Search results for: sterol regulatory element binding proteins
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5506

Search results for: sterol regulatory element binding proteins

4426 The Quantitative Optical Modulation of Dopamine Receptor-Mediated Endocytosis Using an Optogenetic System

Authors: Qiaoyue Kuang, Yang Li, Mizuki Endo, Takeaki Ozawa

Abstract:

G protein-coupled receptors (GPCR) are the largest family of receptor proteins that detect molecules outside the cell and activate cellular responses. Of the GPCRs, dopamine receptors, which recognize extracellular dopamine, are essential to mammals due to their roles in numerous physiological events, including autonomic movement, hormonal regulation, emotions, and the reward system in the brain. To precisely understand the physiological roles of dopamine receptors, it is important to spatiotemporally control the signaling mediated by dopamine receptors, which is strongly dependent on their surface expression. Conventionally, chemical-induced interactions were applied to trigger the endocytosis of cell surface receptors. However, these methods were subjected to diffusion and therefore lacked temporal and special precision. To further understand the receptor-mediated signaling and to control the plasma membrane expression of receptors, an optogenetic tool called E-fragment was developed. The C-terminus of a light-sensitive photosensory protein cyptochrome2 (CRY2) was attached to β-Arrestin, and the E-fragment was generated by fusing the C-terminal peptide of vasopressin receptor (V2R) to CRY2’s binding partner protein CIB. The CRY2-CIB heterodimerization triggered by blue light stimulation brings β-Arrestin to the vicinity of membrane receptors and results in receptor endocytosis. In this study, the E-fragment system was applied to dopamine receptors 1 and 2 (DRD1 and DRD2) to control dopamine signaling. First, confocal fluorescence microscope observation qualitatively confirmed the light-induced endocytosis of E-fragment fused receptors. Second, NanoBiT bioluminescence assay verified quantitatively that the surface amount of E-fragment labeled receptors decreased after light treatment. Finally, GloSensor bioluminescence assay results suggested that the E-fragment-dependent receptor light-induced endocytosis decreased cAMP production in DRD1 signaling and attenuated the inhibition effect of DRD2 on cAMP production. The developed optogenetic tool was able to induce receptor endocytosis by external light, providing opportunities to further understand numerous physiological activities by controlling receptor-mediated signaling spatiotemporally.

Keywords: dopamine receptors, endocytosis, G protein-coupled receptors, optogenetics

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4425 Ebola Virus Glycoprotein Inhibitors from Natural Compounds: Computer-Aided Drug Design

Authors: Driss Cherqaoui, Nouhaila Ait Lahcen, Ismail Hdoufane, Mehdi Oubahmane, Wissal Liman, Christelle Delaite, Mohammed M. Alanazi

Abstract:

The Ebola virus is a highly contagious and deadly pathogen that causes Ebola virus disease. The Ebola virus glycoprotein (EBOV-GP) is a key factor in viral entry into host cells, making it a critical target for therapeutic intervention. Using a combination of computational approaches, this study focuses on the identification of natural compounds that could serve as potent inhibitors of EBOV-GP. The 3D structure of EBOV-GP was selected, with missing residues modeled, and this structure was minimized and equilibrated. Two large natural compound databases, COCONUT and NPASS, were chosen and filtered based on toxicity risks and Lipinski’s Rule of Five to ensure drug-likeness. Following this, a pharmacophore model, built from 22 reported active inhibitors, was employed to refine the selection of compounds with a focus on structural relevance to known Ebola inhibitors. The filtered compounds were subjected to virtual screening via molecular docking, which identified ten promising candidates (five from each database) with strong binding affinities to EBOV-GP. These compounds were then validated through molecular dynamics simulations to evaluate their binding stability and interactions with the target. The top three compounds from each database were further analyzed using ADMET profiling, confirming their favorable pharmacokinetic properties, stability, and safety. These results suggest that the selected compounds have the potential to inhibit EBOV-GP, offering new avenues for antiviral drug development against the Ebola virus.

Keywords: EBOV-GP, Ebola virus glycoprotein, high-throughput drug screening, molecular docking, molecular dynamics, natural compounds, pharmacophore modeling, virtual screening

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4424 Applying Element Free Galerkin Method on Beam and Plate

Authors: Mahdad M’hamed, Belaidi Idir

Abstract:

This paper develops a meshless approach, called Element Free Galerkin (EFG) method, which is based on the weak form Moving Least Squares (MLS) of the partial differential governing equations and employs the interpolation to construct the meshless shape functions. The variation weak form is used in the EFG where the trial and test functions are approximated bye the MLS approximation. Since the shape functions constructed by this discretization have the weight function property based on the randomly distributed points, the essential boundary conditions can be implemented easily. The local weak form of the partial differential governing equations is obtained by the weighted residual method within the simple local quadrature domain. The spline function with high continuity is used as the weight function. The presently developed EFG method is a truly meshless method, as it does not require the mesh, either for the construction of the shape functions, or for the integration of the local weak form. Several numerical examples of two-dimensional static structural analysis are presented to illustrate the performance of the present EFG method. They show that the EFG method is highly efficient for the implementation and highly accurate for the computation. The present method is used to analyze the static deflection of beams and plate hole

Keywords: numerical computation, element-free Galerkin (EFG), moving least squares (MLS), meshless methods

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4423 Capital Market Reaction to Governance and Disclosure Violations: Evidence from the Saudi Arabian Capital Market

Authors: Nasser Alsadoun

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Today's companies in Saudi Arabian capital market must comply with strict criteria and adhere to rigid corporate governance rules and continuous disclosure requirements. Unlike other regulators in the region, decision makers of the Capital Market Authority (hereafter CMA) of Saudi Arabia believes that the announcements of economic sanctions and penalties for non-compliance firms will foster more effective regulatory compliance and hence improve the quality of financial reporting. An implied argument put forward by the opponents, however, states that such penalties are unnecessary and stated to be onerous for non-compliance firms. Over that last years, the CMA has publicly announced several economic fines levied on some listed companies for their failing to comply with corporate governance and continuous disclosure regulation clauses, with the amount of fine levied ranges between 50,000 SR to 100,000 SR for each failing. Economic theory suggests that rational investors make decisions based on a cost-benefit principal. The regulatory intervention made by CMA on the announcement of economic sanctions has been costly to the society (economy) hoping that it improves the transparency of financial statements. It is argued, therefore, that threat of regulators and economic sanctions will provide incentives for firms’ managers to report more relevant and reliable accounting information, and the benefit of such announcements is likely to be reflected in the context of the quality of the financial reports. Yet, the economic consequences of the revealed fines announcement for non-compliance firms in Saudi Arabian market have not been examined. Thus, this study attempts to empirically examine whether market participants are pricing the supposed benefits of rigid governance and disclosure rules in the Saudi market. The study employs an event study methodology to assess the impact of CMA economic sanctions announcements on the market price of non-compliance firms. The study also estimates and examines bid–ask spread behavior of violated firms around the CMA announcements. The findings indicate that the CMA fines announcements for failing to comply with governance and disclosure rules do not appear to play any significant role in securities pricing. In addition, tests of bid-ask behavior does not indicate any significant increases in information asymmetry surrounding these announcements. While the CMA has developed many goals to increase the awareness of listed companies with the best governance and disclosure practices, it seems they have to develop more goals to improve market efficiency and increase investors and public awareness.

Keywords: governance and disclosure violations, financial reporting quality, regulatory intervention, market efficiency

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4422 Assessment of Slope Stability by Continuum and Discontinuum Methods

Authors: Taleb Hosni Abderrahmane, Berga Abdelmadjid

Abstract:

The development of numerical analysis and its application to geomechanics problems have provided geotechnical engineers with extremely powerful tools. One of the most important problems in geotechnical engineering is the slope stability assessment. It is a very difficult task due to several aspects such the nature of the problem, experimental consideration, monitoring, controlling, and assessment. The main objective of this paper is to perform a comparative numerical study between the following methods: The Limit Equilibrium (LEM), Finite Element (FEM), Limit Analysis (LAM) and Distinct Element (DEM). The comparison is conducted in terms of the safety factors and the critical slip surfaces. Through the results, we see the feasibility to analyse slope stability by many methods.

Keywords: comparison, factor of safety, geomechanics, numerical methods, slope analysis, slip surfaces

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4421 Improving the Bioprocess Phenotype of Chinese Hamster Ovary Cells Using CRISPR/Cas9 and Sponge Decoy Mediated MiRNA Knockdowns

Authors: Kevin Kellner, Nga Lao, Orla Coleman, Paula Meleady, Niall Barron

Abstract:

Chinese Hamster Ovary (CHO) cells are the prominent cell line used in biopharmaceutical production. To improve yields and find beneficial bioprocess phenotypes genetic engineering plays an essential role in recent research. The miR-23 cluster, specifically miR-24 and miR-27, was first identified as differentially expressed during hypothermic conditions suggesting a role in proliferation and productivity in CHO cells. In this study, we used sponge decoy technology to stably deplete the miRNA expression of the cluster. Furthermore, we implemented the CRISPR/Cas9 system to knockdown miRNA expression. Sponge constructs were designed for an imperfect binding of the miRNA target, protecting from RISC mediated cleavage. GuideRNAs for the CRISPR/Cas9 system were designed to target the seed region of the miRNA. The expression of mature miRNA and precursor were confirmed using RT-qPCR. For both approaches stable expressing mixed populations were generated and characterised in batch cultures. It was shown, that CRISPR/Cas9 can be implemented in CHO cells with achieving high knockdown efficacy of every single member of the cluster. Targeting of one miRNA member showed that its genomic paralog is successfully targeted as well. The stable depletion of miR-24 using CRISPR/Cas9 showed increased growth and specific productivity in a CHO-K1 mAb expressing cell line. This phenotype was further characterized using quantitative label-free LC-MS/MS showing 186 proteins differently expressed with 19 involved in proliferation and 26 involved in protein folding/translation. Targeting miR-27 in the same cell line showed increased viability in late stages of the culture compared to the control. To evaluate the phenotype in an industry relevant cell line; the miR-23 cluster, miR-24 and miR-27 were stably depleted in a Fc fusion CHO-S cell line which showed increased batch titers up to 1.5-fold. In this work, we highlighted that the stable depletion of the miR-23 cluster and its members can improve the bioprocess phenotype concerning growth and productivity in two different cell lines. Furthermore, we showed that using CRISPR/Cas9 is comparable to the traditional sponge decoy technology.

Keywords: Chinese Hamster ovary cells, CRISPR/Cas9, microRNAs, sponge decoy technology

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4420 Molecular Characterization and Identification of C-Type Lectin in Red Palm Weevil, Rhynchophorus ferrugineus Oliver

Authors: Hafiza Javaria Ashraf, Xinghong Wang, Zhanghong Shi, Youming Hou

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Insect’s innate immunity depends on a variety of defense responses for the recognition of invading pathogens. Pathogen recognition involves particular proteins known as pattern recognition receptors (PRRs). These PRRs interact with pathogen-associated molecular patterns (PAMPs) present on the surface of pathogens to distinguish between self and non-self. C-type lectins (CTLs) belong to a superfamily of PPRs which involved in insect immunity and defense mechanism. Rhynchophorus ferrugineus Olivier is a devastating pest of Palm cultivations in China. Although studies on R. ferrugineus immune mechanism and host defense have conducted, however, the role of CTL in immune responses of R. ferrugineus remains elusive. Here, we report RfCTL, which is a secreted protein containing a single-CRD domain. The open reading frame (ORF) of CTL is 226 bp, which encodes a putative protein of 168 amino acids. Transcript expression analysis revealed that RfCTL highly expressed in immune-related tissues, i.e., hemolymph and fat body. The abundance of RfCTL in the gut and fat body dramatically increased upon Staphylococcus aureus and Escherichia coli bacterial challenges, suggesting a role in defense against gram-positive and gram-negative bacterial infection. Taken together, we inferred that RfCTL might be involved in the immune defense of R. ferrugineus and established a solid foundation for future studies on R. ferrugineus CTL domain proteins for better understanding of insect immunity.

Keywords: biological invasion, c-type lectin, insect immunity, Rhynchophorus ferrugineus Oliver

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4419 Containment/Penetration Analysis for the Protection of Aircraft Engine External Configuration and Nuclear Power Plant Structures

Authors: Dong Wook Lee, Adrian Mistreanu

Abstract:

The authors have studied a method for analyzing containment and penetration using an explicit nonlinear Finite Element Analysis. This method may be used in the stage of concept design for the protection of external configurations or components of aircraft engines and nuclear power plant structures. This paper consists of the modeling method, the results obtained from the method and the comparison of the results with those calculated from simple analytical method. It shows that the containment capability obtained by proposed method matches well with analytically calculated containment capability.

Keywords: computer aided engineering, containment analysis, finite element analysis, impact analysis, penetration analysis

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4418 Organic Co-Polymer Monolithic Columns for Liquid Chromatography Mixed Mode Protein Separations

Authors: Ahmed Alkarimi, Kevin Welham

Abstract:

Organic mixed mode monolithic columns were fabricated from; glycidyl methacrylate-co-ethylene dimethacrylate-co-stearyl methacrylate, using glycidyl methacrylate and stearyl methacrylate as co monomers representing 30% and 70% respectively of the liquid volume with ethylene dimethacrylate crosslinker and 2,2-dimethoxy-2-phenylacetophenone as the free radical initiator. The monomers were mixed with a binary porogenic solvent, comprising propan-1-ol, and methanol (0.825 mL each). The monolith was formed by photo polymerization (365 nm) inside a borosilicate glass tube (1.5 mm ID and 3 mm OD x 50 mm length). The monolith was observed to have formed correctly by optical examination and generated reasonable backpressure, approximately 650 psi at a flow rate of 0.2 mL min⁻¹ 50:50 acetonitrile: water. The morphological properties of the monolithic columns were investigated using scanning electron microscopy images, and Brunauer-Emmett-Teller analysis, the results showed that the monolith was formed properly with 19.98 ± 0.01 mm² surface area, 0.0205 ± 0.01 cm³ g⁻¹ pore volume and 6.93 ± 0.01 nm average pore size. The polymer monolith formed was further investigated using proton nuclear magnetic resonance, and Fourier transform infrared spectroscopy. The monolithic columns were investigated using high-performance liquid chromatography to test their ability to separate different samples with a range of properties. The columns displayed both hydrophobic/hydrophilic and hydrophobic/ion exchange interactions with the compounds tested indicating that true mixed mode separations. The mixed mode monolithic columns exhibited significant separation of proteins.

Keywords: LC separation, proteins separation, monolithic column, mixed mode

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4417 The Reality of E-Commerce in Egypt and Its Role in Enhancing Companies' Competitiveness

Authors: Esam El Gohary

Abstract:

— The companies’ ability to survive and compete in the fierce competition is determined by its competitiveness level. With the spread of information technology use and appearance of online shopping, it became crucial for companies to adopt e-commerce system to increase its competitiveness. This paper was conducted with the purpose of determine how increasing the service value through e-commerce factors (competitive strategy, ICT infrastructures, logistics, security, human resources and innovation) can enhance companies' competitiveness. The problem of this paper is summarized in the absence of the thorough awareness of e-commerce benefits for business owners and customers, as well as how to reduce the intangibility attributes of e-commerce. For this purpose this paper describes the e-commerce in Egypt and its success factors (infrastructures, legal and regulatory environment, human resources and innovation), as well as displays the barriers of such factor, to investigate the significant of these factors on increasing service value and enhance companies' competitiveness. This paper revealed that e-commerce companies have many opportunities to enhance its competitiveness in Egypt, which is enhanced by several factors. The most important factors are “strong ICT infrastructure, qualified and skilled human resources, in addition to the distinctive logistics that distinguish Egypt due to its location, strong legal and regulatory environment and Innovation, as well as the competitive strategy. As well as, companies encounter several threats such as; the lack of infrastructures and logistics in rural areas, the absence of the inclusive understanding and awareness of e-commerce, fear from e-payment transactions and fraud, the ambiguity and burdensome of customs. Through the research findings several recommendations were introduced to both government and companies to overcome threats and exploit opportunities to improve performance and enhance companies' competitiveness.

Keywords: e-commerce competitiveness, e-commerce factors, e-commerce in Egypt, information technology

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4416 Levels of Selected Adipokines in Women with Gestational Diabetes and Type 2 Diabetes, Their Relationship to Metabolic Parameters

Authors: David Karasek, Veronika Kubickova, Ondrej Krystynik, Dominika Goldmannova, Lubica Cibickova, Jan Schovanek

Abstract:

Introduction: Adiponectin, adipocyte-fatty acid-binding protein (A-FABP), and Wnt1 inducible signaling pathway protein-1 (WISP-1) are adipokines particularly associated with insulin resistance. The aim of the study was to compare their levels in women with gestational diabetes (GDM), type 2 diabetes mellitus (T2DM) and healthy controls and determine their relation with metabolic parameters. Methods: Fifty women with GDM, 50 women with T2DM, and 35 healthy women were included in the study. In addition to adipokines, anthropometric, lipid parameters, and markers, insulin resistance, and glucose control were assessed in all participants. Results: Compared to healthy controls only significantly lower levels of adiponectin were detected in women with GDM, whereas lower levels of adiponectin, higher levels of A-FABP and of WISP-1 were present in women with T2DM. Women with T2DM had also lower levels of adiponectin and higher levels of A-FABP compared to women with GDM. In women with GDM or T2DM adiponectin correlated negatively with body mass index (BMI), triglycerides (TG), C-peptide and positively with HDL-cholesterol; A-FABP positively correlated with BMI, TG, waist, and C-peptide. Moreover, there was a positive correlation between WISP-1 and C-peptide in women with T2DM. Conclusion: Adverse adipokines production detecting dysfunctional fat tissue is in women with GDM less presented than in women with T2DM, but more expressed compared to healthy women. Acknowledgment: Supported by AZV NV18-01-00139 and MH CZ DRO (FNOl, 00098892).

Keywords: adiponectin, adipocyte-fatty acid binding protein, wnt1 inducible signaling pathway protein-1, gestational diabetes, type 2 diabetes mellitus

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4415 Dynamic Modeling of Orthotropic Cracked Materials by X-FEM

Authors: S. Houcine Habib, B. Elkhalil Hachi, Mohamed Guesmi, Mohamed Haboussi

Abstract:

In this paper, dynamic fracture behaviors of cracked orthotropic structure are modeled using extended finite element method (X-FEM). In this approach, the finite element method model is first created and then enriched by special orthotropic crack tip enrichments and Heaviside functions in the framework of partition of unity. The mixed mode stress intensity factor (SIF) is computed using the interaction integral technique based on J-integral in order to predict cracking behavior of the structure. The developments of these procedures are programmed and introduced in a self-software platform code. To assess the accuracy of the developed code, results obtained by the proposed method are compared with those of literature.

Keywords: X-FEM, composites, stress intensity factor, crack, dynamic orthotropic behavior

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4414 Novel EGFR Ectodomain Mutations and Resistance to Anti-EGFR and Radiation Therapy in H&N Cancer

Authors: Markus Bredel, Sindhu Nair, Hoa Q. Trummell, Rajani Rajbhandari, Christopher D. Willey, Lewis Z. Shi, Zhuo Zhang, William J. Placzek, James A. Bonner

Abstract:

Purpose: EGFR-targeted monoclonal antibodies (mAbs) provide clinical benefit in some patients with H&N squamous cell carcinoma (HNSCC), but others progress with minimal response. Missense mutations in the EGFR ectodomain (ECD) can be acquired under mAb therapy by mimicking the effect of large deletions on receptor untethering and activation. Little is known about the contribution of EGFR ECD mutations to EGFR activation and anti-EGFR response in HNSCC. Methods: We selected patient-derived HNSCC cells (UM-SCC-1) for resistance to mAb Cetuximab (CTX) by repeated, stepwise exposure to mimic what may occur clinically and identified two concurrent EGFR ECD mutations (UM-SCC-1R). We examined the competence of the mutants to bind EGF ligand or CTX. We assessed the potential impact of the mutations through visual analysis of space-filling models of the native sidechains in the original structures vs. their respective side-chain mutations. We performed CRISPR in combination with site-directed mutagenesis to test for the effect of the mutants on ligand-independent EGFR activation and sorting. We determined the effects on receptor internalization, endocytosis, downstream signaling, and radiation sensitivity. Results: UM-SCC-1R cells carried two non-synonymous missense mutations (G33S and N56K) mapping to domain I in or near the EGF binding pocket of the EGFR ECD. Structural modeling predicted that these mutants restrict the adoption of a tethered, inactive EGFR conformation while not permitting association of EGFR with the EGF ligand or CTX. Binding studies confirmed that the mutant, untethered receptor displayed a reduced affinity for both EGF and CTX but demonstrated sustained activation and presence at the cell surface with diminished internalization and sorting for endosomal degradation. Single and double-mutant models demonstrated that the G33S mutant is dominant over the N56K mutant in its effect on EGFR activation and EGF binding. CTX-resistant UM-SCC-1R cells demonstrated cross-resistance to mAb Panitumuab but, paradoxically, remained sensitive to the reversible receptor tyrosine kinase inhibitor Erlotinib. Conclusions: HNSCC cells can select for EGFR ECD mutations under EGFR mAb exposure that converge to trap the receptor in an open, constitutively activated state. These mutants impede the receptor’s competence to bind mAbs and EGF ligand and alter its endosomal trafficking, possibly explaining certain cases of clinical mAb and radiation resistance.

Keywords: head and neck cancer, EGFR mutation, resistance, cetuximab

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4413 Geometrically Nonlinear Analysis of Initially Stressed Hybrid Laminated Composite Structures

Authors: Moumita Sit, Chaitali Ray

Abstract:

The present article deals with the free vibration analysis of hybrid laminated composite structures with initial stresses developed in the laminates. Generally initial stresses may be developed in the laminates by temperature and moisture effect. In this study, an eight noded isoparametric plate bending element has been used for the finite element analysis of composite plates. A numerical model has been developed to assess the geometric nonlinear response of composite plates based on higher order shear deformation theory (HSDT) considering the Green–Lagrange type nonlinearity. A computer code based on finite element method (FEM) has also been developed in MATLAB to perform the numerical calculations. To validate the accuracy of the proposed numerical model, the results obtained from the present study are compared with those available in published literature. Effects of the side to thickness ratio, different boundary conditions and initial stresses on the natural frequency of composite plates have been studied. The free vibration analysis of a hollow stiffened hybrid laminated panel has also been carried out considering initial stresses and presented as case study.

Keywords: geometric nonlinearity, higher order shear deformation theory (HSDT), hybrid composite laminate, the initial stress

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4412 Heat and Humidity Induced Plastic Changes in Body Lipids and Starvation Resistance in the Tropical Zaprionus indianus of Wet-Dry Seasons

Authors: T. N. Girish, B. E. Pradeep, Ravi Parkash

Abstract:

Insects from tropical wet or dry seasons are likely to cope starvation stress through seasonal phenotypic plasticity in energy metabolites. Accordingly, we analyzed such plastic changes in Zaprionus indianus flies reared under wet or dry season-specific conditions; and also after adult acclimation at 32℃ for 1 to 6 days; and to low (40% RH) or high (70% RH) humidity. Both thermal or humidity acclimation revealed significant accumulation of body lipids for wet season flies but low humidity acclimation did not change the level of body lipids in dry season flies. Developmental and adult acclimation showed sex specific differences i.e., starvation resistance and body lipids were higher in the males of dry season but in females of wet season. We found seasonal and sex specific differences in the relative level for body lipids at death; and in the rates of accumulation or utilization of energy metabolites (body lipids, carbohydrates and proteins). Body lipids constitute the preferred energy source under starvation for flies of both the seasons. However, utilization of carbohydrates (~20% to 30%) and proteins (~20% to 25%) was evident only in dry season flies. Higher starvation resistance after thermal or humidity acclimation is achieved by increased accumulation of lipids. Adult acclimation of wet or dry season flies revealed plastic changes in mean daily fecundity despite reduction in fecundity under starvation. Thus, thermal or humidity induced plastic responses in body lipids support starvation resistance under wet or dry seasons.

Keywords: heat or humidity acclimation, plastic changes in body lipids and starvation resistance, tropical drosophilid, Wet- or Dry seasons, Zaprionus indianus

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4411 Beta-Carotene Attenuates Cognitive and Hepatic Impairment in Thioacetamide-Induced Rat Model of Hepatic Encephalopathy via Mitigation of MAPK/NF-κB Signaling Pathway

Authors: Marawan Abd Elbaset Mohamed, Hanan A. Ogaly, Rehab F. Abdel-Rahman, Ahmed-Farid O.A., Marwa S. Khattab, Reham M. Abd-Elsalam

Abstract:

Liver fibrosis is a severe worldwide health concern due to various chronic liver disorders. Hepatic encephalopathy (HE) is one of its most common complications affecting liver and brain cognitive function. Beta-Carotene (B-Car) is an organic, strongly colored red-orange pigment abundant in fungi, plants, and fruits. The study attempted to know B-Car neuroprotective potential against thioacetamide (TAA)-induced neurotoxicity and cognitive decline in HE in rats. Hepatic encephalopathy was induced by TAA (100 mg/kg, i.p.) three times per week for two weeks. B-Car was given orally (10 or 20 mg/kg) daily for two weeks after TAA injections. Organ body weight ratio, Serum transaminase activities, liver’s antioxidant parameters, ammonia, and liver histopathology were assessed. Also, the brain’s mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-κB), antioxidant parameters, adenosine triphosphate (ATP), adenosine monophosphate (AMP), norepinephrine (NE), dopamine (DA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) cAMP response element-binding protein (CREB) expression and B-cell lymphoma 2 (Bcl-2) expression were measured. The brain’s cognitive functions (Spontaneous locomotor activity, Rotarod performance test, Object recognition test) were assessed. B-Car prevented alteration of the brain’s cognitive function in a dose-dependent manner. The histopathological outcomes supported these biochemical evidences. Based on these results, it could be established that B-Car could be assigned to treat the brain’s neurotoxicity consequences of HE via downregualtion of MAPK/NF-κB signaling pathways.

Keywords: beta-carotene, liver injury, MAPK, NF-κB, rat, thioacetamide

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4410 PV Module as a Design Element of Barriers for Protection against Noise

Authors: Budimir S. Sudimac, Andjela N. Dubljevic

Abstract:

The aim of thisresearch paper is to consider possibilities for improving the street lighting on the E75 highway, which passes through Serbia, using renewable sources of energy. In this paper, we analyzed the possibilities for installing sound barriers along the highway and integrating photovoltaic (PV) modules, which would generate electrical energy to power the lighting on the section of the highway running through Belgrade. The main aim of this paper is to analyze, show and promote innovative, hybrid, multi-functional solar technology using PV modules as an element of sound barriers in urban areas. The paper seeks to show the hybridity of using sustainable technologies in solving environmental issues. This structure solves the problem of noise in populated areas and provides the electricity from renewable source.

Keywords: noise, PV modules, solar energy, sound barriers

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4409 Induction Heating Process Design Using Comsol® Multiphysics Software Version 4.2a

Authors: K. Djellabi, M. E. H. Latreche

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Induction heating computer simulation is a powerful tool for process design and optimization, induction coil design, equipment selection, as well as education and business presentations. The authors share their vast experience in the practical use of computer simulation for different induction heating and heat treating processes. In this paper deals with mathematical modeling and numerical simulation of induction heating furnaces with axisymmetric geometries. For the numerical solution, we propose finite element methods combined with boundary (FEM) for the electromagnetic model using COMSOL® Multiphysics Software. Some numerical results for an industrial furnace are shown with high frequency.

Keywords: numerical methods, induction furnaces, induction heating, finite element method, Comsol multiphysics software

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4408 Die Design for Flashless Forging of a Polymer Insulator Fitting

Authors: Pedram Khazaie, Sajjad Moein

Abstract:

In the conventional hot forging of Tongue, which is a fitting for polymer insulator, the material wasted to flash accounts for 20-30% of workpiece. In order to reduce the cost of forged products, this waste material must be minimized. In this study, a flashless forging die is designed and simulated using the finite element method (FEM). A solution to avoid overloading the die with a simple preform is also presented. Moreover, since in flashless forging, burr is formed on the edge of workpiece, a controlled flash forging method is proposed to solve this problem. The simulation results have been validated by experiments; achieving close agreement between simulated and experimental data. It was shown that numerical modeling is helpful in reducing cost and time in the manufacturing process.

Keywords: burr formation, die design, finite element method, flashless forging

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4407 Commercial Management vs. Quantity Surveying: Hoax or Harmonization

Authors: Zelda Jansen Van Rensburg

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Purpose: This study investigates the perceived disparities between Quantity Surveying and Commercial Management in the construction industry, questioning if these differences are substantive or merely semantic. It aims to challenge the conventional notion of Commercial Managers’ superiority by critically evaluating QS and CM roles, exploring CM integration possibilities, examining qualifications for aspiring Commercial Managers, assessing regulatory frameworks, and considering terminology redefinition for global QS professional enhancement. Design: Utilizing mixed methods like literature reviews, surveys, interviews, and document analyses, this research examines the QS-CM relationship. Insights from industry professionals, academics, and regulatory bodies inform the investigation into changing QS roles. Findings: Empirical data highlight evolving roles, showcasing areas of convergence and divergence between QSs and CM. Potential CM integration into QS practice and qualifications for aspiring Commercial Managers are identified. Limitations/Implications: Limitations include potential bias in self-reported data and findings. Nevertheless, the research informs future practices and educational approaches in QS and CM, reflecting the changing roles and responsibilities of Quantity Surveyors. Practical Implications: Findings inform industry practitioners, educators, and regulators, stressing the need to adapt to changing QS roles and integrate CM principles where applicable. Value to the Conference Theme: Aligned with ‘Evolving roles and responsibilities of Quantity Surveyors,’ this research offers insights crucial for understanding the changing dynamics within the QS profession and informs strategies to navigate these shifts effectively.

Keywords: quantity surveying, commercial management, cost engineering, quantity survey

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4406 Pragmatism in Adaptive Reuse of Obsolete Industrial Land in China

Authors: Yong Li

Abstract:

Major cities in China has experienced a shift from production based on manufacturing industry to tertiary industry. How to make a better use of existing obsolete industrial land within urban cores has become a difficult problem for many policymakers. City governments regard old manufacturing industrial land as an important source of land to facilitate the development of the cities. Despite the announcement of policies in promoting that, a large portion of industrial land is still not properly redeveloped and most of them became obsolete. The study uses the project of Xinyi International Club as a case to examine the process of adaptive reuse of obsolete industrial space in Guangzhou, China. It attempts to elucidate the underlying mechanisms by identifying the key forces from both the government and the private sectors in influencing the process. The study found that market forces in transforming industrial space are exerting a strong impact on the existing land use planning system in Chinese cities. Pragmatic relaxation of the formal land use the regulatory framework and government supportive land-use intervention have also been crucial towards achieving successful implementation of the restructuring project and making it a showcase. This study questions whether these extraordinary measures, in particular, the use of temporary land use permit, are sustainable in facilitating the transformation of derelict industrial land, and in informing future industrial land-use restructuring policies. It concludes that, while the land use regulatory system in China is becoming increasingly dynamic and flexible, it remains ill-equipped in responding positively to the market, which is characterized by an increasing bargaining power of the private sector. A comprehensive appraisal of the overall impacts of these adaptive re-uses on society is wanting.

Keywords: China, land alteration, obsolete industrial properties, urban planning

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4405 Hippocampus Proteomic of Major Depression and Antidepressant Treatment: Involvement of Cell Proliferation, Differentiation, and Connectivity

Authors: Dhruv J. Limaye, Hanga Galfalvy, Cheick A. Sissoko, Yung-yu Huang, Chunanning Tang, Ying Liu, Shu-Chi Hsiung, Andrew J. Dwork, Gorazd B. Rosoklija, Victoria Arango, Lewis Brown, J. John Mann, Maura Boldrini

Abstract:

Memory and emotion require hippocampal cell viability and connectivity and are disrupted in major depressive disorder (MDD). Applying shotgun proteomics and stereological quantification of neural progenitor cells (NPCs), intermediate neural progenitors (INPs), and mature granule neurons (GNs), to postmortem human hippocampus, identified differentially expressed proteins (DEPs), and fewer NPCs, INPs and GNs, in untreated MDD (uMDD) compared with non-psychiatric controls (CTRL) and antidepressant-treated MDD (MDDT). DEPs lower in uMDD vs. CTRL promote mitosis, differentiation, and prevent apoptosis. DEPs higher in uMDD vs. CTRL inhibit the cell cycle, and regulate cell adhesion, neurite outgrowth, and DNA repair. DEPs lower in MDDT vs. uMDD block cell proliferation. We observe group-specific correlations between numbers of NPCs, INPs, and GNs and an abundance of proteins regulating mitosis, differentiation, and apoptosis. Altered protein expression underlies hippocampus cellular and volume loss in uMDD, supports a trophic effect of antidepressants, and offers new treatment targets.

Keywords: proteomics, hippocampus, depression, mitosis, migration, differentiation, mitochondria, apoptosis, antidepressants, human brain

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4404 Finite Element Analysis of Piezolaminated Structures with Both Geometric and Electroelastic Material Nonlinearities

Authors: Shun-Qi Zhang, Shu-Yang Zhang, Min Chen, , Jing Bai

Abstract:

Piezoelectric laminated smart structures can be subjected to the strong driving electric field, which may result in large displacements and rotations. In one hand, piezoelectric materials usually behave very significant material nonlinear effects under strong electric fields. On the other hand, thin-walled structures undergoing large displacements and rotations exist nonnegligible geometric nonlinearity. In order to give a precise prediction of piezo laminated smart structures under the large electric field, this paper develops a finite element (FE) model accounting for material nonlinearity (piezoelectric part) and geometric nonlinearity based on the first order shear deformation (FSOD) hypothesis. The proposed FE model is first validated by both experimental and numerical examples from the literature. Afterwards, it is applied to simulate for plate and shell structures with multiple piezoelectric patches under the strong applied electric field. From the simulation results, it shows that large discrepancies occur between linear and nonlinear predictions for piezoelectric laminated structures driving at the strong electric field. Therefore, both material and geometric nonlinearities should be taken into account for piezoelectric structures under strong electric.

Keywords: piezoelectric smart structures, finite element analysis, geometric nonlinearity, electroelastic material nonlinearities

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4403 Consumer Knowledge of Food Quality Assurance and Use of Food Labels in Trinidad, West Indies

Authors: Daryl Clement Knutt, Neela Badrie, Marsha Singh

Abstract:

Quality assurance and product labelling are vital in the food and drink industry, as a tactical tool in a competitive environment. The food label is a principal marketing tool which also serves as a regulatory mechanism in the safeguarding of consumer well –being. The objective of this study was to evaluate the level of consumers’ use and understanding of food labeling information and knowledge pertaining to food quality assurance systems. The study population consisted of Trinidadian adults, who were over the age of 18 (n=384). Data collection was conducted via a self-administered questionnaire, which contained 31 questions, comprising of four sections: I. socio demographic information; II. food quality and quality assurance; III. use of Labeling information; and IV. laws and regulations. Sampling was conducted at six supermarkets, in five major regions of the country over a period of three weeks in 2014. The demographic profile of the shoppers revealed that majority was female (63.6%). The gender factor and those who were concerned about the nutrient content of their food, were predictive indicators of those who read food labels. Most (93.1%) read food labels before purchase, 15.4% ‘always’; 32.5% ‘most times’ and 45.2% ‘sometimes’. Some (42%) were often satisfied with the information presented on food labels, whilst 35.7% of consumers were unsatisfied. When the respondents were questioned on their familiarity with terms ‘food quality’ and ‘food quality assurance’, 21.3% of consumers replied positively - ‘I have heard the terms and know a lot’ whilst 37% were only ‘somewhat familiar’. Consumers were mainly knowledgeable of the International Standard of Organization (ISO) (51.5%) and Good Agricultural Practices GAP (38%) as quality tools. Participants ranked ‘nutritional information’ as the number one labeling element that should be better presented, followed by ‘allergy notes’ and ‘best before date’. Females were more inclined to read labels being the household shoppers. The shoppers would like better presentation of the food labelling information so as to guide their decision to purchase a product.

Keywords: food labels, food quality, nutrition, marketing, Trinidad, Tobago

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4402 A Structure-Switching Electrochemical Aptasensor for Rapid, Reagentless and Single-Step, Nanomolar Detection of C-Reactive Protein

Authors: William L. Whitehouse, Louisa H. Y. Lo, Andrew B. Kinghorn, Simon C. C. Shiu, Julian. A. Tanner

Abstract:

C-reactive protein (CRP) is an acute-phase reactant and sensitive indicator for sepsis and other life-threatening pathologies, including systemic inflammatory response syndrome (SIRS). Currently, clinical turn-around times for established CRP detection methods take between 30 minutes to hours or even days from centralized laboratories. Here, we report the development of an electrochemical biosensor using redox probe-tagged DNA aptamers functionalized onto cheap, commercially available screen-printed electrodes. Binding-induced conformational switching of the CRP-targeting aptamer induces a specific and selective signal-ON event, which enables single-step and reagentless detection of CRP in as little as 1 minute. The aptasensor dynamic range spans 5-1000nM (R=0.97) or 5-500nM (R=0.99) in 50% diluted human serum, with a LOD of 3nM, corresponding to 2-orders of magnitude sensitivity under the clinically relevant cut-off for CRP. The sensor is stable for up to one week and can be reused numerous times, as judged from repeated real-time dosing and dose-response assays. By decoupling binding events from the signal induction mechanism, structure-switching electrochemical aptamer-based sensors (SS-EABs) provide considerable advantages over their adsorption-based counterparts. Our work expands on the retinue of such sensors reported in the literature and is the first instance of an SS-EAB for reagentless CRP detection. We hope this study can inspire further investigations into the suitability of SS-EABs for diagnostics, which will aid translational R&D toward fully realized devices aimed at point-of-care applications or for use more broadly by the public.

Keywords: structure-switching, C-reactive protein, electrochemical, biosensor, aptasensor.

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4401 Modal Analysis of FGM Plates Using Finite Element Method

Authors: S. J. Shahidzadeh Tabatabaei, A. M. Fattahi

Abstract:

Modal analysis of an FGM plate containing the ceramic phase of Al2O3 and metal phase of stainless steel 304 was performed using ABAQUS, with the assumptions that the material has an elastic mechanical behavior and its Young modulus and density are varying in thickness direction. For this purpose, a subroutine was written in FORTRAN and linked with ABAQUS. First, a simulation was performed in accordance to other researcher’s model, and then after comparing the obtained results, the accuracy of the present study was verified. The obtained results for natural frequency and mode shapes indicate good performance of user-written subroutine as well as FEM model used in present study. After verification of obtained results, the effect of clamping condition and the material type (i.e. the parameter n) was investigated. In this respect, finite element analysis was carried out in fully clamped condition for different values of n. The results indicate that the natural frequency decreases with increase of n, since with increase of n, the amount of ceramic phase in FGM plate decreases, while the amount of metal phase increases, leading to decrease of the plate stiffness and hence, natural frequency, as the Young modulus of Al2O3 is equal to 380 GPa and the Young modulus of stainless steel 304 is equal to 207 GPa.

Keywords: FGM plates, modal analysis, natural frequency, finite element method

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4400 hsa-miR-1204 and hsa-miR-639 Prominent Role in Tamoxifen's Molecular Mechanisms on the EMT Phenomenon in Breast Cancer Patients

Authors: Mahsa Taghavi

Abstract:

In the treatment of breast cancer, tamoxifen is a regularly prescribed medication. The effect of tamoxifen on breast cancer patients' EMT pathways was studied. In this study to see if it had any effect on the cancer cells' resistance to tamoxifen and to look for specific miRNAs associated with EMT. In this work, we used continuous and integrated bioinformatics analysis to choose the optimal GEO datasets. Once we had sorted the gene expression profile, we looked at the mechanism of signaling, the ontology of genes, and the protein interaction of each gene. In the end, we used the GEPIA database to confirm the candidate genes. after that, I investigated critical miRNAs related to candidate genes. There were two gene expression profiles that were categorized into two distinct groups. Using the expression profile of genes that were lowered in the EMT pathway, the first group was examined. The second group represented the polar opposite of the first. A total of 253 genes from the first group and 302 genes from the second group were found to be common. Several genes in the first category were linked to cell death, focal adhesion, and cellular aging. Two genes in the second group were linked to cell death, focal adhesion, and cellular aging. distinct cell cycle stages were observed. Finally, proteins such as MYLK, SOCS3, and STAT5B from the first group and BIRC5, PLK1, and RAPGAP1 from the second group were selected as potential candidates linked to tamoxifen's influence on the EMT pathway. hsa-miR-1204 and hsa-miR-639 have a very close relationship with the candidates genes according to the node degrees and betweenness index. With this, the action of tamoxifen on the EMT pathway was better understood. It's important to learn more about how tamoxifen's target genes and proteins work so that we can better understand the drug.

Keywords: tamoxifen, breast cancer, bioinformatics analysis, EMT, miRNAs

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4399 Fano-Resonance-Based Wideband Acoustic Metamaterials with Highly Efficient Ventilation

Authors: Xi-Wen Xiao, Tzy-Rong Lin, Chien-Hao Liu

Abstract:

Ventilated acoustic metamaterials have attracted considerable research attention due to their low-frequency absorptions and efficient fluid ventilations. In this research, a wideband acoustic metamaterial with auditory filtering ability and efficient ventilation capacity were proposed. In contrast to a conventional Fano-like resonator, a Fano-like resonator composed of a resonant unit and two nonresonant units with a large opening area of 68% for fluid passages was developed. In addition, the coupling mechanism to improve the narrow bandwidths of conventional Fano-resonance-based meta-materials was included. With a suitable design, the output sound waves of the resonant and nonresonant states were out of phase to achieve sound absorptions in the far fields. Therefore, three-element and five-element coupled Fano-like metamaterials were designed and simulated with the help of the finite element software to obtain the filtering fractional bandwidths of 42.5% and 61.8%, respectively. The proposed approach can be extended to multiple coupled resonators for obtaining ultra-wide bandwidths and can be implemented with 3D printing for practical applications. The research results are expected to be beneficial for sound filtering or noise reductions in duct applications and limited-volume spaces.

Keywords: fano resonance, noise reduction, resonant coupling, sound filtering, ventilated acoustic metamaterial

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4398 Inflammatory Changes in Postmenopausal Women including Th17 and Treg

Authors: Ae Ra Han, Seoung Eun Huh, Ji Yeon Kim, Joanne Kwak-Kim, Sung Ki Lee

Abstract:

Objective: Prevalence of osteoporosis, cardiovascular disorders, and Alzheimer's disease rapidly increase after menopause. Immune activation and inflammation are suggested as an important pathogenesis of these serious diseases. Several pro-inflammatory cytokines are increased in women with surgical or natural menopause. However, the little is known about IL-17 producing T cells and Foxp3+ regulatory T (Treg) cells in post-menopause. Methods: A total of 34 postmenopausal women, who had no active cardiovascular, endocrine and infectious disorders were recruited as study group and healthy premenopausal women participated as controls. Peripheral blood mononuclear cells were isolated. Immuno-morphologic (CD3, CD4, CD8, CD19, CD56/CD16), intracellular cytokine (TNF-alpha, IFN-gamma, IL-10, IL-17), and Treg cell (Foxp3) studies were carried out using flow cytometry. The proportion of peripheral lymphocytes, including IL-17 producing and Foxp3+ Treg cells immune cell in each group were statistically analyzed. Results: The proportion of NK cells was significantly increased in menopausal women as compared to that of controls (P=.005). The ratios of TNF-alpha/IL-10 producing CD3+CD4+ T cells were increased in postmenopausal women. CD3+IL-17+ T cell level was higher in postmenopausal women and CD4+ Foxp3+ Treg cells was lower than that of controls. The ratios of CD3+IL-17+ T cell to CD3+Foxp3+ and to CD4+Foxp3+ Treg cells were significantly increased in postmenopausal women (P=.001). Conclusions: We found enhanced innate immunity and Th1- and Th17-mediated adaptive immunity in postmenopausal women. This may explain increasing prevalence of chronic inflammatory diseases after menopause. Further studies are needed to elucidate what factors contribute to this inflammatory shift in the postmenopause.

Keywords: inflammation, immune cell, menopause, Th17, regulatory T cell

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4397 Partial Replacement for Cement and Coarse Aggregate in Concrete by Using Egg Shell Powder and Coconut Shell

Authors: A. K. Jain, M. C. Paliwal

Abstract:

The production of cement leads to the emission of large amounts of carbon-dioxide gas into the atmosphere which is a major contributor for the greenhouse effect and the global warming; hence it is mandatory either to quest for another material or partly replace it with some other material. According to the practical demonstrations and reports, Egg Shell Powder (ESP) can be used as a binding material for different field applications as it contains some of the properties of lime. It can partially replace the cement and further; it can be used in different proportion for enhancing the performance of cement. It can be used as a first-class alternative, for material reuse and waste recycling practices. Eggshell is calcium rich and analogous to limestone in chemical composition. Therefore, use of eggshell waste for partial replacement of cement in concrete is feasible. Different studies reveal that plasticity index of the soil can be improved by adding eggshell wastes in all the clay soil and it has wider application in construction projects including earth canals and earthen dams. The scarcity of aggregates is also increasing nowadays. Utilization of industrial waste or secondary materials is increasing in different construction applications. Coconut shell was successfully used in the construction industry for partial or full replacement for coarse aggregates. The use of coconut shell gives advantage of using waste material to partially replace the coarse aggregate. Studies carried on coconut shell indicate that it can partially replace the aggregate. It has good strength and modulus properties along with the advantage of high lignin content. It absorbs relatively low moisture due to its low cellulose content. In the paper, study carried out on eggshell powder and coconut shell will be discussed. Optimum proportions of these materials to be used for partial replacement of cement and aggregate will also be discussed.

Keywords: greenhouse, egg shell powder, binding material, aggregates, coconut shell, coarse aggregates

Procedia PDF Downloads 253