Search results for: ligand free

Authors: Shai Sarussi

Abstract:

Suppose F is a field with valuation v and valuation domain Oᵥ, and R is an Oᵥ-algebra. It is known that there exists a filter quasi-valuation on R; the existence of a quasi-valuation yields several important connections between Oᵥ and R, in particular with respect to their prime spectra. In this paper, the notion of a module valuation is introduced. It is shown that any torsion-free module over Oᵥ has an induced module valuation. Moreover, several results connecting the filter quasi-valuation and module valuations are presented.

Keywords: valuations, quasi-valuations, prime spectrum, algebras over valuation domains

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Authors: Tahar Tayachi, Ahlam Alrehaili

Abstract:

Purpose: The purpose of this paper is to investigate the relationship between the corporate board characteristics and the dividend policy among firms on the Saudi Stock Exchange. Design/Methodology/Approach: This paper uses a sample of 103 nonfinancial firms over a time period of 4 years from 2015 to 2018. To investigate how corporate governance mechanisms such as board independence, the board size, frequency of meetings, and free cash flow impact dividends, the study uses Logit and Tobit models. Findings: This paper finds that board size, board independence, and frequency of board meetings have no influence on a firm’s decision to pay dividends, while board size has a significantly positive impact on the levels of cash dividends paid to investors. This study also finds that the level of free cash flows has a positively significant influence on both the decision to pay dividends and the magnitude of dividend payouts. Research Limitations/Implications: This paper attempts to study the effectiveness of dividend policy among some firms on the Saudi Stock Exchange. Practical Implications: The findings reveal that board characteristics, which represent one of the crucial mechanisms of corporate governance, were found to be complementary to corporate laws and regulations imposed on the Saudi market in 2015. The findings also imply that capital market authorities should revise their corporate regulations and ensure that protection laws are adequate and strong enough to protect the interests of all shareholders. Originality/Value: This paper is among the few studies focusing on dividend policy in Saudi Arabia. Finally, these findings suggest that the improvements in corporate laws in Saudi Arabia led to such an outcome, and it has become prevalent in dividend policy decisions and behaviors of Saudi firms.

Keywords: agency theory, Tobit, corporate governance, dividend payout, Logit

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Authors: Seyedeh Mozhgan Seyed Talebi, Chih -Hao Lee

Abstract:

With an abrupt rise in the power conservation efficiency (PCE) of perovskite solar cells (PSCs) within a short span of time, the toxicity of lead was raised as a major hurdle in the path toward their commercialization. In the present research, a systematic investigation of the electrical and optical characteristics of the all-inorganic CsSnI₃ perovskite absorber layer was performed with the Vienna Ab Initio Simulation Package (VASP) using the projector-augmented wave method. The presence of inorganic halide perovskite offers the advantages of enhancing the degradation resistance of the device, reducing the cost of cells, and minimizing the recombination of generated carriers. The simulated standard device using a 1D simulator like solar cell capacitance simulator (SCAPS) version 3308 involves FTO/n-TiO₂/CsSnI₃ Perovskite absorber/Spiro OmeTAD HTL/Au contact layer. The variation in the device design key parameters such as the thickness and defect density of perovskite absorber, hole transport layer and electron transport layer and interfacial defects are examined with their impact on the photovoltaic characteristic parameters. The effect of an increase in operating temperature from 300 K to 400 K on the performance of CsSnI3-based perovskite devices is also investigated. The optimized standard device at room temperature shows the highest PCE of 25.18 % with FF of 75.71 %, Voc of 0.96 V, and Jsc of 34.67 mA/cm². The outcomes and interpretation of different inorganic Cu-based HTLs presence, such as CuSCN, Cu₂O, CuO, CuI, SrCu₂O₂, and CuSbS₂, here represent a critical avenue for the possibility of fabricating high PCE perovskite devices made of stable, low-cost, efficient, safe, and eco-friendly all-inorganic materials like CsSnI₃ perovskite light absorber.

Keywords: CsSnI₃, hole transporting layer (HTL), lead-free perovskite solar cell, SCAPS-1D software

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Authors: Srinivasan Chandrasekaran, Shihas A. Khader

Abstract:

Motion response of floating structures is of great concern in marine engineering. Nonlinearity is an inherent property of any floating bodies subjected to irregular waves. These floating structures are continuously subjected to environmental loadings from wave, current, wind etc. This can result in undesirable motions of the vessel which may challenge the operability. For a floating body to remain in its position, it should be able to induce a restoring force when displaced. Mooring is provided to enable this restoring force. This paper discuss the hydrodynamic performance and motion characteristics of an 8 point spread mooring system applied to a pipe laying barge operating in the West African sea. The modelling of the barge is done using a computer aided-design (CAD) software RHINOCEROS. Irregular waves are generated using a suitable wave spectrum. Both frequency domain and time domain analysis is done. Numerical simulations based on potential theory are carried out to find the responses and hydrodynamic performance of the barge in both free floating as well as moored conditions. Initially, potential flow frequency domain analysis is done to obtain the Response Amplitude Operator (RAO) which gives an idea about the structural motion in free floating state. RAOs for different wave headings are analyzed. In the following step, a time domain analysis is carried out to obtain the responses of the structure in the moored condition. In this study, wave induced motions are only taken into consideration. Wind and current loads are ruled out and shall be included in future studies. For the current study, 5000 seconds simulation is taken. The results represent wave-induced motion responses, mooring line tensions and identifies critical mooring lines.

Keywords: irregular wave, moored barge, time domain analysis, numerical simulation

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Authors: Mouna Baassi, Mohamed Moussaoui, Sanchaita Rajkhowa, Hatim Soufi, Said Belaaouad

Abstract:

The objective of this paper is to address the challenging task of targeting Human Immunodeficiency Virus type 1 Reverse Transcriptase (HIV-1 RT) in the treatment of AIDS. Reverse Transcriptase inhibitors (RTIs) have limitations due to the development of Reverse Transcriptase mutations that lead to treatment resistance. In this study, a combination of statistical analysis and bioinformatics tools was adopted to develop a mathematical model that relates the structure of compounds to their inhibitory activities against HIV-1 Reverse Transcriptase. Our approach was based on a series of compounds recognized for their HIV-1 RT enzymatic inhibitory activities. These compounds were designed via software, with their descriptors computed using multiple tools. The most statistically promising model was chosen, and its domain of application was ascertained. Furthermore, compounds exhibiting comparable biological activity to existing drugs were identified as potential inhibitors of HIV-1 RT. The compounds underwent evaluation based on their chemical absorption, distribution, metabolism, excretion, toxicity properties, and adherence to Lipinski's rule. Molecular docking techniques were employed to examine the interaction between the Reverse Transcriptase (Wild Type and Mutant Type) and the ligands, including a known drug available in the market. Molecular dynamics simulations were also conducted to assess the stability of the RT-ligand complexes. Our results reveal some of the new compounds as promising candidates for effectively inhibiting HIV-1 Reverse Transcriptase, matching the potency of the established drug. This necessitates further experimental validation. This study, beyond its immediate results, provides a methodological foundation for future endeavors aiming to discover and design new inhibitors targeting HIV-1 Reverse Transcriptase.

Keywords: QSAR, ADMET properties, molecular docking, molecular dynamics simulation, reverse transcriptase inhibitors, HIV type 1

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Authors: Pooja Kumari, Anandkumar Tengli

Abstract:

Aurora kinase enzyme, a protein on overexpression, leads to metastasis and is extremely important for women’s health in terms of prevention or treatment. While creating a targeted technique, the aim of the work is to design purine molecules that inhibit in aurora kinase enzyme and helps to suppress breast cancer. Purine molecules attached to an amino acid in DNA block protein synthesis or halt the replication and metastasis caused by the aurora kinase enzyme. Various protein related to the overexpression of aurora protein was docked with purine molecule using Biovia Drug Discovery, the perpetual software. Various parameters like X-ray crystallographic structure, presence of ligand, Ramachandran plot, resolution, etc., were taken into consideration for selecting the target protein. A higher negative binding scored molecule has been taken for simulation studies. According to the available research and computational analyses, purine compounds may be powerful enough to demonstrate a greater affinity for the aurora target. Despite being clinically effective now, purines were originally meant to fight breast cancer by inhibiting the aurora kinase enzyme. In in-silico studies, it is observed that purine compounds have a moderate to high potency compared to other molecules, and our research into the literature revealed that purine molecules have a lower risk of side effects. The research involves the design, synthesis, and identification of active purine molecules against breast cancer. Purines are structurally similar to the normal metabolites of adenine and guanine; hence interfere/compete with protein synthesis and suppress the abnormal proliferation of cells/tissues. As a result, purine target metastasis cells and stop the growth of kinase; purine derivatives bind with DNA and aurora protein which may stop the growth of protein or inhibits replication and stop metastasis of overexpressed aurora kinase enzyme.

Keywords: aurora kinases, in silico studies, medicinal chemistry, combination therapies, chronic cancer, clinical translation

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Authors: Akshay Patil

Abstract:

Objective: Mediation analysis identifies causal pathways by testing the relationships between the NCR, the OS, and an intermediate variable that mediates the relationship between the Nimotuzumab-cisplatin-radiation (NCR) and OS. Introduction: In randomized controlled trials, the primary interest is in the mechanisms by which an intervention exerts its effects on the outcomes. Clinicians are often interested in how the intervention works (or why it does not work) through hypothesized causal mechanisms. In this work, we highlight the value of understanding causal mechanisms in randomized trial by applying causal mediation analysis in a randomized trial in oncology. Methods: Data was obtained from a phase III randomized trial (Subgroup of HPVNOCP). NCR is reported to significantly improve the OS of patients locally advanced head and neck cancer patients undergoing definitive chemoradiation. Here, based on trial data, the mediating effect of NCR on patient overall survival was systematically quantified through progression-free survival(PFS), disease free survival (DFS), Loco-regional failure (LRF), and the disease control rate (DCR), Overall response rate (ORR). Effects of potential mediators on the HR for OS with NCR versus cisplatin-radiation (CR) were analyzed by Cox regression models. Statistical analyses were performed using R software Version 3.6.3 (The R Foundation for Statistical Computing) Results: Effects of potential mediator PFS was an association between NCR treatment and OS, with an indirect-effect (IE) 0.76(0.62 – 0.95), which mediated 60.69% of the treatment effect. Taking into account baseline confounders, the overall adjusted hazard ratio of death was 0.64 (95% CI: 0.43 – 0.96; P=0.03). The DFS was also a significant mediator and had an IE 0.77 (95% CI; 0.62-0.93), 58% mediated). Smaller mediation effects (maximum 27%) were observed for LRF with IE 0.88(0.74 – 1.06). Both DCR and ORR mediated 10% and 15%, respectively, of the effect of NCR vs. CR on the OS with IE 0.65 (95% CI; 0.81 – 1.08) and 0.94(95% CI; 0.79 – 1.04). Conclusion: Our findings suggest that PFS and DFS were the most important mediators of the OS with nimotuzumab to weekly cisplatin-radiation in HPVNOCP.

Keywords: mediation analysis, cancer data, survival, NCR, HPV negative oropharyngeal

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Authors: Hichem Sebai, Mohamed Amine Jabri, Kais Rtibi, Haifa Tounsi, Lamjed Marzouki

Abstract:

Artemisia campestris has been widely used in Tunisian traditional medicine for its health beneficial effects. However, the present study aims at evaluating the antiulcer effects of Artemisia campestris aqueous extract (ACAE) as well as the mechanism of action involved in such gastroprotection. In this respect, male Wistar rats were divided into seven groups: control, aspirin (ASPR), ASPR + various doses of ACAE (100, 200 and 400 mg/kg, b.w.), ASPR+ famotidine and ASPR+ caffeic acid. Animals were pre-treated with ACAE extract during 10 days. We firstly showed that aspirin administration was accompanied by an oxidative stress status assessed by an increase of malondialdehyde (MDA) level, a decrease of sulfhydryl -(SH) groups content and depletion of antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Pre-treatment with ACAE protected against aspirin-induced gastric oxidative stress. More importantly, aspirin administration increased plasma and tissue hydrogen peroxide (H₂O₂), free iron and calcium levels while the ACAE pre-treatment reversed all aspirin-induced intracellular mediators disturbance. The results of the present study clearly indicated that AEAC gastroprotection might be related, at least in part, to its antioxidant properties as well as to various gastric mucosal defense mechanisms, including the protection of gastric sulfhydryls and an opposite effect on some intracellular mediators such as free iron, hydrogen peroxide, and calcium. However, our data confirm the use of Artemisia campestris extracts in the Tunisian traditional folk medicine for the treatment of gastrointestinal diseases.

Keywords: gastric ulcer, Artemisia campestris, oxidative stress, sulfhydryl groups, Fenton reaction, rat

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Authors: Younes El Khchine, Mohammed Sriti

Abstract:

A parametric study has been conducted to analyse the flow around S809 airfoil of a wind turbine in order to better understand the characteristics and effects of laminar separation bubble (LSB) on aerodynamic design for maximizing wind turbine efficiency. Numerical simulations were performed at low Reynolds numbers by solving the Unsteady Reynolds Averaged Navier-Stokes (URANS) equations based on C-type structural mesh and using the γ-Reθt turbulence model. A two-dimensional study was conducted for the chord Reynolds number of 1×10⁵ and angles of attack (AoA) between 0 and 20.15 degrees. The simulation results obtained for the aerodynamic coefficients at various angles of attack (AoA) were compared with XFoil results. A sensitivity study was performed to examine the effects of Reynolds number and free-stream turbulence intensity on the location and length of the laminar separation bubble and the aerodynamic performances of wind turbines. The results show that increasing the Reynolds number leads to a delay in the laminar separation on the upper surface of the airfoil. The increase in Reynolds number leads to an accelerated transition process, and the turbulent reattachment point moves closer to the leading edge owing to an earlier reattachment of the turbulent shear layer. This leads to a considerable reduction in the length of the separation bubble as the Reynolds number is increased. The increase in the level of free-stream turbulence intensity leads to a decrease in separation bubble length and an increase in the lift coefficient while having negligible effects on the stall angle. When the AoA increased, the bubble on the suction airfoil surface was found to move upstream to the leading edge of the airfoil, that causes earlier laminar separation.

Keywords: laminar separation bubble, turbulence intensity, S809 airfoil, transition model, Reynolds number

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Authors: Vishal V. R. Nandigana, Mohammad Heiranian, Narayana R. Aluru

Abstract:

Graphene material has found tremendous applications in water desalination, DNA sequencing and energy storage. Multiple nanopores are etched to create opening for water desalination and energy storage applications. The nanopores created are of the order of 3-5 nm allowing multiple ions to transport through the pore. In this paper, we present for the first time, molecular dynamics study of single ion transport, where only one ion passes through the graphene nanopore. The diameter of the graphene nanopore is of the same order as the hydration layers formed around each ion. Analogous to single electron transport resulting from ionic transport is observed for the first time. The current-voltage characteristics of such a device are similar to single electron transport in quantum dots. The current is blocked until a critical voltage, as the ions are trapped inside a hydration shell. The trapped ions have a high energy barrier compared to the applied input electrical voltage, preventing the ion to break free from the hydration shell. This region is called “Coulomb blockade region”. In this region, we observe zero transport of ions inside the nanopore. However, when the electrical voltage is beyond the critical voltage, the ion has sufficient energy to break free from the energy barrier created by the hydration shell to enter into the pore. Thus, the input voltage can control the transport of the ion inside the nanopore. The device therefore acts as a binary storage unit, storing 0 when no ion passes through the pore and storing 1 when a single ion passes through the pore. We therefore postulate that the device can be used for fluidic computing applications in chemistry and biology, mimicking a computer. Furthermore, the trapped ion stores a finite charge in the Coulomb blockade region; hence the device also acts a super capacitor.

Keywords: graphene nanomembrane, single ion transport, Coulomb blockade, nanofluidics

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Authors: Yi Sun, George Ed Rainger, Steve P. Watson

Abstract:

Background: Beyond the classical roles in haemostasis and thrombosis, platelets are important in the initiation and development of various thrombo-inflammatory diseases. In atherosclerosis and deep vein thrombosis, for example, platelets bridge monocytes with endothelium and form heterotypic aggregates with monocytes in the circulation. This can alter monocyte phenotype by inducing their activation, stimulating adhesion and migration. These interactions involve cell surface receptor-ligand pairs on both cells. This list is likely incomplete as new interactions of importance to platelet biology are continuing to be discovered as illustrated by our discovery of PEAR-1 binding to FcεR1α. Results: We have developed a highly sensitive avidity-based assay to identify novel extracellular interactions among 126 recombinantly-expressed platelet cell surface and secreted proteins involved in platelet aggregation. In this study, we will use this method to identify novel platelet-monocyte interactions. We aim to identify ligands for orphan receptors and novel partners of well-known proteins. Identified interactions will be studied in preliminary functional assays to demonstrate relevance to the inflammatory processes supporting atherogenesis. Conclusions: Platelet-monocyte interactions are essential for the development of thromboinflammatory disease. Up until relatively recently, technologies only allow us to limit our studies on each individual protein interaction at a single time. These studies propose for the first time to study the cell surface platelet-monocyte interactions in a systematic large-scale approach using a reliable screening method we have developed. If successful, this will likely to identify previously unknown ligands for important receptors that will be investigated in details and also provide a list of novel interactions for the field. This should stimulate studies on developing alternative therapeutic strategies to treat vascular inflammatory disorders such as atherosclerosis, DVT and sepsis and other clinically important inflammatory conditions.

Keywords: membrane proteins, large-scale screening, platelets, recombinant expression

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Authors: Xiaodi Su, Xin Ting Zheng, Laura Sutarlie, Nur Asinah binte Mohamed Salleh, Yong Yu

Abstract:

Wound healing is a dynamic process with multiple phases. Rapid profiling and quantitative characterization of inflammation and infection remain challenging. We have developed paper-like battery-free multiplexed sensors for holistic wound assessment via quantitative detection of multiple inflammation and infection markers. In one of the designs, the sensor patch consists of a wax-printed paper panel with five colorimetric sensor channels arranged in a pattern resembling a five-petaled flower (denoted as a ‘Petal’ sensor). The five sensors are for temperature, pH, trimethylamine, uric acid, and moisture. The sensor patch is sandwiched between a top transparent silicone layer and a bottom adhesive wound contact layer. In the second design, a palm-like-shaped paper strip is fabricated by a paper-cutter printer (denoted as ‘Palm’ sensor). This sensor strip carries five sensor regions connected by a stem sampling entrance that enables rapid colorimetric detection of multiple bacteria metabolites (aldehyde, lactate, moisture, trimethylamine, tryptophan) from wound exudate. For both the “\’ Petal’ and ‘Palm’ sensors, color images can be captured by a mobile phone. According to the color changes, one can quantify the concentration of the biomarkers and then determine wound healing status and identify/quantify bacterial species in infected wounds. The ‘Petal’ and ‘Palm’ sensors are validated with in-situ animal and ex-situ skin wound models, respectively. These sensors have the potential for integration with wound dressing to allow early warning of adverse events without frequent removal of the plasters. Such in-situ and early detection of non-healing condition can trigger immediate clinical intervention to facilitate wound care management.

Keywords: wound infection, colorimetric sensor, paper fluidic sensor, wound care

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Authors: Rajapaksha Gedara Prasad Tharanga Jayasooriya, Matharage Gayani Dilshara, Yung Hyun Choi, Gi-Young Kim

Abstract:

Camptothecin (CPT) is a quinolone alkaloid which inhibits DNA topoisomerase I that induces cytotoxicity in a variety of cancer cell lines. We previously showed that CPT effectively inhibited invasion of prostate cancer cells and also combined treatment with subtoxic doses of CPT and TNF-related apoptosis-inducing ligand (TRAIL) potentially enhanced apoptosis in a caspase-dependent manner in hepatoma cancer cells. Here, we found that treatment with CPT caused an irreversible cell cycle arrest in the G2/M phase. CPT-induced cell cycle arrest was associated with a decrease in protein levels of cell division cycle 25C (Cdc25C) and increased the level of cyclin B and p21. The CPT-induced decrease in Cdc25C was blocked in the presence of proteasome inhibitor MG132, thus reversed the cell cycle arrest. In addition to that treatment of CPT-increased phosphorylation of Cdc25C was the resulted of activation of checkpoint kinase 2 (Chk2), which was associated with phosphorylation of ataxia telangiectasia-mutated. Interestingly CPT induced G2/M phase of the cell cycle arrest is reactive oxygen species (ROS) dependent where ROS inhibitors NAC and GSH reversed the CPT-induced cell cycle arrest. These results further confirm by using transient knockdown of nuclear factor-erythroid 2-related factor 2 (Nrf2) since it regulates the production of ROS. Our data reveal that treatment of siNrf2 increased the ROS level as well as further increased the CPT induce G2/M phase cell cycle arrest. Our data also indicate CPT-enhanced cell cycle arrest through the extracellular signal-regulated kinase (ERK) and the c-Jun N-terminal kinase (JNK) pathway. Inhibitors of ERK and JNK more decreased the Cdc25C expression and protein expression of p21 and cyclin B. These findings indicate that Chk2-mediated phosphorylation of Cdc25C plays a major role in G2/M arrest by CPT.

Keywords: camptothecin, cell cycle, checkpoint kinase 2, nuclear factor-erythroid 2-related factor 2, reactive oxygen species

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Authors: Ketaki D. Belsare, Nicholas F. Polizzi, Lior Shtayer, William F. DeGrado

Abstract:

Nature utilizes metalloproteins to perform chemical transformations with activities and selectivities that have long been the inspiration for design principles in synthetic and biological systems. The chemical reactivities of metalloproteins are directly linked to local environment effects produced by the protein matrix around the metal cofactor. A complete understanding of how the protein matrix provides these interactions would allow for the design of functional metalloproteins. The de novo computational design of proteins have been successfully used in design of active sites that bind metals like di-iron, zinc, copper containing cofactors; however, precisely designing active sites that can bind small molecule ligands (e.g., substrates) along with metal cofactors is still a challenge in the field. The de novo computational design of a functional metalloprotein that contains a purposefully designed substrate binding site would allow for precise control of chemical function and reactivity. Our research strategy seeks to elucidate the design features necessary to bind the cofactor protoporphyrin IX (hemin) in close proximity to a substrate binding pocket in a four helix bundle. First- and second-shell interactions are computationally designed to control orientation, electronic structure, and reaction pathway of the cofactor and substrate. The design began with a parameterized helical backbone that positioned a single histidine residue (as an axial ligand) to receive a second-shell H-bond from a Threonine on the neighboring helix. The metallo-cofactor, hemin was then manually placed in the binding site. A structural feature, pi-bulge was introduced to give substrate access to the protoporphyrin IX. These de novo metalloproteins are currently being tested for their activity towards hydroxylation and epoxidation. The de novo designed protein shows hydroxylation of aniline to 4-aminophenol. This study will help provide structural information of utmost importance in understanding de novo computational design variables impacting the functional activities of a protein.

Keywords: metalloproteins, protein design, de novo protein, biocatalysis

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Authors: Junaid Jibran Jawed, Prasanta Saini, Subrata Majumdar

Abstract:

Background: Leishmania donovani infection causes severe host immune-suppression through the modulation of pathogen recognition receptors. Apart from TLRs (Toll Like Receptor), recent studies focus on the important contribution of NLR (NOD-Like Receptor) family member NOD1 and NOD2 as these receptors are capable of triggering host innate immunity. The aim of this study was to decipher the role of NOD1/NOD2 receptors during experimental visceral leishmaniasis (VL) and the important link between host failure and parasite evasion strategy. Method: The status of NOD1 and NOD2 receptors were analysed in uninfected and infected cells through western blotting and RT-PCR. The active contributions of these receptors in reducing parasite burden were confirmed by siRNA mediated silencing, and over-expression studies and the parasite numbers were calculated through microscopic examination of the Giemsa-stained slides. In-vivo studies were done by using non-toxic dose of Mw (Mycobacterium indicus pranii), Ara-LAM(Arabinoasylated lipoarabinomannan) along with MDP (Muramyl dipeptide) administration. Result: Leishmania donovani infection of the macrophages reduced the expression of NOD2 receptors whereas NOD1 remain unaffected. MDP, a NOD2-ligand, treatment during over-expression of NOD2, reduced the parasite burden effectively which was associated with increased pro-inflammatory cytokine generation and NO production. In experimental mouse model, Ara-LAM treatment increased the expression of NOD2 and in combination with MDP it showed active therapeutic potential against VL and found to be more effective than Mw which was already reported to be involved in NOD2 modulation. Conclusion: This work explores the essential contribution of NOD2 during experimental VL and mechanistic understanding of Ara-LAM + MDP combination therapy to work against this disease and highlighted NOD2 as an essential therapeutic target.

Keywords: Ara-LAM (Arabinoacylated Lipoarabinomannan), NOD2 (nucleotide binding oligomerization receptor 2), MDP (muramyl di peptide), visceral Leishmaniasis

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Authors: Souad Slimani, Sylvain Gravier, Simon Schmidt

Abstract:

Recently, several vertex identifying notions were introduced (identifying coloring, lid-coloring,...); these notions were inspired by identifying codes. All of them, as well as original identifying code, is based on separating two vertices according to some conditions on their closed neighborhood. Therefore, twins can not be identified. So most of known results focus on twin-free graph. Here, we show how twins can modify optimal value of vertex-identifying parameters for identifying coloring and locally identifying coloring.

Keywords: identifying coloring, locally identifying coloring, twins, separating

Procedia PDF Downloads 140

Authors: Younes El Khchine

Abstract:

A parametric study has been conducted to analyse the flow around S809 airfoil of a wind turbine in order to better understand the characteristics and effects of laminar separation bubble (LSB) on aerodynamic design for maximizing wind turbine efficiency. Numerical simulations were performed at low Reynolds numbers by solving the Unsteady Reynolds Averaged Navier-Stokes (URANS) equations based on C-type structural mesh and using the γ-Reθt turbulence model. A two-dimensional study was conducted for the chord Reynolds number of 1×105 and angles of attack (AoA) between 0 and 20.15 degrees. The simulation results obtained for the aerodynamic coefficients at various angles of attack (AoA) were compared with XFoil results. A sensitivity study was performed to examine the effects of Reynolds number and free-stream turbulence intensity on the location and length of the laminar separation bubble and the aerodynamic performances of wind turbines. The results show that increasing the Reynolds number leads to a delay in the laminar separation on the upper surface of the airfoil. The increase in Reynolds number leads to an accelerated transition process, and the turbulent reattachment point moves closer to the leading edge owing to an earlier reattachment of the turbulent shear layer. This leads to a considerable reduction in the length of the separation bubble as the Reynolds number is increased. The increase in the level of free-stream turbulence intensity leads to a decrease in separation bubble length and an increase in the lift coefficient while having negligible effects on the stall angle. When the AoA increased, the bubble on the suction airfoil surface was found to move upstream to the leading edge of the airfoil, causing earlier laminar separation.

Keywords: laminar separation bubble, turbulence intensity, s809 airfoil, transition model, Reynolds number

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Authors: Younes El Khchine, Mohammed Sriti

Abstract:

A parametric study has been conducted to analyse the flow around S809 airfoil of wind turbine in order to better understand the characteristics and effects of laminar separation bubble (LSB) on aerodynamic design for maximizing wind turbine efficiency. Numerical simulations were performed at low Reynolds number by solving the Unsteady Reynolds Averaged Navier-Stokes (URANS) equations based on C-type structural mesh and using γ-Reθt turbulence model. Two-dimensional study was conducted for the chord Reynolds number of 1×105 and angles of attack (AoA) between 0 and 20.15 degrees. The simulation results obtained for the aerodynamic coefficients at various angles of attack (AoA) were compared with XFoil results. A sensitivity study was performed to examine the effects of Reynolds number and free-stream turbulence intensity on the location and length of laminar separation bubble and aerodynamic performances of wind turbine. The results show that increasing the Reynolds number leads to a delay in the laminar separation on the upper surface of the airfoil. The increase in Reynolds number leads to an accelerate transition process and the turbulent reattachment point move closer to the leading edge owing to an earlier reattachment of the turbulent shear layer. This leads to a considerable reduction in the length of the separation bubble as the Reynolds number is increased. The increase of the level of free-stream turbulence intensity leads to a decrease in separation bubble length and an increase the lift coefficient while having negligible effects on the stall angle. When the AoA increased, the bubble on the suction airfoil surface was found to moves upstream to leading edge of the airfoil that causes earlier laminar separation.

Keywords: laminar separation bubble, turbulence intensity, S809 airfoil, transition model, Reynolds number

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Authors: Kristin Lewis, Howard Steele, Anne Murphy, Miriam Steele, Karen Bonuck, Paul Meissner

Abstract:

The present study examines data collected during the randomized control trial (RCT) of the Group Attachment-Based Intervention (GABI©), a trauma-informed, attachment-based intervention aimed at promoting healthy parent-child relationships that support child development. Families received treatment at Treatment Center and were randomly assigned to either the GABI condition or the treatment as usual condition, a parenting class called Systematic Training for Effective Parenting (STEP). Significant improvements in the parent-child relationship have been reported for families participating in GABI, but not in the STEP control group relying on Coding Interactive Behavior (CIB) as applied to 5-minute video-films of mothers and their toddlers in a free play context. This report considers five additional attachment-relevant 'clinical codes' that were also applied to the 5-minute free play sessions. Seventy-two parent-child dyads (38 in GABI and 34 in STEP) were compared to one another at intake and end-of-treatment, on these five-point dimensions: two-parent codes—the dissociation and ignoring; two child codes—simultaneous display of contradictory behavior and fear; and one parent-child code, i.e., role reversal. Overall, scores were low for these clinical codes; thus, a binary measure was computed contrasting no evidence with some evidence of each clinical code. Crosstab analyses indicate that child fear at end-of-treatment was significantly lower among children who participated in GABI (7% or 3 children) as compared to those whose mothers participated in STEP (29% or 10 children) Chi Sq= 6.57 (1), p < .01. Discussion focuses on the potential for GABI to reduce childhood fearfulness and so enhance the child's health.

Keywords: coding interactive behavior, clinical codes, group attachment based intervention, GABI, attachment, fear

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Authors: Yu-Tzu Hsu, Alice Wu, Hsiang-Kuang Tseng

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Introduction: Hepatitis A virus causes acute hepatitis and is usually transmitted by a fecal-oral route of food contamination, which is more prevalent in areas with poor hygienic practices. However, we described a hepatitis A outbreak associated with a fecal-oral route of sexual behavior in men who has sex with men (MSM) in Northern Taiwan. Methods: We retrospectively collected patients with acute HAV infection in MacKay Memorial Hospital, Taipei, Taiwan between July 2015 and November 2016. Demographic data (age, gender, onset time and infection risk), laboratory data (GOT, GPT, bilirubin, HIV status, HBsAg, HCV antibody and syphilis), clinical symptoms and travel history with a foreign tour were analyzed. We compared variables between HIV and non-HIV group. Unless otherwise stated, continuous variables were expressed as mean ± SD, and categorical variables were expressed as number (percentage) for each item. The t test for continuous variables was applied for the comparison between two groups and chi-square for categorical variables were applied for measures of association. Results: We collected 80 cases during the study period. Among them, 54 (67.5%) cases were MSM and 43 (53.8%) cases were HIV positive. The average age was 32.6±7.59 years-old. The average value of initial liver function was 1324 IU/L for AST (GOT), 2100 IU/L for ALT (GPT), and 5.82 mg/dL for bilirubin. We found seven (8.6%) cases were in the status of HBV carrier, five (6.3%) cases were positive for HCV antibody, and 15 (18.6%) cases were co-infected with syphilis. With regards to associated symptoms, 32 (40%) had fever, 46 (57.5%) had nausea, 34 (42.5%) had abdominal discomfort and 46 (57.5%) had general malaise. To compare the non-HIV patients with HIV patients, HIV patients were more likely to be male (p=0.008), MSM (p=0.000), co-infected syphilis (p=0.000) and slowly improving liver function of transaminases (p=0.033, 0.027). Conclusion: The HAV outbreak in Northern Taiwan was mainly occurred in MSM population. Hereafter, our cohort data support a policy in Taiwan to provide one dose of free HAV vaccine shot in this population. Hopefully, the outbreak could be stop by the free vaccine policy and public education.

Keywords: acute hepatitis A, men who has sex with men, human immunodeficiency virus, vaccine

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Authors: Armando A. Rodríguez, Emilio Salceda, Anoland Garateix, André J. Zaharenko, Steve Peigneur, Omar López, Tirso Pons, Michael Richardson, Maylín Díaz, Yasnay Hernández, Ludger Ständker, Jan Tytgat, Enrique Soto

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Acid-sensing ion channels are cation (Na+) channels activated by a pH drop. These proteins belong to the ENaC/degenerin superfamily of sodium channels. ASICs are involved in sensory perception, synaptic plasticity, learning, memory formation, cell migration and proliferation, nociception, and neurodegenerative disorders, among other processes; therefore those molecules that specifically target these channels are of growing pharmacological and biomedical interest. Sea anemones produce a large variety of ion channels peptide toxins; however, those acting on ligand-gated ion channels, such as Glu-gated, Ach-gated ion channels, and acid-sensing ion channels (ASICs), remain barely explored. The peptide PhcrTx1 is the first compound characterized from the sea anemone Phymanthus crucifer, and it constitutes a novel ASIC inhibitor. This peptide was purified by chromatographic techniques and pharmacologically characterized on acid-sensing ion channels of mammalian neurons using patch-clamp techniques. PhcrTx1 inhibited ASIC currents with an IC50 of 100 nM. Edman degradation yielded a sequence of 32 amino acids residues, with a molecular mass of 3477 Da by MALDI-TOF. No similarity to known sea anemone peptides was found in protein databases. The computational analysis of Cys-pattern and secondary structure arrangement suggested that this is a structurally ICK (Inhibitor Cystine Knot)-type peptide, a scaffold that had not been found in sea anemones but in other venomous organisms. These results show that PhcrTx1 represents the first member of a new structural group of sea anemones toxins acting on ASICs. Also, this peptide constitutes a novel template for the development of drugs against pathologies related to ASICs function.

Keywords: animal toxin, inhibitor cystine knot, ion channel, sea anemone

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Authors: Mpho Agnes Mbeo, Patient Rambe

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The thirteenth year of the Central University of Technology, Free State’s (CUT) transition from a vocational and professional training orientation institution (i.e. a technikon) into a university with a strong research focus has neither been a smooth nor an easy one. At the heart of this transition was the need to transform the psychological faculties of academic and research staffs compliment who were accustomed to training graduates for industrial placement. The lack of a culture of research that fully embraces a strong ethos of conducting world-class research needed to be addressed. The induction and socialisation of academic staff into the development and execution of cutting-edge research also required the provision of research support and the creation of a conducive academic environment for research, both for emerging and non-research active academics. Drawing on ten cases, comprising four heads of departments, three prolific established researchers, and three emerging researchers, this study explores the challenges faced in establishing a strong research culture at the university. Furthermore, it gives an account of the extent to which the current research interventions have addressed the perceivably “missing research culture”, and the implications of these interventions for knowledge management. Evidence suggests that the endowment of an ideal institutional research environment (comprising strong internet networks, persistent connectivity on and off campus), research peer mentorship, and growing publication outputs should be matched by a coherent research incentive culture and strong research leadership. This is critical to building new knowledge and entrenching knowledge management founded on communities of practice and scholarly networking through the documentation and communication of research findings. The study concludes that the multiple policy documents set for the different domains of research may be creating pressure on researchers to engage research activities and increase output at the expense of research quality.

Keywords: Central University of Technology, performance, publication, research culture, university

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Authors: Marianna Ciaccia, Gennaro Agrimi, Isabella Pisano, Maurizio Bettiga, Silvia Rapacioli, Giulia Mensa, Monica Marzagalli

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Objective: Untargeted metabolomic analysis of extracellular metabolites is a powerful approach that focuses on comprehensively profiling in the extracellular space. In this study, we applied extracellular metabolomic analysis to investigate the metabolism of two probiotic microorganisms with health benefits that extend far beyond the digestive tract and the immune system. Methods: Analytical techniques employed in extracellular metabolomic analysis encompass various technologies, including mass spectrometry (MS), which enables the identification of metabolites present in the fermentation media, as well as the comparison of metabolic profiles under different experimental conditions. Multivariate statistical analysis techniques like principal component analysis (PCA) or partial least squares-discriminant analysis (PLS-DA) play a crucial role in uncovering metabolic signatures and understanding the dynamics of metabolic networks. Results: Different types of supernatants from fermentation processes, such as dairy-free, not dairy-free media and media with no cells or pasteurized, were subjected to metabolite profiling, which contained a complex mixture of metabolites, including substrates, intermediates, and end-products. This profiling provided insights into the metabolic activity of the microorganisms. The integration of advanced software tools has facilitated the identification and characterization of metabolites in different fermentation conditions and microorganism strains. Conclusions: In conclusion, untargeted extracellular metabolomic analysis, combined with software tools, allowed the study of the metabolites consumed and produced during the fermentation processes of probiotic microorganisms. Ongoing advancements in data analysis methods will further enhance the application of extracellular metabolomic analysis in fermentation research, leading to improved bioproduction and the advancement of sustainable manufacturing processes.

Keywords: biotechnology, metabolomics, lactic bacteria, probiotics, postbiotics

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Authors: J. A. N. Sandamali, R. P. Hewawasam, K. A. P. W. Jayatilaka, L. K. B. Mudduwa

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Introduction: Doxorubicin is widely used in the treatment of solid organ tumors and hematological malignancies, but the dose-dependent cardiotoxicity due to free radical formation compromises its clinical utility. Therapeutic strategies which enhance cellular endogenous defense systems have been identified as promising approaches to combat oxidative stress-associated conditions. Cinnamomum zeylanicum (Ceylon cinnamon) has a number antioxidant compounds, which can effectively scavenge reactive oxygen including superoxide anions, hydroxyl radicals and as well as other free radicals. Therefore, the objective of the study was to elucidate the most effective dose of Cinnamomum bark extract which ameliorates doxorubicin-induced cardiotoxicity. Materials and methods: Wistar rats were divided into seven groups of 10 animals in each. Group 1: normal control (distilled water, orally, for 14 days, 10 mL/kg saline, ip, after 16 hours fast on the 11th day); Group 2: doxorubicin control (distilled water, orally, for 14 days, 18 mg/kg doxorubicin, ip, after 16 hour fast on the 11th day); Groups 3-7: five doses of freeze dried aqueous bark extracts (0.125, 0.25, 0.5, 1.0, 2.0g/kg, orally, daily for 14 days, 18 mg/kg doxorubicin, ip, after 16 hours fast on the 11th day). Animals were sacrificed on the 15th day and blood was collected for the estimation of cardiac troponin I (cTnI), AST and LDH concentrations and myocardial tissues were collected for histopathological assessment of myocardial damage and irreversible changes were graded by developing a score. Results: cTnI concentration of groups 1-7 were 0, 161.9, 128.6, 95.9, 38, 19.41 & 12.36 pg/mL showing significant differences (p<0.05) between group 2 and groups 4-7. In groups 1-7, serum AST concentration were 26.82, 68.1, 37.18, 36.23, 26.8, 26.62 & 22.43U/L and LDH concentrations were 1166.13, 2428.84, 1658.35, 1474.34, 1277.58, 1110.21 & 974.40U/L and a significant difference (p<0.05) was observed between group 2 and groups 3-7. The maximum score for myocardial necrosis was observed in group 2. Parallel to the increase of the dosage of plant extract, a gradual reduction of the score for myocardial necrosis was observed in groups 3-7. Reversible histological changes such as vacuolation, congestion were observed in group 2 and all plant treated groups. Haemorrhages, inflammatory cell infiltrations, and interstitial oedema were observed in group 2, but absent in groups treated with higher doses of the plant extract. Discussion & Conclusion: According to the in vitro antioxidant assays performed, Cinnamomum zeylanicum (Ceylon cinnamon) bark possesses high amounts of polyphenolic substances and high antioxidant activity. The present study showed that Cinnamomum zeylanicum extract at 2.0 g/kg possesses the most significant cardioprotective effect against doxorubicin-induced cardiotoxicity. It can be postulated that pretreatment with Cinnamomum bark extract may replenish the cardiomyocytes with antioxidants that are needed for the defense against oxidative stress induced by doxorubicin.

Keywords: cardioprotection, Cinnamomum zeylanicum, doxorubicin, free radicals

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Authors: Mohamed M. A. Abumandour

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The red swamp freshwater crayfish breathe through three types of feather-like trichobranchiate gills; podobranchiae, arthrobranchiae and pleurobranchiae. All gills have the same general structure and appearance; plume-like with single broad setiferous, and single axis. The gill consists of axis with numerous finger-like filaments, having three morphological types; round, pointed and somewhat hooked shaped. The direction of filaments vary according their position; in middle region were nearly perpendicular to gill axis while in the apex were nearly parallel to axis. There were characteristic system of gill spines on; central axis (two types were distinguishable by presence of socket), basal plate, setobranch (long non-branched and short multidenticulate) and on the bilobed epipodal plate. There are four shape of spinated-like distal region of setobranch seta; two pointed processes (longitudinal arrangement and irregular arranged) and two broad processes (transverse triangular and multidenticulate). The bilobed epipodal plate devoid from any filaments and extended from outer side of podobranchiae as triangular basal part then extended between the gills as cord-like middle part then pass under the gill to lies against the thoracic body wall. By SEM, the apical part of bilobed epipodal plate have serrated free border and corrugated surface while the middle part have none serrated free border. There are two methods of gill cleaning mechanism in crayfish; passive and active method. The passive method occurred by; setae of setobranch, branchiostegite, bilobed epipodal plate, setiferous arthrodial lamellae and reversing the respiratory water through a narrow spaced branchial chamber.

Keywords: crayfis, gill spines, setobranch, gill setae, cleaning mechanisms

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Authors: Hui Tag, Jambey Tsering, Pallabi Kalita Hui, Baikuntha Jyoti Gogoi, Vijay Veer

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The food security issues and its relevance in High Mountain regions of the world have been often neglected. Wild edible plants have been playing a major role in livelihood security among the tribal Communities of East Himalayan Region of the world since time immemorial. The Eastern Himalayan Region of India is one of the mega diverse regions of world and rated as top 12th Global Biodiversity Hotspots by IUCN and recognized as one of the 200 significant eco-regions of the Globe. The region supports one of the world’s richest alpine floras and about one-third of them are endemic to the region. There are at least 7,500 flowering plants, 700 orchids, 58 bamboo species, 64 citrus species, 28 conifers, 500 mosses, 700 ferns and 728 lichens. The region is the home of more than three hundred different ethnic communities having diverse knowledge on traditional uses of flora and fauna as food, medicine and beverages. Monpa, Memba and Khamba are among the local communities residing in high altitude region of Eastern Himalaya with rich traditional knowledge related to utilization of wild edible plants. The Monpas, Memba and Khamba are the followers Mahayana sect of Himalayan Buddhism and they are mostly agrarian by primary occupation and also heavily relaying on wild edible plants for their livelihood security during famine since millennia. In the present study, we have reported traditional uses of 40 wild edible plant species and out of which 6 species were analysed at biochemical level for nutrients contents and free radical scavenging activities. The results have shown significant free radical scavenging (antioxidant) activity and nutritional potential of the selected 6 wild edible plants used by the local communities of Eastern Himalayan Region of India.

Keywords: East Himalaya, local community, wild edible plants, nutrition, food security

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Authors: Aditi Acharya

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Environmental pollution is threatening the environmental and human health in the most drastic way. This paper provides insight about the affects of environmental pollution in the perspective of water pollution. Sewage in drinking water, the increasing contamination of water bodies and water resources and the human beings are the major contributors, increasing the harsh activities of pollution. The research presents information about the sources of pollution, its impacts and control activities to be undertaken to make our environment free from water pollution.

Keywords: environmental pollution, water pollution, nanotechnology, nanomaterials

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Authors: D. Zhigulskaya, V. Anisimov, A. Pikunov, K. Babanova, S. Zuev, A. Latyshkova, K. Сhernozatonskiy, A. Revazov

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Electrophysiology of information processing in reading is certainly a popular research topic. Natural reading, however, has been relatively poorly studied, despite having broad potential applications for learning and education. In the current study, we explore the relationship between text categories and spontaneous electroencephalogram (EEG) while reading. Thirty healthy volunteers (mean age 26,68 ± 1,84) participated in this study. 15 Russian-language texts were used as stimuli. The first text was used for practice and was excluded from the final analysis. The remaining 14 were opposite pairs of texts in one of 7 categories, the most important of which were: interesting/boring, fiction/non-fiction, free reading/reading with an instruction, reading a text/reading a pseudo text (consisting of strings of letters that formed meaningless words). Participants had to read the texts sequentially on an Apple iPad Pro. EEG was recorded from 12 electrodes simultaneously with eye movement data via ARKit Technology by Apple. EEG spectral amplitude was analyzed in Fz for theta-band (4-8 Hz) and in C3, C4, P3, and P4 for alpha-band (8-14 Hz) using the Friedman test. We found that reading an interesting text was accompanied by an increase in theta spectral amplitude in Fz compared to reading a boring text (3,87 µV ± 0,12 and 3,67 µV ± 0,11, respectively). When instructions are given for reading, we see less alpha activity than during free reading of the same text (3,34 µV ± 0,20 and 3,73 µV ± 0,28, respectively, for C4 as the most representative channel). The non-fiction text elicited less activity in the alpha band (C4: 3,60 µV ± 0,25) than the fiction text (C4: 3,66 µV ± 0,26). A significant difference in alpha spectral amplitude was also observed between the regular text (C4: 3,64 µV ± 0,29) and the pseudo text (C4: 3,38 µV ± 0,22). These results suggest that some brain activity we see on EEG is sensitive to particular features of the text. We propose that changes in theta and alpha bands during reading may serve as electrophysiological tools for assessing the reader’s cognitive state as well as his or her attitude to the text and the perceived information. These physiological markers have prospective practical value for developing technological solutions and biofeedback systems for reading in particular and for education in general.

Keywords: EEG, natural reading, reader's cognitive state, theta-rhythm, alpha-rhythm

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Authors: Simont Toussi

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Cameroon and the Central African Republic arebound by the provisions of many regional and international charters, which condemn the manipulation of information, obstacles to access reliable information, or the limitation of freedoms of expression and opinion. These two countries also have constitutional guarantees for free speech and access to true and liable information. However, they are yet to define specific policies and regulations for access to information, disinformation, or misinformation. Yet, certain countries’ laws and regulations related to information and communication technologies, to criminal procedures, to terrorism, or intelligence services contain provisions that rather hider human rights by condemning false information. Like many other African countries, Cameroon and the Central African Republic face a profound democratic regression, and governments use multiple methods to stifle online discourse and digital rights. Despite the increased uptake of digital tools for political participation, there is a lack of interactivity and adoption of these tools. This enables a scarcity of information and creates room for the spreading of disinformation in the public space, hamperingdemocracy and the respect for human rights. This research aims to analyse the adequacy of stakeholders’ responses to disinformation in Cameroon and the Central African Republic in periods of political contestation, such as elections and anti-government protests, to highlight the nature, perpetrators, strategies, and channels of disinformation, as well as its effects on democratic actors, including civil society, bloggers, government critics, activists, and other human rights defenders. The study follows a qualitative method with literature review, content analysis, andkey informant’sinterviews with stakeholders’ representatives, emphasized crowdsourcing as a data and information collecting method in the two countries.

Keywords: disinformation, democracy, political manipulation, social media, media, fake news, central Africa, cameroon, misinformation, free speech

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Authors: Yong Min You

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The study on the torque ripple of Permanent Magnet Synchronous Motors (PMSMs) has been rapidly progressed, which effects on the noise and vibration of the electric vehicle. There are several ways to reduce torque ripple, which are the increase in the number of slots and poles, the notch of the rotor and stator teeth, and the skew of the rotor and stator. However, the conventional methods have the disadvantage in terms of material cost and productivity. The demagnetization characteristic of PMSMs must be attained for electric vehicle application. Due to rare earth supply issue, the demand for Dy-free permanent magnet has been increasing, which can be applied to PMSMs for the electric vehicle. Dy-free permanent magnet has lower the coercivity; the demagnetization characteristic has become more significant. To improve the torque ripple as well as the demagnetization characteristics, which are significant parameters for electric vehicle application, an unequal air-gap model is proposed for a PMSM. A shape optimization is performed to optimize the design variables of an unequal air-gap model. Optimal design variables are the shape of an unequal air-gap and the angle between V-shape magnets. An optimization process is performed by Latin Hypercube Sampling (LHS), Kriging Method, and Genetic Algorithm (GA). Finite element analysis (FEA) is also utilized to analyze the torque and demagnetization characteristics. The torque ripple and the demagnetization temperature of the initial model of 45kW PMSM with unequal air-gap are 10 % and 146.8 degrees, respectively, which are reaching a critical level for electric vehicle application. Therefore, the unequal air-gap model is proposed, and then an optimization process is conducted. Compared to the initial model, the torque ripple of the optimized unequal air-gap model was reduced by 7.7 %. In addition, the demagnetization temperature of the optimized model was also increased by 1.8 % while maintaining the efficiency. From these results, a shape optimized unequal air-gap PMSM has shown the usefulness of an improvement in the torque ripple and demagnetization temperature for the electric vehicle.

Keywords: permanent magnet synchronous motor, optimal design, finite element method, torque ripple

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