Search results for: nitrogen reduction
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5756

Search results for: nitrogen reduction

1856 India’s Energy System Transition, Survival of the Greenest

Authors: B. Sudhakara Reddy

Abstract:

The transition to a clean and green energy system is an economic and social transformation that is exciting as well as challenging. The world today faces a formidable challenge in transforming its economy from being driven primarily by fossil fuels, which are non-renewable and a major source of global pollution, to becoming an economy that can function effectively using renewable energy sources and by achieving high energy efficiency levels. In the present study, a green economy scenario is developed for India using a bottom-up approach. The results show that the penetration rate of renewable energy resources will reduce the total primary energy demand by 23% under GE. Improvements in energy efficiency (e.g. households, industrial and commercial sectors) will result in reduced demand to the tune of 318 MTOE. The volume of energy-related CO2 emissions decline to 2,218 Mt in 2030 from 3,440 under the BAU scenario and the per capita emissions will reduce by about 35% (from 2.22 to 1.45) under the GE scenario. The reduction in fossil fuel demand and focus on clean energy will reduce the energy intensity to 0.21 (TOE/US$ of GDP) and carbon intensity to 0.42 (ton/US$ of GDP) under the GE scenario. total import bill (coal and oil) will amount to US$ 334 billion by 2030 (at 2010/11 prices), but as per the GE scenario, it would be US$ 194.2 billion, a saving of about US$ 140 billion. The building of a green energy economy can also serve another purpose: to develop new ‘pathways out of poverty’ by creating more than 10 million jobs and thus raise the standard of living of low-income people. The differences between the baseline and green energy scenarios are not so much the consequence of the diffusion of various technologies. It is the result of the active roles of different actors and the drivers that become dominant.

Keywords: emissions, green energy, fossil fuels, green jobs, renewables, scenario

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1855 Blockchain: Institutional and Technological Disruptions in the Public Sector

Authors: Maria Florencia Ferrer, Saulo Fabiano Amancio-Vieira

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The use of the blockchain in the public sector is present today and no longer the future of disruptive institutional and technological models. There are still some cultural barriers and resistance to the proper use of its potential. This research aims to present the strengths and weaknesses of using a public-permitted and distributed network in the context of the public sector. Therefore, bibliographical/documentary research was conducted to raise the main aspects of the studied platform, focused on the use of the main demands of the public sector. The platform analyzed was LACChain, which is a global alliance composed of different actors in the blockchain environment, led by the Innovation Laboratory of the Inter-American Development Bank Group (IDB Lab) for the development of the blockchain ecosystem in Latin America and the Caribbean. LACChain provides blockchain infrastructure, which is a distributed ratio technology (DLT). The platform focuses on two main pillars: community and infrastructure. It is organized as a consortium for the management and administration of an infrastructure classified as public, following the ISO typologies (ISO / TC 307). It is, therefore, a network open to any participant who agrees with the established rules, which are limited to being identified and complying with the regulations. As benefits can be listed: public network (open to all), decentralized, low transaction cost, greater publicity of transactions, reduction of corruption in contracts / public acts, in addition to improving transparency for the population in general. It is also noteworthy that the platform is not based on cryptocurrency and is not anonymous; that is, it is possible to be regulated. It is concluded that the use of record platforms, such as LACChain, can contribute to greater security on the part of the public agent in the migration process of their informational applications.

Keywords: blockchain, LACChain, public sector, technological disruptions

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1854 Plaque Removal Efficacy of Different Dental Care Products during Fixed Orthodontic Appliance Therapy

Authors: Zeynep Karakoc, Hasan Ilhan Mutaf

Abstract:

Plaque removal efficacy of different dental brushes and mouth wash during fixed orthodontic appliance therapy was evaluated in this single-blind, crossover and prospective study. Thirty orthodontic patients aged 18 and over undergoing fixed appliance therapy at the end of leveling stage were divided into three groups. Subjects brushed their teeth with a toothbrush under standardized conditions for a period of 30 days prior to inter-dental care products. The same procedure was repeated each time with a different, randomly assigned inter-dental care products in a crossover design. (Inter-dental brush, powered inter-dental brush and mouth wash). At start and end of each removal period, plaque indexes of participants were scored. Each brush achieved statistically significant plaque removal; however, there were no statistical differences among groups for all surfaces of teeth when the plaque score was evaluated. The mouth wash group presented significant improvement in reduction of visible plaque on mesial and distal surfaces of posterior teeth. (-60.9 %, P< .001) Plaque removal for right and left side of mouth showed no significant differences within groups, only mouth wash was more efficient in right side than left side. It is concluded that effectiveness of plaque removal may not be related to the kind of inter-dental products directly. However, toothbrush when used with inter-dental care products is significantly better at removing plaque deposits from fixed appliance patients.

Keywords: orthodontics, dental care, brush, plaque

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1853 Utilizing Minecraft Java Edition for the Application of Fire Disaster Procedures to Establish Fire Disaster Readiness for Grade 12 STEM students of DLSU-IS

Authors: Aravella Flores, Jose Rafael E. Sotelo, Luis Romulus Phillippe R. Javier, Josh Christian V. Nunez

Abstract:

This study focuses on analyzing the performance of Grade 12 STEM students of De La Salle University - Integrated School that has completed the Disaster Readiness and Risk Reduction course in handling fire hazards through Minecraft Java Edition. This platform is suitable because fire DRRR is challenging to learn in a practical setting as well as questionable with regard to supplementing the successful implementation of textbook knowledge into actual practice. The purpose of this study is to acknowledge whether Minecraft can be a suitable environment to familiarize oneself to fire DRRR. The objectives are achieved through utilizing Minecraft in simulating fire scenarios which allows the participants to freely act upon and practice fire DRRR. The experiment was divided into the grounding and validation phase, where researchers observed the performance of the participants in the simulation. A pre-simulation and post-simulation survey was given to acknowledge the change in participants’ perception of being able to utilize fire DRRR procedures and their vulnerabilities. The paired t-test was utilized, showing significant differences in the pre-simulation and post-simulation survey scores, thus, insinuating improved judgment of DRRR, lessening their vulnerabilities in the possibility of encountering a fire hazard. This research poses a model for future research which can gather more participants and dwell on more complex codes outside just command blocks and into the code lines of Minecraft itself.

Keywords: minecraft, DRRR, fire, disaster, simulation

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1852 Bioactivities and Phytochemical Studies of Petroleum Ether Extract of Pleiogynium timorense Bark

Authors: Gehan F. Abdel Raoof, Ataa A. Said, Khaled Y. Mohamed, Hala M. Mohammed

Abstract:

Pleiogynium timorense(DC.) Leenh is one of the therapeutically active plants belonging to the family Anacardiaceae. The bark of Pleiogynium timorense needs further studies to investigate its phytochemical and biological activities. This work was carried out to investigate the chemical composition of petroleum ether extract of Pleiogynium timorense bark as well as to evaluate the analgesic and anti-inflammatory activities. The unsaponifiable matter and fatty acid methyl esters were analyzed by Gas chromatography–mass spectrometry (GC-MS). Moreover, analgesic and anti-inflammatory activities were evaluated using acetic acid-induced writhing test and carrageen hind paw oedema models in rats, respectively. The results showed that twenty one compounds in the unsaponifiable fraction were identified representing 92.54 % of the total beak area, the major compounds were 1-Heptene (35.32%), Butylated hydroxy toluene (19.42%) and phytol (12.53%), whereas fifteen compounds were identified in the fatty acid methyl esters fraction representing 94.15% of the total identified peak area. The major compounds were 9-Octadecenoic acid methyl ester (35.34%) and 9,12-Octadecadienoic acid methyl ester (29.32%). Moreover, petroleum ether extract showed a significant reduction in pain and inflammation in a dose dependent manner. This study aims to be the first step toward the use of petroleum ether extract of Pleiogynium timorense bark as analgesic and anti-inflammatory drug.

Keywords: analgesic, anti-inflammatory, bark, petroleum ether extract, Pleiogynium timorense

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1851 Soft Computing Employment to Optimize Safety Stock Levels in Supply Chain Dairy Product under Supply and Demand Uncertainty

Authors: Riyadh Jamegh, Alla Eldin Kassam, Sawsan Sabih

Abstract:

In order to overcome uncertainty conditions and inability to meet customers' requests due to these conditions, organizations tend to reserve a certain safety stock level (SSL). This level must be chosen carefully in order to avoid the increase in holding cost due to excess in SSL or shortage cost due to too low SSL. This paper used soft computing fuzzy logic to identify optimal SSL; this fuzzy model uses the dynamic concept to cope with high complexity environment status. The proposed model can deal with three input variables, i.e., demand stability level, raw material availability level, and on hand inventory level by using dynamic fuzzy logic to obtain the best SSL as an output. In this model, demand stability, raw material, and on hand inventory levels are described linguistically and then treated by inference rules of the fuzzy model to extract the best level of safety stock. The aim of this research is to provide dynamic approach which is used to identify safety stock level, and it can be implanted in different industries. Numerical case study in the dairy industry with Yogurt 200 gm cup product is explained to approve the validity of the proposed model. The obtained results are compared with the current level of safety stock which is calculated by using the traditional approach. The importance of the proposed model has been demonstrated by the significant reduction in safety stock level.

Keywords: inventory optimization, soft computing, safety stock optimization, dairy industries inventory optimization

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1850 Effect of Bariatric Surgery on Metabolic Syndrome, Framingham Risk Score and Thyroid Function

Authors: Nuha Alamro

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Besides achieving of weight loss, Bariatric surgery (BS) shown metabolic improvement including reduction of cardiovascular disease, insulin resistance and diabetes. This study aimed to measure BS effects on Framingham Risk Score (FRS) and metabolic syndrome (MetS) among patients who underwent BS. Additionally, to determine the effect of BS on TSH among euthyroid obese patients. A Retrospective follow-up study was conducted in King Abdullah Medical City. A total of 160 participants who underwent BS and completed one year of follow ups. Medical history, biochemical, anthropometric, and hormonal parameters were evaluated at baseline and 3-12 months after BS. International Diabetes Federation (IDF) criteria were used to diagnose MetS pre and postoperative. The mean age of participants was 41.9 ± 10.6 with Body Mass Index (BMI) of 48.8 ± 7.3. After 3 months, Systolic, Diastolic blood pressure (SBP, DBP), glycated haemoglobin (HBA1C), Low-density lipoprotein (LDL), cholesterol, triglycerides and Thyroid stimulating hormone (TSH) were significantly decrease (P < 0.001). Significant decrease was seen in Mets, BMI, FRS, SBP, DBP, HBA1C, LDL, triglycerides, cholesterol, liver enzyme, with significant increase in high-density lipoprotein (HDL) level 12 months post-op (P < 0.001). After 1 year, the prevalence of MetS, DM, HTN, FRS were significantly decrease from 72.5%, 43.1%, 78.1%, 11.4 to 16.3%, 9.4%, 22.5% and 5.4, respectively. Besides achieving substantial weight loss, MetS resolution was linked to improvement in cardiovascular risk profile.

Keywords: bariatric surgery, cardiovascular disease, metabolic syndrome, thyroid stimulating hormone

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1849 Numerical Analysis of the Effect of Geocell Reinforcement above Buried Pipes on Surface Settlement and Vertical Pressure

Authors: Waqed H. Almohammed, Mohammed Y. Fattah, Sajjad E. Rasheed

Abstract:

Dynamic traffic loads cause deformation of underground pipes, resulting in vehicle discomfort. This makes it necessary to reinforce the layers of soil above underground pipes. In this study, the subbase layer was reinforced. Finite element software (PLAXIS 3D) was used to in the simulation, which includes geocell reinforcement, vehicle loading, soil layers and Glass Fiber Reinforced Plastic (GRP) pipe. Geocell reinforcement was modeled using a geogrid element, which was defined as a slender structure element that has the ability to withstand axial stresses but not to resist bending. Geogrids cannot withstand compression but they can withstand tensile forces. Comparisons have been made between the numerical models and experimental works, and a good agreement was obtained. Using the mathematical model, the performance of three different pipes of diameter 600 mm, 800 mm, and 1000 mm, and three different vehicular speeds of 20 km/h, 40 km/h, and 60 km/h, was examined to determine their impact on surface settlement and vertical pressure at the pipe crown for two cases: with and without geocell reinforcement. The results showed that, for a pipe diameter of 600 mm under geocell reinforcement, surface settlement decreases by 94 % when the speed of the vehicle is 20 km/h and by 98% when the speed of the vehicle is 60 km/h. Vertical pressure decreases by 81 % when the diameter of the pipe is 600 mm, while the value decreases to 58 % for a pipe with diameter 1000 mm. The results show that geocell reinforcement causes a significant and positive reduction in surface settlement and vertical stress above the pipe crown, leading to an increase in pipe safety.

Keywords: dynamic loading, finite element, geocell-reinforcement, GRP pipe, PLAXIS 3D, surface settlement

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1848 Spatio-Temporal Variation of Suspended Sediment Concentration in the near Shore Waters, Southern Karnataka, India

Authors: Ateeth Shetty, K. S. Jayappa, Ratheesh Ramakrishnan, A. S. Rajawat

Abstract:

Suspended Sediment Concentration (SSC) was estimated for the period of four months (November, 2013 to February 2014) using Oceansat-2 (Ocean Colour Monitor) satellite images to understand the coastal dynamics and regional sediment transport, especially distribution and budgeting in coastal waters. The coastal zone undergoes continuous changes due to natural processes and anthropogenic activities. The importance of the coastal zone, with respect to safety, ecology, economy and recreation, demands a management strategy in which each of these aspects is taken into account. Monitoring and understanding the sediment dynamics and suspended sediment transport is an important issue for coastal engineering related activities. A study of the transport mechanism of suspended sediments in the near shore environment is essential not only to safeguard marine installations or navigational channels, but also for the coastal structure design, environmental protection and disaster reduction. Such studies also help in assessment of pollutants and other biological activities in the region. An accurate description of the sediment transport, caused by waves and tidal or wave-induced currents, is of great importance in predicting coastal morphological changes. Satellite-derived SSC data have been found to be useful for Indian coasts because of their high spatial (360 m), spectral and temporal resolutions. The present paper outlines the applications of state‐of‐the‐art operational Indian Remote Sensing satellite, Oceansat-2 to study the dynamics of sediment transport.

Keywords: suspended sediment concentration, ocean colour monitor, sediment transport, case – II waters

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1847 Heavy Metal Adsorption from Synthetic Wastewater Using Agro Waste-Based Nanoparticles: A Comparative Study

Authors: Nomthandazo Precious Sibiya, Thembisile Patience Mahlangu, Sudesh Rathilal

Abstract:

Heavy metal removal is critical in the wastewater treatment process due to its numerous harmful effects on human and aquatic life. There are several chemical and physical techniques for removing heavy metals from wastewater, including ion exchange, reverse osmosis, adsorption, electrodialysis, and ultrafiltration. However, adsorption technology has captivated researchers for years due to its low cost, high efficiency, and compatible with the environment. In this study, the adsorption effectiveness of three modified agro-waste materials was explored for the removal of lead from synthetic wastewater: banana peels (BP), orange peels (OP), and sugarcane bagasse (SB). The magnetite (Fe₃O₄) is incorporated with BP, OP, and SB at a ratio of 1:1 to create magnetic biosorbents. Characterization of biosorbents was carried out using and scanning electron microscopy (SEM) combined with energy-dispersive X-ray (EDX) to investigate surface morphology and elemental compositions, respectively. A series of batch experiments were carried out to investigate the effects of adsorbent mass, agitation time, and initial pH concentration on adsorption behaviour, as well as adsorption isotherms and kinetics. The removal efficiency of lead by the modified agro-waste materials proved to be superior to that of non-modified agro-waste materials. The proof of concept was achieved, and agro-waste materials can be paired with adsorption technology to effectively remove lead from aqueous media. The use of agricultural waste as biosorbents will aid in waste reduction and management.

Keywords: adsorption, isotherms, kinetics, agro waste, nanoparticles, batch

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1846 There's No End in Sight: An Interpretative Phenomenological Analysis of Quality of Life in Burning Syndrome Sufferers

Authors: R. McGrath, A. Trace, S. Curtin, C. McCreary

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Introduction: Although, in relation to Burning Mouth Syndrome (BMS), much energy has been expended on its definition and etiology, it still remains a contentious issue. There is agreement on the symptoms, but on little else; and approaches to treatment vary widely. However, it has been established that the condition has a detrimental effect on the sufferer’s quality of life. Much research focus has been put on the physical impact of the syndrome. Recently, some literature has turned the focus to social, functional, and psychological factors. However, there is very little qualitative research on how burning mouth syndrome affects the lives of sufferer’s and the present study seeks to remedy this. Method: The study recruited five male participants who took part in semi-structured interviews lasting between 30 and 50 minutes. Data was analysed using Interpretative Phenomenological Analysis. Results: The study identified four super-ordinate themes: Lack of Control due to Uncertainty about Condition; Disruption to Internal Sense of Self; Negative Future Expectation due to Chronic Symptoms; and Sense of BMS as an Intrusive Force. Aspects of these themes reflect areas of reduction in quality of life. Conclusion: BMS damages an individual’s quality of life in ways that have not been reflected in self-report surveys of health-related quality of life. The condition has serious implications for the individual's sense of self, identity, and future. The study recommends that further qualitative research be carried out in this area. Also, the use of therapeutic interventions with sufferers from BMS is recommended, which would help not only sufferers but best practice in relation to their treatment.

Keywords: burning mouth syndrome, interpretative phenomenological analysis, qualitative research, quality of life

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1845 Avoidance of Brittle Fracture in Bridge Bearings: Brittle Fracture Tests and Initial Crack Size

Authors: Natalie Hoyer

Abstract:

Bridges in both roadway and railway systems depend on bearings to ensure extended service life and functionality. These bearings enable proper load distribution from the superstructure to the substructure while permitting controlled movement of the superstructure. The design of bridge bearings, according to Eurocode DIN EN 1337 and the relevant sections of DIN EN 1993, increasingly requires the use of thick plates, especially for long-span bridges. However, these plate thicknesses exceed the limits specified in the national appendix of DIN EN 1993-2. Furthermore, compliance with DIN EN 1993-1-10 regulations regarding material toughness and through-thickness properties necessitates further modifications. Consequently, these standards cannot be directly applied to the selection of bearing materials without supplementary guidance and design rules. In this context, a recommendation was developed in 2011 to regulate the selection of appropriate steel grades for bearing components. Prior to the initiation of the research project underlying this contribution, this recommendation had only been available as a technical bulletin. Since July 2023, it has been integrated into guideline 804 of the German railway. However, recent findings indicate that certain bridge-bearing components are exposed to high fatigue loads, which necessitate consideration in structural design, material selection, and calculations. Therefore, the German Centre for Rail Traffic Research called a research project with the objective of defining a proposal to expand the current standards in order to implement a sufficient choice of steel material for bridge bearings to avoid brittle fracture, even for thick plates and components subjected to specific fatigue loads. The results obtained from theoretical considerations, such as finite element simulations and analytical calculations, are validated through large-scale component tests. Additionally, experimental observations are used to calibrate the calculation models and modify the input parameters of the design concept. Within the large-scale component tests, a brittle failure is artificially induced in a bearing component. For this purpose, an artificially generated initial defect is introduced at the previously defined hotspot into the specimen using spark erosion. Then, a dynamic load is applied until the crack initiation process occurs to achieve realistic conditions in the form of a sharp notch similar to a fatigue crack. This initiation process continues until the crack length reaches a predetermined size. Afterward, the actual test begins, which requires cooling the specimen with liquid nitrogen until a temperature is reached where brittle fracture failure is expected. In the next step, the component is subjected to a quasi-static tensile test until failure occurs in the form of a brittle failure. The proposed paper will present the latest research findings, including the results of the conducted component tests and the derived definition of the initial crack size in bridge bearings.

Keywords: bridge bearings, brittle fracture, fatigue, initial crack size, large-scale tests

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1844 The Applications of Zero Water Discharge (ZWD) Systems for Environmental Management

Authors: Walter W. Loo

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China declared the “zero discharge rules which leave no toxics into our living environment and deliver blue sky, green land and clean water to many generations to come”. The achievement of ZWD will provide conservation of water, soil and energy and provide drastic increase in Gross Domestic Products (GDP). Our society’s engine needs a major tune up; it is sputtering. ZWD is achieved in world’s space stations – no toxic air emission and the water is totally recycled and solid wastes all come back to earth. This is all done with solar power. These are all achieved under extreme temperature, pressure and zero gravity in space. ZWD can be achieved on earth under much less fluctuations in temperature, pressure and normal gravity environment. ZWD systems are not expensive and will have multiple beneficial returns on investment which are both financially and environmentally acceptable. The paper will include successful case histories since the mid-1970s. ZWD discharge can be applied to the following types of projects: nuclear and coal fire power plants with a closed loop system that will eliminate thermal water discharge; residential communities with wastewater treatment sump and recycle the water use as a secondary water supply; waste water treatment Plants with complete water recycling including water distillation to produce distilled water by very economical 24-hours solar power plant. Landfill remediation is based on neutralization of landfilled gas odor and preventing anaerobic leachate formation. It is an aerobic condition which will render landfill gas emission explosion proof. Desert development is the development of recovering soil moisture from soil and completing a closed loop water cycle by solar energy within and underneath an enclosed greenhouse. Salt-alkali land development can be achieved by solar distillation of salty shallow water into distilled water. The distilled water can be used for soil washing and irrigation and complete a closed loop water cycle with energy and water conservation. Heavy metals remediation can be achieved by precipitation of dissolved toxic metals below the plant or vegetation root zone by solar electricity without pumping and treating. Soil and groundwater remediation - abandoned refineries, chemical and pesticide factories can be remediated by in-situ electrobiochemical and bioventing treatment method without pumping or excavation. Toxic organic chemicals are oxidized into carbon dioxide and heavy metals precipitated below plant and vegetation root zone. New water sources: low temperature distilled water can be recycled for repeated use within a greenhouse environment by solar distillation; nano bubble water can be made from the distilled water with nano bubbles of oxygen, nitrogen and carbon dioxide from air (fertilizer water) and also eliminate the use of pesticides because the nano oxygen will break the insect growth chain in the larvae state. Three dimensional high yield greenhouses can be constructed by complete water recycling using the vadose zone soil as a filter with no farming wastewater discharge.

Keywords: greenhouses, no discharge, remediation of soil and water, wastewater

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1843 Analysis and Comparison of Prototypes of an Ergometric Step in a Multidisciplinary Design Process

Authors: M. B. Ricardo De Oliveira, A. Borghi-Silva, L. Di Thommazo, D. Braatz

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Prototypes can be understood as representations of a product concept. Furthermore, prototyping consists in an important stage in product development and results in better team communication, decision making, testing and problem solving through feedback. Although there are several methods of prototyping suggested by recent studies for designers to choose from, some methods present different advantages, such as cost and time reduction, performance and fidelity, which should be taken in account during a product development project. In this multidisciplinary study, involving areas of physiotherapy, engineering and computer science (hardware and software), we compared four developed prototypes of an ergometric step: a virtual prototype, a 3D printed prototype, a bricolage prototype and a prototype manufactured by a third-party company. These prototypes were evaluated in a comparative-qualitative approach for their contribution to the concept’s maturation of the product, the different prototyping methods used and the advantages and disadvantages of each one based on the product’s design specifications (performance, safety, materials, cost, maintenance, usability, ergonomics and portability). Our results indicated that despite prototypes show overall advantages, all of them have limitations, thus being crucial to have different methods of testing and interacting with the product. Additionally, virtual and 3D printed prototypes were essential at early stages of the project due to their low-cost and high-fidelity representation of the product, while the prototype manufactured by a third-party company and bricolage prototype introduced functional tests in real scenarios, allowing more detailed evaluations. This study also resulted in a patent for an ergometric step.

Keywords: Product Design, Product Development, Prototypes, Step

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1842 Crashworthiness Optimization of an Automotive Front Bumper in Composite Material

Authors: S. Boria

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In the last years, the crashworthiness of an automotive body structure can be improved, since the beginning of the design stage, thanks to the development of specific optimization tools. It is well known how the finite element codes can help the designer to investigate the crashing performance of structures under dynamic impact. Therefore, by coupling nonlinear mathematical programming procedure and statistical techniques with FE simulations, it is possible to optimize the design with reduced number of analytical evaluations. In engineering applications, many optimization methods which are based on statistical techniques and utilize estimated models, called meta-models, are quickly spreading. A meta-model is an approximation of a detailed simulation model based on a dataset of input, identified by the design of experiments (DOE); the number of simulations needed to build it depends on the number of variables. Among the various types of meta-modeling techniques, Kriging method seems to be excellent in accuracy, robustness and efficiency compared to other ones when applied to crashworthiness optimization. Therefore the application of such meta-model was used in this work, in order to improve the structural optimization of a bumper for a racing car in composite material subjected to frontal impact. The specific energy absorption represents the objective function to maximize and the geometrical parameters subjected to some design constraints are the design variables. LS-DYNA codes were interfaced with LS-OPT tool in order to find the optimized solution, through the use of a domain reduction strategy. With the use of the Kriging meta-model the crashworthiness characteristic of the composite bumper was improved.

Keywords: composite material, crashworthiness, finite element analysis, optimization

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1841 Improvement of Sleep Quality Through Manual and Non-Pharmacological Treatment

Authors: Andreas Aceranti, Sergio Romanò, Simonetta Vernocchi, Silvia Arnaboldi, Emilio Mazza

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As a result of the Sars-Cov2 pandemic, the incidence of thymism disorders has significantly increased and, often, patients are reluctant to want to take drugs aimed at stabilizing mood. In order to provide an alternative approach to drug therapies, we have prepared a study in order to evaluate the possibility of improving the quality of life of these subjects through osteopathic treatment. Patients were divided into visceral and fascial manual treatment with the aim of increasing serotonin levels and stimulating the vagus nerve through validated techniques. The results were evaluated through the administration of targeted questionnaires in order to assess quality of life, mood, sleep and intestinal functioning. At a first endpoint we found, in patients undergoing fascial treatment, an increase in quality of life and sleep: in fact, they report a decrease in the number of nocturnal awakenings; a reduction in falling asleep times and greater rest upon waking. In contrast, patients undergoing visceral treatment, as well as those included in the control group, did not show significant improvements. Patients in the fascial group have, in fact, reported an improvement in thymism and subjective quality of life with a generalized improvement in function. Although the study is still ongoing, based on the results of the first endpoint we can hypothesize that fascial stimulation of the vagus nerve with manual and osteopathic techniques may be a valid alternative to pharmacological treatments in mood and sleep disorders.

Keywords: ostheopathy, insomnia, noctural awakening, thymism

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1840 Biodegradable Drinking Straws Made From Naturally Dried and Fallen Coconut Leaves: Impact on Rural Circular Economy and Environmental Sustainability

Authors: Saji Varghese

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Naturally dried and fallen coconut leaves and found in abundance in India and other coconut growing regions of the world. These fallen coconut leaves are usually burnt by farmers in landfills and open kitchens, leading to CO2 and particulate emissions. The innovation of biodegradable drinking straws from naturally dried and fallen coconut leaves by this researcher and his team has opened up opportunities to create value out of this agri-waste leading to i. prevention of burning of these discarded leaves ii. income generating opportunities to women in rural areas of coconut growing regions iii. an alternative to single use plastic straws. The team has developed five special purpose machines, which are deployed in the three villages on a pilot basis where 36 women are employed. The women are trained in the use of these machines, and the straws which are in good demand are sold globally. The present paper analyses the prospective impact of this innovation on the incomes of women working at the straw production centres and the consequent impact on their standards of living, The paper also analyses the impact of this innovation in the reduction of CO2 and particulate emissions and makes a case for support from Govt and Non Govt organizations in coconut growing regions to set up straw production centres to boost rural circular economy and to reduce carbon footprint and eliminate plastic pollution

Keywords: drinking straws, coconut leaves, circular economy, sustainability

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1839 Reducing The Frequency of Flooding Accompanied by Low pH Wastewater In 100/200 Unit of Phosphate Fertilizer 1 Plant by Implementing The 3R Program (Reduce, Reuse and Recycle)

Authors: Pradipta Risang Ratna Sambawa, Driya Herseta, Mahendra Fajri Nugraha

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In 2020, PT Petrokimia Gresik implemented a program to increase the ROP (Run Of Pile) production rate at the Phosphate Fertilizer 1 plant, causing an increase in scrubbing water consumption in the 100/200 area unit. This increase in water consumption causes a higher discharge of wastewater, which can further cause local flooding, especially during the rainy season. The 100/200 area of the Phosphate Fertilizer 1 plant is close to the warehouse and is often a passing area for trucks transporting raw materials. This causes the pH in the wastewater to become acidic (the worst point is up to pH 1). The problem of flooding and exposure to acidic wastewater in the 100/200 area of Phosphate Fertilizer Plant 1 was then resolved by PT Petrokimia Gresik through wastewater optimization steps called the 3R program (Reduce, Reuse, and Recycle). The 3R (Reduce, reuse, and recycle) program consists of an air consumption reduction program by considering the liquid/gas ratio in scrubbing unit of 100/200 Phosphate Fertilizer 1 plant, creating a wastewater interconnection line so that wastewater from unit 100/200 can be used as scrubbing water in the Phonska 1, Phonska 2, Phonska 3 and unit 300 Phosphate Fertilizer 1 plant and increasing scrubbing effectiveness through scrubbing effectiveness simulations. Through a series of wastewater optimization programs, PT Petrokimia Gresik has succeeded in reducing NaOH consumption for neutralization up to 2,880 kg/day or equivalent in saving up to 314,359.76 dollars/year and reducing process water consumption up to 600 m3/day or equivalent in saving up to 63,739.62 dollars/year.

Keywords: fertilizer, phosphate fertilizer, wastewater, wastewater treatment, water management

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1838 An Antidiabetic Dietary Defence Weapon: Oats and Milk Based Probiotic Fermented Product

Authors: Rameshwar Singh Seema

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In today’s world where diabetes has become an epidemic, our aim was to potentiate the effect of probiotics by integrating probiotics with cereals to formulate composite foods using Lactobacillus rhamnosus GG (LGG) and Lactobacillus casei NCDC19 against type 2 diabetes. After optimizing the product by Response Surface Methodology, it was studied for their effect on induction and progression of type 2 diabetes in HFD-fed Wistar rats. After 9 weeks study, best results were shown by the group fed with oat and milk based product fermented with LGG and L. casei NCDC19 which resulted in a significant decrease in blood glucose, HBA1c, improved OGTT, oxidative stress, cholesterol and triglycerides level during progression study of type 2 diabetes. During induction study also, there was significant reduction in blood glucose level, oxidative stress, cholesterol level and triglycerides level but slightly less as compared to progression study. Real time PCR gene expression studies were done for 5 genes (GLUT-4, IRS-2, ppar-γ, TNF-α, IL-6) whose expression is directly related to type 2 diabetes. The relative fold change expression was increased in case of GLUT-4, IRS-2, ppar-γ and decreased in case of TNF-α and IL-6 during both induction and progression study of diabetes but more significantly during progression study. Hence it was concluded that oat and milk based probiotic fermented product showed the synergistic effect of probiotics and oats especially in case of progression of type 2 diabetes. The benefits of these probiotic formulations may be further validated by clinical trials.

Keywords: type 2 diabetes, LGG, L.casei NCDC19, food science

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1837 Quorum Quenching Activities of Bacteria Isolated from Red Sea Sediments

Authors: Zahid Rehman, TorOve Leiknes

Abstract:

Quorum sensing (QS) is the process by which bacteria communicate with each other through small signaling molecules, such as N-acylhomoserine lactones (AHLs). Also, certain bacteria have the ability to degrade AHL molecules by a process referred to as quorum quenching (QQ); therefore, QQ can be used to control bacterial infections and biofilm formation. In this study, we aimed to identify new species of bacteria with QQ activities. To achieve this, sediments from Red Sea were collected either in the close vicinity of Sea grass or from area with no vegetation. From these samples, we isolated 72 bacterial strains and tested their ability to degrade/inactivate AHL molecules. Chromobacterium violaceum based bioassay was used in initial screening of isolates for QQ activity. The QQ activity of the positive isolates was further confirmed and quantified by employing liquid chromatography and mass spectrometry. These analyses showed that isolated bacterial strain could degrade AHL molecules with different acyl chain length and modifications. Sequencing of 16S-rRNA genes of positive isolates revealed that they belong to three different genera. Specifically, two isolates belong to genus Erythrobacter, four to Labrenzia and one isolate belongs to Bacterioplanes. Time course experiment showed that isolate belonging to genus Erythrobacter could degrade AHLs faster than other isolates. Furthermore, these isolates were tested for their ability to inhibit formation of biofilm and degradation of 3OXO-C12 AHLs produced by P. aeruginosa PAO1. Our results showed that isolate VG12 is better at controlling biofilm formation. This aligns with the ability of VG12 to cause at least 10-fold reduction in the amount of different AHLs tested.

Keywords: quorum sensing, biofilm, quorum quenching, anti-biofouling

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1836 In vitro Inhibitory Action of an Aqueous Extract of Carob on the Release of Myeloperoxidase by Human Neutrophils

Authors: Kais Rtibi, Slimen Selmi, Jamel El-Benna, Lamjed Marzouki, Hichem Sebai

Abstract:

Background: Myeloperoxidase (MPO) is a hemic enzyme found in high concentrations in the primary neutrophils granules. In addition to its peroxidase activity, it has a chlorination activity, using hydrogen peroxide and chloride ions to form hypochlorous acid, a strong oxidant, capable of chlorinating molecules. Bioactive compounds contained in medicinal plants could limit the action of this enzyme to reduce the reactive oxygen species production and its chlorination activity. The purpose of this study is to evaluate the effect of the carob aqueous extract (CAE) on the release of MPO by human neutrophils in vitro and its activity following stimulation of these cells by PMA. Methods: Neutrophils were isolated by simple sedimentation using the Dextran/Ficoll method. After stimulation with phorbol 12-myristate 13-acetate (PMA), neutrophils release the MPO by degranulation. The effect of CAE on the release of MPO was analyzed by the Western blot technique, while, its activity was determined by biochemical method using the method of 3,3', 5,5'- Tetramethylbenzidine (TMB) and hydrogen peroxide. The data were expressed as mean ± SEM. Results: The carob aqueous extract causes a decrease in MPO quantity and activity in a concentration-dependent manner which leads to a reduction of the production of the ROS (reactive oxygen species) and the protection of the molecules against oxidation and chlorination mechanisms. Conclusion: Thanks to its richness in bioactive compounds, the aqueous extract of carob could limit the development of damages related to the uncontrolled activity of MPO.

Keywords: carob, MPO, myeloperoxidase, neutrophils, PMA, phorbol 12-myristate 13-acetate

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1835 Assessment of Heavy Metals and Radionuclide Concentrations in Mafikeng Waste Water Treatment Plant

Authors: M. Mathuthu, N. N. Gaxela, R. Y. Olobatoke

Abstract:

A study was carried out to assess the heavy metal and radionuclide concentrations of water from the waste water treatment plant in Mafikeng Local Municipality to evaluate treatment efficiency. Ten water samples were collected from various stages of water treatment which included sewage delivered to the plant, the two treatment stages and the effluent and also the community. The samples were analyzed for heavy metal content using Inductive Coupled Plasma Mass Spectrometer. Gross α/β activity concentration in water samples was evaluated by Liquid Scintillation Counting whereas the concentration of individual radionuclides was measured by gamma spectroscopy. The results showed marked reduction in the levels of heavy metal concentration from 3 µg/L (As)–670 µg/L (Na) in sewage into the plant to 2 µg/L (As)–170 µg/L (Fe) in the effluent. Beta activity was not detected in water samples except in the in-coming sewage, the concentration of which was within reference limits. However, the gross α activity in all the water samples (7.7-8.02 Bq/L) exceeded the 0.1 Bq/L limit set by World Health Organization (WHO). Gamma spectroscopy analysis revealed very high concentrations of 235U and 226Ra in water samples, with the lowest concentrations (9.35 and 5.44 Bq/L respectively) in the in-coming sewage and highest concentrations (73.8 and 47 Bq/L respectively) in the community water suggesting contamination along water processing line. All the values were considerably higher than the limits of South Africa Target Water Quality Range and WHO. However, the estimated total doses of the two radionuclides for the analyzed water samples (10.62 - 45.40 µSv yr-1) were all well below the reference level of the committed effective dose of 100 µSv yr-1 recommended by WHO.

Keywords: gross α/β activity, heavy metals, radionuclides, 235U, 226Ra, water sample

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1834 Women Entrepreneurship as an Inventive Approach to Ensure a Sustainable Development in Anambre State

Authors: S. Muogbo Uju, Akpunonu Uju,

Abstract:

The prevailing harsh environment factors couple with poverty rate and unemployment propels a high rate of entrepreneurial activities in developing countries of the world. Women entrepreneurs operate within gender bias among other constraint that can constitute a threat or create opportunity for women entrepreneurs. This empirical paper investigates and critically examines women entrepreneurship as an inventive approach to sustainable development in Anambra State. The study used descriptive statistics (frequencies, mean, and percentages) to answer the three research questions posed. Hypotheses testing were done with person product moment correlation and multiple regressions were employed in data analysis. SPSS [statistical package for Social Science] software was used to run the analysis. Three hundred and fifty three (353) copies of questionnaires were administered, and one hundred and forty six (146) copies were returned. Consequently, the findings of this study portrayed a significant impact between women entrepreneurship activities, job creation, wealth creation, youth empowerment, poverty reduction, employment generation, and increase in standard of livings of people. Therefore, the findings prescribe that government should ensure that managerial lessons are accompanied with the skill acquisition programs in order for them to understand the rudiment of owing and sustaining a business. The study also recommends that women entrepreneurs that have overcome the inertia of starting a business should come together to create platforms that can help those women who are yet to take a step or kick-start such venture.

Keywords: women entrepreneurship, skill acquisition, sustainability, wealth creation

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1833 Energy Efficient Massive Data Dissemination Through Vehicle Mobility in Smart Cities

Authors: Salman Naseer

Abstract:

One of the main challenges of operating a smart city (SC) is collecting the massive data generated from multiple data sources (DS) and to transmit them to the control units (CU) for further data processing and analysis. These ever-increasing data demands require not only more and more capacity of the transmission channels but also results in resource over-provision to meet the resilience requirements, thus the unavoidable waste because of the data fluctuations throughout the day. In addition, the high energy consumption (EC) and carbon discharges from these data transmissions posing serious issues to the environment we live in. Therefore, to overcome the issues of intensive EC and carbon emissions (CE) of massive data dissemination in Smart Cities, we propose an energy efficient and carbon reduction approach by utilizing the daily mobility of the existing vehicles as an alternative communications channel to accommodate the data dissemination in smart cities. To illustrate the effectiveness and efficiency of our approach, we take the Auckland City in New Zealand as an example, assuming massive data generated by various sources geographically scattered throughout the Auckland region to the control centres located in city centre. The numerical results show that our proposed approach can provide up to 5 times lower delay as transferring the large volume of data by utilizing the existing daily vehicles’ mobility than the conventional transmission network. Moreover, our proposed approach offers about 30% less EC and CE than that of conventional network transmission approach.

Keywords: smart city, delay tolerant network, infrastructure offloading, opportunistic network, vehicular mobility, energy consumption, carbon emission

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1832 Solar Disinfection Potentials of Aqua Lens, Photovoltaic and Glass Bottle Subsequent to Plant‑Based Coagulant: For Low‑Cost Household Water Treatment Systems

Authors: Yonas Lamore, Abebe Beyene, Samuel Fekadu, Moa Megersa

Abstract:

Unaffordable construction cost of conventional water treatment plant and distribution system in most developing countries makes difficult to provide safe and adequate water for all households, especially for the rural setup. Water treatment at the source can be the best alternative. Solar disinfection is one alternative among point of use treatments. In this study, aqua lens, photovoltaic box and glass bottle were used subsequent to plant coagulants to evaluate microbial reduction potentials. Laboratory- and field-based experiments were conducted from May to August 2016. The Escherichia coli, total coliforms and heterotrophic plate counts were used as indicator organisms. The result indicated that aqua lens (AL), photovoltaic box (PV) and glass bottle (GB) have high inactivation rate subsequently almost for all indicator organisms in short solar exposure time. Total coliforms were inactivated in AL (SD = 15.8 °C, R2 = 0.92) followed by PV inactivation temperature associa- tion (SD = 11.6 C, R2 = 0.90), and the GB concentrator was inactivated (SD = 10.9 °C, R2 = 0.70) at turbidity level of 3.41 NTU. As the study indicated, aqua lens coupled with Moringa oleifera coagulant can be an effective with minimum cost for household water treatment system. The study also concludes heterotrophic bacteria were more resistant than other types of bacteria in SODIS with similar exposure time.

Keywords: acrylic glass, aqua lens, moringa olifera, photovoltaic box, solar disinfection, water treatment

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1831 Chemical Fingerprinting of Complex Samples With the Aid of Parallel Outlet Flow Chromatography

Authors: Xavier A. Conlan

Abstract:

Speed of analysis is a significant limitation to current high-performance liquid chromatography/mass spectrometry (HPLC/MS) and ultra-high-pressure liquid chromatography (UHPLC)/MS systems both of which are used in many forensic investigations. The flow rate limitations of MS detection require a compromise in the chromatographic flow rate, which in turn reduces throughput, and when using modern columns, a reduction in separation efficiency. Commonly, this restriction is combated through the post-column splitting of flow prior to entry into the mass spectrometer. However, this results in a loss of sensitivity and a loss in efficiency due to the post-extra column dead volume. A new chromatographic column format known as 'parallel segmented flow' involves the splitting of eluent flow within the column outlet end fitting, and in this study we present its application in order to interrogate the provenience of methamphetamine samples with mass spectrometry detection. Using parallel segmented flow, column flow rates as high as 3 mL/min were employed in the analysis of amino acids without post-column splitting to the mass spectrometer. Furthermore, when parallel segmented flow chromatography columns were employed, the sensitivity was more than twice that of conventional systems with post-column splitting when the same volume of mobile phase was passed through the detector. These finding suggest that this type of column technology will particularly enhance the capabilities of modern LC/MS enabling both high-throughput and sensitive mass spectral detection.

Keywords: chromatography, mass spectrometry methamphetamine, parallel segmented outlet flow column, forensic sciences

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1830 Design of Replication System for Computer-Generated Hologram in Optical Component Application

Authors: Chih-Hung Chen, Yih-Shyang Cheng, Yu-Hsin Tu

Abstract:

Holographic optical elements (HOEs) have recently been one of the most suitable components in optoelectronic technology owing to the requirement of the product system with compact size. Computer-generated holography (CGH) is a well-known technology for HOEs production. In some cases, a well-designed diffractive optical element with multifunctional components is also an important issue and needed for an advanced optoelectronic system. Spatial light modulator (SLM) is one of the key components that has great capability to display CGH pattern and is widely used in various applications, such as an image projection system. As mentioned to multifunctional components, such as phase and amplitude modulation of light, high-resolution hologram with multiple-exposure procedure is also one of the suitable candidates. However, holographic recording under multiple exposures, the diffraction efficiency of the final hologram is inevitably lower than that with single exposure process. In this study, a two-step holographic recording method, including the master hologram fabrication and the replicated hologram production, will be designed. Since there exist a reduction factor M² of diffraction efficiency in multiple-exposure holograms (M multiple exposures), so it seems that single exposure would be more efficient for holograms replication. In the second step of holographic replication, a stable optical system with one-shot copying is introduced. For commercial application, one may utilize this concept of holographic copying to obtain duplications of HOEs with higher optical performance.

Keywords: holographic replication, holography, one-shot copying, optical element

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1829 Decreased Tricarboxylic Acid (TCA) Cycle Staphylococcus aureus Increases Survival to Innate Immunity

Authors: Trenten Theis, Trevor Daubert, Kennedy Kluthe, Austin Nuxoll

Abstract:

Staphylococcus aureus is a gram-positive bacterium responsible for an estimated 23,000 deaths in the United States and 25,000 deaths in the European Union annually. Recurring S. aureus bacteremia is associated with biofilm-mediated infections and can occur in 5 - 20% of cases, even with the use of antibiotics. Despite these infections being caused by drug-susceptible pathogens, they are surprisingly difficult to eradicate. One potential explanation for this is the presence of persister cells—a dormant type of cell that shows a high tolerance to antibiotic treatment. Recent studies have shown a connection between low intracellular ATP and persister cell formation. Specifically, this decrease in ATP, and therefore increase in persister cell formation, is due to an interrupted tricarboxylic acid (TCA) cycle. However, S. aureus persister cells’ role in pathogenesis remains unclear. Initial studies have shown that a fumC (TCA cycle gene) knockout survives challenge from aspects of the innate immune system better than wild-type S. aureus. Specifically, challenges from two antimicrobial peptides--LL-37 and hBD-3—show a log increase in survival of the fumC::N∑ strain compared to wild type S. aureus after 18 hours. Furthermore, preliminary studies show that the fumC knockout has a log more survival within a macrophage. These data lead us to hypothesize that the fumC knockout is better suited to other aspects of the innate immune system compared to wild-type S. aureus. To further investigate the mechanism for increased survival of fumC::N∑ within a macrophage, we tested bacterial growth in the presence of reactive oxygen species (ROS), reactive nitrogen species (RNS), and a low pH. Preliminary results suggest that the fumC knockout has increased growth compared to wild-type S. aureus in the presence of all three antimicrobial factors; however, no difference was observed in any single factor alone. To investigate survival within a host, a nine-day biofilm-associated catheter infection was performed on 6–8-week-old male and female C57Bl/6 mice. Although both sexes struggled to clear the infection, female mice were trending toward more frequently clearing the HG003 wild-type infection compared to the fumC::N∑ infection. One possible reason for the inability to reduce the bacterial burden is that biofilms are largely composed of persister cells. To test this hypothesis further, flow cytometry in conjunction with a persister cell marker was used to measure persister cells within a biofilm. Cap5A (a known persister cell marker) expression was found to be increased in a maturing biofilm, with the lowest levels of expression seen in immature biofilms and the highest expression exhibited by the 48-hour biofilm. Additionally, bacterial cells in a biofilm state closely resemble persister cells and exhibit reduced membrane potential compared to cells in planktonic culture, further suggesting biofilms are largely made up of persister cells. These data may provide an explanation as to why infections caused by antibiotic-susceptible strains remain difficult to treat.

Keywords: antibiotic tolerance, Staphylococcus aureus, host-pathogen interactions, microbial pathogenesis

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1828 Pre and Post IFRS Loss Avoidance in France and the United Kingdom

Authors: T. Miková

Abstract:

This paper analyzes the effect of a single uniform accounting rule on reporting quality by investigating the influence of IFRS on earnings management. This paper examines whether earnings management is reduced after IFRS adoption through the use of “loss avoidance thresholds”, a method that has been verified in earlier studies. This paper concentrates on two European countries: one that represents the continental code law tradition with weak protection of investors (France) and one that represents the Anglo-American common law tradition, which typically implies a strong enforcement system (the United Kingdom). The research investigates a sample of 526 companies (6822 firm-year observations) during the years 2000 – 2013. The results are different for the two jurisdictions. This study demonstrates that a single set of accounting standards contributes to better reporting quality and reduces the pervasiveness of earnings management in France. In contrast, there is no evidence that a reduction in earnings management followed the implementation of IFRS in the United Kingdom. Due to the fact that IFRS benefit France but not the United Kingdom, other political and economic factors, such legal system or capital market strength, must play a significant role in influencing the comparability and transparency cross-border companies’ financial statements. Overall, the result suggests that IFRS moderately contribute to the accounting quality of reported financial statements and bring benefit for stakeholders, though the role played by other economic factors cannot be discounted.

Keywords: accounting standards, earnings management, international financial reporting standards, loss avoidance, reporting quality

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1827 MANIFEST-2, a Global, Phase 3, Randomized, Double-Blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAK Inhibitor-Naïve Myelofibrosis Patients

Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

Abstract:

Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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