Search results for: sequence alignment
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1495

Search results for: sequence alignment

205 The Effect of SIAH1 on PINK1 Homeostasis in Parkinson Disease

Authors: Fatimah Abd Elghani, Raymonde Szargel, Vered Shani, Hazem Safory, Haya Hamza, Mor Savyon, Ruth Rott, Rina Bandopadhyay, Simone Engelender

Abstract:

Background: PINK1 is a mitochondrial kinase mutated in some familial cases of Parkinson’s disease. Down regulation of PINK1 results in abnormal mitochondrial morphology and altered membrane potential. Although PINK1 has a predicted mitochondrial import sequence, it’s cellular, and submitochondrial localization remains unclear, in part because it is rapidly degraded. In this work, we investigated the mechanisms involved in PINK1 degradation and how this may affect PINK1 stability and function, with implications for mitochondrial function in PD. In addition, pharmacological inhibition of proteasome activity was shown to lead to PINK1 accumulation, indicating that PINK1 degradation depends on the ubiquitin-proteasome system (UPS). Methods: Using co-immunoprecipitation assays, we identified E3 ubiquitin ligase SIAH1 as a PINK1-interacting protein in HEK293 cells as well as on rat brain tissues. In addition, we determined the effect of SIAH 1, SIAH2 and Parkin on PINK1 steady-state levels by Western blot analysis, and checked their possibility to ubiquitinate and mediate PINK1 degradation through the proteasome carried out in vivo ubiquitination experiments. Results: We have obtained results showing that SIAH-1 interacts with and ubiquitinates PINK1. The ubiquitination promoted by SIAH-1 leads to the proteasomal degradation of PINK1. We confirmed these findings by knocking down SIAH-1 and observing important accumulation of PINK1 in cells. Besides, we found that SIAH-1 decreases PINK1 steady-state levels but not the E3 ligase Parkin. We also investigated the interaction of SIAH-1 with PINK1 disease mutants and its ability to promote their ubiquitination and degradation. Although, no clear difference in the ability of SIAH-1 to promote the degradation of PINK1 disease mutants was observed. It is possible that dysfunction of proteasomal activity in the disease may lead to the accumulation and aggregation of ubiquitinated PINK1 in patients with PINK1 mutations, with possible implications to the pathogenesis of PD. Conclusions: Here, we demonstrated that SIAH-1 ubiquitinates and promotes the degradation of PINK1. In addition, SIAH-1 represents now a target that may help the improvement of mitophagy in PD. Further investigations needed to understand how mitophagy is regulated by PINK1-SIAH-1 axis to provide targets for future therapeutics.

Keywords: PD, Parkinson's disease, PINK1, PTEN-induced kinase1, SIAH, seven in absentia homolog, SN, substantia nigra

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204 Predicting Aggregation Propensity from Low-Temperature Conformational Fluctuations

Authors: Hamza Javar Magnier, Robin Curtis

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There have been rapid advances in the upstream processing of protein therapeutics, which has shifted the bottleneck to downstream purification and formulation. Finding liquid formulations with shelf lives of up to two years is increasingly difficult for some of the newer therapeutics, which have been engineered for activity, but their formulations are often viscous, can phase separate, and have a high propensity for irreversible aggregation1. We explore means to develop improved predictive ability from a better understanding of how protein-protein interactions on formulation conditions (pH, ionic strength, buffer type, presence of excipients) and how these impact upon the initial steps in protein self-association and aggregation. In this work, we study the initial steps in the aggregation pathways using a minimal protein model based on square-well potentials and discontinuous molecular dynamics. The effect of model parameters, including range of interaction, stiffness, chain length, and chain sequence, implies that protein models fold according to various pathways. By reducing the range of interactions, the folding- and collapse- transition come together, and follow a single-step folding pathway from the denatured to the native state2. After parameterizing the model interaction-parameters, we developed an understanding of low-temperature conformational properties and fluctuations, and the correlation to the folding transition of proteins in isolation. The model fluctuations increase with temperature. We observe a low-temperature point, below which large fluctuations are frozen out. This implies that fluctuations at low-temperature can be correlated to the folding transition at the melting temperature. Because proteins “breath” at low temperatures, defining a native-state as a single structure with conserved contacts and a fixed three-dimensional structure is misleading. Rather, we introduce a new definition of a native-state ensemble based on our understanding of the core conservation, which takes into account the native fluctuations at low temperatures. This approach permits the study of a large range of length and time scales needed to link the molecular interactions to the macroscopically observed behaviour. In addition, these models studied are parameterized by fitting to experimentally observed protein-protein interactions characterized in terms of osmotic second virial coefficients.

Keywords: protein folding, native-ensemble, conformational fluctuation, aggregation

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203 An Impregnated Active Layer Mode of Solution Combustion Synthesis as a Tool for the Solution Combustion Mechanism Investigation

Authors: Zhanna Yermekova, Sergey Roslyakov

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Solution combustion synthesis (SCS) is the unique method which multiple times has proved itself as an effective and efficient approach for the versatile synthesis of a variety of materials. It has significant advantages such as relatively simple handling process, high rates of product synthesis, mixing of the precursors on a molecular level, and fabrication of the nanoproducts as a result. Nowadays, an overwhelming majority of solution combustion investigations performed through the volume combustion synthesis (VCS) where the entire liquid precursor is heated until the combustion self-initiates throughout the volume. Less amount of the experiments devoted to the steady-state self-propagating mode of SCS. Under the beforementioned regime, the precursor solution is dried until the gel-like media, and later on, the gel substance is locally ignited. In such a case, a combustion wave propagates in a self-sustaining mode as in conventional solid combustion synthesis. Even less attention is given to the impregnated active layer (IAL) mode of solution combustion. An IAL approach to the synthesis is implying that the solution combustion of the precursors should be initiated on the surface of the third chemical or inside the third substance. This work is aiming to emphasize an underestimated role of the impregnated active layer mode of the solution combustion synthesis for the fundamental studies of the combustion mechanisms. It also serves the purpose of popularizing the technical terms and clarifying the difference between them. In order to do so, the solution combustion synthesis of γ-FeNi (PDF#47-1417) alloy has been accomplished within short (seconds) one-step reaction of metal precursors with hexamethylenetetramine (HTMA) fuel. An idea of the special role of the Ni in a process of alloy formation was suggested and confirmed with the particularly organized set of experiments. The first set of experiments were conducted in a conventional steady-state self-propagating mode of SCS. An alloy was synthesized as a single monophasic product. In two other experiments, the synthesis was divided into two independent processes which are possible under the IAL mode of solution combustion. The sequence of the process was changed according to the equations which are describing an Experiment A and B below: Experiment A: Step 1. Fe(NO₃)₃*9H₂O + HMTA = FeO + gas products; Step 2. FeO + Ni(NO₃)₂*6H₂O + HMTA = Ni + FeO + gas products; Experiment B: Step 1. Ni(NO₃)₂*6H₂O + HMTA = Ni + gas products; Step 2. Ni + Fe(NO₃)₃*9H₂O + HMTA = Fe₃Ni₂+ traces (Ni + FeO). Based on the IAL experiment results, one can see that combustion of the Fe(NO₃)₃9H₂O on the surface of the Ni is leading to the alloy formation while presence of the already formed FeO does not affect the Ni(NO₃)₂*6H₂O + HMTA reaction in any way and Ni is the main product of the synthesis.

Keywords: alloy, hexamethylenetetramine, impregnated active layer mode, mechanism, solution combustion synthesis

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202 Middle Ordovician (Llanvirnian) Relative Sea-Level Fluctuations

Authors: Ying Jia Teoh

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The Canning Basin is located between the Kimberley and Pilbara Precambrian cratonic blocks. It is a large but relatively poorly explored Paleozoic basin in remote Western Australia. During the early Ordovician period, the Australian continent was located near the equator. Middle Ordovician age Nita and Goldwyer Formations in Canning Basin are therefore warm water carbonates. The Nita Formation carbonates are a regressive sequence which conformably overlies the Goldwyer Formation. It contains numerous progradational cycles of limestone, vuggy dolomitized carbonate beds and shale deposited in subtidal to supratidal environments. The Goldwyer Formation contains transgressive shale sequences and regressive carbonates deposited in shallow subtidal conditions. The shales contain oil-prone Gloeocapsormorpha prisca-bearing source rocks. Llanvirnian relative sea-level fluctuations were reconstructed by using Fischer plots methodology for three key wells (wells McLarty 1, Looma 1 and Robert 1) in Broome Platform and compared with INPEFA data. The Goldwyer lower shale (interval Or1000P) shows increasing relative sea-level and this matches with a transgressive systems tract. Goldwyer middle carbonate (interval Or2000) shows relative sea-level drop and this matches with a regressive systems tract. Goldwyer upper shale (interval Or2000P) shows relative sea-level drop and this matches with a transgressive systems tract. Nita Formation Leo Member (interval Or3000) shows a relative sea level drop and this matches with a regressive systems tract. The Nita Formation Cudalgarra Member (intervals Or3000P and Or4000) with transgressive systems tract then this is followed by a regressive systems tract. This pattern matches with the relative sea-level curves in wells McLarty 1 and Robert 1. The correlation is weak for parts of well Looma 1. This is probably influenced by the fact that the thickness of this section is quite small. As a conclusion, Fischer plots for the Llanvirnian Goldwyer and Nita Formations show good agreement with the third order global sea level cycles of Haq and others. Fischer plots are generally correlated well with trend and cyclicity determined by INPEFA curves and as a method of cross-checking INPEFA data and sea-level change.

Keywords: canning basin, Fischer plots, Llanvirnian, middle Ordovician, sea-level fluctuations, stratigraphy

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201 Complimentary Allusions: Shawl Scenes in Rossellini, Lean, Fellini, Kubrick, and Bertolucci Films

Authors: Misha Nedeljkovich

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In the film’s famous scene (Roma città aperta-1945), Pina (Anna Magnani) collapses in the street when machined-gunned by a German soldier. Her son Marcello (Vito Annchiarico) tries to revive her. Her death is signaling not closure, but the cycle of life; Marcello saves Francesco with the shawl taken from his mother’s corpse. One pivotal scene in Brief Encounter (1945) occurs in the apartment of Alec’s (Trevor Howard) friend Stephen (Valentine Dyall), when Stephen returns to catch Alec and Laura (Celia Johnson) together alone. David Lean directs this scene using her shawl as a sign of in flagrante delicto. In La Strada (1954), Gelsomina (Giulietta Masina) was waving good bye when her mother sensing impending doom changed her mind and desperately tried to stop her waving back with her shawl: Don’t go my daughter! Your shawl! Your shawl! Gelsomina refuses to return, waving back: It’s time to go! Stanley Kubrick’s tale of a boxer who crosses a mobster to win the heart of a lady, Killer’s Kiss (1955), reminds us that Times Square used to contain sweaty boxing gyms and dance halls. The film’s longest Times Square interlude is its oddest: the boxer Davie Gordon played by Jamie Smith has his shawl stolen by two playful men in Shriners’ hats who are silent except for one who blows a harmonica, faintly heard over honking cabs and overheard conversations. This long sequence appears to be joining in on directors’ shawl conversations with Kubrick’s own twist. Principle characters will never know why all this happened to them that evening. Love, death, happiness and everlasting misery all of that is caused by Dave’s shawl. Finally, the decade of cinematic shawl conversations conclude in Betolucci’s Before the Revolution (Prima della rivoluzione–1964). One of his character’s lifts up a shawl asking if this was a Rossellini’s shawl. I argue that exploring complimentary allusions in a film where directors are acknowledging their own great debt to another film or filmmaker will further our knowledge of film history adding both depth and resonance to the great works in cinema.

Keywords: allusions, Bertolucci, Fellini, homage, Kubrick, lean, Rossellini

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200 N-Glycosylation in the Green Microalgae Chlamydomonas reinhardtii

Authors: Pierre-Louis Lucas, Corinne Loutelier-Bourhis, Narimane Mati-Baouche, Philippe Chan Tchi-Song, Patrice Lerouge, Elodie Mathieu-Rivet, Muriel Bardor

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N-glycosylation is a post-translational modification taking place in the Endoplasmic Reticulum and the Golgi apparatus where defined glycan features are added on protein in a very specific sequence Asn-X-Thr/Ser/Cys were X can be any amino acid except proline. Because it is well-established that those N-glycans play a critical role in protein biological activity, protein half-life and that a different N-glycan structure may induce an immune response, they are very important in Biopharmaceuticals which are mainly glycoproteins bearing N-glycans. From now, most of the biopharmaceuticals are produced by mammalian cells like Chinese Hamster Ovary cells (CHO) for their N-glycosylation similar to the human, but due to the high production costs, several other species are investigated as the possible alternative system. In this purpose, the green microalgae Chlamydomonas reinhardtii was investigated as the potential production system for Biopharmaceuticals. This choice was influenced by the facts that C. reinhardtii is a well-study microalgae which is growing fast with a lot of molecular biology tools available. This organism is also producing N-glycan on its endogenous proteins. However, the analysis of the N-glycan structure of this microalgae has revealed some differences as compared to the human. Rather than in Human where the glycans are processed by key enzymes called N-acetylglucosaminyltransferase I and II (GnTI and GnTII) adding GlcNAc residue to form a GlcNAc₂Man₃GlcNAc₂ core N-glycan, C. reinhardtii lacks those two enzymes and possess a GnTI independent glycosylation pathway. Moreover, some enzymes like xylosyltransferases and methyltransferases not present in human are supposed to act on the glycans of C. reinhardtii. Furthermore, the recent structural study by mass spectrometry shows that the N-glycosylation precursor supposed to be conserved in almost all eukaryotic cells results in a linear Man₅GlcNAc₂ rather than a branched one in C. reinhardtii. In this work, we will discuss the new released MS information upon C. reinhardtii N-glycan structure and their impact on our attempt to modify the glycan in a Human manner. Two strategies will be discussed. The first one consisted in the study of Xylosyltransferase insertional mutants from the CLIP library in order to remove xyloses from the N-glycans. The second will go further in the humanization by transforming the microalgae with the exogenous gene from Toxoplasma gondii having an activity similar to GnTI and GnTII with the aim to synthesize GlcNAc₂Man₃GlcNAc₂ in C. reinhardtii.

Keywords: Chlamydomonas reinhardtii, N-glycosylation, glycosyltransferase, mass spectrometry, humanization

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199 An Investigation on the Suitability of Dual Ion Beam Sputtered GMZO Thin Films: For All Sputtered Buffer-Less Solar Cells

Authors: Vivek Garg, Brajendra S. Sengar, Gaurav Siddharth, Nisheka Anadkat, Amitesh Kumar, Shailendra Kumar, Shaibal Mukherjee

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CuInGaSe (CIGSe) is the dominant thin film solar cell technology. The band alignment of Buffer/CIGSe interface is one of the most crucial parameters for solar cell performance. In this article, the valence band offset (VBOff) and conduction band offset (CBOff) values of Cu(In0.70Ga0.30)Se/ 1 at.% Ga: Mg0.25Zn0.75O (GMZO) heterojunction, grown by dual ion beam sputtering system (DIBS), are calculated to understand the carrier transport mechanism at the heterojunction for the realization of all sputtered buffer-less solar cells. To determine the valence band offset (VBOff), ∆E_V at GMZO/CIGSe heterojunction interface, the standard method based on core-level photoemission is utilized. The value of ∆E_V can be evaluated by considering common core-level peaks. In our study, the values of (Valence band onset)VBOn, obtained by linear extrapolation method for GMZO and CIGSe films are calculated to be 2.86 and 0.76 eV. In the UPS spectra peak positions of Se 3d is observed in UPS spectra at 54.82 and 54.7 eV for CIGSe film and GMZO/CIGSe interface respectively, while the peak position of Mg 2p is observed at 50.09 and 50.12 eV for GMZO and GMZO/CIGSe interface respectively. The optical band gap of CIGSe and GMZO are obtained from absorption spectra procured from spectroscopic ellipsometry are 1.26 and 3.84 eV respectively. The calculated average values of ∆E_v and ∆E_C are estimated to be 2.37 and 0.21 eV, respectively, at room temperature. The calculated positive conduction band offset termed as a spike at the absorber junction is the required criterion for the high-efficiency solar cells for the efficient charge extraction from the junction. So we can conclude that the above study confirms GMZO thin films grown by the dual ion beam sputtering system are the suitable candidate for the CIGSe thin films based ultra-thin buffer-less solar cells. We investigated the band-offset properties at the GMZO/CIGSe heterojunction to verify the suitability of the GMZO for the realization of the buffer-less solar cells. The calculated average values of ∆E_V and ∆E_C are estimated to be 2.37 and 0.21 eV, respectively, at room temperature. The calculated positive conduction band offset termed as a spike at the absorber junction is the required criterion for the high-efficiency solar cells for the efficient charge extraction from the junction. So we can conclude that the above study confirms GMZO thin films grown by the dual ion beam sputtering system are the suitable candidate for the CIGSe thin films based ultra-thin buffer-less solar cells. Acknowledgment: We are thankful to DIBS, EDX, and XRD facility equipped at Sophisticated Instrument Centre (SIC) at IIT Indore. The authors B.S.S and A.K acknowledge CSIR and V.G acknowledge UGC, India for their fellowships. B.S.S is thankful to DST and IUSSTF for BASE Internship Award. Prof. Shaibal Mukherjee is thankful to DST and IUSSTF for BASE Fellowship and MEITY YFRF award. This work is partially supported by DAE BRNS, DST CERI, and DST-RFBR Project under India-Russia Programme of Cooperation in Science and Technology. We are thankful to Mukul Gupta for SIMS facility equipped at UGC-DAE Indore.

Keywords: CIGSe, DIBS, GMZO, solar cells, UPS

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198 Comparison of Different Methods of Microorganism's Identification from a Copper Mining in Pará, Brazil

Authors: Louise H. Gracioso, Marcela P.G. Baltazar, Ingrid R. Avanzi, Bruno Karolski, Luciana J. Gimenes, Claudio O. Nascimento, Elen A. Perpetuo

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Introduction: Higher copper concentrations promote a selection pressure on organisms such as plants, fungi and bacteria, which allows surviving only the resistant organisms to the contaminated site. This selective pressure keeps only the organisms most resistant to a specific condition and subsequently increases their bioremediation potential. Despite the bacteria importance for biosphere maintenance, it is estimated that only a small fraction living microbial species has been described and characterized. Due to the molecular biology development, tools based on analysis 16S ribosomal RNA or another specific gene are making a new scenario for the characterization studies and identification of microorganisms in the environment. News identification of microorganisms methods have also emerged like Biotyper (MALDI / TOF), this method mass spectrometry is subject to the recognition of spectroscopic patterns of conserved and features proteins for different microbial species. In view of this, this study aimed to isolate bacteria resistant to copper present in a Copper Processing Area (Sossego Mine, Canaan, PA) and identifies them in two different methods: Recent (spectrometry mass) and conventional. This work aimed to use them for a future bioremediation of this Mining. Material and Methods: Samples were collected at fifteen different sites of five periods of times. Microorganisms were isolated from mining wastes by culture enrichment technique; this procedure was repeated 4 times. The isolates were inoculated into MJS medium containing different concentrations of chloride copper (1mM, 2.5mM, 5mM, 7.5mM and 10 mM) and incubated in plates for 72 h at 28 ºC. These isolates were subjected to mass spectrometry identification methods (Biotyper – MALDI/TOF) and 16S gene sequencing. Results: A total of 105 strains were isolated in this area, bacterial identification by mass spectrometry method (MALDI/TOF) achieved 74% agreement with the conventional identification method (16S), 31% have been unsuccessful in MALDI-TOF and 2% did not obtain identification sequence the 16S. These results show that Biotyper can be a very useful tool in the identification of bacteria isolated from environmental samples, since it has a better value for money (cheap and simple sample preparation and MALDI plates are reusable). Furthermore, this technique is more rentable because it saves time and has a high performance (the mass spectra are compared to the database and it takes less than 2 minutes per sample).

Keywords: copper mining area, bioremediation, microorganisms, identification, MALDI/TOF, RNA 16S

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197 Constitutive Flo1p Expression on Strains Bearing Deletions in Genes Involved in Cell Wall Biogenesis

Authors: Lethukuthula Ngobese, Abin Gupthar, Patrick Govender

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The ability of yeast cell wall-derived mannoproteins (glycoproteins) to positively contribute to oenological properties has been a key factor that stimulates research initiatives into these industrially important glycoproteins. In addition, and from a fundamental research perspective, yeast cell wall glycoproteins are involved in a wide range of biological interactions. To date, and to the best of our knowledge, our understanding of the fine molecular structure of these mannoproteins is fairly limited. Generally, the amino acid sequences of their protein moieties have been established from structural and functional analysis of the genomic sequence of these yeasts whilst far less information is available on the glycosyl moieties of these mannoproteins. A novel strategy was devised in this study that entails the genetic engineering of yeast strains that over-express and release cell wall-associated glycoproteins into the liquid growth medium. To this end, the Flo1p mannoprotein was overexpressed in Saccharomyces cerevisiae laboratory strains bearing a specific deletion in KNR4 and GPI7 genes involved in cell wall biosynthesis that have been previously shown to extracellularly hyper-secrete cell wall-associated glycoproteins. A polymerase chain reaction (PCR) -based cloning strategy was employed to generate transgenic yeast strains in which the native cell wall FLO1 glycoprotein-encoding gene is brought under transcriptional control of the constitutive PGK1 promoter. The modified Helm’s flocculation assay was employed to assess flocculation intensities of a Flo1p over-expressing wild type and deletion mutant as an indirect measure of their abilities to release the desired mannoprotein. The flocculation intensities of the transformed strains were assessed and all the strains showed similar intensities (>98% flocculation). To assess if mannoproteins were released into the growth medium, the supernatant of each strain was subjected to the BCA protein assay and the transformed Δknr4 strain showed a considerable increase in protein levels. This study has the potential to produce mannoproteins in sufficient quantities that may be employed in future investigations to understand their molecular structures and mechanisms of interaction to the benefit of both fundamental and industrial applications.

Keywords: glycoproteins, genetic engineering, flocculation, over-expression

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196 Mapping Context, Roles, and Relations for Adjudicating Robot Ethics

Authors: Adam J. Bowen

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Abstract— Should robots have rights or legal protections. Often debates concerning whether robots and AI should be afforded rights focus on conditions of personhood and the possibility of future advanced forms of AI satisfying particular intrinsic cognitive and moral attributes of rights-holding persons. Such discussions raise compelling questions about machine consciousness, autonomy, and value alignment with human interests. Although these are important theoretical concerns, especially from a future design perspective, they provide limited guidance for addressing the moral and legal standing of current and near-term AI that operate well below the cognitive and moral agency of human persons. Robots and AI are already being pressed into service in a wide range of roles, especially in healthcare and biomedical contexts. The design and large-scale implementation of robots in the context of core societal institutions like healthcare systems continues to rapidly develop. For example, we bring them into our homes, hospitals, and other care facilities to assist in care for the sick, disabled, elderly, children, or otherwise vulnerable persons. We enlist surgical robotic systems in precision tasks, albeit still human-in-the-loop technology controlled by surgeons. We also entrust them with social roles involving companionship and even assisting in intimate caregiving tasks (e.g., bathing, feeding, turning, medicine administration, monitoring, transporting). There have been advances to enable severely disabled persons to use robots to feed themselves or pilot robot avatars to work in service industries. As the applications for near-term AI increase and the roles of robots in restructuring our biomedical practices expand, we face pressing questions about the normative implications of human-robot interactions and collaborations in our collective worldmaking, as well as the moral and legal status of robots. This paper argues that robots operating in public and private spaces be afforded some protections as either moral patients or legal agents to establish prohibitions on robot abuse, misuse, and mistreatment. We already implement robots and embed them in our practices and institutions, which generates a host of human-to-machine and machine-to-machine relationships. As we interact with machines, whether in service contexts, medical assistance, or home health companions, these robots are first encountered in relationship to us and our respective roles in the encounter (e.g., surgeon, physical or occupational therapist, recipient of care, patient’s family, healthcare professional, stakeholder). This proposal aims to outline a framework for establishing limiting factors and determining the extent of moral or legal protections for robots. In doing so, it advocates for a relational approach that emphasizes the priority of mapping the complex contextually sensitive roles played and the relations in which humans and robots stand to guide policy determinations by relevant institutions and authorities. The relational approach must also be technically informed by the intended uses of the biomedical technologies in question, Design History Files, extensive risk assessments and hazard analyses, as well as use case social impact assessments.

Keywords: biomedical robots, robot ethics, robot laws, human-robot interaction

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195 Sedimentary, Diagenesis and Evaluation of High Quality Reservoir of Coarse Clastic Rocks in Nearshore Deep Waters in the Dongying Sag; Bohai Bay Basin

Authors: Kouassi Louis Kra

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The nearshore deep-water gravity flow deposits in the Northern steep slope of Dongying depression, Bohai Bay basin, have been acknowledged as important reservoirs in the rift lacustrine basin. These deep strata term as coarse clastic sediment, deposit at the root of the slope have complex depositional processes and involve wide diagenetic events which made high-quality reservoir prediction to be complex. Based on the integrated study of seismic interpretation, sedimentary analysis, petrography, cores samples, wireline logging data, 3D seismic and lithological data, the reservoir formation mechanism deciphered. The Geoframe software was used to analyze 3-D seismic data to interpret the stratigraphy and build a sequence stratigraphic framework. Thin section identification, point counts were performed to assess the reservoir characteristics. The software PetroMod 1D of Schlumberger was utilized for the simulation of burial history. CL and SEM analysis were performed to reveal diagenesis sequences. Backscattered electron (BSE) images were recorded for definition of the textural relationships between diagenetic phases. The result showed that the nearshore steep slope deposits mainly consist of conglomerate, gravel sandstone, pebbly sandstone and fine sandstone interbedded with mudstone. The reservoir is characterized by low-porosity and ultra-low permeability. The diagenesis reactions include compaction, precipitation of calcite, dolomite, kaolinite, quartz cement and dissolution of feldspars and rock fragment. The main types of reservoir space are primary intergranular pores, residual intergranular pores, intergranular dissolved pores, intergranular dissolved pores, and fractures. There are three obvious anomalous high-porosity zones in the reservoir. Overpressure and early hydrocarbon filling are the main reason for abnormal secondary pores development. Sedimentary facies control the formation of high-quality reservoir, oil and gas filling preserves secondary pores from late carbonate cementation.

Keywords: Bohai Bay, Dongying Sag, deep strata, formation mechanism, high-quality reservoir

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194 Numerical Modelling and Experiment of a Composite Single-Lap Joint Reinforced by Multifunctional Thermoplastic Composite Fastener

Authors: Wenhao Li, Shijun Guo

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Carbon fibre reinforced composites are progressively replacing metal structures in modern civil aircraft. This is because composite materials have large potential of weight saving compared with metal. However, the achievement to date of weight saving in composite structure is far less than the theoretical potential due to many uncertainties in structural integrity and safety concern. Unlike the conventional metallic structure, composite components are bonded together along the joints where structural integrity is a major concern. To ensure the safety, metal fasteners are used to reinforce the composite bonded joints. One of the solutions for a significant weight saving of composite structure is to develop an effective technology of on-board Structural Health Monitoring (SHM) System. By monitoring the real-life stress status of composite structures during service, the safety margin set in the structure design can be reduced with confidence. It provides a means of safeguard to minimize the need for programmed inspections and allow for maintenance to be need-driven, rather than usage-driven. The aim of this paper is to develop smart composite joint. The key technology is a multifunctional thermoplastic composite fastener (MTCF). The MTCF will replace some of the existing metallic fasteners in the most concerned locations distributed over the aircraft composite structures to reinforce the joints and form an on-board SHM network system. Each of the MTCFs will work as a unit of the AU and AE technology. The proposed MTCF technology has been patented and developed by Prof. Guo in Cranfield University, UK in the past a few years. The manufactured MTCF has been successfully employed in the composite SLJ (Single-Lap Joint). In terms of the structure integrity, the hybrid SLJ reinforced by MTCF achieves 19.1% improvement in the ultimate failure strength in comparison to the bonded SLJ. By increasing the diameter or rearranging the lay-up sequence of MTCF, the hybrid SLJ reinforced by MTCF is able to achieve the equivalent ultimate strength as that reinforced by titanium fastener. The predicted ultimate strength in simulation is in good agreement with the test results. In terms of the structural health monitoring, a signal from the MTCF was measured well before the load of mechanical failure. This signal provides a warning of initial crack in the joint which could not be detected by the strain gauge until the final failure.

Keywords: composite single-lap joint, crack propagation, multifunctional composite fastener, structural health monitoring

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193 Prevalence of Cyp2d6 and Its Implications for Personalized Medicine in Saudi Arabs

Authors: Hamsa T. Tayeb, Mohammad A. Arafah, Dana M. Bakheet, Duaa M. Khalaf, Agnieszka Tarnoska, Nduna Dzimiri

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Background: CYP2D6 is a member of the cytochrome P450 mixed-function oxidase system. The enzyme is responsible for the metabolism and elimination of approximately 25% of clinically used drugs, especially in breast cancer and psychiatric therapy. Different phenotypes have been described displaying alleles that lead to a complete loss of enzyme activity, reduced function (poor metabolizers – PM), hyperfunctionality (ultrarapid metabolizers–UM) and therefore drug intoxication or loss of drug effect. The prevalence of these variants may vary among different ethnic groups. Furthermore, the xTAG system has been developed to categorized all patients into different groups based on their CYP2D6 substrate metabolization. Aim of the study: To determine the prevalence of the different CYP2D6 variants in our population, and to evaluate their clinical relevance in personalized medicine. Methodology: We used the Luminex xMAP genotyping system to sequence 305 Saudi individuals visiting the Blood Bank of our Institution and determine which polymorphisms of CYP2D6 gene are prevalent in our region. Results: xTAG genotyping showed that 36.72% (112 out of 305 individuals) carried the CYP2D6_*2. Out of the 112 individuals with the *2 SNP, 6.23% had multiple copies of *2 SNP (19 individuals out of 305 individuals), resulting in an UM phenotype. About 33.44% carried the CYP2D6_*41, which leads to decreased activity of the CYP2D6 enzyme. 19.67% had the wild-type alleles and thus had normal enzyme function. Furthermore, 15.74% carried the CYP2D6_*4, which is the most common nonfunctional form of the CYP2D6 enzyme worldwide. 6.56% carried the CYP2D6_*17, resulting in decreased enzyme activity. Approximately 5.73% carried the CYP2D6_*10, consequently decreasing the enzyme activity, resulting in a PM phenotype. 2.30% carried the CYP2D6_*29, leading to decreased metabolic activity of the enzyme, and 2.30% carried the CYP2D6_*35, resulting in an UM phenotype, 1.64% had a whole-gene deletion CYP2D6_*5, thus resulting in the loss of CYP2D6 enzyme production, 0.66% carried the CYP2D6_*6 variant. One individual carried the CYP2D6_*3(B), producing an inactive form of the enzyme, which leads to decrease of enzyme activity, resulting in a PM phenotype. Finally, one individual carried the CYP2D6_*9, which decreases the enzyme activity. Conclusions: Our study demonstrates that different CYP2D6 variants are highly prevalent in ethnic Saudi Arabs. This finding sets a basis for informed genotyping for these variants in personalized medicine. The study also suggests that xTAG is an appropriate procedure for genotyping the CYP2D6 variants in personalized medicine.

Keywords: CYP2D6, hormonal breast cancer, pharmacogenetics, polymorphism, psychiatric treatment, Saudi population

Procedia PDF Downloads 556
192 Use and Effects of Kanban Board from the Aspects of Brothers Furniture Limited

Authors: Kazi Rizvan, Yamin Rekhu

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Due to high competitiveness in industries throughout the world, every industry is trying hard to utilize all their resources to keep their productivity as high as possible. Many tools have been being used to ensure smoother flow of an operation, to balance tasks, to maintain proper schedules for tasks, to maintain proper sequence for tasks, to reduce unproductive time. All of these tools are used to augment productivity within an industry. Kanban board is one of them and of the many important tools of lean production system. Kanban Board is a visual depiction of the status of tasks. Kanban board shows the actual status of the tasks. It conveys the progress and issues of tasks as well. Using Kanban Board, tasks can be distributed among workers and operation targets can be visually represented to them. In this paper, an example of Kanban board from the aspects of Brothers Furniture Limited was taken and how the Kanban board system was implemented, how the board was designed and how it was made easily perceivable for the less literate or illiterate workers. The Kanban board was designed for the packing section of Brothers Furniture Limited. It was implemented for the purpose of representing the tasks flow to the workers and to mitigate the time that was wasted while the workers remained wondering about what task they should start after they finish one. Kanban board subsumed seven columns and there was a column for comments where if any problem occurred during working on the tasks. Kanban board was helpful for the workers as the board showed the urgency of the tasks. It was also helpful for the store section as they could understand which products and how much of them could be delivered to store at any certain time. Kanban board had all the information centralized which is why the work-flow got paced up and idle time was minimized. Regardless of many workers being illiterate or less literate, Kanban board was still explicable for the workers as the Kanban cards were colored. Since the significance of colors can be conveniently interpretable to them, colored cards helped a great deal in that matter. Hence, the illiterate or less literate workers didn’t have to spend time wondering about the significance of the cards. Even when the workers weren’t told the significance of the colored cards, they could grow a feeling about their meaning as colors can trigger anyone’s mind to perceive the situation. As a result, the board elucidated the workers about what board required them to do, when to do and what to do next. Kanban board alleviated excessive time between tasks by setting day-plan for targeted tasks and it also reduced time during tasks as the workers were acknowledged of forthcoming tasks for a day. Being very specific to the tasks, Kanban board helped the workers become more focused on their tasks helped them do their job with more perfection. As a result, The Kanban board helped achieve a 8.75% increase in productivity than the productivity before the Kanban board was implemented.

Keywords: color, Kanban Board, Lean Tool, literacy, packing, productivity

Procedia PDF Downloads 213
191 The Effect of Organic Matter Maturation and Porosity Evolution on Methane Storage Potential in Shale-Gas Reservoirs

Authors: T. Topór, A. Derkowski, P. Ziemiański

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Formation of organic matter (OM)-hosted nanopores upon thermal maturation are one of the key factor controlling methane storage potential in unconventional shale-gas reservoirs. In this study, the subcritical CO₂ and N₂ gas adsorption measurements combined with scanning electron microscopy and supercritical methane adsorption have been used to characterize pore system and methane storage potential in black shales from the Baltic Basin (Poland). The samples were collected from a virtually equivalent Llandovery strata across the basin and represent a complete digenetic sequence, from thermally immature to overmature. The results demonstrate that the thermal maturation is a dominant mechanism controlling the formation of OM micro- and mesopores in the Baltic Basin shales. The formation of micro- and mesopores occurs in the oil window (vitrinite reflectance; leavedVR; ~0.5-0.9%) as a result of oil expulsion from kerogenleft OM highly porous. The generated hydrocarbons then turn into solid bitumen causing pore blocking and substantial decrease in micro- and mesopore volume in late-mature shales (VR ~0.9-1.2%). Both micro- and mesopores are regenerated in a middle of the catagenesis range (VR 1.4-1.9%) due to secondary cracking of OM and gas formation. The micropore volume in investigated shales is almost exclusively controlled by the OM content. The contribution of clay minerals to micropore volume is insignificant and masked by a strong contribution from OM. Methane adsorption capacity in the Baltic Basin shales is predominantly controlled by microporous OM with pores < 1.5 nm. The mesopore volume (2-50 nm) and mesopore surface area have no effect on methane sorption behavior. The adsorbed methane density equivalent, calculated as absolute methane adsorption divided by micropore volume, reviled a decrease of the methane loading potential in micropores with increasing maturity. The highest methane loading potential in micropores is observed for OM before metagenesis (VR < 2%), where the adsorbed methane density equivalent is greater than the density of liquid methane. This implies that, in addition to physical adsorption, absorption of methane in OM may occur before metagenesis. After OM content reduction using NaOCl solution methane adoption capacity substantially decreases, suggesting significantly greater adsorption potential for OM microstructure than for the clay minerals matrix.

Keywords: maturation, methane sorption, organic matter, porosity, shales

Procedia PDF Downloads 220
190 Composite Electrospun Aligned PLGA/Curcumin/Heparin Nanofibrous Membranes for Wound Dressing Application

Authors: Jyh-Ping Chen, Yu-Tin Lai

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Wound healing is a complicated process involving overlapping hemostasis, inflammation, proliferation, and maturation phases. Ideal wound dressings can replace native skin functions in full thickness skin wounds through faster healing rate and also by reducing scar formation. Poly(lactic-co-glycolic acid) (PLGA) is an U.S. FDA approved biodegradable polymer to be used as ideal wound dressing material. Several in vitro and in vivo studies have demonstrated the effectiveness of curcumin in decreasing the release of inflammatory cytokines, inhibiting enzymes associated with inflammations, and scavenging free radicals that are the major cause of inflammation during wound healing. Heparin has binding affinities to various growth factors. With the unique and beneficial features offered by those molecules toward the complex process of wound healing, we postulate a composite wound dressing constructed from PLGA, curcumin and heparin would be a good candidate to accelerate scarless wound healing. In this work, we use electrospinning to prepare curcumin-loaded aligned PLGA nanofibrous membranes (PC NFMs). PC NFMs were further subject to oxygen plasma modification and surfaced-grafted with heparin through carbodiimide-mediated covalent bond formation to prepare curcumin-loaded PLGA-g-heparin (PCH) NFMs. The nanofibrous membranes could act as three-dimensional scaffolds to attract fibroblast migration, reduce inflammation, and increase wound-healing related growth factors concentrations at wound sites. From scanning electron microscopy analysis, the nanofibers in each NFM are with diameters ranging from 456 to 479 nm and with alignment angles within  0.5°. The NFMs show high tensile strength and good water absorptivity and provide suitable pore size for nutrients/wastes transport. Exposure of human dermal fibroblasts to the extraction medium of PC or PCH NFM showed significant protective effects against hydrogen peroxide than PLGA NFM. In vitro wound healing assays also showed that the extraction medium of PCH NFM showed significantly better migration ability toward fibroblasts than PC NFM, which is further better than PLGA NFM. The in vivo healing efficiency of the NFMs was further evaluated by a full thickness excisional wound healing diabetic rat model. After 14 days, PCH NFMs exhibits 86% wound closure rate, which is significantly different from other groups (79% for PC and 73% for PLGA NFM). Real-time PCR analysis indicated PC and PCH NFMs down regulated anti-oxidative enzymes like glutathione peroxidase (GPx) and superoxide dismutase (SOD), which are well-known transcription factors involved in cellular inflammatory responses to stimuli. From histology, the wound area treated with PCH NFMs showed more vascular lumen formation from immunohistochemistry of α-smooth muscle actin. The wound site also had more collagen type III (65.8%) expression and less collagen type I (3.5%) expression, indicating scar-less wound healing. From Western blot analysis, the PCH NFM showed good affinity toward growth factors from increased concentration of transforming growth factor-β (TGF-β) and fibroblast growth factor-2 (FGF-2) at the wound site to accelerate wound healing. From the results, we suggest PCH NFM as a promising candidate for wound dressing applications.

Keywords: Curcumin, heparin, nanofibrous membrane, poly(lactic-co-glycolic acid) (PLGA), wound dressing

Procedia PDF Downloads 136
189 Machine Learning Model to Predict TB Bacteria-Resistant Drugs from TB Isolates

Authors: Rosa Tsegaye Aga, Xuan Jiang, Pavel Vazquez Faci, Siqing Liu, Simon Rayner, Endalkachew Alemu, Markos Abebe

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Tuberculosis (TB) is a major cause of disease globally. In most cases, TB is treatable and curable, but only with the proper treatment. There is a time when drug-resistant TB occurs when bacteria become resistant to the drugs that are used to treat TB. Current strategies to identify drug-resistant TB bacteria are laboratory-based, and it takes a longer time to identify the drug-resistant bacteria and treat the patient accordingly. But machine learning (ML) and data science approaches can offer new approaches to the problem. In this study, we propose to develop an ML-based model to predict the antibiotic resistance phenotypes of TB isolates in minutes and give the right treatment to the patient immediately. The study has been using the whole genome sequence (WGS) of TB isolates as training data that have been extracted from the NCBI repository and contain different countries’ samples to build the ML models. The reason that different countries’ samples have been included is to generalize the large group of TB isolates from different regions in the world. This supports the model to train different behaviors of the TB bacteria and makes the model robust. The model training has been considering three pieces of information that have been extracted from the WGS data to train the model. These are all variants that have been found within the candidate genes (F1), predetermined resistance-associated variants (F2), and only resistance-associated gene information for the particular drug. Two major datasets have been constructed using these three information. F1 and F2 information have been considered as two independent datasets, and the third information is used as a class to label the two datasets. Five machine learning algorithms have been considered to train the model. These are Support Vector Machine (SVM), Random forest (RF), Logistic regression (LR), Gradient Boosting, and Ada boost algorithms. The models have been trained on the datasets F1, F2, and F1F2 that is the F1 and the F2 dataset merged. Additionally, an ensemble approach has been used to train the model. The ensemble approach has been considered to run F1 and F2 datasets on gradient boosting algorithm and use the output as one dataset that is called F1F2 ensemble dataset and train a model using this dataset on the five algorithms. As the experiment shows, the ensemble approach model that has been trained on the Gradient Boosting algorithm outperformed the rest of the models. In conclusion, this study suggests the ensemble approach, that is, the RF + Gradient boosting model, to predict the antibiotic resistance phenotypes of TB isolates by outperforming the rest of the models.

Keywords: machine learning, MTB, WGS, drug resistant TB

Procedia PDF Downloads 29
188 Understanding the Accumulation of Microplastics in Riverbeds and Soils

Authors: Gopala Krishna Darbha

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Microplastics (MPs) are secondary fragments of large-sized plastic debris released into the environment and fall in the size range of less than 5 mm. Though reports indicate the abundance of MPs in both riverine and soil environments, their fate is still not completely understood due to the complexity of natural conditions. Mineral particles are ubiquitous in the rivers and may play a vital role in accumulating MPs to the riverbed, thus affecting the benthic life and posing a threat to the river's health. Apart, the chemistry (pH, ionic strength, humics) at the interface can be very prominent. The MPs can also act as potential vectors to transport other contaminants in the environment causing secondary water pollution. The present study focuses on understanding the interaction of MPs with weathering sequence of minerals (feldspar, kaolinite and gibbsite) under batch mode under relevant environmental and natural conditions. Simultaneously, we performed stability studies and transport (column) experiments to understand the mobility of MPs under varying soil solutions (SS) chemistry and the influence of contaminants (CuO nanoparticles). Results showed that the charge and morphology of the gibbsite played an significant role in sorption of NPs (108.1 mg/g) compared to feldspar (7.7 mg/g) and kaolinite (11.9 mg/g). The Fourier transform infrared spectroscopy data supports the complexation of NPs with gibbsite particles via hydrogen bonding. In case of feldspar and kaolinite, a weak interaction with NPs was observed which can be due to electrostatic repulsions and low surface area to volume ration of the mineral particles. The study highlights the enhanced mobility in presence of feldspar and kaolinite while gibbsite rich zones can cause entrapment of NPs accumulating in the riverbeds. In the case of soils, in the absence of MPs, a very high aggregation of CuO NPs observed in SS extracted from black, lateritic, and red soils, which can be correlated with ionic strength (IS) and type of ionic species. The sedimentation rate (Ksed(1/h)) for CuO NPs was >0.5 h−1 in the case of these SS. Interestingly, the stability and sedimentation behavior of CuO NPs varied significantly in the presence of MPs. The Ksed for CuO NPs decreased to half and found <0.25 h−1 in the presence of MPs in all SS. C/C0 values in breakthrough curves increased drastically (black < alluvial < laterite < red) in the presence of MPs. Results suggest that the release of MPs in the terrestrial ecosystem is a potential threat leading to increased mobility of metal nanoparticles in the environment.

Keywords: microplastics, minerals, sorption, soils

Procedia PDF Downloads 72
187 The Study of Self-Management of Stress (SMS) of Yoga Program for Pregnant Women in Early Pregnancy in Taiwan

Authors: Shau-Ping Shiu, Shu-Ling Lin

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Pregnancy lead a process of changing in the endocrine system. Either pregnancy itself or the surrounding affect such as the attitude of family to the pregnant lady can bring lots of stress. Sever stress may lead pregnant women display serious mental problem such as mood swings, impulsivity, and abnormal behavior. A method of self management of stress(SMS) has been proved that help patient of cancer in release their stress. This study were going to use SMS to help pregnant women. Methods: In this study, 42 ladies in the first to third months of pregnancy process applied to join SMS of program have divided into 21 participants in both control and experimental group by draw. 24 sessions of Yoga program were conducted once a week for 6 months for experimental group. Verbatim used to gather more feedbacks from the interview followed by each Yoga sessions. Brief symptom Rating scale also conducted pre and post experiment for 42 participations. Results: Overall score of Brief Symptom Rating Scale reduced 17.82 points and suicide drop 9 points in experimental group, compared to the control group increasing 10.24 point of overall score and suicide add 7 points. Feedback from interviews showed participations improved in emotion, physical health and stress management. They indicated having more positive emotion daily, having better gastrointestinal peristalsis movement, releasing back tention, well weight control, reducing stress and changing the quality of interpersonal relationships. Conclusion: SMS of Yoga program in this study included four key training directions which were stimulation, relaxation, awareness and pranayama lead a great improvment of stress management for pregnant lady. Throughout this Yoga program, women learned to ignite eustress, remove distress, create calmness and breath slows down. As the result, Yoga program has helped women in experiment group lower their tension, and bring the extra benifits in emotion and relationships. It support women to overcome their pregnancy. Suggestion: An unexpected result of this study showed all participants had no morning sickness since they engaged in SMS program, and no one absent from course due to the benefits of it. We strongly suggest that SMS of Yoga program can be a add of medication for women in pregnancy, however, the position of Forward in the SMS sequence has been point out pressing participant’s stomach, which can be replace to Bridge position to comfort participants.

Keywords: self-management of stress(SMS), yoga program, pregnant women, early pregnancy

Procedia PDF Downloads 311
186 Characterization of Petrophysical Properties of Reservoirs in Bima Formation, Northeastern Nigeria: Implication for Hydrocarbon Exploration

Authors: Gabriel Efomeh Omolaiye, Jimoh Ajadi, Olatunji Seminu, Yusuf Ayoola Jimoh, Ubulom Daniel

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Identification and characterization of petrophysical properties of reservoirs in the Bima Formation were undertaken to understand their spatial distribution and impacts on hydrocarbon saturation in the highly heterolithic siliciclastic sequence. The study was carried out using nine well logs from Maiduguri and Baga/Lake sub-basins within the Borno Basin. The different log curves were combined to decipher the lithological heterogeneity of the serrated sand facies and to aid the geologic correlation of sand bodies within the sub-basins. Evaluation of the formation reveals largely undifferentiated to highly serrated and lenticular sand bodies from which twelve reservoirs named Bima Sand-1 to Bima Sand-12 were identified. The reservoir sand bodies are bifurcated by shale beds, which reduced their thicknesses variably from 0.61 to 6.1 m. The shale content in the sand bodies ranged from 11.00% (relatively clean) to high shale content of 88.00%. The formation also has variable porosity values, with calculated total porosity ranged as low as 10.00% to as high as 35.00%. Similarly, effective porosity values spanned between 2.00 to 24.00%. The irregular porosity values also accounted for a wide range of field average permeability estimates computed for the formation, which measured between 0.03 to 319.49 mD. Hydrocarbon saturation (Sh) in the thin lenticular sand bodies also varied from 40.00 to 78.00%. Hydrocarbon was encountered in three intervals in Ga-1, four intervals in Da-1, two intervals in Ar-1, and one interval in Ye-1. Ga-1 well encountered 30.78 m thick of hydrocarbon column in 14 thin sand lobes in Bima Sand-1, with thicknesses from 0.60 m to 5.80 m and average saturation of 51.00%, while Bima Sand-2 intercepted 45.11 m thick of hydrocarbon column in 12 thin sand lobes with an average saturation of 61.00% and Bima Sand-9 has 6.30 m column in 4 thin sand lobes. Da-1 has hydrocarbon in Bima Sand-8 (5.30 m, Sh of 58.00% in 5 sand lobes), Bima Sand-10 (13.50 m, Sh of 52.00% in 6 sand lobes), Bima Sand-11 (6.20 m, Sh of 58.00% in 2 sand lobes) and Bima Sand-12 (16.50 m, Sh of 66% in 6 sand lobes). In the Ar-1 well, hydrocarbon occurs in Bima Sand-3 (2.40 m column, Sh of 48% in a sand lobe) and Bima Sand-9 (6.0 m, Sh of 58% in a sand lobe). Ye-1 well only intersected 0.5 m hydrocarbon in Bima Sand-1 with 78% saturation. Although Bima Formation has variable saturation of hydrocarbon, mainly gas in Maiduguri, and Baga/Lake sub-basins of the research area, its highly thin serrated sand beds, coupled with very low effective porosity and permeability in part, would pose a significant exploitation challenge. The sediments were deposited in a fluvio-lacustrine environment, resulting in a very thinly laminated or serrated alternation of sand and shale beds lithofacies.

Keywords: Bima, Chad Basin, fluvio-lacustrine, lithofacies, serrated sand

Procedia PDF Downloads 148
185 Postmortem Genetic Testing to Sudden and Unexpected Deaths Using the Next Generation Sequencing

Authors: Eriko Ochiai, Fumiko Satoh, Keiko Miyashita, Yu Kakimoto, Motoki Osawa

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Sudden and unexpected deaths from unknown causes occur in infants and youths. Recently, molecular links between a part of these deaths and several genetic diseases are examined in the postmortem. For instance, hereditary long QT syndrome and Burgada syndrome are occasionally fatal through critical ventricular tachyarrhythmia. There are a large number of target genes responsible for such diseases, the conventional analysis using the Sanger’s method has been laborious. In this report, we attempted to analyze sudden deaths comprehensively using the next generation sequencing (NGS) technique. Multiplex PCR to subject’s DNA was performed using Ion AmpliSeq Library Kits 2.0 and Ion AmpliSeq Inherited Disease Panel (Life Technologies). After the library was constructed by emulsion PCR, the amplicons were sequenced 500 flows on Ion Personal Genome Machine System (Life Technologies) according to the manufacture instruction. SNPs and indels were analyzed to the sequence reads that were mapped on hg19 of reference sequences. This project has been approved by the ethical committee of Tokai University School of Medicine. As a representative case, the molecular analysis to a 40 years old male who received a diagnosis of Brugada syndrome demonstrated a total of 584 SNPs or indels. Non-synonymous and frameshift nucleotide substitutions were selected in the coding region of heart disease related genes of ANK2, AKAP9, CACNA1C, DSC2, KCNQ1, MYLK, SCN1B, and STARD3. In particular, c.629T-C transition in exon 3 of the SCN1B gene, resulting in a leu210-to-pro (L210P) substitution is predicted “damaging” by the SIFT program. Because the mutation has not been reported, it was unclear if the substitution was pathogenic. Sudden death that failed in determining the cause of death constitutes one of the most important unsolved subjects in forensic pathology. The Ion AmpliSeq Inherited Disease Panel can amplify the exons of 328 genes at one time. We realized the difficulty in selection of the true source from a number of candidates, but postmortem genetic testing using NGS analysis deserves of a diagnostic to date. We now extend this analysis to SIDS suspected subjects and young sudden death victims.

Keywords: postmortem genetic testing, sudden death, SIDS, next generation sequencing

Procedia PDF Downloads 334
184 Petrographic Properties of Sedimentary-Exhalative Type Ores of Filizchay Polymetallic Deposit

Authors: Samir Verdiyev, Fuad Huseynov, Islam Guliyev, Coşqun İsmayıl

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The Filizchay polymetallic deposit is located on the southern slope of the Greater Caucasus Mountain Range, northwest of Azerbaijan in the Balaken district. Filizchay is the largest polymetallic deposit in the region and the second-largest polymetallic deposit in Europe. The mineral deposits in the region are associated with two different geodynamic evolutions that began with the Mesozoic collision along the Eurasian continent and the formation of a magmatic arc after the collision and continued with subduction in the Cenozoic. The bedrocks associated with Filizchay mineralization are Early Jurassic aged. The stratigraphic sequence of the deposit is consisting of black metamorphic clay shales, sandstones, and ore layers. Shales, sandstones, and siltstones are encountered in the upper and middle sections of the ore body, while only shales are observed at the lowest ranges. The ore body is mainly layered by the geometric structure of the bedrock; folding can be observed in the ore layers along with the bedrock foliation, and just in few points indirect laying due to the metamorphism. This suggests that the Filizchay ore mineralization is syngenetic, which is proved by the mineralization by the bedrock. To determine the ore petrography properties of the Filizchay deposit, samples were collected from the region where the ore is concentrated, and a polished section was prepared. These collected samples were examined under the mineralogical microscope to reveal the paragenesis of the mineralization and to explain the relation of ore minerals to each other. In this study, macroscopically observed minerals and textures of these minerals were used in the cores revealed during drilling exploration made by AzerGold CJS company. As a result of all these studies, it has been determined that there are three main mineralization types in the Filizchay deposit: banded, massive, and veinlet ores. The mineralization is in the massive pyrite; furthermore, the basis of the ore-mass contains pyrite, chalcopyrite, sphalerite, and galena. The pyrite in some parts of the ore body transformed to pyrrhotite as a result of metamorphism. Pyrite-chalcopyrite, pyrite-sphalerite-galena, pyrite-pyrrhotite mineral assemblages were determined during microscopic studies of mineralization. The replacement texture is more developed in Filizchay ores. The banded polymetallic type mineralization and near bedrocks are cut by quartz-carbonate veins. The geotectonic position and lithological conditions of the Filizchay deposit, the texture, and interrelationship of the sulfide mineralization indicate that it is a sedimentary-exhalative type of Au-Cu-Ag-Zn-Pb polymetallic deposit that is genetically related to the massive sulfide deposits.

Keywords: Balaken, Filizchay, metamorphism, polymetallic mineralization

Procedia PDF Downloads 170
183 Methodologies for Deriving Semantic Technical Information Using an Unstructured Patent Text Data

Authors: Jaehyung An, Sungjoo Lee

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Patent documents constitute an up-to-date and reliable source of knowledge for reflecting technological advance, so patent analysis has been widely used for identification of technological trends and formulation of technology strategies. But, identifying technological information from patent data entails some limitations such as, high cost, complexity, and inconsistency because it rely on the expert’ knowledge. To overcome these limitations, researchers have applied to a quantitative analysis based on the keyword technique. By using this method, you can include a technological implication, particularly patent documents, or extract a keyword that indicates the important contents. However, it only uses the simple-counting method by keyword frequency, so it cannot take into account the sematic relationship with the keywords and sematic information such as, how the technologies are used in their technology area and how the technologies affect the other technologies. To automatically analyze unstructured technological information in patents to extract the semantic information, it should be transformed into an abstracted form that includes the technological key concepts. Specific sentence structure ‘SAO’ (subject, action, object) is newly emerged by representing ‘key concepts’ and can be extracted by NLP (Natural language processor). An SAO structure can be organized in a problem-solution format if the action-object (AO) states that the problem and subject (S) form the solution. In this paper, we propose the new methodology that can extract the SAO structure through technical elements extracting rules. Although sentence structures in the patents text have a unique format, prior studies have depended on general NLP (Natural language processor) applied to the common documents such as newspaper, research paper, and twitter mentions, so it cannot take into account the specific sentence structure types of the patent documents. To overcome this limitation, we identified a unique form of the patent sentences and defined the SAO structures in the patents text data. There are four types of technical elements that consist of technology adoption purpose, application area, tool for technology, and technical components. These four types of sentence structures from patents have their own specific word structure by location or sequence of the part of speech at each sentence. Finally, we developed algorithms for extracting SAOs and this result offer insight for the technology innovation process by providing different perspectives of technology.

Keywords: NLP, patent analysis, SAO, semantic-analysis

Procedia PDF Downloads 247
182 Genome Sequencing, Assembly and Annotation of Gelidium Pristoides from Kenton-on-Sea, South Africa

Authors: Sandisiwe Mangali, Graeme Bradley

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Genome is complete set of the organism's hereditary information encoded as either deoxyribonucleic acid or ribonucleic acid in most viruses. The three different types of genomes are nuclear, mitochondrial and the plastid genome and their sequences which are uncovered by genome sequencing are known as an archive for all genetic information and enable researchers to understand the composition of a genome, regulation of gene expression and also provide information on how the whole genome works. These sequences enable researchers to explore the population structure, genetic variations, and recent demographic events in threatened species. Particularly, genome sequencing refers to a process of figuring out the exact arrangement of the basic nucleotide bases of a genome and the process through which all the afore-mentioned genomes are sequenced is referred to as whole or complete genome sequencing. Gelidium pristoides is South African endemic Rhodophyta species which has been harvested in the Eastern Cape since the 1950s for its high economic value which is one motivation for its sequencing. Its endemism further motivates its sequencing for conservation biology as endemic species are more vulnerable to anthropogenic activities endangering a species. As sequencing, mapping and annotating the Gelidium pristoides genome is the aim of this study. To accomplish this aim, the genomic DNA was extracted and quantified using the Nucleospin Plank Kit, Qubit 2.0 and Nanodrop. Thereafter, the Ion Plus Fragment Library was used for preparation of a 600bp library which was then sequenced through the Ion S5 sequencing platform for two runs. The produced reads were then quality-controlled and assembled through the SPAdes assembler with default parameters and the genome assembly was quality assessed through the QUAST software. From this assembly, the plastid and the mitochondrial genomes were then sampled out using Gelidiales organellar genomes as search queries and ordered according to them using the Geneious software. The Qubit and the Nanodrop instruments revealed an A260/A280 and A230/A260 values of 1.81 and 1.52 respectively. A total of 30792074 reads were obtained and produced a total of 94140 contigs with resulted into a sequence length of 217.06 Mbp with N50 value of 3072 bp and GC content of 41.72%. A total length of 179281bp and 25734 bp was obtained for plastid and mitochondrial respectively. Genomic data allows a clear understanding of the genomic constituent of an organism and is valuable as foundation information for studies of individual genes and resolving the evolutionary relationships between organisms including Rhodophytes and other seaweeds.

Keywords: Gelidium pristoides, genome, genome sequencing and assembly, Ion S5 sequencing platform

Procedia PDF Downloads 130
181 Identification of a Lead Compound for Selective Inhibition of Nav1.7 to Treat Chronic Pain

Authors: Sharat Chandra, Zilong Wang, Ru-Rong Ji, Andrey Bortsov

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Chronic pain (CP) therapeutic approaches have limited efficacy. As a result, doctors are prescribing opioids for chronic pain, leading to opioid overuse, abuse, and addiction epidemic. Therefore, the development of effective and safe CP drugs remains an unmet medical need. Voltage-gated sodium (Nav) channels act as cardiovascular and neurological disorder’s molecular targets. Nav channels selective inhibitors are hard to design because there are nine closely-related isoforms (Nav1.1-1.9) that share the protein sequence segments. We are targeting the Nav1.7 found in the peripheral nervous system and engaged in the perception of pain. The objective of this project was to screen a 1.5 million compound library for identification of inhibitors for Nav1.7 with analgesic effect. In this study, we designed a protocol for identification of isoform-selective inhibitors of Nav1.7, by utilizing the prior information on isoform-selective antagonists. First, a similarity search was performed; then the identified hits were docked into a binding site on the fourth voltage-sensor domain (VSD4) of Nav1.7. We used the FTrees tool for similarity searching and library generation; the generated library was docked in the VSD4 domain binding site using FlexX and compounds were shortlisted using a FlexX score and SeeSAR hyde scoring. Finally, the top 25 compounds were tested with molecular dynamics simulation (MDS). We reduced our list to 9 compounds based on the MDS root mean square deviation plot and obtained them from a vendor for in vitro and in vivo validation. Whole-cell patch-clamp recordings in HEK-293 cells and dorsal root ganglion neurons were conducted. We used patch pipettes to record transient Na⁺ currents. One of the compounds reduced the peak sodium currents in Nav1.7-HEK-293 stable cell line in a dose-dependent manner, with IC50 values at 0.74 µM. In summary, our computer-aided analgesic discovery approach allowed us to develop pre-clinical analgesic candidate with significant reduction of time and cost.

Keywords: chronic pain, voltage-gated sodium channel, isoform-selective antagonist, similarity search, virtual screening, analgesics development

Procedia PDF Downloads 106
180 Design Challenges for Severely Skewed Steel Bridges

Authors: Muna Mitchell, Akshay Parchure, Krishna Singaraju

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There is an increasing need for medium- to long-span steel bridges with complex geometry due to site restrictions in developed areas. One of the solutions to grade separations in congested areas is to use longer spans on skewed supports that avoid at-grade obstructions limiting impacts to the foundation. Where vertical clearances are also a constraint, continuous steel girders can be used to reduce superstructure depths. Combining continuous long steel spans on severe skews can resolve the constraints at a cost. The behavior of skewed girders is challenging to analyze and design with subsequent complexity during fabrication and construction. As a part of a corridor improvement project, Walter P Moore designed two 1700-foot side-by-side bridges carrying four lanes of traffic in each direction over a railroad track. The bridges consist of prestressed concrete girder approach spans and three-span continuous steel plate girder units. The roadway design added complex geometry to the bridge with horizontal and vertical curves combined with superelevation transitions within the plate girder units. The substructure at the steel units was skewed approximately 56 degrees to satisfy the existing railroad right-of-way requirements. A horizontal point of curvature (PC) near the end of the steel units required the use flared girders and chorded slab edges. Due to the flared girder geometry, the cross-frame spacing in each bay is unique. Staggered cross frames were provided based on AASHTO LRFD and NCHRP guidelines for high skew steel bridges. Skewed steel bridges develop significant forces in the cross frames and rotation in the girder websdue to differential displacements along the girders under dead and live loads. In addition, under thermal loads, skewed steel bridges expand and contract not along the alignment parallel to the girders but along the diagonal connecting the acute corners, resulting in horizontal displacement both along and perpendicular to the girders. AASHTO LRFD recommends a 95 degree Fahrenheit temperature differential for the design of joints and bearings. The live load and the thermal loads resulted in significant horizontal forces and rotations in the bearings that necessitated the use of HLMR bearings. A unique bearing layout was selected to minimize the effect of thermal forces. The span length, width, skew, and roadway geometry at the bridges also required modular bridge joint systems (MBJS) with inverted-T bent caps to accommodate movement in the steel units. 2D and 3D finite element analysis models were developed to accurately determine the forces and rotations in the girders, cross frames, and bearings and to estimate thermal displacements at the joints. This paper covers the decision-making process for developing the framing plan, bearing configurations, joint type, and analysis models involved in the design of the high-skew three-span continuous steel plate girder bridges.

Keywords: complex geometry, continuous steel plate girders, finite element structural analysis, high skew, HLMR bearings, modular joint

Procedia PDF Downloads 165
179 Groundwater Potential Mapping using Frequency Ratio and Shannon’s Entropy Models in Lesser Himalaya Zone, Nepal

Authors: Yagya Murti Aryal, Bipin Adhikari, Pradeep Gyawali

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The Lesser Himalaya zone of Nepal consists of thrusting and folding belts, which play an important role in the sustainable management of groundwater in the Himalayan regions. The study area is located in the Dolakha and Ramechhap Districts of Bagmati Province, Nepal. Geologically, these districts are situated in the Lesser Himalayas and partly encompass the Higher Himalayan rock sequence, which includes low-grade to high-grade metamorphic rocks. Following the Gorkha Earthquake in 2015, numerous springs dried up, and many others are currently experiencing depletion due to the distortion of the natural groundwater flow. The primary objective of this study is to identify potential groundwater areas and determine suitable sites for artificial groundwater recharge. Two distinct statistical approaches were used to develop models: The Frequency Ratio (FR) and Shannon Entropy (SE) methods. The study utilized both primary and secondary datasets and incorporated significant role and controlling factors derived from field works and literature reviews. Field data collection involved spring inventory, soil analysis, lithology assessment, and hydro-geomorphology study. Additionally, slope, aspect, drainage density, and lineament density were extracted from a Digital Elevation Model (DEM) using GIS and transformed into thematic layers. For training and validation, 114 springs were divided into a 70/30 ratio, with an equal number of non-spring pixels. After assigning weights to each class based on the two proposed models, a groundwater potential map was generated using GIS, classifying the area into five levels: very low, low, moderate, high, and very high. The model's outcome reveals that over 41% of the area falls into the low and very low potential categories, while only 30% of the area demonstrates a high probability of groundwater potential. To evaluate model performance, accuracy was assessed using the Area under the Curve (AUC). The success rate AUC values for the FR and SE methods were determined to be 78.73% and 77.09%, respectively. Additionally, the prediction rate AUC values for the FR and SE methods were calculated as 76.31% and 74.08%. The results indicate that the FR model exhibits greater prediction capability compared to the SE model in this case study.

Keywords: groundwater potential mapping, frequency ratio, Shannon’s Entropy, Lesser Himalaya Zone, sustainable groundwater management

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178 Gene Expression and Staining Agents: Exploring the Factors That Influence the Electrophoretic Properties of Fluorescent Proteins

Authors: Elif Tugce Aksun Tumerkan, Chris Lowe, Hannah Krupa

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Fluorescent proteins are self-sufficient in forming chromophores with a visible wavelength from 3 amino acids sequence within their own polypeptide structure. This chromophore – a molecule that absorbs a photon of light and exhibits an energy transition equal to the energy of the absorbed photon. Fluorescent proteins (FPs) consisted of a chain of 238 amino acid residues and composed of 11 beta strands shaped in a cylinder surrounding an alpha helix structure. A better understanding of the system of the chromospheres and the increasing advance in protein engineering in recent years, the properties of FPs offers the potential for new applications. They have used sensors and probes in molecular biology and cell-based research that giving a chance to observe these FPs tagged cell localization, structural variation and movement. For clarifying functional uses of fluorescent proteins, electrophoretic properties of these proteins are one of the most important parameters. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) analysis is used for determining electrophoretic properties commonly. While there are many techniques are used for determining the functionality of protein-based research, SDS-PAGE analysis can only provide a molecular level assessment of the proteolytic fragments. Before SDS-PAGE analysis, fluorescent proteins need to successfully purified. Due to directly purification of the target, FPs is difficult from the animal, gene expression is commonly used which must be done by transformation with the plasmid. Furthermore, used gel within electrophoresis and staining agents properties have a key role. In this review, the different factors that have the impact on the electrophoretic properties of fluorescent proteins explored. Fluorescent protein separation and purification are the essential steps before electrophoresis that should be done very carefully. For protein purification, gene expression process and following steps have a significant function. For successful gene expression, the properties of selected bacteria for expression, used plasmid are essential. Each bacteria has own characteristics which are very sensitive to gene expression, also used procedure is the important factor for fluorescent protein expression. Another important factors are gel formula and used staining agents. Gel formula has an effect on the specific proteins mobilization and staining with correct agents is a key step for visualization of electrophoretic bands of protein. Visuality of proteins can be changed depending on staining reagents. Apparently, this review has emphasized that gene expression and purification have a stronger effect than electrophoresis protocol and staining agents.

Keywords: cell biology, gene expression, staining agents, SDS-page

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177 Sustainable and Responsible Mining - Lundin Mining’s Subsidiary in Portugal, Sociedade Mineira de Neves-Corvo Case

Authors: Jose Daniel Braga Alves, Joaquim Gois, Alexandre Leite

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This abstract presents the responsible and sustainable mining case study of a Portuguese mine operation, highlighting how mine exploitation can sustainably exist in balance with the environment, aligned with all stakeholders. The mining operation is remotely located in a United Nations (UN) biodiversity reserve, away from major industrial centers or logistical ports, and presents an interesting investigation to assess the balanced mine operation in alignment with all key stakeholders, which presents unique opportunities as well as challenges. Based on the sustainable mining framework, it is intended to detail examples of best practices from Sociedade Mineira de Neves-Corvo (SOMINCOR), demonstrating social acceptance by the local community, health, and safety at work, reduction of environmental impacts and management of mining waste, which directly influence the acceptance and recognition of a sustainable operation. The case study aims to present the SOMINCOR approach to sustainable mining, focusing on social responsibility, considering materials provided by Lundin Mining Corporation (LMC) and SOMINCOR and the socially responsible approach of the mining operations., referencing related international guidelines, UN Sustainable Development Goals. The researchers reviewed LMC's annual Sustainability Reports (2019, 2020 and 2021) and updated information regarding material topics of the most significant interest to internal and external stakeholders. These material topics formed the basis of the corporation-wide sustainability strategy. LMC's Responsible Mining Policy (RMP) was reviewed, focusing on the commitment that guides the approach to responsible operation and management of the Company's business. Social performance, compliance, environmental management, governance, human rights, and economic contribution are principles of the RMP. The Human Rights Risk Impact Assessment (HRRIA), based on frameworks including UN Guiding Principles (UNGP), Voluntary Principles on Security and Human Rights, and a community engagement program implemented (SLO index), was part of this research. The program consists of ongoing surveys and perceptions studies using behavioural science insights, data from which was not available within the timeframe of completing this research. LMC stakeholder engagement standards and grievance mechanisms were also reviewed. Stakeholder engagement and the community's perception are key to this operation to ensure social license to operate (SLO). Preliminary surveys with local communities provided input data for the local development strategy. After the implementation of several initiatives, subsequent surveys were performed to assess acceptance and trust from the local communities and changes to the SLO index. SOMINCOR's operation contributes to 12 out of 17 sustainable development goals. From the assessed and available data, local communities and social engagement are priorities to SOMINCOR. Experience to date shows that the continual engagement with local communities and the grievance mechanisms in place are respected and followed for all concerns presented by any stakeholder. It can be concluded that this underground mine in Portugal complies with applicable regulations and goes beyond them with regard to sustainable development and engagement with key stakeholders.

Keywords: sustainable mining, development goals, portuguese mining, zinc copper

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176 Unpacking the Rise of Social Entrepreneurship over Sustainable Entrepreneurship among Sri Lankan Exporters in SMEs Sector: A Case Study in Sri Lanka

Authors: Amarasinghe Shashikala, Pramudika Hansini, Fernando Tajan, Rathnayake Piyumi

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This study investigates the prominence of the social entrepreneurship (SE) model over the sustainable entrepreneurship model among Sri Lankan exporters in the small and medium enterprise (SME) sector. The primary objective of this study is to explore how the unique socio-economic contextual nuances of the country influence this behavior. The study employs a multiple-case study approach, collecting data from thirteen SEs in the SME sector. The findings reveal a significant alignment between SE and the lifestyle of the people in Sri Lanka, attributed largely to its deep-rooted religious setting and cultural norms. A crucial factor driving the prominence of SE is the predominantly labor-intensive nature of production processes within the exporters of the SME sector. These processes inherently lend themselves to SE, providing employment opportunities and fostering community engagement. Further, SE initiatives substantially resonate with community-centric practices, making them more appealing and accessible to the local populace. In contrast, the findings highlight a dilemma between cost-effectiveness and sustainable entrepreneurship. Transitioning to sustainable export products and production processes is demanded by foreign buyers and acknowledged as essential for environmental stewardship, which often requires capital-intensive makeovers. This investment inevitably raises the overall cost of the export product, making it less competitive in the global market. Interestingly, the study notes a disparity between international demand for sustainable products and the willingness of buyers to pay a premium for them. Despite the growing global preference for eco-friendly options, the findings suggest that the additional costs associated with sustainable entrepreneurship are not adequately reflected in the purchasing behavior of international buyers. The abundance of natural resources coupled with a minimal occurrence of natural catastrophes renders exporters less environmentally sensitive. The absence of robust policy support for environmental preservation exacerbates this inclination. Consequently, exporters exhibit a diminished motivation to incorporate environmental sustainability into their business decisions. Instead, attention is redirected towards factors such as the local population's minimum standards of living, prevalent social issues, governmental corruption and inefficiency, and rural poverty. These elements impel exporters to prioritize social well-being when making business decisions. Notably, the emphasis on social impact, rather than environmental impact, appears to be a generational trend, perpetuating a focus on societal aspects in the realm of business. In conclusion, the manifestation of entrepreneurial behavior within developing nations is notably contingent upon contextual nuances. This investigation contributes to a deeper understanding of the dynamics shaping the prevalence of SE over sustainable entrepreneurship among Sri Lankan exporters in the SME sector. The insights generated have implications for policymakers, industry stakeholders, and academics seeking to navigate the delicate balance between socio-cultural values, economic feasibility, and environmental sustainability in the pursuit of responsible business practices within the export sector.

Keywords: small and medium enterprises, social entrepreneurship, Sri Lanka, sustainable entrepreneurship

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