Search results for: lead time variability
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 21443

Search results for: lead time variability

623 Regulation of Desaturation of Fatty Acid and Triglyceride Synthesis by Myostatin through Swine-Specific MEF2C/miR222/SCD5 Pathway

Authors: Wei Xiao, Gangzhi Cai, Xingliang Qin, Hongyan Ren, Zaidong Hua, Zhe Zhu, Hongwei Xiao, Ximin Zheng, Jie Yao, Yanzhen Bi

Abstract:

Myostatin (MSTN) is the master regulator of double muscling phenotype with overgrown muscle and decreased fatness in animals, but its action mode to regulate fat deposition remains to be elucidated. In this study a swin-specific pathway through which MSTN acts to regulate the fat deposition was deciphered. Deep sequenincing of the mRNA and miRNA of fat tissues of MSTN knockout (KO) and wildtype (WT) pigs discovered the positive correlation of myocyte enhancer factor 2C (MEF2C) and fat-inhibiting miR222 expression, and the inverse correlation of miR222 and stearoyl-CoA desaturase 5 (SCD5) expression. SCD5 is rodent-absent and expressed only in pig, sheep and cattle. Fatty acid spectrum of fat tissues revealed a lower percentage of oleoyl-CoA (18:1) and palmitoleyl CoA (16:1) in MSTN KO pigs, which are the catalyzing products of SCD5-mediated desaturation of steroyl CoA (18:0) and palmitoyl CoA (16:0). Blood metrics demonstrated a 45% decline of triglyceride (TG) content in MSTN KO pigs. In light of these observations we hypothesized that MSTN might act through MEF2C/miR222/SCD5 pathway to regulate desaturation of fatty acid as well as triglyceride synthesis in pigs. To this end, real-time PCR and Western blotting were carried out to detect the expression of the three genes stated above. These experiments showed that MEF2C expression was up-regulated by nearly 2-fold, miR222 up-regulated by nearly 3-fold and SCD5 down-regulated by nearly 50% in MSTN KO pigs. These data were consistent with the expression change in deep sequencing analysis. Dual luciferase reporter was then used to confirm the regulation of MEF2C upon the promoter of miR222. Ecotopic expression of MEF2C in preadipocyte cells enhanced miR222 expression by 3.48-fold. CHIP-PCR identified a putative binding site of MEF2C on -2077 to -2066 region of miR222 promoter. Electrophoretic mobility shift assay (EMSA) demonstrated the interaction of MEF2C and miR222 promoter in vitro. These data indicated that MEF2C transcriptionally regulates the expression of miR222. Next, the regulation of miR222 on SCD5 mRNA as well as its physiological consequences were examined. Dual luciferase reporter testing revealed the translational inhibition of miR222 upon the 3´ UTR (untranslated region) of SCD5 in preadipocyte cells. Transfection of miR222 mimics and inhibitors resulted in the down-regulation and up-regulation of SCD5 in preadipocyte cells respectively, consistent with the results from reporter testing. RNA interference of SCD5 in preadipocyte cells caused 26.2% reduction of TG, in agreement with the results of TG content in MSTN KO pigs. In summary, the results above supported the existence of a molecular pathway that MSTN signals through MEF2C/miR222/SCD5 to regulate the fat deposition in pigs. This swine-specific pathway offers potential molecular markers for the development and breeding of a new pig line with optimised fatty acid composition. This would benefit human health by decreasing the takeup of saturated fatty acid.

Keywords: fat deposition, MEF2C, miR222, myostatin, SCD5, pig

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622 Detection of High Fructose Corn Syrup in Honey by Near Infrared Spectroscopy and Chemometrics

Authors: Mercedes Bertotto, Marcelo Bello, Hector Goicoechea, Veronica Fusca

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The National Service of Agri-Food Health and Quality (SENASA), controls honey to detect contamination by synthetic or natural chemical substances and establishes and controls the traceability of the product. The utility of near-infrared spectroscopy for the detection of adulteration of honey with high fructose corn syrup (HFCS) was investigated. First of all, a mixture of different authentic artisanal Argentinian honey was prepared to cover as much heterogeneity as possible. Then, mixtures were prepared by adding different concentrations of high fructose corn syrup (HFCS) to samples of the honey pool. 237 samples were used, 108 of them were authentic honey and 129 samples corresponded to honey adulterated with HFCS between 1 and 10%. They were stored unrefrigerated from time of production until scanning and were not filtered after receipt in the laboratory. Immediately prior to spectral collection, honey was incubated at 40°C overnight to dissolve any crystalline material, manually stirred to achieve homogeneity and adjusted to a standard solids content (70° Brix) with distilled water. Adulterant solutions were also adjusted to 70° Brix. Samples were measured by NIR spectroscopy in the range of 650 to 7000 cm⁻¹. The technique of specular reflectance was used, with a lens aperture range of 150 mm. Pretreatment of the spectra was performed by Standard Normal Variate (SNV). The ant colony optimization genetic algorithm sample selection (ACOGASS) graphical interface was used, using MATLAB version 5.3, to select the variables with the greatest discriminating power. The data set was divided into a validation set and a calibration set, using the Kennard-Stone (KS) algorithm. A combined method of Potential Functions (PF) was chosen together with Partial Least Square Linear Discriminant Analysis (PLS-DA). Different estimators of the predictive capacity of the model were compared, which were obtained using a decreasing number of groups, which implies more demanding validation conditions. The optimal number of latent variables was selected as the number associated with the minimum error and the smallest number of unassigned samples. Once the optimal number of latent variables was defined, we proceeded to apply the model to the training samples. With the calibrated model for the training samples, we proceeded to study the validation samples. The calibrated model that combines the potential function methods and PLSDA can be considered reliable and stable since its performance in future samples is expected to be comparable to that achieved for the training samples. By use of Potential Functions (PF) and Partial Least Square Linear Discriminant Analysis (PLS-DA) classification, authentic honey and honey adulterated with HFCS could be identified with a correct classification rate of 97.9%. The results showed that NIR in combination with the PT and PLS-DS methods can be a simple, fast and low-cost technique for the detection of HFCS in honey with high sensitivity and power of discrimination.

Keywords: adulteration, multivariate analysis, potential functions, regression

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621 The Effects of Adding Vibrotactile Feedback to Upper Limb Performance during Dual-Tasking and Response to Misleading Visual Feedback

Authors: Sigal Portnoy, Jason Friedman, Eitan Raveh

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Introduction: Sensory substitution is possible due to the capacity of our brain to adapt to information transmitted by a synthetic receptor via an alternative sensory system. Practical sensory substitution systems are being developed in order to increase the functionality of individuals with sensory loss, e.g. amputees. For upper limb prosthetic-users the loss of tactile feedback compels them to allocate visual attention to their prosthesis. The effect of adding vibrotactile feedback (VTF) to the applied force has been studied, however its effect on the allocation if visual attention during dual-tasking and the response during misleading visual feedback have not been studied. We hypothesized that VTF will improve the performance and reduce visual attention during dual-task assignments in healthy individuals using a robotic hand and improve the performance in a standardized functional test, despite the presence of misleading visual feedback. Methods: For the dual-task paradigm, twenty healthy subjects were instructed to toggle two keyboard arrow keys with the left hand to retain a moving virtual car on a road on a screen. During the game, instructions for various activities, e.g. mix the sugar in the glass with a spoon, appeared on the screen. The subject performed these tasks with a robotic hand, attached to the right hand. The robotic hand was controlled by the activity of the flexors and extensors of the right wrist, recorded using surface EMG electrodes. Pressure sensors were attached at the tips of the robotic hand and induced VTF using vibrotactile actuators attached to the right arm of the subject. An eye-tracking system tracked to visual attention of the subject during the trials. The trials were repeated twice, with and without the VTF. Additionally, the subjects performed the modified box and blocks, hidden from eyesight, in a motion laboratory. A virtual presentation of a misleading visual feedback was be presented on a screen so that twice during the trial, the virtual block fell while the physical block was still held by the subject. Results: This is an ongoing study, which current results are detailed below. We are continuing these trials with transradial myoelectric prosthesis-users. In the healthy group, the VTF did not reduce the visual attention or improve performance during dual-tasking for the tasks that were typed transfer-to-target, e.g. place the eraser on the shelf. An improvement was observed for other tasks. For example, the average±standard deviation of time to complete the sugar-mixing task was 13.7±17.2s and 19.3±9.1s with and without the VTF, respectively. Also, the number of gaze shifts from the screen to the hand during this task were 15.5±23.7 and 20.0±11.6, with and without the VTF, respectively. The response of the subjects to the misleading visual feedback did not differ between the two conditions, i.e. with and without VTF. Conclusions: Our interim results suggest that the performance of certain activities of daily living may be improved by VTF. The substitution of visual sensory input by tactile feedback might require a long training period so that brain plasticity can occur and allow adaptation to the new condition.

Keywords: prosthetics, rehabilitation, sensory substitution, upper limb amputation

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620 Nurturing Scientific Minds: Enhancing Scientific Thinking in Children (Ages 5-9) through Experiential Learning in Kids Science Labs (STEM)

Authors: Aliya K. Salahova

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Scientific thinking, characterized by purposeful knowledge-seeking and the harmonization of theory and facts, holds a crucial role in preparing young minds for an increasingly complex and technologically advanced world. This abstract presents a research study aimed at fostering scientific thinking in early childhood, focusing on children aged 5 to 9 years, through experiential learning in Kids Science Labs (STEM). The study utilized a longitudinal exploration design, spanning 240 weeks from September 2018 to April 2023, to evaluate the effectiveness of the Kids Science Labs program in developing scientific thinking skills. Participants in the research comprised 72 children drawn from local schools and community organizations. Through a formative psychology-pedagogical experiment, the experimental group engaged in weekly STEM activities carefully designed to stimulate scientific thinking, while the control group participated in daily art classes for comparison. To assess the scientific thinking abilities of the participants, a registration table with evaluation criteria was developed. This table included indicators such as depth of questioning, resource utilization in research, logical reasoning in hypotheses, procedural accuracy in experiments, and reflection on research processes. The data analysis revealed dynamic fluctuations in the number of children at different levels of scientific thinking proficiency. While the development was not uniform across all participants, a main leading factor emerged, indicating that the Kids Science Labs program and formative experiment exerted a positive impact on enhancing scientific thinking skills in children within this age range. The study's findings support the hypothesis that systematic implementation of STEM activities effectively promotes and nurtures scientific thinking in children aged 5-9 years. Enriching education with a specially planned STEM program, tailoring scientific activities to children's psychological development, and implementing well-planned diagnostic and corrective measures emerged as essential pedagogical conditions for enhancing scientific thinking abilities in this age group. The results highlight the significant and positive impact of the systematic-activity approach in developing scientific thinking, leading to notable progress and growth in children's scientific thinking abilities over time. These findings have promising implications for educators and researchers, emphasizing the importance of incorporating STEM activities into educational curricula to foster scientific thinking from an early age. This study contributes valuable insights to the field of science education and underscores the potential of STEM-based interventions in shaping the future scientific minds of young children.

Keywords: Scientific thinking, education, STEM, intervention, Psychology, Pedagogy, collaborative learning, longitudinal study

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619 Boost for Online Language Course through Peer Evaluation

Authors: Kirsi Korkealehto

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The purpose of this research was to investigate how the peer evaluation concept was perceived by language teachers developing online language courses. The online language courses in question were developed in language teacher teams within a nationwide KiVAKO-project funded by the Finnish Ministry of Education and Culture. The participants of the project were 86 language teachers of 26 higher education institutions in Finland. The KiVAKO-project aims to strengthen the language capital at higher education institutions by building a nationwide online language course offering on a shared platform. All higher education students can study the courses regardless of their home institutions. The project covers the following languages: Chinese, Estonian, Finnish Sign Language, French, German, Italian, Japanese, Korean, Portuguese, Russian, and Spanish on the levels CEFR A1-C1. The courses were piloted in the autumn term of 2019, and an online peer evaluation session was organised for all project participating teachers in spring 2020. The peer evaluation utilised the quality criteria for online implementation, which was developed earlier within the eAMK-project. The eAMK-project was also funded by the Finnish Ministry of Education and Culture with the aim to improve higher education institution teachers’ digital and pedagogical competences. In the online peer evaluation session, the teachers were divided into Zoom breakout rooms, in each of which two pilot courses were presented by their teachers dialogically. The other language teachers provided feedback on the course on the basis of the quality criteria. Thereafter good practices and ideas were gathered to an online document. The breakout rooms were facilitated by one teacher who was instructed and provided a slide-set prior to the online session. After the online peer evaluation sessions, the language teachers were asked to respond to an online questionnaire for feedback. The questionnaire included three multiple-choice questions using the Likert-scale rating and two open-ended questions. The online questionnaire was answered after the sessions immediately, the questionnaire link and the QR-code to it was on the last slide of the session, and it was responded at the site. The data comprise online questionnaire responses of the peer evaluation session and the researcher’s observations during the sessions. The data were analysed with a qualitative content analysis method with the help of Atlas.ti programme, and the Likert scale answers provided results per se. The observations were used as complementary data to support the primary data. The findings indicate that the working in the breakout rooms was successful, and the workshops proceeded smoothly. The workshops were perceived as beneficial in terms of improving the piloted courses and developing the participants’ own work as teachers. Further, the language teachers stated that the collegial discussions and sharing the ideas were fruitful. The aspects to improve the workshops were to give more time for free discussions and the opportunity to familiarize oneself with the quality criteria and the presented language courses beforehand. The quality criteria were considered to provide a suitable frame for self- and peer evaluations.

Keywords: higher education, language learning, online learning, peer-evaluation

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618 A Sociological Qualitative Study: Intimate Relationships as a Social Pressure Around HIV-Related Issues Among Young South African Women and Girls (16-28)

Authors: Sunha Ahn

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Intimate relationships have constructed our embodied experiences and emotional memories, which can become grounded as practical knowledge to some extent and play a critical role in social medicine, particularly, in our well-being and mental health. In South Africa, such relational factors are significant for young women and girls in their emotional development period of time, especially, working as the existence of social and relational pressures over feminine sexual health and choices. This, in turn, brings about the absence/lack of communication in intimate relationships, especially with their parents, which leads to a vicious cycle in sexual health behaviour choices. Drawing upon sociological and socio-anthropological understandings of HIV-related issues, this study provides narrative threads of evidence about South African teenage mothers from early-dating debuted to HIV infection. Their stories consist of a visualised figure in chronicle order, illustrating embodied journeys of sexual health choices surrounding uncommunicative relationships and socially-suppressive environments. Methodologically, this qualitative study explored data from mixed online methods: 1) a case study analysing online comments (N = 12,763) on the South African Springster's website, run by the UK-based NGO, namely, Girl Effect; and 2) In-depth online interviews (N = 21) were conducted with young SA women and girls (16-28 ages) recruited in Cape Town, Pretoria, and Johannesburg, SA. Participants consist of both those living with HIV and without. Ethical approval was gained via the College of Social Sciences Ethical Committee at the University of Glasgow, and informed consent was obtained verbally and in writing from participants in due course. Data were thematically applied to an iteratively developed codebook and analysed. There are three kinds of typical pressures as relational factors for them, including peer pressure, partners or boyfriends, and parents’ reactions. Under the patriarchal and religious-devoted social atmospheres, these relationships work as a source of scaredness among young women and girls who could not talk about their sexual health concerns and rights. Such an inability to communicate with intimate relationships, eventually, emerges as a perpetuated or taken-for-granted social environment in South Africa, insistently leading to an increase in unwanted pregnancies or new HIV infections in young South African women and girls. In this sense, this study reveals the pressing need for open communication between generations with accurate information about HIV/AIDS. This also implies that the sociological feminist praxes in South Africa would help eliminate HIV-related stigma as well as construct open space to reduce gender-based violence and sexually-transmitted infection. Ultimately, this will be a road for supporting sexually healthy decisions and well-being across South African generations.

Keywords: HIV, young women, South Africa, intimate relationships, communication, social medicine

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617 Diagnosis, Treatment, and Prognosis in Cutaneous Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma: A Narrative Review Apropos of a Case

Authors: Laura Gleason, Sahithi Talasila, Lauren Banner, Ladan Afifi, Neda Nikbakht

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Primary cutaneous anaplastic large cell lymphoma (pcALCL) accounts for 9% of all cutaneous T-cell lymphomas. pcALCL is classically characterized as a solitary papulonodule that often enlarges, ulcerates, and can be locally destructive, but overall exhibits an indolent course with overall 5-year survival estimated to be 90%. Distinguishing pcALCL from systemic ALCL (sALCL) is essential as sALCL confers a poorer prognosis with average 5-year survival being 40-50%. Although extremely rare, there have been several cases of ALK-positive ALCL diagnosed on skin biopsy without evidence of systemic involvement, which poses several challenges in the classification, prognostication, treatment, and follow-up of these patients. Objectives: We present a case of cutaneous ALK-positive ALCL without evidence of systemic involvement, and a narrative review of the literature to further characterize that ALK-positive ALCL limited to the skin is a distinct variant with a unique presentation, history, and prognosis. A 30-year-old woman presented for evaluation of an erythematous-violaceous papule present on her right chest for two months. With the development of multifocal disease and persistent lymphadenopathy, a bone marrow biopsy and lymph node excisional biopsy were performed to assess for systemic disease. Both biopsies were unrevealing. The patient was counseled on pursuing systemic therapy consisting of Brentuximab, Cyclophosphamide, Doxorubicin, and Prednisone given the concern for sALCL. Apropos of the patient we searched for clinically evident, cutaneous ALK-positive ALCL cases, with and without systemic involvement, in the English literature. Risk factors, such as tumor location, number, size, ALK localization, ALK translocations, and recurrence, were evaluated in cases of cutaneous ALK-positive ALCL. The majority of patients with cutaneous ALK-positive ALCL did not progress to systemic disease. The majority of cases that progressed to systemic disease in adults had recurring skin lesions and cytoplasmic localization of ALK. ALK translocations did not influence disease progression. Mean time to disease progression was 16.7 months, and significant mortality (50%) was observed in those cases that progressed to systemic disease. Pediatric cases did not exhibit a trend similar to adult cases. In both the adult and pediatric cases, a subset of cutaneous-limited ALK-positive ALCL were treated with chemotherapy. All cases treated with chemotherapy did not progress to systemic disease. Apropos of an ALK-positive ALCL patient with clinical cutaneous limited disease in the histologic presence of systemic markers, we discussed the literature data, highlighting the crucial issues related to developing a clinical strategy to approach this rare subtype of ALCL. Physicians need to be aware of the overall spectrum of ALCL, including cutaneous limited disease, systemic disease, disease with NPM-ALK translocation, disease with ALK and EMA positivity, and disease with skin recurrence.

Keywords: anaplastic large cell lymphoma, systemic, cutaneous, anaplastic lymphoma kinase, ALK, ALCL, sALCL, pcALCL, cALCL

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616 CO2 Utilization by Reverse Water-Shift and Fischer-Tropsch Synthesis for Production of Heavier Fraction Hydrocarbons in a Container-Sized Mobile Unit

Authors: Francisco Vidal Vázquez, Pekka Simell, Christian Frilund, Matti Reinikainen, Ilkka Hiltunen, Tim Böltken, Benjamin Andris, Paolo Piermartini

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Carbon capture and utilization (CCU) are one of the key topics in mitigation of CO2 emissions. There are many different technologies that are applied for the production of diverse chemicals from CO2 such as synthetic natural gas, Fischer-Tropsch products, methanol and polymers. Power-to-Gas and Power-to-Liquids concepts arise as a synergetic solution for storing energy and producing value added products from the intermittent renewable energy sources and CCU. VTT is a research and technology development company having energy in transition as one of the key focus areas. VTT has extensive experience in piloting and upscaling of new energy and chemical processes. Recently, VTT has developed and commissioned a Mobile Synthesis Unit (MOBSU) in close collaboration with INERATEC, a spin-off company of Karlsruhe Institute of Technology (KIT, Germany). The MOBSU is a multipurpose synthesis unit for CO2 upgrading to energy carriers and chemicals, which can be transported on-site where CO2 emission and renewable energy are available. The MOBSU is initially used for production of fuel compounds and chemical intermediates by combination of two consecutive processes: reverse Water-Gas Shift (rWGS) and Fischer-Tropsch synthesis (FT). First, CO2 is converted to CO by high-pressure rWGS and then, the CO and H2 rich effluent is used as feed for FT using an intensified reactor technology developed and designed by INERATEC. Chemical equilibrium of rWGS reaction is not affected by pressure. Nevertheless, compression would be required in between rWGS and FT in the case when rWGS is operated at atmospheric pressure. This would also require cooling of rWGS effluent, water removal and reheating. For that reason, rWGS is operated using precious metal catalyst in the MOBSU at similar pressure as FT to simplify the process. However, operating rWGS at high pressures has also some disadvantages such as methane and carbon formation, and more demanding specifications for materials. The main parts of FT module are an intensified reactor, a hot trap to condense the FT wax products, and a cold trap to condense the FT liquid products. The FT synthesis is performed using cobalt catalyst in a novel compact reactor technology with integrated highly-efficient water evaporation cooling cycle. The MOBSU started operation in November 2016. First, the FT module is tested using as feedstock H2 and CO. Subsequently, rWGS and FT modules are operated together using CO2 and H2 as feedstock of ca. 5 Nm3/hr total flowrate. On spring 2017, The MOBSU unit will be integrated together with a direct air capture (DAC) of CO2 unit, and a PEM electrolyser unit at Lappeenranta University of Technology (LUT) premises for demonstration of the SoletAir concept. This would be the first time when synthetic fuels are produced by combination of DAC unit and electrolyser unit which uses solar power for H2 production.

Keywords: CO2 utilization, demonstration, Fischer-Tropsch synthesis, intensified reactors, reverse water-gas shift

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615 Self-Organizing Maps for Exploration of Partially Observed Data and Imputation of Missing Values in the Context of the Manufacture of Aircraft Engines

Authors: Sara Rejeb, Catherine Duveau, Tabea Rebafka

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To monitor the production process of turbofan aircraft engines, multiple measurements of various geometrical parameters are systematically recorded on manufactured parts. Engine parts are subject to extremely high standards as they can impact the performance of the engine. Therefore, it is essential to analyze these databases to better understand the influence of the different parameters on the engine's performance. Self-organizing maps are unsupervised neural networks which achieve two tasks simultaneously: they visualize high-dimensional data by projection onto a 2-dimensional map and provide clustering of the data. This technique has become very popular for data exploration since it provides easily interpretable results and a meaningful global view of the data. As such, self-organizing maps are usually applied to aircraft engine condition monitoring. As databases in this field are huge and complex, they naturally contain multiple missing entries for various reasons. The classical Kohonen algorithm to compute self-organizing maps is conceived for complete data only. A naive approach to deal with partially observed data consists in deleting items or variables with missing entries. However, this requires a sufficient number of complete individuals to be fairly representative of the population; otherwise, deletion leads to a considerable loss of information. Moreover, deletion can also induce bias in the analysis results. Alternatively, one can first apply a common imputation method to create a complete dataset and then apply the Kohonen algorithm. However, the choice of the imputation method may have a strong impact on the resulting self-organizing map. Our approach is to address simultaneously the two problems of computing a self-organizing map and imputing missing values, as these tasks are not independent. In this work, we propose an extension of self-organizing maps for partially observed data, referred to as missSOM. First, we introduce a criterion to be optimized, that aims at defining simultaneously the best self-organizing map and the best imputations for the missing entries. As such, missSOM is also an imputation method for missing values. To minimize the criterion, we propose an iterative algorithm that alternates the learning of a self-organizing map and the imputation of missing values. Moreover, we develop an accelerated version of the algorithm by entwining the iterations of the Kohonen algorithm with the updates of the imputed values. This method is efficiently implemented in R and will soon be released on CRAN. Compared to the standard Kohonen algorithm, it does not come with any additional cost in terms of computing time. Numerical experiments illustrate that missSOM performs well in terms of both clustering and imputation compared to the state of the art. In particular, it turns out that missSOM is robust to the missingness mechanism, which is in contrast to many imputation methods that are appropriate for only a single mechanism. This is an important property of missSOM as, in practice, the missingness mechanism is often unknown. An application to measurements on one type of part is also provided and shows the practical interest of missSOM.

Keywords: imputation method of missing data, partially observed data, robustness to missingness mechanism, self-organizing maps

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614 Impact of Electric Field on the Optical Properties of Hydrophilic Quantum Dots

Authors: Valentina V. Goftman, Vladislav A. Pankratov, Alexey V. Markin, Tangi Aubert, Zeger Hens, Sarah De Saeger, Irina Yu. Goryacheva

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The most important requirements for biochemical applicability of quantum dots (QDs) are: 1) the surface cap should render intact or improved optical properties; 2) mono-dispersion and good stability in aqueous phase in a wide range of pH and ionic strength values; 3) presence of functional groups, available for bioconjugation; 4) minimal impact from the environment on the QDs’ properties and, vice versa, minimal influence of the QDs’ components on the environment; and 5) stability against chemical/biochemical/physical influence. The latter is especially important for in vitro and in vivo applications. For example, some physical intracellular delivery strategies (e.g., electroporation) imply a rapid high-voltage electric field impulse in order to temporarily generate hydrophilic pores in the cell plasma membrane, necessary for the passive transportation of QDs into the cell. In this regard, it is interesting to investigate how different capping layers, which can provide high stability and sufficient fluorescent properties of QDs in a water solution, behave under these abnormal conditions. In this contribution, hydrophobic core-shell CdSe/CdS/CdZnS/ZnS QDs (λem=600 nm), produced by means of the Successive Ion Layer Adsorption and Reaction (SILAR) technique, were transferred to a water solution using two of the most commonly used methods: (i) encapsulation in an amphiphilic brush polymer based on poly(maleic anhydride-alt-1-octadecene) (PMAO) modified with polyethylene glycol (PEG) chains and (ii) silica covering. Polymer encapsulation preserves the initial ligands on the QDs’ surface owing to the hydrophobic attraction between the hydrophobic groups of the amphiphilic molecules and the surface hydrophobic groups of the QDs. This covering process allows maintaining the initial fluorescent properties, but it leads to a considerable increase of the QDs’ size. However, covering with a silica shell, by means of the reverse microemulsion method, allows maintaining both size and fluorescent properties of the initial QDs. The obtained water solutions of polymer covered and silica-coated QDs in three different concentrations were exposed to a low-voltage electric field for a short time and the fluorescent properties were investigated. It is shown that the PMAO-PEG polymer acquires some additional charges in the presence of the electric field, which causes repulsion between the polymer and the QDs’ surface. This process destroys the homogeneity of the whole amphiphilic shell and it dramatically decreases the fluorescent properties (dropping to 10% from its initial value) because of the direct contact of the QDs with the strongly oxidative environment (water). In contrast, a silica shell possesses dielectric properties which allow retaining 90% of its initial fluorescence intensity, even after a longer electric impact. Thus, silica shells are clearly a preferable covering for bio-application of QDs, because – besides the high uniform morphology, controlled size and biocompatibility – it allows protecting QDs from oxidation, even under the influence of an electric field.

Keywords: electric field, polymer coating, quantum dots, silica covering, stability

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613 A Case of Borderline Personality Disorder: An Explanatory Study of Unconscious Conflicts through Dream-Analysis

Authors: Mariam Anwaar, Kiran B. Ahmad

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Borderline Personality Disorder (BPD) is an invasive presence of affect instability, disturbance in self-concept and attachment in relationships. The profound indicator is the dichotomous approach of the world in which the ego categorizes individuals, especially their significant others, into secure or threatful beings, leaving little room for a complex combination of characteristics in one person. This defense mechanism of splitting their world has been described through the explanatory model of unconscious conflict theorized by Sigmund Freud’s Electra Complex in the Phallic Stage. The central role is of the father with whom the daughter experiences penis envy, thus identifying with the mother’s characteristics to receive the father’s attention. However, Margret Mahler, an object relation theorist, elucidates the central role of the mother and that the split occurs during the pre-Electra complex stage. Amid the 14 and 24 months of the infant, it acknowledges the world away from the mother as they have developed milestones such as crawling. In such novelty, the infant crawls away from the mother creating a sense of independence (individuation). On the other hand, being distant causes anxiety, making them return to their original object of security (separation). In BPD, the separation-individuation stage is disrupted, due to contradictory actions of the caregiver, which results in splitting the object into negative and positive aspects, repressing the former and adhering to the latter for survival. Thus, with time, the ego distorts the reality into dichotomous categories, using the splitting defenses, and the mental representation of the self is distorted due to the internalization of the negative objects. The explanatory model was recognized in the case study of Fizza, at 21-year-old Pakistani female, residing in Karachi. Her marital status is single with an occupation being a dental student. Fizza lives in a nuclear family but is surrounded by her extended family as they all are in close vicinity. She came with the complaints of depressive symptoms for two-years along with self-harm due to severe family conflicts. Through the intervention of Dialectical Behavior Therapy (DBT), the self-harming actions were reduced, however, this libidinal energy transformed into claustrophobic symptoms and, along with this, Fizza has always experienced vivid dreams. A retrospective method of Jungian dream-analysis was applied to locate the origins of the splitting in the unconscious. The result was the revelation of a sexual harassment trauma at the age of six-years which was displaced in the form of self-harm. In addition to this, the presence of a conflict at the separation-individuation stage was detected during the dream-analysis, and it was the underlying explanation of the claustrophobic symptoms. This qualitative case study implicates the use of a patient’s subjective experiences, such as dreams, to journey through the spiral of the unconscious in order to not only detect repressed memories but to use them in psychotherapy as a means of healing the patient.

Keywords: borderline personality disorder, dream-analysis, Electra complex, separation-individuation, splitting, unconscious

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612 The Effects of Bisphosphonates on Osteonecrosis of Jaw Bone: A Stem Cell Perspective

Authors: Huseyin Apdik, Aysegul Dogan, Selami Demirci, Ezgi Avsar Apdik, Fikrettin Sahin

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Mesenchymal stem cells (MSCs) are crucial cell types for bone maintenance and growth along with resident bone progenitor cells providing bone tissue integrity during osteogenesis and skeletal growth. Any deficiency in this regulation would result in vital bone diseases. Of those, osteoporosis, characterized by a reduction in bone mass and mineral density, is a critical skeletal disease for especially elderly people. The commonly used drugs for the osteoporosis treatment are bisphosphonates (BPs). The most prominent role of BPs is to prevent bone resorption arisen from high osteoclast activity. However, administrations of bisphosphonates may also cause bisphosphonate-induced osteonecrosis of the jaw (BIONJ). Up to the present, the researchers have proposed several circumstances for BIONJ. However, effects of long-term and/or high dose usage of BPs on stem cell’s proliferation, survival, differentiation or maintenance capacity have not been evaluated yet. The present study will be held to; figure out BPs’ effects on MSCs in vitro in the aspect of cell proliferation and toxicity, migration, angiogenic activity, lineage specific gene and protein expression levels, mesenchymal stem cell properties and potential signaling pathways affected by BP treatment. Firstly, mesenchymal stem cell characteristics of Dental Pulp Stem Cells (DPSCs) and Periodontal Ligament Stem Cells (PDLSCs) were proved using flow cytometry analysis. Cell viability analysis was completed to determine the cytotoxic effects of BPs (Zoledronate (Zol), Alendronate (Ale) and Risedronate (Ris)) on DPSCs and PDLSCs by the 3-(4,5-di-methyl-thiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfo-phenyl)-2H-tetrazolium (MTS) assay. Non-toxic concentrations of BPs were determined at 24 h under growth condition, and at 21 days under osteogenic differentiation condition for both cells. The scratch assay was performed to evaluate their migration capacity under the usage of determined of BPs concentrations at 24 h. The results revealed that while the scratch closure is 70% in the control group for DPSCs, it was 57%, 66% and 66% in Zol, Ale and Ris groups, respectively. For PDLSs, while wound closure is 71% in control group, it was 65%, 66% and 66% in Zol, Ale and Ris groups, respectively. As future experiments, tube formation assay and aortic ring assay will be done to determinate angiogenesis abilities of DPSCs and PDLSCs treated with BPs. Expression levels of osteogenic differentiation marker genes involved in bone development will be determined using real time-polymerase change reaction (RT-PCR) assay and expression profiles of important proteins involved in osteogenesis will be evaluated using western blotting assay for osteogenically differentiated MSCs treated with or without BPs. In addition to these, von Kossa staining will be performed to measure calcium mineralization status of MSCs.

Keywords: bisphosphonates, bisphosphonate-induced osteonecrosis of the jaw, mesenchymal stem cells, osteogenesis

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611 Development of a Miniature Laboratory Lactic Goat Cheese Model to Study the Expression of Spoilage by Pseudomonas Spp. In Cheeses

Authors: Abirami Baleswaran, Christel Couderc, Loubnah Belahcen, Jean Dayde, Hélène Tormo, Gwénaëlle Jard

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Cheeses are often reported to be spoiled by Pseudomonas spp., responsible for defects in appearance, texture, taste, and smell, leading to their non-marketing and even their destruction. Despite preventive actions, problems linked to Pseudomonas spp. are difficult to control by the lack of knowledge and control of these contaminants during the cheese manufacturing. Lactic goat cheese producers are not spared by this problem and are looking for solutions to decrease the number of spoiled cheeses. To explore different hypotheses, experiments are needed. However, cheese-making experiments at the pilot scale are expensive and time consuming. Thus, there is a real need to develop a miniature cheeses model system under controlled conditions. In a previous study, several miniature cheese models corresponding to different type of commercial cheeses have been developed for different purposes. The models were, for example, used to study the influence of milk, starters cultures, pathogen inhibiting additives, enzymatic reactions, microflora, freezing process on cheese. Nevertheless, no miniature model was described on the lactic goat cheese. The aim of this work was to develop a miniature cheese model system under controlled laboratory conditions which resembles commercial lactic goat cheese to study Pseudomonas spp. spoilage during the manufacturing and ripening process. First, a protocol for the preparation of miniature cheeses (3.5 times smaller than a commercial one) was designed based on the cheese factorymanufacturing process. The process was adapted from “Rocamadour” technology and involves maturation of pasteurized milk, coagulation, removal of whey by centrifugation, moulding, and ripening in a little scale cellar. Microbiological (total bacterial count, yeast, molds) and physicochemical (pH, saltinmoisture, moisture in fat-free)analyses were performed on four key stages of the process (before salting, after salting, 1st day of ripening, and end of ripening). Factory and miniature cheeses volatilomewere also obtained after full scan Sift-MS cheese analysis. Then, Pseudomonas spp. strains isolated from contaminated cheeses were selected on their origin, their ability to produce pigments, and their enzymatic activities (proteolytic, lecithinasic, and lipolytic). Factory and miniature curds were inoculated by spotting selected strains on the cheese surface. The expression of cheese spoilage was evaluated by counting the level of Pseudomonas spp. during the ripening and by visual observation and under UVlamp. The physicochemical and microbiological compositions of miniature cheeses permitted to assess that miniature process resembles factory process. As expected, differences involatilomes were observed, probably due to the fact that miniature cheeses are made usingpasteurized milk to better control the microbiological conditions and also because the little format of cheese induced probably a difference during the ripening even if the humidity and temperature in the cellar were quite similar. The spoilage expression of Pseudomonas spp. was observed in miniature and factory cheeses. It confirms that the proposed model is suitable for the preparation of miniature cheese specimens in the spoilage study of Pseudomonas spp. in lactic cheeses. This kind of model could be deployed for other applications and other type of cheese.

Keywords: cheese, miniature, model, pseudomonas spp, spoilage

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610 Use of Proton Pump Inhibitors Medications during the First Years of Life and Late Complications

Authors: Kamelia Hamza

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Background: Proton pump inhibitors (PPIs) are the most prescribed drug classes for pediatric gastroesophageal reflux disease (GERD).Many patients are treated with these drugs for atypical manifestations attributed to gastroesophageal reflux (GER), even in the absence of proved causal relationship. There is an impression of increase use of PPI's treatment for reflux in "clalit health services," the largest health organization in Israel. In the recent years, the medicine is given without restriction, it's not limited to pediatric gastroenterologists only, but pediatricians and family doctors. The objective of this study is to evaluate the hypothesis that exposure to PPIs during the first year of life is associated with an increased risk of developing late adverse diseases: pneumonia, asthma, AGE, IBD, celiac disease, allergic disorders, obesity, attention deficit hyperactivity disorders (ADHD), autism spectrum disorders (ASD). Methods: The study is a retrospective case-control cohort study based on a computerized database of Clalit Health Services (CHS). It includes 9844 children born between 2002-2018 and reported to complain of at least one of the symptoms (reflux/ spitting up, irritability, feeding difficulties, colics). The study population included the study group (n=4922) of children exposed to PPIs at any time prior to the first year of life and a control group (n=4922) child not exposed to PPIs who were matched to each case of the study group on age, race, socioeconomic status, and year of birth. The prevalence of late complications/diseases in the study group was compared with the prevalence of late complications/diseases diagnosis between 2002-2020 in the control group. Odds ratios and 95% confidence intervals were calculated by using logistic regression models. Results: We found that compared to the control group, children exposed to PPIs in the first year of life had an increased risk of developing several late complications/ disorders: pneumonia, asthma, various allergies (urticaria, allergic rhinitis, or allergic conjunctivitis) OR, inhalant allergies, and food allergies. In addition, they showed an increased risk of being diagnosed with ADHD or ASD, but children exposed to PPIs in the first year of life had decrease the risk of obesity by 17% (OR 0.825, 95%CI 0.697-0.976). Conclusions: We found significant associations between the use of PPIs during the first year of life and subsequent development of late complications/diseases such as respiratory diseases, allergy diseases, ADHD, and ASD. More studies are needed to prove causality and determine the mechanism behind the effect of PPIs and the development of late complications.

Keywords: acid suppressing medications, proton pump inhibitors, histamine 2 blocker, late complications, gastroesophageal reflux, gastroesophageal reflux disease, acute gastroenteritis, community acquired pneumonia, asthma, allergic diseases, obesity, inflammatory bowel diseases, ulcerative colitis, crohn disease, attention deficit hyperactivity disorders, autism spectrum disorders

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609 Arisarum Vulgare: Bridging Tradition and Science through Phytochemical Characterization and Exploring Therapeutic Potential via in vitro and in vivo Biological Activities

Authors: Boudjelal Amel

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Arisarum vulgare, a member of the Araceae family, is an herbaceous perennial widely distributed in the Mediterranean region. A. vulgare is recognized for its medicinal properties and holds significant traditional importance in Algeria for the treatment of various human ailments, including pain, infections, inflammation, digestive disorders, skin problems, eczema, cancer, wounds, burns and gynecological diseases. Despite its extensive traditional use, scientific exploration of A. vulgare remains limited. The study aims to investigate for the first time the therapeutic potential of A. vulgare ethanolic extract obtained by ultrasound-assisted extraction. The chemical composition of the extract was determined by LC-MS/MS analysis. For in vitro phytopharmacological evaluation, several assays, including DPPH, ABTS, FRAP and reducing power, were employed to evaluate the antioxidant activity. The antibacterial activity was assessed againt Escherichia coli, Salmonella typhimurium, Staphylococus aureus, Enterococcus feacium by disk diffusion and microdilution methods. The possible inhibitory activity of ethanolic extract was analyzed against the cholinesterases enzymes (AChE and BChE). The DNA protection activity of A. vulgare ethanolic extract was estimated using the agarose gel electrophoresis method. The capacities of the extract to protect plasmid DNA (pBR322) from the oxidizing effects of H2O2 and UV treatment were evaluated by their DNA-breaking forms. The in vivo wound healing potential of a traditional ointment containing 5% of A. vulgare ethanolic extract was also investigated. The LC-MS/MS profiling of the extract revealed the presence of various bioactive compounds, including naringenin, chlorogenic, vanillic, cafeic, coumaric acids, trans-cinnamic and trans ferrulic acids. The plant extract presented considerable antioxidant potential, being the most active for Reducing power (0,07326±0.001 mg/ml) and DPPH (0.14±0.004 mg/ml). The extract showed the highest inhibition zone diameter against Enterococcus feacium (36±0.1 mm). The ethanolic extract of A. vulgare suppressed the growth of Staphylococus aureus, Escherichia coli and Salmonella typhimurium according to the MIC values. The extract of the plant significantly inhibited both AChE and BChE enzymes. DNA protection activity of the A. vulgare extract was determined as 90.41% for form I and 51.92% for form II. The in vivo experiments showed that 5% ethanolic extract ointment accelerated the wound healing process. The topical application of the traditional formulation enhanced wound closure (95,36±0,6 %) and improved histological parameters in the treated group compared to the control groups. The promising biological properties of Arisarum vulgare revealed that the plant could be appraised as a potential origin of bioactive molecules having multifunctional medicinal uses.

Keywords: arisarum vulgare, LC-MS/MS, antioxidant activity, antimicrobial activity, cholinesterases enzymes inhibition, dna-damage activity, in vivo wound healing

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608 Kidney Supportive Care in Canada: A Constructivist Grounded Theory of Dialysis Nurses’ Practice Engagement

Authors: Jovina Concepcion Bachynski, Lenora Duhn, Idevania G. Costa, Pilar Camargo-Plazas

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Kidney failure is a life-limiting condition for which treatment, such as dialysis (hemodialysis and peritoneal dialysis), can exact a tremendously high physical and psychosocial symptom burden. Kidney failure can be severe enough to require a palliative approach to care. The term supportive care can be used in lieu of palliative care to avoid the misunderstanding that palliative care is synonymous with end-of-life or hospice care. Kidney supportive care, encompassing advance care planning, is an approach to care that improves the quality of life for people receiving dialysis through early identification and treatment of symptoms throughout the disease trajectory. Advanced care planning involves ongoing conversations about the values, goals, and preferences for future care between individuals and their healthcare teams. Kidney supportive care is underutilized and often initiated late in this population. There is evidence to indicate nurses are not providing the necessary elements of supportive kidney care. Dialysis nurses’ delay or lack of engagement in supportive care until close to the end of life may result in people dying without receiving optimal palliative care services. Using Charmaz’s constructivist grounded theory, the purpose of this doctoral study is to develop a substantive theory that explains the process of engagement in supportive care by nurses working in dialysis settings in Canada. Through initial purposeful and subsequent theoretical sampling, 23 nurses with current or recent work experience in outpatient hemodialysis, home hemodialysis, and peritoneal dialysis settings drawn from across Canada were recruited to participate in two intensive interviews using the Zoom© teleconferencing platform. Concurrent data collection and data analysis, constant comparative analysis of initial and focused codes until the attainment of theoretical saturation, and memo-writing, as well as researcher reflexivity, have been undertaken to aid the emergence of concepts, categories, and, ultimately, the constructed theory. At the time of abstract submission, data analysis is currently at the second level of coding (i.e., focused coding stage) of the research study. Preliminary categories include: (a) focusing on biomedical care; (b) multi-dimensional challenges to having the conversation; (c) connecting and setting boundaries with patients; (d) difficulty articulating kidney-supportive care; and (e) unwittingly practising kidney-supportive care. For the conference, the resulting theory will be presented. Nurses working in dialysis are well-positioned to ensure the delivery of quality kidney-supportive care. This study will help to determine the process and the factors enabling and impeding nurse engagement in supportive care in dialysis to effect change for normalizing advance care planning conversations in the clinical setting. This improved practice will have substantive beneficial implications for the many individuals living with kidney failure and their supporting loved ones.

Keywords: dialysis, kidney failure, nursing, supportive care

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607 Effects of Oxidized LDL in M2 Macrophages: Implications in Atherosclerosis

Authors: Fernanda Gonçalves, Karla Alcântara, Vanessa Moura, Patrícia Nolasco, Jorge Kalil, Maristela Hernandez

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Introduction: Atherosclerosis is a chronic disease where two striking features are observed: retention of lipids and inflammation. Understanding the interaction between immune cells and lipoproteins involved in atherogenesis are urgent challenges, since cardiovascular diseases are the leading cause of death worldwide. Macrophages are critical to the development of atherosclerotic plaques and in the perpetuation of inflammation in these lesions. These cells are also directly involved in unstable plaque rupture. Recently different populations of macrophages are being identified in atherosclerotic lesions. Although the presence of M2 macrophages (macrophages activated by the alternative pathway, eg. The IL-4) has been identified, the function of these cells in atherosclerosis is not yet defined. M2 macrophages have a high endocytic capacity, they promote remodeling of tissues and to have anti-inflammatory activity. However, in atherosclerosis, especially unstable plaques, severe inflammatory reaction, accumulation of cellular debris and intense degradation of the tissue is observed. Thus, it is possible that the M2 macrophages have altered function (phenotype) in atherosclerosis. Objective: Our aim is to evaluate if the presence of oxidized LDL alters the phenotype and function of M2 macrophages in vitro. Methods: For this, we will evaluate whether the addition of lipoprotein in M2 macrophages differentiated in vitro with IL -4 induces 1) a reduction in the secretion of anti-inflammatory cytokines (CBA and ELISA), 2) secretion of inflammatory cytokines (CBA and ELISA), 3) expression of cell activation markers (Flow cytometry), 4) alteration in gene expression of molecules adhesion and extracellular matrix (Real-Time PCR) and 5) Matrix degradation (confocal microscopy). Results: In oxLDL stimulated M2 macrophages cultures we did not find any differences in the expression of the cell surface markers tested, including: HLA-DR, CD80, CD86, CD206, CD163 and CD36. Also, cultures stimulated with oxLDL had similar phagocytic capacity when compared to unstimulated cells. However, in the supernatant of these cultures an increase in the secretion of the pro-inflammatory cytokine IL-8 was detected. No significant changes where observed in IL-6, IL-10, IL-12 and IL-1b levels. The culture supernatant also induced massive extracellular matrix (produced by mouse embryo fibroblast) filaments degradation. When evaluating the expression of 84 extracellular matrix and adhesion molecules genes, we observed that the stimulation of oxLDL in M2 macrophages decreased 47% of the genes and increased the expression of only 3% of the genes. In particular we noted that oxLDL inhibit the expression of 60% of the genes constituents of extracellular matrix and collagen expressed by these cells, including fibronectin1 and collagen VI. We also observed a decrease in the expression of matrix protease inhibitors, such as TIMP 2. On the opposite, the matricellular protein thrombospondin had a 12 fold increase in gene expression. In the presence of native LDL 90% of the genes had no altered expression. Conclusion: M2 macrophages stimulated with oxLDL secrete the pro-inflammatory cytokine IL-8, have an altered extracellular matrix constituents gene expression, and promote the degradation of extracellular matrix. M2 macrophages may contribute to the perpetuation of inflammation in atherosclerosis and to plaque rupture.

Keywords: atherosclerosis, LDL, macrophages, m2

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606 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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605 Establishing an Evidence-Based Trauma Informed Care Pathway for Survivors of Modern Slavery

Authors: I. Brezeanu, J. Mackrill, A. Cajo, C. Mogollon

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Modern Slavery is a serious crime, where often the victims are unable to leave their situation of exploitation, being controlled by threats, punishment, violence, coercion, and deception. In the UK, this term encompasses both Slavery and Human Trafficking. The number of potential victims who were referred to the National Referral Mechanism (NRM) increased exponentially in the past decade, passing from fewer than 700 potential victims referred in 2010 to more than 12.000 in 2021. Our study aims to explore how the concept of Trauma-Informed Care (TIC) approach can be adopted by services working with survivors of Modern Slavery and Trafficking (MST). Notably, in this paper, we will elaborate on how the complex needs of survivors are related to their traumatic experiences and what are the necessary steps and resources for implementing a Modern Slavery Trauma-Informed model. While there are relatively few services in the UK that have a deep understanding of the survivors’ and practitioners’ views of how trauma impacts their daily life, there is a strong need for developing services that are organised and delivered in ways that prevent retraumatisation and enable trauma survivors to engage safely with the right professionals at the right time, promoting healing through positive relationships. Such models, known as Trauma-Informed Approaches (TIAs), are seen as crucial to the empowerment of survivors, yet they remain a marginal implementation model by governments, law enforcement, judiciary, or care providers, who are frequently survivors’ first point of contact in the recovery process. In order to understand better how to provide best practice and to adopt the concept, this study is based on a multi-disciplinary approach, encompassing both theoretical perspectives and co-production. By combining qualitative and quantitative research and comparing different analysis of applied examples of TIC in the US and the UK, we gained important insights about the prevention and impact of trauma on survivors’ life. The articulation between more general expertise on Trauma-Informed Care developed by other institutions operating in the field, and the SJOG delivery, based on the Salvation Army’s Modern Slavery Victim Care and Coordination Contract (MSVCC) and the Care Quality Commission regulations, allowed to identify on one side what are the complex needs of survivors derived from their traumatic experiences, and on the other side, how could MST services prevent retraumatisation. Additional, two in-depth interviews with survivors, who receive support from one of our services at Olallo House in London, and a survey shared among all colleagues working with MST services completed the findings of the research with their personal experience and knowledge. Ultimately, we developed an evidence-based Trauma-Informed Care Pathway that aims to improve the wellbeing of survivors and to support them to live a meaningful life. The establishedpathway delivers three main outcomes belonging to the social determinants of health criteria – health and wellbeing, purpose and relationship, and covers key themes of the context of trauma, needs of individuals, and service support.

Keywords: trauma-informed care, modern slavery, human trafficking, trauma, retraumatisation

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604 Microbial Biogeography of Greek Olive Varieties Assessed by Amplicon-Based Metagenomics Analysis

Authors: Lena Payati, Maria Kazou, Effie Tsakalidou

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Table olives are one of the most popular fermented vegetables worldwide, which along with olive oil, have a crucial role in the world economy. They are highly appreciated by the consumers for their characteristic taste and pleasant aromas, while several health and nutritional benefits have been reported as well. Until recently, microbial biogeography, i.e., the study of microbial diversity over time and space, has been mainly associated with wine. However, nowadays, the term 'terroir' has been extended to other crops and food products so as to link the geographical origin and environmental conditions to quality aspects of fermented foods. Taking the above into consideration, the present study focuses on the microbial fingerprinting of the most important olive varieties of Greece with the state-of-the-art amplicon-based metagenomics analysis. Towards this, in 2019, 61 samples from 38 different olive varieties were collected at the final stage of ripening from 13 well spread geographical regions in Greece. For the metagenomics analysis, total DNA was extracted from the olive samples, and the 16S rRNA gene and ITS DNA region were sequenced and analyzed using bioinformatics tools for the identification of bacterial and yeasts/fungal diversity, respectively. Furthermore, principal component analysis (PCA) was also performed for data clustering based on the average microbial composition of all samples from each region of origin. According to the composition, results obtained, when samples were analyzed separately, the majority of both bacteria (such as Pantoea, Enterobacter, Roserbergiella, and Pseudomonas) and yeasts/fungi (such as Aureobasidium, Debaromyces, Candida, and Cladosporium) genera identified were found in all 61 samples. Even though interesting differences were observed at the relative abundance level of the identified genera, the bacterial genus Pantoea and the yeast/fungi genus Aureobasidium were the dominant ones in 35 and 40 samples, respectively. Of note, olive samples collected from the same region had similar fingerprint (genera identified and relative abundance level) regardless of the variety, indicating a potential association between the relative abundance of certain taxa and the geographical region. When samples were grouped by region of origin, distinct bacterial profiles per region were observed, which was also evident from the PCA analysis. This was not the case for the yeast/fungi profiles since 10 out of the 13 regions were grouped together mainly due to the dominance of the genus Aureobasidium. A second cluster was formed for the islands Crete and Rhodes, both of which are located in the Southeast Aegean Sea. These two regions clustered together mainly due to the identification of the genus Toxicocladosporium in relatively high abundances. Finally, the Agrinio region was separated from the others as it showed a completely different microbial fingerprinting. However, due to the limited number of olive samples from some regions, a subsequent PCA analysis with more samples from these regions is expected to yield in a more clear clustering. The present study is part of a bigger project, the first of its kind in Greece, with the ultimate goal to analyze a larger set of olive samples of different varieties and from different regions in Greece in order to have a reliable olives’ microbial biogeography.

Keywords: amplicon-based metagenomics analysis, bacteria, microbial biogeography, olive microbiota, yeasts/fungi

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603 Superparamagnetic Sensor with Lateral Flow Immunoassays as Platforms for Biomarker Quantification

Authors: M. Salvador, J. C. Martinez-Garcia, A. Moyano, M. C. Blanco-Lopez, M. Rivas

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Biosensors play a crucial role in the detection of molecules nowadays due to their advantages of user-friendliness, high selectivity, the analysis in real time and in-situ applications. Among them, Lateral Flow Immunoassays (LFIAs) are presented among technologies for point-of-care bioassays with outstanding characteristics such as affordability, portability and low-cost. They have been widely used for the detection of a vast range of biomarkers, which do not only include proteins but also nucleic acids and even whole cells. Although the LFIA has traditionally been a positive/negative test, tremendous efforts are being done to add to the method the quantifying capability based on the combination of suitable labels and a proper sensor. One of the most successful approaches involves the use of magnetic sensors for detection of magnetic labels. Bringing together the required characteristics mentioned before, our research group has developed a biosensor to detect biomolecules. Superparamagnetic nanoparticles (SPNPs) together with LFIAs play the fundamental roles. SPMNPs are detected by their interaction with a high-frequency current flowing on a printed micro track. By means of the instant and proportional variation of the impedance of this track provoked by the presence of the SPNPs, quantitative and rapid measurement of the number of particles can be obtained. This way of detection requires no external magnetic field application, which reduces the device complexity. On the other hand, the major limitations of LFIAs are that they are only qualitative or semiquantitative when traditional gold or latex nanoparticles are used as color labels. Moreover, the necessity of always-constant ambient conditions to get reproducible results, the exclusive detection of the nanoparticles on the surface of the membrane, and the short durability of the signal are drawbacks that can be advantageously overcome with the design of magnetically labeled LFIAs. The approach followed was to coat the SPIONs with a specific monoclonal antibody which targets the protein under consideration by chemical bonds. Then, a sandwich-type immunoassay was prepared by printing onto the nitrocellulose membrane strip a second antibody against a different epitope of the protein (test line) and an IgG antibody (control line). When the sample flows along the strip, the SPION-labeled proteins are immobilized at the test line, which provides magnetic signal as described before. Preliminary results using this practical combination for the detection and quantification of the Prostatic-Specific Antigen (PSA) shows the validity and consistency of the technique in the clinical range, where a PSA level of 4.0 ng/mL is the established upper normal limit. Moreover, a LOD of 0.25 ng/mL was calculated with a confident level of 3 according to the IUPAC Gold Book definition. Its versatility has also been proved with the detection of other biomolecules such as troponin I (cardiac injury biomarker) or histamine.

Keywords: biosensor, lateral flow immunoassays, point-of-care devices, superparamagnetic nanoparticles

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602 Gut Microbial Dynamics in a Mouse Model of Inflammation-Linked Carcinogenesis as a Result of Diet Supplementation with Specific Mushroom Extracts

Authors: Alvarez M., Chapela M. J., Balboa E., Rubianes D., Sinde E., Fernandez de Ana C., Rodríguez-Blanco A.

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The gut microbiota plays an important role as gut inflammation could contribute to colorectal cancer development; however, this role is still not fully understood, and tools able to prevent this progression are yet to be developed. The main objective of this study was to monitor the effects of a mushroom extracts formulation in gut microbial community composition of an Azoxymethane (AOM)/Dextran sodium sulfate (DSS) mice model of inflammation-linked carcinogenesis. For the in vivo study, 41 adult male mice of the C57BL / 6 strain were obtained. 36 of them have been induced in a state of colon carcinogenesis by a single intraperitoneal administration of AOM at a dose of 12.5 mg/kg; the control group animals received instead of the same volume of 0.9% saline. DSS is an extremely toxic polysaccharide sulfate that causes chronic inflammation of the colon mucosa, favoring the appearance of severe colitis and the production of tumors induced by AOM. Induction by AOM/DSS is an interesting platform for chemopreventive intervention studies. This time the model was used to monitor gut microbiota changes as a result of supplementation with a specific mushroom extracts formulation previously shown to have prebiotic activity. The animals have been divided into three groups: (i) Cancer + mushroom extracts formulation experimental group: to which the MicoDigest2.0 mushroom extracts formulation developed by Hifas da Terra S.L has been administered dissolved in drinking water at an estimated concentration of 100 mg / ml. (ii) Control group of animals with Cancer: to which normal water has been administered without any type of treatment. (iii) Control group of healthy animals: these are the animals that have not been induced cancer or have not received any treatment in drinking water. This treatment has been maintained for a period of 3 months, after which the animals were sacrificed to obtain tissues that were subsequently analyzed to verify the effects of the mushroom extract formulation. A microbiological analysis has been carried out to compare the microbial communities present in the intestines of the mice belonging to each of the study groups. For this, the methodology of massive sequencing by molecular analysis of the 16S gene has been used (Ion Torrent technology). Initially, DNA extraction and metagenomics libraries were prepared using the 16S Metagenomics kit, always following the manufacturer's instructions. This kit amplifies 7 of the 9 hypervariable regions of the 16S gene that will then be sequenced. Finally, the data obtained will be compared with a database that makes it possible to determine the degree of similarity of the sequences obtained with a wide range of bacterial genomes. Results obtained showed that, similarly to certain natural compounds preventing colorectal tumorigenesis, a mushroom formulation enriched the Firmicutes and Proteobacteria phyla and depleted Bacteroidetes. Therefore, it was demonstrated that the consumption of the mushroom extracts’ formulation developed could promote the recovery of the microbial balance that is disrupted in the mice model of carcinogenesis. More preclinical and clinical studies are needed to validate this promising approach.

Keywords: carcinogenesis, microbiota, mushroom extracts, inflammation

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601 Comparison between Bernardi’s Equation and Heat Flux Sensor Measurement as Battery Heat Generation Estimation Method

Authors: Marlon Gallo, Eduardo Miguel, Laura Oca, Eneko Gonzalez, Unai Iraola

Abstract:

The heat generation of an energy storage system is an essential topic when designing a battery pack and its cooling system. Heat generation estimation is used together with thermal models to predict battery temperature in operation and adapt the design of the battery pack and the cooling system to these thermal needs guaranteeing its safety and correct operation. In the present work, a comparison between the use of a heat flux sensor (HFS) for indirect measurement of heat losses in a cell and the widely used and simplified version of Bernardi’s equation for estimation is presented. First, a Li-ion cell is thermally characterized with an HFS to measure the thermal parameters that are used in a first-order lumped thermal model. These parameters are the equivalent thermal capacity and the thermal equivalent resistance of a single Li-ion cell. Static (when no current is flowing through the cell) and dynamic (making current flow through the cell) tests are conducted in which HFS is used to measure heat between the cell and the ambient, so thermal capacity and resistances respectively can be calculated. An experimental platform records current, voltage, ambient temperature, surface temperature, and HFS output voltage. Second, an equivalent circuit model is built in a Matlab-Simulink environment. This allows the comparison between the generated heat predicted by Bernardi’s equation and the HFS measurements. Data post-processing is required to extrapolate the heat generation from the HFS measurements, as the sensor records the heat released to the ambient and not the one generated within the cell. Finally, the cell temperature evolution is estimated with the lumped thermal model (using both HFS and Bernardi’s equation total heat generation) and compared towards experimental temperature data (measured with a T-type thermocouple). At the end of this work, a critical review of the results obtained and the possible mismatch reasons are reported. The results show that indirectly measuring the heat generation with HFS gives a more precise estimation than Bernardi’s simplified equation. On the one hand, when using Bernardi’s simplified equation, estimated heat generation differs from cell temperature measurements during charges at high current rates. Additionally, for low capacity cells where a small change in capacity has a great influence on the terminal voltage, the estimated heat generation shows high dependency on the State of Charge (SoC) estimation, and therefore open circuit voltage calculation (as it is SoC dependent). On the other hand, with indirect measuring the heat generation with HFS, the resulting error is a maximum of 0.28ºC in the temperature prediction, in contrast with 1.38ºC with Bernardi’s simplified equation. This illustrates the limitations of Bernardi’s simplified equation for applications where precise heat monitoring is required. For higher current rates, Bernardi’s equation estimates more heat generation and consequently, a higher predicted temperature. Bernardi´s equation accounts for no losses after cutting the charging or discharging current. However, HFS measurement shows that after cutting the current the cell continues generating heat for some time, increasing the error of Bernardi´s equation.

Keywords: lithium-ion battery, heat flux sensor, heat generation, thermal characterization

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600 Process of Production of an Artisanal Brewery in a City in the North of the State of Mato Grosso, Brazil

Authors: Ana Paula S. Horodenski, Priscila Pelegrini, Salli Baggenstoss

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The brewing industry with artisanal concepts seeks to serve a specific market, with diversified production that has been gaining ground in the national environment, also in the Amazon region. This growth is due to the more demanding consumer, with a diversified taste that wants to try new types of beer, enjoying products with new aromas, flavors, as a differential of what is so widely spread through the big industrial brands. Thus, through qualitative research methods, the study aimed to investigate how is the process of managing the production of a craft brewery in a city in the northern State of Mato Grosso (BRAZIL), providing knowledge of production processes and strategies in the industry. With the efficient use of resources, it is possible to obtain the necessary quality and provide better performance and differentiation of the company, besides analyzing the best management model. The research is descriptive with a qualitative approach through a case study. For the data collection, a semi-structured interview was elaborated, composed of the areas: microbrewery characterization, artisan beer production process, and the company supply chain management. Also, production processes were observed during technical visits. With the study, it was verified that the artisan brewery researched develops preventive maintenance strategies with the inputs, machines, and equipment, so that the quality of the product and the production process are achieved. It was observed that the distance from the supplying centers makes the management of processes and the supply chain be carried out with a longer planning time so that the delivery of the final product is satisfactory. The production process of the brewery is composed of machines and equipment that allows the control and quality of the product, which the manager states that for the productive capacity of the industry and its consumer market, the available equipment meets the demand. This study also contributes to highlight one of the challenges for the development of small breweries in front of the market giants, that is, the legislation, which fits the microbreweries as producers of alcoholic beverages. This makes the micro and small business segment to be taxed as a major, who has advantages in purchasing large batches of raw materials and tax incentives because they are large employers and tax pickers. It was possible to observe that the supply chain management system relies on spreadsheets and notes that are done manually, which could be simplified with a computer program to streamline procedures and reduce risks and failures of the manual process. In relation to the control of waste and effluents affected by the industry is outsourced and meets the needs. Finally, the results showed that the industry uses preventive maintenance as a productive strategy, which allows better conditions for the production and quality of artisanal beer. The quality is directly related to the satisfaction of the final consumer, being prized and performed throughout the production process, with the selection of better inputs, the effectiveness of the production processes and the relationship with the commercial partners.

Keywords: artisanal brewery, production management, production processes, supply chain

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599 Seismic Response Control of Multi-Span Bridge Using Magnetorheological Dampers

Authors: B. Neethu, Diptesh Das

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The present study investigates the performance of a semi-active controller using magneto-rheological dampers (MR) for seismic response reduction of a multi-span bridge. The application of structural control to the structures during earthquake excitation involves numerous challenges such as proper formulation and selection of the control strategy, mathematical modeling of the system, uncertainty in system parameters and noisy measurements. These problems, however, need to be tackled in order to design and develop controllers which will efficiently perform in such complex systems. A control algorithm, which can accommodate un-certainty and imprecision compared to all the other algorithms mentioned so far, due to its inherent robustness and ability to cope with the parameter uncertainties and imprecisions, is the sliding mode algorithm. A sliding mode control algorithm is adopted in the present study due to its inherent stability and distinguished robustness to system parameter variation and external disturbances. In general a semi-active control scheme using an MR damper requires two nested controllers: (i) an overall system controller, which derives the control force required to be applied to the structure and (ii) an MR damper voltage controller which determines the voltage required to be supplied to the damper in order to generate the desired control force. In the present study a sliding mode algorithm is used to determine the desired optimal force. The function of the voltage controller is to command the damper to produce the desired force. The clipped optimal algorithm is used to find the command voltage supplied to the MR damper which is regulated by a semi active control law based on sliding mode algorithm. The main objective of the study is to propose a robust semi active control which can effectively control the responses of the bridge under real earthquake ground motions. Lumped mass model of the bridge is developed and time history analysis is carried out by solving the governing equations of motion in the state space form. The effectiveness of MR dampers is studied by analytical simulations by subjecting the bridge to real earthquake records. In this regard, it may also be noted that the performance of controllers depends, to a great extent, on the characteristics of the input ground motions. Therefore, in order to study the robustness of the controller in the present study, the performance of the controllers have been investigated for fourteen different earthquake ground motion records. The earthquakes are chosen in such a way that all possible characteristic variations can be accommodated. Out of these fourteen earthquakes, seven are near-field and seven are far-field. Also, these earthquakes are divided into different frequency contents, viz, low-frequency, medium-frequency, and high-frequency earthquakes. The responses of the controlled bridge are compared with the responses of the corresponding uncontrolled bridge (i.e., the bridge without any control devices). The results of the numerical study show that the sliding mode based semi-active control strategy can substantially reduce the seismic responses of the bridge showing a stable and robust performance for all the earthquakes.

Keywords: bridge, semi active control, sliding mode control, MR damper

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598 Higher Education Benefits and Undocumented Students: An Explanatory Model of Policy Adoption

Authors: Jeremy Ritchey

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Undocumented immigrants in the U.S. face many challenges when looking to progress in society, especially when pursuing post-secondary education. The majority of research done on state-level policy adoption pertaining to undocumented higher-education pursuits, specifically in-state resident tuition and financial aid eligibility policies, have framed the discussion on the potential and actual impacts which implementation can and has achieved. What is missing is a model to view the social, political and demographic landscapes upon which such policies (in their various forms) find a route to legislative enactment. This research looks to address this gap in the field by investigating the correlations and significant state-level variables which can be operationalized to construct a framework for adoption of these specific policies. In the process, analysis will show that past unexamined conceptualizations of how such policies come to fruition may be limited or contradictory when compared to available data. Circling on the principles of Policy Innovation and Policy Diffusion theory, this study looks to use variables collected via Michigan State University’s Correlates of State Policy Project, a collectively and ongoing compiled database project centered around annual variables (1900-2016) collected from all 50 states relevant to policy research. Using established variable groupings (demographic, political, social capital measurements, and educational system measurements) from the time period of 2000 to 2014 (2001 being when such policies began), one can see how this data correlates with the adoption of policies related to undocumented students and in-state college tuition. After regression analysis, the results will illuminate which variables appears significant and to what effect, as to help formulate a model upon which to explain when adoption appears to occur and when it does not. Early results have shown that traditionally held conceptions on conservative and liberal identities of the state, as they relate to the likelihood of such policies being adopted, did not fall in line with the collected data. Democratic and liberally identified states were, overall, less likely to adopt pro-undocumented higher education policies than Republican and conservatively identified states and vis versa. While further analysis is needed as to improve the model’s explanatory power, preliminary findings are showing promise in widening our understanding of policy adoption factors in this realm of policies compared to the gap of such knowledge in the publications of the field as it currently exists. The model also looks to serve as an important tool for policymakers in framing such potential policies in a way that is congruent with the relevant state-level determining factors while being sensitive to the most apparent sources of potential friction. While additional variable groups and individual variables will ultimately need to be added and controlled for, this research has already begun to demonstrate how shallow or unexamined reasoning behind policy adoption in the realm of this topic needs to be addressed or else the risk is erroneous conceptions leaking into the foundation of this growing and ever important field.

Keywords: policy adoption, in-state tuition, higher education, undocumented immigrants

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597 An Interoperability Concept for Detect and Avoid and Collision Avoidance Systems: Results from a Human-In-The-Loop Simulation

Authors: Robert Rorie, Lisa Fern

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The integration of Unmanned Aircraft Systems (UAS) into the National Airspace System (NAS) poses a variety of technical challenges to UAS developers and aviation regulators. In response to growing demand for access to civil airspace in the United States, the Federal Aviation Administration (FAA) has produced a roadmap identifying key areas requiring further research and development. One such technical challenge is the development of a ‘detect and avoid’ system (DAA; previously referred to as ‘sense and avoid’) to replace the ‘see and avoid’ requirement in manned aviation. The purpose of the DAA system is to support the pilot, situated at a ground control station (GCS) rather than in the cockpit of the aircraft, in maintaining ‘well clear’ of nearby aircraft through the use of GCS displays and alerts. In addition to its primary function of aiding the pilot in maintaining well clear, the DAA system must also safely interoperate with existing NAS systems and operations, such as the airspace management procedures of air traffic controllers (ATC) and collision avoidance (CA) systems currently in use by manned aircraft, namely the Traffic alert and Collision Avoidance System (TCAS) II. It is anticipated that many UAS architectures will integrate both a DAA system and a TCAS II. It is therefore necessary to explicitly study the integration of DAA and TCAS II alerting structures and maneuver guidance formats to ensure that pilots understand the appropriate type and urgency of their response to the various alerts. This paper presents a concept of interoperability for the two systems. The concept was developed with the goal of avoiding any negative impact on the performance level of TCAS II (understanding that TCAS II must largely be left as-is) while retaining a DAA system that still effectively enables pilots to maintain well clear, and, as a result, successfully reduces the frequency of collision hazards. The interoperability concept described in the paper focuses primarily on facilitating the transition from a late-stage DAA encounter (where a loss of well clear is imminent) to a TCAS II corrective Resolution Advisory (RA), which requires pilot compliance with the directive RA guidance (e.g., climb, descend) within five seconds of its issuance. The interoperability concept was presented to 10 participants (6 active UAS pilots and 4 active commercial pilots) in a medium-fidelity, human-in-the-loop simulation designed to stress different aspects of the DAA and TCAS II systems. Pilot response times, compliance rates and subjective assessments were recorded. Results indicated that pilots exhibited comprehension of, and appropriate prioritization within, the DAA-TCAS II combined alert structure. Pilots demonstrated a high rate of compliance with TCAS II RAs and were also seen to respond to corrective RAs within the five second requirement established for manned aircraft. The DAA system presented under test was also shown to be effective in supporting pilots’ ability to maintain well clear in the overwhelming majority of cases in which pilots had sufficient time to respond. The paper ends with a discussion of next steps for research on integrating UAS into civil airspace.

Keywords: detect and avoid, interoperability, traffic alert and collision avoidance system (TCAS II), unmanned aircraft systems

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596 Using Virtual Reality Exergaming to Improve Health of College Students

Authors: Juanita Wallace, Mark Jackson, Bethany Jurs

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Introduction: Exergames, VR games used as a form of exercise, are being used to reduce sedentary lifestyles in a vast number of populations. However, there is a distinct lack of research comparing the physiological response during VR exergaming to that of traditional exercises. The purpose of this study was to create a foundationary investigation establishing changes in physiological responses resulting from VR exergaming in a college aged population. Methods: In this IRB approved study, college aged students were recruited to play a virtual reality exergame (Beat Saber) on the Oculus Quest 2 (Facebook, 2021) in either a control group (CG) or training group (TG). Both groups consisted of subjects who were not habitual users of virtual reality. The CG played VR one time per week for three weeks and the TG played 150 min/week three weeks. Each group played the same nine Beat Saber songs, in a randomized order, during 30 minute sessions. Song difficulty was increased during play based on song performance. Subjects completed a pre- and posttests at which the following was collected: • Beat Saber Game Metrics: song level played, song score, number of beats completed per song and accuracy (beats completed/total beats) • Physiological Data: heart rate (max and avg.), active calories • Demographics Results: A total of 20 subjects completed the study; nine in the CG (3 males, 6 females) and 11 (5 males, 6 females) in the TG. • Beat Saber Song Metrics: The TG improved performance from a normal/hard difficulty to hard/expert. The CG stayed at the normal/hard difficulty. At the pretest there was no difference in game accuracy between groups. However, at the posttest the CG had a higher accuracy. • Physiological Data (Table 1): Average heart rates were similar between the TG and CG at both the pre- and posttest. However, the TG expended more total calories. Discussion: Due to the lack of peer reviewed literature on c exergaming using Beat Saber, the results of this study cannot be directly compared. However, the results of this study can be compared with the previously established trends for traditional exercise. In traditional exercise, an increase in training volume equates to increased efficiency at the activity. The TG should naturally increase in difficulty at a faster rate than the CG because they played 150 hours per week. Heart rate and caloric responses also increase during traditional exercise as load increases (i.e. speed or resistance). The TG reported an increase in total calories due to a higher difficulty of play. The song accuracy decreases in the TG can be explained by the increased difficulty of play. Conclusion: VR exergaming is comparable to traditional exercise for loads within the 50-70% of maximum heart rate. The ability to use VR for health could motivate individuals who do not engage in traditional exercise. In addition, individuals in health professions can and should promote VR exergaming as a viable way to increase physical activity and improve health in their clients/patients.

Keywords: virtual reality, exergaming, health, heart rate, wellness

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595 Carbon Nanotubes Functionalization via Ullmann-Type Reactions Yielding C-C, C-O and C-N Bonds

Authors: Anna Kolanowska, Anna Kuziel, Sławomir Boncel

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Carbon nanotubes (CNTs) represent a combination of lightness and nanoscopic size with high tensile strength, excellent thermal and electrical conductivity. By now, CNTs have been used as a support in heterogeneous catalysis (CuCl anchored to pre-functionalized CNTs) in the Ullmann-type coupling with aryl halides toward formation of C-N and C-O bonds. The results indicated that the stability of the catalyst was much improved and the elaborated catalytic system was efficient and recyclable. However, CNTs have not been considered as the substrate itself in the Ullmann-type reactions. But if successful, this functionalization would open new areas of CNT chemistry leading to enhanced in-solvent/matrix nanotube individualization. The copper-catalyzed Ullmann-type reaction is an attractive method for the formation of carbon-heteroatom and carbon-carbon bonds in organic synthesis. This condensation reaction is usually conducted at temperature as high as 200 oC, often in the presence of stoichiometric amounts of copper reagent and with activated aryl halides. However, a small amount of organic additive (e.g. diamines, amino acids, diols, 1,10-phenanthroline) can be applied in order to increase the solubility and stability of copper catalyst, and at the same time to allow performing the reaction under mild conditions. The copper (pre-)catalyst is prepared by in situ mixing of copper salt and the appropriate chelator. Our research is focused on the application of Ullmann-type reaction for the covalent functionalization of CNTs. Firstly, CNTs were chlorinated by using iodine trichloride (ICl3) in carbon tetrachloride (CCl4). This method involves formation of several chemical species (ICl, Cl2 and I2Cl6), but the most reactive is the dimer. The fact (that the dimer is the main individual in CCl4) is the reason for high reactivity and possibly high functionalization levels of CNTs. This method, indeed, yielded a notable amount of chlorine onto the MWCNT surface. The next step was the reaction of CNT-Cl with three substrates: aniline, iodobenzene and phenol for the formation C-N, C-C and C-O bonds, respectively, in the presence of 1,10-phenanthroline and cesium carbonate (Cs2CO3) as a base. As the CNT substrates, two multi-wall CNT (MWCNT) types were used: commercially available Nanocyl NC7000™ (9.6 nm diameter, 1.5 µm length, 90% purity) and thicker MWCNTs (in-house) synthesized in our laboratory using catalytic chemical vapour deposition (c-CVD). In-house CNTs had diameter ranging between 60-70 nm and length up to 300 µm. Since classical Ullmann reaction was found as suffering from poor yields, we have investigated the effect of various solvents (toluene, acetonitrile, dimethyl sulfoxide and N,N-dimethylformamide) on the coupling of substrates. Owing to the fact that the aryl halides show the reactivity order of I>Br>Cl>F, we have also investigated the effect of iodine presence on CNT surface on reaction yield. In this case, in first step we have used iodine monochloride instead of iodine trichloride. Finally, we have used the optimized reaction conditions with p-bromophenol and 1,2,4-trihydroxybenzene for the control of CNT dispersion.

Keywords: carbon nanotubes, coupling reaction, functionalization, Ullmann reaction

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594 Previously Undescribed Cardiac Abnormalities in Two Unrelated Autistic Males with Causative Variants in CHD8

Authors: Mariia A. Parfenenko, Ilya S. Dantsev, Sergei V. Bochenkov, Natalia V. Vinogradova, Olga S. Groznova, Victoria Yu. Voinova

Abstract:

Introduction: Autism is the most common neurodevelopmental disorder. Autism is characterized by difficulties in social interaction and adherence to stereotypic behavioral patterns and frequently co-occurs with epilepsy, intellectual disabilities, connective tissue disorders, and other conditions. CHD8 codes for chromodomain-helicase-DNA-binding protein 8 - a chromatin remodeler that regulates cellular proliferation and neurodevelopment in embryogenesis. CHD8 is one of the genes most frequently involved in autism. Patients and methods: 2 unrelated male patients, P3 and P12, aged 3 and 12 years old, underwent whole genome sequencing, which determined that they both had different likely pathogenic variants, both previously undescribed in literature. Sanger sequencing later determined that P12 inherited the variant from his affected mother. Results: P3 and P12 presented with autism, a developmental delay, ataxia, sleep disorders, overgrowth, and macrocephaly, as well as other clinical features typically present in patients with causative variants in CHD8. The mother of P12 also has autistic traits, as well as ataxia, hypotonia, sleep disorders, and other symptoms. However, P3 and P12 also have different cardiac abnormalities. P3 had signs of a repolarization disorder: a flattened T wave in the III and aVF derivations and a negative T wave in the V1-V2 derivations. He also had structural valve anomalies with associated regurgitation, local contractility impairment of the left ventricular, and diastolic dysfunction of the right ventricle. Meanwhile, P12 had Wolff-Parkinson-White syndrome and underwent radiofrequency ablation at the age of 2 years. At the time of observation, P12 had mild sinus arrhythmia and an incomplete right bundle branch block, as well as arterial hypertension. Discussion: Cardiac abnormalities were not previously reported in patients with causative variants in CHD8. The underlying mechanism for the formation of those abnormalities is currently unknown. However, the two hypotheses are either a disordered interaction with CHD7 – another chromodomain remodeler known to be directly involved in the cardiophenotype of CHARGE syndrome – a rare condition characterized by coloboma, heart defects and growth abnormalities, or the disrupted functioning of CHD8 as an A-Kinase Anchoring Protein, which are known to modulate cardiac function. Conclusion: We observed 2 unrelated autistic males with likely pathogenic variants in CHD8 that presented with typical symptoms of CHD8-related neurodevelopmental disorder, as well as cardiac abnormalities. Cardiac abnormalities have, until now, been considered uncharacteristic for patients with causative variants in CHD8. Further accumulation of data, including experimental evidence of the involvement of CHD8 in heart formation, will elucidate the mechanism underlying the cardiophenotype of those patients. Acknowledgements: Molecular genetic testing of the patients was made possible by the Charity Fund for medical and social genetic aid projects «Life Genome.»

Keywords: autism spectrum disorders, chromodomain-helicase-DNA-binding protein 8, neurodevelopmental disorder, cardio phenotype

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