Search results for: team interactions

Authors: Turgut Ayten, Tayfun Çay

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In the current expropriation of Turkey, the state acquires necessary lands for its investment without permission of the owners and not searching for alternative solutions, so it is determined that neither processor nor processed is not happy. In this study, interactions of enterprises in Turkey are analysed in case the necessary land for public investments are acquired by expropriation purposed land consolidation. Legal basis, positive and negative sides, financial effects to enterprises of this method is evaluated according to Konya Kadınhanı, Kolukısa avenue which is on the Konya-Ankara High-Speed Train Route.

Keywords: expropriation, land consolidation, land consolidation for expropriation purpose, sustainable rural development

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Authors: M. Abdoul-Hakim, A. Zeroual, H. Garmes

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In this work, the reaction of 2-chlorobenzimidazole with two distinct 1,3-dipoles such as benzonitrile N-oxide and an azomethine imine was carried out by DFT at the B3LYP/6-311+G(d, p) level to understand the effect of solvent (MeOH). The results show that MeOH has a significant effect on the evolution of the reaction. The charge transfer interactions n(O) → σ*(C-Cl), n(N)→σ*(C-Cl) and σ(N-C) →σ*(C-Cl) stabilize the transition states in an intramolecular nucleophilic substitution (SNi) step of the imidoyl group. Finally, this study provides a theoretical basis for the design of different polycyclic benzimidazole.

Keywords: azomethine imine, benzonitrile N-oxide, DFT, intramolecular nucleophilic substitution (SNi), polycyclic benzimidazole

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Authors: Irina Peterburgsky

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We have been working on finding internship positions for our math and computer science majors. Among many other positive outcomes of internship for students majoring in mathematics, there are: students see new applications of mathematics to real life and see new scientific problems; they learn new methods, tools, etc. that they have not seen in their classes; they appreciate the power of mathematics that increases their interest in learning mathematics; they make decisions to take more advanced math courses; students understand better what their potentials, strong points, and limitations are; learn what work ethic is; learn how to work as a member of a team at a workplace; understand better how to offer their help and how to ask for help; start building their professional relationship; build self-confidence as young professionals, and what is the most important - they get a better understanding of their goals in their future professional careers.

Keywords: internship, mathematics, positive outcoms for students, workplace

Procedia PDF Downloads 181

Authors: Brooke Sweeney, David White, Felix Amparano, Nick A. Clark, Amy R. Beck, Mathew Lindquist, Lora Edwards, Julie Vandal, Jennifer Lisondra, Katie Cox, Renee Arensberg, Allen Cummins, Jazmine Cedeno, Jason D. Fraser, Kelsey Dean, Helena H. Laroche, Cristina Fernandez

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Background: National organizations call for standardized pre-surgical requirements and education to optimize postoperative outcomes. Since 2017 our surgery program has used defined protocols and educational curricula pre- and post-surgery. In response to patient outcomes, our educational content was refined to include quizzes to assess patient knowledge and surgical preparedness. We aim to optimize adolescent pre-bariatric surgery preparedness by improving overall aggregate pre-surgical assessment performance from 68% to 80% within 12 months. Methods: A multidisciplinary improvement team was developed within the weight management clinic (WMC) of our tertiary care, free-standing children’s hospital. A manual has been utilized since 2017, with limitations in consistent delivery and patient uptake of information. The curriculum has been improved to include quizzes administered during WMC visits prior to bariatric surgery. The initial outcome measure is the pre-surgical quiz score of adolescents preparing for bariatric surgery. Process measure was the number of questions answered correctly to test the questions. Baseline performance was determined by a patient assessment survey of pre-surgical preparedness at patient visits. Plan-Do-Study-Act cycles (PDSA) included: 1) creation and implementation of a refined curriculum, 2) development of 5 new quizzes based upon learning objectives, and 3) improving provider-lead teaching and quiz administration within clinic workflow. Run charts assessed impact over time. Results: A total of 346 quiz questions were administered to 34 adolescents. The outcome measure improved from a baseline mean of 68% to 86% following PDSA 2 cycles, and it was sustained. Conclusion/Implication: Patient/family comprehension of surgical preparedness improved with standardized education via team member-led teaching and assessment using quizzes during pre-surgical clinic visits. The next steps include launching redesigned teaching materials with modules correlated to quizzes and assessment of comprehension and outcomes post-surgically.

Keywords: bariatric surgery, adolescent, clinic, pre-bariatric training

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Authors: Dulani Jayasuriya

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This study outlines the developmental steps of a chatbot for administrative purposes of a large undergraduate course. The chatbot is able to handle student queries about administrative details, including assessment deadlines, course documentation, how to navigate the course, group formation, etc. The development window screenshots are that of a free account on the Snatchbot platform such that this can be adopted by the wider public. While only one connection to an answer based on possible keywords is shown here, one needs to develop multiple connections leading to different answers based on different keywords for the actual chatbot to function. The overall flow of the chatbot showing connections between different interactions is depicted at the end.

Keywords: chatbots, education, technology, snatch bot, artificial intelligence

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Authors: Syue-Wen Lin

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Objective:This article reviews the care experience of a 40-year-old male patient who underwent a thoracoscopic right lower lobectomy following a COVID-19 infection. His complex medical history included multiple metastases (lungs, liver, spleen, and left kidney) and lung damage from COVID-19, which complicated the weaning process from mechanical ventilation. The care involved managing cancer treatment, postoperative pain, wound care, and palliative care. Methods:Nursing care was provided from August 16 to August 17, 2024. Challenges included difficulty with sputum clearance, which exacerbated the patient's anxiety and fear of reintubation. Pain management strategies combined analgesic drugs, non-drug methods, essential oil massages with family members, and playing the patient’s favorite music to reduce pain and anxiety. Progressive rehabilitation began with stabilizing vital signs, followed by assistance with sitting on the edge of the bed and walking within the ward. Strict sterile procedures and advanced wound care technology were used for daily dressing changes, with meticulous documentation of wound conditions and appropriate dressing selection. Holistic cancer care and palliative measures were integrated to address the patient’s physical and psychological needs. Results:The interdisciplinary care team developed a comprehensive plan addressing both physical and psychological aspects. Respiratory therapy, lung expansion exercises, and a high-frequency chest wall oscillation vest facilitated sputum expulsion and assisted in weaning from mechanical ventilation. The integration of cancer care, pain management, wound care, and palliative care led to improved quality of life and recovery. The collaborative approach between nursing staff and family ensured that the patient received compassionate and effective care. Conclusion: The complex interplay of emergency surgery, COVID-19, and advanced cancer required a multifaceted care strategy. The care team’s approach, combining critical care with tailored cancer and palliative care, effectively improved the patient’s quality of life and facilitated recovery. The comprehensive care plan, developed with family collaboration, provided both high-quality medical care and compassionate support for the terminally ill patient.

Keywords: multiple metastases, testicular cancer, palliative care, nursing experience

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Authors: Qudsiya Baig

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Empathy yields an unparalleled therapeutic value within patient physician interactions. Medical research is inundated with evidence to support that a physician’s ability to empathise with patients leads to a greater willingness to report symptoms, an improvement in diagnostic accuracy and safety, and a better adherence and satisfaction with treatment plans. Furthermore, the Institute of Medicine states that empathy leads to a more patient-centred care, which is one of the six main goals of a 21st century health system. However, there is a paradox between the theoretical significance of empathy and its presence, or lack thereof, in clinical practice. Recent studies have reported that empathy declines amongst students and physicians over time. The three most impactful contributors to this decline are: (1) disagreements over the definitions of empathy making it difficult to implement it into practice (2) poor consideration or regulation of empathy leading to burnout and thus, abandonment altogether, and (3) the lack of diversity in the curriculum and the influence of medical culture, which prioritises science over patient experience, limiting some physicians from using ‘too much’ empathy in the fear of losing clinical objectivity. These issues were investigated by conducting a fully inductive thematic narrative analysis of patient narratives in the UK to evaluate the behaviours and attitudes that patients associate with empathy. The principal enquiries underpinning this study included uncovering the factors that affected experience of empathy within provider-patient interactions and to analyse their effects on patient care. This research contributes uniquely to this discourse by examining the phenomenon of empathy directly from patients’ experiences, which were systematically extracted from a repository of online patient narratives of care titled ‘CareOpinion UK’. Narrative analysis was specifically chosen as the methodology to examine narratives from a phenomenological lens to focus on the particularity and context of each story. By enquiring beyond the superficial who-whatwhere, the study of narratives prescribed meaning to illness by highlighting the everyday reality of patients who face the exigent life circumstances created by suffering, disability, and the threat of life. The following six themes were found to be the most impactful in influencing the experience of empathy: dismissive behaviours, judgmental attitudes, undermining patients’ pain or concerns, holistic care and failures and successes of communication or language. For each theme there were overarching themes relating to either a failure to understand the patient’s perspective or a success in taking a person-centred approach. An in-depth analysis revealed that a lack of empathy was greatly associated with an emotive-cognitive imbalance, which disengaged physicians with their patients’ emotions. This study hereby concludes that competent providers require a combination of knowledge, skills, and more importantly empathic attitudes to help create a context for effective care. The crucial elements of that context involve (a) identifying empathy clues within interactions to engage with patients’ situations, (b) attributing a perspective to the patient through perspective-taking and (c) adapting behaviour and communication according to patient’s individual needs. Empathy underpins that context, as does an appreciation of narrative, and the two are interrelated.

Keywords: empathy, narratives, person-centred, perspective, perspective-taking

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Authors: Fadhl Alakwaa

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One of the sustainable goals of the system biology is understanding gene-gene interactions. Hence, gene regulatory networks (GRN) need to be constructed for understanding the disease ontology and to reduce the cost of drug development. To construct gene regulatory from gene expression we need to overcome many challenges such as data denoising and dimensionality. In this paper, we develop an integrated system to reduce data dimension and remove the noise. The generated network from our system was validated via available interaction databases and was compared to previous methods. The result revealed the performance of our proposed method.

Keywords: gene regulatory network, biclustering, denoising, system biology

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Authors: Arun Prasad Jaganathan

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In today's rapidly evolving technological landscape, the need for efficient and proactive maintenance management solutions has become increasingly evident across various industries. Traditional approaches often suffer from drawbacks such as reactive strategies, leading to potential downtime, increased costs, and decreased operational efficiency. In response to these challenges, this paper proposes an AI-enabled approach to object-based maintenance management aimed at enhancing reliability and efficiency. The paper contributes to the growing body of research on AI-driven maintenance management systems, highlighting the transformative impact of intelligent technologies on enhancing object reliability and operational efficiency.

Keywords: AI, machine learning, predictive maintenance, object-based maintenance, expert team scheduling

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Authors: David Sudre

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Today, the National Basketball Association (NBA) is the cultural model of reference for most of the French basketball community stakeholders (players, coaches, team and league managers). In addition to the strong impact it has on how this sport is played and perceived, the NBA also influences the ways professional basketball shows are organized in France (within the Jeep Elite league). The objective of this research is to see how and to what extent the NBA show, as a globalized cultural product, disrupts Jeep Elite's professional basketball cultural codes in the organization of its shows. The article will aim at questioning the intercultural phenomenon at stake in sports cultures in France through the prism of the basketball match. This angle will shed some light on the underlying relationships between local and global elements. The results of this research come from a one-year survey conducted in a small town in northern France, Le Portel, where the Etoile Sportive Saint Michel (ESSM), a Jeep Elite's club, operates. An ethnographic approach was favored. It entailed many participating observations and semi-directive interviews with supporters of the ESSM Le Portel. Through this ethnographic work with the team's fan groups (before the games, during the games and after the games), it was possible for the researchers to understand better all the cultural and identity issues that play out in the "Cauldron," the basketball arena of the ESSM Le Portel. The results demonstrate, at first glance, that many basketball events organized in France are copied from the American model. It seems difficult not to try to imitate the American reference that the NBA represents, whether it be at the French All-Star Game or a Jeep Elite Game at Le Portel. In this case, an acculturation process seems to occur, not only in the way people play but also in the creation of the show (cheerleaders, animations, etc.). However, this American culture of globalized basketball, although re-appropriated, is also being modified by the members of ESSM Le Portel within their locality. Indeed, they juggle between their culture of origin and their culture of reference to build their basketball show within their sociocultural environment. In this way, Le Portel managers and supporters introduce elements that are characteristic of their local culture into the show, such as carnival customs and celebrations, two ingredients that fully contribute to the creation of their identity. Ultimately, in this context of "glocalization," this research will ascertain, on the one hand, that the identity of French basketball becomes harder to outline, and, on the other hand, that the "Cauldron" turns out to be a place to preserve (fantasized) local identities, or even a place of (unconscious) resistance to the dominant model of American basketball culture.

Keywords: basketball, carnival, culture, globalization, identity, show, sport, supporters.

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Authors: Richa Dhingra, Monika, Manav Malhotra, Tilak Raj Bhardwaj, Neelima Dhingra

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5-Alpha-reductases (5AR), a membrane bound, NADPH dependent enzyme and convert male hormone testosterone (T) into more potent androgen dihydrotestosterone (DHT). DHT is the required for the development and function of male sex organs, but its overproduction has been found to be associated with physiological conditions like Benign Prostatic Hyperplasia (BPH). Thus the inhibition of 5ARs could be a key target for the treatment of BPH. In present study, 2D and 3D Quantitative Structure Activity Relationship (QSAR) pharmacophore models have been generated for 5AR based on known inhibitory concentration (IC₅₀) values with extensive validations. The four featured 2D pharmacophore based PLS model correlated the topological interactions (–OH group connected with one single bond) (SsOHE-index); semi-empirical (Quadrupole2) and physicochemical descriptors (Mol. wt, Bromines Count, Chlorines Count) with 5AR inhibitory activity, and has the highest correlation coefficient (r² = 0.98, q² =0.84; F = 57.87, pred r² = 0.88). Internal and external validation was carried out using test and proposed set of compounds. The contribution plot of electrostatic field effects and steric interactions generated by 3D-QSAR showed interesting results in terms of internal and external predictability. The well validated 2D Partial Least Squares (PLS) and 3D k-nearest neighbour (kNN) models were used to search novel 5AR inhibitors with different chemical scaffold. To gain more insights into the molecular mechanism of action of these steroidal derivatives, molecular docking and in silico absorption, distribution, metabolism, and excretion (ADME) studies were also performed. Studies have revealed the hydrophobic and hydrogen bonding of the ligand with residues Alanine (ALA) 63A, Threonine (THR) 60A, and Arginine (ARG) 456A of 4AT0 protein at the hinge region. The results of QSAR, molecular docking, in silico ADME studies provide guideline and mechanistic scope for the identification of more potent 5-Alpha-reductase inhibitors (5ARI).

Keywords: 5α-reductase inhibitor, benign prostatic hyperplasia, ligands, molecular docking, QSAR

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Authors: Fady Tawakol

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BitCoin is a decentralized cryptocurrency that can be used without the need of traditional central banks to accomplish any e-commerce trade. The use of such currency could facilitate new economic interactions and linkages. However, without effective and efficient regulations, cryptocurrency transactions are mostly used by criminals to commit crimes such as money laundering, theft, and blackmailing. And because law is one step behind technological developments, this paper discusses the importance of regulations and supervision for the BitCoin-system, to provide unified regulatory solutions for our digital future in the Middle East. It will provide a detailed analysis of the legal nature of BitCoin along with, its regulation with respect to criminal and civil law.

Keywords: BitCoin, financial protection, crypto currency, money laundering

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Authors: Sumeyra Karatas, Veysel Karatas, Reyhan Safak, Gamze Bulut-Ozturk, Ozgul Kartal

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Productive struggle entails a student's cognitive exertion to comprehend mathematical concepts and uncover solutions not immediately apparent. The significance of productive struggle in learning mathematics is accentuated by influential educational theorists, emphasizing its necessity for learning mathematics with understanding. Consequently, supporting productive struggle in learning mathematics is recognized as a high-leverage and effective mathematics teaching practice. In this study, the investigation into the role of productive struggle in learning mathematics led to the development of a comprehensive rubric for productive struggle pedagogy through an exhaustive literature review. The rubric consists of eight primary criteria and 37 sub-criteria, providing a detailed description of teacher actions and pedagogical choices that foster students' productive struggles. These criteria encompass various pedagogical aspects, including task design, tool implementation, allowing time for struggle, posing questions, scaffolding, handling mistakes, acknowledging efforts, and facilitating discussion/feedback. Utilizing this rubric, a team of researchers and teachers designed eight 90-minute lesson plans, employing a productive struggle pedagogy, for a two-week unit on solving systems of linear equations. Simultaneously, another set of eight lesson plans on the same topic, featuring identical content and problems but employing a traditional lecture-and-practice model, was designed by the same team. The objective was to assess the impact of supporting productive struggle on students' mathematics learning, defined by the strands of mathematical proficiency. This quasi-experimental study compares the control group, which received traditional lecture- and practice instruction, with the treatment group, which experienced a productive struggle in pedagogy. Sixty-six 10th and 11th-grade students from two algebra classes, taught by the same teacher at a high school, underwent either the productive struggle pedagogy or lecture-and-practice approach over two-week eight 90-minute class sessions. To measure students' learning, an assessment was created and validated by a team of researchers and teachers. It comprised seven open-response problems assessing the strands of mathematical proficiency: procedural and conceptual understanding, strategic competence, and adaptive reasoning on the topic. The test was administered at the beginning and end of the two weeks as pre-and post-test. Students' solutions underwent scoring using an established rubric, subjected to expert validation and an inter-rater reliability process involving multiple criteria for each problem based on their steps and procedures. An analysis of covariance (ANCOVA) was conducted to examine the differences between the control group, which received traditional pedagogy, and the treatment group, exposed to the productive struggle pedagogy, on the post-test scores while controlling for the pre-test. The results indicated a significant effect of treatment on post-test scores for procedural understanding (F(2, 63) = 10.47, p < .001), strategic competence (F(2, 63) = 9.92, p < .001), adaptive reasoning (F(2, 63) = 10.69, p < .001), and conceptual understanding (F(2, 63) = 10.06, p < .001), controlling for pre-test scores. This demonstrates the positive impact of supporting productive struggle in learning mathematics. In conclusion, the results revealed the significance of the role of productive struggle in learning mathematics. The study further explored the practical application of productive struggle through the development of a comprehensive rubric describing the pedagogy of supporting productive struggle.

Keywords: effective mathematics teaching practice, high school algebra, learning mathematics, productive struggle

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Authors: Olusola Omolola Olafuyi, Michael Coleman, Raj Kumar Singh Badhan

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Introduction: Malaria in pregnancy has morbidity and mortality implication on both mother and unborn child. Piperaquine (PQ) based antimalarial treatment is emerging as a choice antimalarial for pregnant women in the face of resistance to current antimalarial treatment recommendation in pregnancy. Physiological and biochemical changes in pregnant women may affect the pharmacokinetics of the antimalarial drug in these. In malaria endemic regions other infectious diseases like HIV/AIDs are prevalent. Pregnant women who are co-infected with malaria and HIV/AID are at even more greater risk of death not only due to complications of the diseases but also due to drug-drug interactions (DDIs) between antimalarials (AMT) and antiretroviral (ARVs). In this study, physiologically based pharmacokinetic (PBPK) modelling was used to investigate the effect of physiological and biochemical changes on the impact of ARV mediated DDIs in pregnant women in three countries. Method: A PBPK model for PQ was developed on SimCYP® using published physicochemical and pharmacokinetic data of PQ from literature, this was validated in three customized population groups from Thailand, Sudan and Papua New Guinea with clinical data. Validation of PQ model was also done in presence of interaction with efavirenz (pre-validated on SimCYP®). Different albumin levels and pregnancy stages was simulated in the presence of interaction with standard doses of efavirenz and ritonavir. PQ day 7 concentration of 30ng/ml was used as the efficacy endpoint for PQ treatment.. Results: The median day 7 concentration of PQ remained virtually consistent throughout pregnancy and were satisfactory across the three population groups ranging from 26-34.1ng/ml; this implied the efficacy of PQ throughout pregnancy. DDI interaction with ritonavir and efavirenz resulted in modest effect on the day 7 concentrations of PQ with AUCratio ranging from 0.56-0.8 and 1.64-1.79 for efavirenz and ritonavir respectively over 10-40 gestational weeks, however, a reduction in human serum albumin level reflective of severe malaria resulted in significantly reduced the number of subjects attaining the PQ day 7 concentration in the presence of both DDIs. The model demonstrated that the DDI between PQ and ARV in pregnant women with different malaria severities can alter the pharmacokinetic of PQ.

Keywords: antiretroviral, malaria, piperaquine, pregnancy, physiologically-based pharmacokinetics

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Authors: Jorge Ferro-Diaz, Lazaro Marquez-Llauger, Jose Alberto Camejo-Lamas, Lazaro Marquez-Govea

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The invasion of Scaevola sericea Vahl (Goodeniaceae) in Cuba is a recent process, this exotic invasive species was reported for the first time, in the national territory, by 2008. S. sericea is native to the coasts around the Indian Ocean and western Pacific, common on sandy beaches; it has expanded rapidly around the planet by either natural or anthropic causes, mainly due to its use in hotel gardening. Cuba is highly vulnerable to the colonization of these species, mainly due to tropical hurricanes which have increased in the last decades; it also affects other native species such as Tournefortia gnaphalodes (L.) R. Br. (Boraginaceae) that show invasive manifestations because of the unbalanced state of demographic processes of littoral vegetation, which has been studied by authors during the last 10 years. The fast development of Cuban tourism has encouraged the use of exotic species in gardening that invade large sectors of sandy coasts. Taking into account the importance of assessing the impacts dimensions and adopting effective control measures, a monitoring program for the invasion of S. sericea in Cuba was undertaken. The program has been implemented since 2013 and the main objective was to identify invasive patterns and interactions with other native species of coastal vegetation. This experience also aimed to validate the design and propose a standardized monitoring protocol to be applied throughout the country. In the Cuban territory, 12 sites were chosen, where there were established 24 permanent plots of 100 m2; measurements were taken twice a year taking into consideration variables such as abundance, plant height, soil cover, flora and companion vegetation, density and frequency; other physical variables of the beaches were also measured. Similarly, for associated individuals of T. gnaphalodes, the same variables were measured. The results of these first four years allowed us to document patterns of S. sericea invasion, highlighting the use of adventitious roots to enhance their colonization, and to characterize demographic indicators, ecosystem affections, and interactions with native plants. A density-dependent relationship with T. gnaphalodes was documented, finding a controlling effect on S. sericea, so that a manipulation experiment was applied to evaluate possible management actions to be incorporated in the Plans of the protected areas involved. With these results, it was concluded, for the evaluated sites, that S. sericea has had an invasion dynamics ruled by effects of coastal dynamics, more intense in beaches with affectations to the native vegetation, and more controlled in beaches with more preserved vegetation. It was found that when S. sericea is established, the mechanism that most reinforces its invasion is the use of adventitious roots, used to expand the patches and colonize beach sectors. It was also found that when the density of T. gnaphalodes increases, it detains the expansion of S. sericea and reduces its colonization possibilities, behaving as a natural controller of its biological invasion. The results include a proposal of a new Monitoring Protocol for Scaevola sericea in Cuba, with the possibility of extending its implementation to other countries in the region.

Keywords: biological invasion, exotic invasive species, plant interactions, Scaevola sericea

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Authors: Narges Solaymani

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medical training of patients. Nursing is a very important profession in the societies of the world. Although in the past, all caregivers of the sick and disabled were called nurses, nowadays, a nurse is a person who has a university education in this field. There are nurses in bachelor's, master's, and doctoral degrees in nursing. New courses have been launched in the master's degree based on duty-oriented nurses. A nurse cannot have an independent treatment center but is a member of the treatment team in established treatment centers such as hospitals, clinics, or offices. Nurses can establish counseling centers and provide nursing services at home. According to the standards, the number of nurses should be three times the number of doctors or twice the number of hospital beds, or there should be three nurses for every thousand people. Also, international standards show that in the internal and surgical department, every 4 to 6 patients should have a nurse.

Keywords: Nurse, Intensive Care, CPR, Bandage

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Authors: Sakshi Gupta, Seema Joshi

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Thiosemicarbazones (TSCs) have garnered significant attention in coordination chemistry due to their versatile coordination modes and pharmacological properties. Mixed ligand complexes of TSCs represent a promising area of research, offering enhanced antimicrobial activities compared to their parent compounds. This review provides an overview of the synthesis, characterization, and antimicrobial properties of mixed ligand complexes incorporating thiosemicarbazones. The synthesis of mixed ligand complexes typically involves the reaction of a metal salt with TSC ligands and additional ligands, such as nitrogen- or oxygen-based ligands. Various transition metals, including copper, nickel, and cobalt, have been employed to form mixed ligand complexes with TSCs. Characterization techniques such as spectroscopy, X-ray crystallography, and elemental analysis are commonly utilized to confirm the structures of these complexes. One of the key advantages of mixed ligand complexes is their enhanced antimicrobial activity compared to pure TSC compounds. The synergistic effect between the TSC ligands and additional ligands contributes to increased efficacy, possibly through improved metal-ligand interactions or enhanced membrane permeability. Furthermore, mixed ligand complexes offer the potential for selective targeting of microbial species while minimizing toxicity to mammalian cells. This selectivity arises from the specific interactions between the metal center, TSC ligands, and biological targets within microbial cells. Such targeted antimicrobial activity is crucial for developing effective treatments with minimal side effects. Moreover, the versatility of mixed ligand complexes allows for the design of tailored antimicrobial agents with optimized properties. By varying the metal ion, TSC ligands, and additional ligands, researchers can fine-tune the physicochemical properties and biological activities of these complexes. This tunability opens avenues for the development of novel antimicrobial agents with improved efficacy and reduced resistance. In conclusion, mixed ligand complexes of thiosemicarbazones represent a promising class of compounds with potent antimicrobial activities. Further research in this field holds great potential for the development of novel therapeutic agents to combat microbial infections effectively.

Keywords: metal complex, thiosemicarbazones, mixed ligand, selective targeting, antimicrobial activity

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Authors: Meaghan Bowman

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Soldiers are taught about the importance of effective communication with repetition of the phrase, “Communication is key.” They receive training in preparing for, and carrying out, interactions between foreign and domestic leaders to gain crucial information about a mission. These interactions are known as Key Leader Engagements (KLEs). For the training of KLEs, doctrine mandates the skills needed to conduct these “engagements” such as how to: behave appropriately, identify key leaders, and employ effective strategies. Army officers in training learn how to confront leaders, what information to gain, and how to ask questions respectfully. Unfortunately, soldiers rarely learn how to formulate questions optimally. Since less complex questions are easier to understand, we hypothesize that semantic complexity affects content understanding, and that age and education levels may have an effect on one’s ability to form paraphrases and judge their quality. In this study, we looked at paraphrases of queries as well as judgments of both the paraphrases’ naturalness and their semantic similarity to the query. Queries were divided into three complexity categories based on the number of relations (the first number) and the number of knowledge graph edges (the second number). Two crowd-sourced tasks were completed by Amazon volunteer participants, also known as turkers, to answer the research questions: (i) Are more complex queries harder to paraphrase and judge and (ii) Do age and education level affect the ability to understand complex queries. We ran statistical tests as follows: MANOVA for query understanding and two-way ANOVA to understand the relationship between query complexity and education and age. A probe of the number of given-level queries selected for paraphrasing by crowd-sourced workers in seven age ranges yielded promising results. We found significant evidence that age plays a role and marginally significant evidence that education level plays a role. These preliminary tests, with output p-values of 0.0002 and 0.068, respectively, suggest the importance of content understanding in a communication skill set. This basic ability to communicate, which may differ by age and education, permits reproduction and quality assessment and is crucial in training soldiers for effective participation in KLEs.

Keywords: engagement, key leader, paraphrasing, query complexity, understanding

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Authors: Sven Tackenberg, Sönke Duckwitz, Andreas Petz, Christopher M. Schlick

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This paper introduces an extension to the well-established Resource-Constrained Project Scheduling Problem (RCPSP) to apply it to complex maintenance problems. The problem is to assign technicians to a team which has to process several tasks with multi-level skill requirements during a work shift. Here, several alternative activities for a task allow both, the temporal shift of activities or the reallocation of technicians and tools. As a result, switches from one valid work process variant to another can be considered and may be selected by the developed evolutionary algorithm based on the present skill level of technicians or the available tools. An additional complication of the observed scheduling problem is that the locations of the construction sites are only temporarily accessible during a day. Due to intensive rail traffic, the available time slots for maintenance and repair works are extremely short and are often distributed throughout the day. To identify efficient working periods, a first concept of a Bayesian network is introduced and is integrated into the extended RCPSP with pre-emptive and non-pre-emptive tasks. Thereby, the Bayesian network is used to calculate the probability of a maintenance task to be processed during a specific period of the shift. Focusing on the domain of maintenance of the railway infrastructure in metropolitan areas as the most unproductive implementation process at construction site, the paper illustrates how the extended RCPSP can be applied for maintenance planning support. A multi-criteria evolutionary algorithm with a problem representation is introduced which is capable of revising technician-task allocations, whereas the duration of the task may be stochastic. The approach uses a novel activity list representation to ensure easily describable and modifiable elements which can be converted into detailed shift schedules. Thereby, the main objective is to develop a shift plan which maximizes the utilization of each technician due to a minimization of the waiting times caused by rail traffic. The results of the already implemented core algorithm illustrate a fast convergence towards an optimal team composition for a shift, an efficient sequence of tasks and a high probability of the subsequent implementation due to the stochastic durations of the tasks. In the paper, the algorithm for the extended RCPSP is analyzed in experimental evaluation using real-world example problems with various size, resource complexity, tightness and so forth.

Keywords: maintenance management, scheduling, resource constrained project scheduling problem, genetic algorithms

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Authors: Sajewicz-Krukowska Joanna, Domańska-Blicharz Katarzyna, Tarasiuk Karolina, Marzec-Kotarska Barbara

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Astroviral infections pose a significant problem in the poultry industry, leading to multiple adverse effects such as decreased egg production, breeding disorders, poor weight gain, and even increased mortality. Commonly observed chicken astrovirus (CAstV) was recently reported to be responsible for "white chicks syndrome" associated with increased embryo/chick mortality. The CAstV-mediated pathogenesis in chicken occurs due to complex interactions between the infectious pathogen and the immune system. Many aspects of CAstV-chicken interactions remain unclear, and there is no information available regarding gene expression changes in the chicken's spleen in response to CAstV infection. We aimed to investigate the molecular background triggered by CAstV infection. Ten 21-day-old SPF White Leghorn chickens were divided into two groups of 5 birds each. One group was inoculated with CAstV, and the other was used as the negative control. On 4th dpi, spleen samples were collected and immediately frozen at -70°C for RNA isolation. We analysed transcriptional profiles of the chickens' spleens at the 4th day following infection using RNA-seq to establish differentially expressed genes (DEGs). The RNA-seq findings were verified by quantitative real-time PCR (qRT-PCR). A total of 31959 transcripts were identified in response to CAstV infection. Eventually 45 DEGs (p-value<0.05; Log2Foldchange>1)were recognized in the spleen after CAstV infection (26 upregulated DEGs and 19 downregulated DEGs). qRT-PCR performed on 4 genes (IFIT5, OASL, RASD1, DDX60) confirmed RNAseq results. Top differentially expressed genes belonged to novel putative IFN-induced CAstV restriction factors. Most of the DEGs were associated with RIG-I–like signalling pathway or, more generally, with an innate antiviral response(upregulated: BLEC3, CMPK2, IFIT5, OASL, DDX60, IFI6, and downregulated: SPIK5, SELENOP, HSPA2, TMEM158, RASD1, YWHAB). The study provided a global analysis of host transcriptional changes that occur during CAstV infection in vivo and proved the cell cycle in the spleen and immune signalling in chickens were predominantly affected upon CAstV infection.

Keywords: chicken astrovirus, CastV, RNA-seq, transcriptome, spleen

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Authors: Sanaz Farhangi, Habib Alipour

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The main objective of this paper is to explore how social media as a critical platform would increase the interactions between the tourism sector and stakeholders. Nowadays, human interactions through social media in many areas, especially in tourism, provide various experiences and information that users share and discuss. Organizations and firms can gain customer loyalty through social media platforms, albeit consumers' negative image of the product or services. Such a negative image can be reduced through constant communication between produces and consumers, especially with the availability of the new technology. Therefore, effective management of customer relationships in social media creates an extraordinary opportunity for organizations to enhance value and brand loyalty. In this study, we seek to develop a conceptual model for addressing factors such as social media, SCRM, and customer engagement affecting brand loyalty and diminish co-destruction. To support this model, we scanned the relevant literature using a comprehensive category of ideas in the context of marketing and customer relationship management. This will allow exploring whether there is any relationship between social media, customer engagement, social customer relationship management (SCRM), co-destruction, and brand loyalty. SCRM has been explored as a moderating factor in the relationship between customer engagement and social media to secure brand loyalty and diminish co-destruction of the company’s value. Although numerous studies have been conducted on the impact of social media on customers and marketing behavior, there are limited studies for investigating the relationship between SCRM, brand loyalty, and negative e-WOM, which results in the reduction of the co-destruction of value by customers. This study is an important contribution to the tourism and hospitality industry in orienting customer behavior in social media using SCRM. This study revealed that through social media platforms, management can generate discussion and engagement about the product and services, which facilitates customers feeling in an appositive way towards the firm and its product. Study has also revealed that customers’ complaints through social media have a multi-purpose effect; it can degrade the value of the product, but at the same time, it will motivate the firm to overcome its weaknesses and correct its shortcomings. This study has also implications for the managers and practitioners, especially in the tourism and hospitality sector. Future research direction and limitations of the research were also discussed.

Keywords: brand loyalty, co-destruction, customer engagement, SCRM, tourism and hospitality

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Authors: Thouraya Eshami

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The aim of this study is to understand, interpret and describe the dynamics of the management and leadership practices with its diverse constituents within the middle management cadre in two selected post-1992 UK universities. The information will be gleaned from interviews conducted with academics who became middle-managers (an AD, SGL and TL) in two selected case Higher Education Institutes. The term middle management is used to describe personnel occupying positions at the level of assistant deans, dean (which also referred to as associate deans), and team leaders.

Keywords: academic manager, associate dean, higher education, middle manager, post 1992 universities

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Authors: Madelaine Venzon, Dany S. S. L. Amaral, André L. Perez, Natália S. Diaz, Juliana A. Martinez Chiguachi, Maira C. M. Fonseca, James D. Harwood, Angelo Pallini

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Integrating strategies of sustainable crop production and promoting the provisioning of ecological services on farms and within rural landscapes is a challenge for today’s agriculture. Habitat management, through increasing vegetational diversity, enhances heterogeneity in agroecosystems and has the potential to improve the recruitment of natural enemies of pests, which promotes biological control services. In tropical agroecosystems, however, there is a paucity of information pertaining to the resources provided by associated plants and their interactions with natural enemies. The maintenance of non-crop plants integrated into and/or surrounding crop fields provides the farmer with a low-investment option to enhance biological control. We carried out field experiments in chili pepper agroecosystems with small stakeholders located in the Zona da Mata, State of Minas Gerais, Brazil, from 2011 to 2015 where we assessed: (a) whether non-crop plants within and around chili pepper fields affect the diversity and abundance of aphidophagous species; (b) whether there are direct interactions between non-crop plants and aphidophagous arthropods; and (c) the importance of non-crop plant resources for survival of Coccinellidae and Chrysopidae species. Aphidophagous arthropods were dominated by Coccinellidae, Neuroptera, Syrphidae, Anthocoridae and Araneae. These natural enemies were readily observed preying on aphids, feeding on flowers or extrafloral nectaries and using plant structures for oviposition and/or protection. Aphid populations were lower on chili pepper fields associated with non-crop plants that on chili pepper monocultures. Survival of larvae and adults of different species of Coccinellidae and Chrysopidae on non-crop resources varied according to the plant species. This research provides evidence that non-crop plants in chili pepper agroecosystems can affect aphid abundance and their natural enemy abundance and survival. It is also highlighting the need for further research to fully characterize the structure and function of plant resources in these and other tropical agroecosystems. Financial support: CNPq, FAPEMIG and CAPES (Brazil).

Keywords: Conservation biological control, aphididae, Coccinellidae, Chrysopidae, plant diversification

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Authors: G. Melo, J. Felix, S. Maciel, C. Fernandes, W. Rodrigues

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In Brazilian public policy, the Centres of Reference for Social Assistance (CRAS in Portuguese) are part of the Unified Social Assistance System (SUAS in Portuguese). SUAS is responsible for addressing spontaneous or currently active cases that are brought forth from other services in the social assistance network. The following case was reviewed by CRAS’s team in Recife, Brazil, after a complaint of child abuse was filed against the mother of a 7-year-old girl by the girl’s aunt. The girl is the daughter of an incestuous relationship between her mother and her older brother. The complaint was registered by service staff and five interventions were subsequently carried out on behalf of the child. These interventions provided a secure place for dialogue with both the child and her family and allowed for an investigation of the abuse to proceed. They took place in the child’s school as well as her aunt’s residence. At school, the child (with her classmates) watched a video and listened to a song about the prevention of child abuse. This was followed up with a second intervention to determine any signs of Post-Traumatic Stress Disorder (PTSD), by having the child play with the mobile app ‘My Angela’. Books on the themes of family and fear were also read to the child on different occasions at her school – after every intervention she was asked to draw something related to fear and her concept of a family. After the interventions and discussing the case as a team, we reached several conclusions: 1) The child did not appear to show any symptoms of PTSD; 2) She normally fantasized about her future and life story; 3) She did not allow herself to be touched by strangers with whom she lacks a close relationship (such as classmates or her teacher); 4) Through her drawings, she reproduced the conversations she had had with the staff; 5) She habitually covered her drawings when asked questions about the abuse. In this particular clinical case, we want to highlight that the role of the Psychologist’s intervention at CRAS is to attempt to resolve the issue promptly (and not to develop a prolonged clinical study based on traditional methods), by making use of the available tools from the social assistance network, and by making referrals to the relevant authorities, such as the Public Ministry, so that final protective actions can be taken and enforced. In this case, the Guardian Council of the Brazilian Public Ministry was asked to transfer the custody of the child to her uncle. The mother of the child was sent to a CAPS (Centre for Psychosocial Care), having been diagnosed with psychopathology. The child would then participate in NGO programs that allow for a gradual reduction of social exposure to her mother before being transferred to her uncle’s custody in Sao Paulo.

Keywords: child abuse, intervention, social psychology, violence

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Authors: Mateen A Khan, Taj Mohammad, Md. Imtaiyaz Hassan

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Alzheimer’s disease is characterized by the accumulation of the processing products of the amyloid beta peptide cleaved by amyloid precursor protein (APP). Iron increases the synthesis of amyloid beta peptides, which is why iron is present in Alzheimer's disease patients' amyloid plaques. Iron misregulation in the brain is linked to the overexpression of APP protein, which is directly related to amyloid-β aggregation in Alzheimer’s disease. The APP 5'-UTR region encodes a functional iron-responsive element (IRE) stem-loop that represents a potential target for modulating amyloid production. Targeted regulation of APP gene expression through the modulation of 5’-UTR sequence function represents a novel approach for the potential treatment of AD because altering APP translation can be used to improve both the protective brain iron balance and provide anti-amyloid efficacy. The molecular docking analysis of APP IRE RNA with eukaryotic translation initiation factors yields several models exhibiting substantial binding affinity. The finding revealed that the interaction involved a set of functionally active residues within the binding sites of eIF4F. Notably, APP IRE RNA and eIF4F interaction were stabilized by multiple hydrogen bonds with residues of APP IRE RNA and eIF4F. It was evident that APP IRE RNA exhibited a structural complementarity that tightly fit within binding pockets of eIF4F. The simulation studies further revealed the stability of the complexes formed between RNA and eIF4F, which is crucial for assessing the strength of these interactions and subsequent roles in the pathophysiology of Alzheimer’s disease. In addition, MD simulations would capture conformational changes in the IRE RNA and protein molecules during their interactions, illustrating the mechanism of interaction, conformational change, and unbinding events and how it may affect aggregation propensity and subsequent therapeutic implications. Our binding studies correlated well with the translation efficiency of APP mRNA. Overall, the outcome of this study suggests that the genomic modification and/or inhibiting the expression of amyloid protein by targeting APP IRE RNA can be a viable strategy to identify potential therapeutic targets for AD and subsequently be exploited for developing novel therapeutic approaches.

Keywords: Alzheimer's disease, Protein-RNA interaction analysis, molecular docking simulations, conformational dynamics, binding stability, binding kinetics, protein synthesis.

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Authors: Shveta Bathla, Preeti Rawat, Sudarshan Kumar, Rubina Baithalu, Jogender Singh Rana, Tushar Kumar Mohanty, Ashok Kumar Mohanty

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Pregnancy is a complex process which includes series of events such as fertilization, formation of blastocyst, implantation of embryo, placental formation and development of fetus. The success of these events depends on various interactions which are synchronized by endocrine interaction between a receptive dam and competent embryo. These interactions lead to change in expression of hormones and proteins. But till date no protein biomarker is available which can be used to detect successful completion of these events. We employed quantitative proteomics approach to develop putative serological biomarker which has diagnostic applicability for early detection of pregnancy in cows. For this study, sera were collected from control (non-pregnant, n=6) and pregnant animals on successive days of pregnancy (7, 19, 45, n=6). The sera were subjected to depletion for removal of albumin using Norgen depletion kit. The tryptic peptides were labeled with iTRAQ. The peptides were pooled and fractionated using bRPLC over 80 min gradient. Then 12 fractions were injected to nLC for identification and quantitation in DDA mode using ESI. Identification using Mascot search revealed 2056 proteins out of which 352 proteins were differentially expressed. Twenty proteins were upregulated and twelve proteins were down-regulated with fold change > 1.5 and < 0.6 respectively (p < 0.05). The gene ontology studies of DEPs using Panther software revealed that majority of proteins are actively involved in catalytic activities, binding and enzyme regulatory activities. The DEP'S such as NF2, MAPK, GRIPI, UGT1A1, PARP, CD68 were further subjected to pathway analysis using KEGG and Cytoscape plugin Cluego that showed involvement of proteins in successful implantation, maintenance of pluripotency, regulation of luteal function, differentiation of endometrial macrophages, protection from oxidative stress and developmental pathways such as Hippo. Further efforts are continuing for targeted proteomics, western blot to validate potential biomarkers and development of diagnostic kit for early pregnancy diagnosis in cows.

Keywords: bRPLC, Cluego, ESI, iTRAQ, KEGG, Panther

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Authors: M. H. Ahmadi, A. Mortazavi, H. Zarei

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Several authors have described the main mechanism of formation of cracks in the segment lining during the construction of tunnels with tunnel boring machines. A comprehensive analysis of segmental lining joints may help to guarantee a safe construction during Tunneling and serviceable stages. The most frequent types of segment damage are caused by a condition of uneven segment matching due to contact deficiencies. This paper investigated the interaction mechanism of precast concrete lining joints in tunnels. The Discrete Element Method (DEM) was used to analyze a typical segmental lining model consisting of six segment rings. In the analyses, typical segmental lining design parameters of the Ghomrood water conveyance tunnel, Iran were employed in the study. In the conducted analysis, the worst-case scenario of loading faced during the boring of Ghomrood tunnel was considered. This was associated with the existence of a crushed zone dipping at 75 degree at the location of the key segment. In the analysis, moreover, the effect of changes in horizontal stress ratio on the loads on the segment was assessed. The boundary condition associated with K (ratio of the horizontal to the vertical stress) values of 0.5, 1, 1.5 and 2 were applied to the model and separate analysis was conducted for each case. Important parameters such as stress, moments, and displacements were measured at joint locations and the surrounding rock. Accordingly, the segment joint interactions were assessed and analyzed. Moreover, rock mass properties of the Ghomrood in Ghom were adopted. In this study, the load acting on segments joints are included a crushed zone stratum force that intersect tunnel with 75 slopes in the location of the key segment, gravity force of segments and earth pressures. A numerical investigation was used for different coefficients of stress concentration of 0.5, 1, 1.5, 2 and different geological conditions of saturated crushed zone under the critical scenario. The numerical results also demonstrate that maximum bending moments in longitudinal joints occurred for crushed zone with the weaken strengths (Sandstone). Besides that, increasing the load in segment-stratum interfaces affected radial stress in longitudinal joints and finally the opening of joints occurred.

Keywords: joint, interface, segment, contact

Procedia PDF Downloads 258

Authors: Sinethemba Yakobi, Lindiwe Zuma, Ofentse Pooe

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Gonococcal infections present a notable public health issue, and the major approach for treatment involves using β-lactam antibiotics that specifically target penicillin-binding protein 2 (PBP2) in Neisseria gonorrhoeae. This study examines the influence of flavonoids, namely rutin, on the structural changes of PBP2 in both penicillin-resistant (FA6140) and penicillin-susceptible (FA19) strains. The research clarifies the structural effects of particular mutations, such as inserting an aspartate residue at position 345 (Asp-345a) in the PBP2 protein. The strain FA6140, which is resistant to penicillin, shows specific changes that lead to a decrease in penicillin binding. These mutations, namely P551S and F504L, significantly impact the pace at which acylation occurs and the stability of the strain under high temperatures. Molecular docking analyses investigate the antibacterial activities of rutin and other phytocompounds, emphasizing its exceptional binding affinity and potential as an inhibitor of PBP2. Quercetin and protocatechuic acid have encouraging antibacterial effectiveness, with quercetin displaying characteristics similar to those of drugs. Molecular dynamics simulations offer a detailed comprehension of the interactions between flavonoids and PBP2, highlighting rutin's exceptional antioxidant effects and strong affinity for the substrate binding site. The study's wider ramifications pertain to the pressing requirement for antiviral treatments in the context of the ongoing COVID-19 epidemic. Flavonoids have a strong affinity for binding to PBP2, indicating their potential as inhibitors to impair cell wall formation in N. gonorrhoeae. Ultimately, this study provides extensive knowledge on the interactions between proteins and ligands, the dynamics of the structure, and the ability of flavonoids to combat penicillin-resistant N. gonorrhoeae bacteria. The verified simulation outcomes establish a basis for creating potent inhibitors and medicinal therapies to combat infectious illnesses.

Keywords: phytochemicals, penicillin-binding protein 2, gonococcal infection, ligand-protein interaction, binding energy, neisseria gonorrhoeae FA19, neisseria gonorrhoeae FA6140, flavonoids

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Authors: Evgeny E. Tereshatov

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Astatine-211 is considered one of the most promising radionuclides for Targeted Alpha Therapy. In order to develop reliable procedures to label biomolecules and utilize efficient delivery vehicle principles, one should understand the main chemical characteristics of astatine. The short half-life of 211At (~7.2 h) and absence of any stable isotopes of this element are limiting factors towards studying the behavior of astatine. Our team has developed a procedure for rapid and efficient isolation of astatine from irradiated bismuth material in nitric acid media based on 3-octanone and 1-octanol extraction chromatography resins. This process has been automated and it takes 20 min from the beginning of the target dissolution to the At-211 fraction elution. Our next step is to consider commercially available chromatography resins and their applicability in astatine purification in the same media. Results obtained along with the corresponding sorption mechanisms will be discussed.

Keywords: astatine-211, chromatography, automation, mechanism, radiopharmaceuticals

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Authors: Adenike Adesanya, Nonthaphat Wong, Xiang-Yun Lan, Shea Ping Yip, Chien-Ling Huang

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Background: The most challenging mutation of the oncokinase BCR-ABL protein T315I, which is commonly known as the “gatekeeper” mutation and is notorious for its strong resistance to almost all tyrosine kinase inhibitors (TKIs), especially imatinib. Therefore, this study aims to identify T315I-dependent downstream microRNA (miRNA) pathways associated with drug resistance in chronic myeloid leukemia (CML) for prognostic and therapeutic purposes. Methods: T315I-carrying K562 cell clones (K562-T315I) were generated by the CRISPR-Cas9 system. Imatinib-treated K562-T315I cells were subjected to small RNA library preparation and next-generation sequencing. Putative lncRNA-miRNA-mRNA networks were analyzed with (i) DESeq2 to extract differentially expressed miRNAs, using Padj value of 0.05 as cut-off, (ii) STarMir to obtain potential miRNA response element (MRE) binding sites of selected miRNAs on lncRNA H19, (iii) miRDB, miRTarbase, and TargetScan to predict mRNA targets of selected miRNAs, (iv) IntaRNA to obtain putative interactions between H19 and the predicted mRNAs, (v) Cytoscape to visualize putative networks, and (vi) several pathway analysis platforms – Enrichr, PANTHER and ShinyGO for pathway enrichment analysis. Moreover, mitochondria isolation and transcript quantification were adopted to determine the new mechanism involved in T315I-mediated resistance of CML treatment. Results: Verification of the CRISPR-mediated mutagenesis with digital droplet PCR detected the mutation abundance of ≥80%. Further validation showed the viability of ≥90% by cell viability assay, and intense phosphorylated CRKL protein band being detected with no observable change for BCR-ABL and c-ABL protein expressions by Western blot. As reported by several investigations into hematological malignancies, we determined a 7-fold increase of H19 expression in K562-T315I cells. After imatinib treatment, a 9-fold increment was observed. DESeq2 revealed 171 miRNAs were differentially expressed K562-T315I, 112 out of these miRNAs were identified to have MRE binding regions on H19, and 26 out of the 112 miRNAs were significantly downregulated. Adopting the seed-sequence analysis of these identified miRNAs, we obtained 167 mRNAs. 6 hub miRNAs (hsa-let-7b-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-129-5p, and hsa-miR-372-3p) and 25 predicted genes were identified after constructing hub miRNA-target gene network. These targets demonstrated putative interactions with H19 lncRNA and were mostly enriched in pathways related to cell proliferation, senescence, gene silencing, and pluripotency of stem cells. Further experimental findings have also shown the up-regulation of mitochondrial transcript and lncRNA MALAT1 contributing to the lncRNA-miRNA-mRNA networks induced by BCR-ABL T315I mutation. Conclusions: Our results have indicated that lncRNA-miRNA regulators play a crucial role not only in leukemogenesis but also in drug resistance, considering the significant dysregulation and interactions in the K562-T315I cell model generated by CRISPR-Cas9. In silico analysis has further shown that lncRNAs H19 and MALAT1 bear several complementary miRNA sites. This implies that they could serve as a sponge, hence sequestering the activity of the target miRNAs.

Keywords: chronic myeloid leukemia, imatinib resistance, lncRNA-miRNA-mRNA, T315I mutation

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