Search results for: structural characterization

Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi

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Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.

Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation

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Authors: Umedov Mekhroz, Griaznova Svetlana

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In connection with the growth of oncological diseases, the design of centers for diagnostics and the production of radiopharmaceuticals is the most relevant area of healthcare facilities. The design of new nuclear medicine centers should be carried out from the standpoint of solving the following tasks: the availability of medical care, functionality, environmental friendliness, sustainable development, improving the safety of drugs, the use of which requires special care, reducing the rate of environmental pollution, ensuring comfortable conditions for the internal microclimate, adaptability. The purpose of this article is to substantiate architectural and planning solutions, formulate recommendations and principles for the design of nuclear medicine centers and determine the connections between the production and medical functions of a building. The advantages of combining the production of radiopharmaceuticals and the department of medical care: less radiation activity is accumulated, the cost of the final product is lower, and there is no need to hire a transport company with a special license for transportation. A medical imaging department is a structural unit of a medical institution in which diagnostic procedures are carried out in order to gain an idea of the internal structure of various organs of the body for clinical analysis. Depending on the needs of a particular institution, the department may include various rooms that provide medical imaging using radiography, ultrasound diagnostics, and the phenomenon of nuclear magnetic resonance. The production of radiopharmaceuticals is an object intended for the production of a pharmaceutical substance containing a radionuclide and intended for introduction into the human body or laboratory animal for the purpose of diagnosis, evaluation of the effectiveness of treatment, or for biomedical research. The research methodology includes the following subjects: study and generalization of international experience in scientific research, literature, standards, teaching aids, and design materials on the topic of research; An integrated approach to the study of existing international experience of PET / CT scan centers and the production of radiopharmaceuticals; Elaboration of graphical analysis and diagrams based on the system analysis of the processed information; Identification of methods and principles of functional zoning of nuclear medicine centers. The result of the research is the identification of the design principles of nuclear medicine centers with the functions of the production of radiopharmaceuticals and the department of medical imaging. This research will be applied to the design and construction of healthcare facilities in the field of nuclear medicine.

Keywords: architectural planning solutions, functional zoning, nuclear medicine, PET/CT scan, production of radiopharmaceuticals, radiotherapy

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Authors: Doreen Chemutai

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While women's parliamentary representation has increased over the years, most women contest the affirmative action seat (A.A). There is a lack of knowledge on why women prefer the affirmative seat vis- a- vis the open seat. This study argues that comparing women's path on the reserved and open seat to parliamentary representation enables us to pass judgment on why this trend continues. This paper provides a narrative analysis of women members of parliament's (MPs) trajectory in the open seat and Affirmative Action seat to parliamentary representation. Purposive sampling was used to select participants from the Northern Uganda districts of Kitgum, Pader, Oyam, Agago, and Gulu. The eight women MPs chosen for the study completed in-depth interviews exploring their qualifications, careers, and experiences before joining the political office, their party affiliation, and the kind of seat they currently occupy in the 10th parliament. Findings revealed similarities between women on the open and reserved to include; women generally irrespective of the seat they choose to contest for find it difficult to win elections because voters doubt women's effectiveness as leaders. All women as incumbents find it difficult to be re-elected because their evaluation is harsher than that for men. Findings also revealed that women representatives are motivated by their personal lived experiences, community work, educational leadership, and local leadership. The study establishes that the popularity of the party in a given geographical location and the opponents' quality will determine the success of the parliamentary candidate in question irrespective of whether one is contesting on the open or Affirmative seat. However, the study revealed differences between MPs' experiences in the quest for the parliamentary seat, females on the open seat are subjected to gender discrimination in elections by party leadership, stereotyped, and are victims of propaganda in the initial contesting stages. Women who win elections in the open seat have to be superior to their male opponents. In other circumstances where a woman emerges successful, she may be voted for due to other reasons beyond capability, such as physical appearance or sociability. On the other hand, MPs' revelations on affirmative action seats show that the political terrain is smoother despite larger constituencies. Findings show that women on the Affirmative Action seat do not move to the open seat because of the comfort associated with the seat and maintain consistency, since the constituencies doubt the motives of representatives who change from one seat to another. The study concludes that women MPs who contest on the open seat are likely to suffer structural barriers such as gender discrimination and political recruitment bias instead of women on the affirmative seat. This explains why the majority of women contest on the affirmative seat.

Keywords: affirmative action seats, open seats, parliamentary representation, pathways

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Authors: Yingyi Luo

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Cross-border surrogacy is seen by many as a market in which women are bought and sold commodities at risk of trafficking. A surrogate can be framed as either a fully acknowledged subject, with whom intended parents engage in cross-border surrogacy—or as a tool utilized by intended parents and surrogacy facilitators in the furtherance of their own objectives. In order to identify which frame prevails, this paper applies subjectivity theory to an empirical study of cross-border surrogacy facilitated by facilitators in Australia analysing interviews with surrogate agents, counsellors and lawyers, and observations at trade show. The aim of the paper is to advance understanding of the dynamics of the relationship between intended parents, surrogates, and surrogacy facilitators by collecting new data and applying unique framework. As dominant players, surrogacy facilitators have a significant impact on determining the nature of cross-border surrogacy. However, little is known concerning the manner in which facilitators influence the inter-subjectivity between surrogate mothers and intended parents. Thus, this paper intends to identify how facilitators depict surrogate mothers, the degree to which their perspectives bear upon both the subjectivity of the surrogate mother and the relationship of intended parents with surrogate mothers. For the purpose of introducing and developing this framework in the context of cross-border surrogacy, this paper borrows from the work of theorists not often mentioned in bioethics, including Jacques Lacan, Marco Cavallaro, Michel Foucault, and others. It also applies the concept of 'the gaze' along with the dynamic of 'self' and 'other' to the cross-border surrogacy arrangement. Applying the concept of the gaze can provide a new way to interpret the power dynamic that plays out among surrogacy facilitators, intended parents, and surrogates within the commercial surrogacy arrangement and how the subjectivity is produced through the power. Viewing the relationships between the players in cross-border surrogacy through the lens of gaze theory, this paper finds that, in cross-border surrogacy, due to the structural power imbalance, affluent intended parents and surrogacy facilitators are possessors of the gaze, while surrogate mothers are under the thrall of the gaze. Specifically, facilitators frame surrogate mothers' reproductive abilities as commodities that intended parents can purchase to fulfil their urgent need to have children and experience full subjectivity, and they take a cut of the money that paid by intended parents. Therefore, commodification of the body results in degrading a surrogate mother (the object), reifying her as no more than a walking womb (the other), a process which is highly detrimental to the self of surrogate mothers. This relationship, formalized through contractual means, allows intended parents and facilitators to take advantage of surrogate mothers in the furtherance of their own objectives. This argument is enriched by new data from interviews and observations that provide nuance to this understanding of inter-subjectivity.

Keywords: cross-border surrogacy, facilitators, self, surrogate mothers

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Authors: Sedigheh Kalantari

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Like many countries in the arid and semi-arid belt, Iran experiences a natural limitation in the availability of water resources. However, rapid socioeconomic development has created a serious water crisis in a nation that was once one of the world’s pioneers in sustainable water management, due to the Persians’ contribution to hydraulic engineering inventions – the Qanat – throughout history. The exogenous issues like the changing climate, frequent droughts, and international sanctions are only crisis catalyzers, not the main cause of the water crisis; and a resilient water management system is expected to be capable of coping with these periodic external pressures. The current dramatic water security issues in Iran are rooted in managerial, political, and institutional challenges rather than engineering and technical issues, and the country is suffering from challenges in water governance. The country, instead of rigorous water conservation efforts, is still focused on supply-driven approach, technology and centralized methods, and structural solutions that aim to increase water supply; while the effectiveness of water governance and management has often left unused. To solve these issues, it is necessary to assess the present situation and its evolution over time. In this respect, establishing water governance assessment mechanisms will be a significant aspect of this paper. The research framework, however, is a conceptual framework to assess governance performance of Iran to critically diagnose problematic issues and areas, as well as proffer empirically based solutions and determine the best possible steps towards transformational processes. This concept aims to measure the adequacy of current solutions and strategies designed to ameliorate these problems and then develop and prescribe adequate futuristic solutions. Thus, the analytical framework developed in this paper seeks to provide insights on key factors influencing water governance in Iranian cities, institutional frameworks to manage water across scales and authorities, multi-level management gaps and policy responses, through an evidence-based approach and good practices to drive reform toward sustainability and water resource conservation. The findings of this paper show that the current structure of the water governance system in Iran, coupled with the lack of a comprehensive understanding of the root causes of the problem, leaves minimal hope for developing sustainable solutions to Iran’s increasing water crisis. In order to follow sustainable development approaches, Iran needs to replace symptom management with problem prevention.

Keywords: governance, Iran, sustainable development, water management, water resources

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Authors: Antonella Di Sotto, Cinzia Ingallina, Caterina Fraschetti, Simone Circi, Marcello Locatelli, Simone Carradori, Gabriela Mazzanti, Luisa Mannina, Silvia Di Giacomo

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Cannabis sativa L. is one of the oldest cultivated plant species known not only for its voluptuous use but also for the wide application in food, textile, and therapeutic industries. Recently, the progress of biotechnologies applied to medicinal plants has allowed to produce different hemp varieties with low content of psychotropic phytoconstituents (tetrahydrocannabinol < 0.2% w/v), thus leading to a renewed industrial and therapeutic interest for this plant. In this context, in order to discover new potential remedies of pharmaceutical and/or nutraceutical interest, the chemopreventive properties of different organic and hydroalcoholic extracts, obtained from the inflorescences of C. sativa L. var. USO31, collected in June and September harvesting, were assessed. Particularly, the antimutagenic activity towards the oxidative DNA-damage induced by tert-butyl hydroperoxide (t-BOOH) was evaluated, and the DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid) radical scavenging power of the samples were assessed as possible mechanisms of antimutagenicity. Furthermore, the ability of the extracts to inhibit the glucose-6-phosphate dehydrogenase (G6PD), whose overexpression has been found to play a critical role in neoplastic transformation and tumor progression, has been studied as a possible chemopreventive strategy. A careful phytochemical characterization of the extracts for phenolic and terpenoid composition has been obtained by high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) methods. Under our experimental condition, all the extracts were found able to interfere with the tBOOH-induced mutagenicity in WP2uvrAR strain, although with different potency and effectiveness. The organic extracts from both the harvesting periods were found to be the main effective antimutagenic samples, reaching about a 55% inhibition of the tBOOH-mutagenicity at the highest concentration tested (250 μg/ml). All the extracts exhibited radical scavenger activity against DPPH and ABTS radicals, with a higher potency of the hydroalcoholic samples. The organic extracts were also able to inhibit the G6PD enzyme, being the samples from September harvesting the highly potent (about 50% inhibition respect to the vehicle). At the phytochemical analysis, all the extracts resulted to contain both polar and apolar phenolic compounds. The HPLC analysis revealed the presence of catechin and rutin as the major constituents of the hydroalcoholic extracts, with lower levels of quercetin and ferulic acid. The monoterpene carvacrol was found to be an ubiquitarian constituent. At GC-MS analysis, different terpenoids, among which caryophyllene sesquiterpenes, were identified. This evidence suggests a possible role of both polyphenols and terpenoids in the chemopreventive properties of the extracts from the inflorescences of C. sativa var. USO31. According to the literature, carvacrol and caryophyllene sesquiterpenes can contribute to the strong antimutagenicity although the role of all the hemp phytocomplex cannot be excluded. In conclusion, present results highlight a possible interest for the inflorescences of C. sativa var. USO31 as source of bioactive molecules and stimulate further studies in order to characterize its possible application for nutraceutical and pharmaceutical purposes.

Keywords: antimutagenicity, glucose-6-phosphate dehydrogenase, hemp inflorescences, nutraceuticals, sesquiterpenes

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Authors: Jovie Esquivias Nicolas, Ron Aldrin Lontoc Austria, Crisabelle Belleza Bautista, Mariane Chiho Espinosa Bundalian, Owwen Kervy Del Rosario Castillo, Mary Angelyn Mercado Dela Cruz, Heinrich Theraja Recana De Luna, Chriscell Gipanao Eustaquio, Desiree Laine Lauz Gilbas, Jordan Ignacio Legaspi, Larah Denise David Madrid, Charles Linelle Malapote Mendoza, Hazel Maxine Manalad Reyes, Carl Justine Nabora Saberdo, Claire Mae Rendon Santos

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In response to the global race in discovering the next advanced sustainable material that will reduce our ecological footprint, the researchers aimed to create a masonry unit which is competent in physical edifices and other constructional facets. From different proven researches, mycelium has been concluded that when dried can be used as a robust and waterproof building material that can be grown into explicit forms, thus reducing the processing requirements. Hypothesizing inclusive measures to attest fungi’s impressive structural qualities and absorbency, the researchers projected to perform comparative analyses in creating mycelium bricks from mushroom spores of G. lucidum. Three treatments were intended to classify the most ideal concentration of clay and substrate fixings. The substrate bags fixed with 30% clay and 70% mixings indicated highest numerical frequencies in terms of full occupation of fungal mycelia. Subsequently, sorted parts of white portions from the treatment were settled in a thermoplastic mold and burnt. Three proportional concentrations of cultivated substrate and cement were also prioritized to gather results of variation focused on the weights of the bricks in the Water Absorption Test and Durability Test. Fungal inoculums with solutions of cement showed small to moderate amounts of decrease and increase in load. This proves that the treatments did not show any significant difference when it comes to strength, efficiency and absorption capacity. Each of the concentration is equally valid and could be used in supporting the worldwide demands of creating numerous bricks while also taking into consideration the recovery of our nature.

Keywords: mycelium, fungi, fungal mycelia, durability test, water absorption test

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Authors: Noelene Rose

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The DSM has been plagued with conceptual issues since its inception, not least discriminant validity and comorbidity issues. An attempt to remain a-theoretical in the divide between the psycho-dynamicists and the behaviourists contributed to much of this, in particular relating to the Personality Disorders. With the DSM-5, although the criterion have remained unchanged, major conceptual and structural directions have been flagged and proposed in section III. The biggest changes concern the Personality Disorders. While Narcissistic Personality Disorder (NPD) was initially tagged for removal, instead the addition of section III proposes a move away from a categorical approach to a more dimensional approach, with a measure of Global Function of Personality. This global measure is an assessment of impairment of self-other relations; a measure of trait narcissism. In the same way mainstream psychology has struggled in its diagnosis of narcissism, so too in its treatment. Kohut’s self psychology represents the most significant inroad in theory and treatment for the narcissistic disorders. Kohut had moved away from a categorical system, towards disorders of the self. According to this theory, disorders of the self are the result of childhood trauma (impaired attunement) resulting in a developmental arrest. Self-psychological, Psychodynamic treatment of narcissism, however, is expensive, in time and money and outside the awareness or access of most people. There is more than a suggestion that narcissism is on the increase, created in trauma and worsened by a fearful world climate. A dimensional model of narcissism, from mild to severe, requires cut off points for diagnosis. But where do we draw the line? Mainstream psychology is inclined to set it high when there is some degree of impairment in functioning in daily life. Transpersonal Psychology is inclined to set it low, with the concept that we all have some degree of narcissism and that it is the point and the path of our life journey to transcend our focus on our selves. Mainstream psychology stops its focus on trait narcissism with a healthy level of self esteem, but it is at this point that Transpersonal Psychology can complement the discussion. From a Transpersonal point of view, failure to begin the process of self-transcendence will also create emotional symptoms of meaning or purpose, often later in our lives, and is also conceived of as a developmental arrest. The maps for this transcendence are hidden in plain sight; in the chakras of kundalini yoga, in the sacraments of the Catholic Church, in the Kabbalah tree of life of Judaism, in Maslow’s hierarchy of needs, to name a few. This paper outlines some proposed research exploring the use of daily practices that can be incorporated into the therapy room; practices that utilise meditation, visualisation and imagination: that are informed by spiritual technology and guided by the psychodynamic theory of Self Psychology.

Keywords: narcissism, self-psychology, self-practice, self-transcendence

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Authors: Mohamed El Morsy, Gabriela Achtenová

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Condition monitoring is used to increase machinery availability and machinery performance, whilst reducing consequential damage, increasing machine life, reducing spare parts inventories, and reducing breakdown maintenance. An efficient condition monitoring system provides early warning of faults by predicting them at an early stage. When a localized fault occurs in gears, the vibration signals always exhibit non-stationary behavior. The periodic impulsive feature of the vibration signal appears in the time domain and the corresponding gear mesh frequency (GMF) emerges in the frequency domain. However, one limitation of frequency-domain analysis is its inability to handle non-stationary waveform signals, which are very common when machinery faults occur. Particularly at the early stage of gear failure, the GMF contains very little energy and is often overwhelmed by noise and higher-level macro-structural vibrations. An effective signal processing method would be necessary to remove such corrupting noise and interference. In this paper, a new hybrid method based on optimal Morlet wavelet filter and autocorrelation enhancement is presented. First, to eliminate the frequency associated with interferential vibrations, the vibration signal is filtered with a band-pass filter determined by a Morlet wavelet whose parameters are selected or optimized based on maximum Kurtosis. Then, to further reduce the residual in-band noise and highlight the periodic impulsive feature, an autocorrelation enhancement algorithm is applied to the filtered signal. The test stand is equipped with three dynamometers; the input dynamometer serves as the internal combustion engine, the output dynamometers induce a load on the output joint shaft flanges. The pitting defect is manufactured on the tooth side of a gear of the fifth speed on the secondary shaft. The gearbox used for experimental measurements is of the type most commonly used in modern small to mid-sized passenger cars with transversely mounted powertrain and front wheel drive: a five-speed gearbox with final drive gear and front wheel differential. The results obtained from practical experiments prove that the proposed method is very effective for gear fault diagnosis.

Keywords: wavelet analysis, pitted gear, autocorrelation, gear fault diagnosis

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Authors: Chuanxiang Cheng, Tiantian Min, Jin Yue

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Antimicrobial active packaging enables extensive biological effects to improve food safety. However, the efficacy of antimicrobial packaging hinges on factors including the diffusion rate of the active agent toward the food surface, the initial content in the antimicrobial agent, and the targeted food shelf life. Among the possibilities of antimicrobial packaging design, an interesting approach involves the incorporation of volatile antimicrobial agents into the packaging material. In this case, the necessity for direct contact between the active packaging material and the food surface is mitigated, as the antimicrobial agent exerts its action through the packaging headspace atmosphere towards the food surface. However, it still remains difficult to achieve controlled and precise release of bioactive compounds to the specific target location with required quantity in food packaging applications. Remarkably, the development of stimuli-responsive materials for electrospinning has introduced the possibility of achieving controlled release of active agents under specific conditions, thereby yielding enduring biological effects. Relative humidity (RH) for the storage of food categories such as meat and aquatic products typically exceeds 90%. Consequently, high RH can be used as an abiotic trigger for the release of active agents to prevent microbial growth. Hence, a novel RH - responsive polyvinyl alcohol/chitosan (PVA/CS) composite nanofibrous film incorporated with 4-terpineol/β-cyclodextrin inclusion complexes (4-TA@β-CD ICs) was engineered by electrospinning that can be deposited as a functional packaging materials. The characterization results showed the thermal stability of the films was enhanced after the incorporation due to the hydrogen bonds between ICs and polymers. Remarkably, the 4 wt% 4-TA@β-CD ICs/PVA/CS film exhibited enhanced crystallinity, moderate hydrophilic (Water contact angle of 81.53°), light barrier property (Transparency of 1.96%) and water resistance (Water vapor permeability of 3.17 g mm/m2 h kPa). Moreover, this film also showed optimized mechanical performance with a Young’s modulus of 11.33 MPa, a tensile strength of 19.99 MPa and an elongation at break of 4.44 %. Notably, the antioxidant and antibacterial properties of this packaging material were significantly improved. The film demonstrated the half-inhibitory concentrations (IC50) values of 87.74% and 85.11% for scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2′-azinobis (3-ethylbenzothiazoline-6-sulfonic) (ABTS) free radicals, respectively, in addition to an inhibition efficiency of 65% against Shewanella putrefaciens, the characteristic bacteria in aquatic products. Most importantly, the film achieved controlled release of 4-TA under high 98% RH by inducing the plasticization of polymers caused by water molecules, swelling of polymer chains, and destruction of hydrogen bonds within the cyclodextrin inclusion complex. Consequently, low relative humidity is suitable for the preservation of nanofibrous film, while high humidity conditions typical in fresh food packaging environments effectively stimulated the release of active compounds in the film. This film with a long-term antimicrobial effect successfully extended the shelf life of Litopenaeus vannamei shrimp to 7 days at 4 °C. This attractive design could pave the way for the development of new food packaging materials.

Keywords: controlled release, electrospinning, nanofibrous film, relative humidity–responsive, shrimp preservation

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Authors: Michio Kurosu

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Alterations in glycosylation not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Identification of cell type-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems for certain cancers via immunodetection reagents. N- and O-linked glycans are the most abundant forms of glycoproteins. Recent studies of cancer immunotherapy are based on the immunogenicity of truncated O-glycan chains (e.g., Tn, sTn, T, and sLea/x). The prevalence of N-linked glycan changes in the development of tumor cells is known; however, therapeutic antibodies against N-glycans have not yet been developed. This is due to the lack of specificity of N-linked glycans between normal/healthy and cancer cells. Abnormal branching of N-linked glycans has been observed, particularly in solid cancer cells. While the discovery of drug-like glycosyltransferase inhibitors that block the biosynthesis of specific branching has a very low likelihood of success, altered glycosylation levels can be exploited by suppressing N-glycan biosynthesis through the inhibition of dolichyl-phosphate N-acetylglucosaminephosphotransferase1 (DPAGT1) activity. Inhibition of DPAGT1 function leads to changes of O-glycosylation on proteins associated with mitochondria and zinc finger binding proteins (indirect effects). On the basis of dynamic crosstalk between DPAGT1 and Snail/Slung/ZEB1 (a family of transcription factors that promote the repression of the adhesion molecules), we have developed pharmacologically acceptable selective DPAGT1 inhibitors. Tunicamycin kills a wide range of cancer and healthy cells in a non-selective manner. In sharp contrast, our DPAGT1 inhibitors display strong cytostatic effects against 16 solid cancers, which require the overexpression of DPAGT1 in their progression but do not affect the cell viability of healthy cells. The identified DPAGT1 inhibitors possess impressive anti-metastatic ability in various solid cancer cell lines and induce their mitochondrial structural changes, resulting in apoptosis. A prototype DPAGT1 inhibitor, APPB has already been proven to shrink solid tumors (e.g., pancreatic cancers, triple-negative breast cancers) in vivo while suppressing metastases and has strong synergistic effects when combined with current cytotoxic drugs (e.g., paclitaxel). At this conference, our discovery of selective DPAGT1 inhibitors with drug-like properties and proof-of-pharmaceutical concept studies of a novel DPAGT1 inhibitor are presented.

Keywords: DPAGT1 inhibitors, anti-metastatic drugs, natural product based drug designs, cytostatic effects

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Authors: Ahmed Tamer AlMotasem, Jens Bergström, Anders Gåård, Pavel Krakhmalev, Thijs Jan Holleboom

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In sheet metal forming processes, accumulation and transfer of sheet material to tool surfaces, often referred to as galling, is the major cause of tool failure. Initiation of galling is assumed to occur due to local adhesive wear between two surfaces. Therefore, reducing adhesion between the tool and the work sheet has a great potential to improve the tool materials galling resistance. Experimental observations and theoretical studies show that the presence of primary micro-sized carbides and/or nitrides in alloyed steels may significantly improve galling resistance. Generally, decreased adhesion between the ceramic precipitates and the sheet material counter-surface are attributed as main reason to the latter observations. On the other hand, adhesion processes occur at an atomic scale and, hence, fundamental understanding of galling can be obtained via atomic scale simulations. In the present study, molecular dynamics simulations are used, with utilizing second nearest neighbor embedded atom method potential to investigate the influence of nano-sized cementite precipitates embedded in tool atoms. The main aim of the simulations is to gain new fundamental knowledge on galling initiation mechanisms. Two tool/work piece configurations, iron/iron and iron-cementite/iron, are studied under dry sliding conditions. We find that the average frictional force decreases whereas the normal force increases for the iron-cementite/iron system, in comparison to the iron/iron configuration. Moreover, the average friction coefficient between the tool/work-piece decreases by about 10 % for the iron-cementite/iron case. The increase of the normal force in the case of iron-cementite/iron system may be attributed to the high stiffness of cementite compared to bcc iron. In order to qualitatively explain the effect of cementite on adhesion, the adhesion force between self-mated iron/iron and cementite/iron surfaces has been determined and we found that iron/cementite surface exhibits lower adhesive force than that of iron-iron surface. The variation of adhesion force with temperature was investigated up to 600 K and we found that the adhesive force, generally, decreases with increasing temperature. Structural analyses show that plastic deformation is the main deformation mechanism of the work-piece, accompanied with dislocations generation.

Keywords: adhesion, cementite, galling, molecular dynamics

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Authors: Masilonyane Mokhele

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Across the world, different planning models of the so-called airport-led developments are becoming bandwagons hailed as key to the future of cities. However, in the existing knowledge, there is paucity of empirically informed description and explanation of the economic fundamentals driving the forces of attraction of airports. This void is arguably a result of the absence of an appropriate theoretical framework to guide the analyses. Given this paucity, the aim of the paper is to contribute towards a theoretical framework that could be used to describe and explain forces that drive the location and mix of airport-centric developments. Towards achieving this aim, the objectives of the paper are: one, to establish the type of economic activities that are located on and around O.R. Tambo International Airport (ORTIA), and analyse the reasons for locating there; two, to establish changes that have occurred over time in the form of the airport-centric development of ORTIA; three, to identify the propulsive economic qualities of ORTIA; four, to analyse the spatial, economic and structural linkages within the airport-centric development of ORTIA, between the airport-centric development and the airport, as well as the airport-centric development’s linkages with their metropolitan area and other regional, national and international airport-centric developments and locations. To address the objectives above, the study adopted a case study approach, centred on ORTIA in South Africa: Africa’s busiest airport in terms of passengers and airfreight handled. Using a lens of location theory, a survey was adopted as a main research method, wherein telephonic interviews were conducted with a representative number of firms on and around ORTIA. Other data collection methods encompassed in-depth qualitative interviews (to augment the information obtained through the survey) and analysis of secondary information, particularly as regards establishing changes that have occurred in the form of ORTIA and surrounds. From the empirical findings, ORTIA was discovered to have propulsive economic qualities that act as significant forces of attraction in the clustering of firms. Together with its airport-centric development, ORTIA was discovered to have growth pole properties because of the linkages that occur within the study area, and the linkages that exist between the airport-centric firms and the airport. It was noted that the transport-oriented firms (typified by couriers and freight carriers) act as anchors in some fellow airport-centric firms making use of elements of urbanisation economies, particularly as regards the use of the airport for airfreight services. The empirical findings presented in the paper (in conjunction with results from other airport-centric development case studies) could be used as contribution towards extending theory that describes and explains forces that drive the location and mix of airport-centric developments.

Keywords: airports, airport-centric development, O. R. Tambo international airport, South Africa

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Authors: Ankit Tyagi, Reet Kamal Tiwari, Naveen James

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Landslide is the major geo-environmental problem of Himalaya because of high ridges, steep slopes, deep valleys, and complex system of streams. They are mainly triggered by rainfall and earthquake and causing severe damage to life and property. In Uttarakhand, the Tehri reservoir rim area, which is situated in the lesser Himalaya of Garhwal hills, was selected for landslide hazard zonation (LHZ). The study utilized different types of data, including geological maps, topographic maps from the survey of India, Landsat 8, and Cartosat DEM data. This paper presents the use of a weighted overlay method in LHZ using fourteen causative factors. The various data layers generated and co-registered were slope, aspect, relative relief, soil cover, intensity of rainfall, seismic ground shaking, seismic amplification at surface level, lithology, land use/land cover (LULC), normalized difference vegetation index (NDVI), topographic wetness index (TWI), stream power index (SPI), drainage buffer and reservoir buffer. Seismic analysis is performed using peak horizontal acceleration (PHA) intensity and amplification factors in the evaluation of the landslide hazard index (LHI). Several digital image processing techniques such as topographic correction, NDVI, and supervised classification were widely used in the process of terrain factor extraction. Lithological features, LULC, drainage pattern, lineaments, and structural features are extracted using digital image processing techniques. Colour, tones, topography, and stream drainage pattern from the imageries are used to analyse geological features. Slope map, aspect map, relative relief are created by using Cartosat DEM data. DEM data is also used for the detailed drainage analysis, which includes TWI, SPI, drainage buffer, and reservoir buffer. In the weighted overlay method, the comparative importance of several causative factors obtained from experience. In this method, after multiplying the influence factor with the corresponding rating of a particular class, it is reclassified, and the LHZ map is prepared. Further, based on the land-use map developed from remote sensing images, a landslide vulnerability study for the study area is carried out and presented in this paper.

Keywords: weighted overlay method, GIS, landslide hazard zonation, remote sensing

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Authors: Shankha Pratim Bhattacharya

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In general building repair and renovation projects are minor in nature. It requires less attention as the primary cost involvement is relatively small. Although the building repair and maintenance projects look simple, it involves much complexity during execution. Many of the present research indicate that few uncertain situations are usually linked with maintenance projects. Those may not be read properly in the planning stage of the projects, and finally, lead to time overrun. Building repair and maintenance become essential and periodical after commissioning of the building. In Institutional buildings, the regular maintenance projects also include addition –alteration, modification activities. Increase in the student admission, new departments, and sections, new laboratories and workshops, up gradation of existing laboratories are very common in the institutional buildings in the developing nations like India. The project becomes very critical because it undergoes space problem, architectural design issues, structural modification, etc. One of the prime factors in the institutional building maintenance and modification project is the time constraint. Mostly it required being executed a specific non-work time period. The present research considered only the institutional buildings of the Eastern part of India to analyse the repair and maintenance project delay. A general survey was conducted among the technical institutes to find the causes and corresponding nature of construction delay factors. Five technical institutes are considered in the present study with repair, renovation, modification and extension type of projects. Construction delay factors are categorically subdivided into four groups namely, material, manpower (works), Contract and Site. The survey data are collected for the nature of delay responsible for a specific project and the absolute amount of delay through proposed and actual duration of work. In the first stage of the paper, a relative importance index (RII) is proposed for the delay factors. The occurrence of the delay factors is also judged by its frequency-severity nature. Finally, the delay factors are then rated and linked with the type of work. In the second stage, a regression analysis is executed to establish an empirical relationship between the actual time of a project and the percentage of delay. It also indicates the impact of the factors for delay responsibility. Ultimately, the present paper makes an effort to identify the critical delay factors for the repair and renovation type project in the Eastern Indian Institutional building.

Keywords: delay factor, institutional building, maintenance, relative importance index, regression analysis, repair

Procedia PDF Downloads 248

Authors: Marcin Stasiulewicz, Sebastian Filipkowski, Aneta Panuszko

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Background: The hallmark of neurodegenerative diseases, including Alzheimer's and Parkinson's diseases, is an aggregation of the abnormal forms of peptides and proteins. Water is essential to functioning biomolecules, and it is one of the key factors influencing protein folding and misfolding. However, the hydration studies of proteins are complicated due to the complexity of protein systems. The use of model compounds can facilitate the interpretation of results involving larger systems. Objectives: The goal of the research was to characterize the properties of the hydration water surrounding the two three-residue K peptide fragments INS (Isoleucine - Asparagine - Serine) and NSR (Asparagine - Serine - Arginine). Methods: Fourier-transform infrared spectra of aqueous solutions of the tripeptides were recorded on Nicolet 8700 spectrometer (Thermo Electron Co.) Measurements were carried out at 25°C for varying molality of solute. To remove oscillation couplings from water spectra and, consequently, obtain narrow O-D semi-heavy water bands (HDO), the isotopic dilution method of HDO in H₂O was used. The difference spectra method allowed us to isolate the tripeptide-affected HDO spectrum. Results: The structural and energetic properties of water affected by the tripeptides were compared to the properties of pure water. The shift of the values of the gravity center of bands (related to the mean energy of water hydrogen bonds) towards lower values with respect to the ones corresponding to pure water suggests that the energy of hydrogen bonds between water molecules surrounding tripeptides is higher than in pure water. A comparison of the values of the mean oxygen-oxygen distances in water affected by tripeptides and pure water indicates that water-water hydrogen bonds are shorter in the presence of these tripeptides. The analysis of differences in oxygen-oxygen distance distributions between the tripeptide-affected water and pure water indicates that around the tripeptides, the contribution of water molecules with the mean energy of hydrogen bonds decreases, and simultaneously the contribution of strong hydrogen bonds increases. Conclusions: It was found that hydrogen bonds between water molecules in the hydration sphere of tripeptides are shorter and stronger than in pure water. It means that in the presence of the tested tripeptides, the structure of water is strengthened compared to pure water. Moreover, it has been shown that in the vicinity of the Asparagine - Serine - Arginine, water forms stronger and shorter hydrogen bonds. Acknowledgments: This work was funded by the National Science Centre, Poland (grant 2017/26/D/NZ1/00497).

Keywords: amyloids, K-peptide, hydration, FTIR spectroscopy

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Authors: Virendra Nath, Vipin Kumar

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Background: TypeII Diabetes mellitus is a foremost health problem worldwide, predisposing to increased mortality and morbidity. Undesirable effects of the current medications have prompted the researcher to develop more potential drug(s) against the disease. The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptors family and take part in a vital role in the regulation of metabolic equilibrium. They can induce or repress genes associated with adipogenesis, lipid, and glucose metabolism. Aims: Investigation of PPARα/γ agonistic hits were screened by hierarchical virtual screening followed by molecular dynamics simulation and knowledge-based structure-activity relation (SAR) analysis using approved PPAR α/γ dual agonist. Methods: The PPARα/γ agonistic activity of compounds was searched by using Maestro through structure-based virtual screening and molecular dynamics (MD) simulation application. Virtual screening of nuclear-receptor ligands was done, and the binding modes with protein-ligand interactions of newer entity(s) were investigated. Further, binding energy prediction, Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit along with the structural comparative analysis of approved PPARα/γ agonists with screened hit was done for knowledge-based SAR. Results and Discussion: The silicone chip-based approach recognized the most capable nine hits and had better predictive binding energy as compared to the reference drug compound (Tesaglitazar). In this study, the key amino acid residues of binding pockets of both targets PPARα/γ were acknowledged as essential and were found to be associated in the key interactions with the most potential dual hit (ChemDiv-3269-0443). Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit and found root mean square deviation (RMSD) stabile around 2Å and 2.1Å, respectively. Frequency distribution data also revealed that the key residues of both proteins showed maximum contacts with a potent hit during the MD simulation of 20 nanoseconds (ns). The knowledge-based SAR studies of PPARα/γ agonists were studied using 2D structures of approved drugs like aleglitazar, tesaglitazar, etc. for successful designing and synthesis of compounds PPARγ agonistic candidates with anti-hyperlipidimic potential.

Keywords: computational, diabetes, PPAR, simulation

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Authors: Yari Vecchio, Margherita Masi, Jorgelina Di Pasquale

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Adoption of Precision Agriculture (PA) is involved in a multidimensional and complex scenario. The process of adopting innovations is complex and social inherently, influenced by other producers, change agents, social norms and organizational pressure. Complexity depends on factors that interact and influence the decision to adopt. Farm and operator characteristics, as well as organizational, informational and agro-ecological context directly affect adoption. This influence has been studied to measure drivers and to clarify 'bottlenecks' of the adoption of agricultural innovation. Making decision process involves a multistage procedure, in which individual passes from first hearing about the technology to final adoption. Awareness is the initial stage and represents the moment in which an individual learns about the existence of the technology. 'Static' concept of adoption has been overcome. Awareness is a precondition to adoption. This condition leads to not encountering some erroneous evaluations, arose from having carried out analysis on a population that is only in part aware of technologies. In support of this, the present study puts forward an empirical analysis among Italian farmers, considering awareness as a prerequisite for adoption. The purpose of the present work is to analyze both factors that affect the probability to adopt and determinants that drive an aware individual to not adopt. Data were collected through a questionnaire submitted in November 2017. A preliminary descriptive analysis has shown that high levels of adoption have been found among younger farmers, better educated, with high intensity of information, with large farm size and high labor-intensive, and whose perception of the complexity of adoption process is lower. The use of a logit model permits to appreciate the weight played by the intensity of labor and complexity perceived by the potential adopter in PA adoption process. All these findings suggest important policy implications: measures dedicated to promoting innovation will need to be more specific for each phase of this adoption process. Specifically, they should increase awareness of PA tools and foster dissemination of information to reduce the degree of perceived complexity of the adoption process. These implications are particularly important in Europe where is pre-announced the reform of Common Agricultural Policy, oriented to innovation. In this context, these implications suggest to the measures supporting innovation to consider the relationship between various organizational and structural dimensions of European agriculture and innovation approaches.

Keywords: adoption, awareness, complexity, precision agriculture

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Authors: Xavier McCreanor, Rowena Naidoo, Verusia Chetty

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Background: The growing trend of children with disabilities being excluded from physical education classes due to a lack of inclusive education training for educators is concerning. This poses a significant health risk to disabled children worldwide, including those attending mainstream schools in South Africa. Unfortunately, disabled children often feel left out and uncomfortable in physical education classes. The current public school system faces challenges in providing quality physical education to disabled children, as classes need to be tailored to their specific needs. Although studies have pointed to the need for training, there is limited understanding of the teaching methods and curricula required for the inclusive education of children with disabilities. Objective: Given the lack of practical guidance, teaching methods, and resources, a scoping review was conducted to map and summarise the existing literature on teaching physical education to children with disabilities. The review aimed to identify the information regarding curricula used to teach children with disabilities, elaborate on the teaching methodologies, and report on the findings of relevant studies. Methods: The researchers searched the literature in the following electronic databases: Google Scholar; EBSCOhost; the Cochrane Library; PubMed; and Science Direct. The research team also conducted a reference list search to ensure that all relevant articles were included in the study. The researchers followed an initial screening process and two more screening levels to extract the data collaboratively, organize it into themes and sub-themes, summarise them, and report the results in a descriptive and narrative synthesis. Results and Conclusion: A scoping review of the past decade’s research on inclusive physical education for students with disabilities revealed persistent exclusion and insufficient involvement. The challenges are due to inaccessible facilities and negative attitudes. To address these obstacles, structural changes, inclusive policies, accessible facilities, and comprehensive training for physical education instructors are crucial. However, challenges such as inadequate policies and guidelines, financial limitations, and a shortage of specialists and resources hinder the implementation of inclusive physical education. Overcoming these challenges requires a collaborative effort. Creating a supportive environment, providing customized activities, and adopting effective teaching methods are essential to promote inclusivity and enhance the learning experiences of students with disabilities.

Keywords: adapted physical activity, disability, physical education, schools

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Authors: Mikhail O. Eremin

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Seismic activity around the world is clearly a threat to people's lives, as well as infrastructure and capital construction. It is the instability of the latter to powerful earthquakes that most often causes human casualties. Therefore, during construction it is necessary to take into account the risks of large-scale natural disasters. The task of assessing the risks of natural disasters is one of the most urgent at the present time. The final goal of any study of earthquakes is forecasting. This is especially important for seismically active regions of the planet where earthquakes occur frequently. Gorni Altai is one of such regions. In work, we developed the physical-mathematical model of stress-strain state evolution of loaded geomedium with the purpose of numerical simulation of seismic process accompanying the formation of Chuya-Kuray fault zone Gorni Altay, Russia. We build a structural model on the base of seismotectonic and paleoseismogeological investigations, as well as SRTM-data. Base of mathematical model is the system of equations of solid mechanics which includes the fundamental conservation laws and constitutive equations for elastic (Hooke's law) and inelastic deformation (modified model of Drucker-Prager-Nikolaevskii). An initial stress state of the model correspond to gravitational. Then we simulate an activation of a buried dextral strike-slip paleo-fault located in the basement of the model. We obtain the stages of formation and the structure of Chuya-Kuray fault zone. It is shown that results of numerical simulation are in good agreement with field observations in statistical sense. Simulated seismic process is strongly bound to the faults - lineaments with high degree of inelastic strain localization. Fault zone represents en-echelon system of dextral strike-slips according to the Riedel model. The system of surface lineaments is represented with R-, R'-shear bands, X- and Y-shears, T-fractures. Simulated seismic process obeys the laws of Gutenberg-Richter and Omori. Thus, the model describes a self-similar character of deformation and fracture of rocks and geomedia. We also modified the algorithm of determination of separate slip events in the model due to the features of strain rates dependence vs time.

Keywords: Drucker-Prager model, fault zone, numerical simulation, Riedel bands, seismic process, strike-slip fault

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Authors: Omaima A. Sharaf, Wafaa M. Abd El-Rahim, Hassan Moawad, Michael J. Sadowsky

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Textile industry is one of the important industries in the worldwide. It is known that the eco-friendly industrial and agricultural activities are significant for socio-economic stability of all countries. The absence of appropriate industrial waste water treatments is essential barrier for sustainable development in food and agricultural sectors especially in developing country like Egypt. Thus, the development of enzymatic bioremediation technology for textile dye removal will enhance the collaboration between scientists who develop the technology and industry where this technology will be implemented towards the safe disposal of the textile dye wastes. Highly efficient microorganisms are of most importance in developing and using highly effective biological treatment processes. Bacterial degradation of azo dyes is generally initiated by an enzymatic step that involves cleavage of azo linkages, usually with the aid of an azoreductase as electron donor. Thus, expanding the spectrum of microorganisms with high enzymatic activities as azoreductases and discovering novel azo-dye degrading enzymes, with enhanced stability and superior catalytic properties, are necessary for many environmental and industrial applications. Consequently, the use of molecular tools has become increasingly integrated into the understanding of enzyme properties and characterization. Researchers have utilized a gene cloning and expression methods as a tool to produce recombinant protein for decolorizing dyes more efficiently. Thus, presumptive evidence for the presence of genes encoding azoreductases in the genomes of selected local, and most potent azo-degrading strains were obtained by using specific oligonucleotides primers. These potent strains have been isolated from textile industrial wastewater in Egypt and identified using 16S rRNA sequence analysis as 'Lysinibacillus macrolidesB8, Brevibacillus parabrevisB11, Bacillus coagulansB7, and B. cereusB5'. PCR products of two full length genes designated as (AZO1;621bp and AZO2;534bp) were detected. BLASTx results indicated that AZO1 gene was corresponding to predicted azoreductase from of Bacillus sp. ABP14, complete genome, multispecies azoreductase [Bacillus], It was submitted to the gene bank by an accession no., BankIt2085371 AZO1 MG923210 (621bp; 207 amino acids). AZO1 was generated from the DNA of our identified strains Lysinibacillus macrolidesB8. On the other hand, AZO2 gene was corresponding to a predicted azoreductase from Bacillus cereus strain S2-8. Gene bank accession no. was BankIt2085839 AZO2 MG932081 (534bp;178 amino acids) and it was amplified from our Bacillus coagulansB7. Both genes were successfully cloned into pCR2.1TOPO (Invitrogen) and in pET28b+ vectors, then they transformed into E. coli DH5α and BL21(DE3) cells for heterologous expression studies. Our recombinant azoreductases (AZO1&AZO2) exhibited potential enzyme activity and efficiently decolorized an azo dye (Direct violet). They exhibited pH stability between 6 and 8 with optimum temperature up to 60°C and 37 °C after induction by 1mM and 1.5mM IPTG, for both AZO1 &AZO2, respectively. These results suggested that further optimization and purification of these recombinant proteins by using different heterologous expression systems will give great potential for the sustainable utilization of these recombinant enzymes in several industrial applications especially in wastewater treatments.

Keywords: azoreductases, decolorization, enzyme activity, gene cloning and expression

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Authors: Aussara Panya, Nunghathai Sawasdee, Mutita Junking, Chatchawan Srisawat, Kiattawee Choowongkomon, Pa-Thai Yenchitsomanus

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Dengue virus (DENV) infection is a global public health problem with approximately 100 million infected cases a year. Presently, there is no approved vaccine or effective drug available; therefore, the development of anti-DENV drug is urgently needed. The clinical reports revealing the positive association between the disease severity and viral titer has been reported previously suggesting that the anti-DENV drug therapy can possibly ameliorate the disease severity. Although several anti-DENV agents showed inhibitory activities against DENV infection, to date none of them accomplishes clinical use in the patients. The surface envelope (E) protein of DENV is critical for the viral entry step, which includes attachment and membrane fusion; thus, the blocking of envelope protein is an attractive strategy for anti-DENV drug development. To search the safe anti-DENV agent, this study aimed to search for novel peptide inhibitors to counter DENV infection through the targeting of E protein using a structure-based in silico design. Two selected strategies has been used including to identify the peptide inhibitor which interfere the membrane fusion process whereby the hydrophobic pocket on the E protein was the target, the destabilization of virion structure organization through the disruption of the interaction between the envelope and membrane proteins, respectively. The molecular docking technique has been used in the first strategy to search for the peptide inhibitors that specifically bind to the hydrophobic pocket. The second strategy, the peptide inhibitor has been designed to mimic the ectodomain portion of membrane protein to disrupt the protein-protein interaction. The designed peptides were tested for the effects on cell viability to measure the toxic to peptide to the cells and their inhibitory assay to inhibit the DENV infection in Vero cells. Furthermore, their antiviral effects on viral replication, intracellular protein level and viral production have been observed by using the qPCR, cell-based flavivirus immunodetection and immunofluorescence assay. None of tested peptides showed the significant effect on cell viability. The small peptide inhibitors achieved from molecular docking, Glu-Phe (EF), effectively inhibited DENV infection in cell culture system. Its most potential effect was observed for DENV2 with a half maximal inhibition concentration (IC50) of 96 μM, but it partially inhibited other serotypes. Treatment of EF at 200 µM on infected cells also significantly reduced the viral genome and protein to 83.47% and 84.15%, respectively, corresponding to the reduction of infected cell numbers. An additional approach was carried out by using peptide mimicking membrane (M) protein, namely MLH40. Treatment of MLH40 caused the reduction of foci formation in four individual DENV serotype (DENV1-4) with IC50 of 24-31 μM. Further characterization suggested that the MLH40 specifically blocked viral attachment to host membrane, and treatment with 100 μM could diminish 80% of viral attachment. In summary, targeting the hydrophobic pocket and M-binding site on the E protein by using the peptide inhibitors could inhibit DENV infection. The results provide proof of-concept for the development of antiviral therapeutic peptide inhibitors to counter DENV infection through the use of a structure-based design targeting conserved viral protein.

Keywords: dengue virus, dengue virus infection, drug design, peptide inhibitor

Procedia PDF Downloads 352

Authors: Evangelos G. Ilias, Panagiotis G. Ilias, Vasileios T. Popotas

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The United Kingdom has one of the oldest railway networks in the world dating back to 1825 when the world’s first passenger railway was opened. The network has some 40,000 bridges of various construction types using a wide range of materials including masonry, steel, cast iron, wrought iron, concrete and timber. It is commonly accepted that the successful operation of the network is vital for the economy of the United Kingdom, consequently the cost effective maintenance of the existing infrastructure is a high priority to maintain the operability of the network, prevent deterioration and to extend the life of the assets. Every bridge on the railway network is required to be assessed every eighteen years and a structured approach to assessments is adopted with three main types of progressively more detailed assessments used. These assessment types include Level 0 (standardized spreadsheet assessment tools), Level 1 (analytical hand calculations) and Level 2 (generally finite element analyses). There is a degree of conservatism in the first two types of assessment dictated to some extent by the relevant standards which can lead to some structures not achieving the required load rating. In these situations, a Level 2 Assessment is often carried out using finite element analysis to uncover ‘latent strength’ and improve the load rating. If successful, the more sophisticated analysis can save on costly strengthening or replacement works and avoid disruption to the operational railway. This paper presents the ‘strengthening by assessment’ achieved by Level 2 analyses. The use of more accurate analysis assumptions and the implementation of non-linear modelling and functions (material, geometric and support) to better understand buckling modes and the structural behaviour of historic construction details that are not specifically covered by assessment codes are outlined. Metallic bridges which are susceptible to loss of section size through corrosion have largest scope for improvement by the Level 2 Assessment methodology. Three case studies are presented, demonstrating the effectiveness of the sophisticated Level 2 Assessment methodology using finite element analysis against the conservative approaches employed for Level 0 and Level 1 Assessments. One rail overbridge and two rail underbridges that did not achieve the required load rating by means of a Level 1 Assessment due to the inadequate restraint provided by U-Frame action are examined and the increase in assessed capacity given by the Level 2 Assessment is outlined.

Keywords: assessment, bridges, buckling, finite element analysis, non-linear modelling, strengthening

Procedia PDF Downloads 308

Authors: Faye Cosgrove, Donna Peacock

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This paper examines current state strategies for dealing with vulnerable people in police custody and identifies the underpinning discourses and practices which inform these strategies. It has previously been argued that the state has utilised contradictory and conflicting responses to the control of crime, by employing opposing strategies of denial and adaptation in order to simultaneously both display sovereignty and disclaim responsibility. This paper argues that these contradictory strategies are still being employed in contemporary criminal justice, although the focus and the purpose have now shifted. The focus is upon the ‘vulnerable’ suspect, whose social identity is as incongruous, complex and contradictory as his social environment, and the purpose is to redirect attention away from negative state practices, whilst simultaneously displaying a compassionate and benevolent countenance in order to appeal to the voting public. The findings presented here result from intensive qualitative research with police officers, with health care professionals, and with civilian volunteers who work within police custodial environments. The data has been gathered over a three-year period and includes observational and interview data which has been thematically analysed to expose the underpinning mechanisms from which the properties of the system emerge. What is revealed is evidence of contemporary state practices of denial relating to the harms of austerity and the structural relations of vulnerability, whilst simultaneously adapting through processes of ‘othering’ of the vulnerable, ‘responsibilisation’ of citizens, defining deviance down through diversionary practices, and managing success through redefining the aims of the system. The ‘vulnerable’ suspect is subject to individual pathologising, and yet the nature of risk is aggregated. ‘Vulnerable’ suspects are supported in police custody by private citizens, by multi-agency partnerships, and by for-profit organisations, while the state seeks to collate and control services, and thereby to retain a veneer of control. Late modern ambivalence to crime control and the associated contradictory practices of abjuration and adjustment have extended to state responses to vulnerable suspects. The support available in the custody environment operates to control and minimise operational and procedural risk, rather than for the welfare of the detained person, and in fact, the support available is discovered to be detrimental to the very people that it claims to benefit. The ‘vulnerable’ suspect is now subject to the bifurcated logics employed at the new limits of the sovereign state.

Keywords: custody, policing, sovereign state, vulnerability

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Authors: Aleksandr I. Korobov, Natalia V. Shirgina, Aleksey I. Kokshaiskiy, Vyacheslav M. Prokhorov

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The paper presents the results of an experimental study of the effect of reverse mechanical load-unloading on the mechanical, linear, and nonlinear elastic properties of n-AMg6/C60 nanocomposite. Samples for experimental studies of n-AMg6/C60 nanocomposite were obtained by grinding AMg6 polycrystalline alloy in a planetary mill with 0.3 wt % of C60 fullerite in an argon atmosphere. The resulting product consisted of 200-500-micron agglomerates of nanoparticles. X-ray coherent scattering (CSL) method has shown that the average nanoparticle size is 40-60 nm. The resulting preform was extruded at high temperature. Modifications of C60 fullerite interferes the process of recrystallization at grain boundaries. In the samples of n-AMg6/C60 nanocomposite, the load curve is measured: the dependence of the mechanical stress σ on the strain of the sample ε under its multi-cycle load-unloading process till its destruction. The hysteresis dependence σ = σ(ε) was observed, and insignificant residual strain ε < 0.005 were recorded. At σ≈500 MPa and ε≈0.025, the sample was destroyed. The destruction of the sample was fragile. Microhardness was measured before and after destruction of the sample. It was found that the loading-unloading process led to an increase in its microhardness. The effect of the reversible mechanical stress on the linear and nonlinear elastic properties of the n-AMg6/C60 nanocomposite was studied experimentally by ultrasonic method on the automated complex Ritec RAM-5000 SNAP SYSTEM. In the n-AMg6/C60 nanocomposite, the velocities of the longitudinal and shear bulk waves were measured with the pulse method, and all the second-order elasticity coefficients and their dependence on the magnitude of the reversible mechanical stress applied to the sample were calculated. Studies of nonlinear elastic properties of the n-AMg6/C60 nanocomposite at reversible load-unloading of the sample were carried out with the spectral method. At arbitrary values of the strain of the sample (up to its breakage), the dependence of the amplitude of the second longitudinal acoustic harmonic at a frequency of 2f = 10MHz on the amplitude of the first harmonic at a frequency f = 5MHz of the acoustic wave is measured. Based on the results of these measurements, the values of the nonlinear acoustic parameter in the n-AMg6/C60 nanocomposite sample at different mechanical stress were determined. The obtained results can be used in solid-state physics, materials science, for development of new techniques for nondestructive testing of structural materials using methods of nonlinear acoustic diagnostics. This study was supported by the Russian Science Foundation (project №14-22-00042).

Keywords: nanocomposite, generation of acoustic harmonics, nonlinear acoustic parameter, hysteresis

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Authors: Dicle Aydın, Süheyla Büyükşahin Sıramkaya

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Conservation concept gained importance especially in 19th century, it found value with the change and developments lived globally. Basic values in the essence of the concept are important in the continuity of historical and cultural fabrics which have character special to them. Reuse of settlements and spaces carrying historical and cultural values in the frame of socio-cultural and socio-economic conditions is related with functional value. Functional dimension of reuse signifies interrogation of the usage potential of the building with a different aim other than its determined aim. If a building carrying historical and cultural values cannot be used with its own function because of environmental, economical, structural and functional reasons, it is advantageous to maintain its reuse from the point of environmental ecology. By giving a new function both a requirement of the society is fulfilled and a culture entity is conserved because of its functional value. In this study, functional dimension of reuse is exemplified in Antalya Kaleiçi where has a special location and importance with its natural, cultural and historical heritage characteristics. Antayla Kaleiçi settlement preserves its liveliness as a touristic urban fabric with its almost fifty thousand years of past, traditional urban form, civil architectural examples of 18th–19th century reflecting the life style of the region and monumental buildings. The civil architectural examples in the fabric have a special character formed according to Mediterranean climate with their outer sofa (open or closed), one, two or three storey, courtyards and oriels. In the study reuse of five civil architectural examples as boutique hotel by forming a whole with their environmental arrangements is investigated, it is analyzed how the spatial requirements of a boutique hotel are fulfilled in traditional dwellings. Usage of a cultural entity as a boutique hotel is evaluated under the headlines of i.functional requirement, ii.satisfactoriness of spatial dimensions, iii.functional organization. There are closed and open restaurant, kitchen, pub, lobby, administrative offices in the hotel with 70 bed capacity and 28 rooms in total. There are expansions to urban areas on second and third floors by the means of oriels in the hotel surrounded by narrow streets in three directions. This boutique hotel, formed by unique five different dwellings having similar plan scheme in traditional fabric, is different with its structure opened to outside and connected to each other by the means of courtyards, and its outside spaces which gained mobility because of the elevation differences in courtyards.

Keywords: reuse, adaptive reuse, functional dimension of reuse, traditional dwellings

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Authors: Brahim Mazian, Anne Bergeret, Jean-Charles Benezet, Sandrine Bayle, Luc Malhautier

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Hemp fibers are increasingly used as reinforcements in polymer matrix composites due to their competitive performance (low density, mechanical properties and biodegradability) compared to conventional fibres such as glass fibers. However, the huge variation of their biochemical, physical and mechanical properties limits the use of these natural fibres in structural applications when high consistency and homogeneity are required. In the hemp industry, traditional processes termed field retting are commonly used to facilitate the extraction and separation of stem fibers. This retting treatment consists to spread out the stems on the ground for a duration ranging from a few days to several weeks. Microorganisms (fungi and bacteria) grow on the stem surface and produce enzymes that degrade pectinolytic substances in the middle lamellae surrounding the fibers. This operation depends on the weather conditions and is currently carried out very empirically in the fields so that a large variability in the hemp fibers quality (mechanical properties, color, morphology, chemical composition…) is resulting. Nonetheless, if controlled, retting might be favorable for good properties of hemp fibers and then of hemp fibers reinforced composites. Therefore, the present study aims to investigate the influence of controlled retting within a designed environmental chamber (lab-scale pilot unit) on the quality of the hemp fibres harvested at the seed maturity growth stage. Various assessments were applied directly on fibers: color observations, morphological (optical microscope), surface (ESEM), biochemical (gravimetry) analysis, spectrocolorimetric measurements (pectins content), thermogravimetric analysis (TGA) and tensile testing. The results reveal that controlled retting leads to a rapid change of color from yellow to dark grey due to development of microbial communities (fungi and bacteria) at the stem surface. An increase of thermal stability of fibres due to the removal of non-cellulosic components along retting is also observed. A separation of bast fibers to elementary fibers occurred with an evolution of chemical composition (degradation of pectins) and a rapid decrease in tensile properties (380MPa to 170MPa after 3 weeks) due to accelerated retting process. The influence of controlled retting on the biocomposite material (PP / hemp fibers) properties is under investigation.

Keywords: controlled retting, hemp fibre, mechanical properties, thermal stability

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Authors: Epaminondas G. Kyriakidis, Theodosis D. Dimitrakos, Constantinos C. Karamatsoukis

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The vehicle routing problem (VRP) is a well-known problem in Operations Research and has been widely studied during the last fifty-five years. The context of the VRP is that of delivering products located at a central depot to customers who are scattered in a geographical area and have placed orders for these products. A vehicle or a fleet of vehicles start their routes from the depot and visit the customers in order to satisfy their demands. Special attention has been given to the capacitated VRP in which the vehicles have limited carrying capacity of the goods that must be delivered. In the present work, we present a specific capacitated stochastic vehicle routing problem which has realistic applications to distributions of materials to shops or to healthcare facilities or to military units. A vehicle starts its route from a depot loaded with items of two similar but not identical products. We name these products, product 1 and product 2. The vehicle must deliver the products to N customers according to a predefined sequence. This means that first customer 1 must be serviced, then customer 2 must be serviced, then customer 3 must be serviced and so on. The vehicle has a finite capacity and after servicing all customers it returns to the depot. It is assumed that each customer prefers either product 1 or product 2 with known probabilities. The actual preference of each customer becomes known when the vehicle visits the customer. It is also assumed that the quantity that each customer demands is a random variable with known distribution. The actual demand is revealed upon the vehicle’s arrival at customer’s site. The demand of each customer cannot exceed the vehicle capacity and the vehicle is allowed during its route to return to the depot to restock with quantities of both products. The travel costs between consecutive customers and the travel costs between the customers and the depot are known. If there is shortage for the desired product, it is permitted to deliver the other product at a reduced price. The objective is to find the optimal routing strategy, i.e. the routing strategy that minimizes the expected total cost among all possible strategies. It is possible to find the optimal routing strategy using a suitable stochastic dynamic programming algorithm. It is also possible to prove that the optimal routing strategy has a specific threshold-type structure, i.e. it is characterized by critical numbers. This structural result enables us to construct an efficient special-purpose dynamic programming algorithm that operates only over those routing strategies having this structure. The findings of the present study lead us to the conclusion that the dynamic programming method may be a very useful tool for the solution of specific vehicle routing problems. A problem for future research could be the study of a similar stochastic vehicle routing problem in which the vehicle instead of delivering, it collects products from ordered customers.

Keywords: collection of similar products, dynamic programming, stochastic demands, stochastic preferences, vehicle routing problem

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Authors: Susanne Ferschl, Peter Holzmüller, Elisabeth Wacker

Abstract:

Ageing populations, advances in medical sciences and digitalization, diversity and social disparities, as well as the increasing need for skilled healthcare professionals, are challenging healthcare systems around the globe. To address these challenges, future healthcare systems need to center on human needs taking into account the living environments that shape individuals’ knowledge of and opportunities to access healthcare. Moreover, health should be considered as a common good and an integral part of securing livelihoods for all people. Therefore, the adoption of a systems approach, as well as inter-disciplinary and inter-sectoral cooperation among healthcare providers, are essential. Additionally, the active engagement of target groups in the planning and design of healthcare structures is indispensable to understand and respect individuals’ health and livelihood needs. We will present the research project b4 – identifying needs | building bridges | developing health care in the social space, which is situated within this reasoning and accompanies the cross-sectoral cooperation project Brückenschlag (building bridges) in a Bavarian district. Brückenschlag seeks to explore effective ways of health care linking university medicine (Maximalversorgung | maximum care) with regional inpatient, outpatient, rehabilitative, and preventive care structures (Regionalversorgung | regional care). To create advantages for both (potential) patients and the involved cooperation partners, project b4 qualitatively assesses needs and motivations among professionals, population groups, and political stakeholders at individual and collective levels. Besides providing an overview of the project structure as well as of regional population and healthcare characteristics, the first results of qualitative interviews conducted with different health experts will be presented. Interviewed experts include managers of participating hospitals, nurses, medical specialists working in the hospital and registered doctors operating in practices in rural areas. At the end of the project life and based on the identified factors relevant to the success -and also for failure- of participatory cooperation in health care, the project aims at informing other districts embarking on similar systems-oriented and human-centered healthcare projects. Individuals’ health care needs in dependence on the social space in which they live will guide the development of recommendations.

Keywords: cross-sectoral collaboration in health care, human-centered health care, regional health care, individual and structural health conditions

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Authors: Vanja Vlajkov, Ivana PajčIn, Mila Grahovac, Marta Loc, Dragana Budakov, Jovana Grahovac

Abstract:

The rhizosphere soil refers to the plant roots' dynamic environment characterized by their inhabitants' high biological activity. Rhizospheric bacteria are recognized as effective biocontrol agents and considered cardinal in alternative strategies for securing ecological plant diseases management. The need to suppress fungal pathogens is an urgent task, not only because of the direct economic losses caused by infection but also due to their ability to produce mycotoxins with harmful effects on human health. Aspergillus and Fusarium species are well-known producers of toxigenic metabolites with a high capacity to colonize crops and enter the food chain. The bacteria belonging to the Bacillus genus has been conceded as a plant beneficial species in agricultural practice and identified as plant growth-promoting rhizobacteria (PGPR). Besides incontestable potential, the full commercialization of microbial biopesticides is in the preliminary phase. Thus, there is a constant need for estimating the suitability of novel strains to be used as a central point of viable bioprocess leading to market-ready product development. In the present study, 76 potential producing strains were isolated from the rhizosphere soil, sampled from different localities in the Autonomous Province of Vojvodina, Republic of Serbia. The selective isolation process of strains started by resuspending 1 g of soil samples in 9 ml of saline and incubating at 28° C for 15 minutes at 150 rpm. After homogenization, thermal treatment at 100° C for 7 minutes was performed. Dilution series (10-1-10-3) were prepared, and 500 µl of each was inoculated on nutrient agar plates and incubated at 28° C for 48 h. The pure cultures of morphologically different strains indicating belonging to the Bacillus genus were obtained by the spread-plate technique. The cultivation of the isolated strains was carried out in an Erlenmeyer flask for 96 h, at 28 °C, 170 rpm. The antagonistic activity screening included two phytopathogenic fungi as test microorganisms: Aspergillus sp. and Fusarium sp. The mycelial growth inhibition was estimated based on the antimicrobial activity testing of cultivation broth by the diffusion method. For the Aspergillus sp., the highest antifungal activity was recorded for the isolates Kro-4a and Mah-1a. In contrast, for the Fusarium sp., following 15 isolates exhibited the highest antagonistic effect Par-1, Par-2, Par-3, Par-4, Kup-4, Paš-1b, Pap-3, Kro-2, Kro-3a, Kro-3b, Kra-1a, Kra-1b, Šar-1, Šar-2b and Šar-4. One-way ANOVA was performed to determine the antagonists' effect statistical significance on inhibition zone diameter. Duncan's multiple range test was conducted to define homogenous groups of antagonists with the same level of statistical significance regarding their effect on antimicrobial activity of the tested cultivation broth against tested pathogens. The study results have pointed out the significant in vitro potential of the isolated strains to be used as biocontrol agents for the suppression of the tested mycotoxigenic fungi. Further research should include the identification and detailed characterization of the most promising isolates and mode of action of the selected strains as biocontrol agents. The following research should also involve bioprocess optimization steps to fully reach the selected strains' potential as microbial biopesticides and design cost-effective biotechnological production.

Keywords: Bacillus, biocontrol, bioprocess, mycotoxigenic fungi

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