Search results for: mechanisms
2133 Hydroxy Safflower Yellow A (HSYA) Mediated Neuroprotective Effect against Ischemia Reperfusion (I/R) Injury in Cerebral Stroke
Authors: Sruthi Ramagiri, Rajeev T.
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Free radical damage has been entailed as the major culprit in the ischemic stroke contributing for oxidative damage. Recent investigations on Hydroxy Safflower Yellow A (HSYA) suggested its role in cerebral ischemia and various neurodegenerative disorders with unidentified molecular mechanisms. The current study was designed to investigate putative therapeutic role and possible molecular mechanisms of HSYA administration during the onset of reperfusion in cerebral ischemia-reperfusion (I/R) injury in cerebral stroke. Cerebral stroke was achieved by focal ischemic model. HSYA (10 mg/kg) was injected intravenously via the tail vein 5 minutes before reperfusion. Losses of sensorimotor abilities were evaluated by neurological scoring, spontaneous locomotor activity, and rotarod performance. Extent of oxidative stress was evaluated by biochemical parameters i.e., malondialdehyde (MDA), Glutathione (GSH), Super Oxide Dismutase (SOD) and catalase levels. The infarct volume of brain was assessed by 2,3,5-triphenyl tetrazolium chloride (TTC) staining technique. Increased cerebral injury (I/R) was evidenced by motor impairment, increased infarct volume and elevation of MDA levels along with significant reduction in antioxidant i.e.,MDA levels along with significant reduction in antioxidant i.e., GSH, SOD and catalase levels when compared to sham control. However, post conditioning with HSYA (10 mg/kg, i.v.) at the onset of reperfusion has significantly ameliorated sensorimotor abilities, attenuated MDA levels and reduced the infarct volume as compared with vehicle treated I/R injury group. Moreover, HSYA treatments improved antioxidant enzyme levels as compared with vehicle treated I/R-injury group. In conclusion, it may be suggested that HSYA post conditioning could be novel therapeutic approach against I/R injury in cerebral stroke possibly through its anti-oxidant mechanism.Keywords: HSYA, Ischemia reperfusion injury, oxidative stress, stroke
Procedia PDF Downloads 4272132 Cooperative Replenishment through Bidding
Authors: Behzad Hezarkhani, Greys Sosic
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Collaborative purchasing and replenishment have proven to be beneficial in supply chain management. This talk addresses the situation where buyers, potentially in possession of private procurement channels, carry out cooperative purchasing by submitting their bids to a coordinator. The collaborative organization is faced with two basic decisions: (1) who will be allocated with the products, and (2) how much each party should pay. We discuss mechanisms that could achieve desirable outcomes in this settings with special attention to the strategic behavior of the buyers.Keywords: supply chain management, group purchasing organizations, game theory, mechanism design
Procedia PDF Downloads 3422131 Competition Law as a “Must Have” Course in Legal Education
Authors: Noemia Bessa Vilela, Jose Caramelo Gomes
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All law student are familiarized, in the first years of their bachelor of laws with the concepts of “public goods” and “ private goods”; often, such legal concept does not exactly match such economic concept, and there are consequences are some sort of confusion being created. The list of goods that follow under each category is not exhaustive, nor are students given proper mechanisms to acknowledge that some legal fields can, on its own, be considered as a “public good”; this is the case of Competition. Legal authors consider that “competition law is used to promote public interest” and, as such, it is a “public good”; in economics theory, Competition is the first public good in a market economy, as the enabler of allocation efficiency. Competition law is the legal tool to support the proper functioning of the market economy and democracy itself. It is fact that Competition Law only applies to economic activities, still, competition is object of private litigation as an integral part of Public Law. Still, regardless of the importance of Competition Law in the economic activity and market regulation, most student complete their studies in law, join the Bar Associations and engage in their professional activities never having been given sufficient tools to deal with the increasing demands of a globalized world. The lack of knowledge of economics, market functioning and the mechanisms at their reach in order to ensure proper realization of their duties as lawyers/ attorneys-at-law would be tackled if Competition Law would be included as part of the curricula of Law Schools. Proper teaching of Competition Law would combine the foundations of Competition Law, doctrine, case solving and Case Law study. Students should to understand and apply the analytical model. Special emphasis should be given to EU Competition Law, namely the TFEU Articles 101 to 106. Damages Directive should also be part of the curriculum. Students must in the first place acquire and master the economic rationale as competition and the world of competition law are the cornerstone of sound and efficient market. The teaching of Competition Law in undergraduate programs in Law would contribute to fulfill the potential of the students who will deal with matters related to consumer protection, economic and commercial law issues both in private practice and as in-house lawyers for companies.Keywords: higher education, competition law, legal education, law, market economy, industrial economics
Procedia PDF Downloads 1422130 An Investigation of the Pharmacomechanisms of Shang-Han Lun Formulas as Elucidated in the Qing Dynasty Classic 'Ben-Jing Shu-Zheng'
Authors: William Ceurvels, Dong-Di Zhang
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The true nature of the mechanism by which the pharmaceuticals of the Shang-Han Lun act has been a topic of debate since Wuji Cheng published the first commentary during the Northern Song. Subsequent commentaries employed a number of methodologies in their analysis of pharmaceutical mechanisms, but no commentator was able to garner universal acceptance. During the Qing Dynasty, the proliferation and development of Neo-Confucian scholarship produced a new generation of scholars possessed of rigorous and inventive research methods, one of whom was the famed materia medica scholar, Run-an Zou. Run-an Zou and his successor Zhou Yan advocated analyzing the mechanism of Treatise pharmaceuticals based upon the understanding of those pharmaceuticals during the time period in which the Treatise was written and thereby focused on the Han Dynasty materia medica tract Shen-nong Ben-cao Jing (The Divine Husbandman’s Herbal Foundation Canon). Zou Run-an’s commentary, Ben-jing Shu-zheng won nearly universal praise among materia medica scholars for its scholastic rigor and innovative research methods. However, because Ben-jing Shu-zheng only focuses on individual herbs, as opposed to formulas, its value in analyzing the Shang-Han Lun has limitations. The purpose of this study is to combine Zou Run-an’s single-pharmaceutical commentaries to generate theoretical full formula analyses to gain a fuller picture of Zou’s understanding of the healing mechanism of Shang-Han Lun formulas. Commentaries were gathered from Ben-jing Shu-zheng and Zhou Yan’s Ben-cao Si-bian Lun and combined to produce theoretical full formula model mechanisms of Treatise formulas. Through this study, a new picture of the mechanistic basis of Shang-han formulas emerges, which is based on qi-xue changes as opposed to organ or meridian theory. The author hopes that this modest research study will be of service to scholars of the Shang-han and clinical doctors alike in their pursuit of the true pharmacomechanisms of this great Han dynasty tome.Keywords: Materia medica, Shang-han Lun, Shen-nong Ben-cao Jing, neo-Confucian scholarship
Procedia PDF Downloads 3192129 Criteria for Good Governance in Georgian Defense Sector:Standards and Principles
Authors: Vephkhvia Grigalashvili
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This paper provides an overview of criteria for good governance in Georgian defense sector and scientific outcomes of comparative research. A respect for good governance and its realization into Georgian national defense sector represents a fundamental institutional necessity as well as country`s politico-legal obligation within the framework of the existing collaboration mechanisms with NATO (especially Building Integrity (BI) Programme) and the Association Agreement between the EU and Georgia. Furthermore good governance is considered as a democracy measuring criterion in country`s Euro-Atlantic integration process. Accordingly, integration and further development of the contemporary approaches of good governance into Georgian defense management model represents a burning issue of the country. The assessment of an existing model of the country, identification of defects and determination of course of institutional reforms in a mutual comparison format of good governance mechanisms of NATO or/and the EU member Eastern European or Baltic countries positively assessed by the international organizations is considered as a precondition for its effective realization. Scientific aims of this study are: (a) to conduct comparative analysis of Georgian national principles and generalized standards of NATO or/and the EU member Eastern European and Baltic countries in following segments of good governance: open governance; anticorruption policy; conflict of interests; integrity; internal and external control bodies; (b) to formulate theoretical and practical recommendations on reforms to be implemented in the country`s national defence sector. As research reveals, although, institutional / legal pillars of good governance in Georgian defense sector generally are in compliance with international principles, the quality of implementation of good government norms still remains as an area that needs further development by raising awareness of public servants and community.Keywords: anti-corruption policy within Georgian defense governance, conflict of interests within Georgian defense governance, good governance in Georgian defense sector, principles of integrity in Georgian defense management
Procedia PDF Downloads 1622128 Opportunities and Challenges for Decarbonizing Steel Production by Creating Markets for ‘Green Steel’ Products
Authors: Hasan Muslemani, Xi Liang, Kathi Kaesehage, Francisco Ascui, Jeffrey Wilson
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The creation of a market for lower-carbon steel products, here called ‘green steel’, has been identified as an important means to support the introduction of breakthrough emission reduction technologies into the steel sector. However, the definition of what ‘green’ entails in the context of steel production, the implications on the competitiveness of green steel products in local and international markets, and the necessary market mechanisms to support their successful market penetration remain poorly explored. This paper addresses this gap by holding semi-structured interviews with international sustainability experts and commercial managers from leading steel trade associations, research institutes and steelmakers. Our findings show that there is an urgent need to establish a set of standards to define what ‘greenness’ means in the steelmaking context; standards that avoid market disruptions, unintended consequences, and opportunities for greenwashing. We also highlight that the introduction of green steel products will have implications on product competitiveness on three different levels: 1) between primary and secondary steelmaking routes, 2) with traditional, lesser green steel, and 3) with other substitutable materials (e.g. cement and plastics). This paper emphasises the need for steelmakers to adopt a transitional approach in deploying different low-carbon technologies, based on their stage of technological maturity, applicability in certain country contexts, capacity to reduce emissions over time, and the ability of the investment community to support their deployment. We further identify market mechanisms to support green steel production, including carbon border adjustments and public procurement, highlighting a need for implementing a combination of complementary policies to ensure the products’ roll-out. The study further shows that the auto industry is a likely candidate for green steel consumption, where a market would be supported by price premiums paid by willing consumers, such as those of high-end luxury vehicles.Keywords: green steel, decarbonisation, business model innovation, market analysis
Procedia PDF Downloads 1342127 Fatigue of Multiscale Nanoreinforced Composites: 3D Modelling
Authors: Leon Mishnaevsky Jr., Gaoming Dai
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3D numerical simulations of fatigue damage of multiscale fiber reinforced polymer composites with secondary nanoclay reinforcement are carried out. Macro-micro FE models of the multiscale composites are generated automatically using Python based software. The effect of the nanoclay reinforcement (localized in the fiber/matrix interface (fiber sizing) and distributed throughout the matrix) on the crack path, damage mechanisms and fatigue behavior is investigated in numerical experiments.Keywords: computational mechanics, fatigue, nanocomposites, composites
Procedia PDF Downloads 6072126 The Retinoprotective Effects and Mechanisms of Fungal Ingredient 3,4-Dihydroxybenzalacetone through Inhibition of Retinal Müller and Microglial Activation
Authors: Yu-Wen Cheng, Jau-Der Ho, Liang-Huan Wu, Fan-Li Lin, Li-Huei Chen, Hung-Ming Chang, Yueh-Hsiung Kuo, George Hsiao
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Retina glial activation and neuroinflammation have been confirmed to cause devastating responses in retinodegenerative diseases. The expression and activation of matrix metalloproteinase (MMP)-9 and inducible nitric oxide synthase (iNOS) could be exerted as the crucial pathological factors in glaucoma- and blue light-induced retinal injuries. The present study aimed to investigate the retinoprotective effects and mechanisms of fungal ingredient 3,4-dihydroxybenzalacetone (DBL) isolated from Phellinus linteus in the retinal glial activation and retinodegenerative animal models. According to the cellular studies, DBL significantly and concentration-dependently abrogated MMP-9 activation and expression in TNFα-stimulated retinal Müller (rMC-1) cells. We found the inhibitory activities of DBL were strongly through the STAT- and ERK-dependent pathways. Furthermore, DBL dramatically attenuated MMP-9 activation in the stimulated Müller cells exposed to conditioned media from LPS-stimulated microglia BV-2 cells. On the other hand, DBL strongly suppressed LPS-induced production of NO and ROS and expression of iNOS in microglia BV-2 cells. Consistently, the phosphorylation of STAT was substantially blocked by DBL in LPS-stimulated microglia BV-2 cells. In the evaluation of retinoprotective functions, the high IOP-induced scotopic electroretinographic (ERG) deficit and blue light-induced abnormal pupillary light response (PLR) were assessed. The deficit scotopic ERG responses markedly recovered by DBL in a rat model of glaucoma-like ischemia/reperfusion (I/R)-injury. DBL also reduced the aqueous gelatinolytic activity and retinal MMP-9 expression in high IOP-injured conditions. Additionally, DBL could restore the abnormal PLR and reduce retinal MMP-9 activation. In summary, DBL could ameliorate retinal neuroinflammation and MMP-9 activation by predominantly inhibiting STAT3 activation in the retinal Müller cells and microglia, which exhibits therapeutic potential for glaucoma and other retinal degenerative diseases.Keywords: glaucoma, blue light, DBL, retinal Müller cell, MMP-9, STAT, Microglia, iNOS, ERG, PLR
Procedia PDF Downloads 1392125 Total Plaque Area in Chronic Renal Failure
Authors: Hernán A. Perez, Luis J. Armando, Néstor H. García
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Background and aims Cardiovascular disease rates are very high in patients with renal failure (CRF), but the underlying mechanisms are incompletely understood. Traditional cardiovascular risk factors do not explain the increased risk, and observational studies have observed paradoxical or absent associations between classical risk factors and mortality in dialysis patients. A large randomized controlled trial, the 4D Study, the AURORA and the ALERT study found that statin therapy in CRF do not reduce cardiovascular events. These results may be the results of ‘accelerated atherosclerosis’ observed on these patients. The objective of this study was to investigate if carotid total plaque area (TPA), a measure of carotid plaque burden growth is increased at progressively lower creatinine clearance in patients with CRF. We studied a cohort of patients with CRF not on dialysis, reasoning that risk factor associations might be more easily discerned before end stage renal disease. Methods: The Blossom DMO Argentina ethics committee approved the study and informed consent from each participant was obtained. We performed a cohort study in 412 patients with Stage 1, 2 and 3 CRF. Clinical and laboratory data were obtained. TPA was determined using bilateral carotid ultrasonography. Modification of Diet in Renal Disease estimation formula was used to determine renal function. ANOVA was used when appropriate. Results: Stage 1 CRF group (n= 16, 43±2yo) had a blood pressure of 123±2/78±2 mmHg, BMI 30±1, LDL col 145±10 mg/dl, HbA1c 5.8±0.4% and had the lowest TPA 25.8±6.9 mm2. Stage 2 CRF (n=231, 50±1 yo) had a blood pressure of 132±1/81±1 mmHg, LDL col 125±2 mg/dl, HbA1c 6±0.1% and TPA 48±10mm2 ( p< 0.05 vs CRF stage 1) while Stage 3 CRF (n=165, 59±1 yo) had a blood pressure of 134±1/81±1, LDL col 125±3 mg/dl, HbA1c 6±0.1% and TPA 71±6mm2 (p < 0.05 vs CRF stage 1 and 2). Conclusion: Our data indicate that TPA increases along the renal function deterioration, and it is not related with the LDL cholesterol and triglycerides levels. We suggest that mechanisms other than the classics are responsible for the observed excess of cardiovascular disease in CKD patients and finally, determination of total plaque area should be used to measure effects of antiatherosclerotic therapy.Keywords: hypertension, chronic renal failure, atherosclerosis, cholesterol
Procedia PDF Downloads 2722124 Investigating Legal Consciousness Among Migrants in Greece: A Study of Migrant’s Views of Hate Crime and their Legal Rights
Authors: Violeta Kapageorgiadou
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Over the past decade, millions of individuals from middle-eastern and African countries have migrated to Europe to seek refuge. The majority of these refugees emigrate from Muslim majority countries and seek to integrate into European societies. Notably, Greece has hosted thousands of individuals seeking asylum since 2015. Many of these individuals have applied for asylum. They have sought to integrate into the Greek society and to navigate their way through the national and European legal systems with regard to their status. This paper, drawn from a PhD thesis project, focuses on the legal consciousness of migrants and the processes open to asylum seekers to assert their rights, notably with regard to incidents of hate crime and including their interactions with the legal authorities in Greece. The research seeks to capture the factors that influence the views and behaviors of migrants towards the law and their legal rights, using legal consciousness as a theoretical framework. The research findings indicate that asylum seekers have developed a multidimensional legal consciousness influenced by their religious and political background, legal knowledge, previous (negative) experiences with the legal system and their socio-economic status in Greece. Asylum seekers, while aware of the rights essential for their survival in the host country (such as applying for asylum to obtain a secure status, claiming for benefits and housing), were unaware of, and less willing to engage with, legal authorities and rights which they did not find essential for their survival. They viewed hate incidents against them as less important, not worth reporting and sometimes did not even consider these incidents as crimes. The research suggests that asylum seekers in Greece are a vulnerable population who need mechanisms to support them and raise their legal consciousness around their rights in order to better integrate, develop and thrive in the host society. Moving forwards, a better understanding of refugees' and asylum seekers’ reactions towards hate crime will help to create future policies and support mechanisms that could improve the lives of these individuals.Keywords: hate crime, legal consciousness, legal rights, migrations
Procedia PDF Downloads 2222123 'Value-Based Re-Framing' in Identity-Based Conflicts: A Skill for Mediators in Multi-Cultural Societies
Authors: Hami-Ziniman Revital, Ashwall Rachelly
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The conflict resolution realm has developed tremendously during the last half-decade. Three main approaches should be mentioned: an Alternative Dispute Resolution (ADR) suggesting processes such as Arbitration or Interests-based Negotiation was developed as an answer to obligations and rights-based conflicts. The Pragmatic mediation approach focuses on the gap between interests and needs of disputants. The Transformative mediation approach focusses on relations and suits identity-based conflicts. In the current study, we examine the conflictual relations between religious and non-religious Jews in Israel and the impact of three transformative mechanisms: Inter-group recognition, In-group empowerment and Value-based reframing on the relations between the participants. The research was conducted during four facilitated joint mediation classes. A unique finding was found. Using both transformative mechanisms and the Contact Hypothesis criteria, we identify transformation in participants’ relations and a considerable change from anger, alienation, and suspiciousness to an increased understanding, affection and interpersonal concern towards the out-group members. Intergroup Recognition, In-group empowerment, and Values-based reframing were the skills discovered as the main enablers of the change in the relations and the research participants’ fostered mutual recognition of the out-group values and identity-based issues. We conclude this transformation was possible due to a constant intergroup contact, based on the Contact Hypothesis criteria. In addition, as Interests-based mediation uses “Reframing” as a skill to acknowledge both mutual and opposite needs of the disputants, we suggest the use of “Value-based Reframing” in intergroup identity-based conflicts, as a skill contributes to the empowerment and the recognition of both mutual and different out-group values. We offer to implement those insights and skills to assist conflict resolution facilitators in various intergroup identity-based conflicts resolution efforts and to establish further research and knowledge.Keywords: empowerment, identity-based conflict, intergroup recognition, intergroup relations, mediation skills, multi-cultural society, reframing, value-based recognition
Procedia PDF Downloads 3432122 Intervening between Family Functioning and Depressive Symptoms: Effect of Deprivation of Liberty, Self-Efficacy and Differentiation of Self
Authors: Jasna Hrncic
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Poor family relations predict depression, but also to other mental health issues. Mediating effect of self-efficacy and differentiation of self and moderating effect of decreased accessibility and/or success of other adaptive and defensive mechanisms for overcoming social disadvantages could explain depression as a specific outcome of dysfunctional family relations. The present study analyzes the mediation effect of self-efficacy and differentiation of self from poor family functioning to depressive symptoms and the moderation effect of deprivation of liberty on the listed mediation effect. Deprivation of liberty has, as a general consequence, a decreased accessibility and/or success of many adaptive and defensive mechanisms. It is hypothesized that: 1) self-efficacy and differentiation of self will mediate between family functioning and depressiveness in the total sample, and 2) deprivation of liberty will moderate the stated relations. Cross-sectional study was conducted among 323 male juveniles in Serbia divided in three groups: 98 adolescents deprived of their liberty due to antisocial behavior (incarcerated antisocial group - IAG), 121 adolescents with antisocial behavior in their natural setting (antisocial control group - CAG) and 105 adolescents in general population (general control group - CGG). The CAG was included along with GCG to control the possible influence that comorbidity of antisocial behavior and depressiveness could have on results. Instruments for family relations assessment were: for a whole family of origin the emotional exchange scale and individuation scale from GRADIR by Knezevic, and for a relationship with mother PCS-YSR and CRPBI by barber, and intimacy, rejection, sacrifice, punishment, demands, control and internal control by Opacic and Kos. Differentiation of self (DOS) is measured by emotional self scale (Opacic), self-efficacy (SE) by general incompetence scale by Bezinovic, and depression by BDI (Back), CES-D (Radloff) and D6R (Momirovic). Two-path structural equation modeling based on most commonly reported fit indices, showed that the mediation model had unfavorable fit to our data for total sample [(χ2 (1, N = 324) = 13.73); RMSEA= .20 (90% CI= [.12, .30]); CFI= .98; NFI= .97; AIC=31.73]. Path model provided an adequate fit to the data only for AIG - and not to the data from ACG and GCG. SE and DOS mediated the relationship between PFF and depressiveness. Test of the indirect effects revealed that 23.85% of PFF influences on depressiveness is mediated by these two mediators (the quotient of mediated effect = .24). Test of specific indirect effects showed that SE mediates 22.17%, while DOS mediates 1.67% of PFF influence on depressiveness. Lack of expected mediation effect could be explained by missing other potential mediators (i.e., relationship with that father, social skills, self-esteem) and lower variability of both predictor and criterion variable due to their low levels on the whole sample and on control subsamples. Results suggested that inaccessibility and/or successfulness of other adaptive and defensive mechanisms for overcoming social disadvantages has a strong impact on the mediation effect of self/efficacy and differentiation of self from poor family functioning to depressive symptoms. Further researches could include other potential mediators and a sample of clinically depressed people.Keywords: antisocial behavior, mediating effect, moderating effect, natural setting, incarceration
Procedia PDF Downloads 1172121 Change of Internal Friction on Magnesium Alloy with 5.48% Al Dependence on the Temperature
Authors: Milan Uhríčik, Andrea Soviarová, Zuzana Dresslerová, Peter Palček, Alan Vaško
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The article is focused on the analysis changes dependence on the temperature on the magnesium alloy with 5,48% Al, 0,813% Zn and 0,398% Mn by internal friction. Internal friction is a property of the material is measured on the ultrasonic resonant aparature at a frequency about f = 20470 Hz. The measured temperature range was from 30 °C up to 420 °C. Precisely measurement of the internal friction can be monitored ongoing structural changes and various mechanisms that prevent these changes.Keywords: internal friction, magnesium alloy, temperature, resonant frequency
Procedia PDF Downloads 7012120 Mannosidase Alpha Class 1B Member 1 Targets F Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein and Ebola Virus Glycoprotein to Endoplasmic Reticulum-To-Lysosome-Associated Degradation by Micro-Endoplasmic Reticulum-Phagy
Authors: Yong-Hui Zheng
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Viruses hijack host machineries to propagate and spread, which disrupts cellular homeostasis and activates various counteractive mechanisms. Infection of enveloped viruses is dependent on their fusion proteins, which bind to viral receptors to allow virus entry into cells. Fusion proteins are glycoproteins and expressed in the endoplasmic reticulum (ER) by hijacking the secretory pathway. Previously, we reported that Zaire ebolavirus (EBOV)-glycoprotein (GP) expression induces ER stress, and EBOV-GP is targeted by the calnexin cycle to macro-ER-phagy for degradation. We now report that expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/SARS2)-spike (S) protein also causes ER stress, and its expression is strongly downregulated by mannosidase alpha class 1B member 1 (MAN1B1), a class I α-mannosidase from the ER. MAN1B1 co-localizes with SARS2-S in the ER, and its downregulation of SARS2-S is blocked by inhibitors targeting lysosomes and autophagy, but not proteasomes, indicating SARS2-S degradation by autolysosomes. Notably, the SARS2-S degradation does not require the core autophagy machinery including ATG3, ATG5, ATG7, and phosphatidylinositol 3-kinase catalytic subunit type 3 (PI3KC3)/vacuolar protein sorting 34 (VPS34), and instead, it requires Beclin 1 (BECN1), a core component in the PI3KC3 complex. In addition, MAN1B1 does not trigger SARS2-S polyubiquitination, and consistently, the SARS2-S degradation does not require the autophagy receptor sequestosome 1 (SQSTM1)/p62. MAN1B1 also downregulates EBOV-GP similarly, but this degradation does not require BECN1. Collectively, we conclude that MAN1B1 downregulates viral fusions by micro-ER-phagy, and importantly, we have identified BECN1-dependent and BECN1-independent mechanisms for micro-ER-phagy.Keywords: Micro-ER-phagy, reticulophagy, fusion proteins, ER stress
Procedia PDF Downloads 692119 New Findings on the Plasma Electrolytic Oxidation (PEO) of Aluminium
Authors: J. Martin, A. Nominé, T. Czerwiec, G. Henrion, T. Belmonte
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The plasma electrolytic oxidation (PEO) is a particular electrochemical process to produce protective oxide ceramic coatings on light-weight metals (Al, Mg, Ti). When applied to aluminum alloys, the resulting PEO coating exhibit improved wear and corrosion resistance because thick, hard, compact and adherent crystalline alumina layers can be achieved. Several investigations have been carried out to improve the efficiency of the PEO process and one particular way consists in tuning the suitable electrical regime. Despite the considerable interest in this process, there is still no clear understanding of the underlying discharge mechanisms that make possible metal oxidation up to hundreds of µm through the ceramic layer. A key parameter that governs the PEO process is the numerous short-lived micro-discharges (micro-plasma in liquid) that occur continuously over the processed surface when the high applied voltage exceeds the critical dielectric breakdown value of the growing ceramic layer. By using a bipolar pulsed current to supply the electrodes, we previously observed that micro-discharges are delayed with respect to the rising edge of the anodic current. Nevertheless, explanation of the origin of such phenomena is still not clear and needs more systematic investigations. The aim of the present communication is to identify the relationship that exists between this delay and the mechanisms responsible of the oxide growth. For this purpose, the delay of micro-discharges ignition is investigated as the function of various electrical parameters such as the current density (J), the current pulse frequency (F) and the anodic to cathodic charge quantity ratio (R = Qp/Qn) delivered to the electrodes. The PEO process was conducted on Al2214 aluminum alloy substrates in a solution containing potassium hydroxide [KOH] and sodium silicate diluted in deionized water. The light emitted from micro-discharges was detected by a photomultiplier and the micro-discharge parameters (number, size, life-time) were measured during the process by means of ultra-fast video imaging (125 kfr./s). SEM observations and roughness measurements were performed to characterize the morphology of the elaborated oxide coatings while XRD was carried out to evaluate the amount of corundum -Al203 phase. Results show that whatever the applied current waveform, the delay of micro-discharge appearance increases as the process goes on. Moreover, the delay is shorter when the current density J (A/dm2), the current pulse frequency F (Hz) and the ratio of charge quantity R are high. It also appears that shorter delays are associated to stronger micro-discharges (localized, long and large micro-discharges) which have a detrimental effect on the elaborated oxide layers (thin and porous). On the basis of the results, a model for the growth of the PEO oxide layers will be presented and discussed. Experimental results support that a mechanism of electrical charge accumulation at the oxide surface / electrolyte interface takes place until the dielectric breakdown occurs and thus until micro-discharges appear.Keywords: aluminium, micro-discharges, oxidation mechanisms, plasma electrolytic oxidation
Procedia PDF Downloads 2642118 Signals Monitored During Anaesthesia
Authors: Launcelot McGrath, Xiaoxiao Liu, Colin Flanagan
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It is widely recognised that a comprehensive understanding of physiological data is a vital aid to the anaesthesiologist in monitoring and maintaining the well-being of a patient undergoing surgery. Bio signal analysis is one of the most important topics that researchers have tried to develop over the last century to understand numerous human diseases. There are tremendous biological signals during anaesthesia, and not all of them are important, which to choose to observe is a significant decision. It is important that the anaesthesiologist understand both the signals themselves, and the limitations introduced by the processes of acquisition. In this article, we provide an all-sided overview of different types of biological signals as well as the mechanisms applied to acquire them.Keywords: general biosignals, anaesthesia, biological, electroencephalogram
Procedia PDF Downloads 1052117 Vertical Urbanization Over Public Structures: The Example of Mostar Junction in Belgrade, Serbia
Authors: Sladjana Popovic
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The concept of vertical space urbanization, defined in English as "air rights development," can be considered a mechanism for the development of public spaces in urban areas of high density. A chronological overview of the transformation of space within the vertical projection of the existing traffic infrastructure that penetrates through the central areas of a city is given in this paper through the analysis of two illustrative case studies: more advanced and recent - "Plot 13" in Boston, and less well-known European example of structures erected above highways throughout Italy - the "Pavesi auto grill" chain. The backbone of this analysis is the examination of the possibility of yielding air rights within the vertical projection of public structures in the two examples by considering the factors that would enable its potential application in capitals in Southeastern Europe. The cession of air rights in the Southeastern Europe region, as a phenomenon, has not been a recognized practice in urban planning. In a formal sense, legal and physical feasibility can be seen to some extent in local models of structures built above protected historical heritage (i.e., archaeological sites); however, the mechanisms of the legal process of assigning the right to use and develop air rights above public structures is not a recognized concept. The goal of the analysis is to shed light on the influence of institutional participants in the implementation of innovative solutions for vertical urbanization, as well as strategic planning mechanisms in public-private partnership models that would enable the implementation of the concept in the region. The main question is whether the manipulation of the vertical projection of space could provide for innovative urban solutions that overcome the deficit and excessive use of the available construction land, particularly above the dominant public spaces and traffic infrastructure that penetrate central parts of a city. Conclusions reflect upon vertical urbanization that can bridge the spatial separation of the city, reduce noise pollution and contribute to more efficient urban planning along main transportation corridors.Keywords: air rights development, innovative urbanism, public-private partnership, transport infrastructure, vertical urbanization
Procedia PDF Downloads 762116 Superchaotropicity: Grafted Surface to Probe the Adsorption of Nano-Ions
Authors: Raimoana Frogier, Luc Girard, Pierre Bauduin, Diane Rebiscoul, Olivier Diat
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Nano-ions (NIs) are ionic species or clusters of nanometric size. Their low charge density and the delocalization of their charges give special properties to some of NIs belonging to chemical classes of polyoxometalates (POMs) or boron clusters. They have the particularity of interacting non-covalently with neutral hydrated surface or interfaces such as assemblies of surface-active molecules (micelles, vesicles, lyotropic liquid crystals), foam bubbles or emulsion droplets. This makes possible to classify those NIs in the Hofmeister series as superchaotropic ions. The mechanism of adsorption is complex, linked to the simultaneous dehydration of the ion and the molecule or supramolecular assembly with which it can interact, all with an enthalpic gain on the free energy of the system. This interaction process is reversible and is sufficiently pronounced to induce changes in molecular and supramolecular shape or conformation, phase transitions in the liquid phase, all at sub-millimolar ionic concentrations. This new property of some NIs opens up new possibilities for applications in fields as varied as biochemistry for solubilization, recovery of metals of interest by foams in the form of NIs... In order to better understand the physico-chemical mechanisms at the origin of this interaction, we use silicon wafers functionalized by non-ionic oligomers (polyethylene glycol chains or PEG) to study in situ by X-ray reflectivity this interaction of NIs with the grafted chains. This study carried out at ESRF (European Synchrotron Radiation Facility) and has shown that the adsorption of the NIs, such as POMs, has a very fast kinetics. Moreover the distribution of the NIs in the grafted PEG chain layer was quantify. These results are very encouraging and confirm what has been observed on soft interfaces such as micelles or foams. The possibility to play on the density, length and chemical nature of the grafted chains makes this system an ideal tool to provide kinetic and thermodynamic information to decipher the complex mechanisms at the origin of this adsorption.Keywords: adsorption, nano-ions, solid-liquid interface, superchaotropicity
Procedia PDF Downloads 672115 Epigenetic Modifying Potential of Dietary Spices: Link to Cure Complex Diseases
Authors: Jeena Gupta
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In the today’s world of pharmaceutical products, one should not forget the healing properties of inexpensive food materials especially spices. They are known to possess hidden pharmaceutical ingredients, imparting them the qualities of being anti-microbial, anti-oxidant, anti-inflammatory and anti-carcinogenic. Further aberrant epigenetic regulatory mechanisms like DNA methylation, histone modifications or altered microRNA expression patterns, which regulates gene expression without changing DNA sequence, contribute significantly in the development of various diseases. Changing lifestyles and diets exert their effect by influencing these epigenetic mechanisms which are thus the target of dietary phytochemicals. Bioactive components of plants have been in use since ages but their potential to reverse epigenetic alterations and prevention against diseases is yet to be explored. Spices being rich repositories of many bioactive constituents are responsible for providing them unique aroma and taste. Some spices like curcuma and garlic have been well evaluated for their epigenetic regulatory potential, but for others, it is largely unknown. We have evaluated the biological activity of phyto-active components of Fennel, Cardamom and Fenugreek by in silico molecular modeling, in vitro and in vivo studies. Ligand-based similarity studies were conducted to identify structurally similar compounds to understand their biological phenomenon. The database searching has been done by using Fenchone from fennel, Sabinene from cardamom and protodioscin from fenugreek as a query molecule in the different small molecule databases. Moreover, the results of the database searching exhibited that these compounds are having potential binding with the different targets found in the Protein Data Bank. Further in addition to being epigenetic modifiers, in vitro study had demonstrated the antimicrobial, antifungal, antioxidant and cytotoxicity protective effects of Fenchone, Sabinene and Protodioscin. To best of our knowledge, such type of studies facilitate the target fishing as well as making the roadmap in drug design and discovery process for identification of novel therapeutics.Keywords: epigenetics, spices, phytochemicals, fenchone
Procedia PDF Downloads 1582114 Hepatocyte-Intrinsic NF-κB Signaling Is Essential to Control a Systemic Viral Infection
Authors: Sukumar Namineni, Tracy O'Connor, Ulrich Kalinke, Percy Knolle, Mathias Heikenwaelder
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The liver is one of the pivotal organs in vertebrate animals, serving a multitude of functions such as metabolism, detoxification and protein synthesis and including a predominant role in innate immunity. The innate immune mechanisms pertaining to liver in controlling viral infections have largely been attributed to the Kupffer cells, the locally resident macrophages. However, all the cells of liver are equipped with innate immune functions including, in particular, the hepatocytes. Hence, our aim in this study was to elucidate the innate immune contribution of hepatocytes in viral clearance using mice lacking Ikkβ specifically in the hepatocytes, termed IkkβΔᴴᵉᵖ mice. Blockade of Ikkβ activation in IkkβΔᴴᵉᵖ mice affects the downstream signaling of canonical NF-κB signaling by preventing the nuclear translocation of NF-κB, an important step required for the initiation of innate immune responses. Interestingly, infection of IkkβΔᴴᵉᵖ mice with lymphocytic choriomeningitis virus (LCMV) led to strongly increased hepatic viral titers – mainly confined in clusters of infected hepatocytes. This was due to reduced interferon stimulated gene (ISG) expression during the onset of infection and a reduced CD8+ T-cell-mediated response. Decreased ISG production correlated with increased liver LCMV protein and LCMV in isolated hepatocytes from IkkβΔᴴᵉᵖ mice. A similar phenotype was found in LCMV-infected mice lacking interferon signaling in hepatocytes (IFNARΔᴴᵉᵖ) suggesting a link between NFkB and interferon signaling in hepatocytes. We also observed a failure of interferon-mediated inhibition of HBV replication in HepaRG cells treated with NF-kB inhibitors corroborating our initial findings with LCMV infections. Collectively, these results clearly highlight a previously unknown and influential role of hepatocytes in the induction of innate immune responses leading to viral clearance during a systemic viral infection with LCMV-WE.Keywords: CD8+ T cell responses, innate immune mechanisms in the liver, interferon signaling, interferon stimulated genes, NF-kB signaling, viral clearance
Procedia PDF Downloads 1912113 Signals Monitored During Anaesthesia
Authors: Launcelot McGrath
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A comprehensive understanding of physiological data is a vital aid to the anaesthesiologist in monitoring and maintaining the well-being of a patient undergoing surgery. Bio signal analysis is one of the most important topics that researchers have tried to develop over the last century to understand numerous human diseases. Understanding which biological signals are most important during anaesthesia is critically important. It is important that the anaesthesiologist understand both the signals themselves and the limitations introduced by the processes of acquisition. In this article, we provide an overview of different types of biological signals as well as the mechanisms applied to acquire them.Keywords: biological signals, signal acquisition, anaesthesiology, patient monitoring
Procedia PDF Downloads 1382112 Unequal Contributions of Parental Isolates in Somatic Recombination of the Stripe Rust Fungus
Authors: Xianming Chen, Yu Lei, Meinan Wang
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The dikaryotic basidiomycete fungus, Puccinia striiformis, causes stripe rust, one of the most important diseases of wheat and barley worldwide. The pathogen is largely reproduced asexually, and asexual recombination has been hypothesized to be one of the mechanisms for the pathogen variations. To test the hypothesis and understand the genetic process of asexual recombination, somatic recombinant isolates were obtained under controlled conditions by inoculating susceptible host plants with a mixture of equal quantity of urediniospores of isolates with different virulence patterns and selecting through a series of inoculation on host plants with different genes for resistance to one of the parental isolates. The potential recombinant isolates were phenotypically characterized by virulence testing on the set of 18 wheat lines used to differentiate races of the wheat stripe rust pathogen, P. striiformis f. sp. tritici (Pst), for the combinations of Pst isolates; or on both sets of the wheat differentials and 12 barley differentials for identifying races of the barley stripe rust pathogen, P. striiformis f. sp. hordei (Psh) for combinations of a Pst isolate and a Psh isolate. The progeny and parental isolates were also genotypically characterized with 51 simple sequence repeat and 90 single-nucleotide polymorphism markers. From nine combinations of parental isolates, 68 potential recombinant isolates were obtained, of which 33 (48.5%) had similar virulence patterns to one of the parental isolates, and 35 (51.5%) had virulence patterns distinct from either of the parental isolates. Of the 35 isolates of distinct virulence patterns, 11 were identified as races that had been previously detected from natural collections and 24 were identified as new races. The molecular marker data confirmed 66 of the 68 isolates as recombinants. The percentages of parental marker alleles ranged from 0.9% to 98.9% and were significantly different from equal proportions in the recombinant isolates. Except for a couple of combinations, the greater or less contribution was not specific to any particular parental isolates as the same parental isolates contributed more to some of the progeny isolates but less to the other progeny isolates in the same combination. The unequal contributions by parental isolates appear to be a general role in somatic recombination for the stripe rust fungus, which may be used to distinguish asexual recombination from sexual recombination in studying the evolutionary mechanisms of the highly variable fungal pathogen.Keywords: molecular markers, Puccinia striiformis, somatic recombination, stripe rust
Procedia PDF Downloads 2432111 Characteristics of Children Heart Rhythm Regulation with Acute Respiratory Diseases
Authors: D. F. Zeynalov, T. V. Kartseva, O. V. Sorokin
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Currently, approaches to assess cardiointervalography are based on the calculation of data variance intervals RR. However, they do not allow the evaluation of features related to a period of the cardiac cycle, so how electromechanical phenomena during cardiac subphase are characterized by differently directed changes. Therefore, we have proposed a method of subphase analysis of the cardiac cycle, developed in the department of hominal physiology Novosibirsk State Medical University to identify the features of the dispersion subphase of the cardiac cycle. In the present paper we have examined the 5-minute intervals cardiointervalography (CIG) to isolate RR-, QT-, ST-ranges in healthy children and children with acute respiratory diseases (ARD) in comparison. It is known that primary school-aged children suffer at ARD 5-7 times per year. Consequently, it is one of the most relevant problems in pediatrics. It is known that the spectral indices and indices of temporal analysis of heart rate variability are highly sensitive to the degree of intoxication during immunological process. We believe that the use of subphase analysis of heart rate will allow more thoroughly evaluate responsiveness of the child organism during the course of ARD. The study involved 60 primary school-aged children (30 boys and 30 girls). In order to assess heart rhythm regulation, the record CIG was used on the "VNS-Micro" device of Neurosoft Company (Ivanovo) for 5 minutes in the supine position and 5 minutes during active orthostatic test. Subphase analysis of variance QT-interval and ST-segment was performed on the "KardioBOS" software Biokvant Company (Novosibirsk). In assessing the CIG in the supine position and in during orthostasis of children with acute respiratory diseases only RR-intervals are observed typical trend of general biological reactions through pressosensitive compensation mechanisms to lower blood pressure, but compared with healthy children the severity of the changes is different, of sick children are more pronounced indicators of heart rate regulation. But analysis CIG RR-intervals and analysis subphase ST-segment have yielded conflicting trends, which may be explained by the different nature of the intra- and extracardiac influences on regulatory mechanisms that implement the various phases of the cardiac cycle.Keywords: acute respiratory diseases, cardiointervalography, subphase analysis, cardiac cycle
Procedia PDF Downloads 2752110 Autophagy Defects That Modify Human Immune Cell Metabolism and Promote Aging-Associated Inflammation
Authors: Grace McCambridge, Alanna Keady, Madhur Agrawal, Dequina Nicholas Alvarado, Barbara Nikolajczyk, Leena Panneerseelan-Bharath
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Age is a non-modifiable risk factor for the inflammation that underlies pathologies such as type 2 diabetes mellitus (T2DM). Inflammation, as indicated by circulating cytokines, rises in aging, but mechanisms that promote this ‘inflammaging’ remain poorly defined. Furthermore, downstream consequences of inflammaging, including the development of an inflammatory profile that predicts comorbidities like T2DM, remain speculative. We tested the possibility that natural aging-associated changes in autophagy, a process that is compromised in both aging and T2DM, regulates inflammatory profiles in older subjects. Our data showed that circulating CD4⁺ T cells from older compared to younger subjects have (i) defects in autophagy; (ii) higher mitochondria accumulation; (iii) a failure to metabolically shift from oxidative phosphorylation to anaerobic glycolysis upon αCD3/CD28 activation; (iv) more reactive oxygen species (ROS) accumulation; and (v) a cytokine profile that recapitulates the Th17 profile that predicts T2DM. ROS scavenging in cells from older subjects restored mitochondrial mass and membrane potential (indicators of improved autophagy) and reduced Th17 cytokines to amounts made by T cells from younger subjects. Knock-down of the autophagy protein Atg3 in T cells from younger subjects increased mitochondrial accumulation and Th17 cytokines. To begin translating these findings to clinical practice, we showed that physiological concentrations of the diabetes drug metformin (100 µM) added in vitro enhanced autophagy, prevented mitochondria and ROS accumulation, increased anaerobic glycolysis, and decreased Th17 cytokines in activated CD4⁺ T cells from older subjects. Metformin therefore improves autophagy and multiple downstream pro-inflammatory mechanisms CD4⁺ T cells from older subjects. We conclude that autophagy improvement ameliorates the development of a T2DM-predictive Th17 profile in aging, and thus holds promise for delay or prevention of aging-associated metabolic decline.Keywords: autophagy, mitochondrial turnover, ROS, glycolysis
Procedia PDF Downloads 1642109 The Impact of Water Reservoirs on Biodiversity and Food Security and the Creation of Adaptation Mechanisms
Authors: Inom S. Normatov, Abulqosim Muminov, Parviz I. Normatov
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Problems of food security and the preservation of reserved zones in the region of Central Asia under the conditions of the climate change induced by the placement and construction of large reservoirs are considered. The criteria for the optimum placement and construction of reservoirs that entail the minimum impact on the environment are established. The need for the accounting of climatic parameters is shown by the calculation of the water quantity required for the irrigation of agricultural lands.Keywords: adaptation, biodiversity, food security, water reservoir, risk
Procedia PDF Downloads 2562108 Pathology of Explanted Transvaginal Meshes
Authors: Vladimir V. Iakovlev, Erin T. Carey, John Steege
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The use of polypropylene mesh devices for Pelvic Organ Prolapse (POP) spread rapidly during the last decade, yet our knowledge of the mesh-tissue interaction is far from complete. We aimed to perform a thorough pathological examination of explanted POP meshes and describe findings that may explain mechanisms of complications resulting in product excision. We report a spectrum of important findings, including nerve ingrowth, mesh deformation, involvement of detrusor muscle with neural ganglia, and polypropylene degradation. Analysis of these findings may improve and guide future treatment strategies.Keywords: transvaginal, mesh, nerves, polypropylene degradation
Procedia PDF Downloads 4022107 Heart Rate Variability as a Measure of Dairy Calf Welfare
Authors: J. B. Clapp, S. Croarkin, C. Dolphin, S. K. Lyons
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Chronic pain or stress in farm animals impacts both on their welfare and productivity. Measuring chronic pain or stress can be problematic using hormonal or behavioural changes because hormones are modulated by homeostatic mechanisms and observed behaviour can be highly subjective. We propose that heart rate variability (HRV) can quantify chronic pain or stress in farmed animal and represents a more robust and objective measure of their welfare.Keywords: dairy calf, welfare, heart rate variability, non-invasive, biomonitor
Procedia PDF Downloads 6002106 Exploration of Cone Foam Breaker Behavior Using Computational Fluid Dynamic
Authors: G. St-Pierre-Lemieux, E. Askari Mahvelati, D. Groleau, P. Proulx
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Mathematical modeling has become an important tool for the study of foam behavior. Computational Fluid Dynamic (CFD) can be used to investigate the behavior of foam around foam breakers to better understand the mechanisms leading to the ‘destruction’ of foam. The focus of this investigation was the simple cone foam breaker, whose performance has been identified in numerous studies. While the optimal pumping angle is known from the literature, the contribution of pressure drop, shearing, and centrifugal forces to the foam syneresis are subject to speculation. This work provides a screening of those factors against changes in the cone angle and foam rheology. The CFD simulation was made with the open source OpenFOAM toolkits on a full three-dimensional model discretized using hexahedral cells. The geometry was generated using a python script then meshed with blockMesh. The OpenFOAM Volume Of Fluid (VOF) method was used (interFOAM) to obtain a detailed description of the interfacial forces, and the model k-omega SST was used to calculate the turbulence fields. The cone configuration allows the use of a rotating wall boundary condition. In each case, a pair of immiscible fluids, foam/air or water/air was used. The foam was modeled as a shear thinning (Herschel-Buckley) fluid. The results were compared to our measurements and to results found in the literature, first by computing the pumping rate of the cone, and second by the liquid break-up at the exit of the cone. A 3D printed version of the cones submerged in foam (shaving cream or soap solution) and water, at speeds varying between 400 RPM and 1500 RPM, was also used to validate the modeling results by calculating the torque exerted on the shaft. While most of the literature is focusing on cone behavior using Newtonian fluids, this works explore its behavior in shear thinning fluid which better reflects foam apparent rheology. Those simulations bring new light on the cone behavior within the foam and allow the computation of shearing, pressure, and velocity of the fluid, enabling to better evaluate the efficiency of the cones as foam breakers. This study contributes to clarify the mechanisms behind foam breaker performances, at least in part, using modern CFD techniques.Keywords: bioreactor, CFD, foam breaker, foam mitigation, OpenFOAM
Procedia PDF Downloads 2052105 Operational Measures for Greenhouse Gas Reduction from Ships
Authors: Gorana Jelic Mrcelic
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In order to reduce greenhouse gas emissions from ships, technical and operational measures can be used. Operational measures are easier and cheaper compared to technical measures, so are well recommended. One of the most cost-effective operational measure is fuel consumption. Fuel consumption can be reduced by various options but it sometimes needs investments in new equipment, new procedures and crew education. In order to implement operational measures in everyday procedures and routines on board, good understanding of the mechanisms by which these measures work is essential for the seamen.Keywords: green shipping, gas emission reduction, operational measures, seamen
Procedia PDF Downloads 5162104 Characterization of a Putative Type 1 Toxin-Antitoxin System in Shigella Flexneri
Authors: David Sarpong, Waleed Khursheed, Ernest Danquah, Erin Murphy
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Shigella is a pathogenic bacterium responsible for shigellosis, a severe diarrheal disease that claims the lives of immunocompromised individuals worldwide. To develop therapeutics against this disease, an understanding of the molecular mechanisms underlying the pathogen’s physiology is crucial. Small non-coding RNAs (sRNAs) have emerged as important regulators of bacterial physiology, including as components of toxin-antitoxin systems. In this study, we investigated the role of RyfA in S. flexneri physiology and virulence. RyfA, originally identified as an sRNA in Escherichia coli, is conserved within the Enterobacteriaceae family, including Shigella. Whereas two copies of ryfA are present in S. dysenteriae, all other Shigella species contain only one copy of the gene. Additionally, we identified a putative open reading frame within the RyfA transcript, suggesting that it may be a dual-functioning gene encoding a small protein in addition to its sRNA function. To study ryfA in vitro, we cloned the gene into an inducible plasmid and observed the effect on bacterial growth. Here, we report that RyfA production inhibits the growth of S. flexneri, and this inhibition is dependent on the contained open reading frame. In-silico analyses have revealed the presence of two divergently transcribed sRNAs, RyfB1 and RyfB2, which share nucleotide complementarity with RyfA and thus are predicted to function as anti-toxins. Our data demonstrate that RyfB2 has a stronger antitoxin effect than RyfB1. This regulatory pattern suggests a novel form of a toxin-antitoxin system in which the activity of a single toxin is inhibited to varying degrees by two sRNA antitoxins. Studies are ongoing to investigate the regulatory mechanism(s) of the antitoxin genes, as well as the downstream targets and mechanism of growth inhibition by the RyfA toxin. This study offers distinct insights into the regulatory mechanisms underlying Shigella physiology and may inform the development of new anti-Shigella therapeutics.Keywords: sRNA, shigella, toxin-antitoxin, Type 1 toxin antitoxin
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