Search results for: GAF domain protein

Authors: Yasmin M. Attia, Hanan S. El-Abhar, Mahmoud M. Al Marzabani, Samia A. Shouman

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Background: Tamoxifen (TAM) is the most commonly used hormone therapy for the treatment of early and metastatic breast cancer. Although it significantly decreases the tumor recurrence rate and provides an overall benefit, as much as 20–30% of women still relapse during or after long-term therapy. 3-Bromopyruvate (3-BP) is a promising agent with impressive antitumor effects in several models of animal tumors and cell lines. Aim: This study was designed to investigate the combined effect of (TAM) and (3-BP) in breast cancer cells and to explore their molecular interaction via assessment of apoptotic, angiogenic, and metastatic markers. Methods: In vitro cytotoxicity study was carried out for both compounds to determine the combination regimen producing a synergistic effect and mechanistic pathways were studied using RT-PCR and western techniques. Moreover, the anti-oncolytic and anti-angiogenic potentials were assessed in mice bearing solid Ehrlich carcinoma (SEC). Results: The combined treatment significantly increased the expressions and protein levels of caspase 7, 9, and 3 and decreased of angiogenic markers VEGF, HIF-1α, and HK2 compared to cells treated with either drug individually. However, there were no significant changes in MMP-2 and MMP-9 protein levels. Interestingly, the in vivo results supported the in vitro findings; there was a decrease in the tumor volume and VEFG using immunohistochemistry in the combination-treated groups compared to either TAM or 3-BP treated one. Conclusion: 3-BP synergizes the cytotoxic effect of TAM by increasing apoptosis and decreasing angiogenesis which makes this combination a promising regimen to be applied clinically.

Keywords: tamoxifen, 3-bromopyruvate, breast cancer, cytotoxicity, angiogenesis

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Authors: Mina Rabipour, Elena Pallaske, Floyd Hassenrück, Rocio Rebollido-Rios

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Protein tyrosine kinases, including Lyn kinase of the Src family kinases (SFK), regulate cell proliferation, survival, and differentiation. Lyn kinase has been implicated in various cancers, positioning it as a promising therapeutic target. However, the conserved ATP-binding pocket across SFKs makes developing selective inhibitors challenging. This study aims to address this limitation by exploring the potential for allosteric modulation of Lyn kinase, focusing on how its structural dynamics and specific oncogenic mutations impact its conformation and function. To achieve this, we combined homology modeling, molecular dynamics simulations, and data science techniques to conduct microsecond-length simulations. Our approach allowed a detailed investigation into the interplay between Lyn’s catalytic and regulatory domains, identifying key conformational states involved in allosteric regulation. Additionally, we evaluated the structural effects of Dasatinib, a competitive inhibitor, and ATP binding on Lyn active conformation. Notably, our simulations show that cancer-related mutations, specifically I364L/N and E290D/K, shift Lyn toward an inactive conformation, contrasting with the active state of the wild-type protein. This may suggest how these mutations contribute to aberrant signaling in cancer cells. We conducted a dynamical network analysis to assess residue-residue interactions and the impact of mutations on the Lyn intramolecular network. This revealed significant disruptions due to mutations, especially in regions distant from the ATP-binding site. These disruptions suggest potential allosteric sites as therapeutic targets, offering an alternative strategy for Lyn inhibition with higher specificity and fewer off-target effects compared to ATP-competitive inhibitors. Our findings provide insights into Lyn kinase regulation and highlight allosteric sites as avenues for selective drug development. Targeting these sites may modulate Lyn activity in cancer cells, reducing toxicity and improving outcomes. Furthermore, our computational strategy offers a scalable approach for analyzing other SFK members or kinases with similar properties, facilitating the discovery of selective allosteric modulators and contributing to precise cancer therapies.

Keywords: lyn tyrosine kinase, mutation analysis, conformational changes, dynamic network analysis, allosteric modulation, targeted inhibition

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Authors: Javier Enciso-Benavides, Fredy Fabian, Carlos Castaneda, Luis Alfaro, Alex Choque, Aparicio Aguilar, Javier Enciso

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Background: The use of biomarkers in breast cancer diagnosis, therapy, and prognosis has gained increasing interest. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and may cause relapse. Therefore, due to the importance of diagnosis, therapy, and prognosis, several biomarkers that characterize CSCs have been identified; however, in treatment-naïve triple-negative breast tumors, there is an urgent need to identify new biomarkers and therapeutic targets. According to this, the aim of this study was to identify serum proteins associated with cancer stem cells and pluripotency in women with triple-negative breast tumors in order to subsequently identify a biomarker for this type of breast tumor. Material and Methods: Whole blood samples from 12 women with histopathologically diagnosed triple-negative breast tumors were used after obtaining informed consent from the patient. Blood serum was obtained by conventional procedure and frozen at -80ºC. Identification of cancer stem cell-associated proteins was performed by matrix-assisted laser desorption/ionisation-assisted laser desorption/ionisation mass spectrometry (MALDI-TOF MS), protein analysis was obtained using the AB Sciex TOF/TOF™ 5800 system (AB Sciex, USA). Sequences not aligned by ProteinPilot™ software were analyzed by Protein BLAST. Results: The following proteins related to pluripotency and cancer stem cells were identified by MALDI TOF/TOF mass spectrometry: A-chain, Serpin A12 [Homo sapiens], AIEBP [Homo sapiens], Alpha-one antitrypsin, AT {internal fragment} [human, partial peptide, 20 aa] [Homo sapiens], collagen alpha 1 chain precursor variant [Homo sapiens], retinoblastoma-associated protein variant [Homo sapiens], insulin receptor, CRA_c isoform [Homo sapiens], Hydroxyisourate hydrolase [Streptomyces scopuliridis], MUCIN-6 [Macaca mulatta], Alpha-actinin-3 [Chrysochloris asiatica], Polyprotein M, CRA_d isoform, partial [Homo sapiens], Transcription factor SOX-12 [Homo sapiens]. Recommendations: The serum proteins identified in this study should be investigated in the exosome of triple-negative breast cancer stem cells and in the blood serum of women without breast cancer. Subsequently, proteins found only in the blood serum of women with triple-negative breast cancer should be identified in situ in triple-negative breast cancer tissue in order to identify a biomarker to study the evolution of this type of cancer, or that could be a therapeutic target. Conclusions: Eleven cancer stem cell-related serum proteins were identified in 12 women with triple-negative breast cancer, of which MUCIN-6, retinoblastoma-associated protein variant, transcription factor SOX-12, and collagen alpha 1 chain are the most representative and have not been studied so far in this type of breast tumor. Acknowledgement: This work was supported by Proyecto CONCYTEC–Banco Mundial “Mejoramiento y Ampliacion de los Servicios del Sistema Nacional de Ciencia Tecnología e Innovacion Tecnologica” 8682-PE (104-2018-FONDECYT-BM-IADT-AV).

Keywords: triple-negative breast cancer, MALDI TOF/TOF MS, serum proteins, cancer stem cells

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Authors: Bhawna Chandravanshi, Ramesh Bhonde

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In the present study, we focused on the improvisation of islet survival in hypoxia. The Islet-like cell aggregates (ICAs) derived from Wharton's jelly mesenchymal stem cells (WJ-MSC) were cultured with and without WJ-MSC for 48h in hypoxia and normoxia and tested for their direct trophic effect on β cell survival. The WJ MSCs themselves secreted insulin upon glucose challenge and expressed the pancreatic markers at both transcription and translational level (C-peptide, Insulin, Glucagon and Glut 2). Direct contact of MSCs with ICAs facilitate the highest viability under hypoxia as evidenced by fluorescein diacetate/propidium iodide and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cytokine analysis of the co-cultured ICAs revealed amplification of anti-inflammatory cytokine-like TGFβ and TNFα accompanied by depletion of pro-inflammatory cytokines. The increment in VEGF and PDGFa was also seen showing their ability to vascularize upon transplantation. This was further accompanied by reduction in total reactive oxygen species, nitric oxide, and super oxide ions and down-regulation of Caspase3, Caspase8, p53 and up regulation of Bcl2 confirming prevention of apoptosis in ICAs. There was a significant reduction in the expression of p38 protein in the presence of MSCs making the ICAs responsive to glucose. Taken together our data demonstrate for the first time that the WJ-MSC expressed pancreatic markers and their supplementation protected engineered islets against hypoxia, oxidative stress, and inflammatory cytokines by inhibiting p38 MAPK protein.

Keywords: hypoxia, islet-like cell aggregates, inflammatory cytokines, oxidative stress

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Authors: M. Cabral, A. Verdin, G. Garçon, A. Touré, C. Diop, M. Fall, S. Bouhsina, D. Dewaele, F.Cazier, A. Tall Dia, P. Shirali, A. Diouf

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This case-control study dealt with the health adverse effects within the population neighboring the Mbeubeuss waste dump, which is located near the district of Malika (Diamalaye II) in Dakar (Senegal). All the household and industrial waste arising from Dakar are stored in this open landfill without being covered and are therefore possible sources of Pb and Cd contaminated air emissions and lixiviates. The objective of this study is part of improving the health of the population neighboring Mbeubeuss by determining Pb and Cd concentrations both in environment and humans, and studying possible renal function alterations within the adults. Soil and air samples were collected in the control site (Darou Salam) and the waste dump neighboring site (Diamalaye II). Control and exposed adults were recruited as living in Darou Salam (n = 52) and in Diamalaye II (n = 77). Pb and Cd concentrations in soil, air and biological samples were determined. Moreover, we were interested in analyzing some impregnation (zinc protoporphyrin, d-aminolevulinic acid dehydratase) and oxidative stress biomarkers (malonedialdehyde, gluthatione status), in addition to several nephrotoxicity parameters (creatinuria, proteinuria, lactate dehydrogenase, CC16 protein, glutathione S-transferase-alpha and retinol binding protein) in blood and/or urine. The results showed the significant Pb and Cd contamination of the soil and air samples derived from the landfill, and therefore of the neighboring population of adults. This critical exposure to environmental Pb and Cd had some harmful consequences for their health, as shown by the reported oxidative stress and nephrotoxicity signs.

Keywords: Pb and Cd environmental exposure, impregnation markers, landfill, nephrotoxicity markers

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Authors: Băilă Diana Irinel, Păcurar Răzvan, Păcurar Ancuța

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In the last years, composite materials are increasingly used in automotive, aeronautic, aerospace, construction applications. Composite materials have been used in aerospace in applications such as engine blades, brackets, interiors, nacelles, propellers/rotors, single aisle wings, wide body wings. The fields of use of composite materials have multiplied with the improvement of material properties, such as stability and adaptation to the environment, mechanical tests, wear resistance, moisture resistance, etc. The composite materials are classified concerning type of matrix materials, as metallic, polymeric and ceramic based composites and are grouped according to the reinforcement type as fibre, obtaining particulate and laminate composites. Production of a better material is made more likely by combining two or more materials with complementary properties. The best combination of strength and ductility may be accomplished in solids that consist of fibres embedded in a host material. Polyester is a suitable component for composite materials, as it adheres so readily to the particles, sheets, or fibres of the other components. The important properties of the reinforcing fibres are their high strength and high modulus of elasticity. For applications, as in automotive or in aeronautical domain, in which a high strength-to-weight ratio is important, non-metallic fibres such as fiberglass have a distinct advantage because of their low density. In general, the glass fibres content varied between 9 to 33% wt. in the composites. In this article, high-performance types of composite materials glass-epoxy and glass-polyester used in automotive domain will be analyzed, performing tensile and flexural tests and SEM analyzes.

Keywords: glass-polyester composite, glass fibre, traction and flexion tests, SEM analyzes

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Authors: Rizky Oktaviana

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The main purpose of studying lies in improving students’ understanding. Teachers usually use written test to measure students’ understanding about learning material especially mathematical learning material. This common method actually has a lack point, such that in mathematics content, written test only show procedural steps to solve mathematical problems. Therefore, teachers unable to see whether students actually understand about mathematical concepts and the relation between concepts or not. One of the best tools to observe students’ understanding about the mathematical concepts is concept map. The goal of this research is to describe junior high school students understanding about mathematical concepts through Concept Maps based on the difference of mathematical ability. There were three steps in this research; the first step was choosing the research subjects by giving mathematical ability test to students. The subjects of this research are three students with difference mathematical ability, high, intermediate and low mathematical ability. The second step was giving concept mapping training to the chosen subjects. The last step was giving concept mapping task about the function to the subjects. Nodes which are the representation of concepts of function were provided in concept mapping task. The subjects had to use the nodes in concept mapping. Based on data analysis, the result of this research shows that subject with high mathematical ability has formal understanding, due to that subject could see the connection between concepts of function and arranged the concepts become concept map with valid hierarchy. Subject with intermediate mathematical ability has relational understanding, because subject could arranged all the given concepts and gave appropriate label between concepts though it did not represent the connection specifically yet. Whereas subject with low mathematical ability has poor understanding about function, it can be seen from the concept map which is only used few of the given concepts because subject could not see the connection between concepts. All subjects have instrumental understanding for the relation between linear function concept, quadratic function concept and domain, co domain, range.

Keywords: concept map, concept mapping, mathematical concepts, understanding

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Authors: Jérémy Philippe, Lucien Baldas, Batoul Attar, Jean-Charles Mare

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The proposed communication deals with the research and development of a rotary direct-drive servo valve for aerospace applications. A key challenge of the project is to downsize the electromagnetic torque motor by reducing the torque required to drive the rotary spool. It is intended to optimize the spool and the sleeve geometries by combining a Computational Fluid Dynamics (CFD) approach with commercial optimization software. The present communication addresses an important phase of the project, which consists firstly of gaining confidence in the simulation results. It is well known that the force needed to pilot a sliding spool valve comes from several physical effects: hydraulic forces, friction and inertia/mass of the moving assembly. Among them, the flow force is usually a major contributor to the steady-state (or Root Mean Square) driving torque. In recent decades, CFD has gradually become a standard simulation tool for studying fluid-structure interactions. However, in the particular case of high-pressure valve design, the authors have experienced that the calculated overall hydraulic force depends on the parameterization and options used to build and run the CFD model. To solve this issue, the authors have selected the standard case of the linear spool valve, which is addressed in detail in numerous scientific references (analytical models, experiments, CFD simulations). The first CFD simulations run by the authors have shown that the evolution of the equivalent discharge coefficient vs. Reynolds number at the metering orifice corresponds well to the values that can be predicted by the classical analytical models. Oppositely, the simulated flow force was found to be quite different from the value calculated analytically. This drove the authors to investigate minutely the influence of the studied domain and the setting of the CFD simulation. It was firstly shown that the flow recirculates in the inlet and outlet channels if their length is not sufficient regarding their hydraulic diameter. The dead volume on the uncontrolled orifice side also plays a significant role. These examples highlight the influence of the geometry of the fluid domain considered. The second action was to investigate the influence of the type of mesh, the turbulence models and near-wall approaches, and the numerical solver and discretization scheme order. Two approaches were used to determine the overall hydraulic force acting on the moving spool. First, the force was deduced from the momentum balance on a control domain delimited by the valve inlet and outlet and the spool walls. Second, the overall hydraulic force was calculated from the integral of pressure and shear forces acting at the boundaries of the fluid domain. This underlined the significant contribution of the viscous forces acting on the spool between the inlet and outlet orifices, which are generally not considered in the literature. This also emphasized the influence of the choices made for the implementation of CFD calculation and results analysis. With the step-by-step process adopted to increase confidence in the CFD simulations, the authors propose a set of best practices and recommendations for the efficient use of CFD to design high-pressure spool valves.

Keywords: computational fluid dynamics, hydraulic forces, servovalve, rotary servovalve

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Authors: Yew Mun Yip, Dawei Zhang

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Proteins are the biological machinery that executes specific vital functions in every cell of the human body by folding into their 3D structures. When a protein misfolds from its native structure, the machinery will malfunction and lead to misfolding diseases. Although in vitro experiments are able to conclude that the mutations of the amino acid sequence lead to incorrectly folded protein structures, these experiments are unable to decipher the folding process. Therefore, molecular dynamic (MD) simulations are employed to simulate the folding process so that our improved understanding of the folding process will enable us to contemplate better treatments for misfolding diseases. MD simulations make use of force fields to simulate the folding process of peptides. Secondary structures are formed via the hydrogen bonds formed between the backbone atoms (C, O, N, H). It is important that the hydrogen bond energy computed during the MD simulation is accurate in order to direct the folding process to the native structure. Since the atoms involved in a hydrogen bond possess very dissimilar electronegativities, the more electronegative atom will attract greater electron density from the less electronegative atom towards itself. This is known as the polarization effect. Since the polarization effect changes the electron density of the two atoms in close proximity, the atomic charges of the two atoms should also vary based on the strength of the polarization effect. However, the fixed atomic charge scheme in force fields does not account for the polarization effect. In this study, we introduce the polarized structure-specific backbone charge (PSBC) model. The PSBC model accounts for the polarization effect in MD simulation by updating the atomic charges of the backbone hydrogen bond atoms according to equations derived between the amount of charge transferred to the atom and the length of the hydrogen bond, which are calculated from quantum-mechanical calculations. Compared to other polarizable models, the PSBC model does not require quantum-mechanical calculations of the peptide simulated at every time-step of the simulation and maintains the dynamic update of atomic charges, thereby reducing the computational cost and time while accounting for the polarization effect dynamically at the same time. The PSBC model is applied to two different β-peptides, namely the Beta3s/GS peptide, a de novo designed three-stranded β-sheet whose structure is folded in vitro and studied by NMR, and the trpzip peptides, a double-stranded β-sheet where a correlation is found between the type of amino acids that constitute the β-turn and the β-propensity.

Keywords: hydrogen bond, polarization effect, protein folding, PSBC

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Authors: Liudmila Garzanova, Lidia Ananyeva, Olga Koneva, Olga Ovsyannikova, Oxana Desinova, Mayya Starovoytova, Rushana Shayahmetova, Anna Khelkovskaya-Sergeeva

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Objectives. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are associated with severe course, increased morbidity and mortality in systemic sclerosis (SSc). The aim of our study was to assess changes in CRP and ESR in SSc patients during long-term RTX therapy. Methods. This study included 113 patients with SSc. Mean age was 48.1±13 years, female-85%. The mean disease duration was 6±5 years. The diffuse cutaneous subset of the disease had 55% of patients. All pts had interstitial lung disease (ILD). All patients received prednisolone at a mean dose of 11.6±4.8 mg/day, and 53 of them - were immunosuppressants at inclusion. Patients received RTX due to the ineffectiveness of previous therapy for ILD. The parameters were evaluated over the periods: at baseline (point 0), 13±2.3 month (point 1, n=113), 42±14 month (point 2, n=80) and 79±6.5 month (point 3, n=25) after initiation of RTX therapy. Cumulative mean dose of RTX at point 1 = 1.7±0.6g, at point 2 = 3±1.5g, and at point 3 = 3.8±2.4g. The results are presented in the form of mean values, delta(Δ)-difference between the baseline parameter and follow-up point. Results. There was an improvement in studied parameters on RTX therapy. There was a significant decrease of ESR, CRP and activity index (EScSG-AI) at all observation points (p=0.001). In point 1: ΔCRP was 6.7 mg/l, ΔESR = 7.4 mm/h, ΔActivity index (EScSG-AI) = 1.7. In point 2: ΔCRP was 8.7 mg/l, ΔESR = 7.5 mm/h, ΔActivity index (EScSG-AI) = 1.9. In point 3: ΔCRP was 16.1 mg/l, ΔESR = 11 mm/h, ΔActivity index (EScSG-AI) = 2.1. Conclusion. There was a significant decrease in CRP and ESR during long-term RTX therapy, which correlated with a decrease in the disease activity index. RTX is an effective treatment option for SSc with an elevation of acute-phase reactants.

Keywords: C-reactive protein, interstitial lung disease, systemic sclerosis, rituximab

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Authors: Mahzad Yousefi, Azin Tavakoli

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Periodontal disease is an inflammatory reaction; therefore, it is predicted that changes may occur in some inflammatory parameters that can be detected in routine blood tests. The objective of this study was to evaluate the hematological and biochemistry changes that occur in dogs affected with advanced stages of periodontal disease. 87 dogs were diagnosed with periodontal disease (PD group), and 76 healthy dogs entered the study. The PD dogs had been affected with periodontitis stage 3 or 4 and were candidates for any dental extractions. The healthy dogs were either referred for annual checkups or for issuing health travel certificates that their owners asked for complete lab tests. Neither the diseased nor healthy subjects had a history of infectious, or other general health problems or surgery in the past 3 months. Age, as well as all hematologic including PCV, WBC and RBC count, Hb, MCV, MCH, MCHC, PLT, CBC, NLR, and biochemistry data, including total protein, albumin, glucose, BUN, Creatinine, ALT, AST, and ALP, were recorded and analyzed statistically. Results confirmed that aging has a significant direct relationship with the advanced stages of periodontal disease. Mild leukocytosis occurred in the diseased group; however, it was not significant. Also, the mean total protein of the PD group was lower than that of the healthy dogs, and serum levels of albumin were found to be lower significantly in the diseased group (P<0.05). Mean ±SD amount of Platelet, MCH, and ALT were significantly higher in the diseased group in comparison to the healthy dogs (P<0.05). No significant differences were reported in other evaluated parameters. It is concluded that CBC indices of PD dogs are not systemic inflammatory; however, only a decrease in albumin showed inflammatory responses. Some indices in routine laboratory tests can be changed significantly during advanced stages of the periodontal disease dogs.

Keywords: periodontal disease, dogs, hematological factors, advanced stages, blood tests

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Authors: M. Y. Abubakar, M. Yunisa, A. N. Muhammad

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Constraining the production Clarias gariepinus and Oreochromis niloticus culture is the prohibitive cost of feed. We assess the performance of the species fingerlings on diets substituted with composite. Four dietary treatments (0%, 25%, 45%, and 75%) for C. gariepinus and five (0%, 25%, 50%, 75%, and whole food composite) for O. niloticus were formulated and each fed to 15 fingerlings for C. gariepinus and 10 fingerlings for O. niloticus stocked in 75ltrs plastic bowls, replicated trice in a completely randomized design. The experiment lasted 56 days. Percent survival rate was significantly (p < 0.05) higher (57.78 ± 9.69) in C. gariepinus fed diet III. The growth and nutrient utilization indices were least in the fish fed diet IV, which was significantly (p < 0.05) lower than in other treatments. Fish fed dietary treatment III, recorded the best in growth and nutrient utilization indices and was significantly higher (p < 0.05) than those fed dietary treatments I & II which were non-significant (p > 0.05) and higher than those fed 75% substitution. Better profit index was in the fish fed diet with 50% substitution level. For O. niloticus, the survival (172.62 ± 39.03) was significantly higher (p < 0.05) in those fed 25% substituted diet. For growth indices, the least performed were those fed whole composite while other treatments were non-significant (p > 0.05) different from each other. In terms of nutrient utilization, fish fed diet substituted at 0%, 25%, 50% and 75% food composite had similar food conversion ratio and protein efficiency ratio. However, there was no significant difference in the profit index among the whole treatment. It can be concluded that food composite from Sokoto house-holds can optimally replace groundnut cake up to 50% level as a protein source in the diets of Clarias gariepinus and O. niloticus fingerlings without adverse effects on survival, growth, and nutrient utilization.

Keywords: food composite, nutrient utilization, C. gariepinus, O. niloticus household, substitution levels

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Authors: F. Yılmaz, Y. Saylan, A. Derazshamshir, S. Atay, A. Denizli

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Quartz crystal microbalance (QCM), high-resolution mass-sensing technique, measures changes in mass on oscillating quartz crystal surface by measuring changes in oscillation frequency of crystal in real time. Protein adsorption techniques via hydrophobic interaction between protein and solid support, called hydrophobic interaction chromatography (HIC), can be favorable in many cases. Some nanoparticles can be effectively applied for HIC. HIC takes advantage of the hydrophobicity of proteins by promoting its separation on the basis of hydrophobic interactions between immobilized hydrophobic ligands and nonpolar regions on the surface of the proteins. Lysozyme is found in a variety of vertebrate cells and secretions, such as spleen, milk, tears, and egg white. Its common applications are as a cell-disrupting agent for extraction of bacterial intracellular products, as an antibacterial agent in ophthalmologic preparations, as a food additive in milk products and as a drug for treatment of ulcers and infections. Lysozyme has also been used in cancer chemotherapy. The aim of this study is the synthesis of hydrophobic nanoparticles for Lysozyme detection. For this purpose, methacryoyl-L-phenylalanine was chosen as a hydrophobic matrix. The hydrophobic nanoparticles were synthesized by micro-emulsion polymerization method. Then, hydrophobic QCM nanosensor was characterized by Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, atomic force microscopy (AFM) and zeta size analysis. Hydrophobic QCM nanosensor was tested for real-time detection of Lysozyme from aqueous solution. The kinetic and affinity studies were determined by using Lysozyme solutions with different concentrations. The responses related to a mass (Δm) and frequency (Δf) shifts were used to evaluate adsorption properties.

Keywords: nanosensor, HIC, lysozyme, QCM

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Authors: Ved Vrat Verma, Rani Gupta, Manisha Goel

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γ-glutamyltranspeptidase (GGT: EC 2.3.2.2) is an N-terminal nucleophile hydrolase conserved in all three domains of life. GGT plays a key role in glutathione metabolism where it catalyzes the breakage of the γ-glutamyl bonds and transfer of γ-glutamyl group to water (hydrolytic activity) or amino acids or short peptides (transpeptidase activity). GGTs from bacteria, archaea, and eukaryotes (human, rat and mouse) are homologous proteins sharing >50% sequence similarity and conserved four layered αββα sandwich like three dimensional structural fold. These proteins though similar in their structure to each other, are quite diverse in their enzyme activity: some GGTs are better at hydrolysis reactions but poor in transpeptidase activity, whereas many others may show opposite behaviour. GGT is known to be involved in various diseases like asthma, parkinson, arthritis, and gastric cancer. Its inhibition prior to chemotherapy treatments has been shown to sensitize tumours to the treatment. Microbial GGT is known to be a virulence factor too, important for the colonization of bacteria in host. However, all known inhibitors (mimics of its native substrate, glutamate) are highly toxic because they interfere with other enzyme pathways. However, a few successful efforts have been reported previously in designing species specific inhibitors. We aim to leverage the diversity seen in GGT family (pathogen vs. eukaryotes) for designing specific inhibitors. Thus, in the present study, we have used DIVERGE software to identify sites in GGT proteins, which are crucial for the functional and structural divergence of these proteins. Since, type II divergence sites vary in clade specific manner, so type II divergent sites were our focus of interest throughout the study. Type II divergent sites were identified for pathogen vs. eukaryotes clusters and sites were marked on clade specific representative structures HpGGT (2QM6) and HmGGT (4ZCG) of pathogen and eukaryotes clade respectively. The crucial divergent sites within 15 A radii of the binding cavity were highlighted, and in-silico mutations were performed on these sites to delineate the role of these sites on the mechanism of catalysis and protein folding. Further, the amino acid network (AAN) analysis was also performed by Cytoscape to delineate assortative mixing for cavity divergent sites which could strengthen our hypothesis. Additionally, molecular dynamics simulations were performed for wild complexes and mutant complexes close to physiological conditions (pH 7.0, 0.1 M ionic strength and 1 atm pressure) and the role of putative divergence sites and structural integrities of the homologous proteins have been analysed. The dynamics data were scrutinized in terms of RMSD, RMSF, non-native H-bonds and salt bridges. The RMSD, RMSF fluctuations of proteins complexes are compared, and the changes at protein ligand binding sites were highlighted. The outcomes of our study highlighted some crucial divergent sites which could be used for novel inhibitors designing in a species-specific manner. Since, for drug development, it is challenging to design novel drug by targeting similar protein which exists in eukaryotes, so this study could set up an initial platform to overcome this challenge and help to deduce the more effective targets for novel drug discovery.

Keywords: γ-glutamyltranspeptidase, divergence, species-specific, drug design

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Authors: Shreya Ghosh, Akansha Garg, Chayanika Kala, Ashwani Kumar Thakur

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Background: Granuloma formation is one of the characteristic features of tuberculosis. Besides, chronic inflammation underlying tuberculosis is often indicated by an increase in the concentration of serum amyloid A (SAA) protein. The connection between tuberculosis and SAA-driven secondary amyloidosis is well documented. However, SAA-derived amyloid deposition start sites are not well understood in tuberculosis and other chronic inflammatory conditions. It was hypothesized that granuloma could be a potential site for an amyloid deposition because both SAA protein and proteases that cleave SAA into aggregation-prone fragments are reported to be present in the granuloma. Here the authors have shown the presence of SAA-derived amyloid deposits in the granuloma of tuberculosis patients. Methodology: Over a period of two years, tuberculosis patients were screened, and biopsies were collected from the affected organs of the patients. The gold standard, Congo red dye staining, was used to identify amyloid deposits in the tissue sections of tuberculosis patients containing granulomatous structure. Results: 11 out of 150 FFPE biopsy specimens of tuberculosis patients showed eosinophilic hyaline-rich deposits surrounding granuloma. Upon Congo red staining, these deposits exhibited characteristic apple-green birefringence under polarized light, confirming amyloid deposits. Further, upon immunohistochemical staining with anti-SAA, the amyloid enriched areas showed positive immunoreactivity. Conclusion: In this pilot study, we have shown that granuloma can be a potential site for serum amyloid A-derived amyloid formation in tuberculosis patients. Moreover, the presence of amyloid gave significant cues that granuloma might be a probable amyloid deposition start in tuberculosis patients. This study will set a stage to expand the clinical and fundamental research in the understanding of amyloid formation in granuloma underlying tuberculosis and chronic inflammatory conditions.

Keywords: amyloid, granuloma, periphery, serum amyloid A, tuberculosis

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Authors: Yuanchao Sang, Zhihao Gong, Longsheng Chen, Long Chen

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Clothing fashion represents a human’s aesthetic appreciation towards everyday outfits and appetite for fashion, and it reflects the development of status in society, humanity, and economics. However, modelling fashion by machine is extremely challenging because fashion is too abstract to be efficiently described by machines. Even human beings can hardly reach a consensus about fashion. In this paper, we are dedicated to answering a fundamental fashion-related problem: what image feature best describes clothing fashion? To address this issue, we have designed and evaluated various image features, ranging from traditional low-level hand-crafted features to mid-level style awareness features to various current popular deep neural network-based features, which have shown state-of-the-art performance in various vision tasks. In summary, we tested the following 9 feature representations: color, texture, shape, style, convolutional neural networks (CNNs), CNNs with distance metric learning (CNNs&DML), AutoEncoder, CNNs with multiple layer combination (CNNs&MLC) and CNNs with dynamic feature clustering (CNNs&DFC). Finally, we validated the performance of these features on two publicly available datasets. Quantitative and qualitative experimental results on both intra-domain and inter-domain fashion clothing image retrieval showed that deep learning based feature representations far outweigh traditional hand-crafted feature representation. Additionally, among all deep learning based methods, CNNs with explicit feature clustering performs best, which shows feature clustering is essential for discriminative fashion feature representation.

Keywords: convolutional neural network, feature representation, image processing, machine modelling

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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For chemotherapy, a drug delivery system should be able to specifically target cancer cells and deliver the therapeutic dose without affecting normal cells. Folate receptors (FR) can be considered key targets since they are commonly over-expressed in cancer cells and they are the molecular marker used in this study. Here, cyclodextrin (CD) has being studied as a vehicle for delivering the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within the CD cavity. In this study, β-CD has been modified using folic acid so as to specifically target the FR molecular marker. Thus, the system studied here for drug delivery consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 9.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 10.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 8.5 for A549 and 132.6 µM ± 12.1 and 288.1 µM ± 16.3 for BEAS-2B. These results demonstrate that MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug.

Keywords: cyclodextrins, cancer treatment, drug delivery, folate receptors, reduced folate carriers

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Authors: Shu-Pin Huang, Pai-Chi Teng, Hao-Han Chang, Chia-Hsin Liu, Yung-Lun Lin, Shu-Chi Wang, Hsin-Chih Yeh, Chih-Pin Chuu, Jiun-Hung Geng, Li-Hsin Chang, Wei-Chung Cheng, Chia-Yang Li

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The emergence of immune checkpoint inhibitors (ICIs) targeting proteins like PD-1 and PD-L1 has changed the treatment paradigm of bladder cancer. However, not all patients benefit from ICIs, with some experiencing early death. There's a significant need for biomarkers associated with the PD-1 pathway in bladder cancer. Current biomarkers focus on tumor PD-L1 expression, but a more comprehensive understanding of PD-1-related biology is needed. Our study has developed a seven-gene risk score panel, employing a comprehensive bioinformatics strategy, which could serve as a potential prognostic and predictive biomarker for bladder cancer. This panel incorporates the FYN, GRAP2, TRIB3, MAP3K8, AKT3, CD274, and CD80 genes. Additionally, we examined the relationship between this panel and immune cell function, utilizing validated tools such as ESTIMATE, TIDE, and CIBERSORT. Our seven-genes panel has been found to be significantly associated with bladder cancer survival in two independent cohorts. The panel was also significantly correlated with tumor infiltration lymphocytes, immune scores, and tumor purity. These factors have been previously reported to have clinical implications on ICIs. The findings suggest the potential of a PD-1 pathway-based transcriptomic panel as a prognostic and predictive biomarker in bladder cancer, which could help optimize treatment strategies and improve patient outcomes.

Keywords: bladder cancer, programmed cell death protein 1, prognostic biomarker, immune checkpoint inhibitors, predictive biomarker

Procedia PDF Downloads 78

Authors: Karima Kimouche

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In this paper, we consider the asymptotic problems in spectral analysis of stationary causal random fields. We impose conditions only involving (conditional) moments, which are easily verifiable for a variety of nonlinear random fields. Limiting distributions of periodograms and smoothed periodogram spectral density estimates are obtained and applications to the spectral domain bootstrap are given.

Keywords: spatial nonlinear processes, spectral estimators, GMC condition, bootstrap method

Procedia PDF Downloads 453

Authors: Uchegbu Nneka Nkechi, Okoye Ogochukwu Peace

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The evaluation of the visco-elastic properties and microbial quality of a formulated oat-based dietetic food were investigated. Oat flour, pumpkin seed flour, carrot flour and skimmed milk powder were blended in varying proportions to formulate a product with codes OCF, which contains 70% oat flour, 10 % carrot flour, 10 % pumpkin seed flour and 10% skimmed milk powder, OCF which contains 65 % oat flour, 10 % carrot flour, 10 % pumpkin seed flour and 15 % skimmed milk powder, OCF which contains 60 % oat flour, 10 % carrot flour, 10 % pumpkin seed flour and 20 % skimmed milk powder, OCF which contains 55 % oat flour, 10 % carrot flour, 10 % pumpkin seed flour and 25 % skimmed milk powder and OF with 95 % oat as the commercial control. All the samples were assessed for their proximate composition, microbial quality and visco-elastic properties. The moisture content was highest at sample OF (10.73%) and lowest at OCF (7.10%) (P<0.05). Crude protein ranged from 13.38%-22.86%, with OCF having the highest (P<0.05) protein content and OF having the lowest. Crude fat was 3.74% for OCF and 6.31% for OF. Crude fiber ranged from 3.58% - 17.39% with OF having the lowest (P<0.05) fiber content and OCF having the highest. Ash content was 1.30% for OCF and 2.75% for OCF. There was no mold growth in the samples. The total viable ml/wl count ranged from 1.5×10³ cfu/g - 2.6×10³ cfu/g, with OCF having the lowest and OF having the highest (P<0.05) total viable count. The peak viscosity of the sample ranged from 75.00 cP-2895.00 cP, with OCF having the lowest and OF having the highest value. The final viscosity was 130.50 cP in OCF and 3572.50 cP in OF. The setback viscosity was 58.00 cP in OCF and 1680.50 cP in OF. The peak time was 6.93 mins in OCF to 5.57 mins in OF. There was no pasting temperature for all samples except the OF, which had 86.43. Sample OF was the highest in terms of overall acceptability. This study showed that the oat-based composite flour produced had a nutritional profile that would be acceptable for the aged population.

Keywords: dietetic, pumpkin, visco-elastic, microbial

Procedia PDF Downloads 197

Authors: Arfan Ali, Idrees Ahmad Nasir

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The critical evaluation of tolerance in tomato plants against the induced saline soil were assessed by transcript analysis of genes coding for products potentially involved in stress tolerance. A reverse transcriptase PCR experiment was performed with Hsp90-1, MT2, and GR1like protein genes using RNA isolated from different tissues of tomato plants. Four strains of Bacillus magisterium were inoculated with 100 Mm & 200 Mm concentrations of salt. Eleven treatments each ten replica pots were installed in green house experiment and the parameters taken into account were morphological (length, weight, number of leaves, leaf surface area), chemical (anthocyanin, chlorophyll-a, chlorophyll-b, carotenoids) and biological (gene expression). Results bare a response i.e. highest response of MT2 like gene was at 24 hpi and the highest levels of GR1 like protein transcript accumulation were detected at 36 hpi. The chemical and morphological parameters at diverse salt concentrations bequeath superlative response amongst strains which candidly flank on Zm7 and Zm4. Therefore, Bacillus magisterium Zm7 strains and somehow Zm4 strain can be used in saline condition to make plants tolerant. The overall performance of strains Zm7, Zm6, and Zm4 was found better for all studied traits under salt stress conditions. Significant correlations among traits root length, shoot length, number of leaves, leaf surface area, carotenoids, anthocyanin, chlorophyll-a and chlorophyll-b were found and suggested that the salt tolerance in tomato may be improved through the use of PGPR strains.

Keywords: Bacillus magisterium, gene expression glutathione reductase, metallothionein, PGPR, Rhizobacteria, saline

Procedia PDF Downloads 434

Authors: Sachin K. Samuchiwal, Barbara Balestrieri, Amanda Paskavitz, Hannah Raff, Joshua A. Boyce

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IL-33, a recently discovered member of the IL-1 cytokine family, binds to the TLR/IL1R super family receptor ST2 and induces type 2 immune responses. IL-33 is constitutively expressed in structural cells at barrier sites such as skin, lung, and intestine, and also inducibly expressed by hematopoietic cells including macrophages. Stimulation of macrophages by Lipopolysaccharide (LPS) can induce de novo IL-33 expression, and also causes the production of prostaglandin-E2 (PGE2) via cyclooxygenase (COX)-2 and microsomal PGE2 synthase-1 (mPGES-1). Because PGE2 can regulate macrophage functions through both autocrine and paracrine mechanisms, the potential interplay of endogenous PGE2 on IL-33 production was explored. Bone-marrow derived murine macrophages (bmMF) that lack either mPGES-1 or EP2 receptor expression were stimulated with LPS in the absence or presence of exogenous PGE2 along with pharmacological agonists and antagonists. The study results demonstrate that endogenous PGE2 markedly enhances LPS-induced IL-33 production by bmMFs via EP2 receptors. Moreover, exogenous PGE2 can amplify LPS-induced IL-33 expression dominantly by EP2 and partly by EP4 receptors by a pathway involving cAMP and exchange protein activated by cAMP (EPAC), but not protein kinase A (PKA). Though both IL-33 production and PGE2 generation in response to LPS require activation of both p38 MAPK and NF-κB, PGE2 did not influence this activation. In conclusion, it is demonstrated that endogenous PGE2 signaling through EP2 and EP4 receptors is a prerequisite for LPS-induced IL-33 production in bmMFs and the underlying cAMP mediated pathway involves EPAC. Since IL-33 is a critical pro-inflammatory cytokine in various pathological disorders, this PGE2-EP2/EP4-cAMP mediated pathway can be exploited to intervene in IL-33 driven pathologies.

Keywords: bone marrow macrophages, EPAC, IL-33, PGE2

Procedia PDF Downloads 188

Authors: Olfat Shaker, Miriam Wadie, Reham Ali, Ayman Yosry

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Colorectal cancer (CRC) is a major cause of mortality and morbidity and accounts for over 9% of cancer incidence worldwide. Silent information regulator 2 homolog 1 (SIRT1) gene is located in the nucleus and exert its effects via modulation of histone and non-histone targets. They function in the cell via histone deacetylase (HDAC) and/or adenosine diphosphate ribosyl transferase (ADPRT) enzymatic activity. The aim of this work was to study the relationship between SIRT1 polymorphism and its protein level in colorectal cancer patients in comparison to control cases. This study includes 2 groups: thirty healthy subjects (control group) & one hundred CRC patients. All subjects were subjected to: SIRT-1 serum level was measured by ELISA and gene polymorphisms of rs12778366, rs375891 and rs3740051 were detected by real time PCR. For CRC patients clinical data were collected (size, site of tumor as well as its grading, obesity) CRC patients showed high significant increase in the mean level of serum SIRT-1 compared to control group (P<0.001). Mean serum level of SIRT-1 showed high significant increase in patients with tumor size ≥5 compared to the size < 5 cm (P<0.05). In CRC patients, percentage of T allele of rs12778366 was significantly lower than controls, CC genotype and C allele C of rs 375891 were significantly higher than control group. In CRC patients, the CC genotype of rs12778366, was 75% in rectosigmoid and 25% in cecum & ascending colon. According to tumor size, the percentage of CC genotype was 87.5% in tumor size ≥5 cm. Conclusion: serum level of SIRT-1 and T allele, C allele of rs12778366 and rs 375891 respectively can be used as diagnostic markers for CRC patients.

Keywords: CRC, SIRT1, polymorphisms, ELISA

Procedia PDF Downloads 218

Authors: Mohamed Yousef, Magdy Samuel, Maha El-Meligy, Taher El-Bitar

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The present work is dealing with 2% Si-steel alloy. The alloy contains 0.05% C as well as 0.85% Al. The alloy under investigation would be used for electrical transformation purposes. A heating (expansion) - cooling (contraction) dilation investigation was executed to detect the a, a+g, and g transformation temperatures at the inflection points of the dilation curve. On heating, primary a  was detected at a temperature range between room temperature and 687 ^oC. The domain of a+g was detected in the range between 687 ^oC and 746 ^oC. g phase exists in the closed g region at the range between 746 ^oC and 1043 ^oC. The domain of a phase appears again at a temperature range between 1043 and 1105 ^oC, and followed by secondary a at temperature higher than 1105 ^oC. A physical simulation of thermo-mechanical processing on the as-cast alloy was carried out. The simulation process took into consideration the hot flat rolling pilot plant parameters. The process was executed on the thermo-mechanical simulator (Gleeble 3500). The process was designed to include seven consecutive passes. The 1^st pass represents the roughing stage, while the remaining six passes represent finish rolling stage. The whole process was executed at the temperature range from 1100 ^oC to 900 ^oC. The amount of strain starts with 23.5% at the roughing pass and decreases continuously to reach 7.5 % at the last finishing pass. The flow curve of the alloy can be abstracted from the stress-strain curves representing simulated passes. It shows alloy hardening from a pass to the other up to pass no. 6, as a result of decreasing the deformation temperature and increasing of cumulative strain. After pass no. 6, the deformation process enhances the dynamic recrystallization phenomena to appear, where the z-parameter would be high.

Keywords: si- steel, hot deformability, critical transformation temperature, physical simulation, thermo-mechanical processing, flow curve, dynamic softening.

Procedia PDF Downloads 245

Authors: Felipe M. de Freitas, Icaro V. Soares, Lucas L. L. Fortes, Sandro T. M. Gonçalves, Úrsula D. C. Resende

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The SPICE-based simulators are quite robust and widely used for simulation of electronic circuits, their algorithms support linear and non-linear lumped components and they can manipulate an expressive amount of encapsulated elements. Despite the great potential of these simulators based on SPICE in the analysis of quasi-static electromagnetic field interaction, that is, at low frequency, these simulators are limited when applied to microwave hybrid circuits in which there are both lumped and distributed elements. Usually the spatial discretization of the FDTD (Finite-Difference Time-Domain) method is done according to the actual size of the element under analysis. After spatial discretization, the Courant Stability Criterion calculates the maximum temporal discretization accepted for such spatial discretization and for the propagation velocity of the wave. This criterion guarantees the stability conditions for the leapfrogging of the Yee algorithm; however, it is known that for the field update, the stability of the complete FDTD procedure depends on factors other than just the stability of the Yee algorithm, because the FDTD program needs other algorithms in order to be useful in engineering problems. Examples of these algorithms are Absorbent Boundary Conditions (ABCs), excitation sources, subcellular techniques, grouped elements, and non-uniform or non-orthogonal meshes. In this work, the influence of the stability of the FDTD method in the modeling of concentrated elements such as resistive sources, resistors, capacitors, inductors and diode will be evaluated. In this paper is proposed, therefore, the electromagnetic modeling of electronic components in order to create models that satisfy the needs for simulations of circuits in ultra-wide frequencies. The models of the resistive source, the resistor, the capacitor, the inductor, and the diode will be evaluated, among the mathematical models for lumped components in the LE-FDTD method (Lumped-Element Finite-Difference Time-Domain), through the parametric analysis of Yee cells size which discretizes the lumped components. In this way, it is sought to find an ideal cell size so that the analysis in FDTD environment is in greater agreement with the expected circuit behavior, maintaining the stability conditions of this method. Based on the mathematical models and the theoretical basis of the required extensions of the FDTD method, the computational implementation of the models in Matlab® environment is carried out. The boundary condition Mur is used as the absorbing boundary of the FDTD method. The validation of the model is done through the comparison between the obtained results by the FDTD method through the electric field values and the currents in the components, and the analytical results using circuit parameters.

Keywords: hybrid circuits, LE-FDTD, lumped element, parametric analysis

Procedia PDF Downloads 153

Authors: Przemyslaw Nogly, Tobias Weinert, Daniel James, Sergio Carbajo, Dmitry Ozerov, Antonia Furrer, Dardan Gashi, Veniamin Borin, Petr Skopintsev, Kathrin Jaeger, Karol Nass, Petra Bath, Robert Bosman, Jason Koglin, Matthew Seaberg, Thomas Lane, Demet Kekilli, Steffen Brünle, Tomoyuki Tanaka, Wenting Wu, Christopher Milne, Thomas A. White, Anton Barty, Uwe Weierstall, Valerie Panneels, Eriko Nango, So Iwata, Mark Hunter, Igor Schapiro, Gebhard Schertler, Richard Neutze, Jörg Standfuss

Abstract:

Ultrafast isomerization of retinal is the primary step in a range of photoresponsive biological functions including vision in humans and ion-transport across bacterial membranes. We studied the sub-picosecond structural dynamics of retinal isomerization in the light-driven proton pump bacteriorhodopsin using an X-ray laser. Twenty snapshots with near-atomic spatial and temporal resolution in the femtosecond regime show how the excited all-trans retinal samples conformational states within the protein binding pocket prior to passing through a highly-twisted geometry and emerging in the 13-cis conformation. The aspartic acid residues and functional water molecules in proximity of the retinal Schiff base respond collectively to formation and decay of the initial excited state and retinal isomerization. These observations reveal how the protein scaffold guides this remarkably efficient photochemical reaction.

Keywords: bacteriorhodopsin, free-electron laser, retinal isomerization mechanism, time-resolved crystallography

Procedia PDF Downloads 248

Authors: Ahmad Abdi, M. Golzadeh Gangeraj, Alireza Barari, S. Shirali, S. Amini

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Aims: Diabetes is one of the common metabolic diseases in the world that has the dire adverse effects such as nephropathy, retinopathy and cardiovascular problems. Pharmaceutical and non-pharmaceutical strategies for control and treatment of diabetes are provided. Exercise and nutrition as non-drug strategies for the prevention and control of diabetes are considered. Exercises may increase oxidative stress and myocardium injury, thus it is necessary to take nutrition strategies to help diabetic athletes. Methods: This study was a semi-experimental research. Therefore, 24 men with type 2 diabetes were selected and randomly divided in four groups (1. control, 2. saffron extract, 3. aerobic exercises, 4. compound aerobic exercises and saffron extract). Saffron extract with 100 mg/day was used. Aerobic exercises, three days a week, for eight weeks, with 55-70% of maximum heart rate were performed. At the end, levels of Heart-type fatty acid-binding protein (HFABP) and Troponin T were measured. Data were analyzed by Paired t, One-way ANOVA and Tukey tests. Results: The serum Troponin T increased significantly in saffron extract, aerobic exercises and compound saffron extract -aerobic exercises in type 2 diabetic men(P=0.024, P =0.013, P=0.005 respectively). Saffron extract consumption (100 mg/day) and aerobic exercises did not significantly influence the serum HFABP (P =0.365, P =0.188 respectively). But serum HFABP decreased significantly in compound saffron extract -aerobic exercises group (P =0.003). Conclusions: Raised cardiac Troponin T and HFABP concentration accepted as the standard biochemical markers for the diagnosis of cardiac injury. Saffron intake may beneficially protect the myocardium from injuries. Compound saffron extract -aerobic exercises can decrease levels of Troponin T and HFABP in men with type 2 diabetes.

Keywords: Saffron, aerobic exercises, type 2 diabetes, HFABP, troponin T

Procedia PDF Downloads 267

Authors: Tamar Grdzelishvili, Zaza Sinauridze

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Introduction: Preeclampsia is a complication of the second trimester of pregnancy, which is characterized by high morbidity and multiorgan damage. Many complex pathogenic mechanisms are now implicated to be responsible for this disease (1). Preeclampsia is one of the leading causes of maternal mortality worldwide. Statistics are enough to convince you of the seriousness of this pathology: about 100,000 women die of preeclampsia every year. It occurs in 3-14% (varies significantly depending on racial origin or ethnicity and geographical region) of pregnant women, in 75% of cases - in a mild form, and in 25% - in a severe form. During severe pre-eclampsia-eclampsia, perinatal mortality increases by 5 times and stillbirth by 9.6 times. Considering that the only way to treat the disease is to end the pregnancy, the main thing is timely diagnosis and prevention of the disease. Identification of high-risk pregnant women for PE and giving prophylaxis would reduce the incidence of preterm PE. First-trimester screening model developed by the Fetal Medicine Foundation (FMF), which uses the Bayes-theorem to combine maternal characteristics and medical history together with measurements of mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor, has been proven to be effective and have superior screening performance to that of traditional risk factor-based approach for the prediction of PE (2) Methods: Retrospective single center screening study. The study population consisted of women from the Tbilisi maternity hospital “Pineo medical ecosystem” who met the following criteria: they spoke Georgian, English, or Russian and agreed to participate in the study after discussing informed consent and answering questions. Prior to the study, the informed consent forms approved by the Institutional Review Board were obtained from the study subjects. Early assessment of preeclampsia was performed between 11-13 weeks of pregnancy. The following were evaluated: anamnesis, dopplerography of the uterine artery, mean arterial blood pressure, and biochemical parameter: Pregnancy-associated plasma protein A (PAPP-A). Individual risk assessment was performed with performed by Fast Screen 3.0 software ThermoFisher scientific. Results: A total of 513 women were recruited and through the study, 51 women were diagnosed with preeclampsia (34.5% in the pregnant women with high risk, 6.5% in the pregnant women with low risk; P<0.000 1). Conclusions: First-trimester screening combining maternal factors with uterine artery Doppler, blood pressure, and pregnancy-associated plasma protein-A is useful to predict PE in a routine care setting. More patient studies are needed for final conclusions. The research is still ongoing.

Keywords: first-trimester, preeclampsia, screening, pregnancy-associated plasma protein

Procedia PDF Downloads 77

Authors: Muhammad S. Sajid, Asim Shamim, Muhammad Nisar Khan, Ashfaq A. Chatta, Muhammad Saqib

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Goats (Capra hircus) are a valued asset for resource poor farmers globally. But the parasitic infection especially Haemonchus contortus (Trichostrongylid), impact the health and production of goats globally. The present study intended to evaluate resilient and resistance to Haemonchus contortus in indigenous goat breeds (Teddy and Beetal) of Punjab, Pakistan. Out of 60, 30 goats of each breed were divided into 6 groups and each group contain five goats. Two group of each breed received challenged infection with 12000 and 18000 L3 (third stage) larvae of Haemonchus contortus under two infection protocol that is early and trickle and remaining two group of each breed was kept as control. Resilient and resistance of each breed was then measured on the basis of their phenotypic markers like: faecal egg counts, packed cell volume, FAMACHA score system, body weight, total protein, albumin and worm count on 2nd, 4th, 6th, and 8th week of post infection. Variation in response of each goat breeds to Haemonchus contortus was observed. Teddy breed showed significant (P < 0.05)resistance as compared to Beetal. It is probably first attempt to report an evaluation of goat breed response towards Haemonchus contortus in Pakistan. It was concluded that Teddy goats have a greater genetic tendency to resist against to the Haemonchus contortus infection and this breed could be kept and bred from the economic point of view. Evaluation of genetic markers are like: gene, protein expression, Immunoglobulin, Histamines and interleukins determination are recommended for future studies which can be helpful to be fined resistant breed of goats.

Keywords: goat, beetal, teddy, haemonchus contortus, resistance, resilience, phenotypic markers

Procedia PDF Downloads 361

Authors: S. Dias, A. Tadeu, J. Antonio, F. Pedro, C. Serra

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The goal of the present work is to experimentally evaluate the feasibility of using vibration isolators made of expanded cork agglomerate. Even though this material, also known as insulation cork board (ICB), has mainly been studied for thermal and acoustic insulation purposes, it has strong potential for use in vibration isolation. However, the adequate design of expanded cork blocks vibration isolators will depend on several factors, such as excitation frequency, static load conditions and intrinsic dynamic behavior of the material. In this study, transmissibility tests for different static and dynamic loading conditions were performed in order to characterize the material. Since the material’s physical properties can influence the vibro-isolation performance of the blocks (in terms of density and thickness), this study covered four mass density ranges and four block thicknesses. A total of 72 expanded cork agglomerate specimens were tested. The test apparatus comprises a vibration exciter connected to an excitation mass that holds the test specimen. The test specimens under characterization were loaded successively with steel plates in order to obtain results for different masses. An accelerometer was placed at the top of these masses and at the base of the excitation mass. The test was performed for a defined frequency range, and the amplitude registered by the accelerometers was recorded in time domain. For each of the signals (signal 1- vibration of the excitation mass, signal 2- vibration of the loading mass) a fast Fourier transform (FFT) was applied in order to obtain the frequency domain response. For each of the frequency domain signals, the maximum amplitude reached was registered. The ratio between the amplitude (acceleration) of signal 2 and the amplitude of signal 1, allows the calculation of the transmissibility for each frequency. Repeating this procedure allowed us to plot a transmissibility curve for a certain frequency range. A number of transmissibility experiments were performed to assess the influence of changing the mass density and thickness of the expanded cork blocks and the experimental conditions (static load and frequency of excitation). The experimental transmissibility tests performed in this study showed that expanded cork agglomerate blocks are a good option for mitigating vibrations. It was concluded that specimens with lower mass density and larger thickness lead to better performance, with higher vibration isolation and a larger range of isolated frequencies. In conclusion, the study of the performance of expanded cork agglomerate blocks presented herein will allow for a more efficient application of expanded cork vibration isolators. This is particularly relevant since this material is a more sustainable alternative to other commonly used non-environmentally friendly products, such as rubber.

Keywords: expanded cork agglomerate, insulation cork board, transmissibility tests, sustainable materials, vibration isolators

Procedia PDF Downloads 332