Search results for: accelerated failure time model

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

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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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Authors: Nirit Gavish, Rotem Halutz, Liad Neta

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Nowadays, chatbots are gaining more and more attention due to the advent of large language models. One of the important considerations in chatbot design is how to create an interface to achieve high user satisfaction, trust, and acceptance. Since WhatsApp conversations sometimes substitute for face-to-face communication, we studied whether WhatsAppization of the chatbot -making the conversation resemble a WhatsApp conversation more- will improve user satisfaction, trust, and acceptance, or whether the opposite will occur due to the Uncanny Valley (UV) effect. The task was a drive-sharing task, in which participants communicated with a textual chatbot via WhatsApp and could decide whether to participate in a ride to college with a driver suggested by the chatbot. WhatsAppization of the chatbot was done in two ways: By a dialog-style conversation (Dialog versus No Dialog), and by adding WhatsApp indicators – “Last Seen”, “Connected”, “Read Receipts”, and “Typing…” (Indicators versus No Indicators). Our 120 participants were randomly assigned to one of the four 2 by 2 design groups, with 30 participants in each. They interacted with the WhatsApp chatbot and then filled out a questionnaire. The results demonstrated that, as expected from the manipulation, the interaction with the chatbot was longer for the dialog condition compared to the no dialog. This extra interaction, however, did not lead to higher acceptance -quite the opposite, since participants in the dialog condition were less willing to implement the decision made at the end of the conversation with the chatbot and continue the interaction with the driver they chose. The results are even more striking when considering the Indicators condition. Both for the satisfaction measures and the trust measures, participants’ ratings were lower in the Indicators condition compared to the No Indicators. Participants in the Indicators condition felt that the ride search process was harder to operate, and slower (even though the actual interaction time was similar). They were less convinced that the chatbot suggested real trips and they trusted the person offering the ride and referred to them by the chatbot less. These effects were more evident for participants who preferred to share their rides using WhatsApp compared to participants who preferred chatbots for that purpose. Considering our findings, we can say that the WhatsAppization of the chatbot was detrimental. This is true for the both chatbot WhatsAppization methods – by making the conversation more a dialog and adding WhatsApp indicators. For the chosen drive-sharing task, the results were, in addition to lower satisfaction, less trust in the chatbot’s suggestion and even in the driver suggested by the chatbot, and lower willingness to actually undertake the suggested ride. In addition, it seems that the most problematic WhatsAppization method was using WhatsApp’s indicators during the interaction with the chatbot. The current study suggests that a conversation with an artificial agent should also not imitate a WhatsApp conversation very closely. With the proliferation of WhatsApp use, the emotional and social aspect of face-to face commination are moving to WhatsApp communication. Based on the current study’s findings, it is possible that the UV effect also occurs in WhatsAppization, and not only in humanization, of the chatbot, with a similar feeling of eeriness, and is more pronounced for people who prefer to use WhatsApp over chatbots. The current research can serve as a starting point to study the very interesting and important topic of chatbots WhatsAppization. More methods of WhatsAppization and other tasks could be the focus of further studies.

Keywords: chatbot, WhatsApp, humanization, Uncanny Valley, drive sharing

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Authors: Ewelina Wisnik, Zsolt Regdon, Kinga Chmielewska, Laszlo Virag, Agnieszka Robaszkiewicz

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Apart from protecting genome, PARP1 has been documented to regulate many intracellular processes inter alia gene transcription by physically interacting with chromatin bound proteins and by their ADP-ribosylation. Our recent findings indicate that expression of PARP1 decreases during the differentiation of human CD34+ hematopoietic stem cells to monocytes as a consequence of differentiation-associated cell growth arrest and formation of E2F4-RBL2-HDAC1-SWI/SNF repressive complex at the promoter of this gene. Since the RBL2 complexes repress genes in a E2F-dependent manner and are widespread in the genome in G0 arrested cells, we asked (a) if RBL2 directly contributes to defining monocyte phenotype and function by targeting gene promoters and (b) if RBL2 controls gene transcription indirectly by repressing PARP1. For identification of genes controlled by RBL2 and/or PARP1,we used primer libraries for surface receptors and TLR signaling mediators, genes were silenced by siRNA or shRNA, analysis of gene promoter occupation by selected proteins was carried out by ChIP-qPCR, while statistical analysis in GraphPad Prism 5 and STATISTICA, ChIP-Seq data were analysed in Galaxy 2.5.0.0. On the list of 28 genes regulated by RBL2, we identified only four solely repressed by RBL2-E2F4-HDAC1-BRM complex. Surprisingly, 24 out of 28 emerged genes controlled by RBL2 were co-regulated by PARP1 in six different manners. In one mode of RBL2/PARP1 co-operation, represented by MAP2K6 and MAPK3, PARP1 was found to associate with gene promoters upon RBL2 silencing, which was previously shown to restore PARP1 expression in monocytes. PARP1 effect on gene transcription was observed only in the presence of active EP300, which acetylated gene promoters and activated transcription. Further analysis revealed that PARP1 binding to MA2K6 and MAPK3 promoters enabled recruitment of EP300 in monocytes, while in proliferating cancer cell lines, which actively transcribe PARP1, this protein maintained EP300 at the promoters of MA2K6 and MAPK3. Genome-wide analysis revealed a similar distribution of PARP1 and EP300 around transcription start sites and the co-occupancy of some gene promoters by PARP1 and EP300 in cancer cells. Here, we described a new RBL2/PARP1/EP300 axis which controls gene transcription regardless of the cell type. In this model cell, cycle-dependent transcription of PARP1 regulates expression of some genes repressed by RBL2 upon cell cycle limitation. Thus, RBL2 may indirectly regulate transcription of some genes by controlling the expression of EP300-recruiting PARP1. Acknowledgement: This work was financed by Polish National Science Centre grants nr DEC-2013/11/D/NZ2/00033 and DEC-2015/19/N/NZ2/01735. L.V. is funded by the National Research, Development and Innovation Office grants GINOP-2.3.2-15-2016-00020 TUMORDNS, GINOP-2.3.2-15-2016-00048-STAYALIVE and OTKA K112336. AR is supported by Polish Ministry of Science and Higher Education 776/STYP/11/2016.

Keywords: retinoblastoma transcriptional co-repressor like 2 (RBL2), poly(ADP-ribose) polymerase 1 (PARP1), E1A binding protein p300 (EP300), monocytes

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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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Authors: Stéphanie Looser, Walter Wehrmeyer

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Given the limited research on Small and Mediumsized Enterprises’ (SMEs) contribution to Corporate Social Responsibility (CSR) and even scarcer research on Swiss SMEs, this paper helps to fill these gaps by enabling the identification of supranational SME parameters and to make a contribution to the evolving field of these topics. Thus, the paper investigates the current state of SME practices in Switzerland and across 15 other countries. Combining the degree to which SMEs demonstrate an explicit (or business case) approach or see CSR as an implicit moral activity with the assessment of their attributes for “variety of capitalism” defines the framework of this comparative analysis. According to previous studies, liberal market economies, e.g. in the United States (US) or United Kingdom (UK), are aligned with extrinsic CSR, while coordinated market systems (in Central European or Asian countries) evolve implicit CSR agendas. To outline Swiss small business CSR patterns in particular, 40 SME owner-managers were interviewed. The transcribed interviews were coded utilising MAXQDA for qualitative content analysis. A secondary data analysis of results from different countries (i.e., Australia, Austria, Chile, Cameroon, Catalonia (notably a part of Spain that seeks autonomy), China, Finland, Germany, Hong Kong (a special administrative region of China), Italy, Netherlands, Singapore, Spain, Taiwan, UK, US) lays groundwork for this comparative study on small business CSR. Applying the same coding categories (in MAXQDA) for the interview analysis as well as for the secondary data research while following grounded theory rules to refine and keep track of ideas generated testable hypotheses and comparative power on implicit (and the lower likelihood of explicit) CSR in SMEs retrospectively. The paper identifies Swiss small business CSR as deep, profound, “soul”, and an implicit part of the day-to-day business. Similar to most Central European, Mediterranean, Nordic, and Asian countries, explicit CSR is still very rare in Swiss SMEs. Astonishingly, also UK and US SMEs follow this pattern in spite of their strong and distinct liberal market economies. Though other findings show that nationality matters this research concludes that SME culture and its informal CSR agenda are strongly formative and superseding even forces of market economies, nationally cultural patterns, and language. In a world of “big business”, explicit “business case” CSR, and the mantra that “CSR must pay”, this study points to a distinctly implicit small business CSR model built on trust, physical closeness, and virtues that is largely detached from the bottom line. This pattern holds for different cultural contexts and it is concluded that SME culture is stronger than nationality leading to a supra-national, monolithic SME CSR approach. Hence, classifications of countries by their market system or capitalism, as found in the comparative capitalism literature, do not match the CSR practices in SMEs as they do not mirror the peculiarities of their business. This raises questions on the universality and generalisability of management concepts.

Keywords: CSR, comparative study, cultures of capitalism, small, medium-sized enterprises

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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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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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Authors: Daniel Rowe, Christopher R. Vogel, Richard H. J. Willden

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The University of Oxford’s recirculating water flume is a combined wave and current test tank with a 1 m depth, 1.1 m width, and 10 m long working section, and is capable of flow speeds up to 1 ms−1 . This study documents the hydrodynamic characteristics of the facility in preparation for experimental testing of horizontal axis tidal stream turbine models. The turbine to be tested has a rotor diameter of 0.6 m and is a modified version of one of two model-scale turbines tested in previous experimental campaigns. An Acoustic Doppler Velocimeter (ADV) was used to measure the flow at high temporal resolution at various locations throughout the flume, enabling the spatial uniformity and turbulence flow parameters to be investigated. The mean velocity profiles exhibited high levels of spatial uniformity at the design speed of the flume, 0.6 ms−1 , with variations in the three-dimensional velocity components on the order of ±1% at the 95% confidence level, along with a modest streamwise acceleration through the measurement domain, a target 5 m working section of the flume. A high degree of uniformity was also apparent for the turbulence intensity, with values ranging between 1-2% across the intended swept area of the turbine rotor. The integral scales of turbulence exhibited a far higher degree of variation throughout the water column, particularly in the streamwise and vertical scales. This behaviour is believed to be due to the high signal noise content leading to decorrelation in the sampling records. To achieve more realistic levels of vertical velocity shear in the flume, a simple procedure to practically generate target vertical shear profiles in open-channel flows is described. Here, the authors arranged a series of non-uniformly spaced parallel bars placed across the width of the flume and normal to the onset flow. By adjusting the resistance grading across the height of the working section, the downstream profiles could be modified accordingly, characterised by changes in the velocity profile power law exponent, 1/n. Considering the significant temporal variation in a tidal channel, the choice of the exponent denominator, n = 6 and n = 9, effectively provides an achievable range around the much-cited value of n = 7 observed at many tidal sites. The resulting flow profiles, which we intend to use in future turbine tests, have been characterised in detail. The results indicate non-uniform vertical shear across the survey area and reveal substantial corner flows, arising from the differential shear between the target vertical and cross-stream shear profiles throughout the measurement domain. In vertically sheared flow, the rotor-equivalent turbulence intensity ranges between 3.0-3.8% throughout the measurement domain for both bar arrangements, while the streamwise integral length scale grows from a characteristic dimension on the order of the bar width, similar to the flow downstream of a turbulence-generating grid. The experimental tests are well-defined and repeatable and serve as a reference for other researchers who wish to undertake similar investigations.

Keywords: acoustic doppler Velocimeter, experimental hydrodynamics, open-channel flow, shear profiles, tidal stream turbines

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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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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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Authors: Bai-Chen Xie, Xian-Peng Chen

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China has become the world's largest energy producer and consumer, and its development of renewable energy is of great significance to global energy governance and the fight against climate change. The rapid growth of solar power in China could help achieve its ambitious carbon peak and carbon neutrality targets early. However, the non-technical costs of solar power in China are much higher than at international levels, meaning that inefficiencies are rooted in poor management and improper policy design and that efficiency distortions have become a serious challenge to the sustainable development of the renewable energy industry. Unlike fossil energy generation technologies, the output of solar power is closely related to the volatile solar resource, and the spatial unevenness of solar resource distribution leads to potential efficiency spatial distribution differences. It is necessary to develop an efficiency evaluation method that considers the volatility of solar resources and explores the mechanism of the influence of natural geography and social environment on the spatially varying characteristics of efficiency distribution to uncover the root causes of managing inefficiencies. The study sets solar resources as stochastic inputs, introduces a chance-constrained data envelopment analysis model combined with the directional distance function, and measures the solar resource utilization efficiency of 222 solar power plants in representative photovoltaic bases in northwestern China. By the meta-frontier analysis, we measured the characteristics of different power plant clusters and compared the differences among groups, discussed the mechanism of environmental factors influencing inefficiencies, and performed statistical tests through the system generalized method of moments. Rational localization of power plants is a systematic project that requires careful consideration of the full utilization of solar resources, low transmission costs, and power consumption guarantee. Suitable temperature, precipitation, and wind speed can improve the working performance of photovoltaic modules, reasonable terrain inclination can reduce land cost, and the proximity to cities strongly guarantees the consumption of electricity. The density of electricity demand and high-tech industries is more important than resource abundance because they trigger the clustering of power plants to result in a good demonstration and competitive effect. To ensure renewable energy consumption, increased support for rural grids and encouraging direct trading between generators and neighboring users will provide solutions. The study will provide proposals for improving the full life-cycle operational activities of solar power plants in China to reduce high non-technical costs and improve competitiveness against fossil energy sources.

Keywords: solar power plants, environmental factors, data envelopment analysis, efficiency evaluation

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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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Authors: Jenson George, Thoa Nguyen, Garth Sanewski, Craig Hardner, Heather Eunice Smyth

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Pineapple (Ananas comosus), with its unique sweet flavour, is one of the most popular tropical, non-climacteric fruits consumed worldwide. It is also the third most important tropical fruit in world production. In Australia, 99% of the pineapple production is from the Queensland state due to the favourable subtropical climatic conditions. The flavourful fruit is known to contain around 500 volatile organic compounds (VOC) at varying concentrations and greatly contribute to the flavour quality of pineapple fruit by providing distinct aroma sensory properties that are sweet, fruity, tropical, pineapple-like, caramel-like, coconut-like, etc. The aroma of pineapple is one of the important factors attracting consumers and strengthening the marketplace. To better understand the aroma of Australian-grown pineapples, the matrix-matched Gas chromatography–mass spectrometry (GC-MS), Head Space - Solid-phase microextraction (HS-SPME), Stable-isotope dilution analysis (SIDA) method was developed and validated. The developed method represents a significant improvement over current methods with the incorporation of multiple external reference standards, multiple isotopes labeled internal standards, and a matching model system of pineapple fruit matrix. This method was employed to quantify 28 key aroma compounds in more than 200 genetically diverse pineapple varieties from a breeding program. The Australian pineapple cultivars varied in content and composition of free volatile compounds, which were predominantly comprised of esters, followed by terpenes, alcohols, aldehydes, and ketones. Using selected commercial cultivars grown in Australia, and by employing the sensorial analysis, the appearance (colour), aroma (intensity, sweet, vinegar/tang, tropical fruits, floral, coconut, green, metallic, vegetal, fresh, peppery, fermented, eggy/sulphurous) and texture (crunchiness, fibrousness, and juiciness) were obtained. Relationships between sensory descriptors and volatiles were explored by applying multivariate analysis (PCA) to the sensorial and chemical data. The key aroma compounds of pineapple exhibited a positive correlation with corresponding sensory properties. The sensory and volatile data were also used to explore genetic diversity in the breeding population. GWAS was employed to unravel the genetic control of the pineapple volatilome and its interplay with fruit sensory characteristics. This study enhances our understanding of pineapple aroma (flavour) compounds, their biosynthetic pathways and expands breeding option for pineapple cultivars. This research provides foundational knowledge to support breeding programs, post-harvest and target market studies, and efforts to optimise the flavour of commercial pineapple varieties and their parent lines to produce better tasting fruits for consumers.

Keywords: Ananas comosus, pineapple, flavour, volatile organic compounds, aroma, Gas chromatography–mass spectrometry (GC-MS), Head Space - Solid-phase microextraction (HS-SPME), Stable-isotope dilution analysis (SIDA).

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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

Procedia PDF Downloads 447

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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Authors: Xingyu Gao, Qiang Wu, Yuanyuan Liu, Yue Yang

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In the era of the knowledge economy, the relationship between scientific knowledge and patents has garnered significant attention. Understanding the intricate interplay between the foundations of science and technological innovation has emerged as a pivotal challenge for both researchers and policymakers. This study establishes a coupled network of artificial intelligence patents based on co-cited scientific papers. Leveraging centrality metrics from network analysis offers a fresh perspective on understanding the influence of information flow and knowledge sharing within the network on patent impact. The study initially obtained patent numbers for 446,890 granted US AI patents from the United States Patent and Trademark Office’s artificial intelligence patent database for the years 2002-2020. Subsequently, specific information regarding these patents was acquired using the Lens patent retrieval platform. Additionally, a search and deduplication process was performed on scientific non-patent references (SNPRs) using the Web of Science database, resulting in the selection of 184,603 patents that cited 37,467 unique SNPRs. Finally, this study constructs a coupled network comprising 59,379 artificial intelligence patents by utilizing scientific papers co-cited in patent backward citations. In this network, nodes represent patents, and if patents reference the same scientific papers, connections are established between them, serving as edges within the network. Nodes and edges collectively constitute the patent coupling network. Structural characteristics such as node degree centrality, betweenness centrality, and closeness centrality are employed to assess the scientific connections between patents, while citation count is utilized as a quantitative metric for patent influence. Finally, a negative binomial model is employed to test the nonlinear relationship between these network structural features and patent influence. The research findings indicate that network structural features such as node degree centrality, betweenness centrality, and closeness centrality exhibit inverted U-shaped relationships with patent influence. Specifically, as these centrality metrics increase, patent influence initially shows an upward trend, but once these features reach a certain threshold, patent influence starts to decline. This discovery suggests that moderate network centrality is beneficial for enhancing patent influence, while excessively high centrality may have a detrimental effect on patent influence. This finding offers crucial insights for policymakers, emphasizing the importance of encouraging moderate knowledge flow and sharing to promote innovation when formulating technology policies. It suggests that in certain situations, data sharing and integration can contribute to innovation. Consequently, policymakers can take measures to promote data-sharing policies, such as open data initiatives, to facilitate the flow of knowledge and the generation of innovation. Additionally, governments and relevant agencies can achieve broader knowledge dissemination by supporting collaborative research projects, adjusting intellectual property policies to enhance flexibility, or nurturing technology entrepreneurship ecosystems.

Keywords: centrality, patent coupling network, patent influence, social network analysis

Procedia PDF Downloads 38

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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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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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

Procedia PDF Downloads 242

Authors: Meiling Yu, Nadia Rouatbi, Khuloud T. Al-Jamal

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Background: Treatment of neurological disorders with modern medical and surgical approaches remains difficult. Gene therapy, allowing the delivery of genetic materials that encodes potential therapeutic molecules, represents an attractive option. The treatment of brain diseases with gene therapy requires the gene-editing tool to be delivered efficiently to the central nervous system. In this study, we explored the efficiency of different delivery routes, namely intravenous (i.v.), intra-cranial (i.c.), and intra-nasal (i.n.), to deliver stable nucleic acid-lipid particles (SNALPs) containing gene-editing tools namely Cas9 mRNA and sgRNA encoding for GFP as a reporter protein. We hypothesise that SNALPs can reach the brain and perform gene-editing to different extents depending on the administration route. Intranasal administration (i.n.) offers an attractive and non-invasive way to access the brain circumventing the blood–brain barrier. Successful delivery of gene-editing tools to the brain offers a great opportunity for therapeutic target validation and nucleic acids therapeutics delivery to improve treatment options for a range of neurodegenerative diseases. In this study, we utilised Rosa26-Cas9 knock-in mice, expressing GFP, to study brain distribution and gene-editing efficiency of SNALPs after i.v.; i.c. and i.n. routes of administration. Methods: Single guide RNA (sgRNA) against GFP has been designed and validated by in vitro nuclease assay. SNALPs were formulated and characterised using dynamic light scattering. The encapsulation efficiency of nucleic acids (NA) was measured by RiboGreen™ assay. SNALPs were incubated in serum to assess their ability to protect NA from degradation. Rosa26-Cas9 knock-in mice were i.v., i.n., or i.c. administered with SNALPs to test in vivo gene-editing (GFP knockout) efficiency. SNALPs were given as three doses of 0.64 mg/kg sgGFP following i.v. and i.n. or a single dose of 0.25 mg/kg sgGFP following i.c.. knockout efficiency was assessed after seven days using Sanger Sequencing and Inference of CRISPR Edits (ICE) analysis. In vivo, the biodistribution of DiR labelled SNALPs (SNALPs-DiR) was assessed at 24h post-administration using IVIS Lumina Series III. Results: Serum-stable SNALPs produced were 130-140 nm in diameter with ~90% nucleic acid loading efficiency. SNALPs could reach and stay in the brain for up to 24h following i.v.; i.n. and i.c. administration. Decreasing GFP expression (around 50% after i.v. and i.c. and 20% following i.n.) was confirmed by optical imaging. Despite the small number of mice used, ICE analysis confirmed GFP knockout in mice brains. Additional studies are currently taking place to increase mice numbers. Conclusion: Results confirmed efficient gene knockout achieved by SNALPs in Rosa26-Cas9 knock-in mice expressing GFP following different routes of administrations in the following order i.v.= i.c.> i.n. Each of the administration routes has its pros and cons. The next stages of the project involve assessing gene-editing efficiency in wild-type mice and replacing GFP as a model target with therapeutic target genes implicated in Motor Neuron Disease pathology.

Keywords: CRISPR, nanoparticles, brain diseases, administration routes

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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

Procedia PDF Downloads 100

Authors: Jovana Grahovac, Ivana Pajcin, Natasa Lukic, Jelena Dodic, Aleksandar Jokic

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To obtain purified biomass to be used in the plant pathogen biocontrol or as soil biofertilizer, it is necessary to eliminate residual broth components at the end of the fermentation process. The main drawback of membrane separation techniques is permeate flux decline due to the membrane fouling. Fouling mitigation measures increase the pressure drop along membrane channel due to the increased resistance to flow of the feed suspension, thus increasing the hydraulic power drop. At the same time, these measures lead to an increase in the permeate flux due to the reduced resistance of the filtration cake on the membrane surface. Because of these opposing effects, the energy efficiency of fouling mitigation measures is limited, and the justification of its application is provided by information on a reducing specific energy consumption compared to a case without any measures employed. In this study, the influence of static mixer (Kenics) and air-sparging (two-phase flow) on reduction of specific energy consumption (ER) was investigated. Cultivation Bacillus velezensis was carried out in the 3-L bioreactor (Biostat® Aplus) containing 2 L working volume with two parallel Rushton turbines and without internal baffles. Cultivation was carried out at 28 °C on at 150 rpm with an aeration rate of 0.75 vvm during 96 h. The experiments were carried out in a conventional cross-flow microfiltration unit. During experiments, permeate and retentate were recycled back to the broth vessel to simulate continuous process. The single channel ceramic membrane (TAMI Deutschland) used had a nominal pore size 200 nm with the length of 250 mm and an inner/external diameter of 6/10 mm. The useful membrane channel surface was 4.33×10⁻³ m². Air sparging was brought by the pressurized air connected by a three-way valve to the feed tube by a simple T-connector without diffusor. The different approaches to flux improvement are compared in terms of energy consumption. Reduction of specific energy consumption compared to microfiltration without fouling mitigation is around 49% and 63%, for use of two-phase flow and a static mixer, respectively. In the case of a combination of these two fouling mitigation methods, ER is 60%, i.e., slightly lower compared to the use of turbulence promoter alone. The reason for this result can be found in the fact that flux increase is more affected by the presence of a Kenics static mixer while sparging results in an increase of energy used during microfiltration. By comparing combined method with turbulence promoter flux enhancement method ER is negative (-7%) which can be explained by increased power consumption for air flow with moderate contribution to the flux increase. Another confirmation for this fact can be found by comparing energy consumption values for combined method with energy consumption in the case of two-phase flow. In this instance energy reduction (ER) is 22% that demonstrates that turbulence promoter is more efficient compared to two phase flow. Antimicrobial activity of Bacillus velezensis biomass against phytopathogenic isolates Xanthomonas campestris was preserved under different fouling reduction methods.

Keywords: Bacillus velezensis, microfiltration, static mixer, two-phase flow

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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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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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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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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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Authors: Farnaz Alborzi, Angelika Schmitz, Rainer Stamminger

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Reducing water temperatures in the wash phase of a washing programme and increasing the overall cycle durations are the latest trends in decreasing energy consumption of washing programmes. Since the implementation of the new energy efficiency classes in 2010, manufacturers seem to apply the aforementioned washing strategy with lower temperatures combined with longer programme durations extensively to realise energy-savings needed to meet the requirements of the highest energy efficiency class possible. A semi-representative on-line survey in eleven European countries (Czech Republic, Finland, France, Germany, Hungary, Italy, Poland, Romania, Spain, Sweden and the United Kingdom) was conducted by Bonn University in 2015 to shed light on consumer opinion and behaviour regarding the effects of the lower washing temperature and longer cycle duration in laundry washing on consumers’ acceptance of the programme. The risk of the long wash cycle is that consumers might not use the energy efficient Standard programmes and will think of this option as inconvenient and therefore switch to shorter, but more energy consuming programmes. Furthermore, washing in a lower temperature may lead to the problem of cross-contamination. Washing behaviour of over 5,000 households was studied in this survey to provide support and guidance for manufacturers and policy designers. Qualified households were chosen following a predefined quota: -Involvement in laundry washing: substantial, -Distribution of gender: more than 50 % female , -Selected age groups: -20–39 years, -40–59 years, -60–74 years, -Household size: 1, 2, 3, 4 and more than 4 people. Furthermore, Eurostat data for each country were used to calculate the population distribution in the respective age class and household size as quotas for the consumer survey distribution in each country. Before starting the analyses, the validity of each dataset was controlled with the aid of control questions. After excluding the outlier data, the number of the panel diminished from 5,100 to 4,843. The primary outcome of the study is European consumers are willing to save water and energy in a laundry washing but reluctant to use long programme cycles since they don’t believe that the long cycles could be energy-saving. However, the results of our survey don’t confirm that there is a relation between frequency of using Standard cotton (Eco) or Energy-saving programmes and the duration of the programmes. It might be explained by the fact that the majority of washing programmes used by consumers do not take so long, perhaps consumers just choose some additional time reduction option when selecting those programmes and this finding might be changed if the Energy-saving programmes take longer. Therefore, it may be assumed that introducing the programme duration as a new measure on a revised energy label would strongly influence the consumer at the point of sale. Furthermore, results of the survey confirm that consumers are more willing to use lower temperature programmes in order to save energy than accepting longer programme cycles and majority of them accept deviation from the nominal temperature of the programme as long as the results are good.

Keywords: duration, energy-saving, standard programmes, washing temperature

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Authors: Bozena Tyliszczak, Anna Drabczyk, Sonia Kudlacik-Kramarczyk, Agnieszka Sobczak-Kupiec

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Introduction: Nanomaterials become one of the leading materials in the synthesis of various compounds. This is a reason for the fact that nano-size materials exhibit other properties compared to their macroscopic equivalents. Such a change in size is reflected in a change in optical, electric or mechanical properties. Among nanomaterials, particular attention is currently directed into gold nanoparticles. They find application in a wide range of areas including cosmetology or pharmacy. Additionally, nanogold may be a component of modern wound dressings, which antibacterial activity is beneficial in the viewpoint of the wound healing process. Specific properties of this type of nanomaterials result in the fact that they may also be applied in cancer treatment. Studies on the development of new techniques of the delivery of drugs are currently an important research subject of many scientists. This is due to the fact that along with the development of such fields of science as medicine or pharmacy, the need for better and more effective methods of administering drugs is constantly growing. The solution may be the use of drug carriers. These are materials that combine with the active substance and lead it directly to the desired place. A role of such a carrier may be played by gold nanoparticles that are able to covalently bond with many organic substances. This allows the combination of nanoparticles with active substances. Therefore gold nanoparticles are widely used in the preparation of nanocomposites that may be used for medical purposes with special emphasis on drug delivery. Methodology: As part of the presented research, synthesis of composites was carried out. The mentioned composites consisted of the polymer matrix and gold nanoparticles that were introduced into the polymer network. The synthesis was conducted with the use of a crosslinking agent, and photoinitiator and the materials were obtained by means of the photopolymerization process. Next, incubation studies were conducted using selected liquids that simulated fluids are occurring in the human body. The study allows determining the biocompatibility of the tested composites in relation to selected environments. Next, the chemical structure of the composites was characterized as well as their sorption properties. Conclusions: Conducted research allowed for the preliminary characterization of prepared polymer composites containing gold nanoparticles in the viewpoint of their application for biomedical use. Tested materials were characterized by biocompatibility in tested environments. What is more, synthesized composites exhibited relatively high swelling capacity that is essential in the viewpoint of their potential application as drug carriers. During such an application, composite swells and at the same time releases from its interior introduced active substance; therefore, it is important to check the swelling ability of such material. Acknowledgements: The authors would like to thank The National Science Centre (Grant no: UMO - 2016/21/D/ST8/01697) for providing financial support to this project. This paper is based upon work from COST Action (CA18113), supported by COST (European Cooperation in Science and Technology).

Keywords: nanocomposites, gold nanoparticles, drug carriers, swelling properties

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Authors: Afrah Saad Mohsen Al-Mahfadi

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The construction of dams can provide various ecosystem services, but it can also lead to ecological changes such as habitat loss and coastal degradation. Yemen faces multiple risks, including water crises and inadequate environmental policies, which are particularly detrimental to coastal zones like the Ahwar Delta in Abyan. This study aims to examine the impacts of dam construction on downstream wetlands and propose sustainable management approaches. Research Aim: The main objective of this study is to assess the different impacts of dam construction on downstream wetlands, specifically focusing on the Ahwar Delta in Yemen. Methodology: The study utilizes a literature review approach to gather relevant information on dam impacts and adaptation measures. Interviews with decision-making stakeholders and local community members are conducted to gain insights into the specific challenges faced in the Ahwar Delta. Additionally, sensing data, such as Arc-GIS and precipitation data from 1981 to 2020, are analyzed to examine changes in hydrological dynamics. Questions Addressed: This study addresses the following questions: What are the impacts of dam construction on downstream wetlands in the Ahwar delta? How can environmental management planning activities be implemented to minimize these impacts? Findings: The results indicate several future issues arising from dam construction in the coastal areas, including land loss due to rising sea levels and increased salinity in drinking water wells. Climate change has led to a decrease in rainfall rates, impacting vegetation and increasing sedimentation and erosion. Downstream areas with dams exhibit lower sediment levels and slower flowing habitats compared to those without dams. Theoretical Importance: The findings of this study provide valuable insights into the ecological impacts of dam construction on downstream wetlands. Understanding these dynamics can inform decision-makers about the need for adaptation measures and their potential benefits in improving coastal biodiversity under dam impacts. Data Collection and Analysis Procedures: The study collects data through a literature review, interviews, and sensing technology. The literature review helps identify relevant studies on dam impacts and adaptation measures. Interviews with stakeholders and local community members provide firsthand information on the specific challenges faced in the Ahwar Delta. Sensing data, such as Arc-GIS and precipitation data, are analyzed to understand changes in hydrological dynamics over time. Conclusion: The study concludes that while the situation can worsen due to dam construction, practical adaptation measures can help mitigate the impacts. Recommendations include improving water management, developing integrated coastal zone planning, raising awareness among stakeholders, improving health and education, and implementing emergency projects to combat climate change.

Keywords: dam impact, delta wetland, hydrology, Yemen

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

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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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