Search results for: role of government

Authors: George Shaker, Maike Eylert

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Recurrent urinary tract infections (UTIs) in patients with mesh implants, particularly following pelvic or abdominal surgeries, pose significant clinical challenges. This paper investigates whether flexible cystoscopy is an essential diagnostic and therapeutic tool in managing such patients. With the increasing prevalence of mesh-related complications, it is crucial to explore how diagnostic procedures like cystoscopy can aid in identifying mesh-associated issues that contribute to recurrent UTIs. While flexible cystoscopy is commonly used to evaluate lower urinary tract conditions, its necessity in cases involving patients with mesh implants remains under debate. This study aims to determine the value of flexible cystoscopy in identifying complications such as mesh erosion, fistula formation, and chronic inflammation, which may contribute to recurrent infections. The research compares patients who underwent flexible cystoscopy to those managed without this procedure, examining the diagnostic yield of cystoscopy in detecting mesh-related complications. Furthermore, the study investigates the relationship between recurrent UTIs and the mechanical effects of mesh on the urinary tract, as well as the potential for cystoscopy to guide treatment decisions, such as mesh removal or revision. The results indicate that while flexible cystoscopy can identify mesh-related complications in some cases, its routine use may not be necessary for all patients with recurrent UTIs and mesh. The study emphasizes the importance of patient selection, clinical history, and symptom severity in deciding whether to employ cystoscopy. In cases where there are clear signs of mesh erosion or unexplained recurrent infections despite standard treatments, cystoscopy proves valuable. However, the study also highlights potential risks and discomfort associated with the procedure, suggesting that cystoscopy should be reserved for select cases where non-invasive methods fail to provide clarity. The research concludes that while flexible cystoscopy remains a valuable tool in certain cases, its routine use for all patients with recurrent UTIs and mesh is not justified. The paper provides recommendations for clinical guidelines, emphasizing a more personalized approach to diagnostics that considers the patient’s overall condition, infection history, and mesh type.

Keywords: flexible cystoscopy, recurrent urinary tract infections, mesh implants, mesh erosion, diagnostic procedures, urology

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Authors: Agata Ferreira

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Rapidly increasing debates and initiatives in the area of Corporate Social Responsibility (“CSR”) have reached the world of international investment law. CSR standards that focus on the operations of multinational companies are increasingly relevant in the context of international investment policy making. In the past, the connection between CSR standards and legal framework for foreign direct investment has been largely non-existent. Recently, however, there is a growing trend of a more balance approach to rights and obligations as between investors and states under investment treaties. CSR principles join other social and environmental measures slowly being included in the investment treaties to enhance their sustainable development dimension. Issues of CSR are present on negotiation tables of new mega regional investment treaties like TTIP for example. To date, only a very few bilateral investment treaties and a handful of other international treaties with investment provisions include CSR clauses. In addition, the existing provisions tend to be of a soft type, where parties merely acknowledge importance of good corporate governance and CSR for sustainable development or generally affirm their aim to encourage enterprises to observe internationally recognised guidelines and principles of CSR. The relevant provisions often leave it up to the states to encourage enterprises operating within their territories to voluntarily incorporate CSR principles. The interaction between general non-binding CSR standards, domestic laws and policies and provisions of international investment treaties have not been tested by investment tribunals yet. The role of investment treaties in raising awareness and promoting CSR is still in its infancy. The use of CSR standards in the international investment protection regime for promotion of CSR standards, and as a tool for disciplining investors into complying with such standards, pose a number of questions and is met with resistance from investors` lobbies. Integration of these two areas, CSR and international investment law, both consisting of multilayered, diverse and often overlapping instruments is by no means an easy task. Whether international investment world is ready to embrace CSR standards or shrug them off is a matter of uncertain future. The subject however has been raised, first introductions have been made and the time will show whether the relationship between legal framework of international investment and CSR will flourish or remain dormant.

Keywords: corporate social responsibility, foreign direct investment, investment treaties, sustainable development

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Authors: Bharath Anantharamaiah, Tomas Bouda, Elke Deckers, Stijn Jonckheere, Wim Desmet, Juan J. Garcia

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Automotive tyres are gaining importance recently in terms of their noise emission, not only with respect to reduction in noise, but also their perception and detection. Tyres exhibit a mechanical noise generation mechanism up to 1 kHz. However, owing to the fact that tyre is a composite of several materials, it has been difficult to model it using finite elements to predict noise at high frequencies. The currently available FE models have a reliability of about 500 Hz, the limit which, however, is not enough to perceive the roughness or sharpness of noise from tyre. These noise components are important in order to alert pedestrians on the street about passing by slow, especially electric vehicles. In order to model tyre noise behaviour up to 1 kHz, its dynamic behaviour must be accurately developed up to a 1 kHz limit using finite elements. Materials play a vital role in modelling the dynamic tyre behaviour precisely. Since tyre is a composition of several components, their precise definition in finite element simulations is necessary. However, during the tyre manufacturing process, these components are subjected to various pressures and temperatures, due to which these properties could change. Hence, material definitions are better described based on the tyre responses. In this work, the hyperelasticity of tyre component rubbers is calibrated, using the design of experiments technique from the tyre characteristic responses that are measured on a stiffness measurement machine. The viscoelasticity of rubbers are defined by the Prony series for rubbers, which are determined from the loss factor relationship between the loss and storage moduli, assuming that the rubbers are excited within the linear viscoelasticity ranges. These values of loss factor are measured and theoretically expressed as a function of rubber shore hardness or hyperelasticities. From the results of the work, there exists a good correlation between test and simulation vibrational transfer function up to 1 kHz. The model also allows flexibility, i.e., the frequency limit can also be extended, if required, by calibrating the Prony parameters of rubbers corresponding to the frequency of interest. As future work, these tyre models are used for noise generation at high frequencies and thus for tyre noise perception.

Keywords: tyre dynamics, rubber materials, prony series, hyperelasticity

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Authors: Hana Barak, Alex Sivan, Ariel Kushmaro

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Microorganisms are the most diverse and abundant life forms on Earth and account for a large portion of the Earth’s biomass and biodiversity. To date though, our knowledge regarding microbial life is lacking, as it is based mainly on information from cultivated organisms. Indeed, microbiologists have borrowed from astrophysics and termed the ‘uncultured microbial majority’ as ‘microbial dark matter’. The realization of how diverse and unexplored microorganisms are, actually stems from recent advances in molecular biology, and in particular from novel methods for sequencing microbial small subunit ribosomal RNA genes directly from environmental samples termed next-generation sequencing (NGS). This has led us to use NGS that generates several gigabases of sequencing data in a single experimental run, to identify and classify environmental samples of microorganisms. In metagenomics sequencing analysis (both 16S and shotgun), sequences are compared to reference databases that contain only small part of the existing microorganisms and therefore their taxonomy assignment may reveal groups of unknown microorganisms or origins. These unknowns, or the ‘microbial sequences dark matter’, are usually ignored in spite of their great importance. The goal of this work was to develop an improved bioinformatics method that enables more complete analyses of the microbial communities in numerous environments. Therefore, NGS was used to identify previously unknown microorganisms from three different environments (industrials wastewater, Negev Desert’s rocks and water wells at the Arava valley). 16S rRNA gene metagenome analysis of the microorganisms from those three environments produce about ~4 million reads for 75 samples. Between 0.1-12% of the sequences in each sample were tagged as ‘Unassigned’. Employing relatively simple methodology for resequencing of original gDNA samples through Sanger or MiSeq Illumina with specific primers, this study demonstrates that the mysterious ‘Unassigned’ group apparently contains sequences of candidate phyla. Those unknown sequences can be located on a phylogenetic tree and thus provide a better understanding of the ‘sequences dark matter’ and its role in the research of microbial communities and diversity. Studying this ‘dark matter’ will extend the existing databases and could reveal the hidden potential of the ‘microbial dark matter’.

Keywords: bacteria, bioinformatics, dark matter, Next Generation Sequencing, unknown

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Authors: Asim Laeeq Khan, Mazhar Amjad Gilani, Tayub Raza

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The use of fossil fuels for energy generation leads to the emission of greenhouse gases particularly CO2 into the atmosphere. To date, several techniques have been proposed for the efficient removal of CO2 from flue gas mixtures. Membrane technology is a promising choice due to its several inherent advantages such as low capital cost, high energy efficiency, and low ecological footprint. One of the goals in the development of membranes is to achieve high permeability and selectivity. Mixed matrix membranes comprising of inorganic fillers embedded in polymer matrix are a class of membranes that have showed improved separation properties. One of the biggest challenges in the commercialization if mixed matrix membranes are the removal of non-selective voids existing at the polymer-filler interface. In this work, mixed matrix membranes were prepared using polysulfone as polymer matrix and ordered mesoporous MCM-41 as filler materials. A new approach to removing the interfacial voids was developed by introducing room temperature ionic (RTIL) at the polymer-filler interface. The results showed that the imidazolium based RTIL not only provided wettability characteristics but also helped in further improving the separation properties. The removal of interfacial voids and good contact between polymer and filler was verified by SEM measurement. The synthesized membranes were tested in a custom built gas permeation set-up for the measurement of gas permeability and ideal gas selectivity. The results showed that the mixed matrix membranes showed significantly higher CO2 permeability in comparison to the pristine membrane. In order to have further insight into the role of fillers, diffusion and solubility measurements were carried out. The results showed that the presence of highly porous fillers resulted in increasing the diffusion coefficient while the solubility showed a slight drop. The RTIL filled membranes showed higher CO2/CH4 and CO2/N2 selectivity than unfilled membranes while the permeability dropped slightly. The increase in selectivity was due to the highly selective RTIL used in this work. The study revealed that RTIL filled mixed matrix membranes are an interesting candidate for gas separation membranes.

Keywords: ionic liquids, CO2 separation, membranes, mixed matrix membranes

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Authors: Zahid Ullah, Atlas Khan

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This abstract focuses on the advancements in mathematical modeling and optimization techniques that play a crucial role in enhancing the efficiency, reliability, and performance of these systems. In this era of rapidly evolving technology, mathematical modeling and optimization offer powerful tools to tackle the complex challenges faced by control, signal processing, and energy systems. This abstract presents the latest research and developments in mathematical methodologies, encompassing areas such as control theory, system identification, signal processing algorithms, and energy optimization. The abstract highlights the interdisciplinary nature of mathematical modeling and optimization, showcasing their applications in a wide range of domains, including power systems, communication networks, industrial automation, and renewable energy. It explores key mathematical techniques, such as linear and nonlinear programming, convex optimization, stochastic modeling, and numerical algorithms, that enable the design, analysis, and optimization of complex control and signal processing systems. Furthermore, the abstract emphasizes the importance of addressing real-world challenges in control, signal processing, and energy systems through innovative mathematical approaches. It discusses the integration of mathematical models with data-driven approaches, machine learning, and artificial intelligence to enhance system performance, adaptability, and decision-making capabilities. The abstract also underscores the significance of bridging the gap between theoretical advancements and practical applications. It recognizes the need for practical implementation of mathematical models and optimization algorithms in real-world systems, considering factors such as scalability, computational efficiency, and robustness. In summary, this abstract showcases the advancements in mathematical modeling and optimization techniques for control, signal processing, and energy systems. It highlights the interdisciplinary nature of these techniques, their applications across various domains, and their potential to address real-world challenges. The abstract emphasizes the importance of practical implementation and integration with emerging technologies to drive innovation and improve the performance of control, signal processing, and energy.

Keywords: mathematical modeling, optimization, control systems, signal processing, energy systems, interdisciplinary applications, system identification, numerical algorithms

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Authors: Sankhanil Das, Arunava Dasgupta, Keya Mitra

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This paper investigates the relationship between natural ecological systems and modern urban morphology. Over years, ecological conditions represented by natural resources such as natural landforms, systems of water, urban geography and land covers have been a significant driving factor of how settlements have formed, expanded and functioned. These have played a pivotal role in formation of the community character and the cultural identity of the urban spaces, and have steered cultural behavior within these settings. Such cultural behaviors have been instrumental in transforming mere spaces to places with meaning and symbolism. The natural process of city formation is principally founded upon the idea of balance and harmony, mostly in a subconscious manner. Reimaging such processes of natural evolution, this paper systematically builds a development model that generates a balance between environment and development, with specific focus on the Urban-Rural fringe areas in the Temple Town of Puri, in Eastern India. Puri represents a unique cross section of ecological landscape, cultural practices and religious symbolism with a very rich history and a vibrant heritage. While the city centre gets more and more crowded by tourists and pilgrims to accommodate related businesses, the original residents of Puri relocate to move towards the urban peripheral areas for better living conditions, gradually converting agricultural lands into non agricultural uses. This rapid spread into the rural hinterland is devoid of any connection with the rich cultural identity of Puri. These past four decades of ‘development’ has been at the cost of 810 Hectares of ecological Lake systems in the region. Invaluable ecological resources at urban rural edges are often viewed as hindrances to development and conceptualized as taking away from the image of the city. This paper attempts to understand the language of development over years on existing natural resources through topo-analysis and proposes a sustainable approach of development using different planning tools, with ecological resources as the pivotal factor of development.

Keywords: livability, sustainable development, urbanization, urban-rural edge

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Authors: Styliani Soulioti, Helen Fiddler

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The aim of this study was to investigate the approaches used by physiotherapists in the education of patients with chronic low back pain (cLBP) and the rationale that underpins their choice of approach. Therapeutic patient education (TPE) is considered to be an important aspect of modern physiotherapy practice, as it helps patients achieve better self-management and a better understanding of their problem. Previous studies have explored this subject, but the reasoning behind the choices physiotherapists make as educators has not been widely explored, thus making it difficult to understand areas that could be addressed in order to improve the application of TPE.A qualitative study design, guided by a constructivist epistemology was used in this research project. Semi-structured interviews were used to collect data from 7 physiotherapists. Inductive coding and thematic analysis were used, which allowed key themes to emerge. Data analysis revealed two overarching themes: 1) patient-centred versus therapist-centred educational approaches, and 2) behaviourist versus constructivist educational approaches. Physiotherapists appear to use a patient-centred-approach when they explore patients’ beliefs about cLBP and treatment expectations. However, treatment planning and goal-setting were guided by a therapist-centred approach, as physiotherapists appear to take on the role of the instructor/expert, whereas patients were viewed as students. Using a constructivist approach, physiotherapists aimed to provide guidance to patients by combining their professional knowledge with the patients’ individual knowledge, to help the patient better understand their problem, reflect upon it and find a possible solution. However, educating patients about scientific facts concerning cLBP followed a behaviourist approach, as an instructor/student relationship was observed and the learning content was predetermined and transmitted in a one-way manner. The results of this study suggest that a lack of consistency appears to exist in the educational approaches used by physiotherapists. Although patient-centeredness and constructivism appear to be the aims set by physiotherapists in order to optimise the education they provide, a student-teacher relationship appears to dominate when it comes to goal-setting and delivering scientific information.

Keywords: chronic low back pain, educational approaches, health education, patient education

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Authors: Sayed M. Ahmed, Sawsan S. Darwish, Nagib A. Elmarzugi, Mohammad A. Al-Dosari, Mahmoud A. Adam, Nadia A. Al-Mouallimi

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The preservation of cultural heritage is a worldwide problem. Stone monuments represent an important part of this heritage, but due to their prevalently outdoor location, they are generally subject to a complex series of weathering and decay processes, in addition to physical and chemical factors, also biological agents usually play an important role in deterioration phenomena. The aim of this paper is to experimentally verify applicability and feasibility of titanium dioxide (TiO2) nanoparticles for the preservation of historical (architectural, monumental, archaeological) stone surfaces which enables to reduce the deterioration behaviors mentioned above. TiO2 nanoparticles dispersed in an aqueous colloidal suspension were applied directly on travertine (Marble and limestone often used in historical and monumental buildings) by spray-coating in order to obtain a nanometric film on stone samples. SEM, coupled with EDX microanalysis. (SEM-EDX), in order to obtain information oncoating homogeneity, surface morphology before and after aging and penetration depth of the TiO2 within the samples. Activity of the coated surface was evaluated with UV accelerated aging test. Capillary water absorption, thermal aging and colorimetric measurements have been performed on on coated and uncoated samples to evaluate their properties and estimate change of appearance with colour variation. Results show Tio2 nanoparticles good candidate for coating applications on calcareous stone, good water-repellence was observed on the samples after treatment; analyses were carried out on both untreated and freshly treated samples as well as after artificial aging. Colour change showed negligible variations on the coated or uncoated stone as well as after aging. Results showed that treated stone surfaces seem to be not affected after 1000 hours of exposure to UV radiation, no alteration of the original features.

Keywords: architectural and archaeological heritage, calcareous stone, photocatalysis TiO2, self-cleaning, thermal aging

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Authors: Norazilawati Binti Md Dahlal, Nabiila Binti Mat Yusoff, Anis Najiha Binti Ahmad

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With the increasing demand for halal products, there is a growing emphasis on ensuring their quality and adherence to halal standards. However, the vulnerability of halal goods to fraud and adulteration poses a significant challenge to the integrity of the halal industry. Whistleblowers play a pivotal role in safeguarding the safety and integrity of halal food by exposing wrongdoings, misconduct, and fraudulent practices. This study explores the implementation of whistleblowing practices aligned with halal and toyyib principles to effectively address halal food fraud issues. Whistleblowing is defined as the act of disclosing information about misconduct, immorality, or unlawful activities to relevant authorities or the public. Although whistleblowing is universally recognized as beneficial, it exposes whistleblowers to substantial risks, including career setbacks, reputation damage, and personal safety threats. Despite legal protections, whistleblowers often face retaliation and hesitancy to come forward. By integrating the principles of halal and toyyib, which encompass the physical and spiritual as well as material and supernatural elements, effective whistleblowing practices can be developed. These principles include the physical characteristic of the product in accordance with Shari’ah law (P1); products that are sourced ethically and responsibly (P2); Products that meet high standard of quality and safety (P3); functioning as servant and caliph of Allah in managing according to Allah's commands and prohibitions (P4); not excessively wasteful or extravagant (P5); positive moral and spiritual implications associated with the product (P6); and aimed at achieving prosperity in both this life and the Hereafter (P7). Employing a quantitative research approach, this study examines Islamic primary data sources and secondary data sources to investigate the prevalence and impact of whistleblowing in the halal industry. By analyzing the principles of halal and toyyib and exploring the importance of whistleblowing effective whistleblowing practices, this research aims to enhance our understanding of promoting accountability and justice within the halal industry from an Islamic perspective.

Keywords: whistleblowing, halal and toyyib, food fraud, halal integrity, Islamic practices

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Authors: Nurhajati Hakim, Kiki Amalia, A. Agustian, H. Hermansah, Y. Yulnafatmawita

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Ultisols require greater amounts of fertilizer application compared to other soils and susceptible to erosion. Unfortunately, the price of synthetic fertilizers has increased over time during the years, making them unaffordable for most Indonesian farmers. While terrace technique to control erosion very costly.Over the last century, efforts to reduce reliance on synthetic agro-chemicals fertilizers and erosion control have recently focused on Tithonia diversifolia as a fertilizer alternative, and as hedgerow plant to control erosion. Generally known by its common name of tree marigold or Mexican sunflower, this plant has attracted considerable attention for its prolific production of green biomass, rich in nitrogen, phosphorous and potassium (NPK). In pot experiments has founded some microbial such as Mycorrhizal, Azotobacter, Azospirillum, phosphate solubilizing bacterial (PSB) and fungi (PSF) are expected to play an important role in biomass production and high nutrient uptake of this plant. This issue of importance was pursued further in the following investigation in field condition. The aim of this study was to determine the type of microbial combination suitable for Tithonia cultivation as hedgerow plants in Ultisols which have higher biomass production and nutrient content, and decline soil erosion. The field experiment was conducted with 6 treatments in a randomized block design (RBD) using 3 replications. The treatments were: Tithonia rhizosphere without microbial inoculated (A); Inokulanted by Mycorrhizal + Azotobacter + Azospirillium (B); Mycorrhizal + PSF (C); Mycorrhizal + PSB(D); Mycorrhizal + PSB + PSF(E);and without hedgerow Tithonia (F).The microbial substrates were inoculated into the Tithonia rhizosphere in the nursery. The young Tithonia plants were then planted as hedgerow on Ultisols in the experimental field for 8 months, and pruned once every 2 months. Soil erosion were collected every rainy time. The differences between treatments were statistically significant by HSD test at the 95% level of probability. The result showed that treatment C (mycorrhizal + PSB) was the most effective, and followed by treatment D (mycorrhizal + PSF) in producing higher Tithonia biomass about 8 t dry matter 2000 m-2 ha-1 y-1 and declined soil erosion 71-75%.

Keywords: hedgerow tithonia, microbial inoculants, organic fertilizer, soil erosion control

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Authors: Salah Belaidi

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We have carried out extensive and in-depth research to search for bioactive compounds based on Algerian plants. A selection of 50 ligands from Algerian medicinal plants. Several compounds used in herbal medicine have been drawn using Marvin Sketch software. We determined the three-dimensional structures of the ligands with the MMFF94 force field in order to prepare these ligands for molecular docking. The 3D protein structure of the SARS-CoV-2 main protease was taken from the Protein Data Bank. We used AutoDockVina software to apply molecular docking. The hydrogen atoms were added during the molecular docking process, and all the twist bonds of the ligands were added using the (ligand) module in the AutoDock software. The COVID-19 main protease (Mpro) is a key enzyme that plays a vital role in viral transcription and mediating replication, so it is a very attractive drug target for SARS-CoV-2. In this work, an evaluation was carried out on the biologically active compounds present in these selected medicinal plants as effective inhibitors of the protease enzyme of COVID-19, with an in-depth computational calculation of the molecular docking using the Autodock Vina software. The top 7 ligands: Phloroglucinol, Afzelin, Myricetin-3-O- rutinosidTricin 7-neohesperidoside, Silybin, Silychristinthat and Kaempferol are selected among the 50 molecules studied which are Algerian medicinal plants, whose selection is based on the best binding energy which is relatively low compared to the reference molecule with binding affinities of -9.3, -9.3, -9, -8.9, -8 .5, 8.3 and -8.3 kcal mol-1 respectively. Then, we analyzed the ADME properties of the best7 ligands using the web server SwissADME. Two ligands (Silybin, Silychristin) were found to be potential candidates for the discovery and design of novel drug inhibitors of the protease enzyme of SARS-CoV-2. The stability of the two ligands in complexing with the Mpro protease was validated by molecular dynamics simulation; they revealed a stable trajectory in both techniques, RMSD and RMSF, by showing molecular properties with coherent interactions in molecular dynamics simulations. Finally, we conclude that the Silybin ligand forms a more stable complex with the Mpro protease compared to the Silychristin ligand.

Keywords: COVID-19, medicinal plants, molecular docking, ADME properties, molecular dynamics

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Authors: Meichen He, Xuan Yang

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Background: In the field of psychotherapy, the role of the family of origin is of utmost importance. Over the past few decades, both individual-oriented and family-oriented approaches to child therapy have shown moderate success in reducing children's psychological and behavioral issues. Objective: However, in exploring how the family of origin influences individuals, it has been noted that there is a lack of comprehensive measurement indicators and an absence of an exact model to assess the impact of the family of origin on individual development. Therefore, this study aims to develop a model based on a literature review regarding the influence of the family of origin on children. Specifically, it will examine the effects of factors such as education level, economic status, maternal age, family integration, family violence, marital conflict, parental substance abuse, and alcohol consumption on children's self-confidence and life satisfaction. Through this research, we aim to further investigate the impact of the family of origin on children and provide directions for future research in positive psychology and psychotherapy. Methods: This study will employ a literature review methodology to gather and analyze relevant research articles on the influence of the family of origin on children. Subsequently, we will conduct quantitative analyses to establish a comprehensive model explaining how family of origin factors affect children's psychological and behavioral outcomes. Findings: the research has revealed that family of origin factors, including education level, economic status, maternal age, family integration, family violence, marital conflict, parental drug and alcohol consumption, have an impact on children's self-confidence and life satisfaction. These factors can affect children's psychological well-being and happiness through various pathways. Implications: The results of this study will contribute to a better understanding of the influence of the family of origin on children and provide valuable directions for future research in positive psychology and psychotherapy. This research will enhance awareness of children's psychological well-being and lay the foundation for improving psychotherapeutic methods.

Keywords: family of origion, positive psychology, developmental psychology, family education, social psychology, educational psychology

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Authors: Lidia Lombardi

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Waste management in Europe and North America is evolving towards sustainable materials management, intended as a systemic approach to using and reusing materials more productively over their entire life cycles. Various waste management strategies are prioritized and ranked from the most to the least environmentally preferred, placing emphasis on reducing, reusing, and recycling as key to sustainable materials management. However, non-recyclable materials must also be appropriately addressed, and waste-to-energy (WtE) offers a solution to manage them, especially when a WtE plant is integrated within a complex system of waste and wastewater treatment plants and potential users of the output flows. To evaluate the environmental effects of such system integration, Life Cycle Assessment (LCA) is a helpful and powerful tool. LCA has been largely applied to the waste management sector, dating back to the late 1990s, producing a large number of theoretical studies and applications to the real world as support to waste management planning. However, LCA still has a fundamental role in helping the development of waste management systems supporting decisions. Thus, LCA was applied to evaluate the environmental performances of a Municipal Solid Waste (MSW) management system, with improved separate material collection and recycling and an integrated network of treatment plants including WtE, anaerobic digestion (AD) and also wastewater treatment plant (WWTP), for a reference study case area. The proposed system was compared to the actual situation, characterized by poor recycling, large landfilling and absence of WtE. The LCA results showed that the increased recycling significantly increases the environmental performances, but there is still room for improvement through the introduction of energy recovery (especially by WtE) and through its use within the system, for instance, by feeding the heat to the AD, to sludge recovery processes and supporting the water reuse practice. WtE offers a solution to manage non-recyclable MSW and allows saving important resources (such as landfill volumes and non-renewable energy), reducing the contribution to global warming, and providing an essential contribution to fulfill the goals of really sustainable waste management.

Keywords: anaerobic digestion, life cycle assessment, waste-to-energy, municipal solid waste

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Authors: Natalia Sáez, Dina Shulfman

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There is an important research gap regarding accessible pedagogical techniques for teaching foreign languages to adults with visual impairments. English as a foreign language (EFL), in particular, is needed in many countries to expand occupational opportunities and improve living standards. Within EFL research, teaching and learning prepositions have only recently gained momentum, considering that they constitute one of the most difficult structures to learn in a foreign language and are fundamental for communicating about spatial relations in the world, both on the physical and imaginary levels. Learning to use prepositions would not only facilitate communication when referring to the surrounding tangible environment but also when conveying ideas about abstract topics (e.g., justice, love, society), for which students’ sociocultural knowledge about space could play an important role. By potentiating visually impaired students’ ability to construe mental spatial imagery, this study made efforts to explore pedagogical techniques that cater to their strengths, helping them create new worlds by welcoming and expanding their sociocultural funds of knowledge as they learn to use English prepositions. Fifteen visually impaired adults living in Chile participated in the study. Their first language was Spanish, and they were learning English at the intermediate level of proficiency in an EFL workshop at La Biblioteca Central para Ciegos (The Central Library for the Blind). Within this workshop, a series of activities and interviews were designed and implemented with the intention of uncovering students’ spatial funds of knowledge when learning literal/physical uses of three English prepositions, namely “in,” “at,” and “on”. The activities and interviews also explored whether students used their original spatial funds of knowledge when learning metaphorical uses of these prepositions and if their use of spatial imagery changed throughout the learning activities. Over the course of approximately half a year, it soon became clear that the students construed mental images of space when learning both literal/physical and metaphorical uses of these prepositions. This research could inform a new approach to inclusive language education using pedagogical methods that are relevant and accessible to students with visual impairments.

Keywords: EFL, funds of knowledge, prepositions, spatial cognition, visually impaired students

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Authors: Ashleigh Beales, Anne Whitworth, Jade Cartwright

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Background: While significant benefits of lexical retrieval intervention are evident within the Primary Progressive Aphasia (PPA) and Alzheimer’s disease (AD) literature, an understanding of the mechanisms that underlie change or improvement is limited. Change mechanisms have been explored in the non-progressive post-stroke literature that may offer insight into how interventions affect change with progressive language disorders. The potential influences of cognitive factors may also play a role here, interacting with the aims of intervention. Exploring how such processes have been applied is likely to grow our understanding of how interventions have, or have not, been effective, and how and why generalisation is likely, or not, to occur. Aims: This review of the literature aimed to (1) investigate the proposed mechanisms of change which underpin lexical interventions, mapping the PPA and AD lexical retrieval literature to theoretical accounts of mechanisms that underlie change within the broader intervention literature, (2) identify whether and which nonlinguistic cognitive functions have been engaged in intervention with these populations and any proposed influence, and (3) explore evidence of linguistic generalisation, with particular reference to change mechanisms employed in interventions. Main contribution: A search of Medline, PsycINFO, and CINAHL identified 36 articles that reported data for individuals with PPA or AD following lexical retrieval intervention. A review of the mechanisms of change identified 10 studies that used stimulation, 21 studies utilised relearning, three studies drew on reorganisation, and two studies used cognitive-relay. Significant treatment gains, predominantly based on linguistic performance measures, were reported for all client groups for each of the proposed mechanisms. Reorganisation and cognitive-relay change mechanisms were only targeted in PPA. Eighteen studies incorporated nonlinguistic cognitive functions in intervention; these were limited to autobiographical memory (16 studies), episodic memory (three studies), or both (one study). Linguistic generalisation outcomes were inconsistently reported in PPA and AD studies. Conclusion: This review highlights that individuals with PPA and AD may benefit from lexical retrieval intervention, irrespective of the mechanism of change. Thorough application of a theory of intervention is required to gain a greater understanding of the change mechanisms, as well as the interplay of nonlinguistic cognitive functions.

Keywords: Alzheimer's disease, lexical retrieval, mechanisms of change, primary progressive aphasia

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Authors: Mesih Kocamuftuoglu, Gonca Ozan, Enver Ozan, Nalan Kaya, Sema Temizer Ozan

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Metabolic Syndrome, one of the common metabolic disorder, occurs with co-development of insulin resistance, obesity, dislipidemia and hypertension problems. Insulin resistance appears to play a pathogenic role in the metabolic syndrome. Also, there is a relationship between insulin resistance and infertility as known. Turmeric (Curcuma longa L.) a polyphenolic chemical is widely used for its coloring, flavoring, and medicinal properties, and exhibits a strong antioxidant activity. In this study, we assess the effects of turmeric on rat uterine tissue in metabolic syndrome model induced by high fructose diet. Thirty-two adult female Wistar rats weighing 220±20 g were randomly divided into four groups (n=8) as follows; control, fructose, turmeric, and fructose plus turmeric. Metabolic syndrome was induced by fructose solution 20% (w/v) in tap water, and turmeric (C.Longa) administered at the dose of 80 mg/kg body weight every other day by oral gavage. After the experimental period of 8 weeks, rats were decapitated, serum and uterine tissues were removed. Serum lipid profile, glucose, insülin levels were measured. Uterine tissues were fixed for histological analyzes. The uterine tissue sections were stained with hematoxylin-eosin (H & E) stain, then examined and photographed on a light microscope (Novel N-800Mx20). As a result, fructose consumption effected serum lipids, insulin levels, and insulin resistance significantly. Endometrium and myometrium layers were observed in normal structure in control group of uterine tissues. Perivascular edema, peri glandular fibrosis, and inflammatory cell increase were detected in fructose group. Sections of the fructose plus turmeric group showed a significant improvement in findings when compared to the fructose group. Turmeric group cell structures were observed similar with the control group. These results demonstrated that high-fructose consumption could change the structure of the uterine tissue. On the other hand, turmeric administration has beneficial effects on uterine tissue at that dose and duration when administered with fructose.

Keywords: metabolic syndrome, rat, turmeric, uterus

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Authors: Djurdjica Perovic, Sanja Pekovic, Tatjana Stanovcic, Jovana Vukcevic

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Tourism development in rural areas calls for a discussion of strategies that would attract more tourists. Several scholars argue that rural areas may become more attractive to tourists by leveraging their cultural heritage. The present paper explores the development of sustainable heritage tourism practices in transitional societies of the Western Balkans, specifically targeting Montenegrin rural areas. It addresses the sustainable tourism as a shift in business paradigm, enhancing the centrality of the host community, fostering the encounters with local culture, customs and heritage and minimizing the environmental and social impact. Disseminating part of the results of the interdisciplinary KATUN project, the paper explores the diversification of economic activities related to the cultural heritage of katuns (temporary settlements in Montenegrin mountainous regions where the agricultural households stay with livestock during the summer season) through sustainable agro-tourism. It addresses the role of heritage tourism in creating more dynamic economy of under-developed mountain areas, new employment opportunities, sources of income for the local community and more balanced regional development, all based on the principle of sustainability. Based on the substantial field research (including interviews with over 50 households and tourists, as well as the number of stakeholders such as relevant Ministries, business communities and media representatives), the paper analyses the strategies employed in raising the awareness and katun-sensitivity of both national and international tourists and stimulating their interest in sustainable agriculture, rural tourism and cultural heritage of Montenegrin mountain regions. Studying the phenomena of responsible tourism and tourists’ consumerist consciousness in Montenegro through development of katuns should allow evaluating stages of sustainability and cultural heritage awareness, closely intertwined with the EU integration processes in the country. Offering deeper insight at the relationship between rural tourism, sustainable agriculture and cultural heritage, the paper aims to understand if cultural heritage of the area is valuable for agro-tourism development and in which context.

Keywords: heritage tourism, sustainable tourism, added value, Montenegro

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Authors: Kunyu Yan

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Early childhood music education plays a significant role in an individual’s growth. Music can help children understand themselves and relate to others, and make connections between family, school, and society. In recent years, with the development of early childhood education in China, an increasing number of kindergartens have been established, and many of them pay more attention to music education. This research has two main aims. One is to discover how and why music is used in both public and private kindergartens. The second aim is to make recommendations for widening the use of music in kindergartens. In order to achieve these aims, the research uses two main methods. Firstly, it considers the historical background and cultural context of early childhood education in China; and secondly, it uses an approach that compares public and private kindergartens. In this research, six kindergartens were chosen from Qingdao city in Shandong Province as case studies, including 3 public kindergartens and 3 private kindergartens. This research was based on using three types of data collection methods: observation, semi-structured interviews with teachers, and questionnaires with parents. Participant and non-participant observational methods were used and included in daily routines at the kindergartens in order to experience the situation of music education first-hand. Interviews were associated with teachers’ views of teaching and learning music, the perceptions of the music context, and their strategies of using music. Lastly, the questionnaire was designed to obtain the views of current music education from the children’s parents in the respective kindergartens. The results are shown with three main themes: (1) distinct characteristics of public kindergartens (e.g., similar equipment, low tuition fee, qualified teachers, etc); (2) distinct characteristics of private kindergartens (e.g., various tuition fees, own teaching system, trained teachers, etc); and (3) differences between public and private kindergartens (e.g., funding, requirements for teachers, parents’ demands, etc). According to the results, we can see that the main purpose of using music in China is to develop the musical ability of children, and teachers focus on musical learning, such as singing in tune and playing instruments. However, as revealed in this research, there are many other uses and functions of music in these educational settings, including music used for non-musical learning (e.g., counting, learning language, etc.) or in supporting social routines.

Keywords: differences between private and public school, early childhood education, music education, uses and functions of music

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Authors: Kamila Fethallah, Mahmoud Mekadem, Hamid Ouali

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Active flow control around a cylinder is an extensively studied subject in aerodynamics. Researchers apply a range of techniques to alter the fluid flow surrounding a cylindrical body, with the intent of reducing drag, enhancing lift, and optimizing overall aerodynamic performance. This study investigates the manipulation of flow dynamics around a circular cylinder by introducing an original elliptical cylindrical deformation to the traditionally straight section. Through the use of a crank mechanism, precise control of the deformation is achieved, allowing a comprehensive examination of its effects on fluid flow patterns. The main objective of this research is to evaluate the effectiveness of this advanced approach in reducing the drag coefficient and modifying the wake pattern, providing valuable information on flow control and optimization. Experimental results show that varying deformation amplitudes (10%, 15% and 20%) and control frequencies strongly influence drag and flow structure, the maximum reduction in drag coefficient (approximately 44%) observed at 15% amplitude and optimum frequency. The flow structure is strongly influenced by the deformation amplitude and frequency, particularly in the frequency range close to that of the natural shedding. These results suggest that the deformation frequency and amplitude play a crucial role in modifying the flow structure and reducing the drag coefficient. Numerical simulations further support the efficiency of the active flow control technique using cylindrical-elliptical deformation, underlining a consistent drag reduction of up to 42% at extreme deformation conditions (100%). The present study aims at highlighting the potential of this original approach in the enhancement of efficiency and performance of systems involved in energy exchange with fluids. Concluding this, the current study offers fresh routes toward the development of flow control and optimization strategies in a wide range of engineering applications.

Keywords: control frequencies, deformation amplitudes, drag coefficient, elliptical cylindrical deformation, flow dynamics, wake pattern

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Authors: Sima Aznavi, Poria Fajri, Hanif Livani

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Smart homes are small energy systems which may be equipped with renewable energy sources, storage devices, and loads. Energy management strategy plays a main role in the efficient operation of smart homes. Effective energy scheduling of the renewable energy sources and storage devices guarantees efficient energy management in households while reducing the energy imports from the grid. Nevertheless, despite such strategies, independently day ahead energy schedules for multiple households can cause undesired effects such as high power exchange with the grid at certain times of the day. Therefore, the interactions between multiple smart home day ahead energy projections is a challenging issue in a smart grid system and if not managed appropriately, the imported energy from the power network can impose additional burden on the distribution grid. In this paper, a central energy management strategy for a network consisting of multiple households each equipped with renewable energy sources, storage devices, and Plug-in Electric Vehicles (PEV) is proposed. The decision-making strategy alongside the smart home energy management system, minimizes the energy purchase cost of the end users, while at the same time reducing the stress on the utility grid. In this approach, the smart home energy management system determines different operating scenarios based on the forecasted household daily load and the components connected to the household with the objective of minimizing the end user overall cost. Then, selected projections for each household that are within the same cost range are sent to the central decision-making system. The central controller then organizes the schedules to reduce the overall peak to average ratio of the total imported energy from the grid. To validate this approach simulations are carried out for a network of five smart homes with different load requirements and the results confirm that by applying the proposed central energy management strategy, the overall power demand from the grid can be significantly flattened. This is an effective approach to alleviate the stress on the network by distributing its energy to a network of multiple households over a 24- hour period.

Keywords: energy management, renewable energy sources, smart grid, smart home

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Authors: Debi Konukcu Onal, Tarkan Cavusoglu

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In modern societies, the costs of public goods and services are shared through taxes paid by citizens. However, taxation has always been a frictional issue, as tax obligations are perceived to be a financial burden for taxpayers rather than being merit that fulfills the redistribution, regulation and stabilization functions of the welfare state. The tax compliance literature evolves into discussing why people still pay taxes in systems with low costs of legal enforcement. Related empirical and theoretical works show that a wide range of socially oriented behavioral factors can stimulate voluntary compliance and subversive effects as well. These behavioral motivations are argued to be driven by self-enforcing rules of informal institutions, either independently or through interactions with legal orders set by formal institutions. The main focus of this study is to investigate empirically whether institutional particularities have a significant role in explaining the cross-country differences in the tax noncompliance levels. A part of the controversy about the driving forces behind tax noncompliance may be attributed to the lack of empirical evidence. Thus, this study aims to fill this gap through regression estimates, which help to trace the link between institutional quality and noncompliance on a cross-country basis. Tax evasion estimates of Buehn and Schneider is used as the proxy measure for the tax noncompliance levels. Institutional quality is quantified by three different indicators (percentile ranks of Worldwide Governance Indicators, ratings of the International Country Risk Guide, and the country ratings of the Freedom in the World). Robust Least Squares and Threshold Regression estimates based on the sample of the Organization for Economic Co-operation and Development (OECD) countries imply that tax compliance increases with institutional quality. Moreover, a threshold-based asymmetry is detected in the effect of institutional quality on tax noncompliance. That is, the negative effects of tax burdens on compliance are found to be more pronounced in countries with institutional quality below a certain threshold. These findings are robust to all alternative indicators of institutional quality, supporting the significant interaction of societal values with the individual taxpayer decisions.

Keywords: institutional quality, OECD economies, tax compliance, tax evasion

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Authors: Joane Adeclas, Yoonyoung Kim, Taekyun Hur

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This study investigates individual’s intrinsic motivation to practice their leisure activities, as well as, how the cultural environment may influence their motivation to practice their activities. Focused on the positive psychology, the present study proposed redefinition of leisure activities considering two factors. First, leisure activities could be as any activities that provide pleasure or meaning to individuals. Second, they can be practiced alone or in groups. In fact, based on this definition, a four-dimensional model of leisure activities was developed, to measure individual’s perception of their leisure experience, based on four factors that are: personal pleasure, social pleasure, personal meaning and social meaning. Furthermore, recent studies have argued that leisure activities can be interpreted and understood differently across cultures. Therefore, the present study proposed to examine the possible role of the cultural context of individual’s leisure practices. To do so, two cultural groups (Koreans vs. French) were compared in terms of the four-dimensional model of leisure activities. Three hundred Koreans and three hundred French participants were asked to answer an online survey about their leisure activities. Participants had to respond to questions related to several aspects of leisure practices as followed: the reason why their practice their leisure activities, the reason why they fail to practice their leisure, and their obsession relate to their leisure activities. Factor analyses based on participant’s responses proposed a moderate fit of the four-dimensional model of leisure activities. Furthermore, significant cultural differences were also found. As a result, the cultural context seems to influence the reason why individuals practice their leisure activities based on our model. In fact, Koreans explained more than French, the practice of their leisure activities with social-pleasurable reasons. At a contrary, French explained more than Koreans, the practice of their leisure activities with social-meaningful reasons. The two cultural groups also significantly differ on their perception of failure. The results showed that French participants used more meaningful social factors to explain why they failed to practice their leisure activities than did Koreans participants. Finally, Koreans and French significantly differed regarding their obsession on their leisure activities. In general, French tend to have more obsession than Koreans about their leisure activities. Those results validated the four-dimensional model of leisure, as well as, the cultural differences in leisure practices. However, further studies are needed to validate this model at an individual and cultural level.

Keywords: culture, leisure, meaning, pleasure

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Authors: O. Anwar Beg, Armghan Zubair, Sireetorn Kuharat, Meisam Babaie

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In this work, motivated by rocket channel cooling applications, we describe recent CFD simulations of turbulent convective heat transfer in mini-channels at different aspect ratios. ANSYS FLUENT software has been employed with a mean average error of 5.97% relative to Forrest’s MIT cooling channel study (2014) at a Reynolds number of 50,443 with a Prandtl number of 3.01. This suggests that the simulation model created for turbulent flow was suitable to set as a foundation for the study of different aspect ratios in the channel. Multiple aspect ratios were also considered to understand the influence of high aspect ratios to analyse the best performing cooling channel, which was determined to be the highest aspect ratio channels. Hence, the approximate 28:1 aspect ratio provided the best characteristics to ensure effective cooling. A mesh convergence study was performed to assess the optimum mesh density to collect accurate results. Hence, for this study an element size of 0.05mm was used to generate 579,120 for proper turbulent flow simulation. Deploying a greater bias factor would increase the mesh density to the furthest edges of the channel which would prove to be useful if the focus of the study was just on a single side of the wall. Since a bulk temperature is involved with the calculations, it is essential to ensure a suitable bias factor is used to ensure the reliability of the results. Hence, in this study we have opted to use a bias factor of 5 to allow greater mesh density at both edges of the channel. However, the limitations on mesh density and hardware have curtailed the sophistication achievable for the turbulence characteristics. Also only linear rectangular channels were considered, i.e. curvature was ignored. Furthermore, we only considered conventional water coolant. From this CFD study the variation of aspect ratio provided a deeper appreciation of the effect of small to high aspect ratios with regard to cooling channels. Hence, when considering an application for the channel, the geometry of the aspect ratio must play a crucial role in optimizing cooling performance.

Keywords: rocket channel cooling, ANSYS FLUENT CFD, turbulence, convection heat transfer

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Authors: Rai Sachindra Prasad

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Thought is physical force. This has been well recognized but hardly translated visually or otherwise in the sense of its transfer from one individual to another. In the present world of chaos and disorder with yawning gaps between right and wrong thinking individuals, if it is possible to transfer the right thoughts to replace the wrong ones it would indeed be a great achievement in the present situation of the world which is torn with violence with dangerous thoughts of individuals. Moreover, such a possibility would completely remove the barrier of language between two persons, which at times proves to be a great obstacle in realizing a desired purpose. If a proper instrumentation scheme containing appropriate transducers and electronics is designed and implemented to realize this thought ransfer phenomenon, this would prove to be extremely useful when properly used. Considering the advancements already made in recording the nerve impulses in the brain, which are electrical events of very short durations that move along the axon, it is conceivable that this may be used to good effect in implementing the scheme. In such a proposition one shoud consider the roles played by pineal body, pituitary gland and ‘association’ areas. Pioneer students of brain have thought that associations or connections between sensory input and motor output were made in these areas. It is currently believed that rather than being regions of simple sensory-motor connections, the association areas process and integrate sensory information relayed to them from the primary sensory areas of the cortex and from the thalamus, after the information has been processed, it may be sent to motor areas to be acted upon. Again, even though the role played by pineal body is not known fully to neurologists its interconnection with pituitary gland is a matter of great significance to the ‘Rishis’ and; Seers’ s described in Vedas and Puranas- the ancient Holy books of Hindus. If the pineal body is activated through meditation it would control the pituitary gland thereby the individual’s thoughts and acts. Thus, if thoughts can be picked up by special transducers, these can be connected to suitable electronics circuitry to amplify the signals. These signals in the form of electromagnetic waves can then be transmitted using modems for long distance transmission and eventually received by or passed on to a subject of interest through another set of electronics circuit and devices.

Keywords: modems, pituitary gland, pineal body, thought transfer

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Authors: Chiara Della Rocca, Gavino Piras, Andrea Berti, Alessandro Mameli

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DNA identification of human skeletal remains plays a valuable role in the forensic field, especially in missing persons and mass disaster investigations. Hard tissues, such as bones and teeth, represent a very common kind of samples analyzed in forensic laboratories because they are often the only biological materials remaining. However, the major limitation of using these compact samples relies on the extremely time–consuming and labor–intensive treatment of grinding them into powder before proceeding with the conventional DNA purification and extraction step. In this context, a DNA extraction assay called the TBone Ex kit (DNA Chip Research Inc.) was developed to digest bone chips without powdering. Here, we simultaneously analyzed bone and tooth samples that arrived at our police laboratory and belonged to 15 different forensic casework that occurred in Sardinia (Italy). A total of 27 samples were recovered from different scenarios and were exposed to extreme environmental factors, including sunlight, seawater, soil, fauna, vegetation, and high temperature and humidity. The TBone Ex kit was used prior to the EZ2 DNA extraction kit on the EZ2 Connect Fx instrument (Qiagen), and high-quality autosomal and Y-chromosome STRs profiles were obtained for the 80% of the caseworks in an extremely short time frame. This study provides additional support for the use of the TBone Ex kit for digesting bone fragments/whole teeth as an effective alternative to pulverization protocols. We empirically demonstrated the effectiveness of the kit in processing multiple bone samples simultaneously, largely simplifying the DNA extraction procedure and the good yield of recovered DNA for downstream genetic typing in highly compromised forensic real specimens. In conclusion, this study turns out to be extremely useful for forensic laboratories, to which the various actors of the criminal justice system – such as potential jury members, judges, defense attorneys, and prosecutors – required immediate feedback.

Keywords: DNA, skeletal remains, bones, tbone ex kit, extreme conditions

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Authors: Aymen Arfaoui, Abdelkader Soumaya, Ali Kadri, Noureddine Ben Ayed

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The major contractional events characterized by strike-slip faulting, folding, and thrusting occurred in the Eocene, Late Miocene, and Quaternary along with the NE Tunisian domain between Bou Kornine-Ressas- Msella and Cap Bon Peninsula. During the Plio-Quaternary, the Grombalia and Mornag grabens show a maximum of collapse in parallelism with the NNW-SSE SHmax direction and developed as 3rd order extensive regions within a regional compressional regime. Using available tectonic and geophysical data supplemented by new fault-kinematic observations, we show that Cenozoic deformations are dominated by first order N-S faults reactivation, this sinistral wrench system is responsible for the formation of strike-slip duplexes, thrusts, folds, and grabens. Based on our new structural interpretation, the major faults of N-S Axis, Bou Kornine-Ressas-Messella (MRB), and Hammamet-Korbous (HK) form an N-S first order restraining stepover within a left-lateral strike-slip duplex. The N-S master MRB fault is dominated by contractional imbricate fans, while the parallel HK fault is characterized by a trailing of extensional imbricate fans. The Eocene and Miocene compression phases in the study area caused sinistral strike-slip reactivation of pre-existing N-S faults, reverse reactivation of NE-SW trending faults, and normal-oblique reactivation of NW-SE faults, creating a NE-SW to N-S trending system of east-verging folds and overlaps. Seismic tomography images reveal a key role for the lithospheric subvertical tear or STEP fault (Slab Transfer Edge Propagator) evidenced below this region on the development of the MRB and the HK relay zone. The presence of extensive syntectonic Pliocene sequences above this crustal scale fault may be the result of a recent lithospheric vertical motion of this STEP fault due to the rollback and lateral migration of the Calabrian slab eastward.

Keywords: Tunisia, strike-slip fault, contractional duplex, tectonic stress, restraining stepover, STEP fault

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Authors: Yutong Wan, John N. Wood

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Introduction: SCN9A encoded Nav1.7 is an ideal therapeutic target with minimal side effects for the pharmaceutical industry because SCN9A variants can cause both human gains of function pain-related mutations and loss of function pain-free mutations. This study reviews the clinical effectiveness of existing Nav1.7 inhibitors, which theoretically should be powerful analgesics. Methods: A systematic review is conducted on the effectiveness of current Nav1.7 blockers undergoing clinical trials. Studies were mainly extracted from PubMed, U.S. National Library of Medicine Clinical Trials, World Health Organization International Clinical Trials Registry, ISRCTN registry platform, and Integrated Research Approval System by NHS. Only studies with full text available and those conducted using double-blinded, placebo controlled, and randomised designs and reporting at least one analgesic measurement were included. Results: Overall, 61 trials were screened, and eight studies covering PF 05089771 (Pfizer), TV 45070 (Teva & Xenon), and BIIB074 (Biogen) met the inclusion criteria. Most studies were excluded because results were not published. All three compounds demonstrated insignificant analgesic effects, and the comparison between PF 05089771 and pregabalin/ibuprofen showed that PF 05089771 was a much weaker analgesic. All three drug candidates only have mild side effects, indicating the potentials for further investigation of Nav1.7 antagonists. Discussion: The failure of current Nav1.7 small molecule inhibitors might attribute to ignorance of the key role of endogenous systems in Nav1.7 null mutants, the lack of selectivity and blocking potency, and central impermeability. The synergistic combination of analgesic drugs, a recent UCL patent, combining a small dose of Nav1.7 blockers and opioids or enkephalinase inhibitors dramatically enhanced the analgesic effects. Conclusion: The current clinical testing Nav1.7 blockers are generally disappointing. However, the newer generation of Nav1.7 targeting analgesics has overcome the major constraints of its predecessors.

Keywords: chronic pain, Nav1.7 blockers, SCN9A, systematic review

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Authors: Yueh Hsiu Giffen Cheng, Teng Jung Wang

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According to the study of British national advisory council on creative and cultural education（NACCCE, what the present and the future need awesome innovative and creative people from the perspective of commercial human resources. Therefore, we can know from above, creativity plays an important role in today’s enterprise indeed. Besides, many companies are aimed at developing team work as their main goal, so “creativity” and “teamwork” become more and more important factors to succeed and team creativity also turn into an important issue gradually. Then, the study takes in-depth interviews of design companies’ leaders and uses self-designed questionnaire regarding affecting team creativity to conduct cross-analysis. The results show that for those creative-oriented integrated design companies, their design strategies don’t begin until data collection and their scripts are usually the best way to inspire creativity. Besides, passing down a legacy of experiences are their common educational training. Most important of all, their organizational resources and leaders can assist all the team to learn and grow effectively and the good interaction between the leader and the member can also bring work flexibility and efficiency. In short, the leader’s expectation of members’ performance can cause them to encourage each other to progress. Moreover, the analysis of questionnaire indicates that members who are open-minded and leaders who have transformational leadership style can both help to establish a good team interaction. Furthermore, abundant resources and training system are also good approaches to establish a harmonious relationship. Finally, through integrating the outcomes of interviews and questionnaires, we can infer that those integrated design companies’ circumstances of design progress are mainly from their leaders’ guidance. In addition, the analysis of design problems are focused on their creative strategies and their scripts and sketches can also inspire their creativity. In sum, the feature of all team is influenced by 4 factors: leaders who have transformational leadership style, open-minded members, flexible working environment, resources and interactive relationship. Ultimately, the study hopes that the result above can apply to the design-related industries or help general companies elevate the team creativity.

Keywords: creativity, team creativity, integrated design companies, design process

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Authors: Hager Elsheikh, Juliane Glaubitz, Frank Ulrich Weiss, Matthias Sendler

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Aim: Acute pancreatitis (AP) and chronic pancreatitis (CP) are both accompanied by a prominent immune response which influences the course of disease. Whereas during AP the pro-inflammatory immune response dominates, during CP a fibroinflammatory response regulates organ remodeling. The transcription factor signal transducer and activator of transcription 6 (STAT6) is a crucial part of the Type 2 immune response. Here we investigate the role of STAT6 in a mouse model of AP and CP. Material and Methods: AP was induced by hourly repetitive i.p. injections of caerulein (50µg/kg/bodyweight) in C57Bl/6 J and STAT6-/- mice. CP was induced by repetitive caerulein injections 6 times a day, 3 days a week over 4 weeks. Disease severity was evaluated by serum amylase/lipase measurement, H&E staining of pancreas. Pancreatic infiltrate was characterized by immunofluorescent labeling of CD68, CD206, CCR2, CD4 and CD8. Pancreas fibrosis was evaluated by Azan blue staining. qRT-PCR was performed of Arg1, Nos2, Il6, Il1b, Col3a, Socs3 and Ym1. Affymetrix chip array analyses were done to illustrate the IL4/IL13/STAT6 signaling in bone marrow derived macrophages. Results: AP severity is mitigated in STAT6-/- mice, as shown by decreased serum amylase and lipase, as well as histological damage. CP mice surprisingly showed only slightly reduced fibrosis of the pancreas. Also staining of CD206 a classical marker of alternatively activated macrophages showed no decrease of M2-like polarization in the absence of STAT6. In contrast, transcription profile analysis in BMDM showed complete blockade of the IL4/IL13 pathway in STAT6-/- animals. Conclusion: STAT6 signaling pathway is protective during AP and mitigates the pancreatic damage. During chronic pancreatitis the IL4/IL13 – STAT6 axisis involved in organ fibrogenesis. Notably, fibrosis is not dependent on a single signaling pathway, and alternative macrophage activation is also complex and involves different subclasses (M2a, M2b, M2c and M2d) which could be independent of the IL4/IL13 STAT6 axis.

Keywords: chronic pancreatitis, macrophages, IL4/IL13, Type immune response

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