Search results for: single cell

Authors: Hager Elsheikh

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Context: Pancreatitis is a condition characterized by inflammation in the pancreas, which can lead to serious complications if untreated. Both acute and chronic pancreatitis are associated with immune reactions and fibrosis, which further damage the pancreas. The type 2 immune response, primarily driven by alternative activated macrophages (AAMs), plays a significant role in the development of fibrosis. The IL-4/STAT6 pathway is a crucial signaling pathway for the activation of M2 macrophages. Pancreatic fibrosis is induced by dysregulated inflammatory responses and can result in the autodigestion and necrosis of pancreatic acinar cells. Research Aim: The aim of this study is to investigate the impact of STAT6, a crucial molecule in the IL-4/STAT6 pathway, on the severity and development of fibrosis during acute and chronic pancreatitis. The research also aims to understand the influence of the JAK/STAT6 signaling pathway on the balance between fibrosis and regeneration in the presence of different macrophage populations. Methodology: The research utilizes murine models of acute and chronic pancreatitis induced by cerulean injection. Animal models will be employed to study the effect of STAT6 knockout on disease severity and fibrosis. Isolation of acinar cells and cell culture techniques will be used to assess the impact of different macrophage populations on wound healing and regeneration. Various techniques such as PCR, histology, immunofluorescence, and transcriptomics will be employed to analyze the tissues and cells. Findings: The research aims to provide insights into the mechanisms underlying tissue fibrosis and wound healing during acute and chronic pancreatitis. By investigating the influence of the JAK/STAT6 signaling pathway and different macrophage populations, the study aims to understand their impact on tissue fibrosis, disease severity, and pancreatic regeneration. Theoretical Importance: This research contributes to our understanding of the role of specific signaling pathways, macrophage polarization, and the type 2 immune response in pancreatitis. It provides insights into the molecular mechanisms underlying tissue fibrosis and the potential for targeted therapies. Data Collection and Analysis Procedures: Data will be collected through the use of murine models, isolation and culture of acinar cells, and various experimental techniques such as PCR, histology, immunofluorescence, and transcriptomics. Data will be analyzed using appropriate statistical methods and techniques, and the findings will be interpreted in the context of the research objectives. Conclusion: By investigating the mechanisms of tissue fibrosis and wound healing during acute and chronic pancreatitis, this research aims to enhance our understanding of the disease progression and potential therapeutic targets. The findings have theoretical importance in expanding our knowledge of pancreatic fibrosis and the role of macrophage polarization in the context of the type 2 immune response.

Keywords: immunity in chronic diseases, pancreatitis, macrophages, immune response

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Authors: Emre Kishalı, Neslihan TürkmenoğLu Bayraktar

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Historical buildings may face various impacts throughout their life cycle. There have been environmental, structural, public works actions on old monuments influencing sustainability and maintenance issues. As a result, ancient monuments can have been undergone various changes in the context of restoration and repair. Currently, these buildings face integrated conditions including city planning macro solutions, old intervention methods, modifications in building envelope and artefacts in terms of conservation. Moreover, documentation of phases is an essential for assessing the historical building, yet it can result in highly complicated and interwoven issues. Herein, two monuments constructed in the 16th century are selected as case studies in Kocaeli, Turkey which are located in different micro climatic conditions and/or exposed to different interventions and which are important for the city as cultural property. Pertev Paşa Mosque (also known as Yenicuma Mosque) -constructed by Architect Sinan-; Gebze Çoban Mustafa Paşa Mosque -constructed in 1523 and known as the work of Architect Sinan but various names asserted as the architect of building according to resources. Active water infiltration and damages, recent material interventions, hidden niches, and foundation techniques of the mosque are investigated via Infrared Thermography under the project of 114K284, “Non-Destructive Test Applications, in the Context of Planned Conservation, through Historical Mosques of Kocaeli: Coban Mustafa Pasa Mosque, Fevziye Mosque and Pertev Pasa Mosque” funded by TUBITAK. It is aimed to reveal active deteriorations on building elements generated by unwanted effects of structural and climatic conditions, historical interventions, and modifications by monitoring the variation of surface temperature and humidity by IRT visualization method which is an important non- destructive process for investigation of monuments in the conservation field in the context of planned conservation. It is also concluded that in-situ monitoring process via IRT through different climatic conditions give substantial information on the behaviour of the envelope to the physical environmental conditions by observation of thermal performance, degradations. However, it is obvious that monitoring of historical buildings cannot be pursued by implementing a single non-destructive technique to have complete data of the structure.

Keywords: IRT, non-destructive test, planned conservation, mosque

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Authors: Antoine Villa, Moustapha Mohamedou, Florence Pilliere, Catherine Verdun-Esquer, Mathieu Molimard, Mohamed Sidatt Cheikh El Moustaph, Mireille Canal-Raffin

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Context: In Mauritania, the activity of the National Center of Oncology (NCO) has steadily risen leading to an increase in the handling of antineoplastic drugs (AD) by healthcare professionals. In this context, the AD contamination of those professionals is a major concern for occupational physicians. It has been evaluated using biological monitoring of occupational exposure (BMOE). Methods: The intervention took place in 2015, in 2 care units, and evaluated nurses preparing and/or infusing AD and agents in charge of hygiene. Participants provided a single urine sample, at the end of the week, at the end of their shift. Five molecules were sought using specific high sensitivity methods (UHPLC-MS/MS) with very low limits of quantification (LOQ) (cyclophosphamide (CP), Ifosfamide (IF), methotrexate (MTX): 2.5ng/L; doxorubicin (Doxo): 10ng/L; α-fluoro-β-alanine (FBAL, 5-FU metabolite): 20ng/L). A healthcare worker was considered as 'contaminated' when an AD was detected at a urine concentration equal to or greater than the LOQ of the analytical method or at trace concentration. Results: Twelve persons participated (6 nurses, 6 agents in charge of hygiene). Twelve urine samples were collected and analyzed. The percentage of contamination was 66.6% for all participants (n=8/12), 100% for nurses (6/6) and 33% for agents in charge of hygiene (2/6). In 62.5% (n=5/8) of the contaminated workers, two to four of the AD were detected in the urine. CP was found in the urine of all contaminated workers. FBAL was found in four, MTX in three and Doxo in one. Only IF was not detected. Urinary concentrations (all drugs combined) ranged from 3 to 844 ng/L for nurses and from 3 to 44 ng/L for agents in charge of hygiene. The median urinary concentrations were 87 ng/L, 15.1 ng/L and 4.4 ng/L for FBAL, CP and MTX, respectively. The Doxo urinary concentration was found 218ng/L. Discussion: There is no current biological exposure index for the interpretation of AD contamination. The contamination of these healthcare professionals is therefore established by the detection of one or more AD in urine. These urinary contaminations are higher than the LOQ of the analytical methods, which must be as low as possible. Given the danger of AD, the implementation of corrective measures is essential for the staff. Biological monitoring of occupational exposure is the most reliable process to identify groups at risk, tracing insufficiently controlled exposures and as an alarm signal. These results show the necessity to educate professionals about the risks of handling AD and/or to care for treated patients.

Keywords: antineoplastic drugs, Mauritania, biological monitoring of occupational exposure, contamination

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Authors: Vidya Yadav

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India’s youth bulge is now sharpest at the critical 15-24 age group, even as its youngest, and oldest age groups begin to narrow. As the ‘single year, age data’ for the 2011 Census releases the data on the number of people at each year of age in the population. The data shows that India’s working age population (15-64 years) is now 63.4 percent of the total, as against just short of 60 percent in 2001. The numbers also show that the ‘dependency ratio’ the ratio of children (0-14) and the elderly (65 above) to those in the working age has shrunk further to 0.55. “Even as the western world is in ageing situation, these new numbers show that India’s population is still very young”. As the fertility falls faster in urban areas, rural India is younger than urban India; while 51.73 percent of rural Indians are under the age of 24 and 45.9 percent of urban Indians are under 24. The percentage of the population under the age of 24 has dropped, but many demographers say that it should not be interpreted as a sign of the youth bulge is shrinking. Rather it is because of “declining fertility, the number of infants and children reduces first, and this is what we see with the number of under age 24. Indeed the figure shows that the proportion of children in the 0-4 and 5-9 age groups has fallen in 2011 compared to 2001. For the first time, the percentage of children in the 10-14 age group has also fallen, as the effect of families reducing the number of children they have begins to be felt. The present paper key issue is to examine that “whether this growing youth bulge has the right skills for the workforce or not”. The study seeks to examine the youth population structure and employment distribution among them in India during 2001-2011 in different industrial category. It also tries to analyze the workforce participation rate as main and marginal workers both for male and female workers in rural and urban India by utilizing an abundant source of census data from 2001-2011. Result shows that an unconscionable number of adolescents are working when they should study. In rural areas, large numbers of youths are working as an agricultural labourer. Study shows that most of the youths working are in the 15-19 age groups. In fact, this is the age of entry into higher education, but due to economic compulsion forces them to take up jobs, killing their dreams of higher skills or education. Youths are primarily engaged in low paying irregular jobs which are clearly revealed by census data on marginal workers. That is those who get work for less than six months in a year. Large proportions of youths are involved in the cultivation and household industries works.

Keywords: main, marginal, youth, work

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Authors: Zichun Chu

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The issue of tribal poverty has always attracted attentions. Due to social and economic difficulties, the indigenous people's personal development and tribal development have been greatly restricted. Past studies have pointed out that poverty may come from a lack of education. The United Nations Sustainable Development Goals (SDGs) also stated that if we are to solve the poverty problem, providing education widely is an important key. According to the theory of intellectual capital adaptation, “being capable” and “willing to do” are the keys of development. Therefore, we can say that the "ability" and "will" of tribal residents for their tribal development is the core concern of the tribal development. This research was designed to investigate the career choice development model of indigenous tribe people by investigating the current status of human capital, social capital, and cultural capital of tribal residents. This study collected 327 questionnaires (70% of total households) from Truku tribe to answer the research question: Did education help them for job choosing decisions from the aspects of human capital, social capital, and cultural capital in tribal status. This project highlighted the ‘single tribal research approach’ to gain an in-depth understanding of the human capital formed under the unique culture of the tribe (Truku tribe). The results show that the education level of most research participants was high school, very few high school graduates chose to further their education to college level; due to the lack of education of their parents, the social capital was limited to support them for jobs choice, most of them work for labor and service industries; however, their culture capital was comparably rich for works, the sharing culture of Taiwanese indigenous people made their work status stable. The results suggested that we should emphasize more on the development of vocational education based on the tribe’s location and resources. The self-advocacy of indigenous people should be developed so that they would gain more power on making career decisions. This research project is part of a pilot project called “INDIGENOUS PEOPLES, POVERTY, AND DEVELOPMENT,” sponsored by the National Science and Technology Council of Taiwan. If this paper were accepted to present in the 2023 ICIP, it would be lovely if a panel is formed for me and other co-researchers (Chuanju Cheng, Chih-Yuan Weng, and YiXuan Chen), for the audience will be able to get a full picture of this pilot project.

Keywords: career choices, career model, indegenous career development, indigenous education, tribe

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Authors: Abdullah Almilaibary, Jeremy Jolley, Mark Hayter

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Background: Despite recent progress in enhancing the accessibility of HIV-related health services worldwide, opportunities to diagnose patients are often missed due to genuine barriers at different levels. The aim of the study is to explore the factors that affect the utilization of HIV testing services by young people aged 17-25 in Saudi Arabia. Methods: A non-experimental descriptive cross-sectional design was used to predict factors that influenced HIV testing among Umm- Al Qura University students aged 17-25 years. A newly developed self-completed online questionnaire was used and the study sample was drawn using a convenience sampling technique. The questionnaire consisted of 52 items divided into three scales: 12 items for HIV/AIDS-related knowledge, 3 items for risk perception, and 37 items for attitudes toward HIV testing. Five experts in the field of HIV/AIDS validated the contents of the questionnaire and agreed that the items included were related to the construct being measured. The reliability of the questionnaire was also assessed using a test/re-test strategy with 27 participants recruited from the population under study. The reliability assessment revealed that the questionnaire was consistent as Cronbach’s Alpha was 0.80 for HIV/ADS knowledge, 0.88 for risk perception and 0.78 for attitudes towards HIV testing. The data were collected between 14th of July and 14th of October 2014. Results: 394 participants completed the questionnaires: 116 (29.4%) male and 278 (70%) female. 50.5% of the participants were aged 20 to 22 years, 34.8% were 17-19 years and 14.7% were aged between 23-25 years; about 93% of the participants were single. Only 20 (6%) participants had previously been tested for HIV. The main reasons for not being tested for HIV were: exposure to HIV was considered unlikely (48%), HIV test was not offered (36%) and unawareness of HIV testing centres (16%). On HIV/AIDS-related knowledge, the male participants scored higher than the females as the mean score for males was (M = 6.4, SD = 2.4) while for females it was (M 5.7, SD 2.5). In terms of risk perception, female participants appeared to have lower levels of risk perception than male participants, with the mean score for males being (M 11.7, SD 2.5) and (M 10.5, SD 2.4) for females. The female participants showed slightly more positive attitudes towards HIV testing than male participants: the mean score for males was (M = 108.14, SD = 17.9) and was (M = 111.32, SD = 17.3) for females. Conclusions: The data reveal that misconceptions about HIV/AIDS in Saudi Arabia are still a challenge. Although the attitudes towards HIV testing were reasonably positive, the utilization of the HIV test was low. Thus, tailoring HIV/AIDS preventive strategies in Saudi Arabia should focus on the needs of young people and other high risk groups in the country.

Keywords: attitude toward hiv testing, hiv testing, hiv/aids related knowledge, risk perception

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Authors: K. Al Ammari, B. G. Clarke

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Soil improvement using vibro stone column techniques consists of two main parts: (1) the installed load bearing columns of well-compacted, coarse-grained material and (2) the improvements to the surrounding soil due to vibro compaction. Extensive research work has been carried out over the last 20 years to understand the improvement in the composite foundation performance due to the second part mentioned above. Nevertheless, few of these studies have tried to quantify some of the key design parameters, namely the changes in the stiffness and stress state of the treated soil, or have consider these parameters in the design and calculation process. Consequently, empirical and conservative design methods are still being used by ground improvement companies with a significant variety of results in engineering practice. Two-dimensional finite element study to develop an axisymmetric model of a single stone column reinforced foundation was performed using PLAXIS 2D AE to quantify the effect of the vibro installation of this column in soft saturated clay. Settlement and bearing performance were studied as an essential part of the design and calculation of the stone column foundation. Particular attention was paid to the large deformation in the soft clay around the installed column caused by the lateral expansion. So updated mesh advanced option was taken in the analysis. In this analysis, different degrees of stone column lateral expansions were simulated and numerically analyzed, and then the changes in the stress state, stiffness, settlement performance and bearing capacity were quantified. It was found that application of radial expansion will produce a horizontal stress in the soft clay mass that gradually decrease as the distance from the stone column axis increases. The excess pore pressure due to the undrained conditions starts to dissipate immediately after finishing the column installation, allowing the horizontal stress to relax. Changes in the coefficient of the lateral earth pressure K ٭, which is very important in representing the stress state, and the new stiffness distribution in the reinforced clay mass, were estimated. More encouraging results showed that increasing the expansion during column installation has a noticeable effect on improving the bearing capacity and reducing the settlement of reinforced ground, So, a design method should include this significant effect of the applied lateral displacement during the stone column instillation in simulation and numerical analysis design.

Keywords: bearing capacity, design, installation, numerical analysis, settlement, stone column

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Authors: Elena Maria Scalisi

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Currently, photodegradation by nanoparticles (NPs) is a common solution for wastewater treatment. Nanoparticles are efficient for removing organic and inorganic pollutants, heavy metals from wastewater and killing microorganisms through environmentally friendly. In this context, the major representative of photocatalytic technology for industrial wastewater treatment are TiO₂ nanoparticles (TiO₂-NPs). TiO₂-NPs have a strong catalytic activity that depends to their physicochemical properties. Thanks to their small size (between 1-100 nm), nanoparticles occupy less volume, then their surface area increases. The increase in the surface-to-volume ratio results in the increase of the particle surface energy, which improve their reactivity potential. However, these unique properties represent risks to the ecosystems and organisms when unintentionally TiO₂-NPs are release into the environment and absorbed by living organisms. Several studies confirm that there is a high level of interest concerning the safety of TiO₂-NPs in the aquatic environment, furthermore, ecotoxicological tools are useful to correctly evaluate their toxicity. In the current study, we aimed to characterize potential toxic effects of TiO₂-NP suspension to zebrafish during embryo-larval stages to evaluate parameters such as survival rates, malformation, hatching, the overall length of the larvae heartbeat, and biochemical biomarkers that reflect the acute toxicity and sublethal effects of TiO₂-NPs. Zebrafish embryos were exposed to titanium dioxide nanoparticles (TiO₂-NPs at 1mg/L, 2mg/L, and 4mg/L) from fertilization to the free swimming stage (144hpf). Every day, we recorded the toxicological endpoints, moreover, immunohistochemical analysis has been performed at the end of the exposure. In particular, we have evaluate the expression of the following biomarkers: Heat Shock Protein 70 (HSP70), Poly ADP-Ribose Polymerase-1 (PARP-1), Metallothioneins (MTs). Our results have shown that hatch ability, survival, and malformation rate were not affected by TiO₂ NPs at these exposure levels. However, TiO₂-NPs caused an increase of heartbeat and reduction of body length; at the same time, TiO₂-NPs have inducted the production of ROS and the expression of oxidative stress biomarkers HSP70 and PARP-1. Hight positivity for PARP-1 at all concentration tested was observed. As regards MT, positivity was found in the expression of this biomarker in the whole body of the embryo, with the exception of the end of the tail. Metallothioneins (MT) are biomarkers widely used in environmental monitoring programs for aquatic creatures. At the light of our results i.e. no death until the end of the experiment (144hpf), no malformation and expression of the biomarkers mentioned, it is evident that zebrafish larvae with their natural detoxification pathways are able to resist the presence of toxic substances and then they can tolerate the presence of metal concentrations. However, an excessive oxidative state can compromise cell function, therefore the uncontrolled release of nanoparticles into the environment is severe and must be constantly monitored.

Keywords: nanoparticles, embryo zebrafish, HSP70, PARP-1

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Authors: G. Barański, P. Kacejko, M. Wendeker

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The impact of the ignition advance control algorithms of the ASz-62IR-16X aircraft piston engine on a combustion process has been presented in this paper. This aircraft engine is a nine-cylinder 1000 hp engine with a special electronic control ignition system. This engine has two spark plugs per cylinder with an ignition advance angle dependent on load and the rotational speed of the crankshaft. Accordingly, in most cases, these angles are not optimal for power generated. The scope of this paper is focused on developing algorithms to control the ignition advance angle in an electronic ignition control system of an engine. For this type of engine, i.e. radial engine, an ignition advance angle should be controlled independently for each cylinder because of the design of such an engine and its crankshaft system. The ignition advance angle is controlled in an open-loop way, which means that the control signal (i.e. ignition advance angle) is determined according to the previously developed maps, i.e. recorded tables of the correlation between the ignition advance angle and engine speed and load. Load can be measured by engine crankshaft speed or intake manifold pressure. Due to a limited memory of a controller, the impact of other independent variables (such as cylinder head temperature or knock) on the ignition advance angle is given as a series of one-dimensional arrays known as corrective characteristics. The value of the ignition advance angle specified combines the value calculated from the primary characteristics and several correction factors calculated from correction characteristics. Individual cylinder control can proceed in line with certain indicators determined from pressure registered in a combustion chamber. Control is assumed to be based on the following indicators: maximum pressure, maximum pressure angle, indicated mean effective pressure. Additionally, a knocking combustion indicator was defined. Individual control can be applied to a single set of spark plugs only, which results from two fundamental ideas behind designing a control system. Independent operation of two ignition control systems – if two control systems operate simultaneously. It is assumed that the entire individual control should be performed for a front spark plug only and a rear spark plug shall be controlled with a fixed (or specific) offset relative to the front one or from a reference map. The developed algorithms will be verified by simulation and engine test sand experiments. This work has been financed by the Polish National Centre for Research and Development, INNOLOT, under Grant Agreement No. INNOLOT/I/1/NCBR/2013.

Keywords: algorithm, combustion process, radial engine, spark plug

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Authors: S. Jayasinghe, W. G. D. Wickramasingha, V. Karunaratne, D. N. Karunaratne, A. Ekanayake

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Multi-drug resistant microbial pathogens are a serious global health problem, and hence, there is an urgent necessity for discovering new drug therapeutics. However, finding alternatives is a one of the biggest challenges faced by the global drug industry due to the spiraling high cost and serious side effects associated with modern medicine. On the other hand, plants and their secondary metabolites can be considered as good sources of scaffolds to provide structurally diverse bioactive compounds as potential therapeutic agents. 6β-hydroxy betunolic acid is a triterpenoid isolated from bark of Schumacheria castaneifolia which is an endemic plant to Sri Lanka which has shown antibacterial activity against both Staphylococcus aureus (ATCC 29213) and methicillin-resistant S. aureus with Minimum Inhibition Concentration (MIC) of 16 µg/ml. The objective of this study was to determine the anti-bacterial activity for the derivatives of 6β- hydroxy betunolic acid against standard strains of Staphylococcus aureus (ATCC 29213 and ATCC 25923), Enterococcus faecalis (ATCC 29212), Escherichia coli (ATCC 35218 and ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), carbepenemas produce Kebsiella pneumonia (ATCC BAA 1705) and carbepenemas non produce Kebsiella pneumonia (ATCC BAA 1706) and four stains of clinically isolated methicillin resistance S. aureus and Acinetobacter. Structural analogues of 6β-hydroxy betunolic acid were synthesized by modifying the carbonyl group at C-3 to obtain olefin and oxime, the hydroxyl group at C-6 position to a ketone, the carboxylic acid at C-17 to obtain amide and halo ester and the olefin group at C-20 position to obtain epoxide. Chemical structures of the synthesized analogues were confirmed with spectroscopic data and antibacterial activity was determined through broth micro dilution assay. Results revealed that 6β- hydroxy betunolic acid shows significant antibacterial activity only against the Gram positive strains and it was inactive against all the tested Gram negative strains for the tested concentration range. However, structural modifications into oxime and olefin at C-3, ketone at C-6 and epoxide at C-20 decreased its antibacterial activity against the gram positive organisms and it was totally lost with the both modifications at C-17 into amide and ester. These results concluded that the antibacterial activity of 6β- hydroxy betunolic acid and derivatives is predominantly depending on the cell wall difference of the bacteria and the presence of carboxylic acid at C-17 is highly important for the antibacterial activity against Gram positive organisms.

Keywords: antibacterial activity, 6β- hydroxy betunolic acid, broth micro dilution assay, structure activity relationship

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Authors: Sengul Celik, Alper Ketenci

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In Turkish Constitution about health care in Article 56, it is said that: everyone has the right to live in a healthy and balanced environment. It is the duty of the state and citizens to improve the environment, protect environmental health, and prevent environmental pollution. The state ensures that everyone lives their lives in physical and mental health; it organizes the planning and service of health institutions from a single source in order to realize cooperation by increasing savings and efficiency in human and substance power. The state fulfills this task by utilizing and supervising health and social institutions in the public and private sectors. General health insurance can be established by law for the widespread delivery of health services. To have health care is one of the basic rights of patients. After the coupe attempt in July 2016, the Government of Turkey has announced a state of emergency and issued lots of emergency decrees. By these emergency decrees, lots of people were dismissed from their jobs and lost their some basic social rights. The violations occur in social life. One of the most common observations is the discrimination by government in health care system. This study aims to put forward the violation of human rights in health care system in Turkey due to their discriminated position by an emergency decree. The study is a case study that is based on nine interviews with the people or relatives of people who lost their jobs by an emergency decree in Turkey. In this study, no personally identifiable information was obtained for the safety of individuals. Also no distinctive questions regarding the identity of individuals were asked. The interviews are obtained through internet call applications. The data were analyzed through the requirements of regular health care system in Turkey. The interviews expose that the people or the relatives of people lost their right to have regular health care. They have to pay extra amount both in clinical services and in medication treatment. The patient right to quality medical care without prejudice is violated. It was assessed that the people who are involved in emergency decree and their relatives are discriminated by government and deprived of regular medical care and supervision. Although international legal arrangements and legal responsibilities of the state have been put forward by Article 56, they are violated in practice. To prevent these kinds of violations, some measures should be taken against the deprivation in health care system especially towards the discriminated people by an emergency decree.

Keywords: emergency decree in Turkey, health care, discriminated people, patients rights

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Authors: Abdulaziz Alakeel, Roaa Alamri, Abdulrahman Alomair, Mohammed Fouda

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Introduction: Ibrutinib is a selective, potent, and irreversible small-molecule inhibitor of Bruton's tyrosine kinase (BTK). It forms a covalent bond with a cysteine residue (CYS-481) at the active site of Btk, leading to inhibition of Btk enzymatic activity. The drug is indicated to treat certain type of cancers such as mantle cell lymphoma (MCL), chronic lymphocytic leukaemia and Waldenström's macroglobulinaemia (WM). Cardiac failure is a condition referred to inability of heart muscle to pump adequate blood to human body organs. There are multiple types of cardiac failure including left and right-sided heart failure, systolic and diastolic heart failures. The aim of this review is to evaluate the risk of cardiac failure associated with the use of ibrutinib and to suggest regulatory recommendations if required. Methodology: Signal Detection team at the National Pharmacovigilance Center (NPC) of Saudi Food and Drug Authority (SFDA) performed a comprehensive signal review using its national database as well as the World Health Organization (WHO) database (VigiBase), to retrieve related information for assessing the causality between cardiac failure and ibrutinib. We used the WHO- Uppsala Monitoring Centre (UMC) criteria as standard for assessing the causality of the reported cases. Results: Case Review: The number of resulted cases for the combined drug/adverse drug reaction are 212 global ICSRs as of July 2020. The reviewers have selected and assessed the causality for the well-documented ICSRs with completeness scores of 0.9 and above (35 ICSRs); the value 1.0 presents the highest score for best-written ICSRs. Among the reviewed cases, more than half of them provides supportive association (four probable and 15 possible cases). Data Mining: The disproportionality of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by WHO-UMC to measure the reporting ratio. Positive IC reflects higher statistical association while negative values indicates less statistical association, considering the null value equal to zero. The results of (IC=1.5) revealed a positive statistical association for the drug/ADR combination, which means “Ibrutinib” with “Cardiac Failure” have been observed more than expected when compared to other medications available in WHO database. Conclusion: Health regulators and health care professionals must be aware for the potential risk of cardiac failure associated with ibrutinib and the monitoring of any signs or symptoms in treated patients is essential. The weighted cumulative evidences identified from causality assessment of the reported cases and data mining are sufficient to support a causal association between ibrutinib and cardiac failure.

Keywords: cardiac failure, drug safety, ibrutinib, pharmacovigilance, signal detection

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Authors: I. Wiedemann, A. R. Sharifi, A. Mählmeyer, C. Knorr

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A requirement for sperm motility is a morphologically intact flagellum with a central axoneme. The flagellar beating is caused by the varying activation and inactivation of dynein molecules which are located in the axoneme. DNAL4 (dynein, axonemal, light chain 4) is regarded as a possible functional candidate gene encoding a small subunit of the dyneins. In the present study, 5814bp of the porcine DNAL4 (GenBank Acc. No. AM284696.1, 6097 bp, 4 exons) were comparatively sequenced using three boars with a high motility (>68%) and three with a low motility (<60%). Primers were self-designed except for those covering exons 1, 2 and 3. Prior to sequencing, the PCR products were purified. Sequencing was performed with an ABI PRISM 3100 Genetic Analyzer using the BigDyeTM Terminator v3.1 Cycle Sequencing Reaction Kit. Finally, 23 SNPs were described and genotyped for 82 AI boars representing the breeds Piétrain, German Large White and German Landrace. The genotypes were used to assess possible associations with standard spermatological parameters (ejaculate volume, density, and sperm motility (undiluted (Motud), 24h (Mot1) and 48h (Mot2) after semen collection) that were regularly recorded on the AI station. The analysis included a total of 8,833 spermatological data sets which ranged from 2 to 295 sets per boar in five years. Only SNP g.1007A>G had a significant effect. Finally, the gene substitution effect using the following statistical model was calculated: Yijk= µ+αi+βj+αβij+b1Sijk+b2Aijk+b3T ijk + b4Vijk+b5(α*A)ijk +b6(β*A)ijk+b7(A*T)ijk+Uijk+eijk where Yijk is the semen characteristics, µ is the general mean, α is the main effect of breed, β is the main effect of season, S is the effect of SNP (g.1007A > G), A is the effect of age at semen collection, V is the effect of diluter, αβ, α*A, β*A, A*T are interactions between the fixed effects, b1-b7 are regression coefficients between y and the respective covariate, U is the random effect of repeated observation on animal and e is the random error. The results from the single marker regression analysis revealed highly significant effects (p < 0.0001) of SNP g.1007A > G on Mot1 resp. on Mot2, resulting in a marked reduction by 11.4% resp. 15.4%. Furthermore a loss of Motud by 4.6% was detected (p < 0.0178). Considering the SNP g.1007A > G as a main factor (dominant-recessive model), significant differences between genotypes AA and AG as well as AA and GG for Mot1 and Mot2 exist. For Motud there was a significant difference between AA and GG.

Keywords: association, DNAL4, porcine, sperm traits

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Authors: Julia Gontar, Natalia Buderatskaya, Igor Ilyin, Olga Parnitskaya, Sergey Lavrynenko, Eduard Kapustin, Ekaterina Ilyina, Yana Lakhno

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Introduction: It is well known that oocytes obtained from older reproductive women have accumulated mitochondrial DNA mutations, which negatively affects the morphology of a developing embryo and may lead to the birth of a child with mitochondrial disease. Special techniques have been developed to allow a donor oocyte cytoplasmic transfer with the parents’ biological nuclear DNA retention. At the same time, it is important to understand whether the procedure affects the future embryonic chromosome sets as the nuclear DNA is the transfer subject in this new complex procedure. Material and Methods: From July 2015 to July 2016, the investigation was carried out in the Medical Centre IGR. 34 donor oocytes (group A) were used for the manipulation with the aim of donating cytoplasm: 21 oocytes were used for zygotes pronuclear transfer and oocytes 13 – for the spindle transfer. The mean age of the oocyte donors was 28.4±2.9 years. The procedure was performed using Nikon Ti Eclipse inverted microscope equipped with the micromanipulators Narishige system (Japan), Saturn 3 laser console (UK), Oosight imaging systems (USA). For the preimplantation genetic screening (PGS) blastocyst biopsy was performed, trophectoderm samples were diagnosed using fluorescent in situ hybridization on chromosomes 9, 13, 15, 16, 17, 18, 21, 22, X, Y. For comparison of morphological characteristics and euploidy, was chosen a group of embryos (group B) with the amount of 121 blastocysts obtained from 213 oocytes, which were gotten from the donor programs of assisted reproductive technologies (ART). Group B was not subjected to donor oocyte cytoplasmic transfer procedure and studied on the above mentioned chromosomes. Statistical analysis was carried out using the criteria t, x^2 at a significance levels p<0.05, p<0.01, p<0.001. Results: After the donor cytoplasm transfer process the amount of the third day developing embryos was 27 (79.4%). In this stage, the group B consisted of 189 (88.7%) developing embryos, and there was no statistically significant difference (SSD) between the two groups (p>0.05). After a comparative analysis of the morphological characteristics of the embryos on the fifth day, we also found no SSD among the studied groups (p>0.05): from 34 oocytes exposed to manipulation, 14 (41.2%) blastocysts was obtained, while the group B blastocyst yield was 56.8% (n=121) from 213 oocytes. The following results were obtained after PGS performing: in group A euploidy in studied chromosomes were 28.6%(n=4) blastocysts, whereas in group B this rate was 40.5%(n=49), 28.6%(n=4) and 21.5%(n=26) of mosaic embryos and 42.8%(n=6) and 38.0%(n=46) aneuploid blastocysts respectively were identified. None of these specified parameters had an SSD (p>0.05). But attention was drawn by the blastocysts in group A with identified mosaicism, which was chaotic without any cell having euploid chromosomal set, in contrast to the mosaic embryos in group B where identified chaotic mosaicism was only 2.5%(n=3). Conclusions: According to the obtained results, there is no direct procedural effect on the chromosome in embryos obtained following donor oocyte cytoplasmic transfer. Thus, the technology introduction will enhance the infertility treating effectiveness as well as avoiding having a child with mitochondrial disease.

Keywords: donor oocyte cytoplasmic transfer, embryos’ chromosome set, oocyte spindle transfer, pronuclear transfer

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Authors: Shashi Kant Verma, S. L. Sinha, D. K. Chandraker

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Numerical simulations of selected subchannel tracer (Potassium Nitrate) based experiments have been performed to study the capabilities of state-of-the-art of Computational Fluid Dynamics (CFD) codes. The Computational Fluid Dynamics (CFD) methodology can be useful for investigating the spacer effect on turbulent mixing to predict turbulent flow behavior such as Dimensionless mixing scalar distributions, radial velocity and vortices in the nuclear fuel assembly. A Gibson and Launder (GL) Reynolds stress model (RSM) has been selected as the primary turbulence model to be applied for the simulation case as it has been previously found reasonably accurate to predict flows inside rod bundles. As a comparison, the case is also simulated using a standard k-ε turbulence model that is widely used in industry. Despite being an isotropic turbulence model, it has also been used in the modeling of flow in rod bundles and to produce lateral velocities after thorough mixing of coolant fairly. Both these models have been solved numerically to find out fully developed isothermal turbulent flow in a 30º segment of a 54-rod bundle. Numerical simulation has been carried out for the study of natural mixing of a Tracer (Passive scalar) to characterize the growth of turbulent diffusion in an injected sub-channel and, afterwards on, cross-mixing between adjacent sub-channels. The mixing with water has been numerically studied by means of steady state CFD simulations with the commercial code STAR-CCM+. Flow enters into the computational domain through the mass inflow at the three subchannel faces. Turbulence intensity and hydraulic diameter of 1% and 5.9 mm respectively were used for the inlet. A passive scalar (Potassium nitrate) is injected through the mass fraction of 5.536 PPM at subchannel 2 (Upstream of the mixing section). Flow exited the domain through the pressure outlet boundary (0 Pa), and the reference pressure was 1 atm. Simulation results have been extracted at different locations of the mixing zone and downstream zone. The local mass fraction shows uniform mixing. The effect of the applied turbulence model is nearly negligible just before the outlet plane because the distributions look like almost identical and the flow is fully developed. On the other hand, quantitatively the dimensionless mixing scalar distributions change noticeably, which is visible in the different scale of the colour bars.

Keywords: single-phase flow, turbulent mixing, tracer, sub channel analysis

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Authors: Nadarajah I. Ramesh

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Much of the research on stochastic point process models for rainfall has focused on Poisson cluster models constructed from either the Neyman-Scott or Bartlett-Lewis processes. The doubly stochastic Poisson process provides a rich class of point process models, especially for fine-scale rainfall modelling. This paper provides an account of recent development on this topic and presents the results based on some of the fine-scale rainfall models constructed from this class of stochastic point processes. Amongst the literature on stochastic models for rainfall, greater emphasis has been placed on modelling rainfall data recorded at hourly or daily aggregation levels. Stochastic models for sub-hourly rainfall are equally important, as there is a need to reproduce rainfall time series at fine temporal resolutions in some hydrological applications. For example, the study of climate change impacts on hydrology and water management initiatives requires the availability of data at fine temporal resolutions. One approach to generating such rainfall data relies on the combination of an hourly stochastic rainfall simulator, together with a disaggregator making use of downscaling techniques. Recent work on this topic adopted a different approach by developing specialist stochastic point process models for fine-scale rainfall aimed at generating synthetic precipitation time series directly from the proposed stochastic model. One strand of this approach focused on developing a class of doubly stochastic Poisson process (DSPP) models for fine-scale rainfall to analyse data collected in the form of rainfall bucket tip time series. In this context, the arrival pattern of rain gauge bucket tip times N(t) is viewed as a DSPP whose rate of occurrence varies according to an unobserved finite state irreducible Markov process X(t). Since the likelihood function of this process can be obtained, by conditioning on the underlying Markov process X(t), the models were fitted with maximum likelihood methods. The proposed models were applied directly to the raw data collected by tipping-bucket rain gauges, thus avoiding the need to convert tip-times to rainfall depths prior to fitting the models. One advantage of this approach was that the use of maximum likelihood methods enables a more straightforward estimation of parameter uncertainty and comparison of sub-models of interest. Another strand of this approach employed the DSPP model for the arrivals of rain cells and attached a pulse or a cluster of pulses to each rain cell. Different mechanisms for the pattern of the pulse process were used to construct variants of this model. We present the results of these models when they were fitted to hourly and sub-hourly rainfall data. The results of our analysis suggest that the proposed class of stochastic models is capable of reproducing the fine-scale structure of the rainfall process, and hence provides a useful tool in hydrological modelling.

Keywords: fine-scale rainfall, maximum likelihood, point process, stochastic model

Procedia PDF Downloads 279

Authors: Choupani Andisheh, Temucin Elif Sevval, Bediz Bekir

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Due to their various advantages compared to many other drug delivery systems such as hypodermic injections and oral medications, microneedle arrays (MNAs) are a promising drug delivery system. To achieve enhanced performance of the MN, it is crucial to develop numerical models, optimization methods, and simulations. Accordingly, in this work, the optimized design of dissolvable MNAs, as well as their manufacturing, is investigated. For this purpose, a mechanical model of a single MN, having the geometry of an obelisk, is developed using commercial finite element software. The model considers the condition in which the MN is under pressure at the tip caused by the reaction force when penetrating the skin. Then, a multi-objective optimization based on non-dominated sorting genetic algorithm II (NSGA-II) is performed to obtain geometrical properties such as needle width, tip (apex) angle, and base fillet radius. The objective of the optimization study is to reach a painless and effortless penetration into the skin along with minimizing its mechanical failures caused by the maximum stress occurring throughout the structure. Based on the obtained optimal design parameters, master (male) molds are then fabricated from PMMA using a mechanical micromachining process. This fabrication method is selected mainly due to the geometry capability, production speed, production cost, and the variety of materials that can be used. Then to remove any chip residues, the master molds are cleaned using ultrasonic cleaning. These fabricated master molds can then be used repeatedly to fabricate Polydimethylsiloxane (PDMS) production (female) molds through a micro-molding approach. Finally, Polyvinylpyrrolidone (PVP) as a dissolvable polymer is cast into the production molds under vacuum to produce the dissolvable MNAs. This fabrication methodology can also be used to fabricate MNAs that include bioactive cargo. To characterize and demonstrate the performance of the fabricated needles, (i) scanning electron microscope images are taken to show the accuracy of the fabricated geometries, and (ii) in-vitro piercing tests are performed on artificial skin. It is shown that optimized MN geometries can be precisely fabricated using the presented fabrication methodology and the fabricated MNAs effectively pierce the skin without failure.

Keywords: microneedle, microneedle array fabrication, micro-manufacturing structural optimization, finite element analysis

Procedia PDF Downloads 114

Authors: Atefeh Abdollahi, Maryam Bahreini, Babak Choobi Anzali, Fatemeh Rasooli

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Introduction: Triage becomes the main part of organization of care in Emergency department (ED)s. It is used to describe the sorting of patients for treatment priority in ED. The accurate triage of injured patients has reduced fatalities and improved resource usage. Besides, the nurses’ knowledge and skill are important factors in triage decision-making. The ability to define an appropriate triage level and their need for intervention is crucial to guide to a safe and effective emergency care. Methods: This is a prospective cross-sectional study designed for emergency nurses working in four public university hospitals. Five triage workshops have been conducted every three months for emergency nurses based on a standard triage Emergency Severity Index (ESI) IV slide set - approved by Iranian Ministry of Health. Most influential items on triage performance were discussed through brainstorming in workshops which then, were peer reviewed by five emergency physicians and two head registered nurses expert panel. These factors that might distract nurse’ attention from proper decisions included patients’ past medical diseases, the natural tricks of triage and system failure. After permission had been taken, emergency nurses participated in the study and were given the structured questionnaire. Data were analysed by SPSS 21.0. Results: 92 emergency nurses enrolled in the study. 30 % of nurses reported the past history of chronic disease as the most influential confounding factor to ascertain triage level, other important factors were the history of prior admission, past history of myocardial infarction and heart failure to be 20, 17 and 11 %, respectively. Regarding the concept of difficulties in triage practice, 54.3 % reported that the discussion with patients and family members was difficult and 8.7 % declared that it is hard to stay in a single triage room whole day. Among the participants, 45.7 and 26.1 % evaluated the triage workshops as moderately and highly effective, respectively. 56.5 % reported overcrowding as the most important system-based difficulty. Nurses were mainly doubtful to differentiate between the triage levels 2 and 3 according to the ESI VI system. No significant correlation was found between the work record of nurses in triage and the uncertainty in determining the triage level and difficulties. Conclusion: The work record of nurses hardly seemed to be effective on the triage problems and issues. To correct the deficits, training workshops should be carried out, followed by continuous refresher training and supportive supervision.

Keywords: assessment, education, nurse, triage

Procedia PDF Downloads 235

Authors: Carl-Magnus Everitt, Bo Alfredsson

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Contact mechanics and tribology have been combined with fundamental fatigue and fracture mechanics to form the asperity mechanism which supplies an explanation for the surface-initiated rolling contact fatigue damage, called pitting or spalling. The cracks causing the pits initiates at one surface point and thereafter they slowly grow into the material before chipping of a material piece to form the pit. In the current study, the lubrication aspects on fatigue initiation are simulated by passing a single asperity through a thermal elastohydrodynamic lubricated, TEHL, contact. The physics of the lubricant was described with Reynolds equation and the lubricants pressure-viscosity relation was modeled by Roelands equation, formulated to include temperature dependence. A pressure dependent shear limit was incorporated. To capture the full phenomena of the sliding contact the temperature field was resolved through the incorporation of the energy flow. The heat was mainly generated due to shearing of the lubricant and from dry friction where metal contact occurred. The heat was then transported, and conducted, away by the solids and the lubricant. The fatigue damage caused by the asperities was evaluated through Findley’s fatigue criterion. The results show that asperities, in the size of surface roughness found in applications, may cause surface initiated fatigue damage and crack initiation. The simulations also show that the asperities broke through the lubricant in the inlet, causing metal to metal contact with high friction. When the asperities thereafter moved through the contact, the sliding provided the asperities with lubricant releasing the metal contact. The release of metal contact was possible due to the high viscosity the lubricant obtained from the high pressure. The metal contact in the inlet caused higher friction which increased the risk of fatigue damage. Since the metal contact occurred in the inlet it increased the fatigue risk more for asperities subjected to negative slip than positive slip. Therefore the fatigue evaluations showed that the asperities subjected to negative slip yielded higher fatigue stresses than the asperities subjected to positive slip of equal magnitude. This is one explanation for why pitting is more common in the dedendum than the addendum on pinion gear teeth. The simulations produced further validation for the asperity mechanism by showing that asperities cause surface initiated fatigue and crack initiation.

Keywords: fatigue, rolling, sliding, thermal elastohydrodynamic

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Authors: Joanna Gerszon, Aleksandra Rodacka

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In the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, protein and peptide aggregation processes play a vital role in contributing to the formation of intracellular and extracellular protein deposits. One of the major components of these deposits is the oxidatively modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Therefore, the purpose of this research was to answer the question whether piceatannol, a stilbene derivative, counteracts and/or slows down oxidative stress-induced GAPDH aggregation. The study also aimed to determine if this natural occurring compound prevents unfavorable nuclear translocation of GAPDH in hippocampal cells. The isothermal titration calorimetry (ITC) analysis indicated that one molecule of GAPDH can bind up to 8 molecules of piceatannol (7.3 ± 0.9). As a consequence of piceatannol binding to the enzyme, the loss of activity was observed. Parallel with GAPDH inactivation the changes in zeta potential, and loss of free thiol groups were noted. Nevertheless, the ligand-protein binding does not influence the secondary structure of the GAPDH. Precise molecular docking analysis of the interactions inside the active center allowed to presume that these effects are due to piceatannol ability to assemble a covalent binding with nucleophilic cysteine residue (Cys149) which is directly involved in the catalytic reaction. Molecular docking also showed that simultaneously 11 molecules of ligand can be bound to dehydrogenase. Taking into consideration obtained data, the influence of piceatannol on level of GAPDH aggregation induced by excessive oxidative stress was examined. The applied methods (thioflavin-T binding-dependent fluorescence as well as microscopy methods - transmission electron microscopy, Congo Red staining) revealed that piceatannol significantly diminishes level of GAPDH aggregation. Finally, studies involving cellular model (Western blot analyses of nuclear and cytosolic fractions and confocal microscopy) indicated that piceatannol-GAPDH binding prevents GAPDH from nuclear translocation induced by excessive oxidative stress in hippocampal cells. In consequence, it counteracts cell apoptosis. These studies demonstrate that by binding with GAPDH, piceatannol blocks cysteine residue and counteracts its oxidative modifications, that induce oligomerization and GAPDH aggregation as well as it prevents hippocampal cells from apoptosis by retaining GAPDH in the cytoplasm. All these findings provide a new insight into the role of piceatannol interaction with GAPDH and present a potential therapeutic strategy for some neurological disorders related to GAPDH aggregation. This work was supported by the by National Science Centre, Poland (grant number 2017/25/N/NZ1/02849).

Keywords: glyceraldehyde-3-phosphate dehydrogenase, neurodegenerative disease, neuroprotection, piceatannol, protein aggregation

Procedia PDF Downloads 167

Authors: Vladimíra Kňazovická, Mária Dovičičová, Miroslava Kačániová, Margita Čanigová

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The aim of the study was to test the storage of bee pollen at room temperature and in cold store, and to describe microorganisms originated from it. Fresh bee pollen originating in West Slovakia was collected in May 2010. It was tested for presence of particular microbial groups using dilution plating method, and divided into two parts with different storage (in cold store and at room temperature). Microbial analyses of pollen were repeated after one year of storage. Several bacterial strains were isolated and tested using Gram staining, for catalase and fructose-6-phosphate-phosphoketolase presence, and by rapid ID 32A (BioMérieux, France). Micromycetes were identified at genus level. Fresh pollen contained coliform bacteria, which were not detected after one year of storage in both ways. Total plate count (TPC) of aerobes and anaerobes and of yeasts in fresh bee pollen exceeded 5.00 log CFU/g. TPC of aerobes and anaerobes decreased below 2.00 log CFU/g after one year of storage in both ways. Count of yeasts decreased to 2.32 log CFU/g (at room temperature) and to 3.66 log CFU/g (in cold store). Microscopic filamentous fungi decreased from 3.41 log CFU/g (fresh bee pollen) to 1.13 log CFU/g (at room temperature) and to 1.89 log CFU/g (in cold store). In fresh bee pollen, 12 genera of micromycetes were identified in the following order according to their relative density: Penicillium > Mucor > Absidia > Cladosporium, Fusarium > Alternaria > Eurotium > Aspergillus, Rhizopus > Emericella > Arthrinium and Mycelium sterilium. After one year at room temperature, only three genera were detected in bee pollen (Penicillium > Aspergillus, Mucor) and after one year in cold store, seven genera were detected (Mucor > Penicillium, Emericella > Aspergillus, Absidia > Arthrinium, Eurotium). From the plates designated for anaerobes, eight colonies originating in fresh bee pollen were isolated. Among them, a single yeast isolate occurred. Other isolates were G+ bacteria, with a total of five rod shaped. In three out of these five, catalase was absent and fructose-6-phosphate-phosphoketolase was present. Bacterial isolates originating in fresh pollen belonged probably to genus Bifidobacterium or relative genera, but their identity was not confirmed unequivocally. In general, cold conditions are suitable for maintaining the natural properties of foodstuffs for a longer time. Slight decrease of microscopic fungal number and diversity was recorded in cold temperatures compared with storage at room temperature.

Keywords: bacteria, bee product, microscopic fungi, biosystems engineering

Procedia PDF Downloads 345

Authors: S. A. Bhat, Ahmad Arif, Muneeb U. Rehman, Manzoor R Mir, S. Bilal, Ishraq Hussain, H. M Khan, S. Shanaz, M. I Mir, Sabhiya Majid

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Background: Geologically Climatic conditions of the state range from sub-tropical (Jammu), temperate (Kashmir) to cold artic (Ladakh) zones, which exerts significant influence on its agro-climatic conditions. Gastrointestinal parasitism is a major problem in sheep production worldwide. Materials and Methods: The present study was to evaluate the resistance status of sheep breeds reared in Kashmir Valley for natural resistance against Haemonchus contortus by natural pasture challenge infection. Ten microsatellite markers were used in the study for evaluation of association of Ovar-MHC with parasitic resistance in association with biochemical and parasitological parameters. Following deworming, 500 animals were subjected to selected contaminated pastures in a vicinity of the livestock farms of SKUAST-K and Sheep Husbandry Kashmir. For each animal about 10-15 ml blood was collected aseptically for molecular and biochemical analysis. Weekly fecal samples (3g) were taken, directly from the rectum of all experimental animals and examined for Fecal egg count (FEC) with modified McMaster technique. Packed cell volume (PCV) was determined within 2-5 h of blood collection, all the biochemical parameters were determined in serum by semi automated analyzer. DNA was extracted from all the blood samples with phenol-chloroform method. Microsatellite analysis was done by denaturing sequencing gel electrophoresis Results: Overall sheep from Bakerwal breed followed by Corriediale breed performed relatively better in the trial; however difference between breeds remained low. Both significant (P<0.05) and non-significant differences with respect to resistance against haemonchosis were noted at different intervals in all the parameters.. All the animals were typed for the microsatellites INRA132, OarCP73, DRB1 (U0022), OLA-DQA2, BM1818, TFAP2A, HH56, BM1815, IL-3 and BM-1258. An association study including the effect of FEC, PCV, TSP, SA, LW, and the number of alleles within each marker was done. All microsatellite markers showed degree of heterozygosity of 0.72, 0.72, 0.75, 0.62, 0.84, 0.69, 0.66, 0.65, 0.73 and 0.68 respectively. Significant association between alleles and the parameters measured were only found for the OarCP73, OLA-DQA2 and BM1815 microsatellite marker. Standard alleles of the above markers showed significant effect on the TP, SA and body weight. The three sheep breeds included in the study responded differently to the nematode infection, which may be attributed to their differences in their natural resistance against nematodes. Conclusion: Our data confirms that some markers (OarCP73, OLA-DQA2 and BM1815) within Ovar-MHC are associated with phenotypic parameters of resistance and suggest superiority of Bakerwal sheep breed in natural resistance against Haemonchus contortus.

Keywords: Ovar-Mhc, ovine leukocyte antigen (OLA), sheep, parasitic resistance, Haemonchus contortus, phenotypic & genotypic markers

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Authors: Xianwei Zheng, Yuan Yan Tang

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Classical window Fourier transform has been widely used in signal processing, image processing, machine learning and pattern recognition. The related Gabor transform is powerful enough to capture the texture information of any given dataset. Recently, in the emerging field of graph signal processing, researchers devoting themselves to develop a graph signal processing theory to handle the so-called graph signals. Among the new developing theory, windowed graph Fourier transform has been constructed to establish a time-frequency analysis framework of graph signals. The windowed graph Fourier transform is defined by using the translation and modulation operators of graph signals, following the similar calculations in classical windowed Fourier transform. Specifically, the translation and modulation operators of graph signals are defined by using the Laplacian eigenvectors as follows. For a given graph signal, its translation is defined by a similar manner as its definition in classical signal processing. Specifically, the translation operator can be defined by using the Fourier atoms; the graph signal translation is defined similarly by using the Laplacian eigenvectors. The modulation of the graph can also be established by using the Laplacian eigenvectors. The windowed graph Fourier transform based on these two operators has been applied to obtain time-frequency representations of graph signals. Fundamentally, the modulation operator is defined similarly to the classical modulation by multiplying a graph signal with the entries in each Fourier atom. However, a single Laplacian eigenvector entry cannot play a similar role as the Fourier atom. This definition ignored the relationship between the translation and modulation operators. In this paper, a new definition of the modulation operator is proposed and thus another time-frequency framework for graph signal is constructed. Specifically, the relationship between the translation and modulation operations can be established by the Fourier transform. Specifically, for any signal, the Fourier transform of its translation is the modulation of its Fourier transform. Thus, the modulation of any signal can be defined as the inverse Fourier transform of the translation of its Fourier transform. Therefore, similarly, the graph modulation of any graph signal can be defined as the inverse graph Fourier transform of the translation of its graph Fourier. The novel definition of the graph modulation operator established a relationship of the translation and modulation operations. The new modulation operation and the original translation operation are applied to construct a new framework of graph signal time-frequency analysis. Furthermore, a windowed graph Fourier frame theory is developed. Necessary and sufficient conditions for constructing windowed graph Fourier frames, tight frames and dual frames are presented in this paper. The novel graph signal time-frequency analysis framework is applied to signals defined on well-known graphs, e.g. Minnesota road graph and random graphs. Experimental results show that the novel framework captures new features of graph signals.

Keywords: graph signals, windowed graph Fourier transform, windowed graph Fourier frames, vertex frequency analysis

Procedia PDF Downloads 342

Authors: Ayten Ekin Meşe, Selahattin Şentürk, Melike Duvanoğlu

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Petroleum refineries are a highly complex process industry with continuous production and high operating costs. Physical separation of crude oil starts with the crude oil distillation unit, continues with various conversion and purification units, and passes through many stages until obtaining the final product. To meet the desired product specification, process parameters are strictly followed. To be able to ensure the quality of distillates, routine analyses are performed in quality control laboratories based on appropriate international standards such as American Society for Testing and Materials (ASTM) standard methods and European Standard (EN) methods. The cut point of distillates in the crude distillation unit is very crucial for the efficiency of the upcoming processes. In order to maximize the process efficiency, the determination of the quality of distillates should be as fast as possible, reliable, and cost-effective. In this sense, an alternative study was carried out on the crude oil distillation unit that serves the entire refinery process. In this work, studies were conducted with three different crude oil distillates which are Light Straight Run Naphtha (LSRN), Heavy Straight Run Naphtha (HSRN), and Kerosene. These products are named after separation by the number of carbons it contains. LSRN consists of five to six carbon-containing hydrocarbons, HSRN consist of six to ten, and kerosene consists of sixteen to twenty-two carbon-containing hydrocarbons. Physical properties of three different crude distillation unit products (LSRN, HSRN, and Kerosene) were determined using Near-Infrared Spectroscopy with multivariate calibration. The absorbance spectra of the petroleum samples were obtained in the range from 10000 cm⁻¹ to 4000 cm⁻¹, employing a quartz transmittance flow through cell with a 2 mm light path and a resolution of 2 cm⁻¹. A total of 400 samples were collected for each petroleum sample for almost four years. Several different crude oil grades were processed during sample collection times. Extended Multiplicative Signal Correction (EMSC) and Savitzky-Golay (SG) preprocessing techniques were applied to FT-NIR spectra of samples to eliminate baseline shifts and suppress unwanted variation. Two different multivariate calibration approaches (Partial Least Squares Regression, PLS and Genetic Inverse Least Squares, GILS) and an ensemble model were applied to preprocessed FT-NIR spectra. Predictive performance of each multivariate calibration technique and preprocessing techniques were compared, and the best models were chosen according to the reproducibility of ASTM reference methods. This work demonstrates the developed models can be used for routine analysis instead of conventional analytical methods with over 90% accuracy.

Keywords: crude distillation unit, multivariate calibration, near infrared spectroscopy, data preprocessing, refinery

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Authors: Seyed Mehdi Seyed Alizadeh, Christoph Arns, Shane Latham

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Geomechanical characterization of rocks in detail and its possible implications on flow properties is an important aspect of reservoir characterization workflow. In order to gain more understanding of the microstructure evolution of reservoir rocks under stress a series of axisymmetric triaxial tests were performed on two different analogue rock samples. In-situ compression tests were coupled with high resolution micro-Computed Tomography to elucidate the changes in the pore/grain network of the rocks under pressurized conditions. Two outcrop sandstones were chosen in the current study representing a various cementation status of well-consolidated and weakly-consolidated granular system respectively. High resolution images were acquired while the rocks deformed in a purpose-built compression cell. A detailed analysis of the 3D images in each series of step-wise compression tests (up to the failure point) was conducted which includes the registration of the deformed specimen images with the reference pristine dry rock image. Digital Image Correlation (DIC) technique based on the intensity of the registered 3D subsets and particle tracking are utilized to map the displacement fields in each sample. The results suggest the complex architecture of the localized shear zone in well-cemented Bentheimer sandstone whereas for the weakly-consolidated Castlegate sandstone no discernible shear band could be observed even after macroscopic failure. Post-mortem imaging a sister plug from the friable rock upon undergoing continuous compression reveals signs of a shear band pattern. This suggests that for friable sandstones at small scales loading mode may affect the pattern of deformation. Prior to mechanical failure, the continuum digital image correlation approach can reasonably capture the kinematics of deformation. As failure occurs, however, discrete image correlation (i.e. particle tracking) reveals superiority in both tracking the grains as well as quantifying their kinematics (in terms of translations/rotations) with respect to any stage of compaction. An attempt was made to quantify the displacement field in compression using continuum Digital Image Correlation which is based on the reference and secondary image intensity correlation. Such approach has only been previously applied to unconsolidated granular systems under pressure. We are applying this technique to sandstones with various degrees of consolidation. Such element of novelty will set the results of this study apart from previous attempts to characterize the deformation pattern in consolidated sands.

Keywords: deformation mechanism, displacement field, shear behavior, triaxial compression, X-ray micro-CT

Procedia PDF Downloads 190

Authors: Miraji H. Mohamed

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The purpose of this study is to critique ‘radicalisation’ and more particularly ‘youth radicalisation’ by exploring its usage in online newspapers. ‘Radicalisation’ and ‘extremism’ have become the most common terms in terrorism studies since the 9/11 attacks. Regardless of the geographic location, when the word terrorism is used the terms ‘radicalisation’ and ‘extremism’ always follow to attempt to explore the journey of the perpetrators towards violence. These terms have come to represent a discourse of dominantly pejorative traits often used to describe spaces, groups, and processes identified as problematic. Even though ambiguously defined they feature widely in government documents, political statements, news articles, academic research, social media platforms, religious gatherings, and public discussions. Notably, ‘radicalisation’ and ‘extremism’ have been closely conflated with the term youth to form ‘youth radicalisation’ to refer to a discourse of ‘youth at risk’. The three terms largely continue to be used unquestioningly and interchangeably hence the reason why they are placed in single quotation marks to deliberately question their conventional usage. Albeit this comes timely in the Kenyan context where there has been a proliferation of academic and expert research on ‘youth radicalisation’ (used as a neutral label) without considering the political, cultural and socio-historical contexts that inform this label. This study seeks to draw these nuances by employing a genealogical approach that historicises and deconstructs ‘youth radicalisation’; and by applying a Discourse-Historical Approach (DHA) of Critical Discourse Analysis to analyse Kenyan online newspaper - The Daily Nation between 2015 and 2018. By applying the concept of representation to analyse written texts, the study reveals that the use of ‘youth radicalisation’ as a discursive strategy disproportionately affects young people especially those from cultural/ethnic/religious minority groups. Also, the ambiguous use of ‘radicalisation’ and ‘youth radicalisation’ by the media reinforces the discourse of ‘youth at risk’ which has become the major framework underpinning Countering Violent Extremism (CVE) interventions. Similarly, the findings indicate that the uncritical use of ‘youth radicalisation’ has been used to serve political interests; and has become an instrument of policing young people, thus contributing to their cultural shaping. From this, it is evident that the media could thwart rather than assist CVE efforts. By exposing the political nature of the three terms through evidence-based research, this study offers recommendations on how critical reflective reporting by the media could help to make CVE more nuanced.

Keywords: discourse, extremism, radicalisation, terrorism, youth

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Authors: Tomasz Borowski, Dawid Sołoducha, Agata Markowska-Szczupak, Aneta Wesołowska, Marian Kordas, Rafał Rakoczy

Abstract:

Essential oils (EOs) are fragrant volatile oils obtained from plants. These are used for cooking (for flavor and aroma), cleaning, beauty (e.g., rosemary essential oil is used to promote hair growth), health (e.g. thyme essential oil cures arthritis, normalizes blood pressure, reduces stress on the heart, cures chest infection and cough) and in the food industry as preservatives and antioxidants. Rosemary and thyme essential oils are considered the most eminent herbs based on their history and medicinal properties. They possess a wide range of activity against different types of bacteria and fungi compared with the other oils in both in vitro and in vivo studies. However, traditional uses of EOs are limited due to rosemary and thyme oils in high concentrations can be toxic. In light of the accessible data, the following hypothesis was put forward: Low frequency rotating magnetic field (RMF) increases the antimicrobial potential of EOs. The aim of this work was to investigate the antimicrobial activity of commercial Salvia Rosmarinus L. and Thymus vulgaris L. essential oil from Polish company Avicenna-Oil under Rotating Magnetic Field (RMF) at f = 25 Hz. The self-constructed reactor (MAP) was applied for this study. The chemical composition of oils was determined by gas chromatography coupled with mass spectrometry (GC-MS). Model bacteria Escherichia coli K12 (ATCC 25922) was used. Minimum inhibitory concentrations (MIC) against E. coli were determined for the essential oils. Tested oils in very small concentrations were prepared (from 1 to 3 drops of essential oils per 3 mL working suspensions). From the results of disc diffusion assay and MIC tests, it can be concluded that thyme oil had the highest antibacterial activity against E. coli. Moreover, the study indicates the exposition to the RMF, as compared to the unexposed controls causing an increase in the efficacy of antibacterial properties of tested oils. The extended radiation exposure to RMF at the frequency f= 25 Hz beyond 160 minutes resulted in a significant increase in antibacterial potential against E. coli. Bacteria were killed within 40 minutes in thyme oil in lower tested concentration (1 drop of essential oils per 3 mL working suspension). Rapid decrease (>3 log) of bacteria number was observed with rosemary oil within 100 minutes (in concentration 3 drops of essential oils per 3 mL working suspension). Thus, a method for improving the antimicrobial performance of essential oil in low concentrations was developed. However, it still remains to be investigated how bacteria get killed by the EOs treated by an electromagnetic field. The possible mechanisms relies on alteration in the permeability of ionic channels in ionic channels in the bacterial cell walls that transport in the cells was proposed. For further studies, it is proposed to examine other types of essential oils and other antibiotic-resistant bacteria (ARB), which are causing a serious concern throughout the world.

Keywords: rotating magnetic field, rosemary, thyme, essential oils, Escherichia coli

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Authors: Farahnaz Sadat Golestan Hashemi, Mohd Razi Ismail, Mohd Y. Rafii

Abstract:

Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas) system can facilitate targeted genome editing in organisms. Dual or single guide RNA (gRNA) can program the Cas9 nuclease to cut target DNA in particular areas; thus, introducing concise mutations either via error-prone non-homologous end-joining repairing or via incorporating foreign DNAs by homologous recombination between donor DNA and target area. In spite of high demand of such promising technology, developing a well-organized procedure in order for reliable mining of potential target sites for gRNAs in large genomic data is still challenging. Hence, we aimed to perform high-throughput detection of target sites by specific PAMs for not only common Streptococcus pyogenes (SpCas9) but also for Neisseria meningitides (NmCas9) CRISPR-Cas systems. Previous research confirmed the successful application of such RNA-guided Cas9 orthologs for effective gene targeting and subsequently genome manipulation. However, Cas9 orthologs need their particular PAM sequence for DNA cleavage activity. Activity levels are based on the sequence of the protospacer and specific combinations of favorable PAM bases. Therefore, based on the specific length and sequence of PAM followed by a constant length of the target site for the two orthogonals of Cas9 protein, we created a reliable procedure to explore possible gRNA sequences. To mine CRISPR target sites, four different searching modes of sgRNA binding to target DNA strand were applied. These searching modes are as follows i) coding strand searching, ii) anti-coding strand searching, iii) both strand searching, and iv) paired-gRNA searching. Finally, a complete list of all potential gRNAs along with their locations, strands, and PAMs sequence orientation can be provided for both SpCas9 as well as another potential Cas9 ortholog (NmCas9). The artificial design of potential gRNAs in a genome of interest can accelerate functional genomic studies. Consequently, the application of such novel genome editing tool (CRISPR/Cas technology) will enhance by presenting increased versatility and efficiency.

Keywords: CRISPR/Cas9 genome editing, gRNA mining, SpCas9, NmCas9

Procedia PDF Downloads 263

Authors: É. Vincze

Abstract:

Demand on plant oils has increased to an enormous extent that is due to the change of human nutrition habits on the one hand, while on the other hand to the increase of raw material demand of some industrial sectors, just as to the increase of biofuel production. Besides the determining importance of sunflower in Hungary the production area, just as in part the average yield amount of rapeseed has increased among the produced oil crops. The variety/hybrid palette has changed significantly during the past decade. The available varieties’/hybrids’ palette has been extended to a significant extent. It is agreed that rapeseed production demands professionalism and local experience. Technological elements are successive; high yield amounts cannot be produced without system-based approach. The aim of the present work was to execute the complex study of one of the most critical production technology element of rapeseed production, that was sowing technology. Several sowing technology elements are studied in this research project that are the following: biological basis (the hybrid Arkaso is studied in this regard), sowing time (sowing time treatments were set so that they represent the wide period used in industrial practice: early, optimal and late sowing time) plant density (in this regard reaction of rare, optimal and too dense populations) were modelled. The multifactorial experimental system enables the single and complex evaluation of rapeseed sowing technology elements, just as their modelling using experimental result data. Yield quality and quantity have been determined as well in the present experiment, just as the interactions between these factors. The experiment was set up in four replications at the Látókép Plant Production Research Site of the University of Debrecen. Two different sowing times were sown in the first experimental year (2014), while three in the second (2015). Three different plant densities were set in both years: 200, 350 and 500 thousand plants ha-1. Uniform nutrient supply and a row spacing of 45 cm were applied. Winter wheat was used as pre-crop. Plant physiological measurements were executed in the populations of the Arkaso rapeseed hybrid that were: relative chlorophyll content analysis (SPAD) and leaf area index (LAI) measurement. Relative chlorophyll content (SPAD) and leaf area index (LAI) were monitored in 7 different measurement times.

Keywords: inner quality, plant density, rapeseed, sowing time

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Authors: Jeanne Leblond, Warren Viricel, Amira Mbarek

Abstract:

Although several products have reached the market, gene therapeutics are still in their first stages and require optimization. It is possible to improve their lacking efficiency by the use of carefully engineered vectors, able to carry the genetic material through each of the biological barriers they need to cross. In particular, getting inside the cell is a major challenge, because these hydrophilic nucleic acids have to cross the lipid-rich plasmatic and/or endosomal membrane, before being degraded into lysosomes. It takes less than one hour for newly endocytosed liposomes to reach highly acidic lysosomes, meaning that the degradation of the carried gene occurs rapidly, thus limiting the transfection efficiency. We propose to use a new pH-sensitive lipid able to change its conformation upon protonation at endosomal pH values, leading to the disruption of the lipidic bilayer and thus to the fast release of the nucleic acids into the cytosol. It is expected that this new pH-sensitive mechanism promote endosomal escape of the gene, thereby its transfection efficiency. The main challenge of this work was to design a preparation presenting fast-responding lipidic bilayer destabilization properties at endosomal pH 5 while remaining stable at blood pH value and during storage. A series of pH-sensitive lipids able to perform a conformational switch upon acidification were designed and synthesized. Liposomes containing these switchable lipids, as well as co-lipids were prepared and characterized. The liposomes were stable at 4°C and pH 7.4 for several months. Incubation with siRNA led to the full entrapment of nucleic acids as soon as the positive/negative charge ratio was superior to 2. The best liposomal formulation demonstrated a silencing efficiency up to 10% on HeLa cells, very similar to a commercial agent, with a lowest toxicity than the commercial agent. Using flow cytometry and microscopy assays, we demonstrated that drop of pH was required for the transfection efficiency, since bafilomycin blocked the transfection efficiency. Additional evidence was brought by the synthesis of a negative control lipid, which was unable to switch its conformation, and consequently exhibited no transfection ability. Mechanistic studies revealed that the uptake was mediated through endocytosis, by clathrin and caveolae pathways, as reported for previous lipid nanoparticle systems. This potent system was used for the treatment of hypercholesterolemia. The switchable lipids were able to knockdown PCSK9 expression on human hepatocytes (Huh-7). Its efficiency is currently evaluated on in vivo mice model of PCSK9 KO mice. In summary, we designed and optimized a new cationic pH-sensitive lipid for gene delivery. Its transfection efficiency is similar to the best available commercial agent, without the usually associated toxicity. The promising results lead to its use for the treatment of hypercholesterolemia on a mice model. Anticancer applications and pulmonary chronic disease are also currently investigated.

Keywords: liposomes, siRNA, pH-sensitive, molecular switch

Procedia PDF Downloads 204