Search results for: true time delay phase shifter

Authors: Boudjelal Amel

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

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

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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

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

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

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

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Authors: Andy Ho

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Breast cancer is a common cancer in Australia. Early diagnosis is crucial for improving patient outcomes, as later-stage detection correlates with poorer prognoses. While multiparametric MRI offers superior sensitivity in detecting invasive and high-grade breast cancers compared to conventional mammography, its extended scan duration and high costs limit widespread application. As a result, full protocol MRI screening is typically reserved for patients at elevated risk. Recent advancements in imaging technology have facilitated the development of Abbreviated MRI protocols, which dramatically reduce scan times (<10 minutes compared to >30 minutes for full protocol). The potential for Abbreviated MRI to offer a more time- and cost-efficient alternative has implications for improving patient accessibility, reducing appointment durations, and enhancing compliance—especially relevant for individuals requiring regular annual screening over several decades. The purpose of this study is to assess the diagnostic efficacy of Abbreviated MRI for breast cancer screening among high-risk patients at the Royal Prince Alfred Hospital (RPA). This study aims to determine the sensitivity, specificity, and inter-reader variability of Abbreviated MRI protocols when interpreted by subspecialty-trained Breast Radiologists. A systematic review of the RPA’s electronic Picture Archive and Communication System identified high-risk patients, defined by Australian ‘Medicare Benefits Schedule’ criteria, who underwent Breast MRI from 2021 to 2022. Eligible participants included asymptomatic patients under 50 years old referred by the High-Risk Clinic due to a high-risk genetic profile or relevant familial history. The MRIs were anonymized, randomized, and interpreted by four Breast Radiologists, each independently completing standardized proforma evaluations. Radiological findings were compared against histopathology as the gold standard or follow-up imaging if biopsies were unavailable. Statistical metrics, including sensitivity, specificity, and inter-reader variability, were assessed. The Fleiss-Kappa analysis demonstrated a fair inter-reader agreement (kappa = 0.25; 95% CI: 0.19–0.32; p < 0.0001). The sensitivity for detecting malignancies was 0.75, with a specificity of 0.84. These findings underline the potential of Abbreviated MRI as a reliable screening tool for malignancies with significant specificity, though reduced sensitivity highlights the importance of robust radiologist training and consistent evaluation standards. Abbreviated MRI protocols exhibit promise as a viable screening option for high-risk patients, combining reduced scan times and acceptable diagnostic accuracy. Further work to refine interpretation practices and optimize training is essential to maximize the protocol’s utility in routine clinical screening and facilitate broader accessibility.

Keywords: abbreviated, breast, cancer, MRI

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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

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

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

Keywords: carcinogenesis, microbiota, mushroom extracts, inflammation

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

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

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

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

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

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

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Authors: B. Neethu, Diptesh Das

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

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

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Authors: Jeremy Ritchey

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

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

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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: 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: Ippei Torii, Kaoruko Ohtani, Takahito Niwa, Naohiro Ishii

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This paper shows developing an objectivity index using the measurement of subtle eyeball movement to diagnose autism. The developmentally disabled assessment varies, and the diagnosis depends on the subjective judgment of professionals. Therefore, a supplementary inspection method that will enable anyone to obtain the same quantitative judgment is needed. The diagnosis are made based on a comparison of the time of gazing an object in the conventional autistic study, but the results do not match. First, we divided the pupil into four parts from the center using measurements of subtle eyeball movement and comparing the number of pixels in the overlapping parts based on an afterimage. Then we developed the objective evaluation indicator to judge non-autistic and autistic people more clearly than conventional methods by analyzing the differences of subtle eyeball movements between the right and left eyes. Even when a person gazes at one point and his/her eyeballs always stay fixed at that point, their eyes perform subtle fixating movements (ie. tremors, drifting, microsaccades) to keep the retinal image clear. Particularly, the microsaccades link with nerves and reflect the mechanism that process the sight in a brain. We converted the differences between these movements into numbers. The process of the conversion is as followed: 1) Select the pixel indicating the subject's pupil from images of captured frames. 2) Set up a reference image, known as an afterimage, from the pixel indicating the subject's pupil. 3) Divide the pupil of the subject into four from the center in the acquired frame image. 4) Select the pixel in each divided part and count the number of the pixels of the overlapping part with the present pixel based on the afterimage. 5) Process the images with precision in 24 - 30fps from a camera and convert the amount of change in the pixels of the subtle movements of the right and left eyeballs in to numbers. The difference in the area of the amount of change occurs by measuring the difference between the afterimage in consecutive frames and the present frame. We set the amount of change to the quantity of the subtle eyeball movements. This method made it possible to detect a change of the eyeball vibration in numerical value. By comparing the numerical value between the right and left eyes, we found that there is a difference in how much they move. We compared the difference in these movements between non-autistc and autistic people and analyzed the result. Our research subjects consists of 8 children and 10 adults with autism, and 6 children and 18 adults with no disability. We measured the values through pasuit movements and fixations. We converted the difference in subtle movements between the right and left eyes into a graph and define it in multidimensional measure. Then we set the identification border with density function of the distribution, cumulative frequency function, and ROC curve. With this, we established an objective index to determine autism, normal, false positive, and false negative.

Keywords: subtle eyeball movement, autism, microsaccade, pursuit eye movements, ROC curve

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Authors: Lucia Liu, Matthew Koziol

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Obsessive-compulsive disorder (OCD), a long-lasting anxiety disorder involving recurrent, intrusive thoughts, affects over 2 million adults in the United States. Transcranial magnetic stimulation (TMS) stands out as a noninvasive, cutting-edge therapy that has been shown to reduce symptoms in patients with treatment-resistant OCD. The Food and Drug Administration (FDA) approved protocol pairs TMS sessions with individualized symptom provocation, aiming to improve the susceptibility of brain circuits to stimulation. However, limited standardization or guidance exists on how to conduct symptom provocation and which methods are most effective. This study aims to compare the effect of internal versus external techniques to induce obsessional stress in a clinical setting during TMS therapy. Two symptom provocation methods, (i) Asking patients thought-provoking questions about their obsessions (internal) and (ii) Requesting patients to perform obsession-related tasks (external), were employed in a crossover design with repeated measurement. Thirty-six treatments of NeuroStar TMS were administered to each of two patients over 8 weeks in an outpatient clinic. Patient One received 18 sessions of internal provocation followed by 18 sessions of external provocation, while Patient Two received 18 sessions of external provocation followed by 18 sessions of internal provocation. The primary outcome was the level of self-reported obsessional stress on a visual analog scale from 1 to 10. The secondary outcome was self-reported OCD severity, collected biweekly in a four-level Likert-scale (1 to 4) of bad, fair, good and excellent. Outcomes were compared and tested between provocation arms through repeated measures ANOVA, accounting for intra-patient correlations. Ages were 42 for Patient One (male, White) and 57 for Patient Two (male, White). Both patients had similar moderate symptoms at baseline, as determined through the Yale-Brown Obsessive Compulsive Scale (YBOCS). When comparing obsessional stress induced across the two arms of internal and external provocation methods, the mean (SD) was 6.03 (1.18) for internal and 4.01 (1.28) for external strategies (P=0.0019); ranges were 3 to 8 for internal and 2 to 8 for external strategies. Internal provocation yielded 5 (31.25%) bad, 6 (33.33%) fair, 3 (18.75%) good, and 2 (12.5%) excellent responses for OCD status, while external provocation yielded 5 (31.25%) bad, 9 (56.25%) fair, 1 (6.25%) good, and 1 (6.25%) excellent responses (P=0.58). Internal symptom provocation tactics had a significantly stronger impact on inducing obsessional stress and led to better OCD status (non-significant). This could be attributed to the fact that answering questions may prompt patients to reflect more on their lived experiences and struggles with OCD. In the future, clinical trials with larger sample sizes are warranted to validate this finding. Results support the increased integration of internal methods into structured provocation protocols, potentially reducing the time required for provocation and achieving greater treatment response to TMS.

Keywords: obsessive-compulsive disorder, transcranial magnetic stimulation, mental health, symptom provocation

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Authors: Maria Fatima Almeida, Rodrigo Calili, George Soares, João Krause, Myrthes Marcele Dos Santos, Anna Carolina Suzano E. Silva, Marcos Alexandre Da

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In Brazil, the building sector accounts for 1/6 of energy consumption and 50% of electricity consumption. A complex sector with several driving actors plays an essential role in the country's economy. Currently, the digitalization readiness in this sector is still low, mainly due to the high investment costs and the difficulty of estimating the benefits of digital technologies in buildings. Nevertheless, the potential contribution of digitalization for increasing energy efficiency in the building sector in Brazil has been pointed out as relevant in the political and sectoral contexts, both in the medium and long-term horizons. To contribute to the debate on the possible evolving trajectories of digitalization in the building sector in Brazil and to subsidize the formulation or revision of current public policies and managerial decisions, three future scenarios were created to anticipate the potential energy efficiency in the building sector in Brazil due to digitalization by 2050. This work aims to present these scenarios as a basis to foresight the potential energy efficiency in this sector, according to different digitalization paces - slow, moderate, or fast in the 2050 horizon. A methodological approach was proposed to create alternative prospective scenarios, combining the Global Business Network (GBN) and the Laboratory for Investigation in Prospective Strategy and Organisation (LIPSOR) methods. This approach consists of seven steps: (i) definition of the question to be foresighted and time horizon to be considered (2050); (ii) definition and classification of a set of key variables, using the prospective structural analysis; (iii) identification of the main actors with an active role in the digital and energy spheres; (iv) characterization of the current situation (2021) and identification of main uncertainties that were considered critical in the development of alternative future scenarios; (v) scanning possible futures using morphological analysis; (vi) selection and description of the most likely scenarios; (vii) foresighting the potential energy efficiency in each of the three scenarios, namely slow digitalization; moderate digitalization, and fast digitalization. Each scenario begins with a core logic and then encompasses potentially related elements, including potential energy efficiency. Then, the first scenario refers to digitalization at a slow pace, with induction by the government limited to public buildings. In the second scenario, digitalization is implemented at a moderate pace, induced by the government in public, commercial, and service buildings, through regulation integrating digitalization and energy efficiency mechanisms. Finally, in the third scenario, digitalization in the building sector is implemented at a fast pace in the country and is strongly induced by the government, but with broad participation of private investments and accelerated adoption of digital technologies. As a result of the slow pace of digitalization in the sector, the potential for energy efficiency stands at levels below 10% of the total of 161TWh by 2050. In the moderate digitalization scenario, the potential reaches 20 to 30% of the total 161TWh by 2050. Furthermore, in the rapid digitalization scenario, it will reach 30 to 40% of the total 161TWh by 2050.

Keywords: building digitalization, energy efficiency, scenario building, prospective structural analysis, morphological analysis

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Authors: Robin Anderson, David Nisbet

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Nitrate, 3-nitro-1-propionic acid (NPA) and 3-nitro-1-propanol (NPOH) are biologically active chemicals that can accumulate naturally in rangeland grasses forages consumed by grazing cattle, sheep and goats. While toxic to livestock if accumulations and amounts consumed are high enough, particularly in animals having no recent exposure to the forages, these chemicals are known to be potent inhibitors of methane-producing bacteria inhabiting the rumen. Consequently, there is interest in examining their potential use as anti-methanogenic compounds to decrease methane emissions by grazing ruminants. Presently, rumen microbes, collected freshly from a cannulated Holstein cow maintained on 50:50 corn based concentrate:alfalfa diet were mixed (10 mL fluid) in 18 x 150 mm crimp top tubes with 0.5 of high nitrate-containing barley (Hordeum vulgare; containing 272 µmol nitrate per g forage dry matter), and NPA- or NPOH- containing milkvetch forages (Astragalus canadensis and Astragalus miser containing 80 and 174 soluble µmol NPA or NPOH/g forage dry matter respectively). Incubations containing 0.5 g alfalfa (Medicago sativa) were used as controls. Tubes (3 per each respective forage) were capped and incubated anaerobically (using oxygen free carbon dioxide) for 24 h at 39oC after which time amounts of total gas produced were measured via volume displacement and headspace samples were analyzed by gas chromatography to determine concentrations of hydrogen and methane. Fluid samples were analyzed by gas chromatography to measure accumulations of fermentation acids. A completely randomized analysis of variance revealed that the nitrate-containing barley and both the NPA- and the NPOH-containing milkvetches significantly decreased methane production, by > 50%, when compared to methane produced by populations incubated similarly with alfalfa (70.4 ± 3.6 µmol/ml incubation fluid). Accumulations of hydrogen, which are typically increased when methane production is inhibited, by incubations with the nitrate-containing barley and the NPA- and NPOH-containing milkvetches did not differ from accumulations observed in the alfalfa controls (0.09 ± 0.04 µmol/mL incubation fluid). Accumulations of fermentation acids produced in the incubations containing the high-nitrate barley and the NPA- and NPOH-containing milkvetches likewise did not differ from accumulations observed in incubations containing alfalfa (123.5 ± 10.8, 36.0 ± 3.0, 17.1 ± 1.5, 3.5 ± 0.3, 2.3 ± 0.2, 2.2 ± 0.2 µmol/mL incubation fluid for acetate, propionate, butyrate, valerate, isobutyrate, and isovalerate, respectively). This finding indicates the microbial populations did not compensate for the decreased methane production via compensatory changes in production of fermentative acids. Stoichiometric estimation of fermentation balance revealed that > 77% of reducing equivalents generated during fermentation of the forages were recovered in fermentation products and the recoveries did not differ between the alfalfa incubations and those with the high-nitrate barley or the NPA- or NPOH-containing milkvetches. Stoichiometric estimates of amounts of hexose fermented similarly did not differ between the nitrate-, NPA and NPOH-containing incubations and those with the alfalfa, averaging 99.6 ± 37.2 µmol hexose consumed/mL of incubation fluid. These results suggest that forages containing nitrate, NPA or NPOH may be useful to reduce methane emissions of grazing ruminants provided risks of toxicity can be effectively managed.

Keywords: nitrate, nitropropanol, nitropropionic acid, rumen methane emissions

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Authors: Jason M. Hegenauer, Nicholas Fucci

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In the late 1990s, a major deinstitutionalization movement of elderly patients took place, since which, the design of long-term care facilities has not been adequately analyzed in the United States. Over the course of the last 25 years, major innovations in construction methods, technology, and medicine have been developed, drastically changing the landscape of healthcare architecture. In light of recent events, and the expected increase in elderly populations with the aging of the baby-boomer generation, it is evident that reconsideration of these facilities is essential for the proper care of aging populations. The global response has been effective in stifling this pandemic; however, widespread disease still poses an imminent threat to the human race. Having witnessed the devastation Covid-19 has reaped throughout nursing homes and long-term care facilities, it is evident that the current strategies for protecting our most vulnerable populations are not enough. Light renovation of existing facilities and previously overlooked considerations for new construction projects can drastically lower the risk at nursing homes and long-term care facilities. A reconfigured entry sequence supplements several of the features which have been long-standing essentials of the design of these facilities. This research focuses on several aspects identified as needing improvement, including indoor environment quality, security measures incorporated into healthcare architecture and design, and architectural mitigation strategies for sick building syndrome. The results of this study have been compiled as 'best practices' for the design of future healthcare construction projects focused on the health, safety, and quality of life of the residents of these facilities. These design strategies, which can easily be implemented through renovation of existing facilities and new construction projects, minimize risk of infection and spread of disease while allowing routine functions to continue with minimal impact, should the need for future lockdowns arise. Through the current lockdown procedures, which were implemented during the Covid-19 pandemic, isolation of residents has caused great unrest and worry for family members and friends as they are cut off from their loved ones. At this time, data is still being reported, leaving infection and death rates inconclusive; however, recent projections in some states list long-term care facility deaths as high as 60% of all deaths in the state. The population of these facilities consists of residents who are elderly, immunocompromised, and have underlying chronic medical conditions. According to the Centers for Disease Control, these populations are particularly susceptible to infection and serious illness. The obligation to protect our most vulnerable population cannot be overlooked, and the harsh measures recently taken as a response to the Covid-19 pandemic prove that the design strategies currently utilized for doing so are inadequate.

Keywords: building security, healthcare architecture and design, indoor environment quality, new construction, sick building syndrome, renovation

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Authors: Anna Solovyeva, Ivan Levakin, Nickolai Galaktionov, Olga Podgornaya

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Animals that reproduce asexually were thought to have the same genotypes within generations for a long time. However, some refuting examples were found, and mobile genetic elements (MGEs) or transposons are considered to be the most probable source of genetic instability. Dispersed nature and the ability to change their genomic localization enables MGEs to be efficient mutators. Hence the study of MGEs genomic impact requires an appropriate object which comprehends both representative amounts of various MGEs and options to evaluate the genomic influence of MGEs. Animals that reproduce asexually seem to be a decent model to study MGEs impact in genomic variability. We found a small marine trematode Himasthla elongata (Himasthlidae) to be a good model for such investigation as it has a small genome size, diverse MGEs and parthenogenetic stages in the lifecycle. In the current work, clonal diversity of cercaria was traced with an AFLP (Amplified fragment length polymorphism) method, diverse zones from electrophoretic patterns were cloned, and the nature of the fragments explored. Polymorphic patterns of individual cercariae AFLP-based fingerprints are enriched with retrotransposons of different families. The bulk of those sequences are represented by open reading frames of non-Long Terminal Repeats containing elements(non-LTR) yet Long-Terminal Repeats containing elements (LTR), to a lesser extent in variable figments of AFLP array. The CR1 elements expose both in polymorphic and conservative patterns are remarkably more frequent than the other non-LTR retrotransposons. This data was confirmed with shotgun sequencing-based on Illumina HiSeq 2500 platform. Individual cercaria of the same clone (i.e., originated from a single miracidium and inhabiting one host) has a various distribution of MGE families detected in sequenced AFLP patterns. The most numerous are CR1 and RTE-Bov retrotransposons, typical for trematode genomes. Also, we identified LTR-retrotransposons of Pao and Gypsy families among DNA transposons of CMC-EnSpm, Tc1/Mariner, MuLE-MuDR and Merlin families. We detected many of them in H. elongata transcriptome. Such uneven MGEs distribution in AFLP sequences’ sets reflects the different patterns of transposons spreading in cercarial genomes as transposons affect the genome in many ways (ectopic recombination, gene structure interruption, epigenetic silencing). It is considered that they play a key role in the origins of trematode clonal polymorphism. The authors greatly appreciate the help received at the Kartesh White Sea Biological Station of the Russian Academy of Sciences Zoological Institute. This work is funded with RSF 19-74-20102 and RFBR 17-04-02161 grants and the research program of the Zoological Institute of the Russian Academy of Sciences (project number AAAA-A19-119020690109-2).

Keywords: AFLP, clonal polymorphism, Himasthla elongata, mobile genetic elements, NGS

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Authors: Nazila Dehbari, Javad Tavakoli, Yakani Kambu, Youhong Tang

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Superabsorbent hydrogels (SAP), as an enviro-sensitive material have been widely used for industrial and biomedical applications due to their unique structure and capabilities. Poor mechanical properties of SAPs - which is extremely related to their large volume change – count as a great weakness in adopting for high-tech applications. Therefore, improving SAPs’ mechanical properties via toughening methods by mixing different types of cross-linked polymer or introducing energy-dissipating mechanisms is highly focused. In this work, in order to change the intrinsic brittle character of commercialized Poly Acrylic Acid (here as SAP) to be semi-ductile, a commercial available highly branched tree-like dendritic polymers with numerous –OH end groups known as hyper-branched polymer (HB) has been added to PAA-SAP system in a single step, cost effective and environment friendly solvent casting method. Samples were characterized by FTIR, SEM and TEM and their physico-chemical characterization including swelling capabilities, hydraulic permeability, surface tension and thermal properties had been performed. Toughness energy, stiffness, elongation at breaking point, viscoelastic properties and samples extensibility were mechanical properties that had been performed and characterized as a function of samples lateral cracks’ length in different HB concentration. Addition of HB to PAA-SAP significantly improved mechanical and surface properties. Increasing equilibrium swelling ratio by about 25% had been experienced by the SAP-HB samples in comparison with SAPs; however, samples swelling kinetics remained without changes as initial rate of water uptake and equilibrium time haven’t been subjected to any changes. Thermal stability analysis showed that HB is participating in hybrid network formation while improving mechanical properties. Samples characterization by TEM showed that, the aggregated HB polymer binders into nano-spheres with diameter in range of 10–200 nm. So well dispersion in the SAP matrix occurred as it was predictable due to the hydrophilic character of the numerous hydroxyl groups at the end of HB which enhance the compatibility of HB with PAA-SAP. As the profused -OH groups in HB could react with -COOH groups in the PAA-SAP during the curing process, the formation of a 2D structure in the SAP-HB could be attributed to the strong interfacial adhesion between HB and the PAA-SAP matrix which hinders the activity of PAA chains (SEM analysis). FTIR spectra introduced new peaks at 1041 and 1121 cm-1 that attributed to the C–O(–OH) stretching hydroxyl and O–C stretching ester groups of HB polymer binder indicating the incorporation of HB polymer into the SAP structure. SAP-HB polymer has significant effects on the final mechanical properties. The brittleness of PAA hydrogels are decreased by introducing HB as the fracture energies of hydrogels increased from 8.67 to 26.67. PAA-HBs’ stretch ability enhanced about 10 folds while reduced as a function of different notches depth.

Keywords: superabsorbent polymer, toughening, viscoelastic properties, hydrogel network

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Authors: Bakytzhan Bimbetov, Abay Zhangabilov, Saule Aitbaeva, Galymzhan Meirambekov

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Mare’s milk (saumal) contains in total about 40 biological components necessary for the human body. The most significant among them are amino acids, fats, carbohydrates, enzymes (lysozyme, amylase), more minerals and vitamins which are well balanced with each other. In Kazakhstan, Company "Eurasia Invest Ltd.” produces a freeze-dried saumal in form of powder by the use of modern German innovative technology by means of evaporating at low temperature (-35°C) with an appropriate pasteurization. Research of freeze-dried biomilk for the qualitative content showed that main ingredients of freshly drown milk are being preserved. We are currently studying medical and dietary properties of freeze-dried mare's milk for diseases of the digestive system, including for nonalcoholic steatohepatitis (NASH) and liver cirrhosis (LC) viral etiology. The studied group consisted of 14 patients with NASH, and 7 patients with LC viral etiology of Class A severity degree as per Child-Pugh. Patients took freeze-dried saumal, preliminary dissolved in boiled warm water (24 g. powder per 200 ml water) 3-4 times a day for a month in conjunction with basic therapy. The results were compared to a control group (11 patients with NASH and LC) who received only basic therapy without mare’s milk. Results of preliminary research showed an improvement of subjective and objective conditions of all patients, but more significant improvement of clinical symptoms and syndromes were observed in the treatment group compared to the control one. Patients with NASH significantly over time compared to the beginning of therapy decreased asthenic and dyspeptic syndromes (p<0,01). Hepatomegaly, identified on the basis of ultrasound prior to treatment was observed in 92,8±2,4% of patients, and after combination therapy hepatomegaly the rate decreased by 14,3%, amounting to 78,5±2,8%. Patients with LC also noted the improvement of asthenic (p<0,01) and dyspeptic (p<0,05) syndromes and hemorrhagic syndrome (nosebleeds and bleeding gums when brushing your teeth, p<0,05), and jaundice. Laboratory study also showed improvement in the research group, but more significant changes were observed in the experimental group. Group of patients with NASH showed a significant improvement of index in cytolysis in conjunction with a combination therapy (p<0,05). In the control group, these indicators were also improved, but they were not statistically reliable (p>0,05). Markers of liver failure were additionally studied during the study of laboratory parameters in patients with liver cirrhosis, in particular, bilirubin, albumin and prothrombin index (PTI). Combined therapy with the use of basic treatment and mare's milk showed a significant improvement in cytolysis and bilirubin (p<0,05). In our opinion, a very important and interesting fact is that, in conjunction with basic therapy, the use of mare's milk revealed an improvement of liver function in the form of normalized PTI and albumin in patients with liver cirrhosis viral etiology. Results of this work have shown therapeutic efficiency of the use of mare's milk in complex treatment of patients with liver disease and require further in-depth study.

Keywords: liver cirrhosis, non-alcohol steatohepatitis, saumal, mare’s milk

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Authors: Nathalie Gagnon, Andréanne Gagné, Julie Courcy

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Quebec's vocational education teachers experience an atypical induction process into the workplace and thus face unique challenges. In contrast to elementary and high school teachers, who must undergo initial teacher training in order to access the profession, vocational education teachers, in most cases, are hired based on their professional expertise in the trade they are teaching, without prior pedagogical training. In addition to creating significant stress, which does not foster the acquisition of teaching roles and skills, this approach also forces recruits into a particular posture during their practical training: that of juggling their dual identities as teacher and trainee simultaneously. Recruits are supported by Cooperating Teachers (CPs) who, as experienced educators, take a critical and constructive look at their practices, observe them in the classroom, give them constructive feedback, and encourage them in their reflective practice. Thus, the vocational setting CP also assumes a distinctive posture and role due to the characteristics of the trainees they support. Although it is recognized that preparation, training, and supervision of CPs are essential factors in improving the support provided to trainees, there is little research about how CPs develop their support skills, and very little research focuses on the distinct posture they occupy. However, in order for them to be properly equipped for the important role they play in recruits’ practical training, it is vital to know more about their experience. An individual’s competencies cannot be studied without first examining what characterizes their experience, how they experience any given situation on cognitive, emotional, and motivational levels, in addition to how they act and react in situ. Depending on its nature, the experience will or will not promote the development of a specific competency. The research from which this communication originates focuses on describing the overall experience of vocational education CP in an effort to better understand the mechanisms linked to the development of their mentoring competencies. Experience and competence were, therefore, the two main theoretical concepts leading the research. As per methodology choices, case study methods were used since it proves to be adequate to describe in a rich and detailed way contemporary phenomena within contexts of life. The set of data used was collected from semi-structured interviews conducted with 15 vocational education CP in Quebec (Canada), followed by the use of a data-driven semi-inductive analysis approach to let the categories emerge organically. Focusing on the development needs of vocational education CP to improve their mentoring skills, this paper presents the results of our research, namely the importance of adequate training, better support offered by university supervisors, greater recognition of their role, and specific time slots dedicated to trainee support. The knowledge resulting from this research could improve the quality of support for trainee teachers in vocational education settings and to a more successful induction into the workplace. This communication also presents recommendations regarding the development of training systems that meet the specific needs of vocational education CP.

Keywords: development of competencies, cooperating teacher, mentoring trainee teacher, practical training, vocational education

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Authors: David Dolbow, Daniel Credeur, Mujtaba Rahimi, Dobrivoje Stokic, Jennifer Lemacks, Andrew Courtner

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Introduction: Obesity is at epidemic proportions in the spinal cord injury (SCI) population (66-75%), as individuals who suffer from paralysis undergo a dramatic decrease in muscle mass and a dramatic increase in adipose deposition. Obesity is a major public health concern which includes a doubling of the risk of heart disease, stroke and type II diabetes mellitus. It has been demonstrated that physical activity, and especially HIIT, can promote a healthy body composition and decrease the risk cardiometabolic disease in the able-bodied population. However, SCI typically limits voluntary exercise to the arms, but a high prevalence of shoulder pain in persons with chronic SCI (60-90%) can cause increased arm exercise to be problematic. Functional electrical stimulation (FES) cycling has proven to be a safe and effective way to exercise paralyzed leg muscles in clinical and home settings, saving the often overworked arms. Yet, HIIT-FES cycling had not been investigated prior to the current study. The purpose of this study was to investigate the body composition changes with combined HIIT-FES cycling and nutritional counseling on individuals with SCI. Design: A matched (level of injury, time since injury, body mass index) and controlled trail. Setting: University exercise performance laboratory. Subjects: Ten individuals with chronic SCI (C5-T9) ASIA impairment classification (A & B) were divided into the treatment group (n=5) for 30 minutes of HIIT-FES cycling 3 times per week for 8 weeks and nutritional counseling over the phone for 30 minutes once per week for 8 weeks and the control group (n=5) who received nutritional counseling only. Results: There was a statistically significant difference between the HIIT-FES group and the control group in mean body fat percentage change (-1.14 to +0.24) respectively, p = .030). There was also a statistically significant difference between the HIIT-FES and control groups in mean change in legs lean mass (+0.78 kg to -1.5 kg) respectively, p = 0.004. There was a nominal decrease in weight, BMI, total fat mass and a nominal increase in total lean mass for the HIIT-FES group over the control group. However, these changes were not found to be statistically significant. Additionally, there was a nominal decrease in the mean blood glucose levels for both groups 101.8 to 97.8 mg/dl for the HIIT-FES group and 94.6 to 93 mg/dl for the Nutrition only group, however, neither were found to be statistically significant. Conclusion: HIIT-FES cycling combined with nutritional counseling can provide healthful body composition changes including decreased body fat percentage in just 8 weeks. Future study recommendations include a greater number of participants, a primer electrical stimulation exercise program to better ready participants for HIIT-FES cycling and a greater volume of training above 30 minutes, 3 times per week for 8 weeks.

Keywords: body composition, functional electrical stimulation cycling, high-intensity interval training, spinal cord injury

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Authors: Adrien Chatel, Ehsan Askari Mahvelati, Laurent Fitschy

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Once-Through-Steam-Generators are commonly used in the oil-sand industry in the heavy fuel oil extraction process. They are composed of three main parts: the burner, the radiant and convective sections. Natural gas is burned through staged diffusive flames stabilized by the burner. The heat generated by the combustion is transferred to the water flowing through the piping system in the radiant and convective sections. The steam produced within the pipes is then directed to the ground to reduce the oil viscosity and allow its pumping. With the rapid development of the oil-sand industry, the number of OTSG in operation has increased as well as the associated emissions of environmental pollutants, especially the Nitrous Oxides (NOₓ). To limit the environmental degradation, various international environmental agencies have established regulations on the pollutant discharge and pushed to reduce the NOₓ release. To meet these constraints, OTSG constructors have to rely on more and more advanced tools to study and predict the NOₓ emission. With the increase of the computational resources, Computational Fluid Dynamics (CFD) has emerged as a flexible tool to analyze the combustion and pollutant formation process. Moreover, to optimize the burner operating condition regarding the NOx emission, field characterization and measurements are usually accomplished. However, these kinds of experimental campaigns are particularly time-consuming and sometimes even impossible for industrial plants with strict operation schedule constraints. Therefore, the application of CFD seems to be more adequate in order to provide guidelines on the NOₓ emission and reduction problem. In the present work, two different software are employed to simulate the combustion process in an OTSG, namely the commercial software ANSYS Fluent and the open source software OpenFOAM. RANS (Reynolds-Averaged Navier–Stokes) equations combined with the Eddy Dissipation Concept to model the combustion and closed by the k-epsilon model are solved. A mesh sensitivity analysis is performed to assess the independence of the solution on the mesh. In the first part, the results given by the two software are compared and confronted with experimental data as a mean to assess the numerical modelling. Flame temperatures and chemical composition are used as reference fields to perform this validation. Results show a fair agreement between experimental and numerical data. In the last part, OpenFOAM is employed to simulate several operating conditions, and an Emission Characteristic Map of the combustion system is generated. The sources of high NOₓ production inside the OTSG are pointed and correlated to the physics of the flow. CFD is, therefore, a useful tool for providing an insight into the NOₓ emission phenomena in OTSG. Sources of high NOₓ production can be identified, and operating conditions can be adjusted accordingly. With the help of RANS simulations, an Emission Characteristics Map can be produced and then be used as a guide for a field tune-up.

Keywords: combustion, computational fluid dynamics, nitrous oxides emission, once-through-steam-generators

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Authors: Neelam Taneja, Abhishek Mewara, Ajay Kumar

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Multidrug resistant shigellae have emerged as a therapeutic challenge in India. At our 2000 bed tertiary care referral centre in Chandigarh, North India, which caters to a large population of 7 neighboring states, antibiotic resistance in Shigella is being constantly monitored. Shigellae are isolated from 3 to 5% of all stool samples. In 1990 nalidixic acid was the drug of choice as 82%, and 63% of shigellae were resistant to ampicillin and cotrimoxazole respectively. Nalidixic acid resistance emerged in 1992 and rapidly increased from 6% during 1994-98 to 86% by the turn of 21st century. In the 1990s, the WHO recommended ciprofloxacin as the drug of choice for empiric treatment of shigellosis in view of the existing high level resistance to agents like chloramphenicol, ampicillin, cotrimoxazole and nalidixic acid. First resistance to ciprofloxacin in S. flexneri at our centre appeared in 2000 and rapidly rose to 46% in 2007 (MIC>4mg/L). In between we had an outbreak of ciprofloxacin resistant S.dysenteriae serotype 1 in 2003. Therapeutic failures with ciprofloxacin occurred with both ciprofloxacin-resistant S. dysenteriae and ciprofloxacin-resistant S. flexneri. The severity of illness was more with ciprofloxacin-resistant strains. Till 2000, elsewhere in the world ciprofloxacin resistance in S. flexneri was sporadic and uncommon, though resistance to co-trimoxazole and ampicillin was common and in some areas resistance to nalidixic acid had also emerged. Fluoroquinolones due to extensive use and misuse for many other illnesses in our region are thus no longer the preferred group of drugs for managing shigellosis in India. WHO presently recommends ceftriaxone and azithromycin as alternative drugs to fluoroquinolone-resistant shigellae, however, overreliance on this group of drugs also seems to soon become questionable considering the emerging cephalosporin-resistant shigellae. We found 15.1% of S. flexneri isolates collected over a period of 9 years (2000-2009) resistant to at least one of the third-generation cephalosporins (ceftriaxone/cefotaxime). The first isolate showing ceftriaxone resistance was obtained in 2001, and we have observed an increase in number of isolates resistant to third generation cephalosporins in S. flexneri 2005 onwards. This situation has now become a therapeutic challenge in our region. The MIC values for Shigella isolates revealed a worrisome rise for ceftriaxone (MIC90:12 mg/L) and cefepime (MIC90:8 mg/L). MIC values for S. dysenteriae remained below 1 mg/L for ceftriaxone, however for cefepime, the MIC90 has raised to 4 mg/L. These infections caused by ceftriaxone-resistant S. flexneri isolates were successfully treated by azithromycin at our center. Most worrisome development in the present has been the emergence of DSA(Decreased susceptibility to azithromycin) which surfaced in 2001 and has increased from 4.3% till 2011 to 34% thereafter. We suspect plasmid-mediated resistance as we detected qnrS1-positive Shigella for the first time from the Indian subcontinent in 2 strains from 2010, indicating a relatively new appearance of this PMQR determinant among Shigella in India. This calls for a continuous and strong surveillance of antibiotic resistance across the country. The prevention of shigellosis by developing cost-effective vaccines is desirable as it will substantially reduce the morbidity associated with diarrhoea in the country

Keywords: Shigella, antimicrobial, resistance, India

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Authors: Aleksandra Czubek

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As AI systems increasingly shape content creation, existing copyright frameworks face significant challenges in determining liability for AI-generated outputs. Current legal discussions largely focus on who bears responsibility for infringing works, be it developers, users, or entities benefiting from AI outputs. This paper introduces a novel concept of algorithmic obligations, proposing that AI developers be subject to proactive duties that ensure their models prevent copyright infringement before it occurs. Building on principles of obligations law traditionally applied to human actors, the paper suggests a shift from reactive enforcement to proactive legal requirements. AI developers would be legally mandated to incorporate copyright-aware mechanisms within their systems, turning optional safeguards into enforceable standards. These obligations could vary in implementation across international, EU, UK, and U.S. legal frameworks, creating a multi-jurisdictional approach to copyright compliance. This paper explores how the EU’s existing copyright framework, exemplified by the Copyright Directive (2019/790), could evolve to impose a duty of foresight on AI developers, compelling them to embed mechanisms that prevent infringing outputs. By drawing parallels to GDPR’s “data protection by design,” a similar principle could be applied to copyright law, where AI models are designed to minimize copyright risks. In the UK, post-Brexit text and data mining exemptions are seen as pro-innovation but pose risks to copyright protections. This paper proposes a balanced approach, introducing algorithmic obligations to complement these exemptions. AI systems benefiting from text and data mining provisions should integrate safeguards that flag potential copyright violations in real time, ensuring both innovation and protection. In the U.S., where copyright law focuses on human-centric works, this paper suggests an evolution toward algorithmic due diligence. AI developers would have a duty similar to product liability, ensuring that their systems do not produce infringing outputs, even if the outputs themselves cannot be copyrighted. This framework introduces a shift from post-infringement remedies to preventive legal structures, where developers actively mitigate risks. The paper also breaks new ground by addressing obligations surrounding the training data of large language models (LLMs). Currently, training data is often treated under exceptions such as the EU’s text and data mining provisions or U.S. fair use. However, this paper proposes a proactive framework where developers are obligated to verify and document the legal status of their training data, ensuring it is licensed or otherwise cleared for use. In conclusion, this paper advocates for an obligations-centered model that shifts AI-related copyright law from reactive litigation to proactive design. By holding AI developers to a heightened standard of care, this approach aims to prevent infringement at its source, addressing both the outputs of AI systems and the training processes that underlie them.

Keywords: ip, technology, copyright, data, infringement, comparative analysis

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