Search results for: Vincent Gay-Bellile

Authors: Paul Lemarignier, Olivier Fiquet, Vincent Pateloup

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In line with the strong desire of nuclear energy players to have ever more effective products in terms of safety, research programs on E-ATF (Enhanced-Accident Tolerant Fuels) that are more resilient, particularly to the loss of coolant, have been launched in all countries with nuclear power plants. Among the multitude of solutions being developed internationally, carcinoembryonic antigen (CEA) and its partners are investigating a promising solution, which is the realization of CERMET (CERamic-METal) type fuel pellets made of a matrix of fissile material, uranium dioxide UO2, which has a low thermal conductivity, and a metallic phase with a high thermal conductivity to improve heat evacuation. Work has focused on the development by powder metallurgy of micro-structured CERMETs, characterized by networks of metallic phase embedded in the UO₂ matrix. Other types of macro-structured CERMETs, based on concepts proposed by thermal simulation studies, have been developed with a metallic phase with a specific geometry to optimize heat evacuation. This solution could not be developed using traditional processes, so additive manufacturing, which revolutionizes traditional design principles, is used to produce these innovative prototype concepts. At CEA Cadarache, work is first carried out on a non-radioactive surrogate material, alumina, in order to acquire skills and to develop the equipment, in particular the robocasting machine, an additive manufacturing technique selected for its simplicity and the possibility of optimizing the paste formulations. A manufacturing chain was set up, with the pastes production, the 3D printing of pellets, and the associated thermal post-treatment. The work leading to the first elaborations of macro-structured alumina/molybdenum CERMETs will be presented. This work was carried out with the support of Framatome and EdF.

Keywords: additive manufacturing, alumina, CERMET, molybdenum, nuclear safety

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Authors: Anne Heirman, Vincent van der Noort, Rob van Son, Marije Petersen, Lisette van der Molen, Gyorgy Halmos, Richard Dirven, Michiel van den Brekel

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Objective: Voice prosthesis leakage significantly impacts laryngectomies patients' quality of life, causing insecurity and frequent unplanned hospital visits and costs. In this study, the concept of prophylactic voice prosthesis replacement was explored to prevent leakages. Study Design: A retrospective cohort study. Setting: Tertiary hospital. Methods: Device lifetimes and voice prosthesis replacements of a retrospective cohort, including all patients with laryngectomies between 2000 and 2012 in the Netherlands Cancer Institute, were used to calculate the number of needed voice prostheses per patient per year when preventing 70% of the leakages by prophylactic replacement. Various strategies for the timing of prophylactic replacement were considered: Adaptive strategies based on the individual patient’s history of replacement and fixed strategies based on the results of patients with similar voice prosthesis or treatment characteristics. Results: Patients used a median of 3.4 voice prostheses per year (range 0.1-48.1). We found a high inter-and intrapatient variability in device lifetime. When applying prophylactic replacement, this would become a median of 9.4 voice prostheses per year, which means replacement every 38 days, implying more than six additional voice prostheses per patient per year. The individual adaptive model showed that preventing 70% of the leakages was impossible for most patients, and only a median of 25% can be prevented. Monte-Carlo simulations showed that prophylactic replacement is not feasible due to the high Coefficient of Variation (Standard Deviation/Mean) in device lifetime. Conclusion: Based on our simulations, prophylactic replacement of voice prostheses is not feasible due to high inter-and intrapatient variation in device lifetime.

Keywords: voice prosthesis, voice rehabilitation, total laryngectomy, prosthetic leakage, device lifetime

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Authors: Abolfazl Zaraki, Yoshikatsu Hayashi, Harry Thorpe, Vincent Strong, Gisle-Andre Larsen, William Holderbaum

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Thanks to the high maneuverability of the cable-driven hyper-redundant manipulators (HRMs), this class of robots has shown a superior capability in highly confined and unstructured space applications. Although the large number of degrees of freedom (DOF) of HRMs enhances the motion flexibility and the robot’s reachability range, it highly increases the complexity of the kinematic configuration which makes the kinematic control problem very challenging or even impossible to solve. This paper presents our current progress achieved on the development of a kinematic-based leader-follower control system which is designed to control not only the robot’s body posture but also to control the trajectory of the robot’s movement in a semi-autonomous manner (the human operator is retained in the robot’s control loop). To obtain the forward kinematic model, the coordinate frames are established by the classical Denavit–Hartenburg (D-H) convention for a hyper-redundant serial manipulator which has a controlled cables-driven mechanism. To solve the inverse kinematics of the robot, unlike the conventional methods, a leader-follower mechanism, based on the sequential inverse kinematic, is followed. Using this mechanism, the inverse kinematic problem is solved for all sequential joints starting from the head joint to the base joint of the robot. To verify the kinematic design and simulate the robot motion, the MATLAB robotic toolbox is used. The simulation result demonstrated the promising capability of the proposed leader-follower control system in controlling the robot motion and trajectory in our confined space application.

Keywords: hyper-redundant robots, kinematic analysis, semi-autonomous control, serial manipulators

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Authors: Siddhant Yadav, Ann Vincent, Sanjeev Nanda, Karen M. Fischer, Jessica A. Wright

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Statement of the Problem: Despite the growing popularity of cannabis in the general population, there are several unknowns regarding its use, specific reasons for use, patient’s choice of products, health benefits, and adverse effects. The aim of our study was to evaluate patient-reported information related to cannabis use that was recorded in the electronic medical records. Methodology & Theoretical Orientation: We manually reviewed the electronic medical records of cannabis users who were part of a large pharmacogenomic study. Data abstracted included demographics, level of education, concurrent alcohol and tobacco use, type of cannabis utilized, formulation, indication, symptomatic improvement, or adverse effects reported. Following this, we did a descriptive statistical analysis. Findings: Our sample of 164 cannabis users were predominantly female (73.2%); 66% of users reported using cannabis for medical indications. Of the 109 patients who recorded information pertaining to alcohol/tobacco use, two-thirds of cannabis users reported concurrent use of alcohol, and about half of them were former or current tobacco users. The mean age of cannabis use was 66 years. Regarding the type of cannabis, 34.1% reported using marijuana, 32.3% reported CBD use, 1.8% reported using THC, and 1.2% reported using Marinol. Oral formulations (capsules, oils, suspensions, brownies, cakes, and tea) were the most common route (44 %). Indications for use included chronic pain (n=76), anxiety (n=9), counteracting side effects of chemotherapy (n=4), and palliative reasons (n=2). Fifty-eight of the 76 users endorsed improvement in chronic pain (80%), 5 users reported improvement in anxiety, and 2 reported improvement in side effects of chemotherapy. Conclusion & Significance: The majority of our cannabis users were Caucasian females, and there was a high likelihood of coinciding use of alcohol/tobacco in patients using cannabis. Most of our patients used the oral formulation for chronic pain. Importantly, a considerable number of patients reported improvements in chronic pain, anxiety, and side effects of chemotherapy.

Keywords: cannabis use, adverse effects, medical practice, indications

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Authors: Noe Brice Nkoumbou Kaptchouang, Pierre-Guy Vincent, Yann Monerie

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The present work addresses the modelling and the simulation of crack initiation and propagation in ductile materials which failed by void nucleation, growth, and coalescence. One of the current research frameworks on crack propagation is the use of cohesive-volumetric approach where the crack growth is modelled as a decohesion of two surfaces in a continuum material. In this framework, the material behavior is characterized by two constitutive relations, the volumetric constitutive law relating stress and strain, and a traction-separation law across a two-dimensional surface embedded in the three-dimensional continuum. Several cohesive models have been proposed for the simulation of crack growth in brittle materials. On the other hand, the application of cohesive models in modelling crack growth in ductile material is still a relatively open field. One idea developed in the literature is to identify the traction separation for ductile material based on the behavior of a continuously-deforming unit cell failing by void growth and coalescence. Following this method, the present study proposed a semi-analytical cohesive model for ductile material based on a micromechanical approach. The strain localization band prior to ductile failure is modelled as a cohesive band, and the Gurson-Tvergaard-Needleman plasticity model (GTN) is used to model the behavior of the cohesive band and derived a corresponding traction separation law. The numerical implementation of the model is realized using the non-smooth contact method (NSCD) where cohesive models are introduced as mixed boundary conditions between each volumetric finite element. The present approach is applied to the simulation of crack growth in nuclear ferritic steel. The model provides an alternative way to simulate crack propagation using the numerical efficiency of cohesive model with a traction separation law directly derived from porous continuous model.

Keywords: ductile failure, cohesive model, GTN model, numerical simulation

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Authors: Yiseyon Sunday Hosu, Motebang Dominic Vincent Nakin, Elphina N. Cishe

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Universal access to clean and safe drinking water and basic sanitation is one of the targets of the 6th Sustainable Development Goals (SDGs). This paper explores the evidence-based indicators of Water Rights Acts (2013) among households in the rural communities in the Mthatha River catchment of OR Tambo District Municipality of South Africa. Daily access to minimum 25 litres/person and the factors influencing clean water access were investigated in the catchment. A total number of 420 households were surveyed in the upper, peri-urban, lower and coastal regions of Mthatha Rivier catchment. Descriptive and logistic regression analyses were conducted on the data collected from the households to elicit vital information on domestic water security among rural community dwellers. The results show that approximately 68 percent of total households surveyed have access to the required minimum 25 litre/person/day, with 66.3 percent in upper region, 76 per cent in the peri-urban, 1.1 percent in the lower and 2.3 percent in the coastal regions. Only 30 percent among the total surveyed households had access to piped water either in the house or public taps. The logistic regression showed that access to clean water was influenced by lack of water infrastructure, proximity to urban regions, daily flow of pipe-borne water, household size and distance to public taps. This paper recommends that viable integrated rural community-based water infrastructure provision strategies between NGOs and local authority and the promotion of point of use (POU) technologies to enhance better access to clean water.

Keywords: domestic water, household technology, water security, rural community

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Authors: Vincent Murray

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The glycopeptide bleomycin is used in the treatment of testicular cancer, Hodgkin's lymphoma, and squamous cell carcinoma. Bleomycin damages and cleaves DNA in human cells, and this is considered to be the main mode of action for bleomycin's anti-tumor activity. In particular, double-strand breaks are thought to be the main mechanism for the cellular toxicity of bleomycin. Using Illumina next-generation DNA sequencing techniques, the genome-wide sequence specificity of bleomycin-induced double-strand breaks was determined in human cells. The degree of bleomycin cleavage was also assessed at the transcription start sites (TSSs) of actively transcribed genes and compared with non-transcribed genes. It was observed that bleomycin preferentially cleaved at the TSSs of actively transcribed human genes. There was a correlation between the degree of this enhanced cleavage at TSSs and the level of transcriptional activity. Bleomycin cleavage is also affected by chromatin structure and at TSSs, the peaks of bleomycin cleavage were approximately 200 bp apart. This indicated that bleomycin was able to detect phased nucleosomes at the TSSs of actively transcribed human genes. The genome-wide cleavage pattern of the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin was also investigated in human cells. As found for bleomycin, these bleomycin analogues also preferentially cleaved at the TSSs of actively transcribed human genes. The cytotoxicity (IC₅₀ values) of these bleomycin analogues was determined. It was found that the degree of enhanced cleavage at TSSs was inversely correlated with the IC₅₀ values of the bleomycin analogues. This suggested that the level of cleavage at the TSSs of actively transcribed human genes was important for the cytotoxicity of bleomycin and analogues. Hence this study provided a deeper understanding of the cellular processes involved in the cancer chemotherapeutic activity of bleomycin.

Keywords: anti-tumour activity, bleomycin analogues, chromatin structure, genome-wide study, Illumina DNA sequencing

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Authors: Etienne Gaborit, Dorothy Durnford, Daniel Deacu, Marco Carrera, Nathalie Gauthier, Camille Garnaud, Vincent Fortin

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A new experimental streamflow forecasting system was recently implemented at the Environment and Climate Change Canada’s (ECCC) Canadian Centre for Meteorological and Environmental Prediction (CCMEP). It relies on CaLDAS (Canadian Land Data Assimilation System) for the assimilation of surface variables, and on a surface prediction system that feeds a routing component. The surface energy and water budgets are simulated with the SVS (Soil, Vegetation, and Snow) Land-Surface Scheme (LSS) at 2.5-km grid spacing over Canada. The routing component is based on the Watroute routing scheme at 1-km grid spacing for the Great Lakes and Nelson River watersheds. The system is run in two distinct phases: an analysis part and a forecast part. During the analysis part, CaLDAS outputs are used to force the routing system, which performs streamflow assimilation. In forecast mode, the surface component is forced with the Canadian GEM atmospheric forecasts and is initialized with a CaLDAS analysis. Streamflow performances of this new system are presented over 2019. Performances are compared to the current ECCC’s operational streamflow forecasting system, which is different from the new experimental system in many aspects. These new streamflow forecasts are also compared to persistence. Overall, the new streamflow forecasting system presents promising results, highlighting the need for an elaborated assimilation phase before performing the forecasts. However, the system is still experimental and is continuously being improved. Some major recent improvements are presented here and include, for example, the assimilation of snow cover data from remote sensing, a backward propagation of assimilated flow observations, a new numerical scheme for the routing component, and a new reservoir model.

Keywords: assimilation system, distributed physical model, offline hydro-meteorological chain, short-term streamflow forecasts

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Authors: Vincent Murray

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The chromatin structure at the transcription start sites (TSSs) of genes is very important in the control of gene expression. In order for gene expression to occur, the chromatin structure at the TSS has to be altered so that the transcriptional machinery can be assembled and RNA transcripts can be produced. In particular, the nucleosome structure and positioning around the TSS has to be changed. Bleomycin is utilized as an anti-tumor agent to treat Hodgkin's lymphoma, squamous cell carcinoma, and testicular cancer. Bleomycin produces DNA damage in human cells and DNA strand breaks, especially double-strand breaks, are thought to be responsible for the cancer chemotherapeutic activity of bleomycin. Bleomycin is a large glycopeptide with molecular weight of approximately 1500 Daltons and hence its DNA strand cleavage activity can be utilized as a probe of chromatin structure. In this project, Illumina next-generation DNA sequencing technology was used to determine the position of DNA double-strand breaks at the TSSs of genes in intact cells. In this genome-wide study, it was found that bleomycin cleavage preferentially occurred at the TSSs of actively transcribed human genes in comparison with non-transcribed genes. There was a correlation between the level of enhanced bleomycin cleavage at TSSs and the degree of transcriptional activity. In addition, bleomycin was able to determine the position of nucleosomes at the TSSs of human genes. Bleomycin analogues were also utilized as probes of chromatin structure at the TSSs of human genes. In a similar manner to bleomycin, the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin preferentially cleaved at the TSSs of human genes. Interestingly this degree of enhanced TSS cleavage inversely correlated with the cytotoxicity (IC50 values) of BLM analogues. This indicated that the degree of cleavage by bleomycin analogues at the TSSs of human genes was very important in the cytotoxicity of bleomycin and analogues. It also provided a deeper insight into the mechanism of action of this cancer chemotherapeutic agent since actively transcribed genes were preferentially targeted.

Keywords: anti-cancer activity, chromatin structure, cytotoxicity, gene expression, next-generation DNA sequencing

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Authors: Sophia Cyril Vincent

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Background: As per the Indian Census 2011, there is nearly 104 million elderly population aged above 60 years (53 million females and 51 males), and the count is expected to be 173 million by the end of 2026. Nearly 5.5% of women and 1.5% of men are living alone.1 In India, even though it is the moral duty of the children to take care of aged parents, many elders are landing in old age homes due to the social transformation factors like mushrooming of nuclear families, migration of children, cultural echoes, differences in mindset and values. Nearly 728 old age homes are seen across the country, out of which 78 old age homes with approximately 3000 inmates are seen only in Bangalore2. The existing literature shows that elderly women residing in old age homes experience the challenges like- loneliness, health issues, rejection from children, grief, death anxiety, etc, which leads to mental and physical wellbeing in numerous and tangible ways3. Hence the best and cost-effective way to improve the meaning and quality of life among elderly females is logotherapy, a type of psychotherapeutic analysis and treatment, motivating and driving force4 within the human experience to lead a decent life. Aim: The current research is aimed at studying the effectiveness of a logotherapy intervention on meaning and quality of life among elderly women of old age homes. Samples:200 women aged < 60 years and staying in the old age home for more than 1 year were randomly allocated to the control group and experimental group. Methodology: Using the Meaning in life questionnaire (MLQ)and the World health organization quality of life (WHOQOL) questionnaire, meaning and quality of life were assessed among both groups' women. Intensive Logotherapy and meaning in life program for five days were provided for the experimental group and the control group, with no treatment. Result: Under analysis. Conclusion: It is the right of the elderly woman to lead a happy and peaceful life till her death irrespective of the residing place. Hence, continuous monitoring and effective management are necessary for elderly women.

Keywords: quality of life, meaning of life, logo therapy, old age home

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Authors: Florian Vincent Haase, Adrian Dierl, Anna Henke, Ralf Woll, Ennes Sarradj

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Structured sheet metals and structured sandwich sheet metals are three-dimensional, lightweight structures with increased stiffness which are used in the automotive industry. The impedance, a figure of resistance of a structure to vibrations, will be determined regarding plain sheets, structured sheets, and structured sandwich sheets. The aim of this paper is generating an experimental design in order to minimize costs and duration of experiments. The design of experiments will be used to reduce the large number of single tests required for the determination of correlation between the impedance and its influencing factors. Full and fractional factorials are applied in order to systematize and plan the experiments. Their major advantages are high quality results given the relatively small number of trials and their ability to determine the most important influencing factors including their specific interactions. The developed full factorial experimental design for the study of plain sheets includes three factor levels. In contrast to the study of plain sheets, the respective impedance analysis used on structured sheets and structured sandwich sheets should be split into three phases. The first phase consists of preliminary tests which identify relevant factor levels. These factor levels are subsequently employed in main tests, which have the objective of identifying complex relationships between the parameters and the reference variable. Possible post-tests can follow up in case additional study of factor levels or other factors are necessary. By using full and fractional factorial experimental designs, the required number of tests is reduced by half. In the context of this paper, the benefits from the application of design for experiments are presented. Furthermore, a multistage approach is shown to take into account unrealizable factor combinations and minimize experiments.

Keywords: structured sheet metals, structured sandwich sheet metals, impedance measurement, design of experiment

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Authors: Juan-Pedro Rica-Peromingo

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Teachers constantly need to innovate and redefine materials for their lectures, especially in areas such as Language for Specific Purposes (LSP) and Translation Studies (TS). It is therefore essential for the lecturers to be technically skilled to handle the never-ending evolution in software and technology, which are necessary elements especially in certain courses at university level. This need becomes even more evident in Audiovisual Translation (AVT) Modules and Courses. AVT has undergone considerable growth in the area of teaching and learning of languages for academic purposes. We have witnessed the development of a considerable number of masters and postgraduate courses where AVT becomes a tool for L2 learning. The teaching and learning of different AVT modes are components of undergraduate and postgraduate courses. Universities, in which AVT is offered as part of their teaching programme or training, make use of professional or free software programs. This paper presents an approach in AVT withina specific university context, in which technology is used by means of professional and nonprofessional software. Students take an AVT subject as part of their English Linguistics Master’s Degree at the Complutense University (UCM) in which they are using professional (Spot) and nonprofessional (Subtitle Workshop, Aegisub, Windows Movie Maker) software packages. The students are encouraged to develop their tasks and projects simulating authentic professional experiences and contexts in the different AVT modes: subtitling for hearing and deaf and hard of hearing population, audio description and dubbing. Selected scenes from TV series such as X-Files, Gossip girl, IT Crowd; extracts from movies: Finding Nemo, Good Will Hunting, School of Rock, Harry Potter, Up; and short movies (Vincent) were used. Hence, the complexity of the audiovisual materials used in class as well as the activities for their projects were graded. The assessment of the diverse tasks carried out by all the students are expected to provide some insights into the best way to improve their linguistic accuracy and oral and written productions with the use of different AVT modes in a very specific ESP university context.

Keywords: ESP, audiovisual translation, technology, university teaching, teaching

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Authors: Michael A. Sprayberry, Vincent C. Paquit

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Process parameter optimization in metal powder bed electron beam melting (MPBEBM) is crucial to ensure the technology's repeatability, control, and industry-continued adoption. Despite continued efforts to address the challenges via the traditional design of experiments and process mapping techniques, there needs to be more successful in an on-the-fly optimization framework that can be adapted to MPBEBM systems. Additionally, data-intensive physics-based modeling and simulation methods are difficult to support by a metal AM alloy or system due to cost restrictions. To mitigate the challenge of resource-intensive experiments and models, this paper introduces a Multi-Objective Reinforcement Learning (MORL) methodology defined as an optimization problem for MPBEBM. An off-policy MORL framework based on policy gradient is proposed to discover optimal sets of beam power (P) – beam velocity (v) combinations to maintain a steady-state melt pool depth and phase transformation. For this, an experimentally validated Eagar-Tsai melt pool model is used to simulate the MPBEBM environment, where the beam acts as the agent across the P – v space to maximize returns for the uncertain powder bed environment producing a melt pool and phase transformation closer to the optimum. The culmination of the training process yields a set of process parameters {power, speed, hatch spacing, layer depth, and preheat} where the state (P,v) with the highest returns corresponds to a refined process parameter mapping. The resultant objects and mapping of returns to the P-v space show convergence with experimental observations. The framework, therefore, provides a model-free multi-objective approach to discovery without the need for trial-and-error experiments.

Keywords: additive manufacturing, metal powder bed fusion, reinforcement learning, process parameter optimization

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Authors: Pierluigi Tosi, Ed de Jong, Gerard van Klink, Luc Vincent, Alice Mija

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During the last decades renewable and low-cost resources have attracted increasingly interest. Carbohydrates can be derived by lignocellulosic biomasses, which is an attractive option since they represent the most abundant carbon source available in nature. Carbohydrates can be converted in a plethora of industrially relevant compounds, such as 5-hydroxymethylfurfural (HMF) and levulinic acid (LA), within acid catalyzed dehydration of sugars with mineral acids. Unfortunately, these acid catalyzed conversions suffer of the unavoidable formation of highly viscous heterogeneous poly-disperse carbon based materials known as humins. This black colored low value by-product is made by a complex mixture of macromolecules built by covalent random condensations of the several compounds present during the acid catalyzed conversion. Humins molecular structure is still under investigation but seems based on furanic rings network linked by aliphatic chains and decorated by several reactive moieties (ketones, aldehydes, hydroxyls, …). Despite decades of research, currently there is no way to avoid humins formation. The key parameter for enhance the economic viability of carbohydrate conversion processes is, therefore, increasing the economic value of the humins by-product. Herein are presented new humins based polymeric materials that can be prepared starting from the raw by-product by thermal treatment, without any step of purification or pretreatment. Humins foams can be produced with the control of reaction key parameters, obtaining polymeric porous materials with designed porosity, density, thermal and electrical conductivity, chemical and electrical stability, carbon amount and mechanical properties. Physico chemical properties can be enhanced by modifications on the starting raw material or adding different species during the polymerization. A comparisons on the properties of different compositions will be presented, along with tested applications. The authors gratefully acknowledge the European Community for financial support through Marie-Curie H2020-MSCA-ITN-2015 "HUGS" Project.

Keywords: by-product, humins, polymers, valorization

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Authors: Lancelot Boulet, Pierre Benard, Ghislain Lartigue, Vincent Moureau, Nicolas Chauvet, Sheddia Didorally

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International aeronautic standards demand a fire certification for engines that demonstrate their resistance. This demonstration relies on tests performed with prototype engines in the late stages of the development. Hardest tests require to place a kerosene standardized flame in front of the engine casing during a given time with imposed temperature and heat flux. The purpose of this work is to provide a better characterization of a kerosene/air certification burner in order to minimize the risks of test failure. A first Large-Eddy Simulation (LES) study of the certification burner permitted to model and simulate this burner, including both adiabatic and Conjugate Heat Transfer (CHT) computations. Carried out on unstructured grids with 40 million tetrahedral cells, using the finite-volume YALES2 code, spray combustion, forced convection on walls and conduction in the solid parts of the burner were coupled to achieve a detailed description of heat transfer. It highlighted the fact that conduction inside the solid has a real impact on the flame topology and the combustion regime. However, in the absence of radiative heat transfer, unrealistic temperature of the equipment was obtained. The aim of the present study is to include the radiative heat transfer in order to reach the same temperature given by experimental measurements. First, various test-cases are conducted to validate the coupling between the different heat solvers. Then, adiabatic case, CHT case, as well as CHT including radiative transfer are studied and compared. The LES model is finally applied to investigate the heat transfer in a flame impaction configuration. The aim is to progress on fire test modeling so as to reach a good confidence level as far as success of the certification test is concerned.

Keywords: conjugate heat transfer, fire resistance test, large-eddy simulation, radiative transfer, turbulent combustion

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Authors: Matthew P. Mancini, Vincent Ribiere

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Today’s workers face more numerous and complex challenges and are required to be increasingly interdependent and faster learners. Knowledge sharing activities between people have been understood as a significant element affecting organizational innovation performance. While they do have the potential to spark cognitive conflict, disagreement is important from an organizational perspective because it can stimulate the development of new ideas and perhaps pave the way for creativity, innovation, and competitive advantage. How teams cope with the cognitive conflict dimension of knowledge sharing and the associated interpersonal risk is what captures our attention. Specifically, assertive conflict management strategies have a positive influence on knowledge sharing behaviors, and team psychological safety has a positive influence on knowledge sharing intention. This paper focuses on explaining the impact that these factors have on the shaping of an individual’s decision to engage or not in knowledge sharing activities. To accomplish this, we performed an empirical analysis on the results of our questionnaire about knowledge-sharing related conflict management and team psychological safety in pharmaceutical enterprises located in North America, Europe, and Asia. First, univariate analysis is used to characterize behavior regarding conflict management strategy into two groups. Group 1 presents assertive conflict management strategies and group 2 shows unassertive ones. Then, by using SEM methodology, we evaluated the relationships between them and the team psychological safety construct with the knowledge sharing process. The results of the SEM analysis show that assertive conflict management strategies affect the knowledge sharing process the most with a small, but significant effect from team psychological safety. The findings suggest that assertive conflict management strategies are just as important as knowledge sharing intentions for encouraging knowledge sharing behavior. This paper provides clear insights into how employees manage the sharing of their knowledge in the face of conflict and interpersonal risk and the relative importance of these factors in sustaining productive knowledge sharing activities.

Keywords: cognitive dissonance, conflict management, knowledge sharing, organizational behavior, psychological safety

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Authors: Vincent Mokoka, Kai Behn, Edwin Mudongo, Jan Ruppert, Kingsley Ayisi, Anja Linstädter

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Severe drought may trigger a transition of vegetation composition in dryland grasslands, with productive perennial grasses often being replaced by annual grasses. Grazing pressure is thought to exacerbate drought effects, but little is known on the joint effects of grazing and drought on the functional and taxonomic composition of the herbaceous vegetation in African savannas. This study thus aimed to elucidate which herbaceous species and plant functional types (PFTs) are most resistant to prolonged drought and grazing and whether resting plays a role in this context. Thus, we performed a six-year field experiment in South Africa’s Limpopo province, combining drought and grazing treatments. Aboveground herbaceous biomass was harvested annually and separated into species. We grouped species into five PFTs, i.e. very broad-leaved perennial grasses, broad-leaved perennial grasses, narrow-leaved perennial grasses, annual grasses, and forbs. For all species, we also recorded three-leaf traits (leaf area - LA, specific leaf area – SLA, and leaf dry matter content – LDM) to describe their resource acquisition strategies. We used generalized linear models to test for treatment effects and their interaction. Association indices were used to detect the relationship between species and treatments. We found that there were no absolute winner species or PFTs, as the six-year severe drought had a pronounced negative impact on the biomass production of all species and PFTs. However, we detected relative winners with increases in relative abundances, mainly forbs and less palatable narrow-leafed grasses with comparatively low LA and high LDMC, such as Aristida stipidata Hack. These species and PFTs also tended to be favored by grazing. Although few species profited from resting, for most species, the combination of drought and resting proved to be particularly unfavorable. Winners and losers can indicate ecological transition and may be used to guide management decisions.

Keywords: aboveground net primary production, drought, functional diversity, winner and loser species

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Authors: Barbara Janari

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In this paper it is argued that the effect of the disjunctive temporality in Summertime (the third of J.M. Coetzee’s fictionalised memoirs) is two-fold: firstly, it reflects the memoir’s ambivalent, contradictory representations of place in order to emphasize the fractured sense of self growing up in South Africa during apartheid entailed for Coetzee. Secondly, it reconceives the autobiographical discourse as one that foregrounds the inherent fictionality of all texts. The memoir’s narrative is filtered through intricate textual strategies that disrupt the chronological movement of the narrative, evoking the labyrinthine ways in which the past and present intersect and interpenetrate each other. It is framed by entries from Coetzee’s Notebooks: it opens with entries that cover the years 1972–1975, and ends with a number of undated fragments from his Notebooks. Most of the entries include a short ‘memo’ at the end, added between 1999 and 2000. While the memos follow the Notebook entries in the text, they are separated by decades. Between the Notebook entries is a series of interviews conducted by Vincent, the text’s putative biographer, between 2007 and 2008, based on recollections from five people who had known Coetzee in the 1970s – a key period in John’s life as it marks both his return to South Africa after a failed emigration attempt to America, and the beginning of his writing career, with the publication of Dusklands in 1974. The relationship between the memoir’s various parts is a key feature of Coetzee’s representation of place in Summertime, which is constructed as a composite one in which the principle of reflexive referencing has to be adopted. In other words, readers have to suspend individual references temporarily until the relationships between the parts have been connected to each other. In order to apprehend meaning in the text, the disparate narrative elements have to first be tied together. In this text, then, the experience of time as ordered and chronological is ruptured. Instead, the memoir’s themes and patterns become apparent most clearly through reflexive referencing, by which relationships between disparate sections of the text are linked. The image of the fictional John that emerges from the text is a composite of this John and the author, J.M. Coetzee, and is one which embodies Coetzee’s often fraught relationship with his home country, South Africa.

Keywords: autobiography, place, reflexive referencing, temporality

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Authors: Yasir Bashawri, Vincent N. Chigor James McDonald, Merfyn Williams, Davey Jones, A. Prysor Williams

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Resistance to antibiotics has become a threat to public health. As a result of their misuse and overuse, bacteria have become resistant to many common antibiotics. Βeta lactam (β-lactam) antibiotics are one of the most significant classes of antimicrobials in providing therapeutic benefits for the treatment of bacterial infections in both human and veterinary medicine, for approximately 60% of all antibiotics are used. In particular, some Enterobacteriaceae produce Extend Spectrum Beta Lactamases (ESBLs) that enable them to some break down multi-groups of antibiotics. CTX-M enzymes have rapidly become the most important ESBLs, with increases in mainly CTX-M 15 in many countries during the last decade. Global travel by intercontinental medical ‘tourists’, migrant employees and overseas students could theoretically be a risk factor for spreading antibiotic resistance genes in different parts of the world. Bangor city, North Wales, is subject to sudden demographic changes due to a large proportion (>25%) of the population being students, most of which arrive over a space of days. This makes it a suitable location to study the impacts of large demographic change on the presence of ESBLs. The aim of this study is to monitor the presence of ESBLs in Escherichia coli and faecal coliform bacteria isolated from Bangor wastewater treatment plant, before, during and after the arrival week of students to Bangor University. Over a five-week period, water samples were collected twice a week, from the influent, primary sedimentation tank, aeration tank and the final effluent. Isolation and counts for Escherichia coli and other faecal coliforms were done on selective agar (primary UTI agar). ESBL presence will be confirmed by phenotypic and genotypic methods. Sampling at all points of the tertiary treatment stages will indicate the effectiveness of wastewater treatment in reducing the spread of ESBLs genes. The study will yield valuable information to help tackle a problem which many regard to be the one of the biggest threats to modern-day society.

Keywords: extended spectrum β-lactamase, enterobacteriaceae, international travel, wastewater treatment plant

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Authors: Nafiseh Mirabdolhosseini, Jerry Zhou, Vincent Ho

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The dramatic global rise in acid reflux has also led to oesophageal adenocarcinoma (OAC) becoming the fastest-growing cancer in developed countries. While gastroscopy with biopsy is used to diagnose OAC patients, this labour-intensive and expensive process is not suitable for population screening. This study aims to design, develop, and implement a minimally invasive system to capture optical data of the distal oesophagus for rapid screening of potential abnormalities. To develop the system and understand user requirements, a user-centric approach was employed by utilising co-design strategies. Target users’ segments were identified, and 38 patients and 14 health providers were interviewed. Next, the technical requirements were developed based on consultations with the industry. A minimally invasive optical system was designed and developed considering patient comfort. This system consists of the sensing catheter, controller unit, and analysis program. Its procedure only takes 10 minutes to perform and does not require cleaning afterward since it has a single-use catheter. A prototype system was evaluated for safety and efficacy for both laboratory and clinical performance. This prototype performed successfully when submerged in simulated gastric fluid without showing evidence of erosion after 24 hours. The system effectively recorded a video of the mid-distal oesophagus of a healthy volunteer (34-year-old male). The recorded images were used to develop an automated program to identify abnormalities in the distal oesophagus. Further data from a larger clinical study will be used to train the automated program. This system allows for quick visual assessment of the lower oesophagus in primary care settings and can serve as a screening tool for oesophageal adenocarcinoma. In addition, this system is able to be coupled with 24hr ambulatory pH monitoring to better correlate oesophageal physiological changes with reflux symptoms. It also can provide additional information on lower oesophageal sphincter functions such as opening times and bolus retention.

Keywords: endoscopy, MedTech, oesophageal adenocarcinoma, optical system, screening tool

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Authors: Sophia Melanson Ricciardone

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Common vexations concerning the impact of contemporary media technology on our daily lives tend to conjure mental representations of digital specters that surreptitiously invade the privacy of our most intimate spaces. While legitimacy assuredly sustains these concerns, examining them in isolation from other attributable phenomena to the problems created by our hyper-mediated conditions does not supply a complete account of the deleterious cost of integrating digital affordances into the banal cadence of our shared socio-cultural realities. As we continue to subconsciously delegate facets of our social and cognitive lives to digital technology, the very faculties that have enabled our species to thrive and invent technology in the first place are at risk of attrition – namely our capacity to sustain attention while synthesizing information in working memory to produce creative and inventive constructions for our shared social existence. Though the offloading of knowledge-keeping to fellow social agents belonging to our family and community circles is an enduring intuitive phenomenon across human societies – what social psychologists refer to as transactive memory – in offloading our various socio-cognitive faculties to digital technology, we may plausibly be supplanting the visceral social connections forged by transactive memory. This paper will present related research and literature produced across the disciplines of sociobiology, socio-cultural anthropology, social psychology, cognitive semiotics and communication and media studies that directly and indirectly address the social precarity cultivated by digital technologies. This body of scholarly work will then be situated within common areas of interest belonging to digital anthropology, including the groundbreaking work of Pavel Curtis, Christopher Kelty, Lynn Cherny, Vincent Duclos, Nick Seaver, and Sherry Turkle. It is anticipated that in harmonizing these overlapping areas of intradisciplinary interest, this paper can weave together the disparate connections across spheres of knowledge that help delineate the conditions of our contemporary digital existence.

Keywords: cognition, digital media, knowledge keeping, transactive memory

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Authors: Bao Chen, Frederic Kuznik, Matthieu Horgnies, Kevyn Johannes, Vincent Morin, Edouard Gengembre

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The contradiction between energy consumption, environment protection, and social development is increasingly intensified during recent decade years. At the same time, as avoiding fossil-fuels-thirsty, people turn their view on the renewable green energy, such as solar energy, wind power, hydropower, etc. However, due to the unavoidable mismatch on geography and time for production and consumption, energy storage seems to be one of the most reasonable solutions to enlarge the use of renewable energies. Thermal energy storage (TES), a branch of energy storage solution, mainly concerns the capture, storage and consumption of thermal energy for later use in different scales (individual house, apartment, district, and city). In TES research field, sensible heat and latent heat storage have been widely studied and presented at an advanced stage of development. Compared with them, thermochemical energy storage is still at initial phase but provides a relatively higher theoretical energy density and a long shelf life without heat dissipation during storage. Among thermochemical energy storage materials, inorganic pure or composite compounds like micro-porous silica gel, SrBr₂ hydrate and MgSO₄-Zeolithe have been reported as promising to be integrated into thermal energy storage systems. However, the cost of these materials, one of main obstacles, may hinder the wide use of energy storage systems in real application scales (individual house, apartment, district and even city). New studies on ettringite show promising application for thermal energy storage since its high energy density and large resource from cementitious materials. Ettringite, or calcium trisulfoaluminate hydrate, of which chemical formula is 3CaO∙Al₂O₃∙3CaSO₄∙32H₂O, or C₆AS̅₃H₃₂ as known in cement chemistry notation, is one of the most important members of AFt group. As a common compound in hydrated cements, ettringite has been widely studied for its performances in construction but barely known as a thermochemical material. For this study, we summarize available data about the structure and properties of ettringite and its metastable phase (meta-ettringite), including the processes of hydration, thermal conversion and carbonation durability for thermal energy storage.

Keywords: building materials, ettringite, meta-ettringite, thermal energy storage

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Authors: Omer Burak Iskender, Keck Voon Ling, Vincent Dubanchet, Luca Simonini

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This paper presents Guidance and Control (G&C) strategy to approach and synchronize with potentially rotating targets. The proposed strategy generates and tracks a safe trajectory for space servicing missions, including tasks like approaching, inspecting, and capturing. The main objective of this paper is to validate the G&C laws using a Hardware-In-the-Loop (HIL) setup with realistic rendezvous and docking equipment. Throughout this work, the assumption of full relative state feedback is relaxed by onboard sensors that bring realistic errors and delays and, while the proposed closed loop approach demonstrates the robustness to the above mentioned challenge. Moreover, G&C blocks are unified via the Model Predictive Control (MPC) paradigm, and the coupling between translational motion and rotational motion is addressed via dual quaternion based kinematic description. In this work, G&C is formulated as a convex optimization problem where constraints such as thruster limits and the output constraints are explicitly handled. Furthermore, the Monte-Carlo method is used to evaluate the robustness of the proposed method to the initial condition errors, the uncertainty of the target's motion and attitude, and actuator errors. A capture scenario is tested with the robotic test bench that has onboard sensors which estimate the position and orientation of a drifting satellite through camera imagery. Finally, the approach is compared with currently used robust H-infinity controllers and guidance profile provided by the industrial partner. The HIL experiments demonstrate that the proposed strategy is a potential candidate for future space servicing missions because 1) the algorithm is real-time implementable as convex programming offers deterministic convergence properties and guarantee finite time solution, 2) critical physical and output constraints are respected, 3) robustness to sensor errors and uncertainties in the system is proven, 4) couples translational motion with rotational motion.

Keywords: dual quaternion, model predictive control, real-time experimental test, rendezvous and docking, spacecraft autonomy, space servicing

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Authors: Benjamin Bressolette, S´ebastien Denjean, Vincent Roussarie, Mitsuko Aramaki, Sølvi Ystad, Richard Kronland-Martinet

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New sensors and technologies – such as microphones, touchscreens or infrared sensors – are currently making their appearance in the automotive sector, introducing new kinds of Human-Machine Interfaces (HMIs). The interactions with such tools might be cognitively expensive, thus unsuitable for driving tasks. It could for instance be dangerous to use touchscreens with a visual feedback while driving, as it distracts the driver’s visual attention away from the road. Furthermore, new technologies in car cockpits modify the interactions of the users with the central system. In particular, touchscreens are preferred to arrays of buttons for space improvement and design purposes. However, the buttons’ tactile feedback is no more available to the driver, which makes such interfaces more difficult to manipulate while driving. Gestures combined with an auditory feedback might therefore constitute an interesting alternative to interact with the HMI. Indeed, gestures can be performed without vision, which means that the driver’s visual attention can be totally dedicated to the driving task. In fact, the auditory feedback can both inform the driver with respect to the task performed on the interface and on the performed gesture, which might constitute a possible solution to the lack of tactile information. As audition is a relatively unused sense in automotive contexts, gesture sonification can contribute to reducing the cognitive load thanks to the proposed multisensory exploitation. Our approach consists in using a virtual object (VO) to sonify the consequences of the gesture rather than the gesture itself. This approach is motivated by an ecological point of view: Gestures do not make sound, but their consequences do. In this experiment, the aim was to identify efficient sound strategies, to transmit dynamic information of VOs to users through sound. The swipe gesture was chosen for this purpose, as it is commonly used in current and new interfaces. We chose two VO parameters to sonify, the hand-VO distance and the VO velocity. Two kinds of sound parameters can be chosen to sonify the VO behavior: Spectral or temporal parameters. Pitch and brightness were tested as spectral parameters, and amplitude modulation as a temporal parameter. Performances showed a positive effect of sound compared to a no-sound situation, revealing the usefulness of sounds to accomplish the task.

Keywords: auditory feedback, gesture sonification, sound perception, virtual object

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Authors: Nishanth Venugopal Menon, Chuah Yon Jin, Samantha Phey, Wu Yingnan, Zhang Ying, Vincent Chan, Kang Yuejun

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Cell Migration is a vital phenomenon that the cells undergo in various physiological processes like wound healing, disease progression, embryogenesis, etc. Cell migration depends primarily on the chemical and physical cues available in the cellular environment. The chemical cue involves the chemokines secreted and gradients generated in the environment while physical cues indicate the impact of matrix properties like nanotopography and stiffness on the cells. Mesenchymal Stem Cells (MSCs) have been shown to have a role wound healing in vivo and its migration to the site of the wound has been shown to have a therapeutic effect. In the field of stem cell based tissue regeneration of bones and cartilage, one approach has been to introduce scaffold laden with MSCs into the site of injury to enable tissue regeneration. In this work, we have studied the combinatorial impact of the substrate physical properties on MSC migration. A microfluidic in vitro model was created to perform the migration studies. The microfluidic model used is a three compartment device consisting of two cell seeding compartments and one migration compartment. Four different PDMS substrates with varying substrate roughness, stiffness and hydrophobicity were created. Its surface roughness and stiffness was measured using Atomic Force Microscopy (AFM) while its hydrphobicity was measured from the water contact angle using an optical tensiometer. These PDMS substrates are sealed to the microfluidic chip following which the MSCs are seeded and the cell migration is studied over the period of a week. Cell migration was quantified using fluorescence imaging of the cytoskeleton (F-actin) to find out the area covered by the cells inside the migration compartment. The impact of adhesion proteins on cell migration was also quantified using a real-time polymerase chain reaction (qRT PCR). These results suggested that the optimal substrate for cell migration would be one with an intermediate level of roughness, stiffness and hydrophobicity. A higher or lower value of these properties affected cell migration negatively. These observations have helped us in understanding that different substrate properties need to be considered in tandem, especially while designing scaffolds for tissue regeneration as cell migration is normally impacted by the combinatorial impact of the matrix. These observations may lead us to scaffold optimization in future tissue regeneration applications.

Keywords: cell migration, microfluidics, in vitro model, stem cell migration, scaffold, substrate properties

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Authors: Bruno Tassin, Robin Treilles, Cleo Stratmann, Minh Trang Nguyen, Sam Azimi, Vincent Rocher, Rachid Dris, Johnny Gasperi

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Microplastics (<5mm) in the environment and in hydro systems is one of the major present environmental issues. Over the last five years a research programme was conducted in order to assess the behavior of microplastics in the Seine river catchment, in a Man-Land-Sea continuum approach. Results show that microplastic concentration varies at the seasonal scale, but also at much smaller scales, during flood events and with tides in the estuary for instance. Moreover, microplastic sampling and characterization issues emerged throughout this work. The Seine river is a 750km long river flowing in Northwestern France. It crosses the Paris megacity (12 millions inhabitants) and reaches the English Channel after a 170 km long estuary. This site is a very relevant one to assess the effect of anthropogenic pollution as the mean river flow is low (mean flow around 350m³/s) while the human presence and activities are very intense. Monthly monitoring of the microplastic concentration took place over a 19-month period and showed significant temporal variations at all sampling stations but no significant upstream-downstream increase, indicating a possible major sink to the sediment. At the scale of a major flood event (winter and spring 2018), microplastic concentration shows an evolution similar to the well-known suspended solids concentration, with an increase during the increase of the flow and a decrease during the decrease of the flow. Assessing the position of the concentration peak in relation to the flow peak was unfortunately impossible. In the estuary, concentrations vary with time in connection with tides movements and in the water column in relation to the salinity and the turbidity. Although major gains of knowledge on the microplastic dynamics in the Seine river have been obtained over the last years, major gaps remain to deal mostly with the interaction with the dynamics of the suspended solids, the selling processes in the water column and the resuspension by navigation or shear stress increase. Moreover, the development of efficient chemical characterization techniques during the 5 year period of this pluriannual research programme led to the improvement of the sampling techniques in order to access smaller microplastics (>10µm) as well as larger but rare ones (>500µm).

Keywords: microplastics, Paris megacity, seine river, suspended solids

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Authors: Selina Lin, Justin M Fan, Vincent Zhang, Cindy Chen, Daniel Lam, Jason Yan, Ning Zhang

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Depression is one of the most common mental disorders in the United States, and past studies have shown a concerning increase in the rates of depression in youth populations over time. Furthermore, depression is an especially important issue for Asian Americans because of the anti-Asian violence taking place during the COVID-19 pandemic. While Asian American adolescents are reluctant to seek help for mental health issues, past research has found a prevalence of depressive symptoms in them that have yet to be fully investigated. There have been studies conducted to understand and observe the impacts of multifarious factors influencing the mental well-being of Asian American adolescents; however, they have been generally limited to qualitative investigation, and very few have attempted to quantitatively evaluate the relationship between depression levels and a comprehensive list of factors for those levels at the same time. To better quantify these relationships, this project investigated the prevalence of depression in Asian American teenagers mainly from the Greater Philadelphia Region, aged 12 to 19, and, with an anonymous survey, asked participants 48 multiple-choice questions pertaining to demographic information, daily behaviors, school life, family life, depression levels (quantified by the PHQ-9 assessment), school and family support against depression. Each multiple-choice question was assigned as a factor and variable for statistical and dominance analysis to determine the most influential factors on depression levels of Asian American adolescents. The results were validated via Bootstrap analysis and t-tests. While certain influential factors identified in this survey are consistent with the literature, such as parent-child relationship and peer pressure, several dominant factors were relatively overlooked in the past. These factors include the parents’ relationship with each other, the satisfaction with body image, sex identity, support from the family and support from the school. More than 25% of participants desired more support from their families and schools in handling depression issues. This study implied that it is beneficial for Asian American parents and adolescents to take programs on parents’ relationships with each other, parent-child communication, mental health, and sexual identity. A culturally inclusive school environment and more accessible mental health services would be helpful for Asian American adolescents to combat depression. This survey-based study paved the way for further investigation of effective approaches for helping Asian American adolescents against depression.

Keywords: Asian American adolescents, depression, dominance analysis, t-test, bootstrap analysis

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Authors: Vincent Andrew Cappellano

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In the early phases of critical infrastructure system design, translating distributed computing requirements to an architecture has risk given the multitude of approaches (e.g., cloud, edge, fog). In many systems, a single requirement for system uptime / availability is used to encompass the system’s intended operations. However, when architected systems may perform to those availability requirements only during normal operations and not during component failure, or during outages caused by adversary attacks on critical infrastructure (e.g., physical, cyber). System designers lack a structured method to evaluate availability requirements against candidate system architectures through deep degradation scenarios (i.e., normal ops all the way down to significant damage of communications or physical nodes). This increases risk of poor selection of a candidate architecture due to the absence of insight into true performance for systems that must operate as a piece of critical infrastructure. This research effort proposes a process to analyze critical infrastructure system availability requirements and a candidate set of systems architectures, producing a metric assessing these architectures over a spectrum of degradations to aid in selecting appropriate resilient architectures. To accomplish this effort, a set of simulation and evaluation efforts are undertaken that will process, in an automated way, a set of sample requirements into a set of potential architectures where system functions and capabilities are distributed across nodes. Nodes and links will have specific characteristics and based on sampled requirements, contribute to the overall system functionality, such that as they are impacted/degraded, the impacted functional availability of a system can be determined. A machine learning reinforcement-based agent will structurally impact the nodes, links, and characteristics (e.g., bandwidth, latency) of a given architecture to provide an assessment of system functional uptime/availability under these scenarios. By varying the intensity of the attack and related aspects, we can create a structured method of evaluating the performance of candidate architectures against each other to create a metric rating its resilience to these attack types/strategies. Through multiple simulation iterations, sufficient data will exist to compare this availability metric, and an architectural recommendation against the baseline requirements, in comparison to existing multi-factor computing architectural selection processes. It is intended that this additional data will create an improvement in the matching of resilient critical infrastructure system requirements to the correct architectures and implementations that will support improved operation during times of system degradation due to failures and infrastructure attacks.

Keywords: architecture, resiliency, availability, cyber-attack

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Authors: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery

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Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.

Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking

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Authors: Remy Mpulumba Badiambile, Paul Musa Obadia, Malick Useni Mutayo, Jeef Numbi Mukanya, Patient Nkulu Banza, Tony Kayembe Kitenge, Erik Smolders, Jean-François Picron, Vincent Haufroid, Célestin Banza Lubaba Nkulu, Benoit Nemery

Abstract:

Background: In July 2021, the Tshikapa river became heavily polluted by mining wastes from a diamond mine in neighboring Angola, leading to massive killing of fish, as well as disease and even deaths among residents living along the Tshikapa and Kasai rivers, a major contributory of the Congo river. The exact nature of the pollutants was unknown. Methods: In a cross-sectional study conducted in the city of Tshikapa in August 2021, we enrolled by opportunistic sampling 65 residents (11 children < 16y) living alongside the polluted rivers and 65 control residents (5 children) living alongside a non-affected portion of the Kasai river (upstream from the Tshikapa-Kasai confluence). We administered a questionnaire and obtained spot urine samples for measurements of thiocyanate (a metabolite of cyanide) and 26 trace metals (by ICP-MS). Metals (and pH) were also measured in samples of river water. Results: Participants from both groups consumed river water. In the area affected by the pollution, most participants had eaten dead fish. Prevalences of reported health symptoms were higher in the exposed group than among controls: skin rashes (52% vs 0%), diarrhea (40% vs 8%), abdominal pain (8% vs 3%), nausea (3% vs 0%). In polluted water, concentrations [median (range)] were only higher for nickel [(2.2(1.4–3.5)µg/L] and uranium [78(71–91)ng/L] than in non-polluted water [0.8(0.6–1.9)µg/L; 9(7–19)ng/L]. In urine, concentrations [µg/g creatinine, median(IQR)] were significantly higher in the exposed group than in controls for lithium [19.5(12.4–27.3) vs 6.9(5.9–12.1)], thallium [0.41(0.31–0.57) vs 0.19(0.16–0.39)], and uranium [0.026(0.013–0.037)] vs 0.012(0.006–0.024)]. Other elements did not differ between the groups, but levels were higher than reference values for several metals (including manganese, cobalt, nickel, and lead). Urinary thiocyanate concentrations did not differ. Conclusion: This study, after an ecological disaster in the DRC, has documented contamination of river water by nickel and uranium and high urinary levels of some trace metals among affected riverine populations. However, the exact cause of the massive fish kill and disease among residents remains elusive. The capacity to rapidly investigate toxic pollution events must be increased in the area.

Keywords: metal contaminants, river water and human urine, pollution by mining wastes, DR Congo

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