Search results for: biomolecular sequence synthesis

Authors: Dmitry Usenco

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The greatest paradox about the origin of language is the fact that, while language is always taught by adults to children, it can never be learnt properly unless its acquisition occurs during childhood. The question that naturally arises in that respect is as follows: How could language be taught for the first time by a non-speaker, i.e., by someone who did not have the opportunity to master it as a child? Yet the above paradox will appear less unresolvable if we hypothesise that language was originally introduced not as a means of communication but as a relatively modest training/playing technique that was used to develop the learners’ mimetic skills. Its communicative and expressive properties could have been discovered and exploited later – upon the learners’ reaching their adulthood. The importance of mimesis in children’s development is universally recognised. The most common forms of it are onomatopoeia and mime, which consist in reproducing sounds and imitating shapes/movements of externally observed objects. However, in some cases, neither of these exercises can be adequate to the task. An object, especially an inanimate one, may emit no characteristic sounds, making onomatopoeia problematic. In other cases, it may have no easily reproduceable shape, while its movements may depend on the specific way of our interacting with it. On such occasions, onomatopoeia and mime can perhaps be supplemented, or even replaced, by movements of the tongue which can metonymically represent certain aspects of our interaction with the object. This is especially evident with consonants: e.g., a fricative sound can designate the subject’s relatively slow approach to the object or vice versa, while a plosive one can express the relatively abrupt process of grabbing/sticking or parrying/bouncing. From that point of view, a protoword can be regarded as a sophisticated gesture of the tongue but also as a mnemonic sequence that contains encoded instructions about the way to handle the object. When this originally subjective link between the object and its mimetic/mnemonic representation eventually installs itself in the collective mind (however small at first the community might be), the initially nameless object acquires a name, and the first word is created. (Discussing the difference between proper and common names is out of the scope of this paper). In its very beginning, this word has two major applications. It can be used for interhuman communication because it allows us to invoke the presence of a currently absent object. It can also be used for designing, expressing, and memorising our interaction with the object itself. The first usage gives rise to language, the second to religion. By the act of naming, we attach to the object a mental (‘spiritual’) dimension which has an independent existence in our collective mind. By referring to the name (idea/demon/soul) of the object, we perform our first act of spirituality, our first religious observance. This is the beginning of animism – arguably, the most ancient form of religion. To conclude: the rise of religion is simultaneous with the the emergence of language in human evolution.

Keywords: language, religion, origin, acquisition, childhood, adulthood, play, represntation, onomatopoeia, mime, gesture, consonant, simultaneity, spirituality, animism

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Authors: Nozomi Fujisaka

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This sociological case study analyzes a sequence of student maltreatment in an elementary school in Japan, based on narratives from former students. Among various forms of student maltreatment, emotional maltreatment has received less attention. One reason for this is that emotional maltreatment is often considered part of education and is difficult to capture in surveys. To discuss the challenge of recognizing emotional maltreatment, it's necessary to consider the social background in which student maltreatment occurs. Therefore, from the perspective of the sociology of education, this study aims to clarify the process through which emotional maltreatment was embraced by students within a Japanese classroom. The focus of this study is a series of educational interactions by a homeroom teacher with 11- or 12-year-old students at a small public elementary school approximately 10 years ago. The research employs retrospective narrative data collected through interviews and autoethnography. The semi-structured interviews, lasting one to three hours each, were conducted with 11 young people who were enrolled in the same class as the researcher during their time in elementary school. Autoethnography, as a critical research method, contributes to existing theories and studies by providing a critical representation of the researcher's own experiences. Autoethnography enables researchers to collect detailed data that is often difficult to verbalize in interviews. These research methods are well-suited for this study, which aims to shift the focus from teachers' educational intentions to students' perspectives and gain a deeper understanding of student maltreatment. The research results imply a pattern of emotional maltreatment that is challenging to differentiate from education. In this study's case, the teacher displayed calm and kind behavior toward students after a threat and an explosion of anger. Former students frequently mentioned this behavior of the teacher and perceived emotional maltreatment as part of education. It was not uncommon for former students to offer positive evaluations of the teacher despite experiencing emotional distress. These findings are analyzed and discussed in conjunction with the deschooling theory and the cycle of violence theory. The deschooling theory provides a sociological explanation for how emotional maltreatment can be overlooked in society. The cycle of violence theory, originally developed within the context of domestic violence, explains how violence between romantic partners can be tolerated due to prevailing social norms. Analyzing the case in association with these two theories highlights the characteristics of teachers' behaviors that rationalize maltreatment as education and hinder students from escaping emotional maltreatment. This study deepens our understanding of the causes of student maltreatment and provides a new perspective for future qualitative and quantitative research. Furthermore, since this research is based on the sociology of education, it has the potential to expand research in the fields of pedagogy and sociology, in addition to psychology and social welfare.

Keywords: emotional maltreatment, education, student maltreatment, Japan

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Authors: N. Gopal, K. Jaasminerjiit, L. Z. Xiang

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Quinazoline-4(3H)-one ring system has been consistently regarded as promising privileged structural icon owing to its pharmacodynamic versatility in many of its synthetic derivatives as well as in several naturally occurring alkaloids. The literature reveals that 2nd & 3rd positions of the quinazolin-4(3H)-one pharmacophore are the target for substitution with other moieties. On the other hand, sulphanilamide derivatives and isatin moiety also displayed valuable biological activities. Hence, it was thought worthwhile to study the effects of three pharmacophoric moieties like quinazolinone, sulphanilamide and isatin in a single molecule for the better analgesic activity with lower toxicity. Series of novel 2,3-disubstituted quinazolin-4(3H)-one derivatives have been synthesised from the intermediate Schiff base of 2-(4’-substitutedphenyl)-3-[(N-2-oxoindolin-3-ylidene)-4”-sulphonamidophenyl]-quinazolin-4(3H)-one derivatives, which was prepared from reacting 2-(substituted phenyl)-4H-benzo[d][1,3]-oxazin-4-one with sulphanilamide. The required benzoxazinone derivatives were prepared by reacting anthranilic acid with benzoyl chloride. All the compounds structure was characterised by using H1 NMR, IR and Mass spectroscopy. The intermediate Schiff base and final Mannich base compounds were evaluated for their analgesic activity by acetic acid-induced writhing method at the dose of 25mg/kg, 50 mg/kg, and 100 mg/kg (bw) and Diclofenac (25mg/kg of body weight) will be used as the reference drugs. From the results of the study, it has been observed that final Mannich base showed a better analgesic activity when compared to the parent Schiff bases, it was found that compound substituted with N-methyl piperazine at 1st position of the indole nucleus of the final quinazolinone derivatives (GA4B1) i.e. 2-(4’-methoxy phenyl)-3-[4-(N-(1-N-methyl piperazine amine) methyl-2-oxo indoilin-3-ylidene] benzenesulfonyl quinazolin-4(3H)-one increases the analgesic activity and among the synthesised compounds, GA4B1 exhibited quite superior analgesic activity. The remaining Schiff bases and Mannich base derivatives exhibited moderate analgesic activity. All the compounds showed a dose dependent activity. None of the synthesised compound showed ulcer index whereas the standard drug, diclofenac [25 mg/kg (bw)] showed significantly higher gross ulcer index values.

Keywords: analgesic activity, isatin, mannich base, quinazolin-4(3H)-one

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Authors: Lorena Mihelac, Janez Povh

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In 2017, we conducted a research study using data consisting of 160 musical excerpts from different musical styles, to analyze the impact of entropy of the harmony on the acceptability of music. In measuring the entropy of harmony, we were interested in unigrams (individual chords in the harmonic progression) and bigrams (the connection of two adjacent chords). In this study, it has been found that 53 musical excerpts out from 160 were evaluated by participants as very complex, although the entropy of the harmonic progression (unigrams and bigrams) was calculated as low. We have explained this by particularities of chord progression, which impact the listener's feeling of complexity and acceptability. We have evaluated the same data twice with new participants in 2018 and with the same participants for the third time in 2019. These three evaluations have shown that the same 53 musical excerpts, found to be difficult and complex in the study conducted in 2017, are exhibiting a high feeling of complexity again. It was proposed that the content of these musical excerpts, defined as “irregular,” is not meeting the listener's expectancy and the basic perceptual principles, creating a higher feeling of difficulty and complexity. As the “irregularities” in these 53 musical excerpts seem to be perceived by the participants without being aware of it, affecting the pleasantness and the feeling of complexity, they have been defined as “subliminal irregularities” and the 53 musical excerpts as “irregular.” In our recent study (2019) of the same data (used in previous research works), we have proposed a new measure of the complexity of harmony, “regularity,” based on the irregularities in the harmonic progression and other plausible particularities in the musical structure found in previous studies. We have in this study also proposed a list of 10 different particularities for which we were assuming that they are impacting the participant’s perception of complexity in harmony. These ten particularities have been tested in this paper, by extending the analysis in our 53 irregular musical excerpts from harmony to melody. In the examining of melody, we have used the computational model “Information Dynamics of Music” (IDyOM) and two information-theoretic measures: entropy - the uncertainty of the prediction before the next event is heard, and information content - the unexpectedness of an event in a sequence. In order to describe the features of melody in these musical examples, we have used four different viewpoints: pitch, interval, duration, scale degree. The results have shown that the texture of melody (e.g., multiple voices, homorhythmic structure) and structure of melody (e.g., huge interval leaps, syncopated rhythm, implied harmony in compound melodies) in these musical excerpts are impacting the participant’s perception of complexity. High information content values were found in compound melodies in which implied harmonies seem to have suggested additional harmonies, affecting the participant’s perception of the chord progression in harmony by creating a sense of an ambiguous musical structure.

Keywords: entropy and information content, harmony, subliminal (ir)regularity, IDyOM

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Authors: Fitih Ademe, Kibebew Kibret, Sheleme Beyene, Mezgebu Getnet, Gashaw Meteke

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Pressing demands for agricultural products and its associated pressure on water availability in the semi-arid areas demanded information for strategic decision-making in the changing climate conditions of Ethiopia. Availing such information through traditional agronomic research methods is not sufficient unless supported through the application of decision-support tools. The CERES (Crop Environmental Resource Synthesis) model in DSSAT-CSM was evaluated for estimating yield and water productivity of maize under two soil types (Andosol and Luvisol) of the Central Rift Valley of Ethiopia. A six-year data (2010 – 2017) obtained from national fertilizer determination experiments were used for model evaluation. Pertinent statistical indices were employed to evaluate model performance. Following model evaluation, yield and rain-water productivity of maize was assessed for the baseline (1981-2010) and future climate (2050’s and 2080’s) scenario. The model performed well in predicting phenology, growth, and yield of maize for the different seasons and phosphorous rates. A good agreement between simulated and observed grain yield was indicated by low values of the RMSE (0.15 - 0.37 Mg/ha) and other indices for the two soil types. The evaluated model predicted a decline in the potential (23.8 to 26.7% at Melkassa and from 21.7 to 26.1% at Ziway under RCP4.5 and RCP8.5 climate change scenarios, respectively) and water-limited yield (15 to 18.3% at Melkassa and by 6.5 to 10.5% at Ziway) in the mid-century due to climate change. Consequently, a decline in water productivity was projected in the future periods that necessitate availing options to improve water productivity in the region. In conclusion, the DSSAT-CERES-maize model can be used to simulate maize (Melkassa-2) phenology, growth and grain yield, as well as simulate water productivity under different management scenarios that can help to identify options to improve water productivity in the changing climate of the semi-arid central Rift valley of Ethiopia.

Keywords: andosol, CERES-maize, luvisol, model evaluation, water productivity

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Authors: Ehsan Alishahi, Chuang Deng

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Materials with microstructural heterogeneity have recently attracted dramatic attention in the materials science community. Although most of the metals are identified as crystalline, the new class of amorphous alloys, sometimes are known as metallic glasses (MGs), exhibited remarkable properties, particularly high mechanical strength and elastic limit. The unique properties of MGs led to the wide range of studies in developing and characterizing of new alloys or composites which met the commercial desires. In spite of applicable properties of MGs, commercializing of metallic glasses was limited due to a major drawback, the lack of ductility and sudden brittle failure mode. Hence, crystalline-amorphous (C-A) composites were introduced almost in 2000s as a toughening strategy to improve the ductility of MGs. Despite the considerable progress reported in previous studies, there are still challenges in both synthesis and characterization of metallic C-A composites. In this study, accumulative roll bonding (ARB) was used to synthesize bulk crystalline-amorphous composites starting from crystalline Cu-Zr multilayers. Due to the severe plastic deformation state, new CuZr phases were formed during the rolling process which was reflected in SEM-EDS analysis. EDS elemental analysis showed the variation in the composition of CuZr phases such as 38-62, 50-50 to 68-32 at Cu-Zr % respectively. Moreover, TEM with electron diffraction analysis indicated the presence of both crystalline and amorphous structures for the new formed CuZr phases. In addition to the microstructural analysis, the mechanical properties of the synthesized composites were studied using the nanoindentation technique. Hysitron Nanoindentation instrument was used to conduct nanoindentation tests with cube corner tip. The maximum load of 5000 µN was applied in load control mode to measure the elastic modulus and hardness of different phases. The trend of results indicated three distinct regimes of hardness and elastic modulus including pure Cu, pure Zr, and new formed CuZr phases. More specifically, pure Cu regions showed the lowest values for both nanoindentation hardness and elastic modulus while the CuZr phases take the highest values. Consequently, pure Zr was placed in the intermediate range which is harder than pure Cu but softer than CuZr phases. In overall, it was found that CuZr phases with higher hardness were nucleated during ARB process as a result of mechanical alloying phenomenon.

Keywords: ARB, crystalline-amorphous composites, mechanical alloying, nanoindentation hardness

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Authors: Bright Chukwunwike Uzuegbunam, Wojciech Paslawski, Hans Agren, Christer Halldin, Wolfgang Weber, Markus Luster, Thomas Arzberger, Behrooz Hooshyar Yousefi

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There is a need to develop a PET tracer that will enable to diagnosis and track the progression of Alpha-synucleinopathies (Parkinson’s disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA]) in living subjects over time. Alpha-synuclein aggregates (a-syn), which are present in all the stages of disease progression, for instance, in PD, are a suitable target for in vivo PET imaging. For this reason, we have developed some promising a-syn tracers based on a disarylbisthiazole (DABTA) scaffold. The precursors are synthesized via a modified Hantzsch thiazole synthesis. The precursors were then radiolabeled via one- or two-step radiofluorination methods. The ligands were initially screened using a combination of molecular dynamics and quantum/molecular mechanics approaches in order to calculate the binding affinity to a-syn (in silico binding experiments). Experimental in vitro binding assays were also performed. The ligands were further screened in other experiments such as log D, in vitro plasma protein binding & plasma stability, biodistribution & brain metabolite analyses in healthy mice. Radiochemical yields were up to 30% - 72% in some cases. Molecular docking revealed possible binding sites in a-syn and also the free energy of binding to those sites (-28.9 - -66.9 kcal/mol), which correlated to the high binding affinity of the DABTAs to a-syn (Ki as low as 0.5 nM) and selectivity (> 100-fold) over Aβ and tau, which usually co-exist with a-synin some pathologies. The log D values range from 2.88 - 2.34, which correlated with free-protein fraction of 0.28% - 0.5%. Biodistribution experiments revealed that the tracers are taken up (5.6 %ID/g - 7.3 %ID/g) in the brain at 5 min (post-injection) p.i., and cleared out (values as low as 0.39 %ID/g were obtained at 120 min p.i. Analyses of the mice brain 20 min p.i. Revealed almost no radiometabolites in the brain in most cases. It can be concluded that in silico study presents a new venue for the rational development of radioligands with suitable features. The results obtained so far are promising and encourage us to further validate the DABTAs in autoradiography, immunohistochemistry, and in vivo imaging in non-human primates and humans.

Keywords: alpha-synuclein aggregates, alpha-synucleinopathies, PET imaging, tracer development

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Authors: Gulnaz Erkomaishvili

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The article analyzes the modern level of industrial production in Georgia, shows the export-import of industrial products and evaluates the results of the activities of institutions implementing industrial policy. The research showed us that the level of development of industry in the country and its export potential are quite low. The article concludes that in the modern phase of industrial development, the country should choose a model focused on technological development and maximum growth of export potential. Objectives. The aim of the research is to develop an economic policy that promotes the development of industry and to look for ways to implement it effectively. Methodologies This paper uses general and specific methods, in particular, analysis, synthesis, induction, deduction, scientific abstraction, comparative and statistical methods, as well as experts’ evaluation. In-depth interviews with experts were conducted to determine quantitative and qualitative indicators; Publications of the National Statistics Office of Georgia are used to determine the regularity between analytical and statistical estimations. Also, theoretical and applied research of international organizations and scientist-economists are used. Contributions Based on the identified challenges in the area of industry, recommendations for the implementation of an active industrial policy in short and long term periods were developed. In particular: the government's priority orientation of industrial development; paying special attention to the processing industry sectors that Georgia has the potential to produce; supporting the development of scientific fields; Determination of certain benefits for those investors who invest money in industrial production; State partnership with the private sector, manifested in the fight against bureaucracy, corruption and crime, creating favorable business conditions for entrepreneurs; Coordination between education - science - production should be implemented in the country. Much attention should be paid to basic scientific research, which does not require purely commercial returns in the short term, science should become a real productive force; Special importance should be given to the creation of an environment that will support the expansion of export-oriented production; Overcoming barriers to entry into export markets.

Keywords: industry, sectoral structure of industry, exsport-import of industrial products, industrial policy

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Authors: Neslihan Demirci, Serdar Durdağı

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Mycobacterium tuberculosis is still a worldwide disease-causing agent that, according to WHO, led to the death of 1.5 million people from tuberculosis (TB) in 2020. The bacteria reside in macrophages located specifically in the lung. There is a known quadruple drug therapy regimen for TB consisting of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Over the past 60 years, there have been great contributions to treatment options, such as recently approved delamanid (OPC67683) and bedaquiline (TMC207/R207910), targeting mycolic acid and ATP synthesis, respectively. Also, there are natural compounds that can block the tryptophanyl-tRNA synthetase (TrpRS) enzyme, chuangxinmycin, and indolmycin. Yet, already the drug resistance is reported for those agents. In this study, the newly released TrpRS enzyme structure is investigated for potential inhibitor drugs from already synthesized molecules to help the treatment of resistant cases and to propose an alternative drug for the quadruple drug therapy of tuberculosis. Maestro, Schrodinger is used for docking and molecular dynamic simulations. In-house library containing ~8000 compounds among FDA-approved indole-containing compounds, a total of 57 obtained from the ChemBL were used for both ATP and tryptophan binding pocket docking. Best of indole-containing 57 compounds were subjected to hit expansion and compared later with virtual screening workflow (VSW) results. After docking, VSW was done. Glide-XP docking algorithm was chosen. When compared, VSW alone performed better than the hit expansion module. Best scored compounds were kept for ten ns molecular dynamic simulations by Desmond. Further, 100 ns molecular dynamic simulation was performed for elected molecules according to Z-score. The top three MMGBSA-scored compounds were subjected to steered molecular dynamic (SMD) simulations by Gromacs. While SMD simulations are still being conducted, ponesimod (for multiple sclerosis), vilanterol (β₂ adrenoreceptor agonist), and silodosin (for benign prostatic hyperplasia) were found to have a significant affinity for tuberculosis TrpRS, which is the propulsive force for the urge to expand the research with in vitro studies. Interestingly, top-scored ponesimod has been reported to have a side effect that makes the patient prone to upper respiratory tract infections.

Keywords: drug repurposing, molecular dynamics, tryptophanyl-tRNA synthetase, tuberculosis

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Authors: Pattaka Sa-Ngimnet

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That the University as we have known it is no longer serving the needs of the vast majority of students and potential students has been a topic of much discussion. Institutions of higher education, in this age of global culture, are in a process of metamorphosis. Technology is being used to allow more students, older students, working students and disabled students, who cannot attend conventional classes, to have greater access to higher education through the internet. But change must come about only after much evaluation and experimentation or education will simply become a commodity as, in some cases, it already has. This paper will be concerned with the meaning and methods of change and evaluation as they are applied to institutions of higher education. Organization’s generally have different goals and different approaches in order to be successful. However, the means of reaching those goals requires rational and effective planning. Any plans for successful change in any institution must take into account both effectiveness and efficiency and the differences between them. “Effectiveness” refers to an adequate means of achieving an objective. “Efficiency” refers to the ability to achieve an objective without waste of time or resources (The Free Dictionary). So an effective means may not be efficient and an efficient means may not be effective. The goal is to reach a synthesis of effectiveness and efficiency that will maximize both to the extent each is limited by the other. This focus of this paper then is to determine how an educational institution can become either successful or oppressive depending on the kinds of planning, evaluating and changes that operate by and on the administration. If the plan is concerned only with efficiency, the institution can easily become oppressive and lose sight of its purpose of educating students. If it is overly concentrated on effectiveness, the students may receive a superior education in the short run but the institution will face operating difficulties. In becoming only goal oriented, institutions also face problems. Simply stated, if the institution reaches its goals, the stake holders may become satisfied and fail to change and keep up with the needs of the times. So goals should be seen only as benchmarks in a process of becoming even better in providing quality education. Constant and consistent evaluation is the key to making all these factors come together in a successful process of planning, testing and changing the plans as needed. The focus of the evaluation has to be considered. Evaluations must take into account progress and needs of students, methods and skills of instructors, resources available from the institution and the styles and objectives of administrators. Thus the role of evaluation is pivotal in providing for the maximum of both effective and efficient change in higher education institutions.

Keywords: change, effectiveness, efficiency, education

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Authors: Elsher Lawson-Boyd

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In the wake of the Human Genome Project, the life sciences have undergone some fascinating changes. In particular, conventional beliefs relating to gene expression are being challenged by advances in postgenomic sciences, especially by the field of epigenetics. Epigenetics is the modification of gene expression without changes in the DNA sequence. In other words, epigenetics dictates that gene expression, the process by which the instructions in DNA are converted into products like proteins, is not solely controlled by DNA itself. Unlike gene-centric theories of heredity that characterized much of the 20th Century (where the genes were considered as having almost god-like power to create life), gene expression in epigenetics insists on environmental ‘signals’ or ‘exposures’, a point that radically deviates from gene-centric thinking. Science and Technology Studies (STS) scholars have shown that epigenetic research is having vast implications for the ways in which chronic, non-communicable diseases are conceptualized, treated, and governed. However, to the author’s knowledge, there have not yet been any in-depth sociological engagements with neuroepigenetics that examine how the field is affecting mental health and trauma discourse. In this paper, the author discusses preliminary findings from a doctoral ethnographic study on neuroepigenetics, trauma, and embodiment. Specifically, this study investigates the kinds of causal relations neuroepigenetic researchers are making between experiences of trauma and the development of mental illnesses like complex post-traumatic stress disorder (PTSD), both throughout a human’s lifetime and across generations. Using qualitative interviews and nonparticipant observation, the author focuses on two public-facing research centers based in Melbourne: Florey Institute of Neuroscience and Mental Health (FNMH), and Murdoch Children’s Research Institute (MCRI). Preliminary findings indicate that a great deal of ambiguity characterizes this infant field, particularly when animal-model experiments are employed and the results are translated into human frameworks. Nevertheless, researchers at the FNMH and MCRI strongly suggest that adverse and traumatic life events have a significant effect on gene expression, especially when experienced during early development. Furthermore, they predict that neuroepigenetic research will have substantial implications for the ways in which mental illnesses like complex PTSD are diagnosed and treated. These preliminary findings shed light on why medical and health sociologists have good reason to be chiming in, engaging with and de-black-boxing ideations emerging from postgenomic sciences, as they may indeed have significant effects for vulnerable populations not only in Australia but other developing countries in the Global South.

Keywords: genetics, mental illness, neuroepigenetics, trauma

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Authors: Marine Kobalava

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The article analyzes the level of Georgia's tourism potential usage during the pandemic. The conclusion is drawnthat Georgia, as a tourism brand, is in a significant crisis at this stage, revenues from this sector have been substantially reduced, communication with potential customers is interrupted, no international marketing and PR communication strategies have been developed for the post-pandemic period. In order to rehabilitate the tourism industry of Georgia, it is considered vital to take measures using international marketing and PR communication strategies adjusted to the needs of the sectorthat will improve the use of tourism potential and stimulate the development of the sector. The goal of the research is to identify the factors hindering the use of tourism potential in the direction of international marketing and PR communication strategies in the post-pandemic period and to develop recommendations on ways to solve them. Research methods. The paper uses various theoretical and methodological tools of research, including Bibliographic research has been conducted on the main research issues; Analysis, synthesis, induction, and other methods are used to select and group data, identify similarities and differences, and identify trends; Endogenous and exogenous factors affecting the field of tourism have been studied by means of SWOT and PESTEL analyzes. A comparison model is used to analyze the strategy documents. Primary accounting materials are obtained from the National Statistics Office and the relevant ministries. Based on the results of the research, the directions of correct positioning of tourism products and marketing communication in the post-pandemic period have been developed. It is substantiated that a short-term international marketing strategy should include: probable goals of communication, maintaining a position on a potential traveler's “radar,” focusing communication on key motivating factors (gastronomy, winemaking, folklore, protected areas, mountainous regions). From a marketing point of view, it is important: holding international marketing events, compiling a list of target countries, formation of stimulus mechanisms, development of incentive programs for international tour operators, etc. The paper draws conclusions about the problems of using the tourism potential, recommendations on ways to solve this problems through international marketing and PR communication strategies are offered

Keywords: PR communication, international marketing strategy, tourism potential, post-pandemic period

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Authors: S. D. N. K. Bathige, G. I. Godahewa, Navaneethaiyer Umasuthan, Jehee Lee

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Kunitz-type serine protease inhibitors (KTIs) are identified in various organisms including animals, plants and microbes. These proteins shared single or multiple Kunitz inhibitory domains link together or associated with other types of domains. Characteristic Kunitz type domain composed of around 60 amino acid residues with six conserved cysteine residues to stabilize by three disulfide bridges. KTIs are involved in various physiological processes, such as ion channel blocking, blood coagulation, fibrinolysis and inflammation. In this study, two Kunitz-type domain containing protein was identified from rock bream database and designated as RbKunitz. The coding sequence of RbKunitz encoded for 507 amino acids with 56.2 kDa theoretical molecular mass and 5.7 isoelectric point (pI). There are several functional domains including MANEC superfamily domain, PKD superfamily domain, and LDLa domain were predicted in addition to the two characteristic Kunitz domain. Moreover, trypsin interaction sites were also identified in Kunitz domain. Homology analysis revealed that RbKunitz shared highest identity (77.6%) with Takifugu rubripes. Completely conserved 28 cysteine residues were recognized, when comparison of RbKunitz with other orthologs from different taxonomical groups. These structural evidences indicate the rigidity of RbKunitz folding structure to achieve the proper function. The phylogenetic tree was constructed using neighbor-joining method and exhibited that the KTIs from fish and non-fish has been evolved in separately. Rock bream was clustered with Takifugu rubripes. The SYBR Green qPCR was performed to quantify the RbKunitz transcripts in different tissues and challenged tissues. The mRNA transcripts of RbKunitz were detected in all tissues (muscle, spleen, head kidney, blood, heart, skin, liver, intestine, kidney and gills) analyzed and highest transcripts level was detected in gill tissues. Temporal transcription profile of RbKunitz in rock bream blood tissues was analyzed upon LPS (lipopolysaccharide), Poly I:C (Polyinosinic:polycytidylic acid) and Edwardsiella tarda challenge to understand the immune responses of this gene. Compare to the unchallenged control RbKunitz exhibited strong up-regulation at 24 h post injection (p.i.) after LPS and E. tarda injection. Comparatively robust expression of RbKunits was observed at 3 h p.i. upon Poly I:C challenge. Taken together all these data indicate that RbKunitz may involve into to immune responses upon pathogenic stress, in order to protect the rock bream.

Keywords: Kunitz-type, rock bream, immune response, serine protease inhibitor

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Authors: Dugeree Otgongerel, Kyong Jin Cho, Yu-Han Kim, Sangmee Ahn Jo

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Excessive activation of glutamate receptor is thought to be involved in retinal ganglion cell (RGC) death after ischemia- reperfusion damage. Glutamate carboxypeptidase II (GCPII) is an enzyme responsible for the synthesis of glutamate. Several studies showed that inhibition of GCPII prevents or reduces cellular damage in brain diseases. Thus, in this study, we examined the expression of GCPII in rat retina and the role of GCPII in acute high IOP ischemia-reperfusion damage of eye by using a GCPII inhibitor, 2-(phosphonomethyl) pentanedioic acid (2-PMPA). Animal model of ischemia-reperfusion was induced by raising the intraocular pressure for 60 min and followed by reperfusion for 3 days. Rats were randomly divided into four groups: either intra-vitreous injection of 2-PMPA (11 or 110 ng per eye) or PBS after ischemia-reperfusion, 2-PMPA treatment without ischemia-reperfusion and sham-operated normal control. GCPII immunoreactivity in normal rat retina was detected weakly in retinal nerve fiber layer (RNFL) and retinal ganglionic cell layer (RGL) and also inner plexiform layer (IPL) and outer plexiform layer (OPL) strongly where are co-stained with an anti-GFAP antibody, suggesting that GCPII is expressed mostly in Muller and astrocytes. Immunostaining with anti-BRN antibody showed that ischemia- reperfusion caused RGC death (31.5 %) and decreased retinal thickness in all layers of damaged retina, but the treatment of 2-PMPA twice at 0 and 48 hour after reperfusion blocked these retinal damages. GCPII level in RNFL layer was enhanced after ischemia-reperfusion but was blocked by PMPA treatment. This result was confirmed by western blot analysis showing that the level of GCPII protein after ischemia- reperfusion increased by 2.2- fold compared to control, but this increase was blocked almost completely by 110 ng PMPA treatment. Interestingly, GFAP immunoreactivity in the retina after ischemia- reperfusion followed by treatment with PMPA showed similar pattern to GCPII, increase after ischemia-reperfusion but reduction to the normal level by PMPA treatment. Our data demonstrate that increase of GCPII protein level after ischemia-reperfusion injury is likely to cause glial activation and/or retinal cell death which are mediated by glutamate, and GCPII inhibitors may be useful in treatment of retinal disorders in which glutamate excitotoxicity is pathogenic.

Keywords: glutamate carboxypepptidase II, glutamate excitotoxicity, ischemia-reperfusion, retinal ganglion cell

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Authors: Walter Vera-Ortega, Idoia Busnadiego, Sam J. Wilson

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Introduction: Human Immunodeficiency Virus type 1 (HIV-1) is responsible for the acquired immunodeficiency syndrome (AIDS), a leading cause of death worldwide infecting millions of people each year. Despite intensive research in vaccine development, therapies against HIV-1 infection are not curative, and the huge genetic variability of HIV-1 challenges to drug development. Current animal models for HIV-1 research present important limitations, impairing the progress of in vivo approaches. Macaques require a CD8+ depletion to progress to AIDS, and the maintenance cost is high. Mice are a cheaper alternative but need to be 'humanized,' and breeding is not possible. The development of an HIV-1 clone able to replicate in mice is a challenging proposal. The lack of human co-factors in mice impedes the function of the HIV-1 accessory proteins, Tat and Rev, hampering HIV-1 replication. However, Tat and Rev function can be replaced by constitutive/chimeric promoters, codon-optimized proteins and the constitutive transport element (CTE), generating a novel HIV-1 clone able to replicate in mice without disrupting the amino acid sequence of the virus. By minimally manipulating the genomic 'identity' of the virus, we propose the generation of an HIV-1 clone able to replicate in mice to assist in antiviral drug development. Methods: i) Plasmid construction: The chimeric promoters and CTE copies were cloned by PCR using lentiviral vectors as templates (pCGSW and pSIV-MPCG). Tat mutants were generated from replication competent HIV-1 plasmids (NHG and NL4-3). ii) Infectivity assays: Retroviral vectors were generated by transfection of human 293T cells and murine NIH 3T3 cells. Virus titre was determined by flow cytometry measuring GFP expression. Human B-cells (AA-2) and Hela cells (TZMbl) were used for infectivity assays. iii) Protein analysis: Tat protein expression was determined by TZMbl assay and HIV-1 capsid by western blot. Results: We have determined that NIH 3T3 cells are able to generate HIV-1 particles. However, they are not infectious, and further analysis needs to be performed. Codon-optimized HIV-1 constructs are efficiently made in 293T cells in a Tat and Rev independent manner and capable of packaging a competent genome in trans. CSGW is capable of generating infectious particles in the absence of Tat and Rev in human cells when 4 copies of the CTE are placed preceding the 3’LTR. HIV-1 Tat mutant clones encoding different promoters are functional during the first cycle of replication when Tat is added in trans. Conclusion: Our findings suggest that the development of an HIV-1 Tat-Rev independent clone is challenging but achievable aim. However, further investigations need to be developed prior presenting our HIV-1 clone as a candidate model for research.

Keywords: codon-optimized, constitutive transport element, HIV-1, long terminal repeats, research model

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Authors: Anastasios Georgoulas, Manolia Andredaki, Marco Marengo

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The present paper investigates the hydrodynamics and heat transfer characteristics of slug-plug flows under saturated flow boiling conditions within circular micro-channels. Numerical simulations are carried out, using an enhanced version of the open-source CFD-based solver ‘interFoam’ of OpenFOAM CFD Toolbox. The proposed user-defined solver is based in the Volume Of Fluid (VOF) method for interface advection, and the mentioned enhancements include the implementation of a smoothing process for spurious current reduction, the coupling with heat transfer and phase change as well as the incorporation of conjugate heat transfer to account for transient solid conduction. In all of the considered cases in the present paper, a single phase simulation is initially conducted until a quasi-steady state is reached with respect to the hydrodynamic and thermal boundary layer development. Then, a predefined and constant frequency of successive vapour bubbles is patched upstream at a certain distance from the channel inlet. The proposed numerical simulation set-up can capture the main hydrodynamic and heat transfer characteristics of slug-plug flow regimes within circular micro-channels. In more detail, the present investigation is focused on exploring the interaction between subsequent vapour slugs with respect to their generation frequency, the hydrodynamic characteristics of the liquid film between the generated vapour slugs and the channel wall as well as of the liquid plug between two subsequent vapour slugs. The proposed investigation is carried out for the 3 different working fluids and three different values of applied heat flux in the heated part of the considered microchannel. The post-processing and analysis of the results indicate that the dynamics of the evolving bubbles in each case are influenced by both the upstream and downstream bubbles in the generated sequence. In each case a slip velocity between the vapour bubbles and the liquid slugs is evident. In most cases interfacial waves appear close to the bubble tail that significantly reduce the liquid film thickness. Finally, in accordance with previous investigations vortices that are identified in the liquid slugs between two subsequent vapour bubbles can significantly enhance the convection heat transfer between the liquid regions and the heated channel walls. The overall results of the present investigation can be used to enhance the present understanding by providing better insight of the complex, underpinned heat transfer mechanisms in saturated boiling within micro-channels in the slug-plug flow regime.

Keywords: slug-plug flow regime, micro-channels, VOF method, OpenFOAM

Procedia PDF Downloads 246

Authors: Atitallah Sofien, Bouyahia Olfa, Attar Souleima, Missaoui Nada, Ben Rabeh Rania, Yahyaoui Salem, Mazigh Sonia, Boukthir Samir

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Introduction: Ciliopathies are a spectrum of diseases that have in common a defect in the synthesis of ciliary proteins. It is a rare cause of neonatal cholestasis. Clinical presentation varies extremely, and the main affected organs are the kidneys, liver, and pancreas. Methodology: This is a descriptive case report of a newborn who was admitted for exploration of neonatal cholestasis in the Paediatric Department C at the Children’s Hospital of Tunis, where the investigations concluded with a rare genetic mutation. Results: This is the case of a newborn male with no family history of hepatic and renal diseases, born to consanguineous parents, and from a well-monitored uneventful pregnancy. He developed jaundice on the second day of life, for which he received conventional phototherapy in the neonatal intensive care unit. He was admitted at 15 days for mild bronchiolitis. On clinical examination, intense jaundice was noted with normal stool and urine colour. Initial blood work showed an elevation in conjugated bilirubin and a high gamma-glutamyl transferase level. Transaminases and prothrombin time were normal. Abdominal sonography revealed hepatomegaly, splenomegaly, and undifferentiated renal cortex with bilateral medullar micro-cysts. Kidney function tests were normal. The infant received ursodeoxycholic acid and vitamin therapy. Genetic testing showed a homozygous mutation in the DCDC2 gene that hadn’t been documented before confirming the diagnosis of renal-hepatic ciliopathy. The patient has regular follow-ups, and his conjugated bilirubin and gamma-glutamyl transferase levels have been decreasing. Conclusion: Genetic testing has revolutionized the approach to etiological diagnosis in pediatric cholestasis. It enables personalised treatment strategies to better enhance the quality of life of patients and prevent potential complications following adequate long-term monitoring.

Keywords: cholestasis, newborn, ciliopathy, DCDC2, genetic

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Authors: Nouha Bouayed Abdelmoula, Rim Louati, Nawel Abdellaoui, Balkiss Abdelmoula, Oldez Kaabi, Walid Smaoui, Samir Aloulou

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Background and Aims: Cardiofaciocutaneous syndrome (CFC) is an autosomal dominant disorder with the vast majority of cases arising by a new mutation of BRAF, MEK1, MEK2, or rarely, KRAS genes. Here, we report a rare Tunisian case of CFC syndrome for whom we identify SOS1 mutation. Methods: Genomic DNA was obtained from peripheral blood collected in an EDTA tube and extracted from leukocytes using the phenol/chloroform method according to standard protocols. High resolution melting (HRM) analysis for screening of mutations in the entire coding sequence of PTPN11 was conducted first. Then, HRM assays to look for hot spot mutations coding regions of the other genes of the RAS-MAPK pathway (RAt Sarcoma viral oncogene homolog Mitogen-Activated Protein Kinases Pathway): SOS1, SHOC2, KRAS, RAF1, KRAS, NRAS, CBL, BRAF, MEK1, MEK2, HRAS, and RIT1, were applied. Results: Heterozygous SOS1 point mutation clustered in exon 10, which encodes for the PH domain of SOS1, was identified: c.1655 G > A. The patient was a 9-year-old female born from a consanguineous couple. She exhibited pulmonic valvular stenosis as congenital heart disease. She had facial features and other malformations of Noonan syndrome, including macrocephaly, hypertelorism, ptosis, downslanting palpebral fissures, sparse eyebrows, a short and broad nose with upturned tip, low-set ears, high forehead commonly associated with bitemporal narrowing and prominent supraorbital ridges, short and/or webbed neck and short stature. However, the phenotype is also suggestive of CFC syndrome with the presence of more severe ectodermal abnormalities, including curly hair, keloid scars, hyperkeratotic skin, deep plantar creases, and delayed permanent dentition with agenesis of the right maxillary first molar. Moreover, the familial history of the patient revealed recurrent brain malignancies in the paternal family and epileptic disease in the maternal family. Conclusions: This case report of an overlapping RASopathy associated with SOS1 mutation and familial history of brain tumorigenesis is exceptional. The evidence suggests that RASopathies are truly cancer-prone syndromes, but the magnitude of the cancer risk and the types of cancer partially overlap.

Keywords: cardiofaciocutaneous syndrome, CFC, SOS1, brain cancer, germline mutation

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Authors: Gabriela D. Silva, Rodrigo L. O. R. Cunha, Mauricio D. Coutinho-Neto

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In the last four decades the biological activities of selenium compounds has received great attention, particularly for hypervalent derivates from selenium (IV) used as enzyme inhibitors. The unregulated activity of cysteine proteases are related to the development of several pathologies, such as neurological disorders, cardiovascular diseases, obesity, rheumatoid arthritis, cancer and parasitic infections. These enzymes are therefore a valuable target for designing new small molecule inhibitors such as selenuranes. Even tough there has been advances in the synthesis and design of new selenuranes based inhibitors, little is known about their mechanism of action. It is a given that inhibition occurs through the reaction between the thiol group of the enzyme and the chalcogen atom. However, several open questions remain about the nature of the mechanism (associative vs. dissociative) and about the nature of the reactive species in solution under physiological conditions. In this work we performed a theoretical investigation on model systems to study the possible routes of substitution reactions. Nucleophiles may be present in biological systems, our interest is centered in the thiol groups from the cysteine proteases and the hydroxyls from the aqueous environment. We therefore expect this study to clarify the possibility of a route reaction in two stages, the first consisting of the substitution of chloro atoms by hydroxyl groups and then replacing these hydroxyl groups per thiol groups in selenuranes. The structures of selenuranes and nucleophiles were optimized using density function theory along the B3LYP functional and a 6-311+G(d) basis set. Solvent was treated using the IEFPCM method as implemented in the Gaussian 09 code. Our results indicate that hydrolysis from water react preferably with selenuranes, and then, they are replaced by the thiol group. It show the energy values of -106,0730423 kcal/mol for dople substituition by hydroxyl group and 96,63078511 kcal/mol for thiol group. The solvatation and pH reduction promotes this route, increasing the energy value for reaction with hydroxil group to -50,75637672 kcal/mol and decreasing the energy value for thiol to 7,917767189 kcal/mol. Alternative ways were analyzed for monosubstitution (considering the competition between Cl, OH and SH groups) and they suggest the same route. Similar results were obtained for aliphatic and aromatic selenuranes studied.

Keywords: chalcogenes, computational study, cysteine proteases, enzyme inhibitors

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Authors: Thomas Suarez, Anne-Sophie Grenouilleau, Erwan Autin, Alexandre Biosse-Duplan, Emmanuelle Blondet, Laurence Chazalette, Marie Coniel, Agnes Dessaigne, Sylvie Lascols, Andrea Lasserre, Candice Legris, Pierre Liot, Aline Metais, Karine Petitprez, Christophe Varlet, Christian Saout

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Background: The role of biological sex and gender identity -whether assigned or chosen- as health determinants are far from a recent discovery: several reports have stressed out how being a woman or a man could affect health on various scales. However, taking it into consideration beyond stereotypes and rigid binary assumptions still seems to be a work in progress. Method: The report is a synthesis on a variety of specific topics, each of which was studied by a specialist from the French National Authority for Health (HAS), through an analysis of existing literature on both healthcare policy construction process and instruments (norms, data analysis, clinical trials, guidelines, and professional practices). This work also implied a policy analysis of French recent public health laws and a retrospective study of guidelines with a gender mainstreaming approach. Results: The analysis showed that though sex and gender were well-known determinants of health, their consideration by both public policy and health operators was often incomplete, as it does not incorporate how sex and gender interact, as well as how they interact with other factors. As a result, the health and social care systems and their professionals tend to reproduce some stereotypical and inadequate habits. Though the data available often allows to take sex and gender into consideration, such data is often underused in practice guidelines and policy formulation. Another consequence is a lack of inclusiveness towards transgender or intersex persons. Conclusions: This report first urges for raising awareness of all the actors of health, in its broadest definition, that sex and gender matter beyond first-look conclusions. It makes a series of recommendations in order to reshape policy construction in the health sector on the one hand and to design public health instruments to make them more inclusive regarding sex and gender on the other hand. The HAS finally committed to integrate sex and gender preoccupations in its workings methods, to be a driving force in the spread of these concerns.

Keywords: biological sex, determinants of health, gender, healthcare policy instruments, social accompaniment

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Authors: Mrinal Gupta, Mohammad Rumman, Babita Singh Abbas Ali Mahdi, Shivani Pandey

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Introduction: Berberine (BBR), a bioactive compound isolated from Coptidis Rhizoma, possesses diverse pharmacological activities, including anti-bacterial, anti-inflammatory, antitumor, hypolipidemic, and anti-diabetic. However, its role as an anti-diabetic agent in animal models of dexamethasone (Dex)-induced diabetes remains unknown. Studies have shown that natural compounds, including aloe, caper, cinnamon, cocoa, green and black tea, and turmeric, can be used for treating Type 2 diabetes mellitus (DM). Compared to conventional drugs, natural compounds have fewer side effects and are easily available. Herein, we studied the anti-diabetic effects of BBR in a mice model of Dex-induced diabetes. Methods: HepG2 cell line was used for glucose release and glycogen synthesis studies. Cell proliferation was measured by methylthiotetrazole (MTT) assay. For animal studies, mice were treated with Dex (2 mg/kg, i.m.) for 30 days and the effect of BBR at the doses 100, 200, and 500 mg/kg (p.o.) was analyzed. Glucose, insulin, and pyruvate tests were performed to evaluate the development of the diabetic model. An echo MRI was performed to assess the fat mass. Further, to elucidate the mechanism of action of BBR, mRNA expression of genes regulating gluconeogenesis, glucose uptake, and glycolysis were analyzed. Results: In vitro BBR had no impact on cell viability up to a concentration of 50μM. Moreover, BBR suppressed the hepatic glucose release and improved glucose tolerance in HepG2 cells. In vivo, BBR improved glucose homeostasis in diabetic mice, as evidenced by enhanced glucose clearance, increased glycolysis, elevated glucose uptake, and decreased gluconeogenesis. Further, Dex treatment increased the total fat mass in mice, which was ameliorated by BBR treatment. Conclusion: BBR improves glucose tolerance by increasing glucose clearance, inhibiting hepatic glucose release, and decreasing obesity. Thus, BBR may become a potential therapeutic agent for treating glucocorticoid-induced diabetes and obesity in the future.

Keywords: glucocorticoid, hyperglycemia, berberine, HepG2 cells, insulin resistance, glucose

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Authors: Ersumo Tessema, Bogale Girmaye Tamrat, Mohammed Burka

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Background: Hyperthyroidism is a common thyroid disorder especially in women and characterized by increased thyroid hormone synthesis and secretion. The disorder manifests predominantly as Graves’ disease in iodine-sufficient areas and has increasing prevalence in iodine-deficient countries in patients with nodular thyroid disease and following iodine fortification. In Ethiopia, the magnitude of the disorder is unknown and, in Africa, due to scarcity of resources, its management remains suboptimal. Objective: The aim of this study was to analyze the pattern and management of patients with hyperthyroidism at the United Vision Medical Services Center, Addis Ababa between August 30, 2013, and February 1, 2018. Patients and methods: The study was a retrospective analysis of medical records of all patients with hyperthyroidism at the United Vision Private Medical Services Center, Addis Ababa. A questionnaire was filled out; the collected data entered into a computer and statistically analyzed using the SPSS package. The results were tabulated and discussed with literature review. Results: A total of 589 patients were included in this study. The median age was 40 years, and the male to female ratio was 1.0:7.9. Most patients (93%) presented with goiter and the associated features of toxic goiter except weight loss, sweating and tachycardia were uncommon. Majority of patients presented more than two years after the onset of their presenting symptoms. The most common physical finding (91%), as well as diagnosis, was toxic nodular goiter. The most frequent (83%) derangement in the thyroid function tests was a low thyroid-stimulating hormone, and the most commonly (94%) used antithyroid drug was a propylthiouracil. The most common (96%) surgical procedure in 213 patients was a near-total thyroidectomy with a postoperative course without incident in 92% of all the patients. Conclusion: The incidence and prevalence of hyperthyroidism are apparently on the increase in Addis Ababa, which may be related to the existing severe iodine-deficiency and or the salt iodation program (iodine-induced hyperthyroidism). Hyperthyroidism predominantly affects women and, in surgical services, toxic nodular goiter is more common than diffuse goiter, and the treatment of choice in experienced hands is a near-total thyroidectomy.

Keywords: Ethiopia, grave’s disease, hyperthyroidism, toxic nodular goiter

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Authors: Micael Sousa

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Board games (BGs) are thriving as new designs emerge from the hobby community to greater audiences all around the world. Although digital games are gathering most of the attention in game studies and serious games research fields, the post-digital movement helps to explain why in the world dominated by digital technologies, the analog experiences are still unique and irreplaceable to users, allowing innovation in new hybrid environments. The BG’s new designs are part of these post-digital and hybrid movements because they result from the use of powerful digital tools that enable the production and knowledge sharing about the BGs and their face-to-face unique social experiences. These new BGs, defined as modern by many authors, are providing innovative designs and unique game mechanics that are still not yet fully explored by the main serious games (SG) approaches. Even the most established frameworks settled to address SG, as fun games implemented to achieve predefined goals need more development, especially when considering modern BGs. Despite the many anecdotic perceptions, researchers are only now starting to rediscover BGs and demonstrating their potentials. They are proving that BGs are easy to adapt and to grasp by non-expert players in experimental approaches, with the possibility of easy-going adaptation to players’ profiles and serious objectives even during gameplay. Although there are many design thinking (DT) models and practices, their relations with SG frameworks are also underdeveloped, mostly because this is a new research field, lacking theoretical development and the systematization of the experimental practices. Using BG as case studies promise to help develop these frameworks. Departing from the Design, Experience, and Play (DPE) framework and considering the Common Design Think Tools (CDST), this paper proposes a new experimental framework for the adaptation and development of modern BG design for DT: the Design, Experience, and Play for Think (DPET) experimental framework. This is done through the systematization of the DPE and CDST approaches applied in two case studies, where two different sequences of adapted BG were employed to establish a DT collaborative process. These two sessions occurred with different participants and in different contexts, also using different sequences of games for the same DT approach. The first session took place at the Faculty of Economics at the University of Coimbra in a training session of serious games for project development. The second session took place in the Casa do Impacto through The Great Village Design Jam light. Both sessions had the same duration and were designed to progressively achieve DT goals, using BGs as SGs in a collaborative process. The results from the sessions show that a sequence of BGs, when properly adapted to address the DPET framework, can generate a viable and innovative process of collaborative DT that is productive, fun, and engaging. The DPET proposed framework intents to help establish how new SG solutions could be defined for new goals through flexible DT. Applications in other areas of research and development can also benefit from these findings.

Keywords: board games, design thinking, methodology, serious games

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Authors: Sofia Papadimitriou

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INTRODUCTION: The differential diagnosis between acute viral and bacterial infections is an important cost-effectiveness parameter at the stage of the treatment process in order to achieve the maximum benefits in therapeutic intervention by combining the minimum cost to ensure the proper use of antibiotics.The discovery of sensitive and robust molecular diagnostic tests in response to the role of the host in infections has enhanced the accurate diagnosis and differentiation of infections. METHOD: The study used a sample of six independent blood samples (total=756) which are associated with human proteins-proteins, each of which at the transcription stage expresses a different response in the host network between viral and bacterial infections.Τhe individual blood samples are subjected to a sequence of computer filters that identify a gene panel corresponding to an autonomous diagnostic score. The data set and the correspondence of the gene panel to the diagnostic patents a new Bangalore -Viral Bacterial (BL-VB). FINDING: We use a biomarker based on the blood of 10 genes(Panel-VB) that are an important prognostic value for the detection of viruses from bacterial infections with a weighted average AUROC of 0.97(95% CL:0.96-0.99) in eleven independent samples (sets n=898). We discovered a base with a patient score (VB 10 ) according to the table, which is a significant diagnostic value with a weighted average of AUROC 0.94(95% CL: 0.91-0.98) in 2996 patient samples from 56 public sets of data from 19 different countries. We also studied VB 10 in a new cohort of South India (BL-VB,n=56) and found 97% accuracy in confirmed cases of viral and bacterial infections. We found that VB 10 (a)accurately identifies the type of infection even in unspecified cases negative to the culture (b) shows its clinical condition recovery and (c) applies to all age groups, covering a wide range of acute bacterial and viral infectious, including non-specific pathogens. We applied our VB 10 rating to publicly available COVID 19 data and found that our rating diagnosed viral infection in patient samples. RESULTS: Τhe results of the study showed the diagnostic power of the biomarker VB 10 as a diagnostic test for the accurate diagnosis of acute infections in recovery conditions. We look forward to helping you make clinical decisions about prescribing antibiotics and integrating them into your policies management of antibiotic stewardship efforts. CONCLUSIONS: Overall, we are developing a new property of the RNA-based biomarker and a new blood test to differentiate between viral and bacterial infections to assist a physician in designing the optimal treatment regimen to contribute to the proper use of antibiotics and reduce the burden on antimicrobial resistance, AMR.

Keywords: acute infections, antimicrobial resistance, biomarker, blood transcriptome, systems biology, classifier diagnostic score

Procedia PDF Downloads 135

Authors: Moin Uddin, M. Masroor A. Khan, Faisal Rasheed, Tariq Ahmad Dar, Akbar Ali, Lalit Varshney

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Oligomers, obtained by exposing the natural polysaccharides (alginate, carrageenan, chitosan, etc.) to cobalt-60 generated gamma radiation may prove as potent plant growth promoters when applied as foliar sprays to the plants. They function as endogenous growth elicitors, triggering the synthesis of different enzymes and modulating various plant responses by exploiting the gene expression. Exogenous application of Jasmonic acid or of its methyl ester, methyl jasmonate (MeJ) has been reported to increase the secondary metabolites production in medicinal and aromatic plants. Keeping this in mind, three pot experiments were conducted to test whether the foliar application of irradiated-chitosan (IC) and MeJ, applied alone or in combination, could augment the active constituents as well as growth, physiological and yield attributes of Catharanthus roseus, which carries anticancer alkaloids, viz. vincristine and vinblastine, in its leaves in addition to various other useful alkaloids. Totally, 5 spray treatments, comprising various aqueous solutions of IC [20, 40, 80 and 160 mg L-1 (Experiment 1)], MeJ (10, 20, 30 and 40 mg L-1 (Experiment 2)] and those of IC+MeJ [40+20, 40+30, 80+20, 80+30, 160+20 and 160+30 mg L-1 (Experiment 3)], were applied at seven days interval. Total leaf-alkaloids content as well as growth, physiological and yield parameters, evaluated at 120 days after sowing, were significantly enhanced by IC application. IC application could not increase the leaf-content of vincristine and vinblastine; nonetheless, it significantly augmented the yield of these alkaloids owing to enhancing the dry mass of leaves per plant. MeJ application, particularly at 30 mg L-1, increased both content (17%) and yield (48%) of total leaf-alkaloids as well as the content and yield of vincristine ( 29 and 63%, respectively) and vinblastine (14 and 44%, respectively) alkaloids, though it significantly decreased most other parameters studied, particularly at higher concentrations (30 and 40 mg L-1 of MeJ). As compared to the control (water-spray treatment), collective application of IC (80 mg L-1) and MeJ (20 mg L-1) resulted in the highest values of most of the parameters studied. However, 80 mg L-1 of IC applied with 30 mg L-1 of MeJ gave the best results for the content and yield of total as well as anticancer leaf-alkaloids (vincristine and vinblastine). Comparing the control, it increased the content and yield of total leaf-alkaloids (37 and 118%, respectively) and those of vincristine (65 and 163%, respectively) and vinblastine (31 and 107%, respectively). Conclusively, the applied technique significantly enhanced the production of total as well as anticancer alkaloids of Catharanthus roseus.

Keywords: anticancer alkaloids (vincristine and vinblastine), catharanthus roseus, irradiated chitosan, methyl jasmonate

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Authors: Michela Terlizzi, Chiara Colarusso, Aldo Pinto, Rosalinda Sorrentino

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Sphingosine-1-phosphate (S1P) is a membrane-derived bioactive phospholipid exerting a multitude of effects on respiratory cell physiology and pathology through five S1P receptors (S1PR1-5). Higher levels of S1P have been registered in a broad range of respiratory diseases, including inflammatory disorders and cancer, although its exact role is still elusive. Based on our previous study in which we found that S1P/S1PR3 is involved in an inflammatory pattern via the activation of Toll-like Receptor 9 (TLR9), highly expressed on lung cancer cells, the main goal of the current study was to better understand the involvement of S1P/S1PR3 pathway/signaling during lung carcinogenesis, taking advantage of a mouse model of first-hand smoke exposure and of carcinogen-induced lung cancer. We used human samples of Non-Small Cell Lung Cancer (NSCLC), a mouse model of first-hand smoking, and of Benzo(a)pyrene (BaP)-induced tumor-bearing mice and A549 lung adenocarcinoma cells. We found that the intranuclear, but not the membrane, localization of S1PR3 was associated to the proliferation of lung adenocarcinoma cells, the mechanism that was correlated to human and mouse samples of smoke-exposure and carcinogen-induced lung cancer, which were characterized by higher utilization of S1P. Indeed, the inhibition of the membrane S1PR3 did not alter tumor cell proliferation after TLR9 activation. Instead, according to the nuclear localization of sphingosine kinase (SPHK) II, the enzyme responsible for the catalysis of the S1P last step synthesis, the inhibition of the kinase completely blocked the endogenous S1P-induced tumor cell proliferation. These results prove that the endogenous TLR9-induced S1P can on one side favor pro-inflammatory mechanisms in the tumor microenvironment via the activation of cell surface receptors, but on the other tumor progression via the nuclear S1PR3/SPHK II axis, highlighting a novel molecular mechanism that identifies S1P as one of the crucial mediators for lung carcinogenesis-associated inflammatory processes and that could provide differential therapeutic approaches especially in non-responsive lung cancer patients.

Keywords: sphingosine-1-phosphate (S1P), S1P Receptor 3 (S1PR3), smoking-mice, lung inflammation, lung cancer

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Authors: Alessandra Pardu, Elena Curti, Marco Caredda, Alessio Dedola, Margherita Addis, Massimo Pes, Antonio Pirisi, Tonina Roggio, Sergio Uzzau, Roberto Anedda

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Some of the artisanal cheeses products of European Countries certificated as PDO (Protected Designation of Origin) are made from raw milk. To recognise potential frauds (e.g. pasteurisation or thermisation of milk aimed at raw milk cheese production), the alkaline phosphatase (ALP) assay is currently applied only for pasteurisation, although it is known to have notable limitations for the validation of ALP enzymatic state in nonbovine milk. It is known that frauds considerably impact on customers and certificating institutions, sometimes resulting in a damage of the product image and potential economic losses for cheesemaking producers. Robust, validated, and univocal analytical methods are therefore needed to allow Food Control and Security Organisms, to recognise a potential fraud. In an attempt to develop a new reliable method to overcome this issue, Time-Domain Nuclear Magnetic Resonance (TD-NMR) spectroscopy has been applied in the described work. Daily fresh milk was analysed raw (680.00 µL in each 10-mm NMR glass tube) at least in triplicate. Thermally treated samples were also produced, by putting each NMR tube of fresh raw milk in water pre-heated at temperatures from 68°C up to 72°C and for up to 3 min, with continuous agitation, and quench-cooled to 25°C in a water and ice solution. Raw and thermally treated samples were analysed in terms of 1H T2 transverse relaxation times with a CPMG sequence (Recycle Delay: 6 s, interpulse spacing: 0.05 ms, 8000 data points) and quasi-continuous distributions of T2 relaxation times were obtained by CONTIN analysis. In line with previous data collected by high field NMR techniques, a decrease in the spin-spin relaxation constant T2 of the predominant 1H population was detected in heat-treated milk as compared to raw milk. The decrease of T2 parameter is consistent with changes in chemical exchange and diffusive phenomena, likely associated to changes in milk protein (i.e. whey proteins and casein) arrangement promoted by heat treatment. Furthermore, experimental data suggest that molecular alterations are strictly dependent on the specific heat treatment conditions (temperature/time). Such molecular variations in milk, which are likely transferred to cheese during cheesemaking, highlight the possibility to extend the TD-NMR technique directly on cheese to develop a method for assessing a fraud related to the use of a milk thermal treatment in PDO raw milk cheese. Results suggest that TDNMR assays might pave a new way to the detailed characterisation of heat treatments of milk.

Keywords: cheese fraud, milk, pasteurisation, TD-NMR

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Authors: Amlan Kumar Das, Avinash Marwal, Vikram Pareek

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Liposome plays an important role in medical and pharmaceutical science as e.g. nano scale drug carriers. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment. Magnet-driven liposome used for the targeted delivery of drugs to organs and tissues1. These liposome preparations contain encapsulated drug components and finely dispersed magnetic particles. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment that are generated in vitro. These are useful in terms of biocompatibility, biodegradability, and low toxicity, and can control biodistribution by changing the size, lipid composition, and physical characteristics2. Furthermore, liposomes can entrap both hydrophobic and hydrophilic drugs and are able to continuously release the entrapped substrate, thus being useful drug carriers. Magnetic liposomes (MLs) are phospholipid vesicles that encapsulate magneticor paramagnetic nanoparticles. They are applied as contrast agents for magnetic resonance imaging (MRI)3. The biological synthesis of nanoparticles using plant extracts plays an important role in the field of nanotechnology4. Green-synthesized magnetite nanoparticles-protein hybrid has been produced by treating Iron (III)/Iron(II) chloride with the leaf extract of Dhatura Inoxia. The phytochemicals present in the leaf extracts act as a reducing as well stabilizing agents preventing agglomeration, which include flavonoids, phenolic compounds, cardiac glycosides, proteins and sugars. The magnetite nanoparticles-protein hybrid has been trapped inside the aqueous core of the liposome prepared by reversed phase evaporation (REV) method using oleic and linoleic acid which has been shown to be driven under magnetic field confirming the formation magnetic liposome (ML). Chemical characterization of stealth magnetic liposome has been performed by breaking the liposome and release of magnetic nanoparticles. The presence iron has been confirmed by colour complex formation with KSCN and UV-Vis study using spectrophotometer Cary 60, Agilent. This magnet driven liposome using nanoparticles-protein hybrid can be a smart vesicles for the targeted drug delivery.

Keywords: nanoparticles-protein hybrid, magnetic liposome, medical, pharmaceutical science

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Authors: Mohammad Hassan Ramezan zadeh 1 , Majid Seifi 2 , Hoda Hekmat ara 2 1Biomedical Engineering Department, Near East University, Nicosia, Cyprus 2Physics Department, Guilan University , P.O. Box 41335-1914, Rasht, Iran.

Abstract:

Magnetic nano particles of ferric chloride were synthesised using a co-precipitation technique. For the optimal results, ferric chloride at room temperature was added to different surfactant with different ratio of metal ions/surfactant. The samples were characterised using transmission electron microscopy, X-ray diffraction and Fourier transform infrared spectrum to show the presence of nanoparticles, structure and morphology. Magnetic measurements were also carried out on samples using a Vibrating Sample Magnetometer. To show the effect of surfactant on size distribution and crystalline structure of produced nanoparticles, surfactants with various charge such as anionic cetyl trimethyl ammonium bromide (CTAB), cationic sodium dodecyl sulphate (SDS) and neutral TritonX-100 was employed. By changing the surfactant and ratio of metal ions/surfactant the size and crystalline structure of these nanoparticles were controlled. We also show that using anionic stabilizer leads to smallest size and narrowest size distribution and the most crystalline (polycrystalline) structure. In developing our production technique, many parameters were varied. Efforts at reproducing good yields indicated which of the experimental parameters were the most critical and how carefully they had to be controlled. The conditions reported here were the best that we encountered but the range of possible parameter choice is so large that these probably only represent a local optimum. The samples for our chemical process were prepared by adding 0.675 gr ferric chloride (FeCl3, 6H2O) to three different surfactant in water solution. The solution was sonicated for about 30 min until a transparent solution was achieved. Then 0.5 gr sodium hydroxide (NaOH) as a reduction agent was poured to the reaction drop by drop which resulted to participate reddish brown Fe2O3 nanoparticles. After washing with ethanol the obtained powder was calcinated in 600°C for 2h. Here, the sample 1 contained CTAB as a surfactant with ratio of metal ions/surfactant 1/2, sample 2 with CTAB and ratio 1/1, sample 3 with SDS and ratio 1/2, sample 4 SDS 1/1, sample 5 is triton-X-100 with 1/2 and sample 6 triton-X-100 with 1/1.

Keywords: iron oxide nanoparticles, stabilizer, co-precipitation, surfactant

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Authors: Zbigniew Szklarz, Aldona Garbacz-Klempka, Magdalena Bisztyga-Szklarz

Abstract:

Typical metallic alloys bases on one major alloying component, where the addition of other elements is intended to improve or modify certain properties, most of all the mechanical properties. However, in 1995 a new concept of metallic alloys was described and defined. High Entropy Alloys (HEA) contains at least five alloying elements in an amount from 5 to 20 at.%. A common feature this type of alloys is an absence of intermetallic phases, high homogeneity of the microstructure and unique chemical composition, what leads to obtaining materials with very high strength indicators, stable structures (also at high temperatures) and excellent corrosion resistance. Hence, HEA can be successfully used as a substitutes for typical metallic alloys in various applications where a sufficiently high properties are desirable. For fabricating HEA, a few ways are applied: 1/ from liquid phase i.e. casting (usually arc melting); 2/ from solid phase i.e. powder metallurgy (sintering methods preceded by mechanical synthesis) and 3/ from gas phase e.g. sputtering or 4/ other deposition methods like electrodeposition from liquids. Application of different production methods creates different microstructures of HEA, which can entail differences in their properties. The last two methods also allows to obtain coatings with HEA structures, hereinafter referred to as High Entropy Films (HEF). With reference to above, the crucial aim of this work was the optimization of the manufacturing process of the multi-component metallic layers (HEF) by the low- and high temperature electrochemical deposition ( ED). The low-temperature deposition process was crried out at ambient or elevated temperature (up to 100 ᵒC) in organic electrolyte. The high-temperature electrodeposition (several hundred Celcius degrees), in turn, allowed to form the HEF layer by electrochemical reduction of metals from molten salts. The basic chemical composition of the coatings was CoCrFeMnNi (known as Cantor’s alloy). However, it was modified by other, selected elements like Al or Cu. The optimization of the parameters that allow to obtain as far as it possible homogeneous and equimolar composition of HEF is the main result of presented studies. In order to analyse and compare the microstructure, SEM/EBSD, TEM and XRD techniques were employed. Morover, the determination of corrosion resistance of the CoCrFeMnNi(Cu or Al) layers in selected electrolytes (i.e. organic and non-organic liquids) was no less important than the above mentioned objectives.

Keywords: high entropy alloys, electrodeposition, corrosion behavior, microstructure

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