Search results for: trans resveratrol

Authors: Przemyslaw Nogly, Tobias Weinert, Daniel James, Sergio Carbajo, Dmitry Ozerov, Antonia Furrer, Dardan Gashi, Veniamin Borin, Petr Skopintsev, Kathrin Jaeger, Karol Nass, Petra Bath, Robert Bosman, Jason Koglin, Matthew Seaberg, Thomas Lane, Demet Kekilli, Steffen Brünle, Tomoyuki Tanaka, Wenting Wu, Christopher Milne, Thomas A. White, Anton Barty, Uwe Weierstall, Valerie Panneels, Eriko Nango, So Iwata, Mark Hunter, Igor Schapiro, Gebhard Schertler, Richard Neutze, Jörg Standfuss

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Ultrafast isomerization of retinal is the primary step in a range of photoresponsive biological functions including vision in humans and ion-transport across bacterial membranes. We studied the sub-picosecond structural dynamics of retinal isomerization in the light-driven proton pump bacteriorhodopsin using an X-ray laser. Twenty snapshots with near-atomic spatial and temporal resolution in the femtosecond regime show how the excited all-trans retinal samples conformational states within the protein binding pocket prior to passing through a highly-twisted geometry and emerging in the 13-cis conformation. The aspartic acid residues and functional water molecules in proximity of the retinal Schiff base respond collectively to formation and decay of the initial excited state and retinal isomerization. These observations reveal how the protein scaffold guides this remarkably efficient photochemical reaction.

Keywords: bacteriorhodopsin, free-electron laser, retinal isomerization mechanism, time-resolved crystallography

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Authors: Seema Ahlawat, Parul Saxena, Malik Zainul Abdin

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Malaria is a major health problem in many developing countries. The parasite responsible for the vast majority of fatal malaria infections is Plasmodium falciparum. Unfortunately, most Plasmodium strains including P. falciparum have become resistant to most of the antimalarials including chloroquine, mefloquine, etc. To combat this problem, WHO has recommended the use of artemisinin and its derivatives in artemisinin based combination therapy (ACT). Due to its current use in artemisinin based-combination therapy (ACT), its global demand is increasing continuously. But, the relatively low yield of artemisinin in A. annua L. plants and unavailability of economically viable synthetic protocols are the major bottlenecks for its commercial production and clinical use. Chemical synthesis of artemisinin is also very complex and uneconomical. The hairy root system, using the Agrobacterium rhizogenes LBA 9402 strain to enhance the production of artemisinin in A. annua L., is developed in our laboratory. The transgenic nature of hairy root lines and the copy number of trans gene (rol B) were confirmed using PCR and Southern Blot analyses, respectively. The effect of different concentrations of Piriformospora indica on artemisinin production in hairy root cultures were evaluated. 3% P. indica has resulted 1.97 times increase in artemisinin production in comparison to control cultures. The effects of P. indica on artemisinin production was positively correlated with regulatory genes of MVA, MEP and artemisinin biosynthetic pathways, viz. hmgr, ads, cyp71av1, aldh1, dxs, dxr and dbr2 in hairy root cultures of A. annua L. Mass scale cultivation of A. annua L. hairy roots by plant tissue culture technology may be an alternative route for production of artemisinin. A comprehensive investigation of the hairy root system of A. annua L. would help in developing a viable process for the production of artemisinin. The efficiency of the scaling up systems still needs optimization before industrial exploitation becomes viable.

Keywords: A. annua L., artemisinin, hairy root cultures, malaria

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Authors: Achilles Kameas, Eleni Georgakakou, Anna Lisa Amodeo, Aideen Quilty, Aisling Malone, Roberta Albertazzi, Moises Carmona, Concetta Esposito, Ruben David Fernandez Carrasco, Carmela Ferrara, Francesco Garzillo, Mojca Pusnik, Maria Cristina Scarano

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While researchers, especially in academia, study and research the phenomena of inclusion of sexual minority and gender marginalized groups, seldom the European Higher Education Institutions (HEI) act on lowering the cultural and educational barriers to their proactive inclusion. The challenge in European HEIs is that gender, and sexual orientation discrimination remains an issue not adequately addressed. Following a mixed methods research design of quantitative and qualitative research techniques and tools, which is applied in five (5) European countries (Italy, Greece, Ireland, Slovenia, and Spain) and that combines desk research, evaluation, and weighting processes for a Matrix-based on Objective indicators and Survey for students and staff of the HEI to gauge the perception of inclusiveness in the HEI context, XENIA HEI Inclusiveness Index is an instrument that will allow universities to gauge and assess their inclusiveness in the domain of discrimination and exclusion based on gender identity and sexual orientation. The index will allow capturing the depth and reach of policies, programmes, and initiatives of HEIs in tackling the phenomena and dynamics of exclusion of LGBT+ (lesbian, gay, bisexual, trans, and other marginalized groups on the basis of gender and sexual identity) and cisgender women exposed to the risk of discrimination.

Keywords: gender identity, higher education, LGBT+ rights, XENIA inclusiveness index

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Authors: David Cobham

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In higher education, a great degree of importance is placed on the internationalization of the student experience. This is seen as a valuable contributor to elements such as building confidence, broadening knowledge, creating networks and connections, and enhancing employability for current students who will become the next generation of managers in technology and business. The COVID-19 pandemic has affected all areas of people’s lives. The limitations of travel coupled with the fears and concerns generated by the health risks have dramatically reduced the opportunity for students to engage with this agenda. Institutions of higher education have been required to rethink fundamental aspects of their business model from recruitment and enrolment through learning approaches, assessment methods, and the pathway to employment. This paper presents a case study which focuses on student mobility and how the physical experience of being in another country, either to study, to work, to volunteer or to gain cultural and social enhancement, has of necessity been replaced by alternative approaches. It considers trans-national education as an alternative to physical study overseas, virtual mobility and internships as an alternative to international work experience, and adopting collaborative online projects as an alternative to in-person encounters. The paper concludes that although these elements have been adopted to address the current situation, the lessons learned and the feedback gained suggests that they have contributed successfully in new and sometimes unexpected ways and that they will persist beyond the present to become part of the 'new normal' for the future. That being the case, senior leaders of institutions of higher education will be required to revisit their international plans and to rewrite their international strategies to take account of and build upon these changes.

Keywords: higher education management, internationalization, transnational education, virtual mobility

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Authors: Parvin Goli, Amirhosein Kefayat, Rezvan Goli

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Background: It is well established that parents can influence their offspring's neurodevelopment. It is shown that paternal environment and lifestyle is beneficial for the progeny's fitness and might affect their metabolic mechanisms; however, the effects of paternal exercise on the brain in the offspring have not been explored in detail. Objective: This study aims to review the impact of paternal physical exercise on memory and learning, neuroplasticity, as well as DNA methylation levels in the off-spring's hippocampus. Study design: In this systematic review and meta-analysis, an electronic literature search was conducted in databases including PubMed, Scopus, and Web of Science. Eligible studies were those with an experimental design, including an exercise intervention arm, with the assessment of any type of memory function, learning ability, or any type of brain plasticity as the outcome measures. Standardized mean difference (SMD) and 95% confidence intervals (CI) were computed as effect size. Results: The systematic review revealed the important role of environmental enrichment in the behavioral development of the next generation. Also, offspring of exercised fathers displayed higher levels of memory ability and lower level of brain-derived neurotrophic factor. A significant effect of paternal exercise on the hippocampal volume was also reported in the few available studies. Conclusion: These results suggest an intergenerational effect of paternal physical activity on cognitive benefit, which may be associated with hippocampal epigenetic programming in offspring. However, the biological mechanisms of this modulation remain to be determined.

Keywords: hippocampal plasticity, learning ability, memory, parental exercise

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Authors: Maryam Nazari

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COVID-19 is a respiratory disease triggered by the novel coronavirus, SARS-CoV-2, that has reached pandemic status today. Acute inflammation and immune cells infiltration into lung injuries result in multi-organ failure. The presence of other non-communicable diseases (NCDs) with systemic inflammation derived from COVID-19 may exacerbate the patient's situation and increase the risk for adverse effects and mortality. This pandemic is a novel situation and the scientific community at this time is looking for vaccines or drugs to treat the pathology. One of the biggest challenges is focused on reducing inflammation without compromising the correct immune response of the patient. In this regard, addressing the nutritional factors should not be overlooked not only as a matter of avoiding the presence of NCDs with severe infections but also as an adjunctive way to modulate the inflammatory status of the patients. Despite the pivotal role of nutrition in modifying immune response, due to the novelty of the COVID-19 disease, information about the effects of specific dietary agents is limited in this area. From the macronutrients point of view, protein deficiency (quantity or quality) has negative effects on the number of functional immunoglobulins and gut-associated lymphoid tissue (GALT). High biological value proteins or some amino acids like arginine and glutamine are well known for their ability to augment the immune system. Among lipids, fish oil has the ability to inactivate enveloped viruses, suppress pro-inflammatory prostaglandin production and block platelet-activating factors and their receptors. In addition, protectin D1, which is an Omega-3 PUFAs derivation, is a novel antiviral drug. So it seems that these fatty acids can reduce the severity and/or improve recovery of patients with COVID-19. Carbohydrates with lower glycemic index and fibers are associated with lower levels of inflammatory cytokines (CRP, TNF-α, and IL-6). Short-Chain Fatty acids not only exert a direct anti-inflammatory effect but also provide appropriate gut microbial, which is important in gastrointestinal issues related to COVID-19. From the micronutrients point of view, Vitamins A, C, D, E, iron, magnesium, zinc, selenium and copper play a vital role in the maintenance of immune function. Inadequate status in these nutrients may result in decreased resistance against COVID-19 infection. There are specific bioactive compounds in the diet that interact with the ACE2 receptor, which is the gateway for SARS and SARS-CoV-2, and thus controls the viral infection. Regarding this, the potential benefits of probiotics, resveratrol (a polyphenol found in grape), oleoylethanolamide (derived from oleic acid), and natural peroxisome proliferator-activated receptor γ agonists in foodstuffs (like curcumin, pomegranate, hot pepper) are suggested. Yet, it should be pointed out that most of these results have been reported in animal models and further human studies are needed to be verified.

Keywords: Covid-19, inflammation, nutrition, dietary agents

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Authors: Georgiana Ciobotaru

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The experience of exile is a defining one for the mittleeuropean writers, which is also the generator of an identity discourse manifested in the plan of fiction. In exile, the authors often build their marginality in opposition to that deserted mundi center. The Polish Gombrowicz carried out his existence, for more than twenty-three years, in a geographical exile, distancing himself from his country, and, from a cultural point of view, the writing meant a possibility of escape, of plunge into a literary exile that often constituted a way of conditioning the practice of writers. He opted for one of the attitudes that a writer in exile may have, namely he preferred to continue speaking Polish, although he was far from his homeland, turning to the public in his homeland, his entire literary creation in exile being promoted through Kulturia, the Paris-based immigration magazine. The problem of exile must be constantly related to three essential aspects, namely: territory, identity and language. The exile, both the writer and his characters, displays a characteristic attitude towards the abandoned land, but also towards the adoptive, towards the mother tongue, but also towards the idiom encountered, thus proving an original manner in terms of how it asserts, de-builds or re-builds its identity. In these texts written after leaving Poland, a series of open works by Trans-Atlantic, Gombrowicz assumes and internalizes the inadequacy between his self and the reality outside to make it the principle of his perception of the world. The expression of marginality that characterized the texts developed when the writer was still in Poland seems to acquire a certain coherence against the background of a logic imposed on the new experience, namely that of exile. Texts created during his exile in Argentina appear in a different context, in other words, in a situation of inadequacy towards the world: ignorance of the language, poverty, isolation that characterizes especially the first years spent there. This study aims to highlight how the Polish author de-builds and reconstructs his Mittel-European identity profile through language.

Keywords: discourse, exile, identity, immigration

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Authors: Hachaichi Mohamed Nour El-Islem, Baouni Tahar

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Environmental sustainability rather than a trans-disciplinary and a scientific issue, is the main problem that characterizes all modern cities nowadays. In developing countries, this concern is expressed in a plethora of critical urban ills: traffic congestion, air pollution, noise, urban decay, increase in energy consumption and CO₂ emissions which blemish cities’ landscape and might threaten citizens’ health and welfare. As in the same manner as developing world cities, the rapid growth of Algiers’ human population and increasing in city scale phenomena lead eventually to increase in daily trips, energy consumption and CO₂ emissions. In addition, the lack of proper and sustainable planning of the city’s infrastructure is one of the most relevant issues from which Algiers suffers. The aim of this contribution is to estimate the carbon deficit of the City of Algiers, Algeria, using the Ecological Footprint Model (carbon footprint). In order to achieve this goal, the amount of CO₂ from fuel combustion has been calculated and aggregated into five sectors (agriculture, industry, residential, tertiary and transportation); as well, Algiers’ biocapacity (CO₂ uptake land) has been calculated to determine the ecological overshoot. This study shows that Algiers’ transport system is not sustainable and is generating more than 50% of Algiers total carbon footprint which cannot be sequestered by the local forest land. The aim of this research is to show that the Carbon Footprint Assessment might be a relevant indicator to design sustainable strategies/policies striving to reduce CO₂ by setting in motion the energy consumption in the transportation sector and reducing the use of fossil fuels as the main energy input.

Keywords: biocapacity, carbon footprint, ecological footprint assessment, energy consumption

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Authors: Hitesh Gupta, Surender Dabas

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TORS is increasingly gaining widespread use and has been explored as minimally invasive surgery for the treatment of supraglottic cancer (SGC). Being a central critical role of Supraglottis in deglutition, swallowing outcomes post TORS remain a most important factor. Available published studies show inconsistent swallowing outcomes and are deficient in standardized outcome measures, description of swallowing recovery and rehabilitation. So, the objective of this study is to find out swallowing outcomes in SGC patients after TORS provided with early dysphagia management using standardized measures. Prospectively 16 patients were recruited in the study who underwent TORS for primary tumor of Supraglottis, involving one or more sub-sites or invading to sites other than Supraglottis at the BLK Super Specialty Hospital, New Delhi from March 2019 to June 2020. All patients were evaluated for dysphagia with subsequent swallowing rehabilitation on post operative day 3 in the hospital or at the time of discharge, whichever was earlier. Functional oral intake scale (FOIS) and penetration-aspiration score (PAS) were used as outcome measures to quantify swallowing recovery at one month and six month post operatively. Post TORS, patients achieved functional swallow in less than one month, where resection was limited to Supraglottis, while the recovery was delayed in patients with extended resection to tongue base or hypopharynx. Overall, out of Total 16 cases including all supraglottis sub-catagories, 13 (81%) could remove their NG tube (FOIS ≥5 and PAS=1 ) within 6 months. In which 8 cases(62%) achieved functional swallow in less than one month. Swallowing outcomes post TORS supraglottic laryngectomy are favorable if provided with early dysphagia management (or swallowing rehabilitation).

Keywords: dysphagia, supraglottic cancer, swallowing, TORS

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Authors: Gelu Varghese, Khizer Saeed

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Biodiesel is as a mixture of mono-alkyl esters of long chain fatty acids derived from vegetable oils or animal fats. Recent studies in the literature suggest that end property of biodiesel such as its oxidative stability (OS) is highly influenced by the structure and composition of its alkyl esters than by environmental conditions. The structure and composition of these long chain fatty acid components have been also associated with trends in Cetane number, heat of combustion, cold flow properties viscosity, and lubricity. In the present work, detailed investigation has been carried out to decouple and correlate the fatty acid structure indices of biodiesel such as degree of unsaturation, chain length, double bond orientation, and composition with its oxidative stability. Measurements were taken using the EN14214 established Rancimat oxidative stability test method (EN141120). Firstly, effects of the degree of unsaturation, chain length and bond orientation were tested for the pure fatty acids to establish their oxidative stability. Results for pure Fatty acid show that Saturated FAs are more stable than unsaturated ones to oxidation; superior oxidative stability can be achieved by blending biodiesel fuels with relatively high in saturated fatty acid contents. A lower oxidative stability is noticed when a greater quantity of double bonds is present in the methyl ester. A strong inverse relationship with the number of double bonds and the Rancimat IP values can be identified. Trans isomer Methyl elaidate shows superior stability to oxidation than its cis isomer methyl oleate (7.2 vs. 2.3). Secondly, the effects of the variation in the composition of the biodiesel were investigated and established. Finally, biodiesels with varying structure and composition were investigated and correlated.

Keywords: biodiesel, fame, oxidative stability, fatty acid structure, acid composition

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Authors: Partha Sarathi Mondal, Srabani Sanyal

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Different geomorphic agents produce a different landforms pattern. Similarly rivers also have a distinct and diverse landforms pattern. And even, within a river course different and distinct assemblage of landforms i.e. morphological variability are seen. These morphological variability are produced by different river processes. Channel and floodplain morphology helps to interpret river processes. Consequently morphological variability can be used as an important tool for assessing river processes, hydrological connectivity and river health, which will help us to draw inference about river processes and therefore, management of river health. The present study is documented on West Rapti river, a trans-boundary river flowing through Nepal and India, from its source to confluence with Ghaghra river in India. The river shows a significant morphological variability throughout its course. The present study tries to find out factors and processes responsible for the morphological variability of the river and in which way it can be applied in river management practices. For this purpose channel and floodplain morphology of West Rapti river was mapped as accurately as possible and then on the basis of process-form interactions, inferences are drawn to understand factors of morphological variability. The study shows that the valley setting of West Rapti river, in the Himalayan region, is confined and somewhere partly confined whereas, channel of the West Rapti river is single thread in most part of Himalayan region and braided in valley region. In the foothill region valley is unconfined and channel is braided, in middle part channel is meandering and valley is unconfined, whereas, channel is anthropogenically altered in the lower part of the course. Due to this the morphology of West Rapti river is highly diverse. These morphological variability are produced by different geomorphic processes. Therefore, for any river management it is essential to sustain these morphological variability so that the river could not cross the geomorphic threshold and environmental flow of the river along with the biodiversity of riparian region is maintained.

Keywords: channel morphology, environmental flow, floodplain morphology, geomorphic threshold

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Authors: Durjoy Lahiri, Vishal Madhukar Sawale, Ashwani Bhat, Souvik Dubey, Gautam Das, Biman Kanti Roy, Suparna Chatterjee, Goutam Gangopadhyay

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Crossed aphasia has been an area of considerable interest for cognitive researchers as it offers a fascinating insight into cerebral lateralization for language function. We conducted an observational study in the stroke unit of a tertiary care neurology teaching hospital in eastern India on subjects with crossed aphasia over a period of four years. During the study period, we detected twelve cases of crossed aphasia in strongly right-handed patients, caused by ischemic stroke. The age, gender, vernacular language and educational status of the patients were noted. Aphasia type and severity were assessed using Bengali version of Western Aphasia Battery (validated). Computed tomography, magnetic resonance imaging and angiography were used to evaluate the location and extent of the ischemic lesion in brain. Our series of 12 cases of crossed aphasia included 7 male and 5 female with mean age being 58.6 years. Eight patients were found to have Broca’s aphasia, 3 had trans-cortical motor aphasia and 1 patient suffered from global aphasia. Nine patients were having very severe aphasia and 3 suffered from mild aphasia. Mirror-image type of crossed aphasia was found in 3 patients, whereas 9 had anomalous variety. In our study crossed aphasia was found to be more frequent in males. Anomalous pattern was more common than mirror-image. Majority of the patients had motor-type aphasia and no patient was found to have pure comprehension deficit. We hypothesize that in Bengali-speaking right-handed population, lexical-semantic system of the language network remains loyal to the left hemisphere even if the phonological output system is anomalously located in the right hemisphere.

Keywords: aphasia, crossed, lateralization, language function, vascular

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Authors: Amit Kaushik

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Equus kiang kiang is an indigenous large-bodied herbivore species, and in India, it is restricted to limited geographies of Ladakh. One of such areas is the Tsokar Basin. With the rise in global pashmina demand, the livestock numbers have grown significantly. Previous studies have reported conflict between a nomadic pastoral community, the Changpas, and kiang. Absentee pastoralism (in lieu of pure pastoralism) and tourism are two major economic activities among the local people. However, the social, economic, political, and ecological changes are inevitable in such a contemporary system. The study examines several factors influencing the local pastoral economy and focuses on the presence of two non-human cohabitants, kiang, and the wolf. This study used semi-structured interviews and vehicle count method in four different seasons. The results show that people perceived kiang as a threat but also reveal a level of tolerance towards them. The locals predicted high kiang numbers ranging from 200-3000 in the basin and contrastingly ranked them behind wolves, which are very few in numbers. Due to a lack of scientific pieces of evidence, the kiang population status remains obscure, and local peoples’ concerns remain unaddressed. But how this competitive dysfunctionality does take place? On one side, the rural development or the animal husbandry department aims at developing the area by providing stall-feed and tourism, whereas, on another side, the wildlife department emphasizes wildlife conservation. Therefore, the managers and planners may need to be cautious about the local socio-ecological complexities and may require inter-departmental communications. The study concludes that an interdisciplinary inquiry may be an important tool in understanding such a precarious situation and may be used in the policy-making processes.

Keywords: coexistence, human-livestock-wildlife interactions, interdisciplinary approach, kiang, policymaking, tsokar.

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Authors: Mark Andrew

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Geopolitical tensions are at a thirty-year high, and the pace of technological innovation is driving asymmetry in force capabilities between nation states and between non-state actors. Technology futures are a vital component of defence capability growth, and investments in technology futures need to be informed by accurate and reliable forecasts of the options for ‘systems of systems’ innovation, development, and deployment. This paper describes a method for forecasting technology futures developed through an analysis of four key systems’ development stages, namely: technology domain categorisation, scanning results examining novel systems’ signals and signs, potential system-of systems’ implications in warfare theatres, and political ramifications in terms of funding and development priorities. The method has been applied to several technology domains, including physical systems (e.g., nano weapons, loitering munitions, inflight charging, and hypersonic missiles), biological systems (e.g., molecular virus weaponry, genetic engineering, brain-computer interfaces, and trans-human augmentation), and information systems (e.g., sensor technologies supporting situation awareness, cyber-driven social attacks, and goal-specification challenges to proliferation and alliance testing). Although the current application of the method has been team-centred using paper-based rapid prototyping and iteration, the application of autonomous language models (such as GPT-3) is anticipated as a next-stage operating platform. The importance of forecasting accuracy and reliability is considered a vital element in guiding technology development to afford stronger contingencies as ideological changes are forecast to expand threats to ecology and earth systems, possibly eclipsing the traditional vulnerabilities of nation states. The early results from the method will be subjected to ground truthing using longitudinal investigation.

Keywords: forecasting, technology futures, uncertainty, complexity

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Authors: Marinete Araujo da Silva Fobister

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This presentation aims to discuss how the feeling of ‘nostalgia’ both present on Westerns and migrants could shed light to a mutual recognition and an exchange of ways of life that could enhance mutual possibilities of self-realization. It seems that this feeling of nostalgia is related to another unfolding of the nihilism of the death of God diagnosed by Nietzsche. Westerns are feeling on the margins of the values of their own culture as they feel such values as external to them. At the same time, some groups are claiming the return of the old devalued values. In this scenario, the West is receiving many migrants from different parts of the world since the second half of the last century. Migrants might be suffering from nostalgia or homesickness for having left their home. It might be that sharing a sense of nostalgia, although with different meanings, can bring together Westerns and migrants. Migrants bring ways of life that might be unknown and inexperienced in the West, and these can shed light to new forms of interpretation and cultivation of ones’ drives, and forces and this could become a source of mutual strength cultivation. Therefore, this mutual feeling of nostalgia could lead to ways of exploring the idea of self- realization in Nietzsche detaching it from the idea of being mainly individual to a more trans-individual-cultural claim. Nietzsche argues that nihilism is a European event here translated as a Western event, which would take 200 years until it could be overcome. To overcome nihilism a new kind of human would be needed, a creative and strong kind. For Nietzsche, there is not a fixed or true self, hence one possibility for one to achieve self-realization would reside on cultivating their multiple creative forces. The argument here is that in this recent unfolding of nihilism, translated in the sense of nostalgia, the encounter between the mainstream western immersed on nihilism with migrants could create a sense of a shared temporary home, where these different ways of life could inspire each other to create new meanings. Indeed, contributing to the expansion of one’s world view, drives and forces. Therefore, fertilizing the soil for the cultivation of self-realization and consequently the creation of new values.

Keywords: migration, nihilism, nostalgia, self-realization

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Authors: Harley Stephens

Abstract:

Although fiducial marker insertion is regarded as the ‘gold standard’ in terms of image guided radiotherapy (IGRT), its application must be considered carefully as the procedure can be invasive, time-consuming, and reliant on consultant expertise. Precision of the fiducials is dependent on these markers remaining in the same location and on the prostate not changing shape during the course treatment. To facilitate the acquirement of non-ionising IGRT and intra-fractional prostate tracking, Clarity TPUS was developed as an alternative imaging system. The main benefits of Clarity TPUS are that it is non-invasive, non-ionising and cost-effective. Other studies have compared fiducials to transabdominal ultrasound, which has since been proven to not be as accurate as trans-perineal imaging, as included in this study. CBCT fiducial translations and Clarity TPUS translations for 120 images as part of the PACE-C prostate SABR trial were retrospectively evaluated by three imaging specialists. Differences were analysed using correlation and Bland-Altman plots. Inter-observer matches agreed within 3mm 88.3 % of the time in left/right direction, 86.7 % of the time in in superior/inferior direction, and 91.7% of the time in ant/post direction. They agreed within 5mm more than 98.3 % of the time in all directions. The intra-class correlation co-efficient was calculated for each direction to show agreement between imaging specialist for inter-observer variability. Each was 0.95 or above, with 1 indicating perfect reliability. Agreement between observers was slightly higher for CBCT and fiducials at 98.7% agreement within 5 mm, compared to clarity TPUS where 96.7% agreement was seen within 5mm. Clarity TPUS has the benefit of no additional dose and intra-fractional monitoring, and results show a good correlation between the different modalities. Inter-observer variability is to be considered, and further research with a larger population would be of benefit.

Keywords: oncology, prostate radiotherapy, image guided radiotherapy, IGRT

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Authors: S. Curtin, A. Trace

Abstract:

Introduction: As patients can often be ambivalent about or resistant to any change in their smoking behavior the traditional ‘5 A’ model may be limited as it assumes that patients are ready and motivated to change. However, there is a stage model that is helpful to give guidance for dental students: the Transtheoretical Model (TTM). This model allows students to understand the tasks and goals for the pre-contemplation stage. The TTM was introduced in early stages as a core component of a smoking cessation programme that was integrated into a Behavioral Science programme as applied to dentistry. The aim of the present study is to evaluate and illustrate the students’ current level of knowledge from the questions the students generated in order to engage patients in the tasks and goals of the pre-contemplation stage. Method: N=47 responses of fifth-year undergraduate dental students. These responses were the data set for this study and related to their knowledge base of appropriate questions for a dentist to ask at the pre-contemplation stage of change. A deductive -descriptive analysis was conducted on the data. The goals and tasks of the pre-contemplation stage of the TTM provided a template for this deductive analysis. Results: 51% of students generated relevant, open, exploratory questions for the pre-contemplation stage, whilst 100% of students generated closed questions. With regard to those questions appropriate for the pre-contemplation stage, 19% were open and exploratory, while 66% were closed questions. A deductive analysis of the open exploratory questions revealed that 53% of the questions addressed increased concern about the current pattern of behavior, 38% of the questions concerned increased awareness of a need for change and only 8% of the questions dealt with the envisioning of the possibility of change. Conclusion: All students formulated relevant questions for the pre-contemplation stage, and half of the students generated the open, exploratory questions that increased patients’ awareness of the need to change. More training is required to facilitate a shift in the formulation from closed to open questioning, especially given that, traditionally, smoking cessation was modeled on the ‘5 As’, and that the general training for dentists supports an advisory and directive approach.

Keywords: behaviour change, pre-contemplation stage, trans-theoretical model, undergraduate dentistry students

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Authors: Xinxiu Li, Chuqian Zheng, Yanyan Qian, Hong Fan

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Objectives: In hepatocellular carcinoma (HCC), oncogenes are continuously and robustly transcribed due to aberrant expression of essential components of the trans-acting super-enhancers (SE) complex. Preclinical and clinical trials are now being conducted on small-molecule inhibitors that target core-transcriptional components, including as transcriptional bromodomain protein 4 (BRD4) and cyclin-dependent kinase 7 (CDK7), in a number of malignant tumors. This study aims to explore whether co-overexpression of BRD4 and CDK7 is a potential marker of worse prognosis and a combined therapeutic target in HCC. Methods: The expression pattern of BRD4 and CDK7 and their correlation with prognosis in HCC were analyzed by RNA sequencing data and survival data of HCC patients from TCGA and GEO datasets. The protein levels of BRD4 and CDK7 were determined by immunohistochemistry (IHC), and survival data of patients were analyzed using the Kaplan-Meier method. The mRNA expression levels of genes in HCC cell lines were evaluated by quantitative PCR (q-PCR). CCK-8 and colony formation assays were conducted to assess cell proliferation of HCC upon treatment with BRD4 inhibitor JQ1 or/and CDK7 inhibitor THZ1. Results: It was shown that BRD4 and CDK7 were often overexpressed in HCCs and were associated with poor prognosis of HCC by analyzing the TCGA and GEO datasets. BRD4 or CDK7 overexpression was related to a lower survival rate. It's interesting to note that co-overexpression of CDK7 and BRD4 was a worse prognostic factor in HCC. Treatment with JQ1 or THZ1 alone had an inhibitory effect on cell proliferation; however, when JQ1 and THZ1 were combined, there was a more notable suppression of cell growth. At the same time, the combined use of JQ1 and THZ1 synergistically suppresses the expression of HCC driver genes. Conclusion: Our research revealed that BRD4 and CDK7 coupled can be a useful biomarker in HCC prognosis and the combination of JQ1 and THZ1 can be a promising therapeutic therapy against HCC.

Keywords: BRD4, CDK7, cell proliferation, combined inhibition

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Authors: Mohammad Atiqur Rahman

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The study aimed at inventorying the threatened biodiversity of Bangladesh and assessing the rate of loss of biodiversity caused due to environmental degradation for conservation management. The impact assessment of environmental depletion and rate of biodiversity loss determination have been made by a long term field investigation, examination of preserved herbarium specimens and survey of relevant floristic literature following the IUCN’s threatened criteria of assessing Red List Plants under the Flora Bangladesh Project. Biodiversity of Bangladesh, as evaluated, has been affected to a large extent during the last four and half decades due to spontaneous environmental degradation caused by frequent occurrence of cyclonic storms and tidal bores since 1970 and flooding, draught, unilateral diversion of trans-boundary waters by operating Farakka Barrage since 1975, indiscriminate destruction and over exploitation of natural resources, unplanned development and industrialization, overpopulation etc. Depletion of world’s largest mangrove biodiversity in Sundarbans, coastal and island biodiversity in southern part, agro-biodiversity and agro-fisheries all over the country, Haor and wetland biodiversity of plain lands, terrestrial and forest biodiversity in central and eastern hilly part of Bangladesh, as assessed, have greatly been occurred at a higher rate due to environmental degradation which in turn affect directly or indirectly the economy, food security and environmental health of the country. Complete inventory of 30 plant families resulted in the recognition of 45.18% species of Bangladesh as threatened environmentally and 13.23% species as possibly extinct from the flora since these have neither been reported or could be traced in the field for more than 100 years. The rate of extinction is determined to be 2.65% per 20 years. Hence the study indicates that the loss of biodiversity and environmental degradation in Bangladesh occurring at an alarming rate. The study focuses on the issues of environment, the extent of loss of different plant biodiversities in Bangladesh, prioritizing and implementing national conservation strategies for sustainable management of the environment.

Keywords: Bangladesh, biodiversity, conservation, environmental management

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Authors: Birhane Atnafu, Chemeda Abedeta Garbaba, Fikre Lemessa, Abdi Mohammed, Alemayehu Chala

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Essential oil is a bio-pesticide plant product used as an alternative to pesticides in managing plant pests, including fungal pathogens. Thus, the current study aims to investigate the chemical composition and antifungal activities of essential oils (EO) extracted from three aromatic plants i.e., Thymus vulgaris, Coriandrum sativum, and Cymbopogon martini. The leaf parts of those selected plants were collected from the Jimma area and their essential oil was extracted by hydro-distillation method in a Clevenger apparatus. The chemical composition of selected plant essential oil was analyzed by using Gas chromatography-mass spectrometry (GC/MS) and their inhibitory effects were tested in vitro on toxigenic fungi isolated from maize kernel. Chemical analysis results revealed the presence of 32 compounds in C. sativum with Hexanedioic acid, bis (2-ethylhexyl) ester (46. 9%), 2-Decenal, (E)- (12.6), and linalool (8.3%) being the dominant ones. T. vulgaris essential oils constituted 25 compounds, of which thymol (34.4%), o-cymene (17.5%), and Gamma-Terpinene (16.8%) were the major components. Twenty-five compounds were detected in C. martinii of which geraniol (51.4%), Geranyl acetate (14.5%), and Trans – ß-Ocimene (11.7%) were dominant. The EOs of the tested plants had very high antifungal activity (up to 100% efficacy) against Aspergillus flavus, Aspergillus niger, Fusarium graminearum and Fusarium verticillioides in vitro and on maize grains. The antifungal activities of these essential oils were dependent on the major components such as thymol, hexanedioic acid, bis (2-ethylhexyl) ester, and geraniol. The study affirmed the potential of these essential oils controlling as bio-fungicides to manage the effects of potentially toxigenic fungi associated with maize under post-harvest stages. This can reduce the consequences of the health impacts of the mold and toxigenic compounds produced in maize.

Keywords: bio-activity, bio-pesticides, maize, mycotoxin

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Authors: Olufunke O. Obanla, Oluseye O. Onabanjo, Silifat A. Sanni, Mojisola O. Adegunwa, Wasiu A. O. Afolabi, Omolola O. Oyawoye, Atinuke Titilola Lano-Maduagu

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Background: Dietary fat is implicated in the increasing development of chronic diseases in developing countries while dietary fibre plays a major role in the management of these diseases. Accurate nutrient composition data for composite dishes unique to a population is essential for the development of a nutrient database and the calculation of dietary intake. Methods: Representative samples of standardized Nigerian soups and dishes were analyzed for fatty acids using gas chromatography-mass spectrophotometry (GC-MS) and dietary fibre using an enzymatic-gravimetric standard method of AOAC. Results: The total Saturated Fatty acids (SFAs) ranged from 0.74+0.3g/100g to 73.82+0.07g/100g. The total monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) ranged from 2.16+1.13g/100g for Yam pottage to 22.25+0.58g/100g for Okazi soup and eba, and from 0.42+0.10g/100g for Yam pottage to 10.22+0.1g/100g for Pounded yam with egusi ball soup, respectively. Trans fat was observed in Alapafubu and Tuwo shinkafa (2.80+0.2g/100g), Yam pottage (0.20+0.15g/100g), Steamed bean pudding (1.28+0.53g/100g) and Ikokore (5.33+0.41g/100g). The Total Dietary Fibre (TDF) contents of the dishes ranged from 12.95+2.99g/100g in Jollof rice to 62.00+0.94g/100g in Melon seed and vegetable soup, the Soluble Dietary Fibre (SDF) ranged from 2.05+0.32g/100g in Steamed bean pudding to 7.81+0.74g/100g in Ikokore while the Insoluble Dietary Fibre (IDF) ranged from 8.20+0.43g/100g in Jollof rice to 57.91+4.69g/100g in melon seed and vegetable soup. Conclusions: The study has indicated that some Nigerian dishes are characterized by high SFAs, TFAs and dietary fibre, moderate MUFAs and very low levels of PUFAs. High levels of SFAs in some soups and dishes are a major public health concern.

Keywords: healthy diet, dietary fibre, fatty acid profile, chronic diseases, Nigerian dishes

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Authors: Devanshu Gupta, Kailash Chandra, Priyanka Das, Joyjit Ghosh

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Beetles, in the insect order Coleoptera are the most species-rich group on this planet today. They represent about 40% of the total insect diversity of the world. With a considerable range of landform types including significant mountain ranges, deserts, fertile irrigational plains, and hilly forested areas, India is one of the mega-diverse countries and includes more than 0.1 million faunal species. Despite having rich biodiversity, the efforts to catalogue the beetle diversity of the extant species/taxa reported from India have been less. Therefore, in this paper, the information on the beetle fauna of India is provided based on the data available with the museum collections of Zoological Survey of India and taxa extracted from zoological records and published literature. The species were listed with their valid names, synonyms, type localities, type depositories, and their distribution in states and biogeographic zones of India. The catalogue also incorporates the bibliography on Indian Coleoptera. The exhaustive species inventory, prepared by us include distributional records from Himalaya, Trans Himalaya, Desert, Semi-Arid, Western Ghats, Deccan Peninsula, Gangetic Plains, Northeast, Islands, and Coastal areas of the country. Our study concludes that many of the species are still known from their type localities only, so there is need to revisit and resurvey those collection localities for the taxonomic evaluation of those species. There are species which exhibit single locality records, and taxa-specific biodiversity assessments are required to be undertaken to understand the distributional range of such species. The primary challenge is taxonomic identifications of the species which were described before independence, and the type materials are present in overseas museums. For such species, taxonomic revisions of the different group of beetles are required to solve the problems of identification and classification.

Keywords: checklist, taxonomy, museum collections, biogeographic zones

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Authors: Luciano Tarantino, Emanuele Balzano, Aurelio Nasto

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S.R. 53 years. January 2009: HCV-related cirrhosis, Child-Pugh A5 class, EGDS no aesophageal Varices. No important comorbidities. Treated with PEG-IFN+Ribavirin (march-november 2009) with subsequent sustained virologic response. HCVRNA absent overtime. October 2016 :CT detected small HCC nodule in the VIII segment (diam.=12 mm). Treated with US guided RF-ablation. November 2016 CT: complete necrosis. Unfortunately, the patient dropped out US and CT follow-up controls.September 2018: asthenia and weight loss. CT showed a large tumor infiltrating V-VII-VI segments and complete PVTT of right portal vein and its branches . Surgical Consultation excluded indication to Liver resection and OLT . 23 october 2018: ECT of a large peri-hilar area of the tumor including the PVTT. 1 and 3 months post-treatment CT showed complete necrosis and retraction of the thrombus and residual viable tumor in the peripheral portion of the right lobe . Therefor, the patient was reevaluated for OLT and considered eligible in waiting list . March 2019: CT showed no perihilar or portal vein recurrence and distant progression in the right lobe . March 2019 : Trans-arterial-Radio-therapy (TARE) of the right lobe. Post-treatment CT demonstrated no perihilar or portal vein recurrence and extensive necrosis of the residual tumor . December 2019: CT demonstrated several recurrences of HCC infiltrating the VI and VII segment . Howewer no recurrence was observed at hepatic hilum and in portal vessels . Therefore, on February 2020 the patient received OLT. At 44 months follow-up, no complication or recurrence or liver disfunction have been observed.

Keywords: hepatocellular carcinoma, portal vein tumor thrombosis, interventional ultrasound, liver tumor ablation, liver transplantation

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Authors: Yusuf E. Mustapha, Inioluwa A Akindoyeni, Oluwatoyin G. Ezekiel, Ifeoluwa O. Awogbindin, Ebenezer O. Farombi

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Background: Parkinson's disease (PD) is the most prevalent motor disorder. Available therapies are palliative with no effect on disease progression. Kolaviron (KV), a natural anti-inflammatory and antioxidant agent, has been reported to possess neuroprotective effects in Parkinsonian flies and rats. Objective: The present study investigates the neuroprotective effect of KV, focusing on the DJ1/Nrf2 signaling pathway. Methodology: All-trans retinoic acid (ATRA, 10 mg/kg, i.p.) was used to inhibit Nrf2. Murine model of PD was established with four doses of MPTP (20 mg/kg i.p.) at 2 hours interval. MPTP mice were pre-treated with either KV (200 mg/kg/day p.o), ATRA, or both conditions for seven days before PD induction. Motor behaviour was evaluated, and markers of oxidative stress/damage and its regulators were assessed with immunofluorescence and ELISA techniques. Results: MPTP-treated mice covered less distance with reduced numbers of anticlockwise rotations, heightened freezing, and prolonged immobility when compared to control. However, KV significantly attenuated these deficits. Pretreatment of MPTP mice with KV upregulated Nrf2 expression beyond MPTP level with a remarkable reduction in Keap1 expression and marked elevation of DJ-1 level, whereas co-administration with ATRA abrogated these effects. KV treatment restored MPTP-mediated depletion of endogenous antioxidant, striatal oxidative stress, oxidative damage, and inhibition of acetylcholinesterase activity. However, ATRA treatment potentiated acetylcholinesterase inhibition and attenuated the protective effect of KV on the level of nitric oxide and activities of catalase and superoxide dismutase. Conclusion: Kolaviron protects Parkinsonian mice by stabilizing and activating the Nrf2 signaling pathway. Thus, kolaviron can be explored as a pharmacological lead in PD management.

Keywords: Garcinia kola, Kolaviron, Parkinson Disease, Nrf2, behavioral incompetence, neurodegeneration

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Authors: Umar Saeed

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Peptidyl-prolyl cis/trans isomerases Par14 and Par17 in humans play crucial roles in diverse cellular processes, including protein folding, chromatin remodeling, DNA binding, ribosome biogenesis, and cell cycle progression. However, the effects of Par14 and Par17 on viral replication have been explored to a limited extent. We first time discovered their influential roles in promoting Hepatitis B Virus replication. In this study, we observed that in the presence of HBx, either Par14 or Par17 could upregulate HBV replication. However, in the absence of HBx, neither Par14 nor Par17 had any effect on replication. Their mechanism of action involves binding to specific motifs within HBc and HBx proteins. Notably, they target the conserved 133Arg-Pro134 (RP) motif of HBc and the 19RP20-28RP29 motifs of HBx. This interaction is fundamental for the stability of HBx, core particles, and HBc. Par14 and Par17 exhibit versatility by binding both outside and inside core particles, thereby facilitating core particle assembly through their participation in HBc dimer-dimer interactions. NAGE and immunoblotting analyses unveiled the binding of Par14/Par17 to core particles. Co-immunoprecipitation experiments further demonstrated the interaction of Par14/Par17 with core particle assembly-defective and dimer-positive HBc-Y132A. It's essential to emphasize that R133 is the key residue in the HBc RP motif that governs their interaction with Par14/Par17. Chromatin immunoprecipitation conducted on HBV-infected cells elucidated the participation of residues S19 and E46/D74 in Par14 and S44 and E71/D99 in Par17 in the recruitment of 133RP134 motif-containing HBc into cccDNA. Depleting PIN4 in liver cell lines results in a significant reduction in cccDNA levels, pgRNA, sgRNAs, HBc, core particle assembly, and HBV DNA synthesis. Notably, parvulin inhibitors like juglone and PiB have proven to be effective in substantially reducing HBV replication. These inhibitors weaken the interaction between HBV core particles and Par14/Par17, underscoring the dynamic nature of this interaction. It's also worth noting that specific Par14/Par17 inhibitors hold promise as potential therapeutic options for chronic hepatitis B.

Keywords: Par14Par17, HBx, HBc, cccDNA, HBV

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Authors: María Dolores Caro, Eugenio M. Fedriani, Ángel F. Tenorio

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The transportation of dangerous goods by lorries throughout Europe must be done by using the roads conforming the European Road Transport Network. In this network, there are several parking areas where lorry drivers can park to rest according to the regulations. According to the "European Agreement concerning the International Carriage of Dangerous Goods by Road", parking areas where lorries transporting dangerous goods can park to rest, must follow several security stipulations to keep safe the rest of road users. At this respect, these lorries must be parked in adapted areas with strict and permanent surveillance measures. Moreover, drivers must satisfy several restrictions about resting and driving time. Under these facts, one may expect that there exist enough parking areas for the transport of this type of goods in order to obey the regulations prescribed by the European Union and its member countries. However, the already-existing parking areas are not sufficient to cover all the stops required by drivers transporting dangerous goods. Our main goal is, starting from the already-existing parking areas and the loading-and-unloading location, to provide an optimal answer to the following question: how many additional parking areas must be built and where must they be located to assure that lorry drivers can transport dangerous goods following all the stipulations about security and safety for their stops? The sense of the word “optimal” is due to the fact that we give a global solution for the location of parking areas throughout the whole European Road Transport Network, adjusting the number of additional areas to be as lower as possible. To do so, we have modeled the problem using graph theory since we are working with a road network. As nodes, we have considered the locations of each already-existing parking area, each loading-and-unloading area each road bifurcation. Each road connecting two nodes is considered as an edge in the graph whose weight corresponds to the distance between both nodes in the edge. By applying a new efficient algorithm, we have found the additional nodes for the network representing the new parking areas adapted for dangerous goods, under the fact that the distance between two parking areas must be less than or equal to 400 km.

Keywords: trans-european transport network, dangerous goods, parking areas, graph-based modeling

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Authors: Ahmed Al-Awthan

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This study addresses the prevalence of English terminology in published Arabic documentation on social media. Although the problem of using English terms in translation instead of existing native ones has been addressed in general by researchers around the world, to the best of the author’s knowledge the attitude of the translators as professionals to this phenomenon in Qatar and Yemen has not received a detailed study. This study examines the impact of the use of English, social media terms in the Arab world on aspiring and professional translators; it explores the benefits and drawbacks of linguistic borrowing as identified by the translators and investigates whether translators consider any means of resisting linguistic borrowing and prioritizing Arabic. It also aims to answer the following questions: i. Is there any prevalence of English, social media terms in Arabic translation? Why or why not? ii. Do Arabic translators prefer using English, social media terms to their equivalents in Arabic? If so, why? iii. Which measures could be adopted to help reduce the frequently observed borrowing of English terms? In particular, how do translators see the role of the Arabic Language Academies in preserving Arabic? iv. This research is descriptive, comparative and analytical in nature. It is both qualitative and quantitative. To validate the problem, the researcher will analyze articles published by Al-Jazeera in 2016-2018 that refer to the use of social media in diplomacy. It will be examined whether the increased international discussion of political events in social media increased the amount of transliterated English terminology referring to this mode of communication.To investigate whether the translators recognize the phenomenon of borrowing, the researcher proposes to use a survey. This survey will use multiple choice questions. It will target 20 aspiring translators from Yemen and 20 participants from Qatar. It will offer 15 English, social media terms used in discourse in 15 sentences. For each sentence, the researcher will provide three different translations and will ask the translators to rate them and offer their rendition. After collecting all the answers online, the researcher will analyze the data. The results are expected to confirm whether there is a prevalence of English terms in translating into Arabic. It is also expected to show what measures the translators used to render the English, social media terms, and it raises awareness of borrowing English terms. It will guide the translator toward using Arabicization methods in order to contribute to preserving Arabic.

Keywords: Arabicization, trans lingual borrowing, social media terms, terminology

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Authors: Zelalem B. Gurmessa, Ignatius W. Ferreira, Henry F. Wissink

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The aim of this paper is to critically examine the factors contributing to academic brain drain in the Sub-Saharan Africa with specific reference to the higher education sector. Africa in general and Sub-Saharan African (SSA) countries, in particular, are experiencing an exodus of highly trained, qualified and competent human resources to other developing and developed countries thereby threatening the overall development of the relevant regions and impeding both public and private service delivery systems in the nation states. The region is currently in a dire situation in terms of health care services, education, science, and technology. The contribution of SSA countries to Science, Technology and Innovation is relatively minimal owing to the migration of skilled professionals due to both push and pull factors. The phenomenon calls for both international and trans-boundary, regional, national and institutional interventions to curb the exodus. Based on secondary data and the review of the literature, the article conceptualizes the antecedents and impacts of human capital flight or brain drain in the SSA countries from a higher education perspective. To this end, the article explores the magnitude, causes, and impacts of brain drain in the region. Despite the lack of consistent data on the magnitude of academic brain drain in the region, a critical analysis of the existing sources shows that pay disparity between developing and developed countries, the lack of enabling working conditions at source countries, fear of security due to political turmoil or unrest, the availability of green pastures and opportunity for development in the receiving countries were identified as major factors contributing to academic brain drain in the region. This hampers the socio-economic, technological and political development of the region. The paper also recommends that further research can be undertaken on the magnitude, causes, characteristics and impact of brain drain on the sustainability and competitiveness of SSA higher education institutions in the region.

Keywords: brain drain, higher education, sub-Saharan Africa, sustainable development

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Authors: Navpreet Kaur, Himkusha Thakur, Nirmal Prabhakar

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The most controversial issue in crop production is the use of Organophosphate insecticides. This is evident in many reports that Organophosphate (OP) insecticides, among the broad range of pesticides are mainly involved in acute and chronic poisoning cases. OPs detection is of crucial importance for health protection, food and environmental safety. In our study, a nanocomposite of poly (3,4 ethylenedioxythiophene) (PEDOT) and multi-walled carbon nanotubes (MWCNTs) has been deposited electrochemically onto the surface of fluorine doped tin oxide sheets (FTO) for the analysis of malathion OP. The -COOH functionalization of MWCNTs has been done for the covalent binding with amino groups of AChE enzyme. The use of PEDOT-MWCNT films exhibited an excellent conductivity, enables fast transfer kinetics and provided a favourable biocompatible microenvironment for AChE, for the significant malathion OP detection. The prepared biosensors were characterized by Fourier transform infrared spectrometry (FTIR), Field emission-scanning electron microscopy (FE-SEM) and electrochemical studies. Various optimization studies were done for different parameters including pH (7.5), AChE concentration (50 mU), substrate concentration (0.3 mM) and inhibition time (10 min). Substrate kinetics has been performed and studied for the determination of Michaelis Menten constant. The detection limit for malathion OP was calculated to be 1 fM within the linear range 1 fM to 1 µM. The activity of inhibited AChE enzyme was restored to 98% of its original value by 2-pyridine aldoxime methiodide (2-PAM) (5 mM) treatment for 11 min. The oxime 2-PAM is able to remove malathion from the active site of AChE by means of trans-esterification reaction. The storage stability and reusability of the prepared biosensor is observed to be 30 days and seven times, respectively. The application of the developed biosensor has also been evaluated for spiked lettuce sample. Recoveries of malathion from the spiked lettuce sample ranged between 96-98%. The low detection limit obtained by the developed biosensor made them reliable, sensitive and a low cost process.

Keywords: PEDOT-MWCNT, malathion, organophosphates, acetylcholinesterase, biosensor, oxime (2-PAM)

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Authors: Menna Ewida, Dalal Abou El-Ella, Dina Lasheen, Huessin El-Subbagh

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Introduction: Vascular Endothelial Growth Factor receptor (VEGF) is a signal protein produced by cells that stimulates vasculogenesis to create new blood vessels. VEGF family binds to three trans-membrane tyrosine kinase receptors,Dihydrofolate reductase (DHFR) is an enzyme of crucial importance in medicinal chemistry. DHFR catalyzes the reduction 7,8 dihydro-folate to tetrahydrofolate and intimately couples with thymidylate synthase which is a pivotal enzyme that catalysis the reductive methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) utilizing N5,N10-methylene tetrahydrofolate as a cofactor which functions as the source of the methyl group. Purpose: Novel substituted Thiazole agents were designed as DHFR and VEGF-TK inhibitors with increased synergistic activity and decreased side effects. Methods: Five series of compounds were designed with a rational that mimic the pharmacophoric features present in the reported active compounds that target DHFR & VEGFR. These molecules were docked against Methotrexate & Sorafenib as controls. An in silico ADMET study was also performed to validate the bioavailability of the newly designed compounds. The in silico molecular docking & ADMET study were also applied to the non-classical antifolates for comparison. The interaction energy comparable to that of MTX for DHFRI and Sorafenib for VEGF-TKI activity were recorded. Results: Compound 5 exhibited the highest interaction energy when docked against Sorafenib, While Compound 9 showed the highest interaction energy when docked against MTX with the perfect binding mode. Comparable results were also obtained for the ADMET study. Most of the compounds showed absorption within (95-99) zone which varies according to the type of substituents. Conclusions: The Substituted Thiazole Analogues could be a suitable template for antitumor drugs that possess enhanced bioavailability and act as DHFR and VEGF-TK inhibitors.

Keywords: anti-tumor agents, DHFR, drug design, molecular modeling, VEGFR-TKIs

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