Search results for: asymptotic expansions
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 172

Search results for: asymptotic expansions

22 Evaluation of Soil Erosion Risk and Prioritization for Implementation of Management Strategies in Morocco

Authors: Lahcen Daoudi, Fatima Zahra Omdi, Abldelali Gourfi

Abstract:

In Morocco, as in most Mediterranean countries, water scarcity is a common situation because of low and unevenly distributed rainfall. The expansions of irrigated lands, as well as the growth of urban and industrial areas and tourist resorts, contribute to an increase of water demand. Therefore in the 1960s Morocco embarked on an ambitious program to increase the number of dams to boost water retention capacity. However, the decrease in the capacity of these reservoirs caused by sedimentation is a major problem; it is estimated at 75 million m3/year. Dams and reservoirs became unusable for their intended purposes due to sedimentation in large rivers that result from soil erosion. Soil erosion presents an important driving force in the process affecting the landscape. It has become one of the most serious environmental problems that raised much interest throughout the world. Monitoring soil erosion risk is an important part of soil conservation practices. The estimation of soil loss risk is the first step for a successful control of water erosion. The aim of this study is to estimate the soil loss risk and its spatial distribution in the different fields of Morocco and to prioritize areas for soil conservation interventions. The approach followed is the Revised Universal Soil Loss Equation (RUSLE) using remote sensing and GIS, which is the most popular empirically based model used globally for erosion prediction and control. This model has been tested in many agricultural watersheds in the world, particularly for large-scale basins due to the simplicity of the model formulation and easy availability of the dataset. The spatial distribution of the annual soil loss was elaborated by the combination of several factors: rainfall erosivity, soil erodability, topography, and land cover. The average annual soil loss estimated in several basins watershed of Morocco varies from 0 to 50t/ha/year. Watersheds characterized by high-erosion-vulnerability are located in the North (Rif Mountains) and more particularly in the Central part of Morocco (High Atlas Mountains). This variation of vulnerability is highly correlated to slope variation which indicates that the topography factor is the main agent of soil erosion within these basin catchments. These results could be helpful for the planning of natural resources management and for implementing sustainable long-term management strategies which are necessary for soil conservation and for increasing over the projected economic life of the dam implemented.

Keywords: soil loss, RUSLE, GIS-remote sensing, watershed, Morocco

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21 Functional Dimension of Reuse: Use of Antalya Kaleiçi Traditional Dwellings as Hotel

Authors: Dicle Aydın, Süheyla Büyükşahin Sıramkaya

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Conservation concept gained importance especially in 19th century, it found value with the change and developments lived globally. Basic values in the essence of the concept are important in the continuity of historical and cultural fabrics which have character special to them. Reuse of settlements and spaces carrying historical and cultural values in the frame of socio-cultural and socio-economic conditions is related with functional value. Functional dimension of reuse signifies interrogation of the usage potential of the building with a different aim other than its determined aim. If a building carrying historical and cultural values cannot be used with its own function because of environmental, economical, structural and functional reasons, it is advantageous to maintain its reuse from the point of environmental ecology. By giving a new function both a requirement of the society is fulfilled and a culture entity is conserved because of its functional value. In this study, functional dimension of reuse is exemplified in Antalya Kaleiçi where has a special location and importance with its natural, cultural and historical heritage characteristics. Antayla Kaleiçi settlement preserves its liveliness as a touristic urban fabric with its almost fifty thousand years of past, traditional urban form, civil architectural examples of 18th–19th century reflecting the life style of the region and monumental buildings. The civil architectural examples in the fabric have a special character formed according to Mediterranean climate with their outer sofa (open or closed), one, two or three storey, courtyards and oriels. In the study reuse of five civil architectural examples as boutique hotel by forming a whole with their environmental arrangements is investigated, it is analyzed how the spatial requirements of a boutique hotel are fulfilled in traditional dwellings. Usage of a cultural entity as a boutique hotel is evaluated under the headlines of i.functional requirement, ii.satisfactoriness of spatial dimensions, iii.functional organization. There are closed and open restaurant, kitchen, pub, lobby, administrative offices in the hotel with 70 bed capacity and 28 rooms in total. There are expansions to urban areas on second and third floors by the means of oriels in the hotel surrounded by narrow streets in three directions. This boutique hotel, formed by unique five different dwellings having similar plan scheme in traditional fabric, is different with its structure opened to outside and connected to each other by the means of courtyards, and its outside spaces which gained mobility because of the elevation differences in courtyards.

Keywords: reuse, adaptive reuse, functional dimension of reuse, traditional dwellings

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20 Fine-Scale Modeling the Influencing Factors of Multi-Time Dimensions of Transit Ridership at Station Level: The Study of Guangzhou City

Authors: Dijiang Lyu, Shaoying Li, Zhangzhi Tan, Zhifeng Wu, Feng Gao

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Nowadays, China is experiencing rapidly urban rail transit expansions in the world. The purpose of this study is to finely model factors influencing transit ridership at multi-time dimensions within transit stations’ pedestrian catchment area (PCA) in Guangzhou, China. This study was based on multi-sources spatial data, including smart card data, high spatial resolution images, points of interest (POIs), real-estate online data and building height data. Eight multiple linear regression models using backward stepwise method and Geographic Information System (GIS) were created at station-level. According to Chinese code for classification of urban land use and planning standards of development land, residential land-use were divided into three categories: first-level (e.g. villa), second-level (e.g. community) and third-level (e.g. urban villages). Finally, it concluded that: (1) four factors (CBD dummy, number of feeder bus route, number of entrance or exit and the years of station operation) were proved to be positively correlated with transit ridership, but the area of green land-use and water land-use negative correlated instead. (2) The area of education land-use, the second-level and third-level residential land-use were found to be highly connected to the average value of morning peak boarding and evening peak alighting ridership. But the area of commercial land-use and the average height of buildings, were significantly positive associated with the average value of morning peak alighting and evening peak boarding ridership. (3) The area of the second-level residential land-use was rarely correlated with ridership in other regression models. Because private car ownership is still large in Guangzhou now, and some residents living in the community around the stations go to work by transit at peak time, but others are much more willing to drive their own car at non-peak time. The area of the third-level residential land-use, like urban villages, was highly positive correlated with ridership in all models, indicating that residents who live in the third-level residential land-use are the main passenger source of the Guangzhou Metro. (4) The diversity of land-use was found to have a significant impact on the passenger flow on the weekend, but was non-related to weekday. The findings can be useful for station planning, management and policymaking.

Keywords: fine-scale modeling, Guangzhou city, multi-time dimensions, multi-sources spatial data, transit ridership

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19 Land Use, Land Cover Changes and Woody Vegetation Status of Tsimur Saint Gebriel Monastery, in Tigray Region, Northern Ethiopia

Authors: Abraha Hatsey, Nesibu Yahya, Abeje Eshete

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Ethiopian Orthodox Tewahido Church has a long tradition of conserving the Church vegetation and is an area treated as a refugee camp for many endangered indigenous tree species in Northern Ethiopia. Though around 36,000 churches exist in Ethiopia, only a few churches have been studied so far. Thus, this study assessed the land use land cover change of 3km buffer (1986-2018) and the woody species diversity and regeneration status of Tsimur St. Gebriel monastery in Tigray region, Northern Ethiopia. For vegetation study, systematic sampling was used with 100m spacing between plots and between transects. Plot size was 20m*20m for the main plot and 2 subplots (5m*5m each) for the regeneration study. Tree height, diameter at breast height(DBH) and crown area were measured in the main plot for all trees with DBH ≥ 5cm. In the subplots, all seedlings and saplings were counted with DBH < 5cm. The data was analyzed on excel and Pass biodiversity software for diversity and evenness analysis. The major land cover classes identified include bare land, farmland, forest, shrubland and wetland. The extents of forest and shrubland were declined considerably due to bare land and agricultural land expansions within the 3km buffer, indicating an increasing pressure on the church forest. Regarding the vegetation status, A total of 19 species belonging to 13 families were recorded in the monastery. The diversity (H’) and evenness recorded were 2.4 and 0.5, respectively. The tree density (DBH ≥ 5cm) was 336/ha and a crown cover of 65%. Olea europaea was the dominant (6.4m2/ha out of 10.5m2 total basal area) and a frequent species (100%) with good regeneration in the monastery. The rest of the species are less frequent and are mostly confined to water sources with good site conditions. Juniperus procera (overharvested) and the other indigenous species were with few trees left and with no/very poor regeneration status. The species having poor density, frequency and regeneration (Junperus procera, Nuxia congesta Fersen and Jasminium abyssinica) need prior conservation and enrichment planting. The indigenous species could also serve as a potential seed source for the reproduction and restoration of nearby degraded landscapes. The buffer study also demonstrated expansion of agriculture and bare land, which could be a threat to the forest of the isolated monastery. Hence, restoring the buffer zone is the only guarantee for the healthy existence of the church forest.

Keywords: church forests, regeneration, land use change, vegetation status

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18 Reflections of Narrative Architecture in Transformational Representations on the Architectural Design Studio

Authors: M. Mortas, H. Asar, P. Dursun Cebi

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The visionary works of architectural representation in the 21st century's present situation, are practiced through the methodologies which try to expose the intellectual and theoretical essences of futurologist positions that are revealed with this era's interactions. Expansions of conceptual and contextual inputs related to one architectural design representation, depend on its deepness of critical attitudes, its interactions with the concepts such as experience, meaning, affection, psychology, perception and aura, as well as its communication with spatial, cultural and environmental factors. The purpose of this research study is to be able to offer methodological application areas for the design dimensions of experiential practices into architectural design studios, by focusing on the architectural representative narrations of 'transformation,' 'metamorphosis,' 'morphogenesis,' 'in-betweenness', 'superposition' and 'intertwine’ in which they affect and are affected by the today’s spatiotemporal hybridizations of architecture. The narrative representations and the visual theory paradigms of the designers are chosen under the main title of 'transformation' for the investigation of these visionary and critical representations' dismantlings and decodings. Case studies of this research area are chosen from Neil Spiller, Bryan Cantley, Perry Kulper and Dan Slavinsky’s transformative, morphogenetic representations. The theoretical dismantlings and decodings which are obtained from these artists’ contemporary architectural representations are tried to utilize and practice in the structural design studios as alternative methodologies when to approach architectural design processes, for enriching, differentiating, diversifying and 'transforming' the applications of so far used design process precedents. The research aims to indicate architectural students about how they can reproduce, rethink and reimagine their own representative lexicons and so languages of their architectural imaginations, regarding the newly perceived tectonics of prosthetic, biotechnology, synchronicity, nanotechnology or machinery into various experiential design workshops. The methodology of this work can be thought as revealing the technical and theoretical tools, lexicons and meanings of contemporary-visionary architectural representations of our decade, with the essential contents and components of hermeneutics, etymology, existentialism, post-humanism, phenomenology and avant-gardism disciplines to re-give meanings the architectural visual theorists’ transformative representations of our decade. The value of this study may be to emerge the superposed and overlapped atmospheres of futurologist architectural representations for the students who need to rethink on the transcultural, deterritorialized and post-humanist critical theories to create and use the representative visual lexicons of themselves for their architectural soft machines and beings by criticizing the now, to be imaginative for the future of architecture.

Keywords: architectural design studio, visionary lexicon, narrative architecture, transformative representation

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17 Harnessing Clinical Trial Capacity to Mitigate Zoonotic Diseases: The Role of Expert Scientists in Ethiopia

Authors: Senait Belay Adugna, Mirutse Giday, Tsegahun Manyazewal

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Background: The emergence and resurgence of zoonotic diseases have continued to be a major threat to global health and the economy. Developing countries are particularly vulnerable due to agricultural expansions and the domestication of animals by humans. Scientifically sound clinical trials are important to find better ways to prevent, diagnose, and treat zoonotic diseases, while there is a lack of evidence to inform the clinical trials’ capacity and practice in countries highly affected by the diseases. This study aimed to investigate researchers’ perceptions and experiences in conducting clinical trials on zoonotic diseases in Ethiopia. Methods: This study employed a descriptive, qualitative study design. It included major academic and research institutions in Ethiopia that had active engagements in veterinary and public health research. It included the National Veterinary Institute, the National Animal Health Diagnostic and Investigation Center, the College of Veterinary Medicine at Addis Ababa University, the Ethiopian Public Health Institute, the Armauer Hansen Research Institute, and the College of Health Sciences at Addis Ababa University. In-depth interviews were conducted with 14 senior researcher investigators in the institutions who hold a proven exhibit primarily leading research activities or research units. Data were collected from October 2019 to April 2020. Data analysis was undertaken using open code 4.03 for qualitative data analysis. Results: Five major themes, with 18 sub-themes, emerged from the in-depth interview in connection. These were: challenges in the prevention, control, and treatment of zoonotic diseases; One Health approach to mitigate zoonotic diseases; personal and institutional experiences in conducting clinical trials on zoonotic diseases; barriers in conducting clinical trials towards zoonotic diseases; and strategies that promote conducting clinical trials on zoonotic diseases. Conducting clinical trials on zoonotic diseases in Ethiopia is hampered by a lack of clearly articulated ethics and regulatory frameworks, trial experts, financial resources, and good governance. Conclusions: In Ethiopia, conducting clinical trials on zoonotic diseases deserves due attention. Strengthening institutional and human resources capacity is a precondition to harnessing effective implementation of clinical trials on zoonotic diseases in the country. In Ethiopia, where skilled human resource is scarce, the One Health approach has the potential to form multidisciplinary teams to systematically improve clinical trials capacity and outcomes in the country.

Keywords: Ethiopia, clinical triak, zoonoses, disease

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16 Mathematical Modelling of Spatial Distribution of Covid-19 Outbreak Using Diffusion Equation

Authors: Kayode Oshinubi, Brice Kammegne, Jacques Demongeot

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The use of mathematical tools like Partial Differential Equations and Ordinary Differential Equations have become very important to predict the evolution of a viral disease in a population in order to take preventive and curative measures. In December 2019, a novel variety of Coronavirus (SARS-CoV-2) was identified in Wuhan, Hubei Province, China causing a severe and potentially fatal respiratory syndrome, i.e., COVID-19. Since then, it has become a pandemic declared by World Health Organization (WHO) on March 11, 2020 which has spread around the globe. A reaction-diffusion system is a mathematical model that describes the evolution of a phenomenon subjected to two processes: a reaction process in which different substances are transformed, and a diffusion process that causes a distribution in space. This article provides a mathematical study of the Susceptible, Exposed, Infected, Recovered, and Vaccinated population model of the COVID-19 pandemic by the bias of reaction-diffusion equations. Both local and global asymptotic stability conditions for disease-free and endemic equilibria are determined using the Lyapunov function are considered and the endemic equilibrium point exists and is stable if it satisfies Routh–Hurwitz criteria. Also, adequate conditions for the existence and uniqueness of the solution of the model have been proved. We showed the spatial distribution of the model compartments when the basic reproduction rate $\mathcal{R}_0 < 1$ and $\mathcal{R}_0 > 1$ and sensitivity analysis is performed in order to determine the most sensitive parameters in the proposed model. We demonstrate the model's effectiveness by performing numerical simulations. We investigate the impact of vaccination and the significance of spatial distribution parameters in the spread of COVID-19. The findings indicate that reducing contact with an infected person and increasing the proportion of susceptible people who receive high-efficacy vaccination will lessen the burden of COVID-19 in the population. To the public health policymakers, we offered a better understanding of the COVID-19 management.

Keywords: COVID-19, SEIRV epidemic model, reaction-diffusion equation, basic reproduction number, vaccination, spatial distribution

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15 The Persistence of Abnormal Return on Assets: An Exploratory Analysis of the Differences between Industries and Differences between Firms by Country and Sector

Authors: José Luis Gallizo, Pilar Gargallo, Ramon Saladrigues, Manuel Salvador

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This study offers an exploratory statistical analysis of the persistence of annual profits across a sample of firms from different European Union (EU) countries. To this end, a hierarchical Bayesian dynamic model has been used which enables the annual behaviour of those profits to be broken down into a permanent structural and a transitory component, while also distinguishing between general effects affecting the industry as a whole to which each firm belongs and specific effects affecting each firm in particular. This breakdown enables the relative importance of those fundamental components to be more accurately evaluated by country and sector. Furthermore, Bayesian approach allows for testing different hypotheses about the homogeneity of the behaviour of the above components with respect to the sector and the country where the firm develops its activity. The data analysed come from a sample of 23,293 firms in EU countries selected from the AMADEUS data-base. The period analysed ran from 1999 to 2007 and 21 sectors were analysed, chosen in such a way that there was a sufficiently large number of firms in each country sector combination for the industry effects to be estimated accurately enough for meaningful comparisons to be made by sector and country. The analysis has been conducted by sector and by country from a Bayesian perspective, thus making the study more flexible and realistic since the estimates obtained do not depend on asymptotic results. In general terms, the study finds that, although the industry effects are significant, more important are the firm specific effects. That importance varies depending on the sector or the country in which the firm carries out its activity. The influence of firm effects accounts for around 81% of total variation and display a significantly lower degree of persistence, with adjustment speeds oscillating around 34%. However, this pattern is not homogeneous but depends on the sector and country analysed. Industry effects depends also on sector and country analysed have a more marginal importance, being significantly more persistent, with adjustment speeds oscillating around 7-8% with this degree of persistence being very similar for most of sectors and countries analysed.

Keywords: dynamic models, Bayesian inference, MCMC, abnormal returns, persistence of profits, return on assets

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14 Causal Estimation for the Left-Truncation Adjusted Time-Varying Covariates under the Semiparametric Transformation Models of a Survival Time

Authors: Yemane Hailu Fissuh, Zhongzhan Zhang

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In biomedical researches and randomized clinical trials, the most commonly interested outcomes are time-to-event so-called survival data. The importance of robust models in this context is to compare the effect of randomly controlled experimental groups that have a sense of causality. Causal estimation is the scientific concept of comparing the pragmatic effect of treatments conditional to the given covariates rather than assessing the simple association of response and predictors. Hence, the causal effect based semiparametric transformation model was proposed to estimate the effect of treatment with the presence of possibly time-varying covariates. Due to its high flexibility and robustness, the semiparametric transformation model which shall be applied in this paper has been given much more attention for estimation of a causal effect in modeling left-truncated and right censored survival data. Despite its wide applications and popularity in estimating unknown parameters, the maximum likelihood estimation technique is quite complex and burdensome in estimating unknown parameters and unspecified transformation function in the presence of possibly time-varying covariates. Thus, to ease the complexity we proposed the modified estimating equations. After intuitive estimation procedures, the consistency and asymptotic properties of the estimators were derived and the characteristics of the estimators in the finite sample performance of the proposed model were illustrated via simulation studies and Stanford heart transplant real data example. To sum up the study, the bias of covariates was adjusted via estimating the density function for truncation variable which was also incorporated in the model as a covariate in order to relax the independence assumption of failure time and truncation time. Moreover, the expectation-maximization (EM) algorithm was described for the estimation of iterative unknown parameters and unspecified transformation function. In addition, the causal effect was derived by the ratio of the cumulative hazard function of active and passive experiments after adjusting for bias raised in the model due to the truncation variable.

Keywords: causal estimation, EM algorithm, semiparametric transformation models, time-to-event outcomes, time-varying covariate

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13 Bifurcations of the Rotations in the Thermocapillary Flows

Authors: V. Batishchev, V. Getman

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We study the self-similar fluid flows in the Marangoni layers with the axial symmetry. Such flows are induced by the radial gradients of the temperatures whose distributions along the free boundary obey some power law. The self-similar solutions describe thermo-capillar flows both in the thin layers and in the case of infinite thickness. We consider both positive and negative temperature gradients. In the former case the cooling of free boundary nearby the axis of symmetry gives rise to the rotation of fluid. The rotating flow concentrates itself inside the Marangoni layer while outside of it the fluid does not revolve. In the latter case we observe no rotating flows at all. In the layers of infinite thickness the separation of the rotating flow creates two zones where the flows are directed oppositely. Both the longitudinal velocity and the temperature have exactly one critical point inside the boundary layer. It is worth to note that the profiles are monotonic in the case of non-swirling flows. We describe the flow outside the boundary layer with the use of self-similar solution of the Euler equations. This flow is slow and non-swirling. The introducing of an outer flow gives rise to the branching of swirling flows from the non-swirling ones. There is such the critical velocity of the outer flow that a non-swirling flow exists for supercritical velocities and cannot be extended to the sub-critical velocities. For the positive temperature gradients there are two non-swirling flows. For the negative temperature gradients the non-swirling flow is unique. We determine the critical velocity of the outer flow for which the branching of the swirling flows happens. In the case of a thin layer confined within free boundaries we show that the cooling of the free boundaries near the axis of symmetry leads to the separating of the layer and creates two sub-layers with opposite rotations inside. This makes sharp contrast with the case of infinite thickness. We show that such rotation arises provided the thickness of the layer exceed some critical value. In the case of a thin layer confined within free and rigid boundaries we construct the branching equation and the asymptotic approximation for the secondary swirling flows near the bifurcation point. It turns out that the bifurcation gives rise to one pair of the secondary swirling flows with different directions of swirl.

Keywords: free surface, rotation, fluid flow, bifurcation, boundary layer, Marangoni layer

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12 Safety of Mesenchymal Stem Cells Therapy: Potential Risk of Spontaneous Transformations

Authors: Katarzyna Drela, Miroslaw Wielgos, Mikolaj Wrobel, Barbara Lukomska

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Mesenchymal stem cells (MSCs) have a great potential in regenerative medicine. Since the initial number of isolated MSCs is limited, in vitro propagation is often required to reach sufficient numbers of cells for therapeutic applications. During long-term culture MSCs may undergo genetic or epigenetic alterations that subsequently increase the probability of spontaneous malignant transformation. Thus, factors that influence genomic stability of MSCs following long-term expansions need to be clarified before cultured MSCs are employed for clinical application. The aim of our study was to investigate the potential for spontaneous transformation of human neonatal cord blood (HUCB-MSCs) and adult bone marrow (BM-MSCs) derived MSCs. Materials and Methods: HUCB-MSCs and BM-MSCs were isolated by standard Ficoll gradient centrifugations method. Isolated cells were initially plated in high density 106 cells per cm2. After 48 h medium were changed and non-adherent cells were removed. The malignant transformation of MSCs in vitro was evaluated by morphological changes, proliferation rate, ability to enter cell senescence, the telomerase expression and chromosomal abnormality. Proliferation of MSCs was analyzed with WST-1 reduction method and population doubling time (PDT) was calculated at different culture stages. Then the expression pattern of genes characteristic for mesenchymal or epithelial cells, as well as transcriptions factors were examined by RT-PCR. Concomitantly, immunocytochemical analysis of gene-related proteins was employed. Results: Our studies showed that MSCs from all bone marrow isolations ultimately entered senescence and did not undergo spontaneous malignant transformation. However, HUCB-MSCs from one of the 15 donors displayed an increased proliferation rate, failed to enter senescence, and exhibited an altered cell morphology. In this sample we observed two different cell phenotypes: one mesenchymal-like exhibited spindle shaped morphology and express specific mesenchymal surface markers (CD73, CD90, CD105, CD166) with low proliferation rate, and the second one with round, densely package epithelial-like cells with significantly increased proliferation rate. The PDT of epithelial-like populations was around 1day and 100% of cells were positive for proliferation marker Ki-67. Moreover, HUCB-MSCs showed a positive expression of human telomerase reverse transcriptase (hTERT), cMYC and exhibit increased number of CFU during the long-term culture in vitro. Furthermore, karyotype analysis revealed chromosomal abnormalities including duplications. Conclusions: Our studies demonstrate that HUCB-MSCs are susceptible to spontaneous malignant transformation during long-term culture. Spontaneous malignant transformation process following in vitro culture has enormous effect on the biosafety issues of future cell-based therapies and regenerative medicine regimens.

Keywords: mesenchymal stem cells, spontaneous, transformation, long-term culture

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11 Effect of Climate Change on the Genomics of Invasiveness of the Whitefly Bemisia tabaci Species Complex by Estimating the Effective Population Size via a Coalescent Method

Authors: Samia Elfekih, Wee Tek Tay, Karl Gordon, Paul De Barro

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Invasive species represent an increasing threat to food biosecurity, causing significant economic losses in agricultural systems. An example is the sweet potato whitefly, Bemisia tabaci, which is a complex of morphologically indistinguishable species causing average annual global damage estimated at US$2.4 billion. The Bemisia complex represents an interesting model for evolutionary studies because of their extensive distribution and potential for invasiveness and population expansion. Within this complex, two species, Middle East-Asia Minor 1 (MEAM1) and Mediterranean (MED) have invaded well beyond their home ranges whereas others, such as Indian Ocean (IO) and Australia (AUS), have not. In order to understand why some Bemisia species have become invasive, genome-wide sequence scans were used to estimate population dynamics over time and relate these to climate. The Bayesian Skyline Plot (BSP) method as implemented in BEAST was used to infer the historical effective population size. In order to overcome sampling bias, the populations were combined based on geographical origin. The datasets used for this particular analysis are genome-wide SNPs (single nucleotide polymorphisms) called separately in each of the following groups: Sub-Saharan Africa (Burkina Faso), Europe (Spain, France, Greece and Croatia), USA (Arizona), Mediterranean-Middle East (Israel, Italy), Middle East-Central Asia (Turkmenistan, Iran) and Reunion Island. The non-invasive ‘AUS’ species endemic to Australia was used as an outgroup. The main findings of this study show that the BSP for the Sub-Saharan African MED population is different from that observed in MED populations from the Mediterranean Basin, suggesting evolution under a different set of environmental conditions. For MED, the effective size of the African (Burkina Faso) population showed a rapid expansion ≈250,000-310,000 years ago (YA), preceded by a period of slower growth. The European MED populations (i.e., Spain, France, Croatia, and Greece) showed a single burst of expansion at ≈160,000-200,000 YA. The MEAM1 populations from Israel and Italy and the ones from Iran and Turkmenistan are similar as they both show the earlier expansion at ≈250,000-300,000 YA. The single IO population lacked the latter expansion but had the earlier one. This pattern is shared with the Sub-Saharan African (Burkina Faso) MED, suggesting IO also faced a similar history of environmental change, which seems plausible given their relatively close geographical distributions. In conclusion, populations within the invasive species MED and MEAM1 exhibited signatures of population expansion lacking in non-invasive species (IO and AUS) during the Pleistocene, a geological epoch marked by repeated climatic oscillations with cycles of glacial and interglacial periods. These expansions strongly suggested the potential of some Bemisia species’ genomes to affect their adaptability and invasiveness.

Keywords: whitefly, RADseq, invasive species, SNP, climate change

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10 Quantum Graph Approach for Energy and Information Transfer through Networks of Cables

Authors: Mubarack Ahmed, Gabriele Gradoni, Stephen C. Creagh, Gregor Tanner

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High-frequency cables commonly connect modern devices and sensors. Interestingly, the proportion of electric components is rising fast in an attempt to achieve lighter and greener devices. Modelling the propagation of signals through these cable networks in the presence of parameter uncertainty is a daunting task. In this work, we study the response of high-frequency cable networks using both Transmission Line and Quantum Graph (QG) theories. We have successfully compared the two theories in terms of reflection spectra using measurements on real, lossy cables. We have derived a generalisation of the vertex scattering matrix to include non-uniform networks – networks of cables with different characteristic impedances and propagation constants. The QG model implicitly takes into account the pseudo-chaotic behavior, at the vertices, of the propagating electric signal. We have successfully compared the asymptotic growth of eigenvalues of the Laplacian with the predictions of Weyl law. We investigate the nearest-neighbour level-spacing distribution of the resonances and compare our results with the predictions of Random Matrix Theory (RMT). To achieve this, we will compare our graphs with the generalisation of Wigner distribution for open systems. The problem of scattering from networks of cables can also provide an analogue model for wireless communication in highly reverberant environments. In this context, we provide a preliminary analysis of the statistics of communication capacity for communication across cable networks, whose eventual aim is to enable detailed laboratory testing of information transfer rates using software defined radio. We specialise this analysis in particular for the case of MIMO (Multiple-Input Multiple-Output) protocols. We have successfully validated our QG model with both TL model and laboratory measurements. The growth of Eigenvalues compares well with Weyl’s law and the level-spacing distribution agrees so well RMT predictions. The results we achieved in the MIMO application compares favourably with the prediction of a parallel on-going research (sponsored by NEMF21.)

Keywords: eigenvalues, multiple-input multiple-output, quantum graph, random matrix theory, transmission line

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9 Model Reference Adaptive Approach for Power System Stabilizer for Damping of Power Oscillations

Authors: Jožef Ritonja, Bojan Grčar, Boštjan Polajžer

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In recent years, electricity trade between neighboring countries has become increasingly intense. Increasing power transmission over long distances has resulted in an increase in the oscillations of the transmitted power. The damping of the oscillations can be carried out with the reconfiguration of the network or the replacement of generators, but such solution is not economically reasonable. The only cost-effective solution to improve the damping of power oscillations is to use power system stabilizers. Power system stabilizer represents a part of synchronous generator control system. It utilizes semiconductor’s excitation system connected to the rotor field excitation winding to increase the damping of the power system. The majority of the synchronous generators are equipped with the conventional power system stabilizers with fixed parameters. The control structure of the conventional power system stabilizers and the tuning procedure are based on the linear control theory. Conventional power system stabilizers are simple to realize, but they show non-sufficient damping improvement in the entire operating conditions. This is the reason that advanced control theories are used for development of better power system stabilizers. In this paper, the adaptive control theory for power system stabilizers design and synthesis is studied. The presented work is focused on the use of model reference adaptive control approach. Control signal, which assures that the controlled plant output will follow the reference model output, is generated by the adaptive algorithm. Adaptive gains are obtained as a combination of the "proportional" term and with the σ-term extended "integral" term. The σ-term is introduced to avoid divergence of the integral gains. The necessary condition for asymptotic tracking is derived by means of hyperstability theory. The benefits of the proposed model reference adaptive power system stabilizer were evaluated as objectively as possible by means of a theoretical analysis, numerical simulations and laboratory realizations. Damping of the synchronous generator oscillations in the entire operating range was investigated. Obtained results show the improved damping in the entire operating area and the increase of the power system stability. The results of the presented work will help by the development of the model reference power system stabilizer which should be able to replace the conventional stabilizers in power systems.

Keywords: power system, stability, oscillations, power system stabilizer, model reference adaptive control

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8 Chronic wrist pain among handstand practitioners. A questionnaire study.

Authors: Martonovich Noa, Maman David, Alfandari Liad, Behrbalk Eyal.

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Introduction: The human body is designed for upright standing and walking, with the lower extremities and axial skeleton supporting weight-bearing. Constant weight-bearing on joints not meant for this action can lead to various pathologies, as seen in wheelchair users. Handstand practitioners use their wrists as weight-bearing joints during activities, but little is known about wrist injuries in this population. This study aims to investigate the epidemiology of wrist pain among handstand practitioners, as no such data currently exist. Methods: The study is a cross-sectional online survey conducted among athletes who regularly practice handstands. Participants were asked to complete a three-part questionnaire regarding their workout regimen, training habits, and history of wrist pain. The inclusion criteria were athletes over 18 years old who practice handstands more than twice a month for at least 4 months. All data were collected using Google Forms, organized and anonymized using Microsoft Excel, and analyzed using IBM SPSS 26.0. Descriptive statistics were calculated, and potential risk factors were tested using asymptotic t-tests and Fisher's tests. Differences were considered significant when p < 0.05. Results: This study surveyed 402 athletes who regularly practice handstands to investigate the prevalence of chronic wrist pain and potential risk factors. The participants had a mean age of 31.3 years, with most being male and having an average of 5 years of training experience. 56% of participants reported chronic wrist pain, and 14.4% reported a history of distal radial fracture. Yoga was the most practiced form, followed by Capoeira. No significant differences were found in demographic data between participants with and without chronic wrist pain, and no significant associations were found between chronic wrist pain prevalence and warm-up routines or protective aids. Conclusion: The lower half of the body is meant to handle weight-bearing and impact, while transferring the load to upper extremities can lead to various pathologies. Athletes who perform handstands are particularly prone to chronic wrist pain, which affects over half of them. Warm-up sessions and protective instruments like wrist braces do not seem to prevent chronic wrist pain, and there are no significant differences in age or training volume between athletes with and without the condition. Further research is needed to understand the causes of chronic wrist pain in athletes, given the growing popularity of sports and activities that can cause this type of injury.

Keywords: handstand, handbalance, wrist pain, hand and wrist surgery, yoga, calisthenics, circus, capoeira, movement.

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7 Adaptive Environmental Control System Strategy for Cabin Air Quality in Commercial Aircrafts

Authors: Paolo Grasso, Sai Kalyan Yelike, Federico Benzi, Mathieu Le Cam

Abstract:

The cabin air quality (CAQ) in commercial aircraft is of prime interest, especially in the context of the COVID-19 pandemic. Current Environmental Control Systems (ECS) rely on a prescribed fresh airflow per passenger to dilute contaminants. An adaptive ECS strategy is proposed, leveraging air sensing and filtration technologies to ensure a better CAQ. This paper investigates the CAQ level achieved in commercial aircraft’s cabin during various flight scenarios. The modeling and simulation analysis is performed in a Modelica-based environment describing the dynamic behavior of the system. The model includes the following three main systems: cabin, recirculation loop and air-conditioning pack. The cabin model evaluates the thermo-hygrometric conditions and the air quality in the cabin depending on the number of passengers and crew members, the outdoor conditions and the conditions of the air supplied to the cabin. The recirculation loop includes models of the recirculation fan, ordinary and novel filtration technology, mixing chamber and outflow valve. The air-conditioning pack includes models of heat exchangers and turbomachinery needed to condition the hot pressurized air bled from the engine, as well as selected contaminants originated from the outside or bled from the engine. Different ventilation control strategies are modeled and simulated. Currently, a limited understanding of contaminant concentrations in the cabin and the lack of standardized and systematic methods to collect and record data constitute a challenge in establishing a causal relationship between CAQ and passengers' comfort. As a result, contaminants are neither measured nor filtered during flight, and the current sub-optimal way to avoid their accumulation is their dilution with the fresh air flow. However, the use of a prescribed amount of fresh air comes with a cost, making the ECS the most energy-demanding non-propulsive system within an aircraft. In such a context, this study shows that an ECS based on a reduced and adaptive fresh air flow, and relying on air sensing and filtration technologies, provides promising results in terms of CAQ control. The comparative simulation results demonstrate that the proposed adaptive ECS brings substantial improvements to the CAQ in terms of both controlling the asymptotic values of the concentration of the contaminant and in mitigating hazardous scenarios, such as fume events. Original architectures allowing for adaptive control of the inlet air flow rate based on monitored CAQ will change the requirements for filtration systems and redefine the ECS operation.

Keywords: cabin air quality, commercial aircraft, environmental control system, ventilation

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6 Nonlinear Optics of Dirac Fermion Systems

Authors: Vipin Kumar, Girish S. Setlur

Abstract:

Graphene has been recognized as a promising 2D material with many new properties. However, pristine graphene is gapless which hinders its direct application towards graphene-based semiconducting devices. Graphene is a zero-gapp and linearly dispersing semiconductor. Massless charge carriers (quasi-particles) in graphene obey the relativistic Dirac equation. These Dirac fermions show very unusual physical properties such as electronic, optical and transport. Graphene is analogous to two-level atomic systems and conventional semiconductors. We may expect that graphene-based systems will also exhibit phenomena that are well-known in two-level atomic systems and in conventional semiconductors. Rabi oscillation is a nonlinear optical phenomenon well-known in the context of two-level atomic systems and also in conventional semiconductors. It is the periodic exchange of energy between the system of interest and the electromagnetic field. The present work describes the phenomenon of Rabi oscillations in graphene based systems. Rabi oscillations have already been described theoretically and experimentally in the extensive literature available on this topic. To describe Rabi oscillations they use an approximation known as rotating wave approximation (RWA) well-known in studies of two-level systems. RWA is valid only near conventional resonance (small detuning)- when the frequency of the external field is nearly equal to the particle-hole excitation frequency. The Rabi frequency goes through a minimum close to conventional resonance as a function of detuning. Far from conventional resonance, the RWA becomes rather less useful and we need some other technique to describe the phenomenon of Rabi oscillation. In conventional systems, there is no second minimum - the only minimum is at conventional resonance. But in graphene we find anomalous Rabi oscillations far from conventional resonance where the Rabi frequency goes through a minimum that is much smaller than the conventional Rabi frequency. This is known as anomalous Rabi frequency and is unique to graphene systems. We have shown that this is attributable to the pseudo-spin degree of freedom in graphene systems. A new technique, which is an alternative to RWA called asymptotic RWA (ARWA), has been invoked by our group to discuss the phenomenon of Rabi oscillation. Experimentally accessible current density shows different types of threshold behaviour in frequency domain close to the anomalous Rabi frequency depending on the system chosen. For single layer graphene, the exponent at threshold is equal to 1/2 while in case of bilayer graphene, it is computed to be equal to 1. Bilayer graphene shows harmonic (anomalous) resonances absent in single layer graphene. The effect of asymmetry and trigonal warping (a weak direct inter-layer hopping in bilayer graphene) on these oscillations is also studied in graphene systems. Asymmetry has a remarkable effect only on anomalous Rabi oscillations whereas the Rabi frequency near conventional resonance is not significantly affected by the asymmetry parameter. In presence of asymmetry, these graphene systems show Rabi-like oscillations (offset oscillations) even for vanishingly small applied field strengths (less than the gap parameter). The frequency of offset oscillations may be identified with the asymmetry parameter.

Keywords: graphene, Bilayer graphene, Rabi oscillations, Dirac fermion systems

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5 Numerical Investigation of the Boundary Conditions at Liquid-Liquid Interfaces in the Presence of Surfactants

Authors: Bamikole J. Adeyemi, Prashant Jadhawar, Lateef Akanji

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Liquid-liquid interfacial flow is an important process that has applications across many spheres. One such applications are residual oil mobilization, where crude oil and low salinity water are emulsified due to lowered interfacial tension under the condition of low shear rates. The amphiphilic components (asphaltenes and resins) in crude oil are considered to assemble at the interface between the two immiscible liquids. To justify emulsification, drag and snap-off suppression as the main effects of low salinity water, mobilization of residual oil is visualized as thickening and slip of the wetting phase at the brine/crude oil interface which results in the squeezing and drag of the non-wetting phase to the pressure sinks. Meanwhile, defining the boundary conditions for such a system can be very challenging since the interfacial dynamics do not only depend on interfacial tension but also the flow rate. Hence, understanding the flow boundary condition at the brine/crude oil interface is an important step towards defining the influence of low salinity water composition on residual oil mobilization. This work presents a numerical evaluation of three slip boundary conditions that may apply at liquid-liquid interfaces. A mathematical model was developed to describe the evolution of a viscoelastic interfacial thin liquid film. The base model is developed by the asymptotic expansion of the full Navier-Stokes equations for fluid motion due to gradients of surface tension. This model was upscaled to describe the dynamics of the film surface deformation. Subsequently, Jeffrey’s model was integrated into the formulations to account for viscoelastic stress within a long wave approximation of the Navier-Stokes equations. To study the fluid response to a prescribed disturbance, a linear stability analysis (LSA) was performed. The dispersion relation and the corresponding characteristic equation for the growth rate were obtained. Three slip (slip, 1; locking, -1; and no-slip, 0) boundary conditions were examined using the resulted characteristic equation. Also, the dynamics of the evolved interfacial thin liquid film were numerically evaluated by considering the influence of the boundary conditions. The linear stability analysis shows that the boundary conditions of such systems are greatly impacted by the presence of amphiphilic molecules when three different values of interfacial tension were tested. The results for slip and locking conditions are consistent with the fundamental solution representation of the diffusion equation where there is film decay. The interfacial films at both boundary conditions respond to exposure time in a similar manner with increasing growth rate which resulted in the formation of more droplets with time. Contrarily, no-slip boundary condition yielded an unbounded growth and it is not affected by interfacial tension.

Keywords: boundary conditions, liquid-liquid interfaces, low salinity water, residual oil mobilization

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4 Linear Evolution of Compressible Görtler Vortices Subject to Free-Stream Vortical Disturbances

Authors: Samuele Viaro, Pierre Ricco

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Görtler instabilities generate in boundary layers from an unbalance between pressure and centrifugal forces caused by concave surfaces. Their spatial streamwise evolution influences transition to turbulence. It is therefore important to understand even the early stages where perturbations, still small, grow linearly and could be controlled more easily. This work presents a rigorous theoretical framework for compressible flows using the linearized unsteady boundary region equations, where only the streamwise pressure gradient and streamwise diffusion terms are neglected from the full governing equations of fluid motion. Boundary and initial conditions are imposed through an asymptotic analysis in order to account for the interaction of the boundary layer with free-stream turbulence. The resulting parabolic system is discretize with a second-order finite difference scheme. Realistic flow parameters are chosen from wind tunnel studies performed at supersonic and subsonic conditions. The Mach number ranges from 0.5 to 8, with two different radii of curvature, 5 m and 10 m, frequencies up to 2000 Hz, and vortex spanwise wavelengths from 5 mm to 20 mm. The evolution of the perturbation flow is shown through velocity, temperature, pressure profiles relatively close to the leading edge, where non-linear effects can still be neglected, and growth rate. Results show that a global stabilizing effect exists with the increase of Mach number, frequency, spanwise wavenumber and radius of curvature. In particular, at high Mach numbers curvature effects are less pronounced and thermal streaks become stronger than velocity streaks. This increase of temperature perturbations saturates at approximately Mach 4 flows, and is limited in the early stage of growth, near the leading edge. In general, Görtler vortices evolve closer to the surface with respect to a flat plate scenario but their location shifts toward the edge of the boundary layer as the Mach number increases. In fact, a jet-like behavior appears for steady vortices having small spanwise wavelengths (less than 10 mm) at Mach 8, creating a region of unperturbed flow close to the wall. A similar response is also found at the highest frequency considered for a Mach 3 flow. Larger vortices are found to have a higher growth rate but are less influenced by the Mach number. An eigenvalue approach is also employed to study the amplification of the perturbations sufficiently downstream from the leading edge. These eigenvalue results are compared with the ones obtained through the initial value approach with inhomogeneous free-stream boundary conditions. All of the parameters here studied have a significant influence on the evolution of the instabilities for the Görtler problem which is indeed highly dependent on initial conditions.

Keywords: compressible boundary layers, Görtler instabilities, receptivity, turbulence transition

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3 Estimation of Effective Mechanical Properties of Linear Elastic Materials with Voids Due to Volume and Surface Defects

Authors: Sergey A. Lurie, Yury O. Solyaev, Dmitry B. Volkov-Bogorodsky, Alexander V. Volkov

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The media with voids is considered and the method of the analytical estimation of the effective mechanical properties in the theory of elastic materials with voids is proposed. The variational model of the porous media is discussed, which is based on the model of the media with fields of conserved dislocations. It is shown that this model is fully consistent with the known model of the linear elastic materials with voids. In the present work, the generalized model of the porous media is proposed in which the specific surface properties are associated with the field of defects-pores in the volume of the deformed body. Unlike typical surface elasticity model, the strain energy density of the considered model includes the special part of the surface energy with the quadratic form of the free distortion tensor. In the result, the non-classical boundary conditions take modified form of the balance equations of volume and surface stresses. The analytical approach is proposed in the present work which allows to receive the simple enough engineering estimations for effective characteristics of the media with free dilatation. In particular, the effective flexural modulus and Poisson's ratio are determined for the problem of a beam pure bending. Here, the known voids elasticity solution was expanded on the generalized model with the surface effects. Received results allow us to compare the deformed state of the porous beam with the equivalent classic beam to introduce effective bending rigidity. Obtained analytical expressions for the effective properties depend on the thickness of the beam as a parameter. It is shown that the flexural modulus of the porous beam is decreased with an increasing of its thickness and the effective Poisson's ratio of the porous beams can take negative values for the certain values of the model parameters. On the other hand, the effective shear modulus is constant under variation of all values of the non-classical model parameters. Solutions received for a beam pure bending and the hydrostatic loading of the porous media are compared. It is shown that an analytical estimation for the bulk modulus of the porous material under hydrostatic compression gives an asymptotic value for the effective bulk modulus of the porous beam in the case of beam thickness increasing. Additionally, it is shown that the scale effects appear due to the surface properties of the porous media. Obtained results allow us to offer the procedure of an experimental identification of the non-classical parameters in the theory of the linear elastic materials with voids based on the bending tests for samples with different thickness. Finally, the problem of implementation of the Saint-Venant hypothesis for the transverse stresses in the porous beam are discussed. These stresses are different from zero in the solution of the voids elasticity theory, but satisfy the integral equilibrium equations. In this work, the exact value of the introduced surface parameter was found, which provides the vanishing of the transverse stresses on the free surfaces of a beam.

Keywords: effective properties, scale effects, surface defects, voids elasticity

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2 OpenFOAM Based Simulation of High Reynolds Number Separated Flows Using Bridging Method of Turbulence

Authors: Sagar Saroha, Sawan S. Sinha, Sunil Lakshmipathy

Abstract:

Reynolds averaged Navier-Stokes (RANS) model is the popular computational tool for prediction of turbulent flows. Being computationally less expensive as compared to direct numerical simulation (DNS), RANS has received wide acceptance in industry and research community as well. However, for high Reynolds number flows, the traditional RANS approach based on the Boussinesq hypothesis is incapacitated to capture all the essential flow characteristics, and thus, its performance is restricted in high Reynolds number flows of practical interest. RANS performance turns out to be inadequate in regimes like flow over curved surfaces, flows with rapid changes in the mean strain rate, duct flows involving secondary streamlines and three-dimensional separated flows. In the recent decade, partially averaged Navier-Stokes (PANS) methodology has gained acceptability among seamless bridging methods of turbulence- placed between DNS and RANS. PANS methodology, being a scale resolving bridging method, is inherently more suitable than RANS for simulating turbulent flows. The superior ability of PANS method has been demonstrated for some cases like swirling flows, high-speed mixing environment, and high Reynolds number turbulent flows. In our work, we intend to evaluate PANS in case of separated turbulent flows past bluff bodies -which is of broad aerodynamic research and industrial application. PANS equations, being derived from base RANS, continue to inherit the inadequacies from the parent RANS model based on linear eddy-viscosity model (LEVM) closure. To enhance PANS’ capabilities for simulating separated flows, the shortcomings of the LEVM closure need to be addressed. Inabilities of the LEVMs have inspired the development of non-linear eddy viscosity models (NLEVM). To explore the potential improvement in PANS performance, in our study we evaluate the PANS behavior in conjugation with NLEVM. Our work can be categorized into three significant steps: (i) Extraction of PANS version of NLEVM from RANS model, (ii) testing the model in the homogeneous turbulence environment and (iii) application and evaluation of the model in the canonical case of separated non-homogeneous flow field (flow past prismatic bodies and bodies of revolution at high Reynolds number). PANS version of NLEVM shall be derived and implemented in OpenFOAM -an open source solver. Homogeneous flows evaluation will comprise the study of the influence of the PANS’ filter-width control parameter on the turbulent stresses; the homogeneous analysis performed over typical velocity fields and asymptotic analysis of Reynolds stress tensor. Non-homogeneous flow case will include the study of mean integrated quantities and various instantaneous flow field features including wake structures. Performance of PANS + NLEVM shall be compared against the LEVM based PANS and LEVM based RANS. This assessment will contribute to significant improvement of the predictive ability of the computational fluid dynamics (CFD) tools in massively separated turbulent flows past bluff bodies.

Keywords: bridging methods of turbulence, high Re-CFD, non-linear PANS, separated turbulent flows

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1 Identification of a Panel of Epigenetic Biomarkers for Early Detection of Hepatocellular Carcinoma in Blood of Individuals with Liver Cirrhosis

Authors: Katarzyna Lubecka, Kirsty Flower, Megan Beetch, Lucinda Kurzava, Hannah Buvala, Samer Gawrieh, Suthat Liangpunsakul, Tracy Gonzalez, George McCabe, Naga Chalasani, James M. Flanagan, Barbara Stefanska

Abstract:

Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, is the second leading cause of cancer death worldwide. Late onset of clinical symptoms in HCC results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable early detection biomarkers that can distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed and could increase the cure rate from 5% to 80%. We used Illumina-450K microarray to test whether blood DNA, an easily accessible source of DNA, bear site-specific changes in DNA methylation in response to HCC before diagnosis with conventional tools (pre-diagnostic). Top 11 differentially methylated sites were selected for validation by pyrosequencing. The diagnostic potential of the 11 pyrosequenced probes was tested in blood samples from a prospective cohort of cirrhotic patients. We identified 971 differentially methylated CpG sites in pre-diagnostic HCC cases as compared with healthy controls (P < 0.05, paired Wilcoxon test, ICC ≥ 0.5). Nearly 76% of differentially methylated CpG sites showed lower levels of methylation in cases vs. controls (P = 2.973E-11, Wilcoxon test). Classification of the CpG sites according to their location relative to CpG islands and transcription start site revealed that those hypomethylated loci are located in regulatory regions important for gene transcription such as CpG island shores, promoters, and 5’UTR at higher frequency than hypermethylated sites. Among 735 CpG sites hypomethylated in cases vs. controls, 482 sites were assigned to gene coding regions whereas 236 hypermethylated sites corresponded to 160 genes. Bioinformatics analysis using GO, KEGG and DAVID knowledgebase indicate that differentially methylated CpG sites are located in genes associated with functions that are essential for gene transcription, cell adhesion, cell migration, and regulation of signal transduction pathways. Taking into account the magnitude of the difference, statistical significance, location, and consistency across the majority of matched pairs case-control, we selected 11 CpG loci corresponding to 10 genes for further validation by pyrosequencing. We established that methylation of CpG sites within 5 out of those 10 genes distinguish cirrhotic patients who subsequently developed HCC from those who stayed cancer free (cirrhotic controls), demonstrating potential as biomarkers of early detection in populations at risk. The best predictive value was detected for CpGs located within BARD1 (AUC=0.70, asymptotic significance ˂0.01). Using an additive logistic regression model, we further showed that 9 CpG loci within those 5 genes, that were covered in pyrosequenced probes, constitute a panel with high diagnostic accuracy (AUC=0.887; 95% CI:0.80-0.98). The panel was able to distinguish pre-diagnostic cases from cirrhotic controls free of cancer with 88% sensitivity at 70% specificity. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established biomarker panel has high potential to be developed into a routine clinical test after validation in larger cohorts. This study was supported by Showalter Trust, American Cancer Society (IRG#14-190-56), and Purdue Center for Cancer Research (P30 CA023168) granted to BS.

Keywords: biomarker, DNA methylation, early detection, hepatocellular carcinoma

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