Search results for: knowledge exchange model

Authors: Amir Abbas Fatemi, Zahra Tabrizian, Kabir Sadeghi

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To find the location and severity of damage that occurs in a structure, characteristics changes in dynamic and static can be used. The non-destructive techniques are more common, economic, and reliable to detect the global or local damages in structures. This paper presents a non-destructive method in structural damage detection and assessment using GA and static data. Thus, a set of static forces is applied to some of degrees of freedom and the static responses (displacements) are measured at another set of DOFs. An analytical model of the truss structure is developed based on the available specification and the properties derived from static data. The damages in structure produce changes to its stiffness so this method used to determine damage based on change in the structural stiffness parameter. Changes in the static response which structural damage caused choose to produce some simultaneous equations. Genetic Algorithms are powerful tools for solving large optimization problems. Optimization is considered to minimize objective function involve difference between the static load vector of damaged and healthy structure. Several scenarios defined for damage detection (single scenario and multiple scenarios). The static damage identification methods have many advantages, but some difficulties still exist. So it is important to achieve the best damage identification and if the best result is obtained it means that the method is Reliable. This strategy is applied to a plane truss. This method is used for a plane truss. Numerical results demonstrate the ability of this method in detecting damage in given structures. Also figures show damage detections in multiple damage scenarios have really efficient answer. Even existence of noise in the measurements doesn’t reduce the accuracy of damage detections method in these structures.

Keywords: damage detection, finite element method, static data, non-destructive, genetic algorithm

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Authors: D. S. Gomes, A. T. Silva

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Analysis of the uncertainty quantification related to nuclear safety margins applied to the nuclear reactor is an important concept to prevent future radioactive accidents. The nuclear fuel performance code may involve the tolerance level determined by traditional deterministic models producing acceptable results at burn cycles under 62 GWd/MTU. The behavior of nuclear fuel can simulate applying a series of material properties under irradiation and physics models to calculate the safety limits. In this study, theoretical predictions of nuclear fuel failure under transient conditions investigate extended radiation cycles at 75 GWd/MTU, considering the behavior of fuel rods in light-water reactors under reactivity accident conditions. The fuel pellet can melt due to the quick increase of reactivity during a transient. Large power excursions in the reactor are the subject of interest bringing to a treatment that is known as the Fuchs-Hansen model. The point kinetic neutron equations show similar characteristics of non-linear differential equations. In this investigation, the multivariate logistic regression is employed to a probabilistic forecast of fuel failure. A comparison of computational simulation and experimental results was acceptable. The experiments carried out use the pre-irradiated fuels rods subjected to a rapid energy pulse which exhibits the same behavior during a nuclear accident. The propagation of uncertainty utilizes the Wilk's formulation. The variables chosen as essential to failure prediction were the fuel burnup, the applied peak power, the pulse width, the oxidation layer thickness, and the cladding type.

Keywords: logistic regression, reactivity-initiated accident, safety margins, uncertainty propagation

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Authors: S. Chandrakaran, G. Govind

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Stone columns are effectively used to improve bearing strength of soils and also for many geotechnical applications. In soft soils when stone columns are loaded they undergo large settlements due to insufficient lateral confinement. Use of geosynthetics encasement has proved to be a solution for this problem. In this paper, results of a laboratory experimental study carried out with model stone columns with and without encasement. Sand was used for making test beds, and grain size of soil varies from 0.075mm to 4.75mm. Woven geotextiles produced by Gareware ropes India with mass per unit area of 240gm/M2 and having tensile strength of 52KN/m is used for the present investigation. Tests were performed with large scale direct shear box and also using scaled laboratory plate load tests. Stone column of 50mm and 75mm is used for the present investigation. Diameter of stone column, size of stones used for making stone columns is varied in making stone column in the present study. Two types of stone were used namely small and bigger in size. Results indicate that there is an increase in angle of internal friction and also an increase in the shear strength of soil when stone columns are encased. With stone columns with 50mm dia, an average increase of 7% in shear strength and 4.6 % in angle of internal friction was achieved. When large stones were used increase in the shear strength was 12.2%, and angle of internal friction was increased to 5.4%. When the stone column diameter has increased to 75mm increase in shear strength and angle of internal friction was increased with smaller size of stones to 7.9 and 7.5%, and with large size stones, it was 7.7 and 5.48% respectively. Similar results are obtained in plate load tests, also.

Keywords: stone columns, encasement, shear strength, plate load test

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Authors: Khaled M. Nabil

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This paper introduces the Nested Vortexes conception of the universe structure and interprets all the physical phenomena according this conception. The paper first reviews recent physics theories, either in microscopic scale or macroscopic scale, to collect evidence that the space is not empty. But, these theories describe the property of the space medium without determining its structure. Determining the structure of space medium is essential to understand the mechanism that leads to its properties. Without determining the space medium structure, many phenomena; such as electric and magnetic fields, gravity, or wave-particle duality remain uninterpreted. Thus, this paper introduces a conception about the structure of the universe. It assumes that the universe is a medium of ultra-tiny homogeneous particles which are still undiscovered. Like any medium with certain movements, possibly because of a great asymmetric explosion, vortexes have occurred. A vortex condenses the ultra-tiny particles in its center forming a bigger particle, the bigger particles, in turn, could be trapped in a bigger vortex and condense in its center forming a much bigger particle and so on. This conception describes galaxies, stars, protons as particles at different levels. Existing of the particle’s vortexes make the consistency of the speed of light postulate is not true. This conception shows that the vortex motion dynamic agrees with the motion of all the universe particles at any level. An experiment has been carried out to detect the orbiting effect of aggregated vortexes of aligned atoms of a permanent magnet. Based on the described particle’s structure, the gravity force of a particle and attraction between particles as well as charge, electric and magnetic fields and quantum mechanics characteristics are interpreted. All augmented physics phenomena are solved.

Keywords: astrophysics, cosmology, particles’ structure model, particles’ forces

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Authors: Matthias Haerri, Tobias Huettche, Clemens Kustner

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This article discusses the impact of digitization on business valuation. In order to become and remain ‘digital’, investments are necessary whose return on investment (ROI) often remains vague. This uncertainty is contradictory for a valuation, that rely on predictable cash flows, fixed capital structures and the steady state. However digitisation does not make a company valuation impossible, but traditional approaches must be reconsidered. The authors identify four areas that are to be changing: (1) Tools instead of intuition - In the future, company valuation will neither be art nor science, but craft. This does not require intuition, but experience and good tools. Digital evaluation tools beyond Excel will therefore gain in importance. (2) Real-time instead of deadline - At present, company valuations are always carried out on a case-by-case basis and on a specific key date. This will change with the digitalization and the introduction of web-based valuation tools. Company valuations can thus not only be carried out faster and more efficiently, but can also be offered more frequently. Instead of calculating the value for a previous key date, current and real-time valuations can be carried out. (3) Predictive planning instead of analysis of the past - Past data will also be needed in the future, but its use will not be limited to monovalent time series or key figure analyses. With pictures of ‘black swans’ and the ‘turkey illusion’ it was made clear to us that we build forecasts on too few data points of the past and underestimate the power of chance. Predictive planning can help here. (4) Convergence instead of residual value - Digital transformation shortens the lifespan of viable business models. If companies want to live forever, they have to change forever. For the company valuation, this means that the business model valid on the valuation date only has a limited service life.

Keywords: business valuation, corporate finance, digitisation, disruption

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Authors: Gonzalo Ortiz de Elguea-Culebras, Raúl Sánchez-Vioquea, Adela Mena-Morales, Manuel Alaiz, Enrique Melero-Bravo, Esteban García-Romero, Javier Vioque, Lourdes Marchante-Cuevas, Julio Girón-Calle

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Saffron (Crocus sativus L.) is a highly valued crop for the manufacture of spice that consists of the dried stigma of the flowers. This is in contrast to other underutilized parts of the saffron plant as leaves, which represent abundant biomass whose use might help to enhance the sustainability of the saffron crop. Saffron leaves contain significant amounts of phenolic compounds, 7.8 equivalent grams of gallic acid per 100g of extract, and are very promising compounds in terms of exploring novel uses of saffron leaves. Given that phenolic compounds have numerous effects on cancer-related biological pathways, we have investigated the in vitro antiproliferative effect of saffron leaf polyphenols against human colon adenocarcinoma cells (Caco-2). Polyphenols were extracted from leaves with 70% ethanol, defatted with hexane, and purified by solid phase extraction using C18 silica gel and then silica gel 60. Analysis of polyphenols was performed by HPLC-ESI-MS. Di-, tri-, and tetrahexosides of quercetin, kaempferol, and isorhamnetin, as well as C-hexosides like isoorientin and vitexin, were tentatively identified. Polyphenols strongly inhibited the proliferation of Caco-2 cells, which is consistent with model studies in which several of the polyphenols identified in saffron leaves have demonstrated their potential as chemopreventive agents in cancer. Due to the low profitability that saffron leaf currently represents, we consider these results very encouraging and that this by-product deserves further investigation as a potential source of active molecules against colorectal cancer.

Keywords: saffron leaves, agricultural by-products, polyphenols, antiproliferative effect, human colon adenocarcinoma cells

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Authors: Debasmita Mukhopadhyay, Manika Pal Bhadra

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MiRNAs contribute to oncogenesis either as tumor suppressors or oncogenes. Hence, discovery of miRNA-based therapeutics are imperative to ameliorate cancer. Modulation of miRNA maturation is accomplished via several therapeutic agents, including small molecules and oligonucleotides. Due to the attractive pharmacokinetic properties of small molecules over oligonucleotides, we set to identify small molecule inhibitors of a metastasis-inducing microRNA. Cytotoxicity profile of aza-flavanone C1 was analyzed in a panel of breast cancer cells employing the NCI-60 screen protocols. Flow cytometry, immunofluorescence and western blotting of apoptotic or EMT markers were performed to analyze the effect of C1. A dual luciferase assay unequivocally suggested that C1 repressed endogenous miR-10b in MDA-MB-231 cells. A derivative of aza-flavanone C1 is shown as a strong inhibitor miR-10b. Blockade of miR-10b by C1 resulted in decreased expression of miR-10b targets in an aggressive breast cancer cell line model, MDA-MB-231. Abrogation of TWIST1, an EMT-inducing transcription factor also contributed to C1 mediated apoptosis. Moreover C1 exhibited a specific and selective down-regulation of miR-10b and did not function as a general inhibitor of miRNA biogenesis or other oncomiRs of breast carcinoma. Aza-flavanone congener C1 functions as a potent inhibitor of the metastasis-inducing microRNA, miR-10b. Our present study provides evidence for targeting metastasis-inducing microRNA, miR-10b with a derivative of Aza-flavanone. Better pharmacokinetic properties of small molecules place them as attractive agents compared to nucleic acids based therapies to target miRNA. Further work, in generating analogues based on aza-flavanone moieties will significantly improve the affinity of the small molecules to bind miR-10b. Finally, it is imperative to develop small molecules as novel miRNA-therapeutics in the fight against cancer.

Keywords: breast cancer, microRNA, metastasis, EMT

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Authors: K. O'Malley

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Background: The emergence and rapid evolution of large language models (LLMs) (i.e., models of generative artificial intelligence, or AI) has been unprecedented. ChatGPT is one of the most widely used LLM platforms. Using natural language processing technology, it generates customized responses to user prompts, enabling it to mimic human conversation. Responses are generated using predictive modeling of vast internet text and data swathes and are further refined and reinforced through user feedback. The popularity of LLMs is increasing, with a growing number of students utilizing these platforms for study and revision purposes. Notwithstanding its many novel applications, LLM technology is inherently susceptible to bias and error. This poses a significant challenge in the educational setting, where academic integrity may be undermined. This study aims to evaluate the performance of the latest iteration of ChatGPT (ChatGPT4.0) in standardized state medical licensing examinations. Methods: A considered search strategy was used to interrogate the PubMed electronic database. The keywords ‘ChatGPT’ AND ‘medical education’ OR ‘medical school’ OR ‘medical licensing exam’ were used to identify relevant literature. The search included all peer-reviewed literature published in the past five years. The search was limited to publications in the English language only. Eligibility was ascertained based on the study title and abstract and confirmed by consulting the full-text document. Data was extracted into a Microsoft Excel document for analysis. Results: The search yielded 345 publications that were screened. 225 original articles were identified, of which 11 met the pre-determined criteria for inclusion in a narrative synthesis. These studies included performance assessments in national medical licensing examinations from the United States, United Kingdom, Saudi Arabia, Poland, Taiwan, Japan and Germany. ChatGPT 4.0 achieved scores ranging from 67.1 to 88.6 percent. The mean score across all studies was 82.49 percent (SD= 5.95). In all studies, ChatGPT exceeded the threshold for a passing grade in the corresponding exam. Conclusion: The capabilities of ChatGPT in standardized academic assessment in medicine are robust. While this technology can potentially revolutionize higher education, it also presents several challenges with which educators have not had to contend before. The overall strong performance of ChatGPT, as outlined above, may lend itself to unfair use (such as the plagiarism of deliverable coursework) and pose unforeseen ethical challenges (arising from algorithmic bias). Conversely, it highlights potential pitfalls if users assume LLM-generated content to be entirely accurate. In the aforementioned studies, ChatGPT exhibits a margin of error between 11.4 and 32.9 percent, which resonates strongly with concerns regarding the quality and veracity of LLM-generated content. It is imperative to highlight these limitations, particularly to students in the early stages of their education who are less likely to possess the requisite insight or knowledge to recognize errors, inaccuracies or false information. Educators must inform themselves of these emerging challenges to effectively address them and mitigate potential disruption in academic fora.

Keywords: artificial intelligence, ChatGPT, generative ai, large language models, licensing exam, medical education, medicine, university

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Authors: An Chengrui, Yin Zi, Wu Bingbing, Ma Yuanzhu, Jin Kaixiu, Chen Xiao, Ouyang Hongwei

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Single cell RNA sequence (scRNA-seq) is one of the effective tools to study transcriptomics of biological processes. Recently, similarity measurement of cells is Euclidian distance or its derivatives. However, the process of scRNA-seq is a multi-variate Bernoulli event model, thus we hypothesize that it would be more efficient when the divergence between cells is valued with relative entropy than Euclidian distance. In this study, we compared the performances of Euclidian distance, Spearman correlation distance and Relative Entropy using scRNA-seq data of the early, medial and late stage of limb development generated in our lab. Relative Entropy is better than other methods according to cluster potential test. Furthermore, we developed KL-SNE, an algorithm modifying t-SNE whose definition of divergence between cells Euclidian distance to Kullback–Leibler divergence. Results showed that KL-SNE was more effective to dissect cell heterogeneity than t-SNE, indicating the better performance of relative entropy than Euclidian distance. Specifically, the chondrocyte expressing Comp was clustered together with KL-SNE but not with t-SNE. Surprisingly, cells in early stage were surrounded by cells in medial stage in the processing of KL-SNE while medial cells neighbored to late stage with the process of t-SNE. This results parallel to Heatmap which showed cells in medial stage were more heterogenic than cells in other stages. In addition, we also found that results of KL-SNE tend to follow Gaussian distribution compared with those of the t-SNE, which could also be verified with the analysis of scRNA-seq data from another study on human embryo development. Therefore, it is also an effective way to convert non-Gaussian distribution to Gaussian distribution and facilitate the subsequent statistic possesses. Thus, relative entropy is potentially a better way to determine the divergence of cells in scRNA-seq data analysis.

Keywords: Single cell RNA sequence, Similarity measurement, Relative Entropy, KL-SNE, t-SNE

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Authors: Yujie Zhou, Hee-Seong Byun, Sang-In Bak, Eui-Joon Kil, Kyung Joo Min, Vivek Chavan, Won Kyong Cho, Sukchan Lee, Seung-Woo Hong, Tae-Sun Park

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Fast neutron irradiation (FNI) can cause mutations on plant genome but, in the most of cases, these irradiated plants have not shown significant characteristics phenotypically. In this study, we utilized RNA-Seq to generate a high-resolution transcriptome map of the tomato (Solanum lycopersicum) genome effected by FNI. To quantify the different transcription levels in tomato irradiated by FNI, tomato seeds were irradiated by using MC-50 cyclotron (KIRAMS, Korea) for 0, 30 and 90 minutes, respectively. To investigate the effects on the pre-soaking condition, experimental groups were divided into dry and soaked seeds, which were soaked for 8 hours before irradiation. There was no noticeable difference in the percentage germination (PG) among dry seeds, while irradiated soaked seeds have about 10 % lower PG compared to the unirradiated control group. Using whole transcriptome sequencing by HiSeq 2000, we analyzed the differential gene expression in response to different time of FNI in dry and soaked seeds. More than 1.4 million base pair reads were mapped onto the tomato reference genome and the expression pattern differences between irradiated and unirradiated seeds were assessed. In 0, 30 and 90 minutes irradiation, 12,135, 28,495 and 28,675 transcripts were generated, respectively. Gene ontology analysis suggested the different enrichment of transcripts involved in response to different FNI. The present study showed that FNI effects on plant gene expression, which can become a new parameters for evaluating the responses against FNI on plants. In addition, the comparative analysis of differentially expressed genes in D and S seeds by FNI will also give us a chance to deep explore novel candidate genes for FNI, which could be a good model system to understand the mechanisms behind the adaption of plant to space biology research.

Keywords: tomato (solanum lycopersicum), fast neutron irradiation, RNA-sequence, transcriptome expression

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Authors: Xiaohui Pan

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As the most influential media for the dissemination of Chinese culture, films and television dramas have played cognitive orientation in guiding young audience to understand its cultural value. Taking a retrospective overview of the Chinese domestic film and television dramas in the last decade, it is tangible to notice that Westernization has become irresistible force in the presentation of Chinese youth culture, such as the rise of sensibility, publicity of subjectivity, and the resistance to mainstream discourse. However, the process of deconstruction and transition of these film and television works on Western youth culture brought about more comprehensive conflicts and integration rather than providing a panoramic interpretation to young Chinese. Issues of tradition and modernization, oriental and Western, and serious thinking and the spirit of entertainment overwhelmed those Chinese works. This study attempts to examine the mechanism of young Chinese’s resistance, compromise and re-construction in their marriages during the dynamic cultural intergration between traditional Chinese culture and Western culture. To investigate such a mechanism, this study analyzed four Chinese television dramas themed on family ethics to reveal the conflictions between two generations, mother-in-law and daughter-in-law, aiming to identify their strategies of their struggles. Incorporating the theory of Scott's weapons of the weak, this study examines the dynamic model of the struggles content analysis on their hidden language and the power. The finding shows that young Chinese identified their self-awakening during the resistance. The study also finds out that the external factors might have the functions of switching the power from the strong end to the weak end. The finding of this study can provide useful insights for researchers in this area and for those in the process of exploring cultural integration issues.

Keywords: intergration, integration, resistance, youth culture

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Authors: Shima Soleimani, Steven Eckels

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One area of special importance for the surface-level study of heat exchangers is tubes with internal micro-fins (< 0.5 mm tall). Micro-finned surfaces are a kind of extended solid surface in which energy is exchanged with water that acts as the source or sink of energy. Significant performance gains are possible for either shell, tube, or double pipe heat exchangers if the best surfaces are identified. The parametric studies of micro-finned tubes that have appeared in the literature left some key parameters unexplored. Specifically, they ignored three-dimensional (3D) micro-fin configurations, conduction heat transfer in the fins, and conduction in the solid surface below the micro-fins. Thus, this study aimed at implementing a parametric study of 3D micro-finned tubes that considered micro-fine height and discontinuity features. A 3D conductive and convective heat-transfer simulation through coupled solid and periodic fluid domains is applied in a commercial package, ANSYS Fluent 19.1. The simulation is steady-state with turbulent water flow cooling the inner wall of a tube with micro-fins. The simulation utilizes a constant and uniform temperature on the tube outer wall. Performance is mapped for 18 different simulation cases, including a smooth tube using a realizable k-ε turbulence model at a Reynolds number of 48,928. Results compared the performance of 3D tubes with results for the similar two-dimensional (2D) one. Results showed that the micro-fine height has a greater impact on performance factors than discontinuity features in 3D micro-fin tubes. A transformed 3D micro-fin tube can enhance heat transfer, and pressure drops up to 21% and 56% compared to a 2D one, respectfully.

Keywords: three-dimensional micro-fin tube, heat transfer, friction factor, heat exchanger

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Authors: Catalina Iticescu, Lucian Georgescu, Mihaela Timofti, Dumitru Dima, Gabriel Murariu

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The amounts of sludge resulting from the treatment of domestic and industrial wastewater can create serious environmental problems if no solutions are found to eliminate them. At present, the predominant method of sewage sludge disposal is to store and use them in agricultural applications. The sewage sludge has fertilizer properties and can be used to enrich agricultural soils due to the nutrient content. In addition to plant growth (nitrogen and phosphorus), the sludge also contains heavy metals in varying amounts. An increasingly used method is the incineration of sludge. Thermal processes can be used to convert large amounts of sludge into useful energy. The sewage sludge analyzed for the present paper was extracted from the Wastewater Treatment Station (WWTP) Galati, Romania. The physico-chemical parameters determined were: pH (upH), nutrients and heavy metals. The determination methods were electrochemical, spectrophotometric and energy dispersive X–ray analyses (EDX). The results of the tests made on the content of nutrients in the sewage sludge have shown that existing nutrients can be used to increase the fertility of agricultural soils. The conclusion reached was that these sludge can be safely used on agricultural land and with good agricultural productivity results. To be able to use sewage sludge as a fuel, we need to know its calorific values. For wet sludge, the caloric power is low, while for dry sludge it is high. Higher calorific value and lower calorific value are determined only for dry solids. The apparatus used to determine the calorific power was a Parr 6755 Solution Calorimeter Calorimeter (Parr Instrument Company USA 2010 model). The calorific capacities for the studied sludge indicate that they can be used successfully in incinerators. Mixed with coal, they can also be used to produce electricity. The advantages are: it reduces the cost of obtaining electricity and considerably reduces the amount of sewage sludge.

Keywords: agriculture, incinerators, properties, sewage sludge

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Authors: Morteza Raminnia

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In this study, dynamic analysis of functionally graded nano-composite pipe reinforced by single-walled carbon nano-tubes (SWCNTs) with simply supported boundary condition subjected to moving mechanical loads is investigated. The material properties of functionally graded carbon nano tube-reinforced composites (FG-CNTRCs) are assumed to be graded in the thickness direction and are estimated through a micro-mechanical model. In this paper polymeric matrix considered as isotropic material and for the CNTRC, uniform distribution (UD) and three types of FG distribution patterns of SWCNT reinforcements are considered. The system equation of motion is derived by using Hamilton's principle under the assumptions of first order shear deformation theory (FSDT).The thin piezoelectric layers embedded on inner and outer surfaces of FG-CNTRC layer are acted as distributed sensor and actuator to control dynamic characteristics of the FG-CNTRC laminated pipe. The modal analysis technique and Newmark's integration method are used to calculate the displacement and dynamic stress of the pipe subjected to moving loads. The effects of various material distribution and velocity of moving loads on dynamic behavior of the pipe is presented. This present approach is validated by comparing the numerical results with the published numerical results in literature. The results show that the above-mentioned effects play very important role on dynamic behavior of the pipe .This present work shows that some meaningful results that which are interest to scientific and engineering community in the field of FGM nano-structures.

Keywords: nano-composite, functionally garded material, moving load, active control, PZT layers

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Authors: Yahia Massinissa, Henhouda Affaf, Yahia Mouloud

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The aim of this study was to investigate the toxicity; analgesic and anti-pyretic properties of standardized HA methanolic extract (HAMeOH) in vivo. The acute toxicity study was performed on rats while adopting the OECD-420 Guidelines (fixed dose procedure). Assessment of analgesic activity was performed in rats with two analgesic models. One was acetic acid induced writhing response and the other formalin-induced paw licking. The anti-pyretic effect was tested by brewer’s yeast induced fever in rats. For the acute toxicity test, the higher dose administration of 2000 mg/kg bw. of Hyoscyamus albus did not produce any toxic signs or deaths in rats. There were no significant differences (p>0.05) in the body and organ weights between control and treated groups. The (LD50) of Hyoscyamus albus was higher than 2000 g/kg bw. In subacute toxicity study, no mortality and toxic signs were observed with the doses of 100 and 200 mg/kg bw. of extracts of for 28 consecutive days. These analgesic experimental results indicated that HAMeOH (100 mg/kg and 200 mg/kg) decreased the acetic acid-induced writhing responses and HAMeOH (100 mg/kg and 200 mg/kg) decreased the licking time in the second phase of the formalin test. Moreover, in the model of yeast induced elevation of the body temperature HAMeOH showed dose-dependent lowering of the body temperature up to 3h at both the doses these results obtained, were comparable to that of paracetamol. The present findings indicate that the leaves of Hyoscyamus albus L. possess potent analgesic and antipyretic activity.

Keywords: Hyoscyamus albus, methanolic extract, toxicity, analgesic activity, antipyretic activity, formalin test

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Authors: Betül Gelengül Eki̇mci̇, Semra Günay Aktaş

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Festive, habitual activities celebrated on the specified date by a local community, are conducive to recognition of the region. The main function of festive events is to help gathering people via an annual celebration to create an atmosphere of understanding and the opportunity to participate in the joy of life. At the same time, festive events may serve as special occasions on which immigrants return home to celebrate with their family and community, reaffirming their identity and link to the community’s traditions. Festivals also support the local economy by bringing in different visitors to the region. The tradition of “Beet Brewing-Molasses Production,” which is held in İdrisyayla Village is an intangible cultural heritage with customs, traditions, and rituals carrying impacts of cuisine culture of Rumelian immigrants in the Ottoman. After the harvest of the beet plant in the autumn season of the year, Beet Brewing Molasses syrup is made by traditional production methods with co-op of the local community. Festive occurring brewing paste made process provided transmission of knowledge and experience to the young generations. Making molasses, which is a laborious process, is accompanied by folk games such as "sayacı," which is vital element of the festive performed in İdrisyayla. Performance provides enjoyable time and supporting motivation. Like other forms of intangible cultural heritage, “Beet Brewing-Molasses Festive in İdrasyayla is threatened by rapid urbanisation, young generation migration, industrialisation and environmental change. The festive events are threatened with gradual disappearance due to changes communities undergo in modern societies because it depends on the broad participation of practitioners. Ensuring the continuity of festive events often requires the mobilization of large numbers of individuals and the social, political and legal institutions and mechanisms of society. In 2015, Intangible cultural heritage research project with the title of "İdrisyayla Molasses Process" managed by the Eskişehir Governorship, City Directorate of Culture and Tourism and Anadolu University, project members took part in the festival organization to promote sustainability, making it visible, to encourage the broadest public participation possible, to ensure public awareness on the cultural importance. To preserve the originality of and encourage participation in the festive İdrisyayla, local associations, researchers and institutions created foundation and supports festive events, such as "sayacı" folk game, which is vital element of the festive performed in İdrisyayla. Practitioners find new opportunity to market İdrisyayla Molasses production. Publicity program through the press and exhibition made it possible to stress the cultural importance of the festive in İdrisyayla Village. The research reported here used a survey analysis to evaluate an affect of the festive after the spirit of the 2015 Festive in İdrisyayla Village. Particular attention was paid to the importance of the cultural aspects of the festival. Based on a survey of more than a hundred festival attendees, several recommendations are made to festival planners. Results indicate that the variety of festive activities and products offered for sale very important to attendees. The local participants care product sales rather than cultural heritage.

Keywords: agritourism, cultural tourism, festival, sustainable cultural heritage

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Authors: Mohammadreza Khanmohammadi, Noureddin Nakhostin Ansari, Soofia Naghdi

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Purpose: Our study aimed to validate single item presenteeism question (SIPQ) into the Persian language for patients with low back pain. Background information: low back pain is a common health problem, and it is one of the most prevalent disorder in working people. There are the different subjective way to evaluate the effect of back pain on work productivity that one of them is by implementing single item presenteeism question. This question has not been validated into the Persian language. Method: Patients were asked to answer SIPQ and pain from 0 to 10 according to numerical rating scale (NRS). The functional rating index was administrated to evaluate construct validity. For test-retest reliability, almost 50 patients re-completed the Persian SIPQ. The construct validity of SIPQ was assessed by analyzing Spearman rank correlation between this question and the Persian version of Functional rating index questionnaire. To analyze test-retest reliability, we assessed intraclass correlation coefficient (agreement) (ICC agreement) (two-way random effects model, single measure). Results: The SIPQ score of two groups of patients (84 males, 16 females, mean age ±SD: 33.85±11.16 years, range: 19-67 years) and healthy subjects (48 male, 2 female ones, mean age ±SD: 24.24 ±8.07 years) was statistically significant. (Mann-Whitney U =198.00, P<.001). The Spearman correlation of data showed that there is a significant correlation between Persian SIPQ score and Persian FRI band (r= .559, P<.001). The ICC was .62. So, the analysis indicated good, test-retest reliability. Conclusion: This study showed that Persian version of SIPQ is reliable and valid when applied to back pain patients.

Keywords: cross cultural adaptation, economic burden, low back pain, Persian language, translation

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Authors: Mehran Nasiri, Ardeshir Poornemat

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The aim of this study was to investigate the current and ideal situations of the process of talent identification in Iranian football from the point of view of Iranian instructors of the Asian Football Confederation (AFC). This research was a descriptive-analytical study; in data collection phase a questionnaire was used, whose face validity was confirmed by experts of Physical Education and Sports Science. The reliability of questionnaire was estimated through the use of Cronbach's alpha method (0.91). This study involved 122 participants of Iranian instructors of the AFC who were selected based on stratified random sampling method. Descriptive statistics were used to describe the variables and inferential statistics (Chi-square) were used to test the hypotheses of the study at significant level (p ≤ 0.05). The results of Chi-square test related to the point of view of Iranian instructors of the AFC showed that the grass-roots scientific method was the best way to identify football players (0.001), less than 10 years old were the best ages for talent identification (0.001), the Football Federation was revealed to be the most important organization in talent identification (0.002), clubs were shown to be the most important institution in developing talents (0.001), trained scouts of Football Federation were demonstrated to be the best and most appropriate group for talent identification (0.001), and being referred by the football academy coaches was shown to be the best way to attract talented football players in Iran (0.001). It was also found that there was a huge difference between the current and ideal situation of the process of talent identification in Iranian football from the point of view of Iranian instructors of the AFC. Hence, it is recommended that the policy makers of talent identification for Iranian football provide a comprehensive, clear and systematic model of talent identification and development processes for the clubs and football teams, so that the talent identification process helps to nurture football talents more efficiently.

Keywords: current situation, talent finding, ideal situation, instructors (AFC)

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Authors: Nasim Abuali Galehdari, Thomas J. Ryan, Ajit D. Kelkar

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In recent years, nanotechnology has played an important role in the design of an efficient radiation shielding polymeric composites. It is well known that, high loading of nanomaterials with radiation absorption properties can enhance the radiation attenuation efficiency of shielding structures. However, due to difficulties in dispersion of nanomaterials into polymer matrices, there has been a limitation in higher loading percentages of nanoparticles in the polymer matrix. Therefore, the objective of the present work is to provide a methodology to fabricate and then to characterize the functionally graded radiation shielding structures, which can provide an efficient radiation absorption property along with good structural integrity. Sandwich structures composed of Ultra High Molecular Weight Polyethylene (UHMWPE) fabric as face sheets and functionally graded epoxy nanocomposite as core material were fabricated. A method to fabricate a functionally graded core panel with controllable gradient dispersion of nanoparticles is discussed. In order to optimize the design of functionally graded sandwich composites and to analyze the stress distribution throughout the sandwich composite thickness, a finite element method was used. The sandwich panels were discretized using 3-Dimensional 8 nodded brick elements. Classical laminate analysis in conjunction with simplified micromechanics equations were used to obtain the properties of the face sheets. The presented finite element model would provide insight into deformation and damage mechanics of the functionally graded sandwich composites from the structural point of view.

Keywords: nanotechnology, functionally graded material, radiation shielding, sandwich composites, finite element method

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Authors: Mohammad Mokhtari, Gires Usup, Zaidi Che Cob

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Bacteria communities as mediators of the biogeochemical process are the main component of the mangrove ecosystems. Crab burrows by increasing oxic-anoxic interfaces and facilitating the flux rate between sediment and tidal water affect biogeochemical properties of sediments. The effect of fiddler crab burrows on the density and diversity of bacteria were investigated to elucidate the effect of burrow on bacterial distribution. Samples collected from the burrow walls of three species of fiddler crabs including Uca paradussumieri, Uca rosea, and Uca forcipata. Sediment properties including grain size, temperature, Redox potential, pH, chlorophyll, water and organic content were measured from the burrow walls to assess the correlation between environmental variables and bacterial communities. Bacteria were enumerated with epifluorescence microscopy after staining with SYBR green. Bacterial DNA extracted from sediment samples and the community profiles of bacteria were determined with Terminal Restriction Fragment Length Polymorphism (T-RFLP). High endemism was observed among bacterial communities. Among the 152 observed OTU’s, 22 were found only in crab burrows. The highest bacterial density and diversity were recorded in burrow wall. The results of ANOSIM indicated a significant difference between the bacterial communities from the three species of fiddler crab burrows. Only 3% of explained bacteria variability in the constrained ordination model of CCA was contributed to depth, while much of the bacteria’s variability was attributed to coarse sand, pH, and chlorophyll content. Our findings suggest that crab burrows by affecting sediment properties such as redox potential, pH, water, and chlorophyll content induce significant effects on the bacterial communities.

Keywords: bioturbation, canonical corresponding analysis, fiddler crab, microbial ecology

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Authors: G. De Matteis, L. Martina, V. Turco

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The work is focused on determining and comparing special nonlinear static configurations in cholesteric liquid crystals (CLCs), confined between two parallel plates and in the presence of an external static electric/magnetic field. The solutions are stabilised by topological and non-topological conservation laws since they are described in terms of integrable or partially integrable nonlinear boundary value problems. In cholesteric liquid crystals which are subject to geometric frustration; anchoring conditions at boundaries, i.e., homeotropic conditions, are incompatible with the cholesteric twist. This aspect turns out to be essential in the admissible classes of solutions, allowing also for disclination type singularities. Within the framework of Frank-Oseen theory, we study the static configurations for CLCs. First, we find numerical solutions for isolated axisymmetric states in confined CLCs with weak homeotropic anchoring at the boundaries. These solutions describe 3-dimensional modulations, namely spherulites or cholesteric bubbles, actually observed in these systems, of standard baby skyrmions. Relations with well-known nonlinear integrable systems are found and are used to explore the asymptotic behavior of the solutions. Then we turn our attention to extended periodic static configurations called Helicoids or cholesteric fingers, described by an elliptic sine-Gordon model with appropriate boundary conditions, showing how their period and energies are determined by both the thickness of the cell and the intensity of the external electric/magnetic field. We explicitly show that helicoids with π or 2π of rotations of the molecular director are different in many aspects and are not simply algebraically related. The behaviour of the solutions, their energy and the properties of the associated disclinations are discussed in detail, both analytically and numerically.

Keywords: cholesteric liquid crystals, geometric frustration, helicoids, skyrmions

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Authors: Axel Priambodo, Dwiharso Nugroho

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Studies conducted to map the reservoir properties based on facies architecture in which to determine the distribution of the petrophysical properties and calculate hydrocarbon reserves in study interval. Facies Architecture analysis begins with stratigraphic correlation that indicates the area is divided into different system tracts. The analysis of distribution patterns and compiling core analysis with facies architecture model show that there are three estuarine facies appear. Formation evaluation begins with shale volume calculation using Asquith-Krygowski and Volan Triangle Method. Proceed to the calculation of the total and effective porosity using the Bateman-Konen and Volan Triangle Method. After getting the value of the porosity calculation was continued to determine the effective water saturation and non-effective by including parameters of water resistivity and resistivity clay. The results of the research show that the Facies Architecture on the field in divided into three main facies which are Estuarine Channel, Estuarine Sand Bar, and Tidal Flat. The petrophysics analysis are done by comparing different methods also shows that the Volan Triangle Method does not give a better result of the Volume Shale than the Gamma Ray Method, but on the other hand, the Volan Triangle Methode is better on calculating porosity compared to the Bateman-Konen Method. The effective porosity distributions are affected by the distribution of the facies. Estuarine Sand Bar has a low porosity number and Estuarine Channel has a higher number of the porosity. The effective water saturation is controlled by structure where on the closure zone the water saturation is lower than the area beneath it. It caused by the hydrocarbon accumulation on the closure zone.

Keywords: petrophysics, geology, petroleum, reservoir

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Authors: Diptimayee Nayak

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Ecotourism has been recognised as a popular component of alternative tourism, which claims to guard host local environment and economy. This concept of ecological tourism (eco-tourism) has become more meaningful in evaluating the recreational function and services of any pristine ecosystem in context of ‘The Economics of Ecosystem and Biodiversity (TEEB)’. This ecotourism is said to be a local solution to the global problem of conserving ecosystems and optimising the utilisations of their services. This paper takes a case of recreational services of an Indian protected area ecosystems ‘Bhitarakanika mangrove protected area’ discussing how ecotourism is functioning taking the perspectives of different stakeholders. Specific stakeholders are taken for analysis, viz., tourists and local people, as they are believed to be the major beneficiaries of ecotourism. The stakeholders’ analysis is evaluated on the basis of travel cost techniques (by using truncated Poisson distribution model) for tourists and descriptive and analytical tools for local people. The evaluation of stakeholders’ analysis of ecotourism has gained its impetus after the formulation of Ecotourism guidelines by the Ministry of Environment and Forest (MoEF), Government of India. The paper concludes that ecotourism issues and challenges are site-specific and region-specific; without critically focussing challenges of ecotourism faced at local level the discourses of ecotourism at global level cannot be tackled. Mere integration and replication of policies at global level to be followed at local level will not be successful (top down policies). Rather mainstreaming the decision making process at local level with the global policy stature helps to solve global issues to a bigger extent (bottom up).

Keywords: ecosystem services, ecotourism, TEEB, economic valuation, stakeholders, travel cost techniques

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Authors: Asad Yousuf

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Purpose: The aim of the present study was to audit treatment planning system beam dataset for small field output factors against standard dataset produced by radiological physics center (RPC) from a multicenter study. Such data are crucial for validity of special techniques, i.e., IMRT or stereotactic radiosurgery. Materials/Method: In this study, multiple small field size output factor datasets were measured and calculated for 6 to 18 MV x-ray beams using the RPC recommend methods. These beam datasets were measured at 10 cm depth for 10 × 10 cm2 to 2 × 2 cm2 field sizes, defined by collimator jaws at 100 cm. The measurements were made with a Landauer’s nanoDot OSLDs whose volume is small enough to gather a full ionization reading even for the 1×1 cm2 field size. At our institute the beam data including output factors have been commissioned at 5 cm depth with an SAD setup. For comparison with the RPC data, the output factors were converted to an SSD setup using tissue phantom ratios. SSD setup also enables coverage of the ion chamber in 2×2 cm2 field size. The measured output factors were also compared with those calculated by Eclipse™ treatment planning software. Result: The measured and calculated output factors are in agreement with RPC dataset within 1% and 4% respectively. The large discrepancies in TPS reflect the increased challenge in converting measured data into a commissioned beam model for very small fields. Conclusion: OSLDs are simple, durable, and accurate tool to verify doses that delivered using small photon beam fields down to a 1x1 cm2 field sizes. The study emphasizes that the treatment planning system should always be evaluated for small field out factors for the accurate dose delivery in clinical setting.

Keywords: small field dosimetry, optically stimulated luminescence, audit treatment, radiological physics center

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Authors: Igor Sukhotnik

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Objectives: Notch signaling is thought to act to drive cell versification in the lining of the small intestine. When Notch signaling is blocked, proliferation ceases, and epithelial cells become secretory. The purpose of the present study was to evaluate the role of Notch signaling pathway in stem cell differentiation in a rat model of intestinal ischemia-reperfusion (IR). Methods: Male Sprague-Dawley rats were randomly divided into four experimental groups: Sham-24 and Sham-48 rats underwent laparotomy and were killed 24 or 48 h later, respectively; IR-24 and IR-48 rats underwent occlusion of SMA and portal vein for 30 min followed by 24 or 48 h of reperfusion, respectively. Notch-related gene and protein expression were determined using Real Time PCR, Western blotting and immunohistochemistry. Wax histology and immunohistochemistry was used to determine cell differentiation toward absorptive (enterocytes) or secretory progenitors (goblet cells, enteroendocrine cells or Paneth cells). Results: IR-48 rats exhibited a significant decrease in Notch-1 protein expression (Western blot) that was coincided with a significant decrease in the number of Notch-1 positive cells (immunohistochemistry) in jejunum and ileum as well as Hes-1 positive cells in jejunum and ileum compared to Sham-48 rats. A significant down-regulation of Notch signaling related genes and proteins in IR animals was accompanied by a significant increase in the number of goblet and Paneth cells and decreased number of absorptive cells compared to control rats. Conclusions: Forty-eight hours following intestinal IR in rats, inhibited Notch signaling pathway was accompanied by intestinal stem cells differentiation toward secretory progenitors.

Keywords: Intestine, notch, ischemia-reperfusion, cell differentiation, secretory

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Authors: Hsiao-Tien Pao, Yi-Ying Li, Hsin-Chia Fu

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This paper addressed the impacts of energy consumption, economic growth, financial development, and population size on environmental degradation using grey relational analysis (GRA) for China, where foreign direct investment (FDI) inflows is the proxy variable for financial development. The more recent historical data during the period 2004–2011 are used, because the use of very old data for data analysis may not be suitable for rapidly developing countries. The results of the GRA indicate that the linkage effects of energy consumption–emissions and GDP–emissions are ranked first and second, respectively. These reveal that energy consumption and economic growth are strongly correlated with emissions. Higher economic growth requires more energy consumption and increasing environmental pollution. Likewise, more efficient energy use needs a higher level of economic development. Therefore, policies to improve energy efficiency and create a low-carbon economy can reduce emissions without hurting economic growth. The finding of FDI–emissions linkage is ranked third. This indicates that China do not apply weak environmental regulations to attract inward FDI. Furthermore, China’s government in attracting inward FDI should strengthen environmental policy. The finding of population–emissions linkage effect is ranked fourth, implying that population size does not directly affect CO₂ emissions, even though China has the world’s largest population, and Chinese people are very economical use of energy-related products. Overall, the energy conservation, improving efficiency, managing demand, and financial development, which aim at curtailing waste of energy, reducing both energy consumption and emissions, and without loss of the country’s competitiveness, can be adopted for developing economies. The GRA is one of the best way to use a lower data to build a dynamic analysis model.

Keywords: China, CO₂ emissions, foreign direct investment, grey relational analysis

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Authors: Jinlu Sun, Shouxiang Lu, Siuming Lo

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Large passenger ship, especially luxury cruise, is one of the most prevalent means of marine transportation and tourism nowadays. In case of an accident, an effective evacuation would be the ultimate way to minimize the consequence. Ship heeling and trim has a considerable influence on passenger walking speed and posture during ship evacuation. To investigate passenger movement pattern under the combined effect of ship heeling and trim, a ship corridor simulator was developed. Both fast and freely individual walking experiments by male and female experimental subjects under heeling and trim conditions were conducted and recorded therein. It is found that routes of experimental subjects would change due to the heeling and trim angles, although they always walk along the right side because of cultural factors. Experimental subjects would also change their posture to adapt the combined heeling and trim conditions, such as leaning forward, adopting larger arm swaying, shorter and more frequent steps. While for individual walking speed, the speed would decrease with the increasing heeling and trim angles. But the maximum individual walking speed is achieved at heeling angle of 0° with trim angle ranging from -15° to -5 °, instead of on level ground, which may be attributable to the effect of the gravitational acceleration. Female is approximately 10% slower than male due to the discrepancy in physical quality. Besides, individual walking speed shows similar trends in both fast and freely walking modes, and the speed value in freely walking mode is about 78% of that in fast walking mode under each experimental condition. Furthermore, to designate the movement pattern of passengers in heeling and trim conditions, a model of the walking speed reduction was proposed. This work would provide guidance on the development of evacuation models and the design of evacuation facilities on board.

Keywords: evacuation, heeling, individual walking speed, ship corridor simulator, trim

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Authors: L. Salomon, P. Sklenar

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The Andes hold the highest plant species diversity in the world. How this occurred is one of the most intriguing questions in studies addressing the origin and patterning of plant diversity worldwide. Recently, the explosive adaptive radiations found in high Andean groups have been pointed as triggers to this spectacular diversity. The Andes is the species-richest area for the biggest genus from the Asteraceae family: Senecio. There, the genus presents an incredible diversity of species, striking growth form variation, and large niche span. Even when some studies tried to disentangle the evolutionary story for some Andean species in Senecio, they obtained partially resolved and low supported phylogenies, as expected for recently radiated groups. The high-throughput sequencing (HTS) approaches have proved to be a powerful tool answering phylogenetic questions in those groups whose evolutionary stories are recent and traditional techniques like Sanger sequencing are not informative enough. Although these tools have been used to understand the evolution of an increasing number of Andean groups, nowadays, their scope has not been applied for Senecio. This project aims to contribute to a better knowledge of the mechanisms shaping the hyper diversity of Senecio in the Andean region, using HTS focusing on Senecio ser. Culcitium (Asteraceae), recently recircumscribed. Firstly, reconstructing a highly resolved and supported phylogeny, and after assessing the role of allopatric differentiation, hybridization, and genome duplication in the diversification of the group. Using the Hyb-Seq approach, combining target enrichment using Asteraceae COS loci baits and genome skimming, more than 100 new accessions were generated. HybPhyloMaker and HybPiper pipelines were used for the phylogenetic analyses, and another pipeline in development (Paralogue Wizard) was used to deal with paralogues. RAxML was used to generate gene trees and Astral for species tree reconstruction. Phyparts were used to explore as first step of gene tree discordance along the clades. Fully resolved with moderated supported trees were obtained, showing Senecio ser. Culcitium as monophyletic. Within the group, some species formed well-supported clades with morphologically related species, while some species would not have exclusive ancestry, in concordance with previous studies using amplified fragment length polymorphism (AFLP) showing geographical differentiation. Discordance between gene trees was detected. Paralogues were detected for many loci, indicating possible genome duplications; ploidy level estimation using flow cytometry will be carried out during the next months in order to identify the role of this process in the diversification of the group. Likewise, TreeSetViz package for Mesquite, hierarchical likelihood ratio congruence test using Concaterpillar, and Procrustean Approach to Cophylogeny (PACo), will be used to evaluate the congruence among different inheritance patterns. In order to evaluate the influence of hybridization and Incomplete Lineage Sorting (ILS) in each resultant clade from the phylogeny, Joly et al.'s 2009 method in a coalescent scenario and Paterson’s D-statistic will be performed. Even when the main discordance sources between gene trees were not explored in detail yet, the data show that at least to some degree, processes such as genome duplication, hybridization, and/or ILS could be involved in the evolution of the group.

Keywords: adaptive radiations, Andes, genome duplication, hybridization, Senecio

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Authors: Seung-Min Ko, Seung-Jai Choi, Gun Jung, Jang-Ho Jay Kim

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Although extensive explosion-related research has been performed in the past several decades, almost no research has focused on internal blasts. However, internal blast research is needed to understand about the behavior of a containment structure or building under internal blast loading, as in the case of the Chornobyl and Fukushima nuclear accidents. Therefore, the internal blast study concentrated on RC and PSC structures is performed. The test data obtained from reinforced concrete (RC) and prestressed concrete (PSC) tubular structures applied with an internal explosion using ammonium nitrate/fuel oil (ANFO) charge are used to assess their deformation resistance and ultimate failure load based on the structural stiffness change under various charge weight. For the internal blast charge weight, ANFO explosive charge weights of 15.88, 20.41, 22.68 and 24.95 kg were selected for the RC tubular structures, and 22.68, 24.95, 27.22, 29.48, and 31.75 kg were selected for PSC tubular structures, which were detonated at the center of cross section at the mid-span with a standoff distance of 1,000mm to the inner wall surface. Then, the test data were used to predict the internal charge weight required to fail a real scale reinforced concrete containment vessels (RCCV) and prestressed concrete containment vessel (PCCV). Then, the analytical results based on the experimental data were derived using the simple assumptions of the models, and another approach using the stiffness, deformation and explosion weight relationship was used to formulate a general method for analyzing internal blasted tubular structures. A model of the internal explosion of a steel tube was used as an example for validation. The proposed method can be used generically, using factors according to the material characteristics of the target structures. The results of the study are discussed in detail in the paper.

Keywords: internal blast, reinforced concrete, RCCV, PCCV, stiffness, blast safety

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Authors: Ziyad S. Haidar

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Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs, followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology

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