Search results for: block chain
Commenced in January 2007
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Edition: International
Paper Count: 2897

Search results for: block chain

137 Preliminary Studies on Poloxamer-Based Hydrogels with Oregano Essential Oil as Potential Topical Treatment of Cutaneous Papillomas

Authors: Ana Maria Muț, Georgeta Coneac, Ioana Olariu, Ștefana Avram, Ioana Zinuca Pavel, Ionela Daliana Minda, Lavinia Vlaia, Cristina Adriana Dehelean, Corina Danciu

Abstract:

Oregano essential oil is obtained from different parts of the plant Origanum vulgare (fam. Lamiaceae) and carvacrol and thymol are primary components, widely recognized for their antimicrobial activity, as well as their antiviral and antifungal properties. Poloxamers are triblock copolymers (Pluronic®), formed of three non-ionic blocks with a hydrophobic polyoxypropylene central chain flanked by two polyoxyethylene hydrophilic chains. They are known for their biocompatibility, sensitivity to temperature changes (sol-to-gel transition of aqueous solution with temperature increase), but also for their amphiphilic and surface active nature determining the formation of micelles, useful for solubilization of different hydrophobic compounds such as the terpenes and terpenoids contained in essential oils. Thus, these polymers, listed in European and US Pharmacopoeia and approved by FDA, are widely used as solubilizers and gelling agents for various pharmaceutical preparations, including topical hydrogels. The aim of this study was to investigate the posibility of solubilizing oregano essential oil (OEO) in polymeric micelles using polyoxypropylene (PPO)-polyoxyethylene (PEO)-polyoxypropylene (PPO) triblock polymers to obtain semisolid systems suitable for topical application. A formulation screening was performed, using Pluronic® F-127 in concentration of 20%, Pluronic® L-31, Pluronic® L-61 and Pluronic® L-62 in concentration of 0.5%, 0.8% respectively 1% to obtain the polymeric micelles-based systems. Then, to each selected system, with or without 10% absolute ethanol, 5% or 8% OEO was added. The obtained transparent poloxamer-based hydrogels containing solubilized OEO were further evaluated for pH, rheological characteristics (flow behaviour, viscosity, consistency and spreadability), using consacrated techniques like potentiometric titration, stationary shear flow test, penetrometric method and parallel plate method. Also, in vitro release and permeation of carvacrol from the hydrogels was carried out, using vertical diffusion cells and synthetic hydrophilic membrane and porcine skin respectively. The pH values and rheological features of all tested formulations were in accordance with official requirements for semisolid cutaneous preparations. But, the formulation containing 0.8% Pluronic® L-31, 10% absolute ethanol, 8% OEO and water and the formulation with 1% Pluronic® L-31, 5% OEO and water, produced the highest cumulative amounts of carvacrol released/permeated through the membrane. The present study demonstrated that oregano essential oil can be successfully solubilized in the investigated poloxamer-based hydrogels. These systems can be further investigated as potential topical therapy for cutaneous papillomas. Funding: This research was funded by Project PN-III-P1-1.1-TE2019-0130, Contract number TE47, Romania.

Keywords: oregano essential oil, carvacrol, poloxamer, topical hydrogels

Procedia PDF Downloads 113
136 Investigating the Key Success Factors of Supplier Collaboration Governance in the Aerospace Industry

Authors: Maria Jose Granero Paris, Ana Isabel Jimenez Zarco, Agustin Pablo Alvarez Herranz

Abstract:

In the industrial sector collaboration with suppliers is key to the development of innovations in the field of processes. Access to resources and expertise that are not available in the business, obtaining a cost advantage, or the reduction of the time needed to carry out innovation are some of the benefits associated with the process. However, the success of this collaborative process is compromised, when from the beginning not clearly rules have been established that govern the relationship. Abundant studies developed in the field of innovation emphasize the strategic importance of the concept of “Governance”. Despite this, there have been few papers that have analyzed how the governance process of the relationship must be designed and managed to ensure the success of the collaboration process. The lack of literature in this area responds to the wide diversity of contexts where collaborative processes to innovate take place. Thus, in sectors such as the car industry there is a strong collaborative tradition between manufacturers and suppliers being part of the value chain. In this case, it is common to establish mechanisms and procedures that fix formal and clear objectives to regulate the relationship, and establishes the rights and obligations of each of the parties involved. By contrast, in other sectors, collaborative relationships to innovate are not a common way of working, particularly when their aim is the development of process improvements. It is in this case, it is when the lack of mechanisms to establish and regulate the behavior of those involved, can give rise to conflicts, and the failure of the cooperative relationship. Because of this the present paper analyzes the similarities and differences in the processes of governance in collaboration with suppliers in the European aerospace industry With these ideas in mind, we present research is twofold: Understand the importance of governance as a key element of the success of the collaboration in the development of product and process innovations, Establish the mechanisms and procedures to ensure the proper management of the processes of collaboration. Following the methodology of the case study, we analyze the way in which manufacturers and suppliers cooperate in the development of new products and processes in two industries with different levels of technological intensity and collaborative tradition: the automotive and aerospace. The identification of those elements playing a key role to establish a successful governance and relationship management and the compression of the mechanisms of regulation and control in place at the automotive sector can be use to propose solutions to some of the conflicts that currently arise in aerospace industry. The paper concludes by analyzing the strategic implications for the aerospace industry entails the adoption of some of the practices traditionally used in other industrial sectors. Finally, it is important to highlight that in this paper are presented the first results of a research project currently in progress describing a model of governance that explains the way to manage outsourced services to suppliers in the European aerospace industry, through the analysis of companies in the sector located in Germany, France and Spain.

Keywords: supplier collaboration, supplier relationship governance, innovation management, product innovation, process innovation

Procedia PDF Downloads 459
135 Spatial Transformation of Heritage Area as The Impact of Tourism Activity (Case Study: Kauman Village, Surakarta City, Central Java, Indonesia

Authors: Nafiah Solikhah Thoha

Abstract:

One area that has spatial character as Heritage area is Kauman Villages. Kauman village in The City of Surakarta, Central Java, Indonesia was formed in 1757 by Paku Buwono III as the King of Kasunanan kingdom (Mataram Kingdom) for Kasunanan kingdom courtiers and scholars of Madrasa. Spatial character of Kauman village influenced by Islamic planning and socio-cultural rules of Kasunanan Kingdom. As traditional settlements influenced by Islamic planning, the Grand Mosque is a binding part of the whole area. Circulation pattern forming network (labyrinth) with narrow streets that ended at the Grand Mosque. The outdoor space can be used for circulation. Social activity is dominated by step movement from one place to a different place. Stalemate (the fina/cul de sac) generally only passable on foot, bicycles, and motorcycles. While the pass (main and branch) can be traversed by motor, vehicles. Kauman village has an area that can not be used as a public road that penetrates and serves as a liaison between the outside world to the other. Hierarchy of hall in Kauman village shows that the existence of a space is getting into more important. Firstly, woman in Kauman make the handmade batik for themself. In 2005 many people improving batik tradisional into commercial, and developed program named "Batik Tourism village of Kauman". That program affects the spatial transformations. This study aimed to explore the influence of tourism program towards spatial transformations. The factors that studied are the organization of space, circulation patterns, hierarchical space, and orientation through the descriptive-evaluation approach methods. Based on the study, tourism activity engenders transformations on the spatial scale (macro), residential block (mezo), homes (micro). First, the Grand Mosque and madrasa (religious school) as a binding zoning; tangle of roads as forming the structure of the area developed as a liaison with outside Kauman; organization of space in the residential of batik entrepreneurs firstly just a residential, then develop into residential, factory of batik including showroom. Second, the circulation pattern forming network (labyrinth) and ends at the Grand Mosque. Third, the hierarchy in the form of public space (the shari), semi-public, and private (the fina/culdesac) is no longer to provide protection to women, only as hierarchy of circulation path. Fourth, cluster building orientation does not follow the kiblat direction or axis oriented to cosmos, but influence by the new function as the showroom. It was need the direction of the main road. Kauman grow as an appropriate area for the community. During its development, the settlement function changes according to community activities, especially economic activities. The new function areas as tourism area affect spatial pattern of Kauman village. Spatial existence and activity as a local wisdom that has been done for generations have meaning of holistic, encompassing socio-cultural sustainability, economics, and the heritage area. By reviewing the local wisdom and the way of life of that society, we can learn how to apply the culture as education for sustainable of heritage area.

Keywords: impact of tourism, Kauman village, spatial transformation, sustainable of heritage area

Procedia PDF Downloads 433
134 Modeling and Performance Evaluation of an Urban Corridor under Mixed Traffic Flow Condition

Authors: Kavitha Madhu, Karthik K. Srinivasan, R. Sivanandan

Abstract:

Indian traffic can be considered as mixed and heterogeneous due to the presence of various types of vehicles that operate with weak lane discipline. Consequently, vehicles can position themselves anywhere in the traffic stream depending on availability of gaps. The choice of lateral positioning is an important component in representing and characterizing mixed traffic. The field data provides evidence that the trajectory of vehicles in Indian urban roads have significantly varying longitudinal and lateral components. Further, the notion of headway which is widely used for homogeneous traffic simulation is not well defined in conditions lacking lane discipline. From field data it is clear that following is not strict as in homogeneous and lane disciplined conditions and neighbouring vehicles ahead of a given vehicle and those adjacent to it could also influence the subject vehicles choice of position, speed and acceleration. Given these empirical features, the suitability of using headway distributions to characterize mixed traffic in Indian cities is questionable, and needs to be modified appropriately. To address these issues, this paper attempts to analyze the time gap distribution between consecutive vehicles (in a time-sense) crossing a section of roadway. More specifically, to characterize the complex interactions noted above, the influence of composition, manoeuvre types, and lateral placement characteristics on time gap distribution is quantified in this paper. The developed model is used for evaluating various performance measures such as link speed, midblock delay and intersection delay which further helps to characterise the vehicular fuel consumption and emission on urban roads of India. Identifying and analyzing exact interactions between various classes of vehicles in the traffic stream is essential for increasing the accuracy and realism of microscopic traffic flow modelling. In this regard, this study aims to develop and analyze time gap distribution models and quantify it by lead lag pair, manoeuvre type and lateral position characteristics in heterogeneous non-lane based traffic. Once the modelling scheme is developed, this can be used for estimating the vehicle kilometres travelled for the entire traffic system which helps to determine the vehicular fuel consumption and emission. The approach to this objective involves: data collection, statistical modelling and parameter estimation, simulation using calibrated time-gap distribution and its validation, empirical analysis of simulation result and associated traffic flow parameters, and application to analyze illustrative traffic policies. In particular, video graphic methods are used for data extraction from urban mid-block sections in Chennai, where the data comprises of vehicle type, vehicle position (both longitudinal and lateral), speed and time gap. Statistical tests are carried out to compare the simulated data with the actual data and the model performance is evaluated. The effect of integration of above mentioned factors in vehicle generation is studied by comparing the performance measures like density, speed, flow, capacity, area occupancy etc under various traffic conditions and policies. The implications of the quantified distributions and simulation model for estimating the PCU (Passenger Car Units), capacity and level of service of the system are also discussed.

Keywords: lateral movement, mixed traffic condition, simulation modeling, vehicle following models

Procedia PDF Downloads 342
133 Motives for Reshoring from China to Europe: A Hierarchical Classification of Companies

Authors: Fabienne Fel, Eric Griette

Abstract:

Reshoring, whether concerning back-reshoring or near-reshoring, is a quite recent phenomenon. Despite the economic and political interest of this topic, academic research questioning determinants of reshoring remains rare. Our paper aims at contributing to fill this gap. In order to better understand the reasons for reshoring, we conducted a study among 280 French firms during spring 2016, three-quarters of which sourced, or source, in China. 105 firms in the sample have reshored all or part of their Chinese production or supply in recent years, and we aimed to establish a typology of the motives that drove them to this decision. We asked our respondents about the history of their Chinese supplies, their current reshoring strategies, and their motivations. Statistical analysis was performed with SPSS 22 and SPAD 8. Our results show that change in commercial and financial terms with China is the first motive explaining the current reshoring movement from this country (it applies to 54% of our respondents). A change in corporate strategy is the second motive (30% of our respondents); the reshoring decision follows a change in companies’ strategies (upgrading, implementation of a CSR policy, or a 'lean management' strategy). The third motive (14% of our sample) is a mere correction of the initial offshoring decision, considered as a mistake (under-estimation of hidden costs, non-quality and non-responsiveness problems). Some authors emphasize that developing a short supply chain, involving geographic proximity between design and production, gives a competitive advantage to companies wishing to offer innovative products. Admittedly 40% of our respondents indicate that this motive could have played a part in their decision to reshore, but this reason was not enough for any of them and is not an intrinsic motive leading to leaving Chinese suppliers. Having questioned our respondents about the importance given to various problems leading them to reshore, we then performed a Principal Components Analysis (PCA), associated with an Ascending Hierarchical Classification (AHC), based on Ward criterion, so as to point out more specific motivations. Three main classes of companies should be distinguished: -The 'Cost Killers' (23% of the sample), which reshore their supplies from China only because of higher procurement costs and so as to find lower costs elsewhere. -The 'Realists' (50% of the sample), giving equal weight or importance to increasing procurement costs in China and to the quality of their supplies (to a large extend). Companies being part of this class tend to take advantage of this changing environment to change their procurement strategy, seeking suppliers offering better quality and responsiveness. - The 'Voluntarists' (26% of the sample), which choose to reshore their Chinese supplies regardless of higher Chinese costs, to obtain better quality and greater responsiveness. We emphasize that if the main driver for reshoring from China is indeed higher local costs, it is should not be regarded as an exclusive motivation; 77% of the companies in the sample, are also seeking, sometimes exclusively, more reactive suppliers, liable to quality, respect for the environment and intellectual property.

Keywords: China, procurement, reshoring, strategy, supplies

Procedia PDF Downloads 326
132 Design, Development and Testing of Polymer-Glass Microfluidic Chips for Electrophoretic Analysis of Biological Sample

Authors: Yana Posmitnaya, Galina Rudnitskaya, Tatyana Lukashenko, Anton Bukatin, Anatoly Evstrapov

Abstract:

An important area of biological and medical research is the study of genetic mutations and polymorphisms that can alter gene function and cause inherited diseases and other diseases. The following methods to analyse DNA fragments are used: capillary electrophoresis and electrophoresis on microfluidic chip (MFC), mass spectrometry with electrophoresis on MFC, hybridization assay on microarray. Electrophoresis on MFC allows to analyse small volumes of samples with high speed and throughput. A soft lithography in polydimethylsiloxane (PDMS) was chosen for operative fabrication of MFCs. A master-form from silicon and photoresist SU-8 2025 (MicroChem Corp.) was created for the formation of micro-sized structures in PDMS. A universal topology which combines T-injector and simple cross was selected for the electrophoretic separation of the sample. Glass K8 and PDMS Sylgard® 184 (Dow Corning Corp.) were used for fabrication of MFCs. Electroosmotic flow (EOF) plays an important role in the electrophoretic separation of the sample. Therefore, the estimate of the quantity of EOF and the ways of its regulation are of interest for the development of the new methods of the electrophoretic separation of biomolecules. The following methods of surface modification were chosen to change EOF: high-frequency (13.56 MHz) plasma treatment in oxygen and argon at low pressure (1 mbar); 1% aqueous solution of polyvinyl alcohol; 3% aqueous solution of Kolliphor® P 188 (Sigma-Aldrich Corp.). The electroosmotic mobility was evaluated by the method of Huang X. et al., wherein the borate buffer was used. The influence of physical and chemical methods of treatment on the wetting properties of the PDMS surface was controlled by the sessile drop method. The most effective way of surface modification of MFCs, from the standpoint of obtaining the smallest value of the contact angle and the smallest value of the EOF, was the processing with aqueous solution of Kolliphor® P 188. This method of modification has been selected for the treatment of channels of MFCs, which are used for the separation of mixture of oligonucleotides fluorescently labeled with the length of chain with 10, 20, 30, 40 and 50 nucleotides. Electrophoresis was performed on the device MFAS-01 (IAI RAS, Russia) at the separation voltage of 1500 V. 6% solution of polydimethylacrylamide with the addition of 7M carbamide was used as the separation medium. The separation time of components of the mixture was determined from electropherograms. The time for untreated MFC was ~275 s, and for the ones treated with solution of Kolliphor® P 188 – ~ 220 s. Research of physical-chemical methods of surface modification of MFCs allowed to choose the most effective way for reducing EOF – the modification with aqueous solution of Kolliphor® P 188. In this case, the separation time of the mixture of oligonucleotides decreased about 20%. The further optimization of method of modification of channels of MFCs will allow decreasing the separation time of sample and increasing the throughput of analysis.

Keywords: electrophoresis, microfluidic chip, modification, nucleic acid, polydimethylsiloxane, soft lithography

Procedia PDF Downloads 414
131 Spectroscopic Autoradiography of Alpha Particles on Geologic Samples at the Thin Section Scale Using a Parallel Ionization Multiplier Gaseous Detector

Authors: Hugo Lefeuvre, Jerôme Donnard, Michael Descostes, Sophie Billon, Samuel Duval, Tugdual Oger, Herve Toubon, Paul Sardini

Abstract:

Spectroscopic autoradiography is a method of interest for geological sample analysis. Indeed, researchers may face different issues such as radioelement identification and quantification in the field of environmental studies. Imaging gaseous ionization detectors find their place in geosciences for conducting specific measurements of radioactivity to improve the monitoring of natural processes using naturally-occurring radioactive tracers, but also for the nuclear industry linked to the mining sector. In geological samples, the location and identification of the radioactive-bearing minerals at the thin-section scale remains a major challenge as the detection limit of the usual elementary microprobe techniques is far higher than the concentration of most of the natural radioactive decay products. The spatial distribution of each decay product in the case of uranium in a geomaterial is interesting for relating radionuclides concentration to the mineralogy. The present study aims to provide spectroscopic autoradiography analysis method for measuring the initial energy of alpha particles with a parallel ionization multiplier gaseous detector. The analysis method has been developed thanks to Geant4 modelling of the detector. The track of alpha particles recorded in the gas detector allow the simultaneous measurement of the initial point of emission and the reconstruction of the initial particle energy by a selection based on the linear energy distribution. This spectroscopic autoradiography method was successfully used to reproduce the alpha spectra from a 238U decay chain on a geological sample at the thin-section scale. The characteristics of this measurement are an energy spectrum resolution of 17.2% (FWHM) at 4647 keV and a spatial resolution of at least 50 µm. Even if the efficiency of energy spectrum reconstruction is low (4.4%) compared to the efficiency of a simple autoradiograph (50%), this novel measurement approach offers the opportunity to select areas on an autoradiograph to perform an energy spectrum analysis within that area. This opens up possibilities for the detailed analysis of heterogeneous geological samples containing natural alpha emitters such as uranium-238 and radium-226. This measurement will allow the study of the spatial distribution of uranium and its descendants in geo-materials by coupling scanning electron microscope characterizations. The direct application of this dual modality (energy-position) of analysis will be the subject of future developments. The measurement of the radioactive equilibrium state of heterogeneous geological structures, and the quantitative mapping of 226Ra radioactivity are now being actively studied.

Keywords: alpha spectroscopy, digital autoradiography, mining activities, natural decay products

Procedia PDF Downloads 151
130 Housing Recovery in Heavily Damaged Communities in New Jersey after Hurricane Sandy

Authors: Chenyi Ma

Abstract:

Background: The second costliest hurricane in U.S. history, Sandy landed in southern New Jersey on October 29, 2012, and struck the entire state with high winds and torrential rains. The disaster killed more than 100 people, left more than 8.5 million households without power, and damaged or destroyed more than 200,000 homes across the state. Immediately after the disaster, public policy support was provided in nine coastal counties that constituted 98% of the major and severely damaged housing units in NJ overall. The programs include Individuals and Households Assistance Program, Small Business Loan Program, National Flood Insurance Program, and the Federal Emergency Management Administration (FEMA) Public Assistance Grant Program. In the most severely affected counties, additional funding was provided through Community Development Block Grant: Reconstruction, Rehabilitation, Elevation, and Mitigation Program, and Homeowner Resettlement Program. How these policies individually and as a whole impacted housing recovery across communities with different socioeconomic and demographic profiles has not yet been studied, particularly in relation to damage levels. The concept of community social vulnerability has been widely used to explain many aspects of natural disasters. Nevertheless, how communities are vulnerable has been less fully examined. Community resilience has been conceptualized as a protective factor against negative impacts from disasters, however, how community resilience buffers the effects of vulnerability is not yet known. Because housing recovery is a dynamic social and economic process that varies according to context, this study examined the path from community vulnerability and resilience to housing recovery looking at both community characteristics and policy interventions. Sample/Methods: This retrospective longitudinal case study compared a literature-identified set of pre-disaster community characteristics, the effects of multiple public policy programs, and a set of time-variant community resilience indicators to changes in housing stock (operationally defined by percent of building permits to total occupied housing units/households) between 2010 and 2014, two years before and after Hurricane Sandy. The sample consisted of 51 municipalities in the nine counties in which between 4% and 58% of housing units suffered either major or severe damage. Structural equation modeling (SEM) was used to determine the path from vulnerability to the housing recovery, via multiple public programs, separately and as a whole, and via the community resilience indicators. The spatial analytical tool ArcGIS 10.2 was used to show the spatial relations between housing recovery patterns and community vulnerability and resilience. Findings: Holding damage levels constant, communities with higher proportions of Hispanic households had significantly lower levels of housing recovery while communities with households with an adult >age 65 had significantly higher levels of the housing recovery. The contrast was partly due to the different levels of total public support the two types of the community received. Further, while the public policy programs individually mediated the negative associations between African American and female-headed households and housing recovery, communities with larger proportions of African American, female-headed and Hispanic households were “vulnerable” to lower levels of housing recovery because they lacked sufficient public program support. Even so, higher employment rates and incomes buffered vulnerability to lower housing recovery. Because housing is the "wobbly pillar" of the welfare state, the housing needs of these particular groups should be more fully addressed by disaster policy.

Keywords: community social vulnerability, community resilience, hurricane, public policy

Procedia PDF Downloads 373
129 Collaborative Procurement in the Pursuit of Net- Zero: A Converging Journey

Authors: Bagireanu Astrid, Bros-Williamson Julio, Duncheva Mila, Currie John

Abstract:

The Architecture, Engineering, and Construction (AEC) sector plays a critical role in the global transition toward sustainable and net-zero built environments. However, the industry faces unique challenges in planning for net-zero while struggling with low productivity, cost overruns and overall resistance to change. Traditional practices fall short due to their inability to meet the requirements for systemic change, especially as governments increasingly demand transformative approaches. Working in silos and rigid hierarchies and a short-term, client-centric approach prioritising immediate gains over long-term benefit stands in stark contrast to the fundamental requirements for the realisation of net-zero objectives. These practices have limited capacity to effectively integrate AEC stakeholders and promote the essential knowledge sharing required to address the multifaceted challenges of achieving net-zero. In the context of built environment, procurement may be described as the method by which a project proceeds from inception to completion. Collaborative procurement methods under the Integrated Practices (IP) umbrella have the potential to align more closely with net-zero objectives. This paper explores the synergies between collaborative procurement principles and the pursuit of net zero in the AEC sector, drawing upon the shared values of cross-disciplinary collaboration, Early Supply Chain involvement (ESI), use of standards and frameworks, digital information management, strategic performance measurement, integrated decision-making principles and contractual alliancing. To investigate the role of collaborative procurement in advancing net-zero objectives, a structured research methodology was employed. First, the study focuses on a systematic review on the application of collaborative procurement principles in the AEC sphere. Next, a comprehensive analysis is conducted to identify common clusters of these principles across multiple procurement methods. An evaluative comparison between traditional procurement methods and collaborative procurement for achieving net-zero objectives is presented. Then, the study identifies the intersection between collaborative procurement principles and the net-zero requirements. Lastly, an exploration of key insights for AEC stakeholders focusing on the implications and practical applications of these findings is made. Directions for future development of this research are recommended. Adopting collaborative procurement principles can serve as a strategic framework for guiding the AEC sector towards realising net-zero. Synergising these approaches overcomes fragmentation, fosters knowledge sharing, and establishes a net-zero-centered ecosystem. In the context of the ongoing efforts to amplify project efficiency within the built environment, a critical realisation of their central role becomes imperative for AEC stakeholders. When effectively leveraged, collaborative procurement emerges as a powerful tool to surmount existing challenges in attaining net-zero objectives.

Keywords: collaborative procurement, net-zero, knowledge sharing, architecture, built environment

Procedia PDF Downloads 74
128 Investigating the Governance of Engineering Services in the Aerospace and Automotive Industries

Authors: Maria Jose Granero Paris, Ana Isabel Jimenez Zarco, Agustin Pablo Alvarez Herranz

Abstract:

In the industrial sector collaboration with suppliers is key to the development of innovations in the field of processes. Access to resources and expertise that are not available in the business, obtaining a cost advantage, or the reduction of the time needed to carry out innovation are some of the benefits associated with the process. However, the success of this collaborative process is compromised, when from the beginning not clearly rules have been established that govern the relationship. Abundant studies developed in the field of innovation emphasize the strategic importance of the concept of “Goverance”. Despite this, there have been few papers that have analyzed how the governance process of the relationship must be designed and managed to ensure the success of the cooperation process. The lack of literature in this area responds to the wide diversity of contexts where collaborative processes to innovate take place. Thus, in sectors such as the car industry there is a strong collaborative tradition between manufacturers and suppliers being part of the value chain. In this case, it is common to establish mechanisms and procedures that fix formal and clear objectives to regulate the relationship, and establishes the rights and obligations of each of the parties involved. By contrast, in other sectors, collaborative relationships to innovate are not a common way of working, particularly when their aim is the development of process improvements. It is in this case, it is when the lack of mechanisms to establish and regulate the behavior of those involved, can give rise to conflicts, and the failure of the cooperative relationship. Because of this the present paper analyzes the similarities and differences in the processes of governance in collaboration with service providers in engineering R & D in the European aerospace industry. With these ideas in mind, we present research is twofold: - Understand the importance of governance as a key element of the success of the cooperation in the development of process innovations, - Establish the mechanisms and procedures to ensure the proper management of the processes of cooperation. Following the methodology of the case study, we analyze the way in which manufacturers and suppliers cooperate in the development of new processes in two industries with different levels of technological intensity and collaborative tradition: the automotive and aerospace. The identification of those elements playing a key role to establish a successful governance and relationship management and the compression of the mechanisms of regulation and control in place at the automotive sector can be use to propose solutions to some of the conflicts that currently arise in aerospace industry. The paper concludes by analyzing the strategic implications for the aerospace industry entails the adoption of some of the practices traditionally used in other industrial sectors. Finally, it is important to highlight that in this paper are presented the first results of a research project currently in progress describing a model of governance that explains the way to manage outsourced engineering services to suppliers in the European aerospace industry, through the analysis of companies in the sector located in Germany, France and Spain.

Keywords: innovation management, innovation governance, managing collaborative innovation, process innovation

Procedia PDF Downloads 301
127 Engineered Control of Bacterial Cell-to-Cell Signaling Using Cyclodextrin

Authors: Yuriko Takayama, Norihiro Kato

Abstract:

Quorum sensing (QS) is a cell-to-cell communication system in bacteria to regulate expression of target genes. In gram-negative bacteria, activation on QS is controlled by a concentration increase of N-acylhomoserine lactone (AHL), which can diffuse in and out of the cell. Effective control of QS is expected to avoid virulence factor production in infectious pathogens, biofilm formation, and antibiotic production because various cell functions in gram-negative bacteria are controlled by AHL-mediated QS. In this research, we applied cyclodextrins (CDs) as artificial hosts for the AHL signal to reduce the AHL concentration in the culture broth below its threshold for QS activation. The AHL-receptor complex induced under the high AHL concentration activates transcription of the QS-target gene. Accordingly, artificial reduction of the AHL concentration is one of the effective strategies to inhibit the QS. A hydrophobic cavity of the CD can interact with the acyl-chain of the AHL due to hydrophobic interaction in aqueous media. We studied N-hexanoylhomoserine lactone (C6HSL)-mediated QS in Serratia marcescens; accumulation of C6HSL is responsible for regulation of the expression of pig cluster. Inhibitory effects of added CDs on QS were demonstrated by determination of prodigiosin amount inside cells after reaching stationary phase, because production of prodigiosin depends on the C6HSL-mediated QS. By adding approximately 6 wt% hydroxypropyl-β-CD (HP-β-CD) in Luria-Bertani (LB) medium prior to inoculation of S. maecescens AS-1, the intracellularly accumulated prodigiosin was drastically reduced to 7-10%, which was determined after the extraction of prodigiosin in acidified ethanol. The AHL retention ability of HP-β-CD was also demonstrated by Chromobacterium violacuem CV026 bioassay. The CV026 strain is an AHL-synthase defective mutant that activates QS solely by adding AHLs from outside of cells. A purple pigment violacein is induced by activation of the AHL-mediated QS. We demonstrated that the violacein production was effectively suppressed when the C6HSL standard solution was spotted on a LB agar plate dispersing CV026 cells and HP-β-CD. Physico-chemical analysis was performed to study the affinity between the immobilized CD and added C6HSL using a quartz crystal microbalance (QCM) sensor. The COOH-terminated self-assembled monolayer was prepared on a gold electrode of 27-MHz AT-cut quartz crystal. Mono(6-deoxy-6-N, N-diethylamino)-β-CD was immobilized on the electrode using water-soluble carbodiimide. The C6HSL interaction with the β-CD cavity was studied by injecting the C6HSL solution to a cup-type sensor cell filled with buffer solution. A decrement of resonant frequency (ΔFs) clearly showed the effective C6HSL complexation with immobilized β-CD and its stability constant for MBP-SpnR-C6HSL complex was on the order of 102 M-1. The CD has high potential for engineered control of QS because it is safe for human use.

Keywords: acylhomoserine lactone, cyclodextrin, intracellular signaling, quorum sensing

Procedia PDF Downloads 241
126 Inhibition of Influenza Replication through the Restrictive Factors Modulation by CCR5 and CXCR4 Receptor Ligands

Authors: Thauane Silva, Gabrielle do Vale, Andre Ferreira, Marilda Siqueira, Thiago Moreno L. Souza, Milene D. Miranda

Abstract:

The exposure of A(H1N1)pdm09-infected epithelial cells (HeLa) to HIV-1 viral particles, or its gp120, enhanced interferon-induced transmembrane protein (IFITM3) content, a viral restriction factor (RF), resulting in a decrease in influenza replication. The gp120 binds to CCR5 (R5) or CXCR4 (X4) cell receptors during HIV-1 infection. Then, it is possible that the endogenous ligands of these receptors also modulate the expression of IFITM3 and other cellular factors that restrict influenza virus replication. Thus, the aim of this study is to analyze the role of cellular receptors R5 and X4 in modulating RFs in order to inhibit the replication of the influenza virus. A549 cells were treated with 2x effective dose (ED50) of endogenous R5 or X4 receptor agonists, CCL3 (20 ng/ml), CCL4 (10 ng/ml), CCL5 (10 ng/ml) and CXCL12 (100 ng/mL) or exogenous agonists, gp120 Bal-R5, gp120 IIIB-X4 and its mutants (5 µg/mL). The interferon α (10 ng/mL) and oseltamivir (60 nM) were used as a control. After 24 h post agonists exposure, the cells were infected with virus influenza A(H3N2) at 2 MOI (multiplicity of infection) for 1 h. Then, 24 h post infection, the supernatant was harvested and, the viral titre was evaluated by qRT-PCR. To evaluate IFITM3 and SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) protein levels, A549 were exposed to agonists for 24 h, and the monolayer was lysed with Laemmli buffer for western blot (WB) assay or fixed for indirect immunofluorescence (IFI) assay. In addition to this, we analyzed other RFs modulation in A549, after 24 h post agonists exposure by customized RT² Profiler Polymerase Chain Reaction Array. We also performed a functional assay in which SAMHD1-knocked-down, by single-stranded RNA (siRNA), A549 cells were infected with A(H3N2). In addition, the cells were treated with guanosine to assess the regulatory role of dNTPs by SAMHD1. We found that R5 and X4 agonists inhibited influenza replication in 54 ± 9%. We observed a four-fold increase in SAMHD1 transcripts by RFs mRNA quantification panel. After 24 h post agonists exposure, we did not observe an increase in IFITM3 protein levels through WB or IFI assays, but we observed an upregulation up to three-fold in the protein content of SAMHD1, in A549 exposed to agonists. Besides this, influenza replication enhanced in 20% in cell cultures that SAMDH1 was knockdown. Guanosine treatment in cells exposed to R5 ligands further inhibited influenza virus replication, suggesting that the inhibitory mechanism may involve the activation of the SAMHD1 deoxynucleotide triphosphohydrolase activity. Thus, our data show for the first time a direct relationship of SAMHD1 and inhibition of influenza replication, and provides perspectives for new studies on the signaling modulation, through cellular receptors, to induce proteins of great importance in the control of relevant infections for public health.

Keywords: chemokine receptors, gp120, influenza, virus restriction factors

Procedia PDF Downloads 142
125 Statistical Analysis to Compare between Smart City and Traditional Housing

Authors: Taha Anjamrooz, Sareh Rajabi, Ayman Alzaatreh

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Smart cities are playing important roles in real life. Integration and automation between different features of modern cities and information technologies improve smart city efficiency, energy management, human and equipment resource management, life quality and better utilization of resources for the customers. One of difficulties in this path, is use, interface and link between software, hardware, and other IT technologies to develop and optimize processes in various business fields such as construction, supply chain management and transportation in parallel to cost-effective and resource reduction impacts. Also, Smart cities are certainly intended to demonstrate a vital role in offering a sustainable and efficient model for smart houses while mitigating environmental and ecological matters. Energy management is one of the most important matters within smart houses in the smart cities and communities, because of the sensitivity of energy systems, reduction in energy wastage and maximization in utilizing the required energy. Specially, the consumption of energy in the smart houses is important and considerable in the economic balance and energy management in smart city as it causes significant increment in energy-saving and energy-wastage reduction. This research paper develops features and concept of smart city in term of overall efficiency through various effective variables. The selected variables and observations are analyzed through data analysis processes to demonstrate the efficiency of smart city and compare the effectiveness of each variable. There are ten chosen variables in this study to improve overall efficiency of smart city through increasing effectiveness of smart houses using an automated solar photovoltaic system, RFID System, smart meter and other major elements by interfacing between software and hardware devices as well as IT technologies. Secondly to enhance aspect of energy management by energy-saving within smart house through efficient variables. The main objective of smart city and smart houses is to reproduce energy and increase its efficiency through selected variables with a comfortable and harmless atmosphere for the customers within a smart city in combination of control over the energy consumption in smart house using developed IT technologies. Initially the comparison between traditional housing and smart city samples is conducted to indicate more efficient system. Moreover, the main variables involved in measuring overall efficiency of system are analyzed through various processes to identify and prioritize the variables in accordance to their influence over the model. The result analysis of this model can be used as comparison and benchmarking with traditional life style to demonstrate the privileges of smart cities. Furthermore, due to expensive and expected shortage of natural resources in near future, insufficient and developed research study in the region, and available potential due to climate and governmental vision, the result and analysis of this study can be used as key indicator to select most effective variables or devices during construction phase and design

Keywords: smart city, traditional housing, RFID, photovoltaic system, energy efficiency, energy saving

Procedia PDF Downloads 113
124 Hybrid Materials on the Basis of Magnetite and Magnetite-Gold Nanoparticles for Biomedical Application

Authors: Mariia V. Efremova, Iana O. Tcareva, Anastasia D. Blokhina, Ivan S. Grebennikov, Anastasia S. Garanina, Maxim A. Abakumov, Yury I. Golovin, Alexander G. Savchenko, Alexander G. Majouga, Natalya L. Klyachko

Abstract:

During last decades magnetite nanoparticles (NPs) attract a deep interest of scientists due to their potential application in therapy and diagnostics. However, magnetite nanoparticles are toxic and non-stable in physiological conditions. To solve these problems, we decided to create two types of hybrid systems based on magnetite and gold which is inert and biocompatible: gold as a shell material (first type) and gold as separate NPs interfacially bond to magnetite NPs (second type). The synthesis of the first type hybrid nanoparticles was carried out as follows: Magnetite nanoparticles with an average diameter of 9±2 nm were obtained by co-precipitation of iron (II, III) chlorides then they were covered with gold shell by iterative reduction of hydrogen tetrachloroaurate with hydroxylamine hydrochloride. According to the TEM, ICP MS and EDX data, final nanoparticles had an average diameter of 31±4 nm and contained iron even after hydrochloric acid treatment. However, iron signals (K-line, 7,1 keV) were not localized so we can’t speak about one single magnetic core. Described nanoparticles covered with mercapto-PEG acid were non-toxic for human prostate cancer PC-3/ LNCaP cell lines (more than 90% survived cells as compared to control) and had high R2-relaxivity rates (>190 mМ-1s-1) that exceed the transverse relaxation rate of commercial MRI-contrasting agents. These nanoparticles were also used for chymotrypsin enzyme immobilization. The effect of alternating magnetic field on catalytic properties of chymotrypsin immobilized on magnetite nanoparticles, notably the slowdown of catalyzed reaction at the level of 35-40 % was found. The synthesis of the second type hybrid nanoparticles also involved two steps. Firstly, spherical gold nanoparticles with an average diameter of 9±2 nm were synthesized by the reduction of hydrogen tetrachloroaurate with oleylamine; secondly, they were used as seeds during magnetite synthesis by thermal decomposition of iron pentacarbonyl in octadecene. As a result, so-called dumbbell-like structures were obtained where magnetite (cubes with 25±6 nm diagonal) and gold nanoparticles were connected together pairwise. By HRTEM method (first time for this type of structure) an epitaxial growth of magnetite nanoparticles on gold surface with co-orientation of (111) planes was discovered. These nanoparticles were transferred into water by means of block-copolymer Pluronic F127 then loaded with anti-cancer drug doxorubicin and also PSMA-vector specific for LNCaP cell line. Obtained nanoparticles were found to have moderate toxicity for human prostate cancer cells and got into the intracellular space after 45 minutes of incubation (according to fluorescence microscopy data). These materials are also perspective from MRI point of view (R2-relaxivity rates >70 mМ-1s-1). Thereby, in this work magnetite-gold hybrid nanoparticles, which have a strong potential for biomedical application, particularly in targeted drug delivery and magnetic resonance imaging, were synthesized and characterized. That paves the way to the development of special medicine types – theranostics. The authors knowledge financial support from Ministry of Education and Science of the Russian Federation (14.607.21.0132, RFMEFI60715X0132). This work was also supported by Grant of Ministry of Education and Science of the Russian Federation К1-2014-022, Grant of Russian Scientific Foundation 14-13-00731 and MSU development program 5.13.

Keywords: drug delivery, magnetite-gold, MRI contrast agents, nanoparticles, toxicity

Procedia PDF Downloads 382
123 Enhancing Scalability in Ethereum Network Analysis: Methods and Techniques

Authors: Stefan K. Behfar

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The rapid growth of the Ethereum network has brought forth the urgent need for scalable analysis methods to handle the increasing volume of blockchain data. In this research, we propose efficient methodologies for making Ethereum network analysis scalable. Our approach leverages a combination of graph-based data representation, probabilistic sampling, and parallel processing techniques to achieve unprecedented scalability while preserving critical network insights. Data Representation: We develop a graph-based data representation that captures the underlying structure of the Ethereum network. Each block transaction is represented as a node in the graph, while the edges signify temporal relationships. This representation ensures efficient querying and traversal of the blockchain data. Probabilistic Sampling: To cope with the vastness of the Ethereum blockchain, we introduce a probabilistic sampling technique. This method strategically selects a representative subset of transactions and blocks, allowing for concise yet statistically significant analysis. The sampling approach maintains the integrity of the network properties while significantly reducing the computational burden. Graph Convolutional Networks (GCNs): We incorporate GCNs to process the graph-based data representation efficiently. The GCN architecture enables the extraction of complex spatial and temporal patterns from the sampled data. This combination of graph representation and GCNs facilitates parallel processing and scalable analysis. Distributed Computing: To further enhance scalability, we adopt distributed computing frameworks such as Apache Hadoop and Apache Spark. By distributing computation across multiple nodes, we achieve a significant reduction in processing time and enhanced memory utilization. Our methodology harnesses the power of parallelism, making it well-suited for large-scale Ethereum network analysis. Evaluation and Results: We extensively evaluate our methodology on real-world Ethereum datasets covering diverse time periods and transaction volumes. The results demonstrate its superior scalability, outperforming traditional analysis methods. Our approach successfully handles the ever-growing Ethereum data, empowering researchers and developers with actionable insights from the blockchain. Case Studies: We apply our methodology to real-world Ethereum use cases, including detecting transaction patterns, analyzing smart contract interactions, and predicting network congestion. The results showcase the accuracy and efficiency of our approach, emphasizing its practical applicability in real-world scenarios. Security and Robustness: To ensure the reliability of our methodology, we conduct thorough security and robustness evaluations. Our approach demonstrates high resilience against adversarial attacks and perturbations, reaffirming its suitability for security-critical blockchain applications. Conclusion: By integrating graph-based data representation, GCNs, probabilistic sampling, and distributed computing, we achieve network scalability without compromising analytical precision. This approach addresses the pressing challenges posed by the expanding Ethereum network, opening new avenues for research and enabling real-time insights into decentralized ecosystems. Our work contributes to the development of scalable blockchain analytics, laying the foundation for sustainable growth and advancement in the domain of blockchain research and application.

Keywords: Ethereum, scalable network, GCN, probabilistic sampling, distributed computing

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122 Theoretical Study on the Visible-Light-Induced Radical Coupling Reactions Mediated by Charge Transfer Complex

Authors: Lishuang Ma

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Charge transfer (CT) complex, also known as Electron donor-acceptor (EDA) complex, has received attentions increasingly in the field of synthetic chemistry community, due to the CT complex can absorb the visible light through the intermolecular charge transfer excited states, various of catalyst-free photochemical transformations under mild visible-light conditions. However, a number of fundamental questions are still ambiguous, such as the origin of visible light absorption, the photochemical and photophysical properties of the CT complex, as well as the detailed mechanism of the radical coupling pathways mediated by CT complex. Since these are critical factors for target-specific design and synthesis of more new-type CT complexes. To this end, theoretical investigations were performed in our group to answer these questions based on multiconfigurational perturbation theory. The photo-induced fluoroalkylation reactions are mediated by CT complexes, which are formed by the association of an acceptor of perfluoroalkyl halides RF−X (X = Br, I) and a suitable donor molecule such as β-naphtholate anion, were chosen as a paradigm example in this work. First, spectrum simulations were carried out by both CASPT2//CASSCF/PCM and TD-DFT/PCM methods. The computational results showed that the broadening spectra in visible light range (360-550nm) of the CT complexes originate from the 1(σπ*) excitation, accompanied by an intermolecular electron transfer, which was also found closely related to the aggregate states of the donor and acceptor. Moreover, from charge translocation analysis, the CT complex that showed larger charge transfer in the round state would exhibit smaller charge transfer in excited stated of 1(σπ*), causing blue shift relatively. Then, the excited-state potential energy surface (PES) was calculated at CASPT2//CASSCF(12,10)/ PCM level of theory to explore the photophysical properties of the CT complexes. The photo-induced C-X (X=I, Br) bond cleavage was found to occur in the triplet state, which is accessible through a fast intersystem crossing (ISC) process that is controlled by the strong spin-orbit coupling resulting from the heavy iodine and bromine atoms. Importantly, this rapid fragmentation process can compete and suppress the backward electron transfer (BET) event, facilitating the subsequent effective photochemical transformations. Finally, the reaction pathways of the radical coupling were also inspected, which showed that the radical chain propagation pathway could easy to accomplish with a small energy barrier no more than 3.0 kcal/mol, which is the key factor that promote the efficiency of the photochemical reactions induced by CT complexes. In conclusion, theoretical investigations were performed to explore the photophysical and photochemical properties of the CT complexes, as well as the mechanism of radical coupling reactions mediated by CT complex. The computational results and findings in this work can provide some critical insights into mechanism-based design for more new-type EDA complexes

Keywords: charge transfer complex, electron transfer, multiconfigurational perturbation theory, radical coupling

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121 Effective Affordable Housing Finance in Developing Economies: An Integration of Demand and Supply Solutions

Authors: Timothy Akinwande, Eddie Hui, Karien Dekker

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Housing the urban poor remains a persistent challenge, despite evident research attention over many years. It is, therefore, pertinent to investigate affordable housing provision challenges with novel approaches. For innovative solutions to affordable housing constraints, it is apposite to thoroughly examine housing solutions vis a vis the key elements of the housing supply value chain (HSVC), which are housing finance, housing construction and land acquisition. A pragmatic analysis will examine affordable housing solutions from demand and supply perspectives to arrive at consolidated solutions from bilateral viewpoints. This study thoroughly examined informal housing finance strategies of the urban poor and diligently investigated expert opinion on affordable housing finance solutions. The research questions were: (1) What mutual grounds exist between informal housing finance solutions of the urban poor and housing expert solutions to affordable housing finance constraints in developing economies? (2) What are effective approaches to affordable housing finance in developing economies from an integrated demand - supply perspective? Semi-structured interviews were conducted in the 5 largest slums of Lagos, Nigeria, with 40 informal settlers for demand-oriented solutions, while focus group discussion and in-depth interviews were conducted with 12 housing experts in Nigeria for supply-oriented solutions. Following a rigorous thematic, content and descriptive analyses of data using NVivo and Excel, findings ascertained mutual solutions from both demand and supply standpoints that can be consolidated into more effective affordable housing finance solutions in Nigeria. Deliberate finance models that recognise and include the finance realities of the urban poor was found to be the most significant supply-side housing finance solution, representing 25.4% of total expert responses. Findings also show that 100% of sampled urban poor engage in vocations where they earn little irregular income or zero income, limiting their housing finance capacities and creditworthiness. Survey revealed that the urban poor are involved in community savings and employ microfinance institutions within the informal settlements to tackle their housing finance predicaments. These are informal finance models of the urban poor, revealing common grounds between demand and supply solutions for affordable housing financing. Effective, affordable housing approach will be to modify, institutionalise and incorporate the informal finance strategies of the urban poor into deliberate government policies. This consolidation of solutions from demand and supply perspectives can eliminate the persistent misalliance between affordable housing demand and affordable housing supply. This study provides insights into mutual housing solutions from demand and supply perspectives, and findings are informative for effective, affordable housing provision approaches in developing countries. This study is novel in consolidating affordable housing solutions from demand and supply viewpoints, especially in relation to housing finance as a key component of HSVC. The framework for effective, affordable housing finance in developing economies from a consolidated viewpoint generated in this study is significant for the achievement of sustainable development goals, especially goal 11 for sustainable, resilient and inclusive cities. Findings are vital for future housing studies.

Keywords: affordable housing, affordable housing finance, developing economies, effective affordable housing, housing policy, urban poor, sustainable development goal, sustainable affordable housing

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120 Impact of Sufism on Indian Cinema: A New Cultural Construct for Mediating Conflict

Authors: Ravi Chaturvedi, Ghanshyam Beniwal

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Without going much into the detail of long history of Sufism in the world and the etymological definition of the word ‘Sufi’, it will be sufficient to underline that the concept of Sufism was to focus the mystic power on the spiritual dimension of Islam with a view-shielding the believers from the outwardly and unrealistic dogma of the faith. Sufis adopted rather a liberal view in propagating the religious order of Islam suitable to the cultural and social environment of the land. It is, in fact, a mission of higher religious order of any faith, which disdains strife and conflict in any form. The joy of self-realization being the essence of religion is experienced after a long spiritual practice. India had Sufi and Bhakti (devotion) traditions in Islam and Hinduism, respectively. Both Sufism and Bhakti traditions were based on respect for different religions. The poorer and lower caste Hindus and Muslims were greatly influenced by these traditions. Unlike Ulemas and Brahmans, the Sufi and Bhakti saints were highly tolerant and open to the truth in other faiths. They never adopted sectarian attitudes and were never involved in power struggles. They kept away from power structures. Sufism is integrated with the Indian cinema since its initial days. In the earliest Bollywood movies, Sufism was represented in the form of qawwali which made its way from dargahs (shrines). Mixing it with pop influences, Hindi movies began using Sufi music in a big way only in the current decade. However, of late, songs with Sufi influences have become de rigueur in almost every film being released these days, irrespective of the genre, whether it is a romantic Gangster or a cerebral Corporate. 'Sufi is in the DNA of the Indian sub-continent', according to several contemporary filmmakers, critics, and spectators.The inherent theatricality motivates the performer of the 'Sufi' rituals for a dramatic behavior. The theatrical force of these stages of Sufi practice is so powerful that even the spectator cannot resist himself from being moved. In a multi-cultural country like India, the mediating streams have acquired a multi-layered importance in recent history. The second half of Indian post-colonial era has witnessed a regular chain of some conflicting religio-political waves arising from various sectarian camps in the country, which have compelled the counter forces to activate for keeping the spirit of composite cultural ethos alive. The study has revealed that the Sufi practice methodology is also being adapted for inclusion of spirituality in life at par to Yoga practice. This paper, a part of research study, is an attempt to establish that the Sufism in Indian cinema is one such mediating voice which is very active and alive throughout the length and width of the country continuously bridging the gap between various religious and social factions, and have a significant role to play in future as well.

Keywords: Indian cinema, mediating voice, Sufi, yoga practice

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119 Safety and Efficacy of RM-001, Autologous HBG1/2 Promoter-Modified CD34+Hematopoietic Stem and Progenitor Cells, in Transfusion-Dependent β-Thalassemia

Authors: Rongrong Liu, Li Wang, Hui Xu, Jianpei Fang, Sixi Liu, Xiaolin Yin, Junbin Liang, Gaohui Yan, Yaoyun Li, Yali Zhou, Xinyu Li, Yue Li, Lei Shi, Yongrong Lai, Junjiu Huang, Xinhua Zhang

Abstract:

Background: Beta-Thalassemia is caused by reduced (β+) or absent (β0) synthesis of the β-globin chains of hemoglobin. Transfusions and oral iron chelation therapy have improved the quality of life for patients with Transfusion-Dependent thalassemia (TDT). Recent advances in genome editing platforms of CRISPR-Cas9 have paved the way for induction of HbF by reactivating expression of γ-chain.Aims: We performed CRISPR-Cas9-mediated genome editing of hematopoietic stem cells to mutate HBG1/HBG2 promoter sequence, thereby representing a naturally occurring HPFH-liked mutation, producing RM-001. Here, we present an initial assessment of safety and efficacy of RM-001 in patients with TDT. Methods: Patients (6–35 y of age) with TDT receiving packed red blood cell (pRBC) transfusions of ≥100 mL/kg/y or ≥10 units/y in the previous 2 y were eligible. CD34+ cells were edited with CRISPR-Cas9 using a guide RNA specific for the binding site of BCL11A on the HBG1/2 promoter. Prior to RM-001 product infusion (day 0), patients received myeloablative conditioning with Busulfan from day-7 to day-4. Patients were monitored for AEs Hb expression.Results: Data cut as of 28 Feb 2024, 16 TDT patients have been treated with RM-001 and followed ≥3 months. 5 of these 16 patients had finished their 24 months follow up. Eleven patients have β0/β0 genotype and five patients have β0/β+ genotype. In addition to β-thalassemia, two patients had α- deletion with the genotype of --/αα. Efficacy:All patients received a single dose intravenous infusion of RM-001 cells. 5 of them had been followed 24 months or longer. All patients achieved transfusion-independent (TI, total Hb continued ≥ 9g/dL) (Figure1). Patients demonstrated sustained and clinically meaningful increases in HbF levels since 4 month post-RM-001 infusion (Figure.2). Total hemoglobin in all patients was stable at 10-12g/dL during the follow-up period. Safety:The adverse events observed after RM-001 infusion were consistent with those that are typical of Busulfan-based myeloablation. The allelic editing analysis at 6-month visit showed that the on-target allelic editing frequency in bone marrow cells was 73.44% (64.65% to 84.6%, n=13).Summary/Conclusion: This interim analysis, in which all the 19 patients age from 7.9 to 25yo met the success criteria for the trial with respect to transfusion independence, showed that autologous HBG1/2 promoter-modified CD34+ HSPCs gene therapy resulted in an adequate amount of HbF as early as 2 months after infusion led to near-normal hemoglobin levels, remained transfusion-free through the reported period without product related SAE. After RM-001 infusion, high levels of HbF proportion and on-target editing in bone marrow cells were maintained. Submitted on behalf of the RM-001 Investigators.

Keywords: thalassemian, genetherapy, CRISPR/Cas9, HbF

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118 Improving Binding Selectivity in Molecularly Imprinted Polymers from Templates of Higher Biomolecular Weight: An Application in Cancer Targeting and Drug Delivery

Authors: Ben Otange, Wolfgang Parak, Florian Schulz, Michael Alexander Rubhausen

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The feasibility of extending the usage of molecular imprinting technique in complex biomolecules is demonstrated in this research. This technique is promising in diverse applications in areas such as drug delivery, diagnosis of diseases, catalysts, and impurities detection as well as treatment of various complications. While molecularly imprinted polymers MIP remain robust in the synthesis of molecules with remarkable binding sites that have high affinities to specific molecules of interest, extending the usage to complex biomolecules remains futile. This work reports on the successful synthesis of MIP from complex proteins: BSA, Transferrin, and MUC1. We show in this research that despite the heterogeneous binding sites and higher conformational flexibility of the chosen proteins, relying on their respective epitopes and motifs rather than the whole template produces highly sensitive and selective MIPs for specific molecular binding. Introduction: Proteins are vital in most biological processes, ranging from cell structure and structural integrity to complex functions such as transport and immunity in biological systems. Unlike other imprinting templates, proteins have heterogeneous binding sites in their complex long-chain structure, which makes their imprinting to be marred by challenges. In addressing this challenge, our attention is inclined toward the targeted delivery, which will use molecular imprinting on the particle surface so that these particles may recognize overexpressed proteins on the target cells. Our goal is thus to make surfaces of nanoparticles that specifically bind to the target cells. Results and Discussions: Using epitopes of BSA and MUC1 proteins and motifs with conserved receptors of transferrin as the respective templates for MIPs, significant improvement in the MIP sensitivity to the binding of complex protein templates was noted. Through the Fluorescence Correlation Spectroscopy FCS measurements on the size of protein corona after incubation of the synthesized nanoparticles with proteins, we noted a high affinity of MIPs to the binding of their respective complex proteins. In addition, quantitative analysis of hard corona using SDS-PAGE showed that only a specific protein was strongly bound on the respective MIPs when incubated with similar concentrations of the protein mixture. Conclusion: Our findings have shown that the merits of MIPs can be extended to complex molecules of higher biomolecular mass. As such, the unique merits of the technique, including high sensitivity and selectivity, relative ease of synthesis, production of materials with higher physical robustness, and higher stability, can be extended to more templates that were previously not suitable candidates despite their abundance and usage within the body.

Keywords: molecularly imprinted polymers, specific binding, drug delivery, high biomolecular mass-templates

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117 Partially Aminated Polyacrylamide Hydrogel: A Novel Approach for Temporary Oil and Gas Well Abandonment

Authors: Hamed Movahedi, Nicolas Bovet, Henning Friis Poulsen

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Following the advent of the Industrial Revolution, there has been a significant increase in the extraction and utilization of hydrocarbon and fossil fuel resources. However, a new era has emerged, characterized by a shift towards sustainable practices, namely the reduction of carbon emissions and the promotion of renewable energy generation. Given the substantial number of mature oil and gas wells that have been developed inside the petroleum reservoir domain, it is imperative to establish an environmental strategy and adopt appropriate measures to effectively seal and decommission these wells. In general, the cement plug serves as a material for plugging purposes. Nevertheless, there exist some scenarios in which the durability of such a plug is compromised, leading to the potential escape of hydrocarbons via fissures and fractures within cement plugs. Furthermore, cement is often not considered a practical solution for temporary plugging, particularly in the case of well sites that have the potential for future gas storage or CO2 injection. The Danish oil and gas industry has promising potential as a prospective candidate for future carbon dioxide (CO2) injection, hence contributing to the implementation of carbon capture strategies within Europe. The primary reservoir component consists of chalk, a rock characterized by limited permeability. This work focuses on the development and characterization of a novel hydrogel variant. The hydrogel is designed to be injected via a low-permeability reservoir and afterward undergoes a transformation into a high-viscosity gel. The primary objective of this research is to explore the potential of this hydrogel as a new solution for effectively plugging well flow. Initially, the synthesis of polyacrylamide was carried out using radical polymerization inside the confines of the reaction flask. Subsequently, with the application of the Hoffman rearrangement, the polymer chain undergoes partial amination, facilitating its subsequent reaction with the crosslinker and enabling the formation of a hydrogel in the subsequent stage. The organic crosslinker, glutaraldehyde, was employed in the experiment to facilitate the formation of a gel. This gel formation occurred when the polymeric solution was subjected to heat within a specified range of reservoir temperatures. Additionally, a rheological survey and gel time measurements were conducted on several polymeric solutions to determine the optimal concentration. The findings indicate that the gel duration is contingent upon the starting concentration and exhibits a range of 4 to 20 hours, hence allowing for manipulation to accommodate diverse injection strategies. Moreover, the findings indicate that the gel may be generated in environments characterized by acidity and high salinity. This property ensures the suitability of this substance for application in challenging reservoir conditions. The rheological investigation indicates that the polymeric solution exhibits the characteristics of a Herschel-Bulkley fluid with somewhat elevated yield stress prior to solidification.

Keywords: polyacrylamide, hofmann rearrangement, rheology, gel time

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116 Investigation of Alumina Membrane Coated Titanium Implants on Osseointegration

Authors: Pinar Erturk, Sevde Altuntas, Fatih Buyukserin

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In order to obtain an effective integration between an implant and a bone, implant surfaces should have similar properties to bone tissue surfaces. Especially mimicry of the chemical, mechanical and topographic properties of the implant to the bone is crucial for fast and effective osseointegration. Titanium-based biomaterials are more preferred in clinical use, and there are studies of coating these implants with oxide layers that have chemical/nanotopographic properties stimulating cell interactions for enhanced osseointegration. There are low success rates of current implantations, especially in craniofacial implant applications, which are large and vital zones, and the oxide layer coating increases bone-implant integration providing long-lasting implants without requiring revision surgery. Our aim in this study is to examine bone-cell behavior on titanium implants with an aluminum oxide layer (AAO) on effective osseointegration potential in the deformation of large zones with difficult spontaneous healing. In our study, aluminum layer coated titanium surfaces were anodized in sulfuric, phosphoric, and oxalic acid, which are the most common used AAO anodization electrolytes. After morphologic, chemical, and mechanical tests on AAO coated Ti substrates, viability, adhesion, and mineralization of adult bone cells on these substrates were analyzed. Besides with atomic layer deposition (ALD) as a sensitive and conformal technique, these surfaces were coated with pure alumina (5 nm); thus, cell studies were performed on ALD-coated nanoporous oxide layers with suppressed ionic content too. Lastly, in order to investigate the effect of the topography on the cell behavior, flat non-porous alumina layers on silicon wafers formed by ALD were compared with the porous ones. Cell viability ratio was similar between anodized surfaces, but pure alumina coated titanium and anodized surfaces showed a higher viability ratio compared to bare titanium and bare anodized ones. Alumina coated titanium surfaces, which anodized in phosphoric acid, showed significantly different mineralization ratios after 21 days over other bare titanium and titanium surfaces which anodized in other electrolytes. Bare titanium was the second surface that had the highest mineralization ratio. Otherwise, titanium, which is anodized in oxalic acid electrolyte, demonstrated the lowest mineralization. No significant difference was shown between bare titanium and anodized surfaces except AAO titanium surface anodized in phosphoric acid. Currently, osteogenic activities of these cells on the genetic level are investigated by quantitative real-time polymerase chain reaction (qRT-PCR) analysis results of RUNX-2, VEGF, OPG, and osteopontin genes. Also, as a result of the activities of the genes mentioned before, Western Blot will be used for protein detection. Acknowledgment: The project is supported by The Scientific and Technological Research Council of Turkey.

Keywords: alumina, craniofacial implant, MG-63 cell line, osseointegration, oxalic acid, phosphoric acid, sulphuric acid, titanium

Procedia PDF Downloads 131
115 Inputs and Outputs of Innovation Processes in the Colombian Services Sector

Authors: Álvaro Turriago-Hoyos

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Most research tends to see innovation as an explanatory factor in achieving high levels of competitiveness and productivity. More recent studies have begun to analyze the determinants of innovation in the services sector as opposed to the much-discussed industrial sector of a country’s economy. This research paper focuses on the services sector in Colombia, one of Latin America’s fastest growing and biggest economies. Over the past decade, much of Colombia’s economic expansion has relied on commodity exports (mainly oil and coffee) whilst the industrial sector has performed relatively poorly. Such developments highlight the potential of the innovative role played by the services sector of the Colombian economy and its future growth prospects. This research paper analyzes the relationship between inputs, which at the same time are internal sources of innovation (such as R&D activities), and external sources that are improved by technology acquisition. The outputs are basically the four kinds of innovation that the OECD Oslo Manual recognizes: product, process, marketing and organizational innovations. The instrument used to measure this input-output relationship is based on Knowledge Production Function approaches. We run Probit models in order to identify the existing relationships between the above inputs and outputs, but also to identify spill-overs derived from interactions of the components of the value chain of the services firms analyzed: customers, suppliers, competitors, and complementary firms. Data are obtained from the Colombian National Administrative Department of Statistics for the period 2008 to 2013 published in the II and III Colombian National Innovation Survey. A short summary of the results obtained lead to conclude that firm size and a firm’s level of technological development turn out to be important discriminating factors for the description of the innovative process at the firm level. The model’s outcomes show a positive impact on the probability of introducing any kind of innovation both on R&D and Technology Acquisition investment. Also, cooperation agreements with customers, research institutes, competitors, and the suppliers are significant. Belonging to a particular industrial group is an important determinant but only to product and organizational innovation. It is possible to establish that Health Services, Education, Computer, Wholesale trade, and Financial Intermediation are the ISIC sectors, which report the highest number of frequencies of the considered set of firms. Those five sectors of the sixteen considered, in all cases, explained more than half of the total of all kinds of innovations. Product Innovation, which is followed by Marketing Innovation, gets the highest results. Displaying the same set of firms distinguishing by size, and belonging to high and low tech services sector shows that the larger the firms the larger a number of innovations, but also that always high-tech firms show a better innovation performance.

Keywords: Colombia, determinants of innovation, innovation, services sector

Procedia PDF Downloads 268
114 Single Cell Rna Sequencing Operating from Benchside to Bedside: An Interesting Entry into Translational Genomics

Authors: Leo Nnamdi Ozurumba-Dwight

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Single-cell genomic analytical systems have proved to be a platform to isolate bulk cells into selected single cells for genomic, proteomic, and related metabolomic studies. This is enabling systematic investigations of the level of heterogeneity in a diverse and wide pool of cell populations. Single cell technologies, embracing techniques such as high parameter flow cytometry, single-cell sequencing, and high-resolution images are playing vital roles in these investigations on messenger ribonucleic acid (mRNA) molecules and related gene expressions in tracking the nature and course of disease conditions. This entails targeted molecular investigations on unit cells that help us understand cell behavoiur and expressions, which can be examined for their health implications on the health state of patients. One of the vital good sides of single-cell RNA sequencing (scRNA seq) is its probing capacity to detect deranged or abnormal cell populations present within homogenously perceived pooled cells, which would have evaded cursory screening on the pooled cell populations of biological samples obtained as part of diagnostic procedures. Despite conduction of just single-cell transcriptome analysis, scRNAseq now permits comparison of the transcriptome of the individual cells, which can be evaluated for gene expressional patterns that depict areas of heterogeneity with pharmaceutical drug discovery and clinical treatment applications. It is vital to strictly work through the tools of investigations from wet lab to bioinformatics and computational tooled analyses. In the precise steps for scRNAseq, it is critical to do thorough and effective isolation of viable single cells from the tissues of interest using dependable techniques (such as FACS) before proceeding to lysis, as this enhances the appropriate picking of quality mRNA molecules for subsequent sequencing (such as by the use of Polymerase Chain Reaction machine). Interestingly, scRNAseq can be deployed to analyze various types of biological samples such as embryos, nervous systems, tumour cells, stem cells, lymphocytes, and haematopoietic cells. In haematopoietic cells, it can be used to stratify acute myeloid leukemia patterns in patients, sorting them out into cohorts that enable re-modeling of treatment regimens based on stratified presentations. In immunotherapy, it can furnish specialist clinician-immunologist with tools to re-model treatment for each patient, an attribute of precision medicine. Finally, the good predictive attribute of scRNAseq can help reduce the cost of treatment for patients, thus attracting more patients who would have otherwise been discouraged from seeking quality clinical consultation help due to perceived high cost. This is a positive paradigm shift for patients’ attitudes primed towards seeking treatment.

Keywords: immunotherapy, transcriptome, re-modeling, mRNA, scRNA-seq

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113 Molecular Dynamics Simulation Study of Sulfonated Polybenzimidazole Polymers as Promising Forward Osmosis Membranes

Authors: Seyedeh Pardis Hosseini

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With increased levels of clean and affordable water scarcity crises in many countries, wastewater treatment has been chosen as a viable method to produce freshwater for various consumptions. Even though reverse osmosis dominates the wastewater treatment market, forward osmosis (FO) processes have significant advantages, such as potentially using a renewable and low-grade energy source and improving water quality. FO is an osmotically driven membrane process that uses a high concentrated draw solution and a relatively low concentrated feed solution across a semi-permeable membrane. Among many novel FO membranes that have been introduced over the past decades, polybenzimidazole (PBI) membranes, a class of aromatic heterocyclic-based polymers, have shown high thermal and chemical stability because of their unique chemical structure. However, the studies reviewed indicate that the hydrophilicity of PBI membranes is comparatively low. Hence, there is an urgent need to develop novel FO membranes with modified PBI polymers to promote hydrophilicity. A few studies have been undertaken to improve the PBI hydrophilicity by fabricating mixed matrix polymeric membranes and surface modification. Thereby, in this study, two different sulfonated polybenzimidazole (SPBI) polymers with the same backbone but different functional groups, namely arylsulfonate PBI (PBI-AS) and propylsulfonate PBI (PBI-PS), are introduced as FO membranes and studied via the molecular dynamics (MD) simulation method. The FO simulation box consists of three distinct regions: a saltwater region, a membrane region, and a pure-water region. The pure-water region is situated at the upper part of the simulation box, while the saltwater region, which contains an aqueous salt solution of Na+ and Cl− ions along with water molecules, occupies the lower part of the simulation box. Specifically, the saltwater region includes 710 water molecules and 24 Na+ and 24 Cl− ions, resulting in a combined concentration of 10 weight percent (wt%). The pure-water region comprises 788 water molecules. Both the saltwater and pure-water regions have a density of 1.0 g/cm³. The membrane region, positioned between the saltwater and pure-water regions, is constructed from three types of polymers: PBI, PBI-AS, and PBI-PS, each consisting of three polymer chains with 30 monomers per chain. The structural and thermophysical properties of the polymers, water molecules, and Na+ and Cl− ions were analyzed using the COMPASS forcefield. All simulations were conducted using the BIOVIA Materials Studio 2020 software. By monitoring the variation in the number of water molecules over the simulation time within the saltwater region, the water permeability of the polymer membranes was calculated and subsequently compared. The results indicated that SPBI polymers exhibited higher water permeability compared to PBI polymers. This enhanced permeability can be attributed to the structural and compositional differences between SPBI and PBI polymers, which likely facilitate more efficient water transport through the membrane. Consequently, the adoption of SPBI polymers in the FO process is anticipated to result in significantly improved performance. This improvement could lead to higher water flux rates, better salt rejection, and overall more efficient use of resources in desalination and water purification applications.

Keywords: forward osmosis, molecular dynamics simulation, sulfonated polybenzimidazole, water permeability

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112 Role of Vitamin-D in Reducing Need for Supplemental Oxygen Among COVID-19 Patients

Authors: Anita Bajpai, Sarah Duan, Ashlee Erskine, Shehzein Khan, Raymond Kramer

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Introduction: This research focuses on exploring the beneficial effects if any, of Vitamin-D in reducing the need for supplemental oxygen among hospitalized COVID-19 patients. Two questions are investigated – Q1)Doeshaving a healthy level of baselineVitamin-D 25-OH (≥ 30ng/ml) help,andQ2) does administering Vitamin-D therapy after-the-factduring inpatient hospitalization help? Methods/Study Design: This is a comprehensive, retrospective, observational study of all inpatients at RUHS from March through December 2020 who tested positive for COVID-19 based on real-time reverse transcriptase–polymerase chain reaction assay of nasal and pharyngeal swabs and rapid assay antigen test. To address Q1, we looked atall N1=182 patients whose baseline plasma Vitamin-D 25-OH was known and who needed supplemental oxygen. Of this, a total of 121 patients had a healthy Vitamin-D level of ≥30 ng/mlwhile the remaining 61 patients had low or borderline (≤ 29.9ng/ml)level. Similarly, for Q2, we looked at a total of N2=893 patients who were given supplemental oxygen, of which713 were not given Vitamin-D and 180 were given Vitamin-D therapy. The numerical value of the maximum amount of oxygen flow rate(dependent variable) administered was recorded for each patient. The mean values and associated standard deviations for each group were calculated. Thesetwo sets of independent data served as the basis for independent, two-sample t-Test statistical analysis. To be accommodative of any reasonable benefitof Vitamin-D, ap-value of 0.10(α< 10%) was set as the cutoff point for statistical significance. Results: Given the large sample sizes, the calculated statistical power for both our studies exceeded the customary norm of 80% or better (β< 0.2). For Q1, the mean value for maximumoxygen flow rate for the group with healthybaseline level of Vitamin-D was 8.6 L/min vs.12.6L/min for those with low or borderline levels, yielding a p-value of 0.07 (p < 0.10) with the conclusion that those with a healthy level of baseline Vitamin-D needed statistically significant lower levels of supplemental oxygen. ForQ2, the mean value for a maximum oxygen flow rate for those not administered Vitamin-Dwas 12.5 L/min vs.12.8L/min for those given Vitamin-D, yielding a p-valueof 0.87 (p > 0.10). We thereforeconcludedthat there was no statistically significant difference in the use of oxygen therapy between those who were or were not administered Vitamin-D after-the-fact in the hospital. Discussion/Conclusion: We found that patients who had healthy levels of Vitamin-D at baseline needed statistically significant lower levels of supplemental oxygen. Vitamin-D is well documented, including in a recent article in the Lancet, for its anti-inflammatory role as an adjuvant in the regulation of cytokines and immune cells. Interestingly, we found no statistically significant advantage for giving Vitamin-D to hospitalized patients. It may be a case of “too little too late”. A randomized clinical trial reported in JAMA also did not find any reduction in hospital stay of patients given Vitamin-D. Such conclusions come with a caveat that any delayed marginal benefits may not have materialized promptly in the presence of a significant inflammatory condition. Since Vitamin-D is a low-cost, low-risk option, it may still be useful on an inpatient basis until more definitive findings are established.

Keywords: COVID-19, vitamin-D, supplemental oxygen, vitamin-D in primary care

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111 A Study of the Carbon Footprint from a Liquid Silicone Rubber Compounding Facility in Malaysia

Authors: Q. R. Cheah, Y. F. Tan

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In modern times, the push for a low carbon footprint entails achieving carbon neutrality as a goal for future generations. One possible step towards carbon footprint reduction is the use of more durable materials with longer lifespans, for example, silicone data cableswhich show at least double the lifespan of similar plastic products. By having greater durability and longer lifespans, silicone data cables can reduce the amount of trash produced as compared to plastics. Furthermore, silicone products don’t produce micro contamination harmful to the ocean. Every year the electronics industry produces an estimated 5 billion data cables for USB type C and lightning data cables for tablets and mobile phone devices. Material usage for outer jacketing is 6 to 12 grams per meter. Tests show that the product lifespan of a silicone data cable over plastic can be doubled due to greater durability. This can save at least 40,000 tonnes of material a year just on the outer jacketing of the data cable. The facility in this study specialises in compounding of liquid silicone rubber (LSR) material for the extrusion process in jacketing for the silicone data cable. This study analyses the carbon emissions from the facility, which is presently capable of producing more than 1,000 tonnes of LSR annually. This study uses guidelines from the World Business Council for Sustainable Development (WBCSD) and World Resources Institute (WRI) to define the boundaries of the scope. The scope of emissions is defined as 1. Emissions from operations owned or controlled by the reporting company, 2. Emissions from the generation of purchased or acquired energy such as electricity, steam, heating, or cooling consumed by the reporting company, and 3. All other indirect emissions occurring in the value chain of the reporting company, including both upstream and downstream emissions. As the study is limited to the compounding facility, the system boundaries definition according to GHG protocol is cradle-to-gate instead of cradle-to-grave exercises. Malaysia’s present electricity generation scenario was also used, where natural gas and coal constitute the bulk of emissions. Calculations show the LSR produced for the silicone data cable with high fire retardant capability has scope 1 emissions of 0.82kg CO2/kg, scope 2 emissions of 0.87kg CO2/kg, and scope 3 emissions of 2.76kg CO2/kg, with a total product carbon footprint of 4.45kg CO2/kg. This total product carbon footprint (Cradle-to-gate) is comparable to the industry and to plastic materials per tonne of material. Although per tonne emission is comparable to plastic material, due to greater durability and longer lifespan, there can be significantly reduced use of LSR material. Suggestions to reduce the calculated product carbon footprint in the scope of emissions involve 1. Incorporating the recycling of factory silicone waste into operations, 2. Using green renewable energy for external electricity sources and 3. Sourcing eco-friendly raw materials with low GHG emissions.

Keywords: carbon footprint, liquid silicone rubber, silicone data cable, Malaysia facility

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110 Carbohydrate Intake and Physical Activity Levels Modify the Association between FTO Gene Variants and Obesity and Type 2 Diabetes: First Nutrigenetics Study in an Asian Indian Population

Authors: K. S. Vimal, D. Bodhini, K. Ramya, N. Lakshmipriya, R. M. Anjana, V. Sudha, J. A. Lovegrove, V. Mohan, V. Radha

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Gene-lifestyle interaction studies have been carried out in various populations. However, to date there are no studies in an Asian Indian population. Hence, we examined whether lifestyle factors such as diet and physical activity modify the association between fat mass and obesity–associated (FTO) gene variants and obesity and type 2 diabetes (T2D) in an Asian Indian population. We studied 734 unrelated T2D and 884 normal glucose-tolerant (NGT) participants randomly selected from the Chennai Urban Rural Epidemiology Study (CURES) in Southern India. Obesity was defined according to the World Health Organization Asia Pacific Guidelines (non-obese, BMI < 25 kg/m2; obese, BMI ≥ 25 kg/m2). Six single nucleotide polymorphisms (SNPs) in the FTO gene (rs9940128, rs7193144, rs8050136, rs918031, rs1588413 and rs11076023) identified from recent genome-wide association studies for T2D were genotyped by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Dietary assessment was carried out using a validated food frequency questionnaire and physical activity was based upon the self-report. Interaction analyses were performed by including the interaction terms in the model. A joint likelihood ratio test of the main SNP effects and the SNP-diet/physical activity interaction effects was used in the linear regression analyses to maximize statistical power. Statistical analyses were performed using STATA version 13. There was a significant interaction between FTO SNP rs8050136 and carbohydrate energy percentage (Pinteraction=0.04) on obesity, where the ‘A’ allele carriers of the SNP rs8050136 had 2.46 times higher risk of obesity than those with ‘CC’ genotype (P=3.0x10-5) among individuals in the highest tertile of carbohydrate energy percentage. Furthermore, among those who had lower levels of physical activity, the ‘A’ allele carriers of the SNP rs8050136 had 1.89 times higher risk of obesity than those with ‘CC’ genotype (P=4.0x10-5). We also found a borderline interaction between SNP rs11076023 and carbohydrate energy percentage (Pinteraction=0.08) on T2D, where the ‘A’ allele carriers in the highest tertile of carbohydrate energy percentage, had 1.57 times higher risk of T2D than those with ‘TT’ genotype (P=0.002). There was also a significant interaction between SNP rs11076023 and physical activity (Pinteraction=0.03) on T2D. No further significant interactions between SNPs and macronutrient intake or physical activity on obesity and T2D were observed. In conclusion, this is the first study to provide evidence for a gene-diet and gene-physical activity interaction on obesity and T2D in an Asian Indian population. These findings suggest that the association between FTO gene variants and obesity and T2D is influenced by carbohydrate intake and physical activity levels. Greater understanding of how FTO gene influences obesity and T2D through dietary and exercise interventions will advance the development of behavioral intervention and personalised lifestyle strategies predicted to reduce the development of metabolic diseases in ‘A’ allele carriers of both SNPs in this Asian Indian population.

Keywords: dietary intake, FTO, obesity, physical activity, type 2 diabetes, Asian Indian.

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109 The Concept of Path in Original Buddhism and the Concept of Psychotherapeutic Improvement

Authors: Beth Jacobs

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The landmark movement of Western clinical psychology in the 20th century was the development of psychotherapy. The landmark movement of clinical psychology in the 21st century will be the absorption of meditation practices from Buddhist psychology. While millions of people explore meditation and related philosophy, very few people are exposed to the materials of original Buddhism on this topic, especially to the Theravadan Abhidharma. The Abhidharma is an intricate system of lists and matrixes that were used to understand and remember Buddha’s teaching. The Abhidharma delineates the first psychological system of Buddhism, how the mind works in the universe of reality and why meditation training strengthens and purifies the experience of life. Its lists outline the psychology of mental constructions, perception, emotion and cosmological causation. While the Abhidharma is technical, elaborate and complex, its essential purpose relates to the central purpose of clinical psychology: to relieve human suffering. Like Western depth psychology, the methodology rests on understanding underlying processes of consciousness and perception. What clinical psychologists might describe as therapeutic improvement, the Abhidharma delineates as a specific pathway of purified actions of consciousness. This paper discusses the concept of 'path' as presented in aspects of the Theravadan Abhidharma and relates this to current clinical psychological views of therapy outcomes and gains. The core path in Buddhism is the Eight-Fold Path, which is the fourth noble truth and the launching of activity toward liberation. The path is not composed of eight ordinal steps; it’s eight-fold and is described as opening the way, not funneling choices. The specific path in the Abhidharma is described in many steps of development of consciousness activities. The path is not something a human moves on, but something that moments of consciousness develop within. 'Cittas' are extensively described in the Abhidharma as the atomic-level unit of a raw action of consciousness touching upon an object in a field, and there are 121 types of cittas categorized. The cittas are embedded in the mental factors, which could be described as the psychological packaging elements of our experiences of consciousness. Based on these constellations of infinitesimal, linked occurrences of consciousness, citta are categorized by dimensions of purification. A path is a chain of citta developing through causes and conditions. There are no selves, no pronouns in the Abhidharma. Instead of me walking a path, this is about a person working with conditions to cultivate a stream of consciousness that is pure, immediate, direct and generous. The same effort, in very different terms, informs the work of most psychotherapies. Depth psychology seeks to release the bound, unconscious elements of mental process into the clarity of realization. Cognitive and behavioral psychologies work on breaking down automatic thought valuations and actions, changing schemas and interpersonal dynamics. Understanding how the original Buddhist concept of positive human development relates to the clinical psychological concept of therapy weaves together two brilliant systems of thought on the development of human well being.

Keywords: Abhidharma, Buddhist path, clinical psychology, psychotherapeutic outcome

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108 Microbiological and Physicochemical Evaluation of Traditional Greek Kopanisti Cheese Produced by Different Starter Cultures

Authors: M. Kazou, A. Gavriil, O. Kalagkatsi, T. Paschos, E. Tsakalidou

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Kopanisti cheese is a Greek soft Protected Designation of Origin (PDO) cheese made of raw cow, sheep or goat milk, or mixtures of them, with similar organoleptic characteristics to that of Roquefort cheese. Traditional manufacturing of Kopanisti cheese is limited in small-scale dairies, without the addition of starter cultures. Instead, an amount of over-mature Kopanisti cheese, called Mana Kopanisti, is used to initiate ripening. Therefore, the selection of proper starter cultures and the understanding of the contribution of various microbial groups to its overall quality is crucial for the production of a high-quality final product with standardized organoleptic and physicochemical characteristics. Taking the above into account, the aim of the present study was the investigation of Kopanisti cheese microbiota and its role in cheese quality. For this purpose, four different types of Kopanisti were produced in triplicates, all with pasteurized cow milk, with the addition of (A) the typical mesophilic species Lactococcus lactis and Lactobacillus paracasei used as starters in the production of soft spread cheeses, (B) strains of Lactobacillus acidipiscis and Lactobacillus rennini previously isolated from Kopanisti and Mana Kopanisti, (C) all the species from (A) and (B) as inoculum, and finally (D) the species from (A) and Mana Kopanisti. Physicochemical and microbiological analysis was performed for milk and cheese samples during ripening. Enumeration was performed for major groups of lactic acid bacteria (LAB), total mesophilic bacteria, yeasts as well as hygiene indicator microorganisms. Bacterial isolates from all the different LAB groups, apart from enterococci, alongside yeasts isolates, were initially grouped using repetitive sequence-based polymerase chain reaction (rep-PCR) and then identified at the species level using 16S rRNA gene and internal transcribed spacer (ITS) DNA region sequencing, respectively. Sensory evaluation was also performed for final cheese samples at the end of the ripening period (35 days). Based on the results of the classical microbiological analysis, the average counts of the total mesophilic bacteria and LAB, apart from enterococci, ranged between 7 and 10 log colony forming unit (CFU) g⁻¹, phychrotrophic bacteria, and yeast extract glucose chloramphenicol (YGC) isolates between 4 and 8 log CFU g⁻¹, while coliforms and enterococci up to 2 log CFU g⁻¹ throughout ripening in cheese samples A, C and D. In contrast, in cheese sample B, the average counts of the total mesophilic bacteria and LAB, apart from enterococci, phychrotrophic bacteria, and YGC isolates ranged between 0 and 10 log CFU g⁻¹ and coliforms and enterococci up to 2 log CFU g⁻¹. Although the microbial counts were not that different among samples, identification of the bacterial and yeasts isolates revealed the complex microbial community structure present in each cheese sample. Differences in the physicochemical characteristics among the cheese samples were also observed, with pH ranging from 4.3 to 5.3 and moisture from 49.6 to 58.0 % in the final cheese products. Interestingly, the sensory evaluation also revealed differences among samples, with cheese sample B ranking first based on the total score. Overall, the combination of these analyses highlighted the impact of different starter cultures on the Kopanisti microbiota as well as on the physicochemical and sensory characteristics of the final product.

Keywords: Kopanisti cheese, microbiota, classical microbiological analysis, physicochemical analysis

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