Search results for: co-processing of signaling parameters
8850 Transcriptional Evidence for the Involvement of MyD88 in Flagellin Recognition: Genomic Identification of Rock Bream MyD88 and Comparative Analysis
Authors: N. Umasuthan, S. D. N. K. Bathige, W. S. Thulasitha, I. Whang, J. Lee
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The MyD88 is an evolutionarily conserved host-expressed adaptor protein that is essential for proper TLR/ IL1R immune-response signaling. A previously identified complete cDNA (1626 bp) of OfMyD88 comprised an ORF of 867 bp encoding a protein of 288 amino acids (32.9 kDa). The gDNA (3761 bp) of OfMyD88 revealed a quinquepartite genome organization composed of 5 exons (with the sizes of 310, 132, 178, 92 and 155 bp) separated by 4 introns. All the introns displayed splice signals consistent with the consensus GT/AG rule. A bipartite domain structure with two domains namely death domain (24-103) coded by 1st exon, and TIR domain (151-288) coded by last 3 exons were identified through in silico analysis. Moreover, homology modeling of these two domains revealed a similar quaternary folding nature between human and rock bream homologs. A comprehensive comparison of vertebrate MyD88 genes showed that they possess a 5-exonic structure. In this structure, the last three exons were strongly conserved, and this suggests that a rigid structure has been maintained during vertebrate evolution. A cluster of TATA box-like sequences were found 0.25 kb upstream of cDNA starting position. In addition, putative 5'-flanking region of OfMyD88 was predicted to have TFBS implicated with TLR signaling, including copies of NFB1, APRF/ STAT3, Sp1, IRF1 and 2 and Stat1/2. Using qPCR technique, a ubiquitous mRNA expression was detected in liver and blood. Furthermore, a significantly up-regulated transcriptional expression of OfMyD88 was detected in head kidney (12-24 h; >2-fold), spleen (6 h; 1.5-fold), liver (3 h; 1.9-fold) and intestine (24 h; ~2-fold) post-Fla challenge. These data suggest a crucial role for MyD88 in antibacterial immunity of teleosts.Keywords: MyD88, innate immunity, flagellin, genomic analysis
Procedia PDF Downloads 4088849 Implementation of Clinical Monitoring System of Physiological Parameters
Authors: Abdesselam Babouri, Ahcène Lemzadmi, M Rahmane, B. Belhadi, N. Abouchi
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Medical monitoring aims at monitoring and remotely controlling the vital physiological parameters of the patient. The physiological sensors provide repetitive measurements of these parameters in the form of electrical signals that vary continuously over time. Various measures allow informing us about the health of the person's physiological data (weight, blood pressure, heart rate or specific to a disease), environmental conditions (temperature, humidity, light, noise level) and displacement and movements (physical efforts and the completion of major daily living activities). The collected data will allow monitoring the patient’s condition and alerting in case of modification. They are also used in the diagnosis and decision making on medical treatment and the health of the patient. This work presents the implementation of a monitoring system to be used for the control of physiological parameters.Keywords: clinical monitoring, physiological parameters, biomedical sensors, personal health
Procedia PDF Downloads 4638848 Analysis of the IEEE 802.15.4 MAC Parameters to Achive Lower Packet Loss Rates
Authors: Imen Bouazzi
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The IEEE-802.15.4 standard utilizes the CSMA-CA mechanism to control nodes access to the shared wireless communication medium. It is becoming the popular choice for various applications of surveillance and control used in wireless sensor network (WSN). The benefit of this standard is evaluated regarding of the packet loss probability who depends on the configuration of IEEE 802.15.4 MAC parameters and the traffic load. Our exigency is to evaluate the effects of various configurable MAC parameters on the performance of beaconless IEEE 802.15.4 networks under different traffic loads, static values of IEEE 802.15.4 MAC parameters (macMinBE, macMaxCSMABackoffs, and macMaxFrame Retries) will be evaluated. To performance analysis, we use ns-2[2] network simulator.Keywords: WSN, packet loss, CSMA/CA, IEEE-802.15.4
Procedia PDF Downloads 3318847 Design and Synthesis of Some Pyrimidine Derivatives as Bruton’s Tyrosine Kinase Inhibitors for Hematologic Malignancies
Authors: Ibrahim M. Labouta, Gina N. Tageldin, Salwa M. Fahmy, Hayam M. Ashour, Mounir A. Khalil, Tamer M. Ibrahim, Nefertiti A. El-Nikhely
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Bruton’s tyrosine kinase (BTK) is a critical effector molecule in B cell antigen receptor (BCR) signaling transduction. It regulates B cell proliferation, development and survival. Since BTK is widely expressed in many B cell leukaemias and lymphomas, targeting BTK by small molecules inhibitors became an attractive idea as new treatment modalities for B cell mediated hematologic malignancies. Ibrutinib is the 1st generation BTK inhibitor, approved by FDA for treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). It binds irreversibly to the unique cysteine (Cys481) within the ATP-binding pocket of BTK. Besides ibrutinib, many irreversible covalent BTK inhibitors comprising pyrimidine nucleus such as spebrutinib (phase IIb) showed high selectivity and potency when compared to it. In this study, the designed compounds were based on 5-cyano-2-methylsulfanyl pyrimidine core and decorated with electrophilic warheads which are essential for the optimal activity for targeted covalent inhibition (TCI). However, modifications at pyrimidine C4 or C6 were made by introduction of substituted amines which are provided to behave differently. The synthesized derivatives were evaluated for their anticancer activity in leukemia cell lines (e.g. THP-1). Results showed that, some derivatives exhibited antiproliferative activity with IC50 ranged from 5-50 μM, The in vitro enzymatic inhibitory assay for these compounds against BTK is still under investigation. Nevertheless, we could conclude from the initial biological screening that, the synthesized 4 or 6-subsitituted aminopyrimidines represent promising and novel antileukemic agents. Meanwhile, further studies are still needed to attribute this activity through targeting BTK enzyme and inhibition of BCR signaling pathway.Keywords: BTK inhibitors, hematologic malignancies, structure based drug design (SBDD), targeted covalent inhibitors (TCI)
Procedia PDF Downloads 1418846 Optimization of Friction Stir Spot Welding Process Parameters for Joining 6061 Aluminum Alloy Using Taguchi Method
Authors: Mohammed A. Tashkandi, Jawdat A. Al-Jarrah, Masoud Ibrahim
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This paper investigates the shear strength of the joints produced by friction stir spot welding process (FSSW). FSSW parameters such as tool rotational speed, plunge depth, shoulder diameter of the welding tool and dwell time play the major role in determining the shear strength of the joints. The effect of these four parameters on FSSW process as well as the shear strength of the welded joints was studied via five levels of each parameter. Taguchi method was used to minimize the number of experiments required to determine the fracture load of the friction stir spot-welded joints by incorporating independently controllable FSSW parameters. Taguchi analysis was applied to optimize the FSSW parameters to attain the maximum shear strength of the spot weld for this type of aluminum alloy.Keywords: Friction Stir Spot Welding, Al6061 alloy, Shear Strength, FSSW process parameters
Procedia PDF Downloads 4208845 Angiogenesis and Blood Flow: The Role of Blood Flow in Proliferation and Migration of Endothelial Cells
Authors: Hossein Bazmara, Kaamran Raahemifar, Mostafa Sefidgar, Madjid Soltani
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Angiogenesis is formation of new blood vessels from existing vessels. Due to flow of blood in vessels, during angiogenesis, blood flow plays an important role in regulating the angiogenesis process. Multiple mathematical models of angiogenesis have been proposed to simulate the formation of the complicated network of capillaries around a tumor. In this work, a multi-scale model of angiogenesis is developed to show the effect of blood flow on capillaries and network formation. This model spans multiple temporal and spatial scales, i.e. intracellular (molecular), cellular, and extracellular (tissue) scales. In intracellular or molecular scale, the signaling cascade of endothelial cells is obtained. Two main stages in development of a vessel are considered. In the first stage, single sprouts are extended toward the tumor. In this stage, the main regulator of endothelial cells behavior is the signals from extracellular matrix. After anastomosis and formation of closed loops, blood flow starts in the capillaries. In this stage, blood flow induced signals regulate endothelial cells behaviors. In cellular scale, growth and migration of endothelial cells is modeled with a discrete lattice Monte Carlo method called cellular Pott's model (CPM). In extracellular (tissue) scale, diffusion of tumor angiogenic factors in the extracellular matrix, formation of closed loops (anastomosis), and shear stress induced by blood flow is considered. The model is able to simulate the formation of a closed loop and its extension. The results are validated against experimental data. The results show that, without blood flow, the capillaries are not able to maintain their integrity.Keywords: angiogenesis, endothelial cells, multi-scale model, cellular Pott's model, signaling cascade
Procedia PDF Downloads 4138844 Development of a Robust Protein Classifier to Predict EMT Status of Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (CESC) Tumors
Authors: ZhenlinJu, Christopher P. Vellano, RehanAkbani, Yiling Lu, Gordon B. Mills
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The epithelial–mesenchymal transition (EMT) is a process by which epithelial cells acquire mesenchymal characteristics, such as profound disruption of cell-cell junctions, loss of apical-basolateral polarity, and extensive reorganization of the actin cytoskeleton to induce cell motility and invasion. A hallmark of EMT is its capacity to promote metastasis, which is due in part to activation of several transcription factors and subsequent downregulation of E-cadherin. Unfortunately, current approaches have yet to uncover robust protein marker sets that can classify tumors as possessing strong EMT signatures. In this study, we utilize reverse phase protein array (RPPA) data and consensus clustering methods to successfully classify a subset of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) tumors into an EMT protein signaling group (EMT group). The overall survival (OS) of patients in the EMT group is significantly worse than those in the other Hormone and PI3K/AKT signaling groups. In addition to a shrinkage and selection method for linear regression (LASSO), we applied training/test set and Monte Carlo resampling approaches to identify a set of protein markers that predicts the EMT status of CESC tumors. We fit a logistic model to these protein markers and developed a classifier, which was fixed in the training set and validated in the testing set. The classifier robustly predicted the EMT status of the testing set with an area under the curve (AUC) of 0.975 by Receiver Operating Characteristic (ROC) analysis. This method not only identifies a core set of proteins underlying an EMT signature in cervical cancer patients, but also provides a tool to examine protein predictors that drive molecular subtypes in other diseases.Keywords: consensus clustering, TCGA CESC, Silhouette, Monte Carlo LASSO
Procedia PDF Downloads 4578843 The Function of Polycomb Repressive Complex 2 (PRC2) In Plant Retrograde Signaling Pathway
Authors: Mingxi Zhou, Jiří Kubásek, Iva Mozgová
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In Arabidopsis thaliana, histone 3 lysine 27 tri-methylation catalysed byPRC2 is playing essential functions in the regulation of plant development, growth, and reproduction[1-2]. Despite numerous studies related to the role of PRC2 in developmental control, how PRC2 works in the operational control in plants is unknown. In the present, the evidence that PRC2 probably participates in the regulation of retrograde singalling pathway in Arabidopsisis found. Firstly, we observed that the rosette size and biomass in PRC2-depletion mutants (clf-29 and swn-3) is significantly higher than WTunder medium light condition (ML: 125 µmol m⁻² s⁻²), while under medium high light condition (MHL: 300 µmol m⁻² s-2), the increase was reverse. Under ML condition, the photosynthesis related parameters determined by fluorCam did not show significant differences between WT and mutants, while the pigments concentration increased in the leaf of PRC2-depletion mutants, especially in swn. The dynamic of light-responsive genes and circadian clock genes expression by RT-qPCRwithin 24 hours in the mutants were comparable to WT. However, we observed upregulation of photosynthesis-associated nuclear genes in the PRC2-depletion mutants under chloroplast damaging condition (treated by lincomycin), corresponding to the so-called genome uncoupled (gun) phenotype. Here, we will present our results describing these phenotypes and our suggestion and outlook for studying the involvement of PRC2 in chloroplast-to-nucleus retrograde signalling.Keywords: PRC2, retrograde signalling, light acclimation, photosyntheis
Procedia PDF Downloads 968842 Room Level Indoor Localization Using Relevant Channel Impulse Response Parameters
Authors: Raida Zouari, Iness Ahriz, Rafik Zayani, Ali Dziri, Ridha Bouallegue
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This paper proposes a room level indoor localization algorithm based on the use Multi-Layer Neural Network (MLNN) classifiers and one versus one strategy. Seven parameters of the Channel Impulse Response (CIR) were used and Gram-Shmidt Orthogonalization was performed to study the relevance of the extracted parameters. Simulation results show that when relevant CIR parameters are used as position fingerprint and when optimal MLNN architecture is selected good room level localization score can be achieved. The current study showed also that some of the CIR parameters are not correlated to the location and can decrease the localization performance of the system.Keywords: mobile indoor localization, multi-layer neural network (MLNN), channel impulse response (CIR), Gram-Shmidt orthogonalization
Procedia PDF Downloads 3478841 Parameters Tuning of a PID Controller on a DC Motor Using Honey Bee and Genetic Algorithms
Authors: Saeid Jalilzadeh
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PID controllers are widely used to control the industrial plants because of their robustness and simple structures. Tuning of the controller's parameters to get a desired response is difficult and time consuming. With the development of computer technology and artificial intelligence in automatic control field, all kinds of parameters tuning methods of PID controller have emerged in endlessly, which bring much energy for the study of PID controller, but many advanced tuning methods behave not so perfect as to be expected. Honey Bee algorithm (HBA) and genetic algorithm (GA) are extensively used for real parameter optimization in diverse fields of study. This paper describes an application of HBA and GA to the problem of designing a PID controller whose parameters comprise proportionality constant, integral constant and derivative constant. Presence of three parameters to optimize makes the task of designing a PID controller more challenging than conventional P, PI, and PD controllers design. The suitability of the proposed approach has been demonstrated through computer simulation using MATLAB/SIMULINK.Keywords: controller, GA, optimization, PID, PSO
Procedia PDF Downloads 5358840 Effect of Electron Beam Irradiated Cottonseed Meal on Carcass and Blood Parameters of Broiler Chickens
Authors: Somayyeh Salari, Marziyeh Nayefi, Mohsen Sari, Mehdi Behgar
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This study was conducted to evaluate the effect of electron beam- irradiated cottonseed meal at a dose of 30 KGy on carcass characteristics and some blood parameters of broiler chicks. Various levels of cottonseed meal (CSM) (0, 12, and 24%, radiation and no radiation) were used with 5 dietary treatments, 4 replicates and 10 birds of each for 42 days in completely randomized design. At 42 d of age, two birds per pen were randomly selected for determination of carcass characteristics and blood parameters. Relative weights of liver, gastrointestinal tract (GI), pancreatic, gizzard and abdominal fat were increased with increasing levels of CSM in the diet (p<0/05). Glucose, cholesterol, HDL, triglyceride, and phosphorous concentrations increased and LDL concentration decreased as the dietary CSM levels increased (p<0/05). But radiation had not significant effect on blood parameters. Electron irradiation seems to be a good procedure to improve the nutritional quality of CSM but it seems higher dose of it was needed to improve blood parameters of chickens.Keywords: blood parameters, carcass characteristics, cottonseed meal, electron beam
Procedia PDF Downloads 4718839 Improvement of the Q-System Using the Rock Engineering System: A Case Study of Water Conveyor Tunnel of Azad Dam
Authors: Sahand Golmohammadi, Sana Hosseini Shirazi
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Because the status and mechanical parameters of discontinuities in the rock mass are included in the calculations, various methods of rock engineering classification are often used as a starting point for the design of different types of structures. The Q-system is one of the most frequently used methods for stability analysis and determination of support systems of underground structures in rock, including tunnel. In this method, six main parameters of the rock mass, namely, the rock quality designation (RQD), joint set number (Jn), joint roughness number (Jr), joint alteration number (Ja), joint water parameter (Jw) and stress reduction factor (SRF) are required. In this regard, in order to achieve a reasonable and optimal design, identifying the effective parameters for the stability of the mentioned structures is one of the most important goals and the most necessary actions in rock engineering. Therefore, it is necessary to study the relationships between the parameters of a system and how they interact with each other and, ultimately, the whole system. In this research, it has attempted to determine the most effective parameters (key parameters) from the six parameters of rock mass in the Q-system using the rock engineering system (RES) method to improve the relationships between the parameters in the calculation of the Q value. The RES system is, in fact, a method by which one can determine the degree of cause and effect of a system's parameters by making an interaction matrix. In this research, the geomechanical data collected from the water conveyor tunnel of Azad Dam were used to make the interaction matrix of the Q-system. For this purpose, instead of using the conventional methods that are always accompanied by defects such as uncertainty, the Q-system interaction matrix is coded using a technique that is actually a statistical analysis of the data and determining the correlation coefficient between them. So, the effect of each parameter on the system is evaluated with greater certainty. The results of this study show that the formed interaction matrix provides a reasonable estimate of the effective parameters in the Q-system. Among the six parameters of the Q-system, the SRF and Jr parameters have the maximum and minimum impact on the system, respectively, and also the RQD and Jw parameters have the maximum and minimum impact on the system, respectively. Therefore, by developing this method, we can obtain a more accurate relation to the rock mass classification by weighting the required parameters in the Q-system.Keywords: Q-system, rock engineering system, statistical analysis, rock mass, tunnel
Procedia PDF Downloads 618838 Modeling and Optimization of Performance of Four Stroke Spark Ignition Injector Engine
Authors: A. A. Okafor, C. H. Achebe, J. L. Chukwuneke, C. G. Ozoegwu
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The performance of an engine whose basic design parameters are known can be predicted with the assistance of simulation programs into the less time, cost and near value of actual. This paper presents a comprehensive mathematical model of the performance parameters of four stroke spark ignition engine. The essence of this research work is to develop a mathematical model for the analysis of engine performance parameters of four stroke spark ignition engine before embarking on full scale construction, this will ensure that only optimal parameters are in the design and development of an engine and also allow to check and develop the design of the engine and it’s operation alternatives in an inexpensive way and less time, instead of using experimental method which requires costly research test beds. To achieve this, equations were derived which describe the performance parameters (sfc, thermal efficiency, mep and A/F). The equations were used to simulate and optimize the engine performance of the model for various engine speeds. The optimal values obtained for the developed bivariate mathematical models are: sfc is 0.2833kg/kwh, efficiency is 28.77% and a/f is 20.75.Keywords: bivariate models, engine performance, injector engine, optimization, performance parameters, simulation, spark ignition
Procedia PDF Downloads 3178837 Physical Characterization of a Watershed for Correlation with Parameters of Thomas Hydrological Model and Its Application in Iber Hidrodinamic Model
Authors: Carlos Caro, Ernest Blade, Nestor Rojas
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This study determined the relationship between basic geo-technical parameters and parameters of the hydro logical model Thomas for water balance of rural watersheds, as a methodological calibration application, applicable in distributed models as IBER model, which represents a distributed system simulation models for unsteady flow numerical free surface. There was an exploration in 25 points (on 15 sub) basin of Rio Piedras (Boy.) obtaining soil samples, to which geo-technical characterization was performed by laboratory tests. Thomas model has a physical characterization of the input area by only four parameters (a, b, c, d). Achieve measurable relationship between geo technical parameters and 4 values of hydro logical parameters helps to determine subsurface, underground and surface flow more agile manner. It is intended in this way to reach some solutions regarding limits initial model parameters on the basis of Thomas geo-technical characterization. In hydro geological models of rural watersheds, calibration is an important process in the characterization of the study area. This step can require a significant computational cost and time, especially if the initial values or parameters before calibration are outside of the geo-technical reality. A better approach in these initial values means optimization of these process through a geo-technical materials area, where is obtained an important approach to the study as in the starting range of variation for the calibration parameters.Keywords: distributed hydrology, hydrological and geotechnical characterization, Iber model
Procedia PDF Downloads 5138836 Sensitivity Analysis of Pile-Founded Fixed Steel Jacket Platforms
Authors: Mohamed Noureldin, Jinkoo Kim
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The sensitivity of the seismic response parameters to the uncertain modeling variables of pile-founded fixed steel jacket platforms are investigated using tornado diagram, first-order second-moment, and static pushover analysis techniques. The effects of both aleatory and epistemic uncertainty on seismic response parameters have been investigated for an existing offshore platform. The sources of uncertainty considered in the present study are categorized into three different categories: the uncertainties associated with the soil-pile modeling parameters in clay soil, the platform jacket structure modeling parameters, and the uncertainties related to ground motion excitations. It has been found that the variability in parameters such as yield strength or pile bearing capacity has almost no effect on the seismic response parameters considered, whereas the global structural response is highly affected by the ground motion uncertainty. Also, some uncertainty in soil-pile property such as soil-pile friction capacity has a significant impact on the response parameters and should be carefully modeled. Based on the results, it is highlighted that which uncertain parameters should be considered carefully and which can be assumed with reasonable engineering judgment during the early structural design stage of fixed steel jacket platforms.Keywords: fixed jacket offshore platform, pile-soil structure interaction, sensitivity analysis
Procedia PDF Downloads 3678835 Data Protection and Regulation Compliance on Handling Physical Child Abuse Scenarios- A Scoping Review
Authors: Ana Mafalda Silva, Rebeca Fontes, Ana Paula Vaz, Carla Carreira, Ana Corte-Real
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Decades of research on the topic of interpersonal violence against minors highlight five main conclusions: 1) it causes harmful effects on children's development and health; 2) it is prevalent; 3) it violates children's rights; 4) it can be prevented and 5) parents are the main aggressors. The child abuse scenario is identified through clinical observation, administrative data and self-reports. The most used instruments are self-reports; however, there are no valid and reliable self-report instruments for minors, which consist of a retrospective interpretation of the situation by the victim already in her adult phase and/or by her parents. Clinical observation and collection of information, namely from the orofacial region, are essential in the early identification of these situations. The management of medical data, such as personal data, must comply with the General Data Protection Regulation (GDPR), in Europe, and with the General Law of Data Protection (LGPD), in Brazil. This review aims to answer the question: In a situation of medical assistance to minors, in the suspicion of interpersonal violence, due to mistreatment, is it necessary for the guardians to provide consent in the registration and sharing of personal data, namely medical ones. A scoping review was carried out based on a search by the Web of Science and Pubmed search engines. Four papers and two documents from the grey literature were selected. As found, the process of identifying and signaling child abuse by the health professional, and the necessary early intervention in defense of the minor as a victim of abuse, comply with the guidelines expressed in the GDPR and LGPD. This way, the notification in maltreatment scenarios by health professionals should be a priority and there shouldn’t be the fear or anxiety of legal repercussions that stands in the way of collecting and treating the data necessary for the signaling procedure that safeguards and promotes the welfare of children living with abuse.Keywords: child abuse, disease notifications, ethics, healthcare assistance
Procedia PDF Downloads 898834 Gene Expression Signature-Based Chemical Genomic to Identify Potential Therapeutic Compounds for Colorectal Cancer
Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee
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There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor
Procedia PDF Downloads 3018833 Determination of LS-DYNA MAT162 Material input Parameters for Low Velocity Impact Analysis of Layered Composites
Authors: Mustafa Albayrak, Mete Onur Kaman, Ilyas Bozkurt
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In this study, the necessary material parameters were determined to be able to conduct progressive damage analysis of layered composites under low velocity impact by using the MAT162 material module in the LS-DYNA program. The material module MAT162 based on Hashin failure criterion requires 34 parameters in total. Some of these parameters were obtained directly as a result of dynamic and quasi-static mechanical tests, and the remaining part was calibrated and determined by comparing numerical and experimental results. Woven glass/epoxy was used as the composite material and it was produced by vacuum infusion method. In the numerical model, composites are modeled as three-dimensional and layered. As a result, the acquisition of MAT162 material module parameters, which will enable progressive damage analysis, is given in detail and step by step, and the selection methods of the parameters are explained. Numerical data consistent with the experimental results are given in graphics.Keywords: Composite Impact, Finite Element Simulation, Progressive Damage Analyze, LS-DYNA, MAT162
Procedia PDF Downloads 948832 Rapid Formation of Ortho-Boronoimines and Derivatives for Reversible and Dynamic Bioconjugation Under Physiological Conditions
Authors: Nicholas C. Rose, Christopher D. Spicer
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The regeneration of damaged or diseased tissues would provide an invaluable therapeutic tool in biological research and medicine. Cells must be provided with a number of different biochemical signals in order to form mature tissue through complex signaling networks that are difficult to recreate in synthetic materials. The ability to attach and detach bioactive proteins from material in an iterative and dynamic manner would therefore present a powerful way to mimic natural biochemical signaling cascades for tissue growth. We propose to reversibly attach these bioactive proteins using ortho-boronoimine (oBI) linkages and related derivatives formed by the reaction of an ortho-boronobenzaldehyde with a nucleophilic amine derivative. To enable the use of oBIs for biomaterial modification, we have studied binding and cleavage processes with precise detail in the context of small molecule models. A panel of oBI complexes has been synthesized and screened using a novel Förster resonance energy transfer (FRET) assay, using a cyanine dye FRET pair (Cy3 and Cy5), to identify the most reactive boron-aldehyde/amine nucleophile pairs. Upon conjugation of the dyes, FRET occurs under Cy3 excitation and the resultant ratio of Cy3:Cy5 emission directly correlates to conversion. Reaction kinetics and equilibria can be accurately quantified for reactive pairs, with dissociation constants of oBI derivatives in water (KD) found to span 9-orders of magnitude (10⁻²-10⁻¹¹ M). These studies have provided us with a better understanding of oBI linkages that we hope to exploit to reversibly attach bioconjugates to materials. The long-term aim of the project is to develop a modular biomaterial platform that can be used to help combat chronic diseases such as osteoarthritis, heart disease, and chronic wounds by providing cells with potent biological stimuli for tissue engineering.Keywords: dynamic, bioconjugation, bornoimine, rapid, physiological
Procedia PDF Downloads 898831 Singular Value Decomposition Based Optimisation of Design Parameters of a Gearbox
Authors: Mehmet Bozca
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Singular value decomposition based optimisation of geometric design parameters of a 5-speed gearbox is studied. During the optimisation, a four-degree-of freedom torsional vibration model of the pinion gear-wheel gear system is obtained and the minimum singular value of the transfer matrix is considered as the objective functions. The computational cost of the associated singular value problems is quite low for the objective function, because it is only necessary to compute the largest and smallest singular values (µmax and µmin) that can be achieved by using selective eigenvalue solvers; the other singular values are not needed. The design parameters are optimised under several constraints that include bending stress, contact stress and constant distance between gear centres. Thus, by optimising the geometric parameters of the gearbox such as, the module, number of teeth and face width it is possible to obtain a light-weight-gearbox structure. It is concluded that the all optimised geometric design parameters also satisfy all constraints.Keywords: Singular value, optimisation, gearbox, torsional vibration
Procedia PDF Downloads 3508830 Parallel Self Organizing Neural Network Based Estimation of Archie’s Parameters and Water Saturation in Sandstone Reservoir
Authors: G. M. Hamada, A. A. Al-Gathe, A. M. Al-Khudafi
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Determination of water saturation in sandstone is a vital question to determine the initial oil or gas in place in reservoir rocks. Water saturation determination using electrical measurements is mainly on Archie’s formula. Consequently accuracy of Archie’s formula parameters affects water saturation values rigorously. Determination of Archie’s parameters a, m, and n is proceeded by three conventional techniques, Core Archie-Parameter Estimation (CAPE) and 3-D. This work introduces the hybrid system of parallel self-organizing neural network (PSONN) targeting accepted values of Archie’s parameters and, consequently, reliable water saturation values. This work focuses on Archie’s parameters determination techniques; conventional technique, CAPE technique, and 3-D technique, and then the calculation of water saturation using current. Using the same data, a hybrid parallel self-organizing neural network (PSONN) algorithm is used to estimate Archie’s parameters and predict water saturation. Results have shown that estimated Arche’s parameters m, a, and n are highly accepted with statistical analysis, indicating that the PSONN model has a lower statistical error and higher correlation coefficient. This study was conducted using a high number of measurement points for 144 core plugs from a sandstone reservoir. PSONN algorithm can provide reliable water saturation values, and it can supplement or even replace the conventional techniques to determine Archie’s parameters and thereby calculate water saturation profiles.Keywords: water saturation, Archie’s parameters, artificial intelligence, PSONN, sandstone reservoir
Procedia PDF Downloads 1228829 Cardiac Hypertrophy in Diabetes; The Role of Factor Forkhead Box Class O-Regulation by O-GlcNAcylation
Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian
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Cardiac hypertrophy arises in response to persistent increases in hemodynamic loads. In comparison, diabetic cardiomyopathy is defined by an abnormal myocardial changes without other cardiac-related risk factors. Pathological cardiac hypertrophy and myocardial remodeling are hallmarks of cardiovascular diseases and are risk factors for heart failure. The transcription factor forkhead box class O (FOXOs) can protect heart tissue by hostile oxidative stress and stimulating apoptosis and autophagy. FOXO proteins, as sensitive elements and mediators in response to environmental changes, have been revealed to prevent and inverse cardiac hypertrophy. FOXOs are inhibited by insulin and are critical mediators of insulin action. Insulin deficiency and uncontrolled diabetes lead to a catabolic state. FOXO1 acts downstream of the insulin-dependent pathways, which are dysregulated in diabetes. It regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K/Akt activation, which are critical regulators of cardiac hypertrophy. The complex network of signaling pathways comprising insulin/IGF-1 signaling, AMPK, JNK, and Sirtuins regulate the development of cardiovascular dysfunction by modulating the activity of FOXOs. Insulin receptors and IGF1R act via the PI3k/Akt and the MAPK/ERK pathways. Activation of Akt in response to insulin or IGF-1 induces phosphorylation of FOXOs. Increased protein synthesis induced by activation of the IGF-I/Akt/mTOR signaling pathway leads to hypertrophy. This pathway and the myostatin/Smad pathway are potent negative muscle development regulators. In cardiac muscle, insulin receptor substrates (IRS)-1 or IRS-2 activates the Akt signaling pathway and inactivate FOXO1. Under metabolic stress, p38 MAPK promotes degradation of IRS-1 and IRS-2 in cardiac myocytes and activates FOXO1, leading to cardiomyopathy. Sirt1 and FOXO1 interaction play an essential role in starvation-induced autophagy in cardiac metabolism. Inhibition of Angiotensin-II induced cardiomyocyte hypertrophy is associated with reduced FOXO1 acetylation and activation of Sirt1. The NF-κB, ERK, and FOXOs are de-acetylated by SIRT1. De-acetylation of FOXO1 induces the expression of genes involved in autophagy and stimulates autophagy flux. Therefore, under metabolic stress, FOXO1 can cause diabetic cardiomyopathy. The overexpression of FOXO1 leads to decreased cardiomyocyte size and suppresses cardiac hypertrophy through inhibition of the calcineurin–NFAT pathway. Diabetes mellitus is associated with elevation of O-GlcNAcylation. Some of its binding partners regulate the substrate selectivity of O-GlcNAc transferase (OGT). O-GlcNAcylation of essential contractile proteins may inhibit protein-protein interactions, reduce calcium sensitivity, and modulate contractile function. Uridine diphosphate (UDP)-GlcNAc is the obligatory substrate of OGT, which catalyzes a reversible post-translational protein modification. The increase of O-GlcNAcylation is accompanied by impaired cardiac hypertrophy in diabetic hearts. Inhibition of O-GlcNAcylation blocks activation of ERK1/2 and hypertrophic growth. O-GlcNAc modification on NFAT is required for its translocation from the cytosol to the nucleus, where NFAT stimulates the transcription of various hypertrophic genes. Inhibition of O-GlcNAcylation dampens NFAT-induced cardiac hypertrophic growth. Transcriptional activity of FOXO1 is enriched by improved O-GlcNAcylation upon high glucose stimulation or OGT overexpression. In diabetic conditions, the modification of FOXO1 by O-GlcNAc is promoted in cardiac troponin I and myosin light chain 2. Therefore targeting O-GlcNAcylation represents a potential therapeutic option to prevent hypertrophy in the diabetic heart.Keywords: diabetes, cardiac hypertrophy, O-GlcNAcylation, FOXO1, Akt, PI3K, AMPK, insulin
Procedia PDF Downloads 1038828 Soil Parameters Identification around PMT Test by Inverse Analysis
Authors: I. Toumi, Y. Abed, A. Bouafia
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This paper presents a methodology for identifying the cohesive soil parameters that takes into account different constitutive equations. The procedure, applied to identify the parameters of generalized Prager model associated to the Drucker & Prager failure criterion from a pressuremeter expansion curve, is based on an inverse analysis approach, which consists of minimizing the function representing the difference between the experimental curve and the simulated curve using a simplex algorithm. The model response on pressuremeter path and its identification from experimental data lead to the determination of the friction angle, the cohesion and the Young modulus. Some parameters effects on the simulated curves and stresses path around pressuremeter probe are presented. Comparisons between the parameters determined with the proposed method and those obtained by other means are also presented.Keywords: cohesive soils, cavity expansion, pressuremeter test, finite element method, optimization procedure, simplex algorithm
Procedia PDF Downloads 2878827 Proteomic Analysis of the Inhibition of Prolyl Oligopeptidase Induced by Z-Pro-Prolinal in Filarial Parasites
Authors: Mohit Wadhawan, Sushma Rathaur
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Lymphatic filariasis, also called elephantiasis is a tropical disease afflicting over 120 million people in 81 countries worldwide. Existing anti filarial drugs are effective against the larval stages of filarial parasites which call for an urgent need of drugs which are macrofilaricidal. Identification of molecular targets crucial for survival of filarial parasites is a prerequisite for drug designing. Prolyl oligopeptidase (POP) is one such crucial enzyme involved in the maturation and degradation of neuropeptides and peptide hormones. We have identified this peptidase in the bovine filarial parasite, Setaria cervi. Effect of inhibition of POP on the proteome profile of filarial parasite has been discussed in this study. Filarial parasites were exposed to Z-pro-prolinal (ZPP), a specific POP inhibitor for 8 h and the motility and viability of the parasites was observed. It significantly reduced the motility and viability of the parasites. To study the proteome profile, the cytosolic, endoplasmic reticulum (ER) and mitochondrial extracts of the adult female parasites were subjected to 2-dimensional electrophoresis. As analyzed by the PD-Quest software, the ZPP caused the alteration in the different subcellular proteins, and the significantly altered proteins were identified using MALDI-MS/MS spectrometry. The major proteins identified were found to play important role in diverse biological functions like signaling, redox regulation, energy metabolism, stress response, and cytoskeleton formation. Moreover, we found upregulation in the calcium binding proteins such as calreticulin, calponin, and calpain-6 suggesting that POP inhibition regulates calcium release. This relates to earlier reports that POP plays non-catalytic role in inositol 1,4,5-trisphosphate (IP3) signaling inducing release of calcium from ER. Taken together, the data demonstrated that inhibition of prolyl oligopeptidase alter the overall proteome signifying its role in survival of the filarial parasites. Thus this study provides a basis for the use of POP as a chemotherapeutic target for the treatment of lymphatic filariasis.Keywords: lymphatic filariasis, setaria cervi, prolyl oligopeptidase, proteomics
Procedia PDF Downloads 2778826 Chemotrophic Signal Exchange between the Host Plant Helianthemum sessiliflorum and Terfezia boudieri
Authors: S. Ben-Shabat, T. Turgeman, O. Leubinski, N. Roth-Bejerano, V. Kagan-Zur, Y. Sitrit
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The ectomycorrhizal (ECM) desert truffle Terfezia boudieri produces edible fruit bodies and forms symbiosis with its host plant Helianthemum sessiliflorum (Cistaceae) in the Negev desert of Israel. The symbiosis is vital for both partners' survival under desert conditions. Under desert habitat conditions, ECMs must form symbiosis before entering the dry season. To secure a successful encounter, in the course of evolution, both partners have responded by evolving special signals exchange that facilitates recognition. Members of the Cistaceae family serve as host plants for many important truffles. Conceivably, during evolution a common molecule present in Cistaceae plants was recruited to facilitate successful encounter with ectomycorrhizas. Arbuscular vesicular fungi (AM) are promiscuous in host preferences, in contrast, ECM fungi show specificity to host plants. Accordingly, we hypothesize that H. sessiliflorum secretes a chemotrophic-signaling, which is common to plants hosting ECM fungi belonging to the Pezizales. However, thus far no signaling molecules have been identified in ECM fungi. We developed a bioassay for chemotrophic activity. Fractionation of root exudates revealed a substance with chemotrophic activity and molecular mass of 534. Following the above concept, screening the transcriptome of Terfezia, grown under chemoattraction, discovered genes showing high homology to G proteins-coupled receptors of plant pathogens involved in positive chemotaxis and chemotaxis suppression. This study aimed to identify the active molecule using analytical methods (LC-MS, NMR etc.). This should contribute to our understanding of how ECM fungi communicate with their hosts in the rhizosphere. In line with the ability of Terfezia to form also endomycorrhizal symbiosis like AM fungi, analysis of the mechanisms may likewise be applicable to AM fungi. Developing methods to manipulate fungal growth by the chemoattractant can open new ways to improve inoculation of plants.Keywords: chemotrophic signal, Helianthemum sessiliflorum, Terfezia boudieri, ECM
Procedia PDF Downloads 4018825 Estimation of Transition and Emission Probabilities
Authors: Aakansha Gupta, Neha Vadnere, Tapasvi Soni, M. Anbarsi
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Protein secondary structure prediction is one of the most important goals pursued by bioinformatics and theoretical chemistry; it is highly important in medicine and biotechnology. Some aspects of protein functions and genome analysis can be predicted by secondary structure prediction. This is used to help annotate sequences, classify proteins, identify domains, and recognize functional motifs. In this paper, we represent protein secondary structure as a mathematical model. To extract and predict the protein secondary structure from the primary structure, we require a set of parameters. Any constants appearing in the model are specified by these parameters, which also provide a mechanism for efficient and accurate use of data. To estimate these model parameters there are many algorithms out of which the most popular one is the EM algorithm or called the Expectation Maximization Algorithm. These model parameters are estimated with the use of protein datasets like RS126 by using the Bayesian Probabilistic method (data set being categorical). This paper can then be extended into comparing the efficiency of EM algorithm to the other algorithms for estimating the model parameters, which will in turn lead to an efficient component for the Protein Secondary Structure Prediction. Further this paper provides a scope to use these parameters for predicting secondary structure of proteins using machine learning techniques like neural networks and fuzzy logic. The ultimate objective will be to obtain greater accuracy better than the previously achieved.Keywords: model parameters, expectation maximization algorithm, protein secondary structure prediction, bioinformatics
Procedia PDF Downloads 4668824 Technical Parameters Evaluation for Caps to Apucarana/Parana - Brazil APL
Authors: Cruz, G. P., Nagamatsu, R. N., Scacchetti, F. A. P., Merlin, F. K.
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This study aims to assess a set of technical parameters that provide quality products to the companies that produce caps, APL Apucarana / PR, the city that produces most Brazilian caps, in order to verify the potential of Brazilian caps to compete with international brands, recognized by the standard of excellence when it comes to quality of its products. The determination of the technical parameters was arbitrated from textile ABNT, a total of six technical parameters, providing eight tests for cotton caps. For the evaluation, we used as reference a leading brand recognized worldwide (based on their sales volume in $) for comparison with 3 companies of the APL Apucarana. The results showed that, of the 8 tests, of 8 tests, the companies Apucarana did not obtain better performance than the competitor. They obtained the same results in three tests and lower performance in 5. Given these values, it is concluded that local caps are not far from reaching the quality of leading brand. It is recommended that the APL companies use the parameters to evaluate their products, using this information to support decision-making that seek to improve both the product design and its production process, enabling the feasibility for faster international recognition . Thus, they may have an edge over its main competitor.Keywords: technical parameters, making caps, quality, evaluation
Procedia PDF Downloads 3358823 Involvement of Nrf2 in Kolaviron-Mediated Attenuation of Behavioural Incompetence and Neurodegeneration in a Murine Model of Parkinson's Disease
Authors: Yusuf E. Mustapha, Inioluwa A Akindoyeni, Oluwatoyin G. Ezekiel, Ifeoluwa O. Awogbindin, Ebenezer O. Farombi
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Background: Parkinson's disease (PD) is the most prevalent motor disorder. Available therapies are palliative with no effect on disease progression. Kolaviron (KV), a natural anti-inflammatory and antioxidant agent, has been reported to possess neuroprotective effects in Parkinsonian flies and rats. Objective: The present study investigates the neuroprotective effect of KV, focusing on the DJ1/Nrf2 signaling pathway. Methodology: All-trans retinoic acid (ATRA, 10 mg/kg, i.p.) was used to inhibit Nrf2. Murine model of PD was established with four doses of MPTP (20 mg/kg i.p.) at 2 hours interval. MPTP mice were pre-treated with either KV (200 mg/kg/day p.o), ATRA, or both conditions for seven days before PD induction. Motor behaviour was evaluated, and markers of oxidative stress/damage and its regulators were assessed with immunofluorescence and ELISA techniques. Results: MPTP-treated mice covered less distance with reduced numbers of anticlockwise rotations, heightened freezing, and prolonged immobility when compared to control. However, KV significantly attenuated these deficits. Pretreatment of MPTP mice with KV upregulated Nrf2 expression beyond MPTP level with a remarkable reduction in Keap1 expression and marked elevation of DJ-1 level, whereas co-administration with ATRA abrogated these effects. KV treatment restored MPTP-mediated depletion of endogenous antioxidant, striatal oxidative stress, oxidative damage, and inhibition of acetylcholinesterase activity. However, ATRA treatment potentiated acetylcholinesterase inhibition and attenuated the protective effect of KV on the level of nitric oxide and activities of catalase and superoxide dismutase. Conclusion: Kolaviron protects Parkinsonian mice by stabilizing and activating the Nrf2 signaling pathway. Thus, kolaviron can be explored as a pharmacological lead in PD management.Keywords: Garcinia kola, Kolaviron, Parkinson Disease, Nrf2, behavioral incompetence, neurodegeneration
Procedia PDF Downloads 888822 Moment Estimators of the Parameters of Zero-One Inflated Negative Binomial Distribution
Authors: Rafid Saeed Abdulrazak Alshkaki
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In this paper, zero-one inflated negative binomial distribution is considered, along with some of its structural properties, then its parameters were estimated using the method of moments. It is found that the method of moments to estimate the parameters of the zero-one inflated negative binomial models is not a proper method and may give incorrect conclusions.Keywords: zero one inflated models, negative binomial distribution, moments estimator, non negative integer sampling
Procedia PDF Downloads 2838821 Correlation between General Intelligence, Emotional Intelligence and Stress Response after One Month Practice of Moderate Intensity Physical Exercise
Authors: Mohita Singh, Sunil Sachdev, Amrita Singh
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Background and Aim: Physical aerobic exercises promote positive changes in one’s mental health, intelligence, and ability to cope with stressful encounters. The present study was designed to explore the correlation between intelligence and stress parameters and to assess the correlation between the same parameters after the practice of one month of moderate-intensity physical exercise. Method: The study was conducted on thirty-five healthy male volunteer students to assess the correlation between stress parameters in subjects with varying level of general intelligence (GI) and emotional intelligence (EI). Correlation studies were again conducted after one month between the same parameters to evaluate the effect of moderate-intensity physical exercise (MIPE). Baseline values were recorded using standard scales. Result: IQ and EQ correlated negatively with both acute and chronic stress parameters and positively with each other. A positive correlation was found between acute and chronic stress. With the practice of one month of moderate-intensity physical exercise, there was significant increment between the parameters under study and hence improved results. Conclusion: MIPE improved correlation between GI, EI, stress parameters, and thus reduced stress and improved intelligence.Keywords: emotional intelligence, general intelligence, moderate intensity physical exercise, stress response
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