research has been deployed to access available literature. This task has been coupled with the reading of articles that are not indexed by online scientific search engine but that mention part of a history of agriculture and of farmers in Madagascar. This literature review has informed the interactions between human illnesses and those affecting animals and plants (breeded or wild) with any unexpected event (ecological or economic) that has modified the equilibrium of the ecosystem, or that has disturbed the livelihoods of agrarian communities. Besides, drivers that may either accentuate or attenuate the devasting effects of these illnesses and changes were revealed. The study has established that the reasons of human worries are not only physiological. Among the factors that regulate global health, food system and contemporary medicine have helped to the improvement of life expectancy from 55 to 63 years in Madagascar during the last 50 years. However, threats to global health are still occurring. New human or animal illnesses and livestock / plant pathology or enemies may also appear, whereas ancient illnesses that are supposed to have disappeared may be back. This study has highlighted how much important are the risks associated to the impact of unmanaged externalities that weaken community’s life. Many risks, and also solutions, come from abroad and have long term effects even though those happen as punctual event. Thus, a constructivist strategy is suggested to the « One Health » global concept throughout the record of local facts. This approach should facilitate the exploration of methodological pathways and the identification of relevant indicators for research related to HIA.

Keywords: agrarian system, health integrated approach, history, madagascar, resilience, risk

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Authors: Mustafa Abdul Rahman, Maisarah Abdullah, Nurfarahin Azizan, Mohd-Azlan Jayasilan, Andrew Alek Tuen

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Common myna (Acridotheres tristis) and Javan myna (A. javanicus) belong to the family Sturnidae. These two species range from Iran, Afghanistan, and east through the Indian subcontinent to south China, Indochina and the mainland Southeast Asia. It was introduced to Sarawak in 1980’s and since then the population has increased tremendously. A study to determine the density of these two species was conducted in the Kuching and Samarahan Districts, Sarawak, Malaysian Borneo between November 2013 and January 2014. In Kuching City a total of 12 transect lines of 500 m each were established totaling 6 km. In Samarahan District, six 500 m transect lines were established both within Universiti Malaysia Sarawak (UNIMAS) campus and in Serian Town totaling 6 km. The results showed that the density of Javan myna in Kuching City (east) was 13.9 birds/ha, Kuching City (center) was 21.3 birds/ha and Kuching City (west) was 43.1 birds/ha. The density of common myna at UNIMAS campus was 20.3 birds/ha and Serian Town was 13.2 birds/ha. The density of human population probably plays an important role in determining the density of mynas in an area as it is associated with the availability of food sources, roosting and nesting places originating from human activity.

Keywords: density, myna, transect, invasive, Sarawak, Borneo

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Authors: Nicholas Fieseler

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The nature of religion implicit in popular culture is relevant both in and out of the university. The traditional rules-based conception of religion and the ethical systems that emerge from them do not necessarily convey the behavior of daily life as it exists apart from spaces deemed sacred. This paper proposes to examine the religion implicit in the popular culture phenomenon of professional wrestling and how that affects the understanding of popular religion. Pro wrestling, while frequently dismissed, offers a unique manner through which to re-examine religion in popular culture. A global phenomenon, pro wrestling occupies a distinct space in numerous countries and presents a legitimate reflection of human behavior cross-culturally on a scale few other phenomena can equal. Given its global viewership of millions, it should be recognized as a significant means of interpreting the human attraction to violence and its association with religion in general. Hans Urs von Balthasar’s theory of Theodrama will be used to interrogate the inchoate religion within pro wrestling. While Balthasar developed theodrama within the confines of Christian theology; theodrama contains remarkable versatility in its potential utility. Since theodrama re-envisions reality as drama, the actions of every human actor on the stage contributes to the play’s development, and all action contains some transcendent value. It is in this sense that even the “low brow” activity of pro wrestling may be understood in religious terms. Moreover, a pro wrestling storyline acts as a play within a play: the struggles in a pro wrestling match reflect the human attitudes toward life as it exists in the sacred and profane realms. The indistinct lines separating traditionally good (face) from traditionally bad (heel)wrestlers mirror the moral ambiguity in which many people interpret life. This blurred distinction between good and bad, and large segments of an audience’s embrace of the heel wrestlers, reveal ethical constraints that guide the everyday values of pro wrestling spectators, a moral ambivalence that is often overlooked by traditional religious systems, and which has hitherto been neglected in the academic literature on pro wrestling. The significance of interpreting the religion implicit in pro wrestling through a the dramatic lens extends beyond pro wrestling specifically and can examine the religion implicit in popular culture in general. The use of theodrama mitigates the rigid separation often ascribed to areas deemed sacred/ profane, ortranscendent / immanent, enabling a re-evaluation of religion and ethical systems as practiced in popular culture. The use of theodrama will be expressed by utilizing the pro wrestling match as a literary text that reflects the society from which it emerges. This analysis will also reveal the complex nature of religion in popular culture and provides new directions for the academic study of religion. This project consciously bridges the academic and popular realms. The goal of the research is not to add only to the academic literature on implicit religion in popular culture but to publish it in a form which speaks to those outside the standard academic audiences for such work.

Keywords: ethics, popular religion, professional wrestling, theodrama

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Authors: Monir Ahmed

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The main purpose of this paper is to analyze existing conceptual papers on the divine relationship. The primary objective of the paper is to illustrate cognitive orientation as a determinant of divine relationship. A further aim of the paper is to establish whether spiritual or religious practices, rituals, or acts alone could confirm a relationship with the sacred or the divine. Searching for the sacred or the divine is known to be a novel way of understanding the meaning and purpose of human existence, including the existence of everything around us. Inevitably, searching for the sacred provides an opportunity for human beings to form a relationship with the divine. Research suggests that discovering meaning and purpose through searching for the sacred or forming relationship with the divine enhances psychological well-being and eventually helps individuals to flourish. The search for the sacred and the discovery of the divine relationship thus have become interesting areas of study in Psychology of Religion and Spirituality. The existing conceptual papers on the relationship with the transcendent source, i.e., the divine creator, were systematically reviewed and analyzed. The outcome of the review reveals that the existing understanding of the relationship with the divine source is inadequate and that such understanding is unable to indicate or confirm a relationship with psychological well-being, including spiritual well-being. The importance of cognitive orientation, including cognitive processes as well as ‘creatio ex nihilo’ doctrine in searching for the sacred, is indicated. The author of this paper proposes that cognitive-theological understanding involving faith and belief about the creation and the divine source, the transcendent God is likely to offer a comprehensive understanding of the divine relationship.

Keywords: divine, well-being, analysis, cognitive orientation, ‘creatio ex nihilo’ doctrine

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Authors: Fantu Lombamo Untiso, Sylvia Murphy, Emily Pieracci

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Background: Rabies is a highly fatal viral disease of all warm-blooded animals including human globally. However, effective rabies control program still remains to be a reality and needs to be strengthened. Objective: Reviewing of recorded data and analyzing it to generate information on the status of rabies in Addis Ababa in the year 2012/13. Methods: A retrospective data were used from the Ethiopian Public Health Institute rabies case record book registered in the year 2012/13. Results: Among 1357 suspected rabid animals clinically examined; only 8.84% were positive for rabies. Out of 216 animal brains investigated in the laboratory with Fluorescent Antibody Technique, 55.5% were confirmed rabies positive. Among the laboratory confirmed positive rabies cases, high percentage of the animals came from Yeka (20%) and lower number from Kirkos subcity (3.3%). Out of 1149 humans who came to the institute seeking anti-rabies post-exposure prophylaxis, 85.65% and 7.87% of them were exposed to suspected dogs and cats respectively. 3 human deaths due to rabies were reported in the year after exposure to dog bite of unknown vaccination status. Conclusion: The principal vector of rabies in Addis Ababa is dog. Effective rabies management and control based on confirmed cases and mass-immunization and control of stray dog populations is recommended.

Keywords: Addis Ababa, exposure, rabies, surveillance

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Authors: Vera Lúcia Raposo

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The right to health care – usually known as the right to health – is recognized in many national laws and Constitutions, as well as in international human rights documents. The kind of health care that citizens are entitled to receive, especially in the framework of the National Health Service, is usually identified with conventional medicine. However, since ancient times that a different form of medicine – alternative, traditional or nonconventional medicine – exists. In recent times it is attracting increasing interest, as it is demonstrated by the use of its specific knowledge either by pharmaceutical companies either by modern health technologies. Alternative medicine refers to a holistic approach to body and mind using herbal products, animal parts and minerals instead of technology and pharmaceutical drugs. These notes contributed to a sense of distrust towards it, accusing alternative medicine of being based on superstition and ignorance. However, and without denying that some particular practices lack indeed any kind of evidence or scientific grounds, the fact is that a substantial part of alternative medicine can actually produce satisfactory results. The paper will not advocate the substitution of conventional medicine by alternative medicine, but the complementation between the two and their specific knowledge. In terms of the right to health, as a fundamental right and a human right, this thesis leads to the implementation of a wider range of therapeutic choices for patients, who should be entitled to receive different forms of health care that complement one another, both in public and private health facilities. This scenario would demand a proper regulation for alternative medicine, which nowadays does not exist in most countries, but it is essential to protect patients and public health in general and to reinforce confidence in alternative medicine.

Keywords: alternative medicine, conventional medicine, patient’s rights, right to health

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Authors: Georgios A. Fragkiadakis, Antonia Psaroudaki, Theodora Mouratidou, Eirini Sfakianaki

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Research: Within the project "Actions for the optimal utilization of the potential of carob in the Region of Crete" which is financed-supervised by the Region, with collaboration of Crete University and Hellenic Mediterranean University, a SWOT (strengths, weaknesses, opportunities, threats) survey was carried out, to evaluate the prospects of carob in human nutrition, in Crete. Results and conclusions: 1). Strengths: There exists a local production of carob for human consumption, based on international reports, and local-product reports. The data on products in the market (over 100 brands of carob food), indicates a sufficiency of carob materials offered in Crete. The variety of carob food products retailed in Crete indicates a strong demand-production-consumption trend. There is a stable number (core) of businesses that invest significantly (Creta carob, Cretan mills, etc.). The great majority of the relevant food stores (bakery, confectionary etc.) do offer carob products. The presence of carob products produced in Crete is strong on the internet (over 20 main professionally designed websites). The promotion of the carob food-products is based on their variety and on a few historical elements connected with the Cretan diet. 2). Weaknesses: The international prices for carob seed affect the sector; the seed had an international price of €20 per kg in 2021-22 and fell to €8 in 2022, causing losses to carob traders. The local producers do not sort the carobs they deliver for processing, causing 30-40% losses of the product in the industry. The occasional high price triggers the collection of degraded raw material; large losses may emerge due to the action of insects. There are many carob trees whose fruits are not collected, e.g. in Apokoronas, Chania. The nutritional and commercial value of the wild carob fruits is very low. Carob trees-production is recorded by Greek statistical services as "other cultures" in combination with prickly pear i.e., creating difficulties in retrieving data. The percentage of carob used for human nutrition, in contrast to animal feeding, is not known. The exact imports of carob are not closely monitored. We have no data on the recycling of carob by-products in Crete. 3). Opportunities: The development of a culture of respect for carob trade may improve professional relations in the sector. Monitoring carob market and connecting production with retailing-industry needs may allow better market-stability. Raw material evaluation procedures may be implemented to maintain carob value-chain. The state agricultural services may be further involved in carob-health protection. The education of farmers on carob cultivation/management, can improve the quality of the product. The selection of local productive varieties, may improve the sustainability of the culture. Connecting the consumption of carob with health-food products, may create added value in the sector. The presence and extent of wild carob threes in Crete, represents, potentially, a target for grafting. 4). Threats: The annual fluctuation of carob yield challenges the programming of local food industry activities. Carob is a forest species also - there is danger of wrong classification of crops as forest areas, where land ownership is not clear.

Keywords: human nutrition, carob food, SWOT analysis, crete, greece

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Authors: Temosho Promise Chuene, T. Chitura

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Background: Foot and mouth disease is a real challenge in South Africa. The disease is a serious threat to the viability of livestock farming initiatives and affects local and international livestock trade. In Limpopo Province, the Kruger National Park and other game reserves are home to the African buffalo (Syncerus caffer), a notorious reservoir of the picornavirus, which causes foot and mouth disease. Out of the virus’s seven (7) distinct serotypes, Southern African Territories (SAT) 1, 2, and 3 are commonly endemic in South Africa. The broad objective of the study was to establish the trend of foot and mouth disease in Limpopo Province over a seven-year period (2014-2020), as well as the adoption and comprehensive reporting of the measures that are taken to contain disease outbreaks in the study area. Methods: The study used secondary data from the World Organization for Animal Health (WOAH) on reported cases of foot and mouth disease in South Africa. Descriptive analysis (frequencies and percentages) and Analysis of variance (ANOVA) were used to present and analyse the data. Result: The year 2020 had the highest prevalence of foot and mouth disease (3.72%), while 2016 had the lowest prevalence (0.05%). Serotype SAT 2 was the most endemic, followed by SAT 1. Findings from the study demonstrated the seasonal nature of foot and mouth disease in the study area, as most disease cases were reported in the summer seasons. Slaughter of diseased and at-risk animals was the only documented disease control strategy, and information was missing for some of the years. Conclusion: The study identified serious underreporting of the adopted control strategies following disease outbreaks. Adoption of comprehensive disease control strategies coupled with thorough reporting can help to reduce outbreaks of foot and mouth disease and prevent losses to the livestock farming sector of South Africa and Limpopo Province in particular.

Keywords: livestock farming, African buffalo, prevalence, serotype, slaughter

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Authors: Gobinathan Devathasan, Kezia Devathasan

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Objective: To improve the current modified Broca-Wernicke-Lichtheim-Kussmaul speech schema and provide insight into autism. Methods: We reviewed the pertinent literature. Current findings, involving Brodmann areas 22, 46, 9,44,45,6,4 are based on neuropathology and functional MRI studies. However, in primary autism, there is no lucid explanation and changes described, whether neuropathology or functional MRI, appear consequential. Findings: We forward an enhanced model which may explain the enigma related to autism. Vowel output is subcortical and does need cortical representation whereas consonant speech is cortical in origin. Left lateralization is needed to commence the circuitry spin as our life have evolved with L-amino acids and left spin of electrons. A fundamental species difference is we are capable of three syllable-consonants and bi-syllable expression whereas cetaceans and songbirds are confined to single or dual consonants. The 4 key sites for speech are superior auditory cortex, Broca’s two areas, and the supplementary motor cortex. Using the Argand’s diagram and Reimann’s projection, we theorize that the Euclidean three dimensional synaptic neuronal circuits of speech are quantized to coherent waves, and then decoherence takes place at area 6 (spherical representation). In this quantum state complex, 3-consonant languages are instantaneously integrated and multiple languages can be learned, verbalized and differentiated. Conclusion: We postulate that evolutionary human speech is elevated to quantum interaction unlike cetaceans and birds to achieve the three consonants/bi-syllable speech. In classical primary autism, the sudden speech switches off and on noted in several cases could now be explained not by any anatomical lesion but failure of coherence. Area 6 projects directly into prefrontal saccadic area (8); and this further explains the second primary feature in autism: lack of eye contact. The third feature which is repetitive finger gestures, located adjacent to the speech/motor areas, are actual attempts to communicate with the autistic child akin to sign language for the deaf.

Keywords: quantum neuronal paradigm, cetaceans and human speech, autism and rapid magnetic stimulation, coherence and decoherence of speech

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Authors: Caroline Provost, Francois Dumont

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Production of insects for human and animal consumption is an increasingly important activity in Canada. Protein production is more efficient and less harmful to the environment using insect rearing compared to the impact of traditional livestock, poultry and fish farms. Insects are rich in essential amino acids, essential fatty acids and trace elements. Thus, insect-based products could be used as a food supplement for livestock and domestic animals and may even find their way into the diets of high performing athletes or fine dining. Nevertheless, several parameters remain to be determined to ensure efficient and profitable production that meet the potential of these sectors. This project proposes to improve the production processes, rearing diets and processing methods for three species with valuable gastronomic and nutritional potential: the common mealworms (Tenebrio molitor), the small mealworm (Alphitobius diaperinus), and the giant mealworm (Zophobas morio). The general objective of the project is to acquire specific knowledge for mass rearing of insects dedicated to animal and human consumption in order to respond to current market opportunities and meet a growing demand for these products. Mass rearing of the three species of mealworm was produced to provide the individuals needed for the experiments. Mealworms eat flour from different cereals (e.g. wheat, barley, buckwheat). These cereals vary in their composition (protein, carbohydrates, fiber, vitamins, antioxidant, etc.), but also in their purchase cost. Seven different diets were compared to optimize the yield of the rearing. Diets were composed of cereal flour (e.g. wheat, barley) and were either mixed or left alone. Female fecundity, larvae mortality and growing curves were observed. Some flour diets have positive effects on female fecundity and larvae performance while each mealworm was found to have specific diet requirements. Trade-offs between mealworm performance and costs need to be considered. Experiments on the effect of flour composition on several parameters related to performance and nutritional and gastronomic value led to the identification of a more appropriate diet for each mealworm.

Keywords: mass rearing, mealworm, human consumption, diet

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Authors: Sukru Dursun, Zeynep Cansu Ayturan, Mostafa Maroof

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Metal coating which is important method used for protecting metals against oxidation and corrosion, decreasing friction, protecting metals from chemicals, easing cleaning of the metals. There are several methods used for metal coating such as hot-dip galvanizing, thermal spraying, electroplating and sherardizing. Method which will be used for metal coating depends on the type of metal. The materials mostly used for coating are zinc, nickel, brass, chrome, gold, cadmium, copper, brass, and silver. Within these materials, chrome ion has significant negative impacts on human, other living organisms and environment. Moreover, especially on human chrome may cause lung cancer, stomach ulcer, kidney and liver function disorders and death. Therefore, wastewaters of metal coating industry including chrome should be treated very carefully. In this study, wastewater containing chrome produced by metal coating industry was analysed with phytotoxicity method that is based on measuring the reaction of some plant species against different concentrations of chrome solution. Main plants used for phytotoxicity tests are Lepidium sativum and Lemna minor. Owing to phytotoxicity test, assessing the negative effects of chrome which may harm plants and offering more accurate wastewater treatment techniques against chromium wastewater is possible. Furthermore, the results taken from phytotoxicity tests were analysed with respect to their variance and their importance against different concentrations of chrome solution were determined.

Keywords: metal coating wastewater, chrome, phytotoxicity, Lepidium sativum, Lemna minor

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Authors: Samia Khadhar, Anis Chekirbene, Nouha Khiari, Amira Mabrouki

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The persistent organic pollutants (POPs) in aquatic environments are one of the most worrying problems for environmental sustainability and human health because of their carcinogenic and toxic characteristics. Human anthropogenic actions (wastewater discharges, agricultural and industrial activities) without prior treatment are the main cause of this organic pollution. Oued Madjerda is considered the most important river in Tunisia, hence the importance of assessing the level of organic pollution of water and sediments, taking into account the anthropogenic stress exerted on this river. Water and sediment samples were taken from the middle and lower valley of the Medjerda to determine the state of contamination by 7PCBs, priority 15PAHs, and pesticides. The analysis was performed by gas chromatography (GC) and liquid phase coupled to HPLC MS-MS mass spectroscopy. The results showed that for the waters, the total PAH and PCB contents vary respectively from 0.0023 to 7.72 mg/l and from 0.0001 to 0.179 mg/l. In surface sediments 0 to 15 cm, 7PCB levels vary from 1,112 to 110,062 µg/kg-1. In this study, we tried to determine the concentration of 96 pesticides in surface sediments; analyzes showed the presence of Buprofezin, propamocarb-HCl, hexaconazole, flutriafol, quinalphos, and tebufenpyrad with concentrations varying from 1.06 to 2.388 µg/kg-1. The pace of the spatial variation confirms the impact of wastewater discharged on the quality of water and sediments despite the perennial aspect of the river.

Keywords: Wadi Madjerda, organic pollution, water and sediments surface, anthropics stress

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Authors: Shraddha Palikhe, Sunkuk Kim

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The construction industry is the most labor intensive in Nepal. It is obvious that construction is a major sector and any productivity enhancement activity in this sector will have a positive impact in the overall improvement of the national economy. Previous studies have stated that Nepal has poor labor productivity among other south Asian countries. Though considerable research has been done on productivity factors in other countries, no study has addressed labor productivity issues in Nepal. Therefore, the main objective of this study is to identify and hierarchy the influence factors for poor labor productivity. In this study, a questionnaire approach is chosen as a method of the survey from thirty experts involved in the construction industry, such as Architects, Civil Engineers, Project Engineers and Site Engineers. A survey was conducted in Nepal, to identify the major factors impacting construction labor productivity. Analytic Hierarchy Process (AHP) analysis method was used to understand the underlying relationships among the factors, categorized into five groups, namely (1) Labor-management group; (2) Material management group; (3) Human labor group; (4) Technological group and (5) External group and was divided into 33 subfactors. AHP was used to establish the relative importance of the criteria. The AHP makes pairwise comparisons of relative importance between hierarchy elements grouped by labor productivity decision criteria. Respondents were asked to answer based on their experience of construction works. On the basis of the respondent’s response, weight of all the factors were calculated and ranked it. The AHP results were tabulated based on weight and ranking of influence factors. AHP model consists of five main criteria and 33 sub-criteria. Among five main criteria, the scenario assigns a weight of highest influential factor i.e. 26.15% to human labor group followed by 23.01% to technological group, 22.97% to labor management group, 17.61% material management group and 10.25% to external group. While in 33 sub-criteria, the most influential factor for poor productivity in Nepal are lack of monetary incentive (20.53%) for human labor group, unsafe working condition (17.55%) for technological group, lack of leadership (18.43%) for labor management group, unavailability of tools at site (25.03%) for material management group and strikes (35.01%) for external group. The results show that AHP model associated criteria are helpful to predict the current situation of labor productivity. It is essential to consider these influence factors to improve the labor productivity in the construction industry of Nepal.

Keywords: construction, hierarchical analysis, influence factors, labor productivity

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Authors: Felice Elefant, Akanksha Bhatnaghar, Keegan Krick, Elizabeth Heller

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Context: The severity of Alzheimer’s Disease (AD) progression involves an interplay of genetics, age, and environmental factors orchestrated by histone acetyltransferase (HAT) mediated neuroepigenetic mechanisms. While disruption of Tip60 HAT action in neural gene control is implicated in AD, alternative mechanisms underlying Tip60 function remain unexplored. Altered RNA splicing has recently been highlighted as a widespread hallmark in the AD transcriptome that is implicated in the disease. Research Aim: The aim of this study was to identify a novel RNA binding/splicing function for Tip60 in human hippocampus and impaired in brains from AD fly models and AD patients. Methodology/Analysis: The authors used RNA immunoprecipitation using RNA isolated from 200 pooled wild type Drosophila brains for each of the 3 biological replicates. To identify Tip60’s RNA targets, they performed genome sequencing (DNB-SequencingTM technology, BGI genomics) on 3 replicates for Input RNA and RNA IPs by Tip60. Findings: The authors' transcriptomic analysis of RNA bound to Tip60 by Tip60-RNA immunoprecipitation (RIP) revealed Tip60 RNA targets enriched for critical neuronal processes implicated in AD. Remarkably, 79% of Tip60’s RNA targets overlap with its chromatin gene targets, supporting a model by which Tip60 orchestrates bi-level transcriptional regulation at both the chromatin and RNA level, a function unprecedented for any HAT to date. Since RNA splicing occurs co-transcriptionally and splicing defects are implicated in AD, the authors investigated whether Tip60-RNA targeting modulates splicing decisions and if this function is altered in AD. Replicate multivariate analysis of transcript splicing (rMATS) analysis of RNA-Seq data sets from wild-type and AD fly brains revealed a multitude of mammalian-like AS defects. Strikingly, over half of these altered RNAs were bonafide Tip60-RNA targets enriched for in the AD-gene curated database, with some AS alterations prevented against by increasing Tip60 in fly brain. Importantly, human orthologs of several Tip60-modulated spliced genes in Drosophila are well characterized aberrantly spliced genes in human AD brains, implicating disruption of Tip60’s splicing function in AD pathogenesis. Theoretical Importance: The authors' findings support a novel RNA interaction and splicing regulatory function for Tip60 that may underlie AS impairments that hallmark AD etiology. Data Collection: The authors collected data from RNA immunoprecipitation experiments using RNA isolated from 200 pooled wild type Drosophila brains for each of the 3 biological replicates. They also performed genome sequencing (DNBSequencingTM technology, BGI genomics) on 3 replicates for Input RNA and RNA IPs by Tip60. Questions: The question addressed by this study was whether Tip60 has a novel RNA binding/splicing function in human hippocampus and whether this function is impaired in brains from AD fly models and AD patients. Conclusions: The authors' findings support a novel RNA interaction and splicing regulatory function for Tip60 that may underlie AS impairments that hallmark AD etiology.

Keywords: Alzheimer's disease, cognition, aging, neuroepigenetics

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