Search results for: the quantum dispersion relation of rotation mode
Commenced in January 2007
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Paper Count: 6243

Search results for: the quantum dispersion relation of rotation mode

1563 Online Information Seeking: A Review of the Literature in the Health Domain

Authors: Sharifah Sumayyah Engku Alwi, Masrah Azrifah Azmi Murad

Abstract:

The development of the information technology and Internet has been transforming the healthcare industry. The internet is continuously accessed to seek for health information and there are variety of sources, including search engines, health websites, and social networking sites. Providing more and better information on health may empower individuals, however, ensuring a high quality and trusted health information could pose a challenge. Moreover, there is an ever-increasing amount of information available, but they are not necessarily accurate and up to date. Thus, this paper aims to provide an insight of the models and frameworks related to online health information seeking of consumers. It begins by exploring the definition of information behavior and information seeking to provide a better understanding of the concept of information seeking. In this study, critical factors such as performance expectancy, effort expectancy, and social influence will be studied in relation to the value of seeking health information. It also aims to analyze the effect of age, gender, and health status as the moderator on the factors that influence online health information seeking, i.e. trust and information quality. A preliminary survey will be carried out among the health professionals to clarify the research problems which exist in the real world, at the same time producing a conceptual framework. A final survey will be distributed to five states of Malaysia, to solicit the feedback on the framework. Data will be analyzed using SPSS and SmartPLS 3.0 analysis tools. It is hoped that at the end of this study, a novel framework that can improve online health information seeking is developed. Finally, this paper concludes with some suggestions on the models and frameworks that could improve online health information seeking.

Keywords: information behavior, information seeking, online health information, technology acceptance model, the theory of planned behavior, UTAUT

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1562 Anatomical Adaptations of Three Astragalus Species under Salt Stress

Authors: Faycal Boughalleb, Raoudha Abdellaoui

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The effect of NaCl stress on root and leaf anatomy was investigated in three Astragalus species grown in 0-300 mM NaCl for 30 days under greenhouse conditions. Root cross section and cortex thickness was reduced under salt stress in both species while A. tenuifolius showed thinner cortex and the root cross section was unchanged. The epidermis stele thickness was unaffected by salinity in A. armatus and A. tenuifolius and was reduced in A. mareoticus with smaller xylem vessel size. In addition, vessel density and wall thickness of xylem was increased under salt conditions in the studies species. The entire lamina and mesophyll of the three species were thinner in salt-stressed plants. A. armatus and A. tenuifolius showed the higher thickness with increased size of the lower epidermis. NaCl (300 mM) reduced leaf water content by 41.5 % in A. mareoticus while it was unchanged in the other species. The size of the vascular bundle increased under salinity in A. tenuifolius leaves and it was unchanged in the other ones. A longer distance between leaf vascular bundle was occurred in A. mareoticus. The effects of NaCl on root and leaf ultrastructure are discussed in relation to the degree of salt resistance of these species. The unchanged biomass production under salt stress confirmed the higher tolerance oft A. tenuifolius to salinity. A. armatus was moderately salt tolerant with decrease of biomass production by 14.2 % while A. mareoticus was considered as salt sensitive plant when the decrease in biomass production reached 56.8%.

Keywords: Astragalus species, leaf ultrastructure, root anatomy, salt stress

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1561 A Possible Connection Between Taste Change and Zinc Deficiency after Bariatric Surgery: A Literature Review

Authors: Boshra Mozaffar, Iskandar Idris

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Taste change is a common complication after Bariatric surgery (BS). However, the cause of this is still not clear. Since zinc is important fortaste perception, zinc deficiency, which is common after BS, may play an important role for taste change after BS. In this review, we aimto collate evidence relating to taste change and zinc deficiencyin relation to BS; effects of zinc replacement on taste perception in general and thereafter discuss the possible role of zinc deficiency to induce taste change after BS. A literature search was conducted, using four electronic bibliographical databases—EMBASE, PubMed, AMED and MEDLINE. We identified all available and relevant articles published before 30th February 2021.In total, 33 studies were included. The total number of participants analysed was N= 3264. We showed that taste change is a frequent complication after BS, especially after Roux-en-Y gastric bypass RYGBP comparing to other types of procedures. Patients' taste sensitivity differs among studies, but the most important decline in taste preference was observed for sweet food. Twelve studies investigating zinc deficiency following BS showed a significant decrease in zinc levels at six months after surgery. Supplementation with 45–50 mg of zinc sulphate was effective in improving taste, except in cancer patients, who showed no improvement in taste following zinc supplementation. Zinc deficiency appears to be associated with taste change after BS. Supplementation with much higher levels of zinc, at 45–50 mg, was effective in taste change treatment for many cases of taste disorder. The currently recommended levels of zinc replacements currently prescribed to patients following BS were not effective for avoiding zinc deficiency after BS—and thus not effective for averting taste change. It is therefore suggested that taste change following BS is closely related to zinc deficiency induced by the surgery.

Keywords: taste change, taste disorder, bariatric surgery, zinc, zinc sulphate or Zn, deficiency, supplementation, and micro-nutrient deficiencies

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1560 Relationship between Perceived Level of Emotional Intelligence and Organizational Role Stress of Fire Fighters in Mumbai

Authors: Payal Maheshwari, Bansari Shah

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The research aimed to study the level of emotional intelligence (EI) and organizational role stress (ORS) of fire-fighters and the relationship between the two variables. Hundred and twenty fire-fighters were selected from different fire stations of Mumbai by purposive sampling. The firefighters who had the basic training, a minimum experience of 2 years and had been on the field during a crisis situation were selected for the study. The firefighters selected ranged from 23-58 years of age, and the number of years of experience ranged from 2 to 33 years. The findings of the study revealed that majority of the firefighters perceived themselves to be at an above average (57) and high (58) level of EI (M=429.35, SD=38.712). Domain-wise analysis disclosed that compared to self-awareness (92) and relationship management (93), more number of participants perceived themselves in the high category in the domains of self-management (108) and social management (106). Further, examination of the subdomain scores conveyed that a large number of participants rated themselves in the average level of these skills of accurate self-assessment (50), emotional self-control (50), adaptability (56) initiative (41), influence (66), change catalyst (53), and conflict management (50). With relation to the stress variable, it was found that almost half the number of the participants (59) rated themselves as having an average level of stress (M=137.44, SD=28.800). In most of the domains, majority of the participants perceived themselves as having an average level of stress, while in the domain of role isolation, self-role distance, and role ambiguity, majority of the firefighters rated themselves as having a low level of stress. A strong negative correlation (r=-.360**, p=.000) was found between EI and ORS. This study is a contribution to the literature and has implications for fire-fighters at the personal level, for the policymakers, and the fire department.

Keywords: emotional intelligence, organizational role stress, firefighters, relationship

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1559 Relation between Biochemical Parameters and Bone Density in Postmenopausal Women with Osteoporosis

Authors: Shokouh Momeni, Mohammad Reza Salamat, Ali Asghar Rastegari

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Background: Osteoporosis is the most prevalent metabolic bone disease in postmenopausal women associated with reduced bone mass and increased bone fracture. Measuring bone density in the lumbar spine and hip is a reliable measure of bone mass and can therefore specify the risk of fracture. Dual-energy X-ray absorptiometry(DXA) is an accurate non-invasive system measuring the bone density, with low margin of error and no complications. The present study aimed to investigate the relationship between biochemical parameters with bone density in postmenopausal women. Materials and methods: This cross-sectional study was conducted on 87 postmenopausal women referred to osteoporosis centers in Isfahan. Bone density was measured in the spine and hip area using DXA system. Serum levels of calcium, phosphorus, alkaline phosphatase and magnesium were measured by autoanalyzer and serum levels of vitamin D were measured by high-performance liquid chromatography(HPLC). Results: The mean parameters of calcium, phosphorus, alkaline phosphatase, vitamin D and magnesium did not show a significant difference between the two groups(P-value>0.05). In the control group, the relationship between alkaline phosphatase and BMC and BA in the spine was significant with a correlation coefficient of -0.402 and 0.258, respectively(P-value<0.05) and BMD and T-score in the femoral neck area showed a direct and significant relationship with phosphorus(Correlation=0.368; P-value=0.038). There was a significant relationship between the Z-score with calcium(Correlation=0.358; P-value=0.044). Conclusion: There was no significant relationship between the values ​​of calcium, phosphorus, alkaline phosphatase, vitamin D and magnesium parameters and bone density (spine and hip) in postmenopaus

Keywords: osteoporosis, menopause, bone mineral density, vitamin d, calcium, magnesium, alkaline phosphatase, phosphorus

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1558 Effects of Moisture on Fatigue Behavior of Asphalt Concrete Mixtures Using Four-Point Bending Test

Authors: Mohit Chauhan, Atul Narayan

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Moisture damage is the continuous deterioration of asphalt concrete mixtures by the loss of adhesive bond between the asphalt binder and aggregates, or loss of cohesive bonds within the asphalt binder in the presence of moisture. Moisture has been known to either cause or exacerbates distresses in asphalt concrete pavements. Since moisture would often retain for a relatively long duration at the bottom of asphalt concrete layer, the movement of traffic loading in this saturated condition would cause excess stresses or strains within the mixture. This would accelerate the degradation of the adhesion and cohesion within the mixture and likely to contribute the development of fatigue cracking in asphalt concrete pavements. In view of this, it is important to investigate the effect of moisture on the fatigue behavior of asphalt concrete mixtures. In this study, changes in fatigue characteristics after moisture conditioning were evaluated by conducting four-point beam fatigue tests on dry and moisture conditioned specimens. For this purpose, mixtures with two different types of binders were prepared and saturated with moisture using 700 mm Hg vacuum. Beam specimens, in this way, were taken to a saturation level of 65-75 percent. After preconditioning specimens in this degree of saturation and 60°C for a period of 24 hours, they were subjected to four point beam fatigue tests in strain-controlled mode with a strain amplitude of 400 microstrain. The results were then compared with the fatigue test results obtained with beam specimens that were not subjected to moisture conditioning. Test results show that the conditioning reduces both fatigue life and initial flexural stiffness of specimen significantly. The moisture conditioning was also found to increase the rate of reduction of flexural stiffness. Moreover, it was observed that the fatigue life ratio (FLR), the ratio of the fatigue life of the moisture conditioned sample to that of the dry sample, is significantly lower than the flexural stiffness ratio (FSR). The study indicates that four-point bending test is an appropriate tool with FLR and FSR as the potential parameters for moisture-sensitivity evaluation.

Keywords: asphalt concrete, fatigue cracking, moisture damage, preconditioning

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1557 Spatial and Geostatistical Analysis of Surficial Soils of the Contiguous United States

Authors: Rachel Hetherington, Chad Deering, Ann Maclean, Snehamoy Chatterjee

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The U.S. Geological Survey conducted a soil survey and subsequent mineralogical and geochemical analyses of over 4800 samples taken across the contiguous United States between the years 2007 and 2013. At each location, samples were taken from the top 5 cm, the A-horizon, and the C-horizon. Many studies have looked at the correlation between the mineralogical and geochemical content of soils and influencing factors such as parent lithology, climate, soil type, and age, but it seems little has been done in relation to quantifying and assessing the correlation between elements in the soil on a national scale. GIS was used for the mapping and multivariate interpolation of over 40 major and trace elements for surficial soils (0-5 cm depth). Qualitative analysis of the spatial distribution across the U.S. shows distinct patterns amongst elements both within the same periodic groups and within different periodic groups, and therefore with different behavioural characteristics. Results show the emergence of 4 main patterns of high concentration areas: vertically along the west coast, a C-shape formed through the states around Utah and northern Arizona, a V-shape through the Midwest and connecting to the Appalachians, and along the Appalachians. The Band Collection Statistics tool in GIS was used to quantitatively analyse the geochemical raster datasets and calculate a correlation matrix. Patterns emerged, which were not identified in qualitative analysis, many of which are also amongst elements with very different characteristics. Preliminary results show 41 element pairings with a strong positive correlation ( ≥ 0.75). Both qualitative and quantitative analyses on this scale could increase knowledge on the relationships between element distribution and behaviour in surficial soils of the U.S.

Keywords: correlation matrix, geochemical analyses, spatial distribution of elements, surficial soils

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1556 A Randomised Controlled Trial on the Nurse-Led Smartphone-Based Self-Management Programme for Type 2 Diabetes Patients with Poor Glycemic Control

Authors: Wenru Wang

Abstract:

Over the past decades, Asia has emerged as the ‘diabetes epicentre’ in the world due to rapid economic development, urbanization and nutrition transition. There is an urgent need to develop more effective and cost-effective care management strategies in response to this rising diabetes epidemic. This study aims to develop and compare a nurse-led smartphone-based self-management programme with an existing nurse-led diabetes service on health-related outcomes among type 2 diabetes patients with poor glycemic control in Singapore. We proposed a randomized controlled trial with pre- and repeated post-tests control group design. A total of 128 type 2 diabetes patients with poor glycemic control will be recruited from the diabetes clinic of an acute public hospital in Singapore through convenience sampling. Study participants will be either randomly allocated to the experimental group or control group. Outcome measures used will include the 10-item General Self-Efficacy Scale, 11-item Revised Summary of Diabetes Self-care Activities, and 19-item Diabetes-Dependent Quality of Life. Data will be collected at 3-time points: baseline, three months and six months from the baseline, respectively. It is expected that this programme will be an alternative offered to diabetes patients to master their self-care management skills, in addition to the existing diabetes service provided in diabetes clinics in Singapore hospitals. Also, the self-supporting and less resource-intensive nature of this programme, through the use of smartphone app as a mode of intervention delivery, will greatly reduce nurses’ direct contact time with patients and allow more time to be allocated to those who require more attention. The study has been registered with clinicaltrials.gov. The trial registration number is NCT03088475.

Keywords: type 2 diabetes, poor glycaemic control, nurse-led, smartphone-based, self-management, health-relevant outcomes

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1555 Cybersecurity Assessment of Decentralized Autonomous Organizations in Smart Cities

Authors: Claire Biasco, Thaier Hayajneh

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A smart city is the integration of digital technologies in urban environments to enhance the quality of life. Smart cities capture real-time information from devices, sensors, and network data to analyze and improve city functions such as traffic analysis, public safety, and environmental impacts. Current smart cities face controversy due to their reliance on real-time data tracking and surveillance. Internet of Things (IoT) devices and blockchain technology are converging to reshape smart city infrastructure away from its centralized model. Connecting IoT data to blockchain applications would create a peer-to-peer, decentralized model. Furthermore, blockchain technology powers the ability for IoT device data to shift from the ownership and control of centralized entities to individuals or communities with Decentralized Autonomous Organizations (DAOs). In the context of smart cities, DAOs can govern cyber-physical systems to have a greater influence over how urban services are being provided. This paper will explore how the core components of a smart city now apply to DAOs. We will also analyze different definitions of DAOs to determine their most important aspects in relation to smart cities. Both categorizations will provide a solid foundation to conduct a cybersecurity assessment of DAOs in smart cities. It will identify the benefits and risks of adopting DAOs as they currently operate. The paper will then provide several mitigation methods to combat cybersecurity risks of DAO integrations. Finally, we will give several insights into what challenges will be faced by DAO and blockchain spaces in the coming years before achieving a higher level of maturity.

Keywords: blockchain, IoT, smart city, DAO

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1554 Measuring the Influence of Functional Proximity on Environmental Urban Performance via IMM: Four Study Cases in Milan

Authors: Massimo Tadi, M. Hadi Mohammad Zadeh, Ozge Ogut

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Although how cities’ forms are structured is studied, more efforts are needed on systemic comprehensions and evaluations of the urban morphology through quantitative metrics that are able to describe the performance of a city in relation to its formal properties. More research is required in this direction in order to better describe the urban form characteristics and their impact on the environmental performance of cities and to increase their sustainability stewardship. With the aim of developing a better understanding of the built environment’s systemic structure, the intention of this paper is to present a holistic methodology for studying the behavior of the built environment and investigate the methods for measuring the effect of urban structure to the environmental performance. This goal will be pursued through an inquiry into the morphological components of the urban systems and the complex relationships between them. Particularly, this paper focuses on proximity, referring to the proximity of different land-uses, is a concept with which Integrated Modification Methodology (IMM) explains how land-use allocation might affect the choice of mobility in neighborhoods, and especially, encourage or discourage non-motived mobility. This paper uses proximity to demonstrate that the structure attributes can quantifiably relate to the performing behavior in the city. The target is to devise a mathematical pattern from the structural elements and correlate it directly with urban performance indicators concerned with environmental sustainability. The paper presents some results of this rigorous investigation of urban proximity and its correlation with performance indicators in four different areas in the city of Milan, each of them characterized by different morphological features.

Keywords: built environment, ecology, sustainable indicators, sustainability, urban morphology

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1553 Increasing Sustainability Using the Potential of Urban Rivers in Developing Countries with a Biophilic Design Approach

Authors: Mohammad Reza Mohammadian, Dariush Sattarzadeh, Mir Mohammad Javad Poor Hadi Hosseini

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Population growth, urban development and urban buildup have disturbed the balance between the nature and the city, and so leading to the loss of quality of sustainability of proximity to rivers. While in the past, the sides of urban rivers were considered as urban green space. Urban rivers and their sides that have environmental, social and economic values are important to achieve sustainable development. So far, efforts have been made at various scales in various cities around the world to revitalize these areas. On the other hand, biophilic design is an innovative design approach in which attention to natural details and relation to nature is a fundamental concept. The purpose of this study is to provide an integrated framework of urban design using the potential of urban rivers (in order to increase sustainability) with a biophilic design approach to be used in cities in developing countries. The methodology of the research is based on the collection of data and information from research and projects including a study on biophilic design, investigations and projects related to the urban rivers, and a review of the literature on sustainable urban development. Then studying the boundary of urban rivers is completed by examining case samples. Eventually, integrated framework of urban design, to design the boundaries of urban rivers in the cities of developing countries is presented regarding the factors affecting the design of these areas. The result shows that according to this framework, the potential of the river banks is utilized to increase not only the environmental sustainability but also social, economic and physical stability with regard to water, light, and the usage of indigenous materials, etc.

Keywords: urban rivers, biophilic design, urban sustainability, nature

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1552 In vivo Antidiarrheal and ex-vivo Spasmolytic Activities of the Aqueous Extract of the Roots of Echinops kebericho Mesfin in Rodents and Isolated Guinea-Pig Ileum

Authors: Fisseha Shiferie (Bpharm, Mpharm)

Abstract:

Diarrhea is a common gastrointestinal disorder characterized by an increase in stool frequency and a change in stool consistency. Inspite of the availability of many drugs as antidiarrheal agents, the search for a drug with affordable cost and better efficacy is essential to overcome diarrheal problems. The root extract of Echinops kebericho, is used by traditional practitioners for the treatment of diarrhea. However, the scientific basis for this usage has not been yet established. The purpose of the present study was to evaluate the antidiarrheal and spasmolytic activities of the aqueous extract of the roots of E. kebericho in rodents and isolated guinea-pig ileum preparations. In the castor oil induced intestinal transit test, E. kebericho produced a significant (p < 0.01) dose dependent decrease in propulsion with peristaltic index values of 45.05±3.3, 42.71±2.25 and 33.17±3.3%, respectively at doses of 100, 200 and 400 mg/kg compared with 63.43±7.3% for control. In the castor oil-induced diarrhea test, the mean defecation was reduced from 1.81±0.18 to 0.99 ± 0.21 compared with 2.59 ±0.81 for control. The extract (at doses stated above) significantly decreased the volume of intestinal fluid secretion induced by castor oil (2.31±0.1 to 2.01±0.2) in relation to 3.28±0.3 for control. When tested on a guinea-pig ileum, root extract of Echinops kebericho exhibited a dose dependent spasmolytic effect, 23.07 % being its highest inhibitory effect. The results obtained in this study give some scientific support to the use of Echinops kebericho as an antidiarrheal agent due to its inhibitory effects on the different diarrheal parameters used in this study.

Keywords: antidiarrheal activity, E. kebericho, traditional medicine, diarrhea, enteropooling, and intestinal transit

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1551 Consumers of Counterfeit Goods and the Role of Context: A Behavioral Perspective of the Process

Authors: Carla S. C. da Silva, Cristiano Coelho, Junio Souza

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The universe of luxury has charmed and seduced consumers for centuries. Since the middle ages, their symbols are displayed as objects of power and status, arousing desire and provoking social covetousness. In this way, the counterfeit market is growing every day, offering a group of consumers the opportunity to enter into a distinct social position, where the beautiful and shiny brand logo signals an inclusion passport to everything this group wants. This work sought to investigate how the context and the social environment can influence consumers to choose products of symbolic brands even if they are not legitimate and how this behavior is accepted in society. The study proposed: a) to evaluate the measures of knowledge and quality of a set of marks presented in the manipulation of two contexts (luxury x academic) between buyers and non-buyers of forgeries, both for original products and their correspondence with counterfeit products; b) measure the effect of layout on the verbal responses of buyers and non-buyers in relation to their assessment of the behavior of buyers of counterfeits. The present study, in addition to measuring the level of knowledge and quality attributed to each brand investigated, also verified the willingness of consumers to pay for a falsified good of the brands of predilection compared to the original study. This data can serve as a parameter for luxury brand managers in their counterfeit coping strategies. The investigation into the frequency of purchase has shown that those who buy counterfeit goods do so regularly, and there is a propensity to repeat the purchase. It was noted that a significant majority of buyers of counterfeits are prone to invest in illegality to meet their expectations of being in line with the standards of their interest groups.

Keywords: luxury, consumers, counterfeits, context, behaviorism

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1550 A Preliminary Analysis of Sustainable Development in the Belgrade Metropolitan Area

Authors: Slavka Zeković, Miodrag Vujošević, Tamara Maričić

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The paper provides a comprehensive analysis of the sustainable development in the Belgrade Metropolitan Region - BMA (level NUTS 2) preliminary evaluating the three chosen components: 1) economic growth and developmental changes; 2) competitiveness; and 3) territorial concentration and industrial specialization. First, we identified the main results of development changes and economic growth by applying Shift-share analysis on the metropolitan level. Second, the empirical evaluation of competitiveness in the BMA is based on the analysis of absolute and relative values of eight indicators by Spider method. Paper shows that the consideration of the national share, industrial mix and metropolitan/regional share in total Shift share of the BMA, as well as economic/functional specialization of the BMA indicate very strong process of deindustrialization. Allocative component of the BMA economic growth has positive value, reflecting the above-average sector productivity compared to the national average. Third, the important positive role of metropolitan/regional component in decomposition of the BMA economic growth is highlighted as one of the key results. Finally, comparative analysis of the industrial territorial concentration in the BMA in relation to Serbia is based on location quotient (LQ) or Balassa index as a valid measure. The results indicate absolute and relative differences in decrease of industry territorial concentration as well as inefficiency of utilizing territorial capital in the BMA. Results are important for the increase of regional competitiveness and territorial distribution in this area as well as for improvement of sustainable metropolitan and sector policies, planning and governance on this level.

Keywords: Belgrade Metropolitan Area (BMA), comprehensive analysis / evaluation, economic growth, competitiveness, sustainable development

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1549 Combustion Improvements by C4/C5 Bio-Alcohol Isomer Blended Fuels Combined with Supercharging and EGR in a Diesel Engine

Authors: Yasufumi Yoshimoto, Enkhjargal Tserenochir, Eiji Kinoshita, Takeshi Otaka

Abstract:

Next generation bio-alcohols produced from non-food based sources like cellulosic biomass are promising renewable energy sources. The present study investigates engine performance, combustion characteristics, and emissions of a small single cylinder direct injection diesel engine fueled by four kinds of next generation bio-alcohol isomer and diesel fuel blends with a constant blending ratio of 3:7 (mass). The tested bio-alcohol isomers here are n-butanol and iso-butanol (C4 alcohol), and n-pentanol and iso-pentanol (C5 alcohol). To obtain simultaneous reductions in NOx and smoke emissions, the experiments employed supercharging combined with EGR (Exhaust Gas Recirculation). The boost pressures were fixed at two conditions, 100 kPa (naturally aspirated operation) and 120 kPa (supercharged operation) provided with a roots blower type supercharger. The EGR rates were varied from 0 to 25% using a cooled EGR technique. The results showed that both with and without supercharging, all the bio-alcohol blended diesel fuels improved the trade-off relation between NOx and smoke emissions at all EGR rates while maintaining good engine performance, when compared with diesel fuel operation. It was also found that regardless of boost pressure and EGR rate, the ignition delays of the tested bio-alcohol isomer blends are in the order of iso-butanol > n-butanol > iso-pentanol > n-pentanol. Overall, it was concluded that, except for the changes in the ignition delays the influence of bio-alcohol isomer blends on the engine performance, combustion characteristics, and emissions are relatively small.

Keywords: alternative fuel, butanol, diesel engine, EGR (Exhaust Gas Recirculation), next generation bio-alcohol isomer blended fuel, pentanol, supercharging

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1548 On the Existence of Homotopic Mapping Between Knowledge Graphs and Graph Embeddings

Authors: Jude K. Safo

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Knowledge Graphs KG) and their relation to Graph Embeddings (GE) represent a unique data structure in the landscape of machine learning (relative to image, text and acoustic data). Unlike the latter, GEs are the only data structure sufficient for representing hierarchically dense, semantic information needed for use-cases like supply chain data and protein folding where the search space exceeds the limits traditional search methods (e.g. page-rank, Dijkstra, etc.). While GEs are effective for compressing low rank tensor data, at scale, they begin to introduce a new problem of ’data retreival’ which we observe in Large Language Models. Notable attempts by transE, TransR and other prominent industry standards have shown a peak performance just north of 57% on WN18 and FB15K benchmarks, insufficient practical industry applications. They’re also limited, in scope, to next node/link predictions. Traditional linear methods like Tucker, CP, PARAFAC and CANDECOMP quickly hit memory limits on tensors exceeding 6.4 million nodes. This paper outlines a topological framework for linear mapping between concepts in KG space and GE space that preserve cardinality. Most importantly we introduce a traceable framework for composing dense linguistic strcutures. We demonstrate performance on WN18 benchmark this model hits. This model does not rely on Large Langauge Models (LLM) though the applications are certainy relevant here as well.

Keywords: representation theory, large language models, graph embeddings, applied algebraic topology, applied knot theory, combinatorics

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1547 Evaluation of National Research Motivation Evolution with Improved Social Influence Network Theory Model: A Case Study of Artificial Intelligence

Authors: Yating Yang, Xue Zhang, Chengli Zhao

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In the increasingly interconnected global environment brought about by globalization, it is crucial for countries to timely grasp the development motivations in relevant research fields of other countries and seize development opportunities. Motivation, as the intrinsic driving force behind actions, is abstract in nature, making it difficult to directly measure and evaluate. Drawing on the ideas of social influence network theory, the research motivations of a country can be understood as the driving force behind the development of its science and technology sector, which is simultaneously influenced by both the country itself and other countries/regions. In response to this issue, this paper improves upon Friedkin's social influence network theory and applies it to motivation description, constructing a dynamic alliance network and hostile network centered around the United States and China, as well as a sensitivity matrix, to remotely assess the changes in national research motivations under the influence of international relations. Taking artificial intelligence as a case study, the research reveals that the motivations of most countries/regions are declining, gradually shifting from a neutral attitude to a negative one. The motivation of the United States is hardly influenced by other countries/regions and remains at a high level, while the motivation of China has been consistently increasing in recent years. By comparing the results with real data, it is found that this model can reflect, to some extent, the trends in national motivations.

Keywords: influence network theory, remote assessment, relation matrix, dynamic sensitivity matrix

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1546 Workload and Task Distribution in Public Healthcare: A Qualitative Explorative Study From Nurse Leaders’ Perceptions

Authors: Jessica Hemberg, Mikaela Miller

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Unreasonable workload and work-related stress can reduce nurse leaders’ job satisfaction and productivity and can increase absence and burnout. Nurse leaders’ workload in public healthcare settings is relatively unresearched. The aim of this study was to investigate nurse leaders’ perceptions of workload and task distribution with relation to leading work tasks in public healthcare. A qualitative explorative design was used. The data material consisted of texts from interviews with nurse leaders in public healthcare (N=8). The method was inspired by content analysis. The COREQ checklist was used. Informed consent was sought from the participants regarding study participation and the storage and handling of data for research purposes. Six main themes were found: Increased and unreasonable workload, Length of work experience as nurse leader affects perception of workload, Number of staff and staff characteristics affect perception of workload, Versatile and flexible task distribution, Working overtime as a way of managing high workload, and Insufficient time for leadership mission. The workload for nurse leaders in a public healthcare setting was perceived to be unreasonable. Common measures for managing high workload included working overtime, delegating work tasks and organizing more staff resources in the form of additional staff. How nurse leaders perceive their workload was linked to both the number of staff and staff characteristics. These should both be considered equally important when determining staff levels and measuring nurse leaders’ workload. Future research should focus on investigating workload and task distribution from nurses’ perspectives.

Keywords: nurse leaders, workload, task distribution, public healthcare, qualitative

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1545 Students with Hearing Impairment and Their Access to Inclusive Education in Nagpur City, India: An Exploratory Study

Authors: Avanika Gupta

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Education plays a significant and remedial role in balancing the socio-economic fabric of a country. Inclusive education is considered as the most appropriate mode of teaching students with hearing impairment (SwHI) by various national and international legislations. But inclusive education is still an evolving concept among the disability studies scholars and policy makers in India. The study aimed to examine accessibility of SwHI in mainstream schools if there are special provisions for SwHI. The study also intended to identify if the provisions are same for deaf and hard-of-hearing students. Using stratified random sampling technique, a school was selected from each of the six administrative zones of Nagpur city. All the selected schools had primary and secondary level education and were co-educational in nature. Interview with principals of these schools and focused-group- observation method showcased lack of accessibility for SwHI in attending schools. Not even a single school had a hearing impaired student, either deaf or hard-of-hearing depicting the double marginalization of SwHI. This is despite the fact that the right to education is a fundamental right in India, and national legislation on disability has special provisions for ensuring educational opportunities to SwHI. None of the schools even had an Indian Sign Language (ISL) instructor. Both observations seemed cause and effect of one another. One of the principals informed that they have seats for all students with disabilities but they usually lie vacant due to lack of awareness among the parents. One school had 2 students with locomotive impairment while another had a student with visual impairment. Principals of two special schools were also interviewed to understand the reason behind the low enrollment rate of SwHI in mainstream schools. Guardian preference, homogeneity, relatable faculty, familiar environment were some of the chief reasons mentioned. Few suggestions for the policymakers, teachers, guardians and the students are also recommended so that Indian education system could become inclusive in true sense.

Keywords: deaf, hard-of-hearing, inclusive education, India, Nagpur, students with hearing impairment

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1544 Impact of Digitization and Diversification in Reducing Volatility in Art Markets

Authors: Nishi Malhotra

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Art has developed as a mode of investment and saving. Art and culture of any nation is the source of foreign direct investment (FDI) generation and growth development. Several intermediaries and skill-building organizations thrive on at and culture for their earnings. Indian art market has grown to Rs. 2000 Crores. Art establishment houses access to privileged information is the main reason for arbitrariness and volatility in the market. The commercialization of art and development of the markets with refinement in the taste of the customers have led to the development of art as an investment avenue. Investors keen on investing in these products can do so, and earnings from art are taxable too, like any other capital asset. This research paper is aimed at exploring the role of art and culture as an investment avenue in India and reasons for increasing volatilities in the art market. Based on an extensive literature review and secondary research, a benchmarking study has been conducted to capture the growth of the art as an investment avenue. These studies indicate that during the financial crisis of 2008-10, the art emerged as an alternative investment avenue. The paper aims at discussing the financial engineering of various art funds and instruments. Based on secondary data available from Sotheby’s, Christies, Bonham, there is a positive correlation between strategic diversification and increasing return in the Art market. Similarly, digitization has led to disintermediation in the art markets and also helped to increase the market base. The data clearly enumerates the growing interest of the Indian investor towards art as an investment option. Much like any other broad asset class, art market too thrives on excess returns provided by diversification. Many financial intermediaries and art funds have emerged, to offer valuable investment planning advisory to a genuine investor. This paper clearly highlights the increasing returns of strategic diversification and its impact on reducing volatility in the art markets. Moreover, with coming up of e-auctions and websites, investors are able to analyse art more objectively. Digitization and commercialization of art have definitely helped in reducing volatility in world art markets.

Keywords: art, investment avenue, diversification, digitization

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1543 Reduction Behavior of Medium Grade Manganese Ore from Karangnunggal during a Sintering Process in Methane Gas

Authors: H. Aripin, I. Made Joni, Edvin Priatna, Nundang Busaeri, Svilen Sabchevski

Abstract:

In this investigation, manganese has been produced from medium grade manganese ore from Karangnunggal mine (West Java, Indonesia). The ores were grinded using a jar mill to pass through a 150 mesh sieve. The effects of keeping it at a temperature of 1200 °C in methane gas on the structural properties have been studied. The material’s properties have been characterized on the basis of the experimental data obtained using X-ray fluorescence (XRF), X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy. It has been found that the ore contains MnO₂ as the main constituents at about 46.80 wt.%. It can be also observed that the ore particles are agglomerated forming dense grains with different texture and morphology. The irregular-shaped grains with dark contrast, the large brighter grains, and smaller grains with bright texture and smooth surfaces are associated with the presence of manganese, calcium, and quartz, respectively. From XRD patterns, MnO₂ is reduced to hausmannite (Mn₃O₄), manganosite (MnO) and manganese carbide (Mn₇C₃). At a temperature of 1200°C the keeping time does not have any effect on the formation of crystals and the crystalline phases remain almost unchanged in the time range from 15 to 90 minutes. An increase of the keeping time up to 45 minutes during the sintering process leads to an increase of the MnO concentration, while at 90 minutes, the concentration decreases. At longer keeping times the excess reaction of the methane gas and manganese oxide in the ore causes an increase of carbon deposition. As a result, it blocks the particle surface and then hinders the reduction process of manganese oxide. From FTIR spectrum allows one to explain that the appearance of C=O stretching mode arises from absorption of atmospheric methane and manganese oxide of the ore. The intensity of this band increases with increasing the keeping time, indicating an increase of carbon deposition on the surface of manganese oxide.

Keywords: manganese, medium grade manganese ore, structural properties, keeping the temperature, carbon deposition

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1542 The Cleavage of DNA by the Anti-Tumor Drug Bleomycin at the Transcription Start Sites of Human Genes Using Genome-Wide Techniques

Authors: Vincent Murray

Abstract:

The glycopeptide bleomycin is used in the treatment of testicular cancer, Hodgkin's lymphoma, and squamous cell carcinoma. Bleomycin damages and cleaves DNA in human cells, and this is considered to be the main mode of action for bleomycin's anti-tumor activity. In particular, double-strand breaks are thought to be the main mechanism for the cellular toxicity of bleomycin. Using Illumina next-generation DNA sequencing techniques, the genome-wide sequence specificity of bleomycin-induced double-strand breaks was determined in human cells. The degree of bleomycin cleavage was also assessed at the transcription start sites (TSSs) of actively transcribed genes and compared with non-transcribed genes. It was observed that bleomycin preferentially cleaved at the TSSs of actively transcribed human genes. There was a correlation between the degree of this enhanced cleavage at TSSs and the level of transcriptional activity. Bleomycin cleavage is also affected by chromatin structure and at TSSs, the peaks of bleomycin cleavage were approximately 200 bp apart. This indicated that bleomycin was able to detect phased nucleosomes at the TSSs of actively transcribed human genes. The genome-wide cleavage pattern of the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin was also investigated in human cells. As found for bleomycin, these bleomycin analogues also preferentially cleaved at the TSSs of actively transcribed human genes. The cytotoxicity (IC₅₀ values) of these bleomycin analogues was determined. It was found that the degree of enhanced cleavage at TSSs was inversely correlated with the IC₅₀ values of the bleomycin analogues. This suggested that the level of cleavage at the TSSs of actively transcribed human genes was important for the cytotoxicity of bleomycin and analogues. Hence this study provided a deeper understanding of the cellular processes involved in the cancer chemotherapeutic activity of bleomycin.

Keywords: anti-tumour activity, bleomycin analogues, chromatin structure, genome-wide study, Illumina DNA sequencing

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1541 The Alarming Caesarean-Section Delivery Rate in Addis Ababa, Ethiopia

Authors: Yibeltal T. Bayou, Yohana S. Mashalla, Gloria Thupayagale-Tshweneagae

Abstract:

Background: According to the World Health Organization, caesarean section delivery rates of more than 10-15% caesarean section deliveries in any specific geographic region in the world are not justifiable. The aim of the study was to describe the level and analyse determinants of caesarean section delivery in Addis Ababa. Methods: Data was collected in Addis Ababa using a structured questionnaire administered to 901 women aged 15-49 years through a stratified two-stage cluster sampling technique. Binary logistic regression model was employed to identify predictors of caesarean section delivery. Results: Among the 835 women who delivered their last birth at healthcare facilities, 19.2% of them gave birth by caesarean section. About 9.0% of the caesarean section births were due to mother’s request or service provider’s influence without any medical indication. The caesarean section delivery rate was much higher than the recommended rate particularly among the non-slum residents (27.2%); clients of private healthcare facilities (41.1%); currently married women (20.6%); women with secondary (22.2%) and tertiary (33.6%) level of education; and women belonging to the highest wealth quintile household (28.2%). The majority (65.8%) of the caesarean section clients were not informed about the consequences of caesarean section delivery by service providers. The logistic regression model shows that older age (30-49), secondary and above education, non-slum residence, high-risk pregnancy and receiving adequate antenatal care were significantly positively associated with caesarean section delivery. Conclusion: Despite the unreserved effort towards achieving MDG 5 through safe skilled delivery assistance among others, the high caesarean section rate beyond the recommend limit, and the finding that caesarean sections done without medical indications were also alarming. The government and city administration should take appropriate measures before the problems become setbacks in healthcare provision. Further investigations should focus on the effect of caesarean section delivery on maternal and child health outcomes in the study area.

Keywords: Addis Ababa, caesarean section, mode of delivery, slum residence

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1540 The Population Death Model and Influencing Factors from the Data of The "Sixth Census": Zhangwan District Case Study

Authors: Zhou Shangcheng, Yi Sicen

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Objective: To understand the mortality patterns of Zhangwan District in 2010 and provide the basis for the development of scientific and rational health policy. Methods: Data are collected from the Sixth Census of Zhangwan District and disease surveillance system. The statistical analysis include death difference between age, gender, region and time and the related factors. Methods developed for the Global Burden of Disease (GBD) Study by the World Bank and World Health Organization (WHO) were adapted and applied to Zhangwan District population health data. DALY rate per 1,000 was calculated for varied causes of death. SPSS 16 is used by statistic analysis. Results: From the data of death population of Zhangwan District we know the crude mortality rate was 6.03 ‰. There are significant differences of mortality rate in male and female population which was respectively 7.37 ‰ and 4.68 ‰. 0 age group population life expectancy in Zhangwan District in 2010 was 78.40 years old(Male 75.93, Female 81.03). The five leading causes of YLL in descending order were: cardiovascular diseases(42.63DALY/1000), malignant neoplasm (23.73DALY/1000), unintentional injuries (5.84DALY/1000), Respiratory diseases(5.43 DALY/1000), Respiratory infections (2.44DALY/1000). In addition, there are strong relation between the marital status , educational level and mortality in some to a certain extend. Conclusion Zhangwan District, as city level, is at lower mortality levels. The mortality of the total population of Zhangwan District has a downward trend and life expectancy is rising.

Keywords: sixth census, Zhangwan district, death level differences, influencing factors, cause of death

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1539 Capacity Oversizing for Infrastructure Sharing Synergies: A Game Theoretic Analysis

Authors: Robin Molinier

Abstract:

Industrial symbiosis (I.S) rely on two basic modes of cooperation between organizations that are infrastructure/service sharing and resource substitution (the use of waste materials, fatal energy and recirculated utilities for production). The former consists in the intensification of use of an asset and thus requires to compare the incremental investment cost to be incurred and the stand-alone cost faced by each potential participant to satisfy its own requirements. In order to investigate the way such a cooperation mode can be implemented we formulate a game theoretic model integrating the grassroot investment decision and the ex-post access pricing problem. In the first period two actors set cooperatively (resp. non-cooperatively) a level of common (resp. individual) infrastructure capacity oversizing to attract ex-post a potential entrant with a plug-and-play offer (available capacity, tariff). The entrant’s requirement is randomly distributed and known only after investments took place. Capacity cost exhibits sub-additive property so that there is room for profitable overcapacity setting in the first period under some conditions that we derive. The entrant willingness-to-pay for the access to the infrastructure is driven by both her standalone cost and the complement cost to be incurred in case she chooses to access an infrastructure whose the available capacity is lower than her requirement level. The expected complement cost function is thus derived, and we show that it is decreasing, convex and shaped by the entrant’s requirements distribution function. For both uniform and triangular distributions optimal capacity level is obtained in the cooperative setting and equilibrium levels are determined in the non-cooperative case. Regarding the latter, we show that competition is deterred by the first period investor with the highest requirement level. Using the non-cooperative game outcomes which gives lower bounds for the profit sharing problem in the cooperative one we solve the whole game and describe situations supporting sharing agreements.

Keywords: capacity, cooperation, industrial symbiosis, pricing

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1538 Effect of Food Supplies Holstein Calves Supplemented with Bacillus Subtilis PB6 in Morbidity and Mortality

Authors: Banca Patricia Pena Revuelta, Ramiro Gonzalez Avalos, Juan Leonardo Rocha Valdez, Jose Gonzalez Avalos, Karla Rodriguez Hernandez

Abstract:

Probiotics are a promising alternative to improve productivity and animals' health. In addition, they can be part of the composition of different types of products, including foods (functional foods), medicines, and dietary supplements. The objective of the present work was to evaluate the effect of the feeding of Holstein calves supplemented with bacillus subtilis PB6 in morbidity and mortality. 60 newborn animals were used, randomly included in 1 of 3 treatments. The treatments were as follows: T1 = control, T2 = 10 g / calf / day. The first takes within 20 min after birth, T3 = 10 g / calf/day. The first takes between 12 and 24 h after birth. In all the treatments, 432 L of pasteurized whole milk divided into two doses/day 07:00 and 15:00, respectively, were given for 60 days. The addition of bacillus subtilis PB6 was carried out in the milk tub at the time of feeding them. The first colostrum intake (2 L • intake) was given within 2 h after birth, after which they were given a second 6 h after the first one. The diseases registered to monitor the morbidity and mortality of the calves were: diarrhea and pneumonia. The registry was carried out from birth to 60 days of life. The parameter evaluated was food consumption. The variable statistical analysis was performed using analysis of variance, and comparison of means was performed using the Tukey test. The value of P < 0.05 was used to consider the statistical difference. The results of the present study in relation to the consumption of food show no statistical difference P < 0.05 between treatments (14,762, 11,698, and 12,403 kg of food average, respectively). Calves group to which they were not provided Bacillus subtilis PB6 obtained higher feed intake. The addition of Bacillus subtilis PB6 in feeding calves does not increase feed intake.

Keywords: feeding, development, milk, probiotic

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1537 Development and application of Humidity-Responsive Controlled Release Active Packaging Based on Electrospinning Nanofibers and In Situ Growth Polymeric Film in Food preservation

Authors: Jin Yue

Abstract:

Fresh produces especially fruits, vegetables, meats and aquatic products have limited shelf life and are highly susceptible to deterioration. Essential oils (EOs) extracted from plants have excellent antioxidant and broad-spectrum antibacterial activities, and they can play as natural food preservatives. But EOs are volatile, water insoluble, pungent, and easily decomposing under light and heat. Many approaches have been developed to improve the solubility and stability of EOs such as polymeric film, coating, nanoparticles, nano-emulsions and nanofibers. Construction of active packaging film which can incorporate EOs with high loading efficiency and controlled release of EOs has received great attention. It is still difficult to achieve accurate release of antibacterial compounds at specific target locations in active packaging. In this research, a relative humidity-responsive packaging material was designed, employing the electrospinning technique to fabricate a nanofibrous film loaded with a 4-terpineol/β-cyclodextrin inclusion complexes (4-TA/β-CD ICs). Functioning as an innovative food packaging material, the film demonstrated commendable attributes including pleasing appearance, thermal stability, mechanical properties, and effective barrier properties. The incorporation of inclusion complexes greatly enhanced the antioxidant and antibacterial activity of the film, particularly against Shewanella putrefaciens, with an inhibitory efficiency of up to 65%. Crucially, the film realized controlled release of 4-TA under 98% high relative humidity conditions by inducing the plasticization of polymers caused by water molecules, swelling of polymer chains, and destruction of hydrogen bonds within the cyclodextrin inclusion complex. This film with a long-term antimicrobial effect successfully extended the shelf life of Litopenaeus vannamei shrimp to 7 days at 4 °C. To further improve the loading efficiency and long-acting release of EOs, we synthesized the γ-cyclodextrin-metal organic frameworks (γ-CD-MOFs), and then efficiently anchored γ-CD-MOFs on chitosan-cellulose (CS-CEL) composite film by in situ growth method for controlled releasing of carvacrol (CAR). We found that the growth efficiency of γ-CD-MOFs was the highest when the concentration of CEL dispersion was 5%. The anchoring of γ-CD-MOFs on CS-CEL film significantly improved the surface area of CS-CEL film from 1.0294 m2/g to 43.3458 m2/g. The molecular docking and 1H NMR spectra indicated that γ-CD-MOF has better complexing and stabilizing ability for CAR molecules than γ-CD. In addition, the release of CAR reached 99.71±0.22% on the 10th day, while under 22% RH, the release pattern of CAR was a plateau with 14.71 ± 4.46%. The inhibition rate of this film against E. coli, S. aureus and B. cinerea was more than 99%, and extended the shelf life of strawberries to 7 days. By incorporating the merits of natural biopolymers and MOFs, this active packaging offers great potential as a substitute for traditional packaging materials.

Keywords: active packaging, antibacterial activity, controlled release, essential oils, food quality control

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1536 Polymer Nanocoatings With Enhanced Self-Cleaning and Icephobic Properties

Authors: Bartlomiej Przybyszewski, Rafal Kozera, Katarzyna Zolynska, Anna Boczkowska, Daria Pakula

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The build-up and accumulation of dirt, ice, and snow on structural elements and vehicles is an unfavorable phenomenon, leading to economic losses and often also posing a threat to people. This problem occurs wherever the use of polymer coatings has become a standard, among others in photovoltaic farms, aviation, wind energy, and civil engineering. The accumulated pollution on the photovoltaic modules can reduce their efficiency by several percent, and snow stops power production. Accumulated ice on the blades of wind turbines or the wings of airplanes and drones disrupts the airflow by changing their shape, leading to increased drag and reduced efficiency. This results in costly maintenance and repairs. The goal of the work is to reduce or completely eliminate the accumulation of dirt, snow, and ice build-up on polymer coatings by achieving self-cleaning and icephobic properties. It is done by the use of a multi-step surface modification of the polymer nanocoatings. For this purpose, two methods of surface structuring and the preceding volumetric modification of the chemical composition with proprietary organosilicon compounds and/or mineral additives were used. To characterize the surface topography of the modified coatings, light profilometry was utilized. Measurements of the wettability parameters (static contact angle and contact angle hysteresis) on the investigated surfaces allowed to identify their wetting behavior and determine relation between hydrophobic and anti-icing properties. Ice adhesion strength was measured to assess coatings' anti-icing behavior.

Keywords: anti-icing properties, self-cleaning, polymer coatings, icephobic coatings

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1535 Detection of Pollution in the Catchment Area of Baha Region by Using Some Common Plants as a Bioindicators

Authors: Saad M. Howladar

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Although, there are a little data on the use of littoral plants as heavy metals bioaccumulators over large areas of the wetlands environment. So, soil samples and biomass of the five plant species: Pluchea dioscroides, Pulicaria crispa, Lavandula pubescens, Tarchononthus comporatus and Argemone ochroleuca were collected from two different sites (basin and mouth) of four dams at Baha province, KSA. Nutrients and heavy metals were extracted from plant samples (leaves and stems) for analyzing elements (Na, K, Ca, P and N) and heavy metals (Pb, Cu and Ni). The soils of the mouth of the dam had the highest concentrations of all elements, while that of basin had the highest ones of most heavy metals except Pb. The soil elements in relation to the two sites arranged as: Ca > K > P > Na > N; and the heavy metals as: Cu > Ni > Pb. The present study indicated that Pluchea dioscroides had the highest values of most elements and heavy metals, while Lavandula pubescens had the lowest. In general, leaves attain the highest concentrations of all nutrients and heavy metals in most studied species as compared with stem. It was indicated that Pluchea dioscroides showed a high transfer factor for almost elements and heavy metals such as K, Na, Cu, Ni and Pb, while Pulicaria crispa showed the highest translocation factor of N, P, Ca-Na ratio and Cu. All studied species growing in the basin had almost the highest concentrations of elements and heavy metals as compared with that in the mouth of dam except K in Pluchea dioscroides, Tarchononthus comporatus and Argemone ochroleuca tissues. Otherwise tissues of Tarchononthus comporatus growing in the basin had the lowest concentrations of K and Ni, while that growing in the mouth had the highest of P and N.

Keywords: Baha Region, bioindicators, plant, pollution, dams, heavy metals

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1534 Development of Positron Emission Tomography (PET) Tracers for the in-Vivo Imaging of α-Synuclein Aggregates in α-Synucleinopathies

Authors: Bright Chukwunwike Uzuegbunam, Wojciech Paslawski, Hans Agren, Christer Halldin, Wolfgang Weber, Markus Luster, Thomas Arzberger, Behrooz Hooshyar Yousefi

Abstract:

There is a need to develop a PET tracer that will enable to diagnosis and track the progression of Alpha-synucleinopathies (Parkinson’s disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA]) in living subjects over time. Alpha-synuclein aggregates (a-syn), which are present in all the stages of disease progression, for instance, in PD, are a suitable target for in vivo PET imaging. For this reason, we have developed some promising a-syn tracers based on a disarylbisthiazole (DABTA) scaffold. The precursors are synthesized via a modified Hantzsch thiazole synthesis. The precursors were then radiolabeled via one- or two-step radiofluorination methods. The ligands were initially screened using a combination of molecular dynamics and quantum/molecular mechanics approaches in order to calculate the binding affinity to a-syn (in silico binding experiments). Experimental in vitro binding assays were also performed. The ligands were further screened in other experiments such as log D, in vitro plasma protein binding & plasma stability, biodistribution & brain metabolite analyses in healthy mice. Radiochemical yields were up to 30% - 72% in some cases. Molecular docking revealed possible binding sites in a-syn and also the free energy of binding to those sites (-28.9 - -66.9 kcal/mol), which correlated to the high binding affinity of the DABTAs to a-syn (Ki as low as 0.5 nM) and selectivity (> 100-fold) over Aβ and tau, which usually co-exist with a-synin some pathologies. The log D values range from 2.88 - 2.34, which correlated with free-protein fraction of 0.28% - 0.5%. Biodistribution experiments revealed that the tracers are taken up (5.6 %ID/g - 7.3 %ID/g) in the brain at 5 min (post-injection) p.i., and cleared out (values as low as 0.39 %ID/g were obtained at 120 min p.i. Analyses of the mice brain 20 min p.i. Revealed almost no radiometabolites in the brain in most cases. It can be concluded that in silico study presents a new venue for the rational development of radioligands with suitable features. The results obtained so far are promising and encourage us to further validate the DABTAs in autoradiography, immunohistochemistry, and in vivo imaging in non-human primates and humans.

Keywords: alpha-synuclein aggregates, alpha-synucleinopathies, PET imaging, tracer development

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