Search results for: auction mechanism
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3055

Search results for: auction mechanism

2545 Interaction of GCN5L1 with WHAMM and KIF5B Regulates Autolysosome Tubulation

Authors: Allen Seylani

Abstract:

Lysosome-dependent autophagy is a nutrient-deprivation-induced evolutionarily conserved intracellular recycling program that sequestrates intracellular cargo into autophagosomes (AP), which then fuse with lysosomes to form autolysosomes (ALs) for cargo digestion. To restore free lysosomes, autophagic lysosome reformation (ALR) is initiated by extrusion of tubular structures from autolysosomes at the final stage of autophagy, in a process called lysosomal tubulation (LT). This project aimed to investigate the molecular mechanism of GCN5L1 in LT and the following lysosomal signaling. GCN5L1 belongs to the BORC multiprotein complexes and is involved in controlling lysosomal trafficking; however, the effect of GCN5L1 on lysosome tubulation remains largely unknown. Genetic ablation of GCN5L1 in the mouse primary hepatocytes showed dramatically increased autolysosomes (ALs), decreased lysosome regeneration and absence of lysosomal tubulation. This phenotype suggests the possibility of disruption in lysosome tubulation, which results in the disturbance of the overall lysosome homeostasis. The formation of tubulars from ALs requires kinesin motor protein KIF5B. Immunoprecipitation was employed and confirmed the interaction of GCN5L1 with the ARL8B-KIF5B complex, which recruited KIF5B to ALs. At the same time, GCN5L1 interacted with WHAMM, which promotes the actin nucleation factor, which brings actin cytoskeleton to ALs and initiates LT. Furthermore, impaired LT in GCN5L1 deficient hepatocytes was restored by overexpression of GCN5L1, and this rescue effect was attenuated by knockdown of KIF5B. Additionally, lysosomal mTORC1 activity was upregulated in GCN5L1-/- hepatocytes, while inhibition of mTORC1 abrogated the GCN5L1 mediated rescue of LT in knockout hepatocytes. Altogether these findings revealed a novel mechanism of ALR, in which a simultaneous interaction of GCN5L1 with KIF5B and WHAMM is required for LT and downstream mTORC1 signaling.

Keywords: autophagy, autolysosome, GCN5L1, lysosome

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2544 Deubiquitinase USP35 Regulates Mitosis Progression by Blocking CDH1-Mediated Degradation of Aurora B.

Authors: Jinyoung Park, Eun Joo Song

Abstract:

Introduction: Deubiquitinating enzymes (DUBs) are proteases that cleave ubiquitin or ubiquitin-like modifications on substrates. Deubiquitination could regulate cellular physiology, such as signal transduction, DNA damage and repair, and cell cycle progression. Although more than 100 DUBs are encoded in the human and the importance of DUBs has been realized, the functions of most DUBs are unknown. This study aims to identify the molecular mechanism by which deubiquitinating enzyme USP35 regulates cell cycle progression for the first time. Methods: USP35 RNAi was mainly used to identify the function of USP35 in cell cycle progression. To find substrates of USP35, we analyzed protein-protein interaction using LC-MS. Several biological methods, such as ubiquitination assay, cell synchronization, immunofluorescence, and immunoprecipitation assay were used to investigate the exact mechanism by which USP35 affects successful completion of mitosis. Results: USP35 knockdown caused not only reduction of mitotic cell number but also induction of mitotic cells with abnormal spindle formation. Actually, cell proliferation was decreased by USP35 knockdown. Interestingly, we found that loss of USP35 decreased the stability and expression of Aurora B, a member of chromosomal passenger complex (CPC), and the phosphorylation of its substrate. Indeed, USP35 interacted with Aurora B and deubiquitinated it. In addition, USP35 knockdown induced abnormal localization of Aurora B in mitotic cells. Finally, CDH1-mediated ubiquitination of Aurora B level was rescued by USP35 overexpression, but not inactive form of USP35, USP35 C450A. Discussion: Our findings suggest that USP35 regulates Aurora B-mediated mitotic spindle assembly and G2-M transition by blocking CDH1-induced degradation of Aurora B.

Keywords: USP35, HSP90, Aurora B, cell cycle progression

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2543 Sudan’s Approach to Knowledge Management in Disaster Management

Authors: Mohamed Abdalla Elamein Boshara, Peter Charles Woods, Nour Eldin Mohamed Elshaiekh

Abstract:

Knowledge Management has become very important for Disaster Management response and planning. This paper proposes the implementation of a Knowledge Management System with a sustainable data collection mechanism for reliable and timely information management to support decision makers in making the right decisions in the timely manner.

Keywords: knowledge management, disaster management, incident tracking, web application

Procedia PDF Downloads 754
2542 Metaphors Underlying Idiomatic Expressions in Trilingual Perspective: Contributions to the Teaching of Lexicon and to Materials Development

Authors: Marilei Amadeu Sabino

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Idiomatic expressions are linguistic phraseologisms present in natural languages. Known to be metaphorical linguistic combinations, a good majority of them provide elements that reveal important cultural aspects of their linguistic community through their metaphors. With the advent of Cognitive Linguistics (more specifically of Cognitive Semantics), the metaphor ceased to be related to poetic language and rhetorical embellishment and came to be seen as part of simple everyday language, reflecting the way human beings think, act and conceive reality, i. e., a fundamental mechanism of human conceptualizations of the world. In this sense, it came to be conceived as an inevitable mechanism for representing the nature of thought and language. The speakers, in conceptualizing reality, often use metaphorically parts of the body in expressions known as somatic. Several conceptual metaphors appear to be potentially universal or near-universal, because people across the world share certain bodily experiences. In these terms, many linguistic metaphors may be identical or very similar in several languages. These similarities, according to the Theory of Conceptual Metaphor, derive from universal aspects of the human body. Thus, this research aims to investigate the nature of some metaphors underlying somatic idiomatic expressions of Portuguese, Italian and English languages, establishing a pattern of similarities and differences among them from a trilingual perspective. The analysis shows that much of the studied expressions are really structurally, semantically and metaphorically identical or similar in the three languages. These findings incite relevant discussions concerning mother and foreign language learning and aim to contribute to the teaching of phraseological Lexicon as well as to materials development in mono and multilingual perspectives.

Keywords: idiomatic expressions, materials development, metaphors, phraseological lexicon, teaching and learning

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2541 Corrosion Protection and Failure Mechanism of ZrO₂ Coating on Zirconium Alloy Zry-4 under Varied LiOH Concentrations in Lithiated Water at 360°C and 18.5 MPa

Authors: Guanyu Jiang, Donghai Xu, Huanteng Liu

Abstract:

After the Fukushima-Daiichi accident, the development of accident tolerant fuel cladding materials to improve reactor safety has become a hot topic in the field of nuclear industry. ZrO₂ has a satisfactory neutron economy and can guarantee the fission chain reaction process, which enables it to be a promising coating for zirconium alloy cladding. Maintaining a good corrosion resistance in primary coolant loop during normal operations of Pressurized Water Reactors is a prerequisite for ZrO₂ as a protective coating on zirconium alloy cladding. Research on the corrosion performance of ZrO₂ coating in nuclear water chemistry is relatively scarce, and existing reports failed to provide an in-depth explanation for the failure causes of ZrO₂ coating. Herein, a detailed corrosion process of ZrO₂ coating in lithiated water at 360 °C and 18.5 MPa was proposed based on experimental research and molecular dynamics simulation. Lithiated water with different LiOH solutions in the present work was deaerated and had a dissolved oxygen concentration of < 10 ppb. The concentration of Li (as LiOH) was determined to be 2.3 ppm, 70 ppm, and 500 ppm, respectively. Corrosion tests were conducted in a static autoclave. Modeling and corresponding calculations were operated on Materials Studio software. The calculation of adsorption energy and dynamics parameters were undertaken by the Energy task and Dynamics task of the Forcite module, respectively. The protective effect and failure mechanism of ZrO₂ coating on Zry-4 under varied LiOH concentrations was further revealed by comparison with the coating corrosion performance in pure water (namely 0 ppm Li). ZrO₂ coating provided a favorable corrosion protection with the occurrence of localized corrosion at low LiOH concentrations. Factors influencing corrosion resistance mainly include pitting corrosion extension, enhanced Li+ permeation, short-circuit diffusion of O²⁻ and ZrO₂ phase transformation. In highly-concentrated LiOH solutions, intergranular corrosion, internal oxidation, and perforation resulted in coating failure. Zr ions were released to coating surface to form flocculent ZrO₂ and ZrO₂ clusters due to the strong diffusion and dissolution tendency of α-Zr in the Zry-4 substrate. Considering that primary water of Pressurized Water Reactors usually includes 2.3 ppm Li, the stability of ZrO₂ make itself a candidate fuel cladding coating material. Under unfavorable conditions with high Li concentrations, more boric acid should be added to alleviate caustic corrosion of ZrO₂ coating once it is used. This work can provide some references to understand the service behavior of nuclear coatings under variable water chemistry conditions and promote the in-pile application of ZrO₂ coating.

Keywords: ZrO₂ coating, Zry-4, corrosion behavior, failure mechanism, LiOH concentration

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2540 Anti-Phosphorylcholine T Cell Dependent Antibody

Authors: M. M. Rahman, A. Liu, A. Frostegard, J. Frostegard

Abstract:

The human immune system plays an essential role in cardiovascular disease (CVD) and atherosclerosis. Our earlier studies showed that major immunocompetent cells including T cells are activated by phosphorylcholine epitope. Further, we have determined for the first time in a clinical cohort that antibodies against phosphorylcholine (anti-PC) are negatively and independently associated with the development of atherosclerosis and thus a low risk of cardiovascular diseases. It is still unknown whether activated T cells play a role in anti-PC production. Here we aim to clarify the role of T cells in anti-PC production. B cell alone, or with CD3 T, CD4 T or with CD8 T cells were cultured in polystyrene plates to examine anti-PC IgM production. In addition to mixed B cell with CD3 T cell culture, B cells with CD3 T cells were also cultured in transwell co-culture plates. Further, B cells alone and mixed B cell with CD3 T cell cultures with or without anti-HLA 2 antibody were cultured for 6 days. Anti-PC IgM was detected by ELISA in independent experiments. More than 8 fold higher levels of anti-PC IgM were detected by ELISA in mixed B cell with CD3 T cell cultures in comparison to B cells alone. After the co-culture of B and CD3 T cells in transwell plates, there were no increased antibody levels indicating that B and T cells need to interact to augment anti-PC IgM production. Furthermore, anti-PC IgM was abolished by anti-HLA 2 blocking antibody in mixed B and CD3 T cells culture. In addition, the lack of increased anti-PC IgM in mixed B with CD8 T cells culture and the increased levels of anti-PC in mixed B with CD4 T cells culture support the role of helper T cell for the anti-PC IgM production. Atherosclerosis is a major cause of cardiovascular diseases, but anti-PC IgM is a protection marker for atherosclerosis development. Understanding the mechanism involved in the anti-PC IgM regulation could play an important role in strategies to raise anti-PC IgM. Studies suggest that anti-PC is T-cell independent antibody, but our study shows the major role of T cell in anti-PC IgM production. Activation of helper T cells by immunization could be a possible mechanism for raising anti-PC levels.

Keywords: anti-PC, atherosclerosis, aardiovascular diseases, phosphorylcholine

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2539 Oxidosqualene Cyclase: A Novel Inhibitor

Authors: Devadrita Dey Sarkar

Abstract:

Oxidosqualene cyclase is a membrane bound enzyme in which helps in the formation of steroid scaffold in higher organisms. In a highly selective cyclization reaction oxidosqualene cyclase forms LANOSTEROL with seven chiral centres starting from the linear substrate 2,3-oxidosqualene. In humans OSC in cholesterol biosynthesis it represents a target for the discovery of novel anticholesteraemic drugs that could complement the widely used statins. The enzyme oxidosqualene: lanosterol cyclase (OSC) represents a novel target for the treatment of hypercholesterolemia. OSC catalyzes the cyclization of the linear 2,3-monoepoxysqualene to lanosterol, the initial four-ringed sterol intermediate in the cholesterol biosynthetic pathway. OSC also catalyzes the formation of 24(S), 25-epoxycholesterol, a ligand activator of the liver X receptor. Inhibition of OSC reduces cholesterol biosynthesis and selectively enhances 24(S),25-epoxycholesterol synthesis. Through this dual mechanism, OSC inhibition decreases plasma levels of low-density lipoprotein (LDL)-cholesterol and prevents cholesterol deposition within macrophages. The recent crystallization of OSC identifies the mechanism of action for this complex enzyme, setting the stage for the design of OSC inhibitors with improved pharmacological properties for cholesterol lowering and treatment of atherosclerosis. While studying and designing the inhibitor of oxidosqulene cyclase, I worked on the pdb id of 1w6k which was the most worked on pdb id and I used several methods, techniques and softwares to identify and validate the top most molecules which could be acting as an inhibitor for oxidosqualene cyclase. Thus, by partial blockage of this enzyme, both an inhibition of lanosterol and subsequently cholesterol formation as well as a concomitant effect on HMG-CoA reductase can be achieved. Both effects complement each other and lead to an effective control of cholesterol biosynthesis. It is therefore concluded that 2,3-oxidosqualene cyclase plays a crucial role in the regulation of intracellular cholesterol homeostasis. 2,3-Oxidosqualene cyclase inhibitors offer an attractive approach for novel lipid-lowering agents.

Keywords: anticholesteraemic, crystallization, statins, homeostasis

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2538 Implementation of European Court of Human Right Judgments and State Sovereignty

Authors: Valentina Tereshkova

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The paper shows how the relationship between international law and national sovereignty is viewed through the implementation of European Court of Human Right judgments. Methodology: Сonclusions are based on a survey of representatives of the legislative authorities and judges of the Krasnoyarsk region, the Rostov region, Sverdlovsk region and Tver region. The paper assesses the activities of the Russian Constitutional Court from 1998 to 2015 related to the establishment of the implementation mechanism and the Russian Constitutional Court judgments of 14.07.2015, № 21-P and of 19.04.2016, № 12-P where the Constitutional Court stated the impossibility of executing ECtHR judgments. I. Implementation of ECHR judgments by courts and other authorities. Despite the publication of the report of the RF Ministry of Justice on the implementation, we could not find any formal information on the Russian policy of the ECtHR judgment implementation. Using the results of the survey, the paper shows the effect of ECtHR judgments on law and legal practice in Russia. II. Implementation of ECHR judgments by Russian Constitutional Court. Russian Constitutional Court had implemented the ECtHR judgments. However, the Court determined on July, 14, 2015 its competence to consider the question of implementation of ECHR judgments. Then, it stated that the execution of the judgment [Anchugov and Gladkov case] was impossible because the Russian Constitution has the highest legal force on April, 19, 2016. Recently the CE Committee of Ministers asked Russia to provide ‘without further delay’ a compensation plan for the Yukos case. On November 11, 2016, Constitutional Court accepted a request from the Ministry of Justice to consider the possibility of execution of the ECtHR judgment in the Yukos case. Such a request has been made possible due to a lack of implementation mechanism. Conclusion: ECtHR judgments are as an effective tool to solve the structural problems of a legal system. However, Russian experts consider the ECHR as a tool of protection of individual rights. The paper shows link between the survey results and the absence of the implementation mechanism. New Article 104 par. 2 and Article 106 par. 2 of the Federal Law of the Constitutional Court are in conflict with international obligations of the Convention on the Law on Treaties 1969 and Article 46 ECHR. Nevertheless, a dialogue may be possible between Constitutional Court and the ECtHR. In its judgment [19.04.2016] the Constitutional Court determined that the general measures to ensure fairness, proportionality and differentiation of the restrictions of voting rights were possible in judicial practice. It also stated the federal legislator had the power ‘to optimize the system of Russian criminal penalties’. Despite the fact that the Constitutional Court presented the Görgülü case [Görgülü v Germany] as an example of non-execution of the ECtHR judgment, the paper proposes to draw on the experience of German Constitutional Court, which in the Görgülü case, on the one hand, stressed national sovereignty and, on the other hand, took advantage of this sovereignty, to resolve the issue in accordance with the ECHR.

Keywords: implementation of ECtHR judgments, sovereignty, supranational jurisdictions, principle of subsidiarity

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2537 Institutional Levels Entrepreneurial Orientations and Social Entrepreneurial Intentions: Understanding the Mediating Role of Empathy

Authors: Paulson Young Ofenimu Okhawere

Abstract:

Research suggests that the main trait differentiating social entrepreneurs from traditional entrepreneurs is empathy. And although prior research has established the relevance of empathy in predicting social entrepreneurial intentions in different contexts, its usefulness at predicting social entrepreneurial intentions in emerging economy like Nigeria is yet to be well established. Whereas, it is well known that students in tertiary institutions in Nigeria (e.g. Universities, Polytechnics, and Colleges of Education) are given entrepreneurial orientations by being made to offer compulsory courses in entrepreneurship, research focusing on the effect of such students’ entrepreneurial orientation on entrepreneurial intentions is scant. To address this gap in the entrepreneurship literature, this study attempts to enhance our understanding by focusing on students selected from one University of Technology, one Polytechnic, and one College of Education in Niger State of Nigeria. The purpose of this study, therefore, is to examine the mechanism through which students’ institutional level entrepreneurial orientations affect their social entrepreneurial intentions and the role empathy plays in this relationship. Building on complexity theory (Satish & Streufert, 2003, 2001), this study proposes empathy as a proximal antecedent of social entrepreneurial intentions and that it is the mechanism through which the students’ entrepreneurial orientations affect their social entrepreneurial intentions. Data collected from 598 respondents were analyzed using multilevel structural equation modelling with Mplus version 7.3. The findings reveal that (i) although students’ entrepreneurial orientation directly relates to their social entrepreneurial intentions, this relationship differs according to the kind of institution; and (ii) students’ entrepreneurial orientations positively relates to social entrepreneurial intentions indirectly through empathy. Finally, the paper discusses the theoretical and practical implications of the findings, highlights the study’s strengths and limitations, and then maps out some directions for future research.

Keywords: institutional level, entrepreneurial orientation, empathy, social entrepreneurial intentions

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2536 A Sentence-to-Sentence Relation Network for Recognizing Textual Entailment

Authors: Isaac K. E. Ampomah, Seong-Bae Park, Sang-Jo Lee

Abstract:

Over the past decade, there have been promising developments in Natural Language Processing (NLP) with several investigations of approaches focusing on Recognizing Textual Entailment (RTE). These models include models based on lexical similarities, models based on formal reasoning, and most recently deep neural models. In this paper, we present a sentence encoding model that exploits the sentence-to-sentence relation information for RTE. In terms of sentence modeling, Convolutional neural network (CNN) and recurrent neural networks (RNNs) adopt different approaches. RNNs are known to be well suited for sequence modeling, whilst CNN is suited for the extraction of n-gram features through the filters and can learn ranges of relations via the pooling mechanism. We combine the strength of RNN and CNN as stated above to present a unified model for the RTE task. Our model basically combines relation vectors computed from the phrasal representation of each sentence and final encoded sentence representations. Firstly, we pass each sentence through a convolutional layer to extract a sequence of higher-level phrase representation for each sentence from which the first relation vector is computed. Secondly, the phrasal representation of each sentence from the convolutional layer is fed into a Bidirectional Long Short Term Memory (Bi-LSTM) to obtain the final sentence representations from which a second relation vector is computed. The relations vectors are combined and then used in then used in the same fashion as attention mechanism over the Bi-LSTM outputs to yield the final sentence representations for the classification. Experiment on the Stanford Natural Language Inference (SNLI) corpus suggests that this is a promising technique for RTE.

Keywords: deep neural models, natural language inference, recognizing textual entailment (RTE), sentence-to-sentence relation

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2535 Precipitation Kinetics of Al-7%Mg Alloy Studied by DSC and XRD

Authors: M. Fatmi, T. Chihi, M. A. Ghebouli, B. Ghebouli

Abstract:

This work presents the experimental results of the differential scanning calorimetry (DSC), hardness measurements (Hv) and XRD analysis, for order to investigate the kinetics of precipitation phenomena in Al-7%wt. Mg alloy. In the XRD and DSC curves indicates the formation of the intermediate precipitation of β-(Al3Mg2) phase respectively. The activation energies associated with the processes have been determined according to the three models proposed by Kissinger, Ozawa, and Boswell. Consequently, the nucleation mechanism of the precipitates can be explained. These phases are confirmed by XRD analysis.

Keywords: discontinuous precipitation, hardening, Al–Mg alloys, mechanical and mechatronics engineering

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2534 Biophysical Characterization of the Inhibition of cGAS-DNA Sensing by KicGAS, Kaposi's Sarcoma-Associated Herpesvirus Inhibitor of cGAS

Authors: D. Bhowmik, Y. Tian, Q. Yin, F. Zhu

Abstract:

Cyclic GMP-AMP synthase (cGAS), recognises cytoplasmic double-stranded DNA (dsDNA), indicative of bacterial and viral infections, as well as the leakage of self DNA by cellular dysfunction and stresses, to elicit the host's immune responses. Viruses also have developed numerous strategies to antagonize the cGAS-STING pathway. Kaposi's sarcoma-associated herpesvirus (KSHV) is a human DNA tumor virus that is the causative agent of Kaposi’s sarcoma and several other malignancies. To persist in the host, consequently causing diseases, KSHV must overcome the host innate immune responses, including the cGAS-STING DNA sensing pathway. We already found that ORF52 or KicGAS (KSHV inhibitor of cGAS), an abundant and basic gamma herpesvirus-conserved tegument protein, directly inhibits cGAS enzymatic activity. To better understand the mechanism, we have performed the biochemical and structural characterization of full-length KicGAS and various mutants in regarding binding to DNA. We observed that KicGAS is capable of self-association and identified the critical residues involved in the oligomerization process. We also characterized the DNA-binding of KicGAS and found that KicGAS cooperatively oligomerizes along the length of the double stranded DNA, the highly conserved basic residues at the c-terminal disordered region are crucial for DNA recognition. Deficiency in oligomerization also affects DNA binding. Thus DNA binding by KicGAS sequesters DNA and prevents it from being detected by cGAS, consequently inhibiting cGAS activation. KicGAS homologues also inhibit cGAS efficiently, suggesting inhibition of cGAS is evolutionarily conserved mechanism among gamma herpesvirus. These results highlight the important viral strategy to evade this innate immune sensor.

Keywords: Kaposi's sarcoma-associated herpesvirus, KSHV, cGAS, DNA binding, inhibition

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2533 A New Criterion for Removal of Fouling Deposit

Authors: D. Bäcker, H. Chaves

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The key to improve surface cleaning of the fouling is understanding of the mechanism of separation process of the deposit from the surface. The authors give basic principles of characterization of separation process and introduce a corresponding criterion. The developed criterion is a measure for the moment of separation of the deposit from the surface. For this purpose a new measurement technique is described.

Keywords: cleaning, fouling, separation, criterion

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2532 Experimental Research on Neck Thinning Dynamics of Droplets in Cross Junction Microchannels

Authors: Yilin Ma, Zhaomiao Liu, Xiang Wang, Yan Pang

Abstract:

Microscale droplets play an increasingly important role in various applications, including medical diagnostics, material synthesis, chemical engineering, and cell research due to features of high surface-to-volume ratio and tiny scale, which can significantly improve reaction rates, enhance heat transfer efficiency, enable high-throughput parallel studies as well as reduce reagent usage. As a mature technique to manipulate small amounts of liquids, droplet microfluidics could achieve the precise control of droplet parameters such as size, uniformity, structure, and thus has been widely adopted in the engineering and scientific research of multiple fields. Necking processes of the droplet in the cross junction microchannels are experimentally and theoretically investigated and dynamic mechanisms of the neck thinning in two different regimes are revealed. According to evolutions of the minimum neck width and the thinning rate, the necking process is further divided into different stages and the main driving force during each stage is confirmed. Effects of the flow rates and the cross-sectional aspect ratio on the necking process as well as the neck profile at different stages are provided in detail. The distinct features of the two regimes in the squeezing stage are well captured by the theoretical estimations of the effective flow rate and the variations of the actual flow rates in different channels are reasonably reflected by the channel width ratio. In the collapsing stage, the quantitative relation between the minimum neck width and the remaining time is constructed to identify the physical mechanism.

Keywords: cross junction, neck thinning, force analysis, inertial mechanism

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2531 Field-observed Thermal Fractures during Reinjection and Its Numerical Simulation

Authors: Wen Luo, Phil J. Vardon, Anne-Catherine Dieudonne

Abstract:

One key process that partly controls the success of geothermal projects is fluid reinjection, which benefits in dealing with waste water, maintaining reservoir pressure, and supplying heat-exchange media, etc. Thus, sustaining the injectivity is of great importance for the efficiency and sustainability of geothermal production. However, the injectivity is sensitive to the reinjection process. Field experiences have illustrated that the injectivity can be damaged or improved. In this paper, the focus is on how the injectivity is improved. Since the injection pressure is far below the formation fracture pressure, hydraulic fracturing cannot be the mechanism contributing to the increase in injectivity. Instead, thermal stimulation has been identified as the main contributor to improving the injectivity. For low-enthalpy geothermal reservoirs, which are not fracture-controlled, thermal fracturing, instead of thermal shearing, is expected to be the mechanism for increasing injectivity. In this paper, field data from the sedimentary low-enthalpy geothermal reservoirs in the Netherlands were analysed to show the occurrence of thermal fracturing due to the cooling shock during reinjection. Injection data were collected and compared to show the effects of the thermal fractures on injectivity. Then, a thermo-hydro-mechanical (THM) model for the near field formation was developed and solved by finite element method to simulate the observed thermal fractures. It was then compared with the HM model, decomposed from the THM model, to illustrate the thermal effects on thermal fracturing. Finally, the effects of operational parameters, i.e. injection temperature and pressure, on the changes in injectivity were studied on the basis of the THM model. The field data analysis and simulation results illustrate that the thermal fracturing occurred during reinjection and contributed to the increase in injectivity. The injection temperature was identified as a key parameter that contributes to thermal fracturing.

Keywords: injectivity, reinjection, thermal fracturing, thermo-hydro-mechanical model

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2530 An Analysis on the Hidden Transcripts and Power: A Cultural Study on Confliction between Mother and Daughter-in-Law in Contemporary Chinese Television Dramas

Authors: Xiaohui Pan

Abstract:

As the most influential media for the dissemination of Chinese culture, films and television dramas have played cognitive orientation in guiding young audience to understand its cultural value. Taking a retrospective overview of the Chinese domestic film and television dramas in the last decade, it is tangible to notice that Westernization has become irresistible force in the presentation of Chinese youth culture, such as the rise of sensibility, publicity of subjectivity, and the resistance to mainstream discourse. However, the process of deconstruction and transition of these film and television works on Western youth culture brought about more comprehensive conflicts and integration rather than providing a panoramic interpretation to young Chinese. Issues of tradition and modernization, oriental and Western, and serious thinking and the spirit of entertainment overwhelmed those Chinese works. This study attempts to examine the mechanism of young Chinese’s resistance, compromise and re-construction in their marriages during the dynamic cultural intergration between traditional Chinese culture and Western culture. To investigate such a mechanism, this study analyzed four Chinese television dramas themed on family ethics to reveal the conflictions between two generations, mother-in-law and daughter-in-law, aiming to identify their strategies of their struggles. Incorporating the theory of Scott's weapons of the weak, this study examines the dynamic model of the struggles content analysis on their hidden language and the power. The finding shows that young Chinese identified their self-awakening during the resistance. The study also finds out that the external factors might have the functions of switching the power from the strong end to the weak end. The finding of this study can provide useful insights for researchers in this area and for those in the process of exploring cultural integration issues.

Keywords: intergration, integration, resistance, youth culture

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2529 Time-Dependent Modulation on Depressive Responses and Circadian Rhythms of Corticosterone in Models of Melatonin Deficit

Authors: Jana Tchekalarova, Milena Atanasova, Katerina Georgieva

Abstract:

Melatonin deficit can cause a disturbance in emotional status and circadian rhythms of the endocrine system in the body. Both pharmacological and alternative approaches are applied for correction of dysfunctions driven by changes in circadian dynamics of many physiological indicators. In the present study, we tested and compare the beneficial effect of agomelatine (40 mg/kg, i.p. for 3 weeks) and endurance training on depressive behavior in two models of melatonin deficit in rat. The role of disturbed circadian rhythms of plasma melatonin and corticosterone secretion in the mechanism of these treatments was also explored. The continuous exercise program attenuated depressive responses associated with disrupted diurnal rhythm of home-cage motor activity, anhedonia in the sucrose preference test, and despair-like behavior in the forced swimming test were attenuated by agomelatine exposed to chronic constant light (CCL) and long-term exercise in pinealectomized rats. Parallel to the observed positive effect on the emotional status, agomelatine restored CCL-induced impairment of circadian patterns of plasma melatonin but not that of corticosterone. In opposite, exercise training diminished total plasma corticosterone levels and corrected its flattened pattern while it was unable to correct melatonin deficit in pinealectomy. These results suggest that the antidepressant-like effect of pharmacological and alternative approach might be mediated via two different mechanism, correction of the disturbed circadian rhythm of melatonin and corticosterone, respectively. Therefore, these treatment approaches might have a potential therapeutic application in different subpopulations of people characterized by a melatonin deficiency. This work was supported by the National Science Fund of Bulgaria (research grant # № DN 03/10; DN# 12/6).

Keywords: agomelatine, exercise training, melatonin deficit, corticosterone

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2528 Infusion Pump Historical Development, Measurement and Parts of Infusion Pump

Authors: Samuel Asrat

Abstract:

Infusion pumps have become indispensable tools in modern healthcare, allowing for precise and controlled delivery of fluids, medications, and nutrients to patients. This paper provides an overview of the historical development, measurement, and parts of infusion pumps. The historical development of infusion pumps can be traced back to the early 1960s when the first rudimentary models were introduced. These early pumps were large, cumbersome, and often unreliable. However, advancements in technology and engineering over the years have led to the development of smaller, more accurate, and user-friendly infusion pumps. Measurement of infusion pumps involves assessing various parameters such as flow rate, volume delivered, and infusion duration. Flow rate, typically measured in milliliters per hour (mL/hr), is a critical parameter that determines the rate at which fluids or medications are delivered to the patient. Accurate measurement of flow rate is essential to ensure the proper administration of therapy and prevent adverse effects. Infusion pumps consist of several key parts, including the pump mechanism, fluid reservoir, tubing, and control interface. The pump mechanism is responsible for generating the necessary pressure to push fluids through the tubing and into the patient's bloodstream. The fluid reservoir holds the medication or solution to be infused, while the tubing serves as the conduit through which the fluid travels from the reservoir to the patient. The control interface allows healthcare providers to program and adjust the infusion parameters, such as flow rate and volume. In conclusion, infusion pumps have evolved significantly since their inception, offering healthcare providers unprecedented control and precision in delivering fluids and medications to patients. Understanding the historical development, measurement, and parts of infusion pumps is essential for ensuring their safe and effective use in clinical practice.

Keywords: dip, ip, sp, is

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2527 A Design Framework for an Open Market Platform of Enriched Card-Based Transactional Data for Big Data Analytics and Open Banking

Authors: Trevor Toy, Josef Langerman

Abstract:

Around a quarter of the world’s data is generated by financial with an estimated 708.5 billion global non-cash transactions reached between 2018 and. And with Open Banking still a rapidly developing concept within the financial industry, there is an opportunity to create a secure mechanism for connecting its stakeholders to openly, legitimately and consensually share the data required to enable it. Integration and data sharing of anonymised transactional data are still operated in silos and centralised between the large corporate entities in the ecosystem that have the resources to do so. Smaller fintechs generating data and businesses looking to consume data are largely excluded from the process. Therefore there is a growing demand for accessible transactional data for analytical purposes and also to support the rapid global adoption of Open Banking. The following research has provided a solution framework that aims to provide a secure decentralised marketplace for 1.) data providers to list their transactional data, 2.) data consumers to find and access that data, and 3.) data subjects (the individuals making the transactions that generate the data) to manage and sell the data that relates to themselves. The platform also provides an integrated system for downstream transactional-related data from merchants, enriching the data product available to build a comprehensive view of a data subject’s spending habits. A robust and sustainable data market can be developed by providing a more accessible mechanism for data producers to monetise their data investments and encouraging data subjects to share their data through the same financial incentives. At the centre of the platform is the market mechanism that connects the data providers and their data subjects to the data consumers. This core component of the platform is developed on a decentralised blockchain contract with a market layer that manages transaction, user, pricing, payment, tagging, contract, control, and lineage features that pertain to the user interactions on the platform. One of the platform’s key features is enabling the participation and management of personal data by the individuals from whom the data is being generated. This framework developed a proof-of-concept on the Etheruem blockchain base where an individual can securely manage access to their own personal data and that individual’s identifiable relationship to the card-based transaction data provided by financial institutions. This gives data consumers access to a complete view of transactional spending behaviour in correlation to key demographic information. This platform solution can ultimately support the growth, prosperity, and development of economies, businesses, communities, and individuals by providing accessible and relevant transactional data for big data analytics and open banking.

Keywords: big data markets, open banking, blockchain, personal data management

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2526 Experimental and Numerical Study on the Effects of Oxygen Methane Flames with Water Dilution for Different Pressures

Authors: J. P. Chica Cano, G. Cabot, S. de Persis, F. Foucher

Abstract:

Among all possibilities to combat global warming, CO2 capture and sequestration (CCS) is presented as a great alternative to reduce greenhouse gas (GHG) emission. Several strategies for CCS from industrial and power plants are being considered. The concept of combined oxy-fuel combustion has been the most alternative solution. Nevertheless, due to the high cost of pure O2 production, additional ways recently emerged. In this paper, an innovative combustion process for a gas turbine cycle was studied: it was composed of methane combustion with oxygen enhanced air (OEA), exhaust gas recirculation (EGR) and H2O issuing from STIG (Steam Injection Gas Turbine), and the CO2 capture was realized by membrane separator. The effect on this combustion process was emphasized, and it was shown that a study of the influence of H2O dilution on the combustion parameters by experimental and numerical approaches had to be carried out. As a consequence, the laminar burning velocities measurements were performed in a stainless steel spherical combustion from atmospheric pressure to high pressure (up to 0.5 MPa), at 473 K for an equivalence ratio at 1. These experimental results were satisfactorily compared with Chemical Workbench v.4.1 package in conjunction with GRIMech 3.0 reaction mechanism. The good correlations so obtained between experimental and calculated flame speed velocities showed the validity of the GRIMech 3.0 mechanism in this domain of combustion: high H2O dilution, low N2, medium pressure. Finally, good estimations of flame speed and pollutant emissions were determined in other conditions compatible with real gas turbine. In particular, mixtures (composed of CH4/O2/N2/H2O/ or CO2) leading to the same adiabatic temperature were investigated. Influences of oxygen enrichment and H2O dilution (compared to CO2) were disused.

Keywords: CO₂ capture, oxygen enrichment, water dilution, laminar burning velocity, pollutants emissions

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2525 Decentralized Forest Policy for Natural Sal (Shorea robusta) Forests Management in the Terai Region of Nepal

Authors: Medani Prasad Rijal

Abstract:

The study outlines the impacts of decentralized forest policy on natural Sal (shorea robusta) forests in the Terai region of Nepal. The government has implemented community forestry program to manage the forest resources and improve the livelihood of local people collectively. The forest management authorities such as conserve, manage, develop and use of forest resources were shifted to the local communities, however, the ownership right of the forestland retained by the government. Local communities took the decision on harvesting, distribution, and sell of forest products by fixing the prices independently. The local communities were putting the low value of forest products and distributed among the user households on the name of collective decision. The decision of low valuation is devaluating the worth of forest products. Therefore, the study hypothesized that decision-making capacities are equally prominent next to the decentralized policy and program formulation. To accomplish the study, individual to group level discussions and questionnaire survey methods were applied with executive committee members and user households. The study revealed that the local intuition called Community Forest User Group (CFUG) committee normally took the decisions on consensus basis. Considering to the access and affording capacity of user households having poor economic backgrounds, low pricing mechanism of forest products has been practiced, even though the Sal timber is far expensive in the local market. The local communities thought that low pricing mechanism is accessible to all user households from poor to better off households. However, the analysis of forest products distribution opposed the assumption as most of the Sal timber, which is the most valuable forest product of community forest only purchased by the limited households of better economic conditions. Since the Terai region is heterogeneous by socio-economic conditions, better off households always have higher affording capacity and possibility of taking higher timber benefits because of low price mechanism. On the other hand, the minimum price rate of forest products has poor contribution in community fund collection. Consequently, it has poor support to carry out poverty alleviation activities to poor people. The local communities have been fixed Sal timber price rate around three times cheaper than normal market price, which is a strong evidence of forest product devaluation itself. Finally, the study concluded that the capacity building of local executives as the decision-makers of natural Sal forests is equally indispensable next to the policy and program formulation for effective decentralized forest management. Unilateral decentralized forest policy may devaluate the forest products rather than devolve of power to the local communities and empower to them.

Keywords: community forestry program, decentralized forest policy, Nepal, Sal forests, Terai

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2524 The Moderating Effect of Pathological Narcissism in the Relationship between Victim Justice Sensitivity and Anger Rumination

Authors: Isil Coklar-Okutkan, Miray Akyunus

Abstract:

Victim sensitivity is a form of justice sensitivity that reflects the tendency to perceive injustice to one’s disadvantage. Victim sensitivity is considered as a dysfunctional trait that predicts anger, aggression, uncooperative behavior, depression and anxiety. Indeed, exploring the mechanism of association between victim sensitivity and anger is clinically important since it can lead to externalizing and internalizing problems. This study aims to investigate the moderating role of pathological narcissism in the relationship between victim sensitivity and anger rumination. Through testing different models where subtypes of narcissism and anger rumination components are included independently, the specific mechanism of different ruminative processes in anger is investigated. The sample consisted of 311 undergraduate students from Turkey, 107 of whom were males, and 204 were females. Participants completed Justice Sensitivity Inventory-Victim Subscale, Pathological Narcissism Inventory and Anger Rumination Scale. In the proposed double moderation model, vulnerable and grandiose narcissism was the moderators in the relationship between victim justice sensitivity and anger rumination. Four separate models were tested where one of the four components of anger rumination (angry afterthoughts, thoughts of revenge, angry memories, understanding of causes) were the dependent variable in each model. Results revealed that two of the moderation models are significant. Firstly, grandiose narcissism is the only moderator in the relationship between victim sensitivity and thoughts of revenge. Secondly, vulnerable narcissism is the only moderator in the relationship between victim sensitivity and understanding causes. Accordingly, grandiose narcissism is positively associated with the thoughts of revenge, and vulnerable narcissism is positively associated with understanding causes, only when the level of victim sensitivity is high. To summarize, increased victim sensitivity leads to ruminative thoughts of revenge in individuals with grandiose narcissism, whereas it leads to rumination on causes of the incident in individuals with vulnerable narcissism. The clinical implications of the findings are discussed.

Keywords: anger rumination, victim sensitivity, grandiose narcissism, vulnerable narcissism

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2523 Temperature Dependent Current-Voltage (I-V) Characteristics of CuO-ZnO Nanorods Based Heterojunction Solar Cells

Authors: Venkatesan Annadurai, Kannan Ethirajalu, Anu Roshini Ramakrishnan

Abstract:

Copper oxide (CuO) and zinc oxide (ZnO) based coaxial (CuO-ZnO nanorods) heterojunction has been the interest of various research communities for solar cells, light emitting diodes (LEDs) and photodetectors applications. Copper oxide (CuO) is a p-type material with the band gap of 1.5 eV and it is considered to be an attractive absorber material in solar cells applications due to its high absorption coefficient and long minority carrier diffusion length. Similarly, n-type ZnO nanorods possess many attractive advantages over thin films such as, the light trapping ability and photosensitivity owing to the presence of oxygen related hole-traps at the surface. Moreover, the abundant availability, non-toxicity, and inexpensiveness of these materials make them suitable for potentially cheap, large area, and stable photovoltaic applications. However, the efficiency of the CuO-ZnO nanorods heterojunction based devices is greatly affected by interface defects which generally lead to the poor performance. In spite of having much potential, not much work has been carried out to understand the interface quality and transport mechanism involved across the CuO-ZnO nanorods heterojunction. Therefore, a detailed investigation of CuO-ZnO heterojunction is needed to understand the interface which affects its photovoltaic performance. Herein, we have fabricated the CuO-ZnO nanorods based heterojunction by simple hydrothermal and electrodeposition technique and investigated its interface quality by carrying out temperature (300 –10 K) dependent current-voltage (I-V) measurements under dark and illumination of visible light. Activation energies extracted from the temperature dependent I-V characteristics reveals that recombination and tunneling mechanism across the interfacial barrier plays a significant role in the current flow.

Keywords: heterojunction, electrical transport, nanorods, solar cells

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2522 Storm-water Management for Greenfield Area Using Low Impact Development Concept for Town Planning Scheme Mechanism

Authors: Sahil Patel

Abstract:

Increasing urbanization leads to a concrete forest. The effects of new development practices occur in the natural hydrologic cycle. Here the concerns have been raised about the groundwater recharge in sufficient quantity. With further development, porous surfaces reduce rapidly. A city like Ahmedabad, with a non-perennial river, is 100% dependent on groundwater. The Ahmedabad city receives its domestic use water from the Narmada river, located about 200 km away. The expenses to bring water is much higher. Ahmedabad city receives annually 800 mm rainfall, and mostly this water increases the local level waterlogging problems; after that, water goes to the Sabarmati river and merges into the sea. The existing developed area of Ahmedabad city is very dense, and does not offer many chances to change the built form and increase porous surfaces to absorb storm-water. Therefore, there is a need to plan upcoming areas with more effective solutions to manage storm-water. This paper is focusing on the management of stormwater for new development by retaining natural hydrology. The Low Impact Development (LID) concept is used to manage storm-water efficiently. Ahmedabad city has a tool called the “Town Planning Scheme,” which helps the local body drive new development by land pooling mechanism. This paper gives a detailed analysis of the selected area (proposed Town Planning Scheme area by the local authority) in Ahmedabad. Here the development control regulations for individual developers and some physical elements for public places are presented to manage storm-water. There is a different solution for the Town Planning scheme than that of the conventional way. A local authority can use it for any area, but it can be site-specific. In the end, there are benefits to locals with some financial analysis and comparisons.

Keywords: water management, green field development, low impact development, town planning scheme

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2521 Standards of Toxicity and Food Security in Brazil

Authors: Ana Luiza Da Gama E Souza

Abstract:

This article aims to discuss the problem of food insecurity in Brazil in what it refers to contamination of food by chemical substances such as herbicides, pesticides, and other contaminants. The issue will be faced by analyzing, on the one hand, the standards that guide the food system in the world and, on the other hand, human rights indicators whose purpose is to provide an effective monitoring of the State's obligations to guarantee food security, analyzing the implications of the former for the success of the latter. The methodology adopted in this article was bibliographic-documentary and consists of three moments of analysis. The first moment consists in the analysis of the reports of the Commission on Human Rights of the Organization of American States to identify the set of progress indicators developed by the Commission. This analysis will involve the new methodology used to evaluate the efficiency in monitoring food security in Brazil the case of using pesticides in the production of food at levels of toxicity not admitted by the inspection bodies. The second moment consists in evaluating the mechanism for monitoring food security in Brazil, which was initially established by the National Food Security Plan (PLANSAN) for 2012-2015 and improved by the II National Food Security Plan for 2016-2019. Those mechanisms were prepared by the Chamber (CAISAN), and have the function to compare the monitoring proposals with the results presented by CAISAN on the Indicators and Results Report of the National Plan for Food and Nutrition Security 2012-2015. The third moment was intended to understand, analyze and evaluate the standardization process of the agri-food system, especially regarding the level of toxicity standards, that is related to food safety monitoring as a guarantee of pesticide-free food. The results show the dependence between private standards of toxicity and the indicators of food safety that leads to inefficiency on monitoring that mechanism in Brazil.

Keywords: standards, indicators, human rights, food security

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2520 Multi-Particle Finite Element Modelling Simulation Based on Cohesive Zone Method of Cold Compaction Behavior of Laminar Al and NaCl Composite Powders

Authors: Yanbing Feng, Deqing Mei, Yancheng Wang, Zichen Chen

Abstract:

With the advantage of low volume density, high specific surface area, light weight and good permeability, porous aluminum material has the potential to be used in automotive, railway, chemistry and construction industries, etc. A layered powder sintering and dissolution method were developed to fabricate the porous surface Al structure with high efficiency. However, the densification mechanism during the cold compaction of laminar composite powders is still unclear. In this study, multi particle finite element modelling (MPFEM) based on the cohesive zone method (CZM) is used to simulate the cold compaction behavior of laminar Al and NaCl composite powders. To obtain its densification mechanism, the macro and micro properties of final compacts are characterized and analyzed. The robustness and accuracy of the numerical model is firstly verified by experimental results and data fitting. The results indicate that the CZM-based multi particle FEM is an effective way to simulate the compaction of the laminar powders and the fracture process of the NaCl powders. In the compaction of the laminar powders, the void is mainly filled by the particle rearrangement, plastic deformation of Al powders and brittle fracture of NaCl powders. Large stress is mainly concentrated within the NaCl powers and the contact force network is formed. The Al powder near the NaCl powder or the mold has larger stress distribution on its contact surface. Therefore, the densification process of cold compaction of laminar Al and NaCl composite powders is successfully analyzed by the CZM-based multi particle FEM.

Keywords: cold compaction, cohesive zone, multi-particle FEM, numerical modeling, powder forming

Procedia PDF Downloads 124
2519 Comparison Study of Capital Protection Risk Management Strategies: Constant Proportion Portfolio Insurance versus Volatility Target Based Investment Strategy with a Guarantee

Authors: Olga Biedova, Victoria Steblovskaya, Kai Wallbaum

Abstract:

In the current capital market environment, investors constantly face the challenge of finding a successful and stable investment mechanism. Highly volatile equity markets and extremely low bond returns bring about the demand for sophisticated yet reliable risk management strategies. Investors are looking for risk management solutions to efficiently protect their investments. This study compares a classic Constant Proportion Portfolio Insurance (CPPI) strategy to a Volatility Target portfolio insurance (VTPI). VTPI is an extension of the well-known Option Based Portfolio Insurance (OBPI) to the case where an embedded option is linked not to a pure risky asset such as e.g., S&P 500, but to a Volatility Target (VolTarget) portfolio. VolTarget strategy is a recently emerged rule-based dynamic asset allocation mechanism where the portfolio’s volatility is kept under control. As a result, a typical VTPI strategy allows higher participation rates in the market due to reduced embedded option prices. In addition, controlled volatility levels eliminate the volatility spread in option pricing, one of the frequently cited reasons for OBPI strategy fall behind CPPI. The strategies are compared within the framework of the stochastic dominance theory based on numerical simulations, rather than on the restrictive assumption of the Black-Scholes type dynamics of the underlying asset. An extended comparative quantitative analysis of performances of the above investment strategies in various market scenarios and within a range of input parameter values is presented.

Keywords: CPPI, portfolio insurance, stochastic dominance, volatility target

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2518 Deciphering Specific Host-Selective Toxin Interaction of Cassiicolin with Lipid Membranes and its Cytotoxicity on Rubber Leaves

Authors: Kien Xuan Ngo

Abstract:

Cassiicolin (Cas), a toxin produced by Corynespora cassiicola, is responsible for corynespora leaf fall (CLF) disease in rubber trees. Currently, the molecular mechanism of the cytotoxicity of Cas isoforms (i.e., Cas1, Cas2) on rubber leaves and its host selectivity have not been fully elucidated. This study analyzed the binding of Cas1 and Cas2 to membranes consisting of different plant lipids and their membrane-disruption activities. Using high-speed atomic force microscopy and confocal microscopy, this study reveals that the binding and disruption activities of Cas1 and Cas2 on lipid membranes are strongly dependent on the specific plant lipids. The negative phospholipids, glycerolipids, and sterols are more susceptible to membrane damage caused by Cas1 and Cas2 than neutral phospholipids and betaine lipids. In summary, This study unveils that (i) Cas1 and Cas2 directly damage and cause necrosis in the leaves of specific rubber clones; (ii) Cas1 and Cas2 can form biofilm-like structures on specific lipid membranes (negative phospholipids, glycerolipids, and sterols). The biofilm-like formation of Cas toxin plays an important role in selective disruption on lipid membranes; (iii) Vulnerability of the specific cytoplasmic membranes to the selective Cas toxin is the most remarkable feature of cytotoxicity of Cas toxin on plant cells. Finally, researcher’s exploration is crucial to understand the basic molecular mechanism underlying the host-selective toxic interaction of Cas toxin with cytoplasmic membranes in plant cells.

Keywords: cassiicolin, corynespora leaf fall disease, high-speed AFM, giant liposome vesicles

Procedia PDF Downloads 95
2517 Understanding Inhibitory Mechanism of the Selective Inhibitors of Cdk5/p25 Complex by Molecular Modeling Studies

Authors: Amir Zeb, Shailima Rampogu, Minky Son, Ayoung Baek, Sang H. Yoon, Keun W. Lee

Abstract:

Neurotoxic insults activate calpain, which in turn produces truncated p25 from p35. p25 forms hyperactivated Cdk5/p25 complex, and thereby induces severe neuropathological aberrations including hyperphosphorylated tau, neuroinflammation, apoptosis, and neuronal death. Inhibition of Cdk5/p25 complex alleviates aberrant phosphorylation of tau to mitigate AD pathology. PHA-793887 and Roscovitine have been investigated as selective inhibitors of Cdk5/p25 with IC50 values 5nM and 160nM, respectively, but their mechanistic studies remain unknown. Herein, computational simulations have explored the binding mode and interaction mechanism of PHA-793887 and Roscovitine with Cdk5/p25. Docking results suggested that PHA-793887 and Rsocovitine have occupied the ATP-binding site of Cdk5 and obtained highest docking (GOLD) score of 66.54 and 84.03, respectively. Furthermore, molecular dynamics (MD) simulation demonstrated that PHA-793887 and Roscovitine established stable RMSD of 1.09 Å and 1.48 Å with Cdk5/p25, respectively. Profiling of polar interactions suggested that each inhibitor formed hydrogen bonds (H-bond) with catalytic residues of Cdk5 and could remain stable throughout the molecular dynamics simulation. Additionally, binding free energy calculation by molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) suggested that PHA-793887 and Roscovitine had lowest binding free energies of -150.05 kJ/mol and -113.14 kJ/mol, respectively with Cdk5/p25. Free energy decomposition demonstrated that polar energy by H-bond between the Glu81 of Cdk5 and PHA-793887 is the essential factor to make PHA-793887 highly selective towards Cdk5/p25. Overall, this study provided substantial evidences to explore mechanistic interactions of the selective inhibitors of Cdk5/p25 and could be used as fundamental considerations in the development of structure-based selective inhibitors of Cdk5/p25.

Keywords: Cdk5/p25 inhibition, molecular modeling of Cdk5/p25, PHA-793887 and roscovitine, selective inhibition of Cdk5/p25

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2516 Susceptibility of Spodoptera littoralis, Field Populations in Egypt to Chlorantraniliprole and the Role of Detoxification Enzymes

Authors: Mohamed H. Khalifa, Fikry I. El-Shahawi, Nabil A. Mansour

Abstract:

The cotton leafworm, Spodoptera littoralis (Boisduval) is a major insect pest of vegetables and cotton crops in Egypt, and exhibits different levels of tolerance to certain insecticides. Chlorantraniliprole has been registered recently in Egypt for control this insect. The susceptibilities of three S. littoralis populations collected from El Behaira governorate, north Egypt to chlorantraniliprole were determined by leaf-dipping technique on 4th instar larvae. Obvious variation of toxicity was observed among the laboratory susceptible, and three field populations with LC50 values ranged between 1.53 µg/ml and 6.22 µg/ml. However, all the three field populations were less susceptible to chlorantraniliprole than a laboratory susceptible population. The most tolerant populations were sampled from El Delengat (ED) Province where S. littoralis had been frequently challenged by insecticides. Certain enzyme activity assays were carried out to be correlated with the mechanism of the observed field population tolerance. All field populations showed significantly enhanced activities of detoxification enzymes compared with the susceptible strain. The regression analysis between chlorantraniliprole toxicities and enzyme activities revealed that the highest correlation is between α-esterase or β-esterase (α-β-EST) activity and collected field strains susceptibility, otherwise this correlation is not significant (P > 0.05). Synergism assays showed the ED and susceptible strains could be synergized by known detoxification inhibitors such as piperonyl butoxide (PBO), triphenyl phosphate (TPP) and diethyl-maleate (DEM) at different levels (1.01-8.76-fold and 1.09-2.94 fold, respectively), TPP showed the maximum synergism in both strains. The results show that there is a correlation between the enzyme activity and tolerance, and carboxylic-esterase (Car-EST) is likely the main detoxification mechanism responsible for tolerance of S. littoralis to chlorantraniliprole.

Keywords: chlorantraniliprole, detoxification enzymes, Egypt, Spodoptera littoralis

Procedia PDF Downloads 249