Search results for: molecular modeling of Cdk5/p25

Authors: Jillian M. Hagel, Joseph E. Tucker, Peter J. Facchini

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With the aim of establishing a holistic approach for the treatment of central nervous system (CNS) disorders, we are pursuing a drug development program rapidly progressing through discovery and characterization phases. The drug candidates identified in this program are referred to as neuroplastogens owing to their ability to mediate neuroplasticity, which can be beneficial to patients suffering from anxiety, depression, or posttraumatic stress disorder. These and other related neuropsychiatric conditions are associated with the onset of neuronal atrophy, which is defined as a reduction in the number and/or productivity of neurons. The stimulation of neuroplasticity results in an increase in the connectivity between neurons and promotes the restoration of healthy brain function. We have synthesized a substantial catalogue of proprietary indolethylamine derivatives based on the general structures of serotonin (5-hydroxytryptamine) and psychedelic molecules such as N,N-dimethyltryptamine (DMT) and psilocin (4-hydroxy-DMT) that function as neuroplastogens. A primary objective in our screening protocol is the identification of derivatives associated with a significant reduction in hallucination, which will allow administration of the drug at a dose that induces neuroplasticity and triggers other efficacious outcomes in the treatment of targeted CNS disorders but which does not cause a psychedelic response in the patient. Both neuroplasticity and hallucination are associated with engagement of the 5HT2A receptor, requiring drug candidates differentially coupled to these two outcomes at a molecular level. We use novel and proprietary artificial intelligence algorithms to predict the mode of binding to the 5HT2A receptor, which has been shown to correlate with the hallucinogenic response. Hallucination is tested using the mouse head-twitch response model, whereas mouse marble-burying and sucrose preference assays are used to evaluate anxiolytic and anti-depressive potential. Neuroplasticity is assays using dendritic outgrowth assays and cell-based ELISA analysis. Pharmacokinetics and additional receptor-binding analyses also contribute the selection of lead candidates. A summary of the program is presented.

Keywords: neuroplastogen, non-hallucinogenic, drug development, anxiety, depression, PTSD, indolethylamine derivatives, psychedelic-inspired, 5-HT2A receptor, computational chemistry, head-twitch response behavioural model, neurite outgrowth assay

Procedia PDF Downloads 138

Authors: Farideh Halakou, Emel Sen, Attila Gursoy, Ozlem Keskin

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Protein–Protein Interactions (PPIs) mediate major biological processes in living cells. The study of PPIs as networks and analyze the network properties contribute to the identification of genes and proteins associated with diseases. In this study, we have created the sub-networks of brain and lung metastasis from primary tumor in breast cancer. To do so, we used seed genes known to cause metastasis, and produced their interactions through a network-topology based prioritization method named GUILDify. In order to have the experimental support for the sub-networks, we further curated them using STRING database. We proceeded by modeling structures for the interactions lacking complex forms in Protein Data Bank (PDB). The functional enrichment analysis shows that KEGG pathways associated with the immune system and infectious diseases, particularly the chemokine signaling pathway, are important for lung metastasis. On the other hand, pathways related to genetic information processing are more involved in brain metastasis. The structural analyses of the sub-networks vividly demonstrated their difference in terms of using specific interfaces in lung and brain metastasis. Furthermore, the topological analysis identified genes such as RPL5, MMP2, CCR5 and DPP4, which are already known to be associated with lung or brain metastasis. Additionally, we found 6 and 9 putative genes that are specific for lung and brain metastasis, respectively. Our analysis suggests that variations in genes and pathways contributing to these different breast metastasis types may arise due to change in tissue microenvironment. To show the benefits of using structural PPI networks instead of traditional node and edge presentation, we inspect two case studies showing the mutual exclusiveness of interactions and effects of mutations on protein conformation which lead to different signaling.

Keywords: breast cancer, metastasis, PPI networks, protein conformational changes

Procedia PDF Downloads 244

Authors: Gileade P. Freitas, Helena B. Lopes, Alann T. P. Souza, Paula G. F. P. Oliveira, Adriana L. G. Almeida, Paulo G. Coelho, Marcio M. Beloti, Adalberto L. Rosa

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Bone tissue presents great capacity to regenerate when injured by trauma, infectious processes, or neoplasia. However, the extent of injury may exceed the inherent tissue regeneration capability demanding some kind of additional intervention. In this scenario, cell therapy has emerged as a promising alternative to treat challenging bone defects. This study aimed at evaluating the effect of local injection of bone marrow-derived mesenchymal stem cells (BM-MSCs) and adipose tissue-derived mesenchymal stem cells (AT-MSCs) on bone regeneration of rat calvaria defects. BM-MSCs and AT-MSCs were isolated and characterized by expression of surface markers; cell viability was evaluated after injection through a 21G needle. Defects of 5 mm in diameter were created in calvaria and after two weeks a single injection of BM-MSCs, AT-MSCs or vehicle-PBS without cells (Control) was carried out. Cells were tracked by bioluminescence and at 4 weeks post-injection bone formation was evaluated by micro-computed tomography (μCT) and histology, nanoindentation, and through gene expression of bone remodeling markers. The data were evaluated by one-way analysis of variance (p≤0.05). BM-MSCs and AT-MSCs presented characteristics of mesenchymal stem cells, kept viability after passing through a 21G needle and remained in the defects until day 14. In general, injection of both BM-MSCs and AT-MSCs resulted in higher bone formation compared to Control. Additionally, this bone tissue displayed elastic modulus and hardness similar to the pristine calvaria bone. The expression of all evaluated genes involved in bone formation was upregulated in bone tissue formed by BM-MSCs compared to AT-MSCs while genes involved in bone resorption were upregulated in AT-MSCs-formed bone. We show that cell therapy based on the local injection of BM-MSCs or AT-MSCs is effective in delivering viable cells that displayed local engraftment and induced a significant improvement in bone healing. Despite differences in the molecular cues observed between BM-MSCs and AT-MSCs, both cells were capable of forming bone tissue at comparable amounts and properties. These findings may drive cell therapy approaches toward the complete bone regeneration of challenging sites.

Keywords: cell therapy, mesenchymal stem cells, bone repair, cell culture

Procedia PDF Downloads 184

Authors: Puneet Kumar, Jonnalagadda Srinivas

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The authors report here vibration and buckling analysis of functionally graded carbon nanotube-polymer composite (FG-CNTPC) beams under hygro-thermo-mechanical environments using higher order shear deformation theory. The material properties of CNT and polymer matrix are often affected by temperature and moisture content. A micromechanical model with agglomeration effect is employed to compute the elastic, thermal and moisture properties of the composite beam. The governing differential equation of FG-CNTRPC beam is developed using higher-order shear deformation theory to account shear deformation effects. The elastic, thermal and hygroscopic strain terms are derived from variational principles. Moreover, thermal and hygroscopic loads are determined by considering uniform, linear and sinusoidal variation of temperature and moisture content through the thickness. Differential equations of motion are formulated as an eigenvalue problem using appropriate displacement fields and solved by using finite element modeling. The obtained results of natural frequencies and critical buckling loads show a good agreement with published data. The numerical illustrations elaborate the dynamic as well as buckling behavior under uniaxial load for different environmental conditions, boundary conditions and volume fraction distribution profile, beam slenderness ratio. Further, comparisons are shown at different boundary conditions, temperatures, degree of moisture content, volume fraction as well as agglomeration of CNTs, slenderness ratio of beam for different shear deformation theories.

Keywords: hygrothermal effect, free vibration, buckling load, agglomeration

Procedia PDF Downloads 264

Authors: Fatemeh Daneshvartarigh

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New technologies and applications have radically altered construction techniques in recent years. In order to anticipate how the building will act, perform, and appear, these technologies encompass a wide range of visualization, simulation, and analytic tools. These new technologies and applications have a considerable impact on completing construction projects in today's (architecture, engineering and construction)AEC industries. The rate of changes in BIM-related topics is different worldwide, and it depends on many factors, e.g., the national policies of each country. Therefore, there is a need for comprehensive research focused on a specific area with common characteristics. Therefore, one of the necessary measures to increase the use of this new approach is to examine the challenges and obstacles facing it. In this research, based on the Delphi method, at first, the background and related literature are reviewed. Then, using the knowledge obtained from the literature, a primary questionnaire is generated and filled by experts who are selected using snowball sampling. It covered the experts' attitudes towards implementing BIM in renovation projects and their view of the benefits and obstacles in this regard. By analyzing the primary questionnaire, the second group of experts is selected among the participants to be interviewed. The results are analyzed using Theme analysis. Six themes, including Management support, staff resistance, client willingness, Cost of software and implementation, the difficulty of implementation, and other reasons, are obtained. Then a final questionnaire is generated from the themes and filled by the same group of experts. The result is analyzed by the Fuzzy Delphi method, showing the exact ranking of the obtained themes. The final results show that management support, staff resistance, and client willingness are the most critical barrier to BIM usage in renovation projects.

Keywords: building information modeling, BIM, BIM implementation, BIM barriers, BIM in renovation

Procedia PDF Downloads 167

Authors: Hengki Eko Putra, Dennish Ari Putro, Tri Wahyu Hadi, Edi Riawan, Junnaedhi Dewa Gede, Aditia Rojali, Fariza Dian Prasetyo, Yudhistira Satya Pribadi, Dita Fatria Andarini, Mila Khaerunisa, Raditya Hanung Prakoswa

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Catastrophe risk management can only be done if we are able to calculate the exposed risks. Jakarta is an important city economically, socially, and politically and in the same time exposed to severe floods. On the other hand, flood risk calculation is still very limited in the area. This study has calculated the risk of flooding for Jakarta using 2-Dimensional Model ANUGA. 2-Dimensional model ANUGA and 1-Dimensional Model HEC-RAS are used to calculate the risk of flooding from 13 major rivers in Jakarta. ANUGA can simulate physical and dynamical processes between the streamflow against river geometry and land cover to produce a 1-meter resolution inundation map. The value of streamflow as an input for the model obtained from hydrological analysis on rainfall data using hydrologic model HEC-HMS. The probabilistic streamflow derived from probabilistic rainfall using statistical distribution Log-Pearson III, Normal and Gumbel, through compatibility test using Chi Square and Smirnov-Kolmogorov. Flood event on 2007 is used as a comparison to evaluate the accuracy of model output. Property damage estimations were calculated based on flood depth for 1, 5, 10, 25, 50, and 100 years return period against housing value data from the BPS-Statistics Indonesia, Centre for Research and Development of Housing and Settlements, Ministry of Public Work Indonesia. The vulnerability factor was derived from flood insurance claim. Jakarta's flood loss estimation for the return period of 1, 5, 10, 25, 50, and 100 years, respectively are Rp 1.30 t; Rp 16.18 t; Rp 16.85 t; Rp 21.21 t; Rp 24.32 t; and Rp 24.67 t of the total value of building Rp 434.43 t.

Keywords: 2D hydrodynamic model, ANUGA, flood, flood modeling

Procedia PDF Downloads 275

Authors: H. Taylan Selamlar, I. Yavuz, G. Yapar

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It is difficult to make predictions especially about the future and making accurate predictions is not always easy. However, better predictions remain the foundation of all science therefore the development of accurate, robust and reliable forecasting methods is very important. Numerous number of forecasting methods have been proposed and studied in the literature. There are still two dominant major forecasting methods: Box-Jenkins ARIMA and Exponential Smoothing (ES), and still new methods are derived or inspired from them. After more than 50 years of widespread use, exponential smoothing is still one of the most practically relevant forecasting methods available due to their simplicity, robustness and accuracy as automatic forecasting procedures especially in the famous M-Competitions. Despite its success and widespread use in many areas, ES models have some shortcomings that negatively affect the accuracy of forecasts. Therefore, a new forecasting method in this study will be proposed to cope with these shortcomings and it will be called ATA method. This new method is obtained from traditional ES models by modifying the smoothing parameters therefore both methods have similar structural forms and ATA can be easily adapted to all of the individual ES models however ATA has many advantages due to its innovative new weighting scheme. In this paper, the focus is on modeling the trend component and handling seasonality patterns by utilizing classical decomposition. Therefore, ATA method is expanded to higher order ES methods for additive, multiplicative, additive damped and multiplicative damped trend components. The proposed models are called ATA trended models and their predictive performances are compared to their counter ES models on the M3 competition data set since it is still the most recent and comprehensive time-series data collection available. It is shown that the models outperform their counters on almost all settings and when a model selection is carried out amongst these trended models ATA outperforms all of the competitors in the M3- competition for both short term and long term forecasting horizons when the models’ forecasting accuracies are compared based on popular error metrics.

Keywords: accuracy, exponential smoothing, forecasting, initial value

Procedia PDF Downloads 177

Authors: K. S. Zaytsev, Y. R. Nartsissov

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Glycine is one of the key inhibitory neurotransmitters in Central nervous system (CNS) meanwhile glycinergic transmission is highly dependable on its appropriate reuptake from synaptic cleft. Glycine transporters (GlyT) of types 1 and 2 are the enzymes providing glycine transport back to neuronal and glial cells along with Na⁺ and Cl⁻ co-transport. The distribution and stoichiometry of GlyT1 and GlyT2 differ in details, and GlyT2 is more interesting for the research as it reuptakes glycine to neuron cells, whereas GlyT1 is located in glial cells. In the process of GlyT2 activity, the translocation of the amino acid is accompanied with binding of both one chloride and three sodium ions consequently (two sodium ions for GlyT1). In the present study, we developed a computer simulator of GlyT2 and GlyT1 activity based on known experimental data for quantitative estimation of membrane glycine transport. The trait of a single protein functioning was described using the probability approach where each enzyme state was considered separately. Created scheme of transporter functioning realized as a consequence of elemental steps allowed to take into account each event of substrate association and dissociation. Computer experiments using up-to-date kinetic parameters allowed receiving the number of translocated glycine molecules, Na⁺ and Cl⁻ ions per time period. Flexibility of developed software makes it possible to evaluate glycine reuptake pattern in time under different internal characteristics of enzyme conformational transitions. We investigated the behavior of the system in a wide range of equilibrium constant (from 0.2 to 100), which is not determined experimentally. The significant influence of equilibrium constant in the range from 0.2 to 10 on the glycine transfer process is shown. The environmental conditions such as ion and glycine concentrations are decisive if the values of the constant are outside the specified range.

Keywords: glycine, inhibitory neurotransmitters, probability approach, single protein functioning

Procedia PDF Downloads 119

Authors: Darren Edwards, Thomas Pinna

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Background: Interoception and heart rate variability have been found to predict outcomes of mental health and well-being. However, these have usually been investigated independently of one another. Objectives: This review aimed to explore the associations between interoception and heart rate variability (HRV) with emotion regulation (ER) and ER strategies within the existing literature and utilizing systematic review methodology. Methods: The process of article retrieval and selection followed the preferred reporting items for systematic review and meta-analyses (PRISMA) guidelines. Databases PsychINFO, Web of Science, PubMed, CINAHL, and MEDLINE were scanned for papers published. Preliminary inclusion and exclusion criteria were specified following the patient, intervention, comparison, and outcome (PICO) framework, whilst the checklist for critical appraisal and data extraction for systematic reviews of prediction modeling studies (CHARMS) framework was used to help formulate the research question, and to critically assess for bias in the identified full-length articles. Results: 237 studies were identified after initial database searches. Of these, eight studies were included in the final selection. Six studies explored the associations between HRV and ER, whilst three investigated the associations between interoception and ER (one of which was included in the HRV selection too). Overall, the results seem to show that greater HRV and interoception are associated with better ER. Specifically, high parasympathetic activity largely predicted the use of adaptive ER strategies such as reappraisal, and better acceptance of emotions. High interoception, instead, was predictive of effective down-regulation of negative emotions and handling of social uncertainty, there was no association with any specific ER strategy. Conclusions: Awareness of one’s own bodily feelings and vagal activation seem to be of central importance for the effective regulation of emotional responses.

Keywords: emotional regulation, vagal tone, interoception, chronic conditions, health and well-being, psychological flexibility

Procedia PDF Downloads 112

Authors: Abdulmohsen Alruwaili

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A partial differential system featuring momentum and energy balance is often used to describe simulations of flow initiation and thermal shifting in boundary layers. The buoyancy force in terms of temperature is factored in the momentum balance equation. Buoyancy force causes the flow quantity to fluctuate along the streamwise direction 𝑋; therefore, the problem can be, to our best knowledge, analyzed through nonsimilar modeling. In this analysis, a nonsimilar model is evolved for radiative mixed convection of a magnetized power-law nanoliquid flow on top of a vertical plate installed in a stationary fluid. The upward linear stretching initiated the flow in the vertical direction. Assuming nanofluids are composite of copper (Cu) and alumina (Al₂O₃) nanoparticles, the viscous dissipation in this case is negligible. The nonsimilar system is dealt with analytically by local nonsimilarity (LNS) via numerical algorithm bvp4c. Surface temperature and flow field are shown visually in relation to factors like mixed convection, magnetic field strength, nanoparticle volume fraction, radiation parameters, and Prandtl number. The repercussions of magnetic and mixed convection parameters on the rate of energy transfer and friction coefficient are represented in tabular forms. The results obtained are compared to the published literature. It is found that the existence of nanoparticles significantly improves the temperature profile of considered nanoliquid. It is also observed that when the estimates of the magnetic parameter increase, the velocity profile decreases. Enhancement in nanoparticle concentration and mixed convection parameter improves the velocity profile.

Keywords: nanofluid, power law model, mixed convection, thermal radiation

Procedia PDF Downloads 32

Authors: Ryoma Tokonami, Teruya Goto, Tatsuhiro Takahashi,

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For enhancing the mechanical property ofcarbon fiber reinforced plastic (CFRP), the surface modification of carbon fiber (CF) by multi-walled carbon nanotube (MWCNT) has received considerable attention using direct MWCNT growth on CF with a catalysis, MWCNT electrophoresis, and layer-by-layer of MWCNT with reactive polymers, etc. Among above approaches, the layer-by-layer method is the simplest process, however, the amount of MWCNTs on CF is very little, resulting in the small amount of improvement of the mechanical property of the composite. The remaining amount of MWCNT on CF after melt mixing of CF (short fiber) with thermoplastic matrix polymer was not examined clearly in the former studies. The present research aims to propose an effective layer-by-layer chemical grafting of a highly reactive oxazoline polymer, which has not been used before, and MWCNTs onto CF using the highly reactivity of oxazoline and COOH on the surface of CF and MWCNTs.With layer-by-layer method, the first uniform chemically bonded mono molecular layer on carbon fiber was formed by chemical surface reaction of carbon fiber, a reactive oxazoline polymer solution between COOH of carbon fiber and oxazoline. The second chemically bonded uniform layer of MWCNTs on the first layer was prepared through the first layer coated carbon fiber in MWCNT dispersion solution by chemical reaction between oxazoline and COOH of MWCNTs. The quantitative analysis of MWCNTs on carbon fiber was performed, showing 0.44 wt.% of MWCNTs based on carbon fiber, which is much larger amount compared with the former studies in layer-by-layer method. In addition, MWCNTs were also observed uniform coating on carbon fiber by scanning electron micrograph (SEM). Carbon fiber composites were prepared by melting mixing using polystyrene (PS) as a thermoplastic matrix because of easy removal of PS by solvent for additional analysis, resulting the 20% of enhancement of tensile strength and modulus by tensile strength test. It was confirmed bySEM the layer-by-layer structure on carbon fibers were remained after the melt mixing by removing PS with a solvent. As a conclusion, the effectiveness for the enhancement of the mechanical properties of CF(short fiber)/PS composite using the highly reactive oxazoline polymer for the first layer and MWCNT for the second layer, which act as the physical anchor, was demonstrated.

Keywords: interface, layer-by-layer, multi walled carbon nanotubes (MWCNTs), oxazoline

Procedia PDF Downloads 203

Authors: Dorcas Ropo Abejide, Olamide Ahmed Falusi, Oladipupo Abdulazeez Yusuf Daudu, Bolaji Zuluqurineen Salihu, Muhammad Liman Muhammad

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This study evaluated the morpho-agronomic response of twenty-four (24) Nigerian Bambara groundnut landraces to water stress and genetic diversity of some selected accessions using SSR markers. The studies were carried out in the botanical garden of the Department of Plant Biology, Federal University of Technology, Minna, Niger State, Nigeria in a randomized complete block design using three replicates. Molecular analysis using SSR primers was carried out at the International Institute of Tropical Agriculture (IITA) Ibadan in order to characterize ten selected accessions comprising the seven most drought tolerant and three most susceptible accessions from the 24 accessions evaluated. Results revealed that water stress decreased morpho-agronomic traits such as plant height, leaf area, number of leaves per plant, seed yield, etc. A total of 22 alleles were detected by the SSR markers used with a mean number of 4 allelles. SSR markers MBamCO₃₃, Primer 65, and G358B2-D15 each detected 4 allelles, while Primer 3FR and 4FR detected 5 allelles each. The study revealed significantly high polymorphisms in 10 Loci. The mean value of polymorpic information content was 0.6997, implying the usefulness of the primers used in identifying genetic similarities and differences among the Bambara groundnut genotypes. The SSR analysis revealed a comparable pattern between genetic diversity and drought tolerance of the genotypes. The UPGMA dendrogram showed that at a genetic distance of 0.1, the accessions were grouped into three groups according to their level of tolerance to drought. The two most drought-tolerant accessions were grouped together, and the 5th and 6th most drought-tolerant accessions were also grouped together. This suggests that the genotypes grouped together may be genetically close, may possess similar genes, or have a common origin. The degree of genetic variants obtained from this profiling could be useful in Bambara groundnut breeding for drought tolerance. The identified drought tolerant Bambara groundnut landraces are important genetic resources for drought stress tolerance breeding programme of Bambara groundnut. The genotypes are also useful for germplasm conservation and global implications.

Keywords: Bambara groundnut, genetic diversity, germplasm, SSR markers, water stress

Procedia PDF Downloads 59

Authors: Zhanna Yermekova, Sergey Roslyakov

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Solution combustion synthesis (SCS) is the unique method which multiple times has proved itself as an effective and efficient approach for the versatile synthesis of a variety of materials. It has significant advantages such as relatively simple handling process, high rates of product synthesis, mixing of the precursors on a molecular level, and fabrication of the nanoproducts as a result. Nowadays, an overwhelming majority of solution combustion investigations performed through the volume combustion synthesis (VCS) where the entire liquid precursor is heated until the combustion self-initiates throughout the volume. Less amount of the experiments devoted to the steady-state self-propagating mode of SCS. Under the beforementioned regime, the precursor solution is dried until the gel-like media, and later on, the gel substance is locally ignited. In such a case, a combustion wave propagates in a self-sustaining mode as in conventional solid combustion synthesis. Even less attention is given to the impregnated active layer (IAL) mode of solution combustion. An IAL approach to the synthesis is implying that the solution combustion of the precursors should be initiated on the surface of the third chemical or inside the third substance. This work is aiming to emphasize an underestimated role of the impregnated active layer mode of the solution combustion synthesis for the fundamental studies of the combustion mechanisms. It also serves the purpose of popularizing the technical terms and clarifying the difference between them. In order to do so, the solution combustion synthesis of γ-FeNi (PDF#47-1417) alloy has been accomplished within short (seconds) one-step reaction of metal precursors with hexamethylenetetramine (HTMA) fuel. An idea of the special role of the Ni in a process of alloy formation was suggested and confirmed with the particularly organized set of experiments. The first set of experiments were conducted in a conventional steady-state self-propagating mode of SCS. An alloy was synthesized as a single monophasic product. In two other experiments, the synthesis was divided into two independent processes which are possible under the IAL mode of solution combustion. The sequence of the process was changed according to the equations which are describing an Experiment A and B below: Experiment A: Step 1. Fe(NO₃)₃*9H₂O + HMTA = FeO + gas products; Step 2. FeO + Ni(NO₃)₂*6H₂O + HMTA = Ni + FeO + gas products; Experiment B: Step 1. Ni(NO₃)₂*6H₂O + HMTA = Ni + gas products; Step 2. Ni + Fe(NO₃)₃*9H₂O + HMTA = Fe₃Ni₂+ traces (Ni + FeO). Based on the IAL experiment results, one can see that combustion of the Fe(NO₃)₃9H₂O on the surface of the Ni is leading to the alloy formation while presence of the already formed FeO does not affect the Ni(NO₃)₂*6H₂O + HMTA reaction in any way and Ni is the main product of the synthesis.

Keywords: alloy, hexamethylenetetramine, impregnated active layer mode, mechanism, solution combustion synthesis

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Authors: Gozel Judakova, Markus Bause

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We present and analyze reliable numerical techniques for simulating complex flow and transport phenomena related to natural gas transportation in pipelines. Such kind of problems are of high interest in the field of petroleum and environmental engineering. Modeling and understanding natural gas flow and transformation processes during transportation is important for the sake of physical realism and the design and operation of pipeline systems. In our approach a two fluid flow model based on a system of coupled hyperbolic conservation laws is considered for describing natural gas flow undergoing hydratization. The accurate numerical approximation of two-phase gas flow remains subject of strong interest in the scientific community. Such hyperbolic problems are characterized by solutions with steep gradients or discontinuities, and their approximation by standard finite element techniques typically gives rise to spurious oscillations and numerical artefacts. Recently, stabilized and discontinuous Galerkin finite element techniques have attracted researchers’ interest. They are highly adapted to the hyperbolic nature of our two-phase flow model. In the presentation a streamline upwind Petrov-Galerkin approach and a discontinuous Galerkin finite element method for the numerical approximation of our flow model of two coupled systems of Euler equations are presented. Then the efficiency and reliability of stabilized continuous and discontinous finite element methods for the approximation is carefully analyzed and the potential of the either classes of numerical schemes is investigated. In particular, standard benchmark problems of two-phase flow like the shock tube problem are used for the comparative numerical study.

Keywords: discontinuous Galerkin method, Euler system, inviscid two-fluid model, streamline upwind Petrov-Galerkin method, twophase flow

Procedia PDF Downloads 329

Authors: Naseem Fatima, A. N. Srivastava, Tasleem Raza, Vijay Kumar

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Introduction: Carcinoma gallbladder is third most common gastrointestinal lethal disease with the highest incidence and mortality rate among women in Northern India. Scientists have found several risk factors that make a person more likely to develop gallbladder cancer; among these risk factors, deregulation of miRNAs has been demonstrated to be one of the most crucial factors. The changes in the expression of specific miRNA genes result in the control of inflammation, cell cycle regulation, stress response, proliferation, differentiation, apoptosis and invasion thus mediate the process in tumorgenesis. The aim of this study was to investigate the role of MiRNA-335 and may as a molecular marker in early detection of gallbladder cancer in suspected cases. Material and Methods: A total of 20 consecutive patients with gallbladder cancer aged between 30-75 years were registered for the study. Total RNA was extracted from tissue by using the mirVANA MiRNA isolation Kit according to the manufacturer’s protocol. The MiRNA- 335 and U6 snRNA-specific cDNA were reverse-transcribed from total RNA using Taqman microRNA reverse-transcription kit according to the manufacturer’s protocol. TaqMan MiRNA probes hsa-miR-335 and Taqman Master Mix without AmpEase UNG, Individual real-time PCR assays were performed in a 20 μL reaction volume on a Real-Time PCR system (Applied Biosystems StepOnePlus™) to detect MiRNA-335 expression in tissue. Relative quantification of target MiRNA expression was evaluated using the comparative cycle threshold (CT) method. The correlation was done in between cycle threshold (CT Value) of target MiRNA in gallbladder cancer with respect to non-cancerous Cholelithiasis gallbladder. Each sample was examined in triplicate. The Newman-Keuls Multiple Comparison Test was used to determine the expression of miR-335. Results: MiRNA335 was found to be significantly downregulated in the gallbladder cancer tissue (P<0.001), when compared with non-cancerous Cholelithiasis gallbladder cases. Out of 20 cases, 75% showed reduced expression of MiRNA335, were at last stage of disease with low overall survival rate and remaining 25% were showed up-regulated expression of MiRNA335 with high survival rate. Conclusion: The present study showed that reduced expression of MiRNA335 is associated with the advancement of the disease, and its deregulation may provide important clues to understanding it as a prognostic marker and opportunities for future research.

Keywords: carcinoma gallbladder, downregulation, MiRNA-335, RT-PCR assay

Procedia PDF Downloads 360

Authors: Virag Vass, Ilona Bereczki, Erzsebet Szabo, Nora Debreczeni, Aniko Borbas, Pal Herczegh, Arpad Tosaki

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Hydrogen sulfide (H₂S) is a toxic gas, but it is produced by certain tissues in a small quantity. According to earlier studies, ibuprofen and H₂S has a protective effect against damaging heart tissue caused by ischemia-reperfusion. Recently, we have been investigating the effect of a new water-soluble H₂S releasing ibuprofen molecule administered after artificially generated ischemia-reperfusion on isolated rat hearts. The H₂S releasing property of the new ibuprofen derivative was investigated in vitro in medium derived from heart endothelial cell isolation at two concentrations. The ex vivo examinations were carried out on rat hearts. Rats were anesthetized with an intraperitoneal injection of ketamine, xylazine, and heparin. After thoracotomy, hearts were excised and placed into ice-cold perfusion buffer. Perfusion of hearts was conducted in Langendorff mode via the cannulated aorta. In our experiments, we studied the dose-effect of the H₂S releasing molecule in Langendorff-perfused hearts with the application of gradually increasing concentration of the compound (0- 20 µM). The H₂S releasing ibuprofen derivative was applied before the ischemia for 10 minutes. H₂S concentration was measured with an H₂S detecting electrochemical sensor from the coronary effluent solution. The 10 µM concentration was chosen for further experiments when the treatment with this solution was occurred after the ischemia. The release of H₂S is occurred by the hydrolyzing enzymes that are present in the heart endothelial cells. The protective effect of the new H₂S releasing ibuprofen molecule can be confirmed by the infarct sizes of hearts using the Triphenyl-tetrazolium chloride (TTC) staining method. Furthermore, we aimed to define the effect of the H₂S releasing ibuprofen derivative on autophagic and apoptotic processes in damaged hearts after investigating the molecular markers of these events by western blotting and immunohistochemistry techniques. Our further studies will include the examination of LC3I/II, p62, Beclin1, caspase-3, and other apoptotic molecules. We hope that confirming the protective effect of new H₂S releasing ibuprofen molecule will open a new possibility for the development of more effective cardioprotective agents with exerting fewer side effects. Acknowledgment: This study was supported by the grants of NKFIH- K-124719 and the European Union and the State of Hungary co- financed by the European Social Fund in the framework of GINOP- 2.3.2-15-2016-00043.

Keywords: autophagy, hydrogen sulfide, ibuprofen, ischemia, reperfusion

Procedia PDF Downloads 140

Authors: Prince Vivek, Vijay K. Bharti, Manishi Mukesh, Ankita Sharma, Om Prakash Chaurasia, Bhuvnesh Kumar

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High performance of endurance in equid requires adaptive changes involving physio-biochemical, and molecular responses in an attempt to regain homeostasis. We hypothesized that the identification of the suitable reference genes might be considered for assessing of endurance related traits in pony at high altitude and may ensure for individuals struggling to potent endurance trait in ponies at high altitude. A total of 12 mares of ponies, Zanskar breed, were divided into three groups, group-A (without load), group-B, (60 Kg) and group-C (80 Kg) on backpack loads were subjected to a load carry protocol, on a steep climb of 4 km uphill, and of gravel, uneven rocky surface track at an altitude of 3292 m to 3500 m (endpoint). Blood was collected before and immediately after the load carry on sodium heparin anticoagulant, and the peripheral blood mononuclear cell was separated for total RNA isolation and thereafter cDNA synthesis. Real time-PCR reactions were carried out to evaluate the mRNAs expression profile of a panel of putative internal control genes (ICGs), related to different functional classes, namely glyceraldehyde 3-phosphate dehydrogenase (GAPDH), β₂ microglobulin (β₂M), β-actin (ACTB), ribosomal protein 18 (RS18), hypoxanthine-guanine phosophoribosyltransferase (HPRT), ubiquitin B (UBB), ribosomal protein L32 (RPL32), transferrin receptor protein (TFRC), succinate dehydrogenase complex subunit A (SDHA) for normalizing the real-time quantitative polymerase chain reaction (qPCR) data of native pony’s. Three different algorithms, geNorm, NormFinder, and BestKeeper software, were used to evaluate the stability of reference genes. The result showed that GAPDH was best stable gene and stability value for the best combination of two genes was observed TFRC and β₂M. In conclusion, the geometric mean of GAPDH, TFRC and β₂M might be used for accurate normalization of transcriptional data for assessing endurance related traits in Zanskar ponies during load carrying.

Keywords: endurance exercise, ubiquitin B (UBB), β₂ microglobulin (β₂M), high altitude, Zanskar ponies, reference gene

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Authors: Min Wang, Sergey Utev

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The lessons from the 2007-09 global financial crisis have driven scientific research, which considers the design of new methodologies and financial models in the global market. The quantum mechanics approach was introduced in the unpredictable stock market modeling. One famous quantum tool is Feynman path integral method, which was used to model insurance risk by Tamturk and Utev and adapted to formalize the path-dependent option pricing by Hao and Utev. The research is based on the path-dependent calculation method, which is motivated by the Feynman path integral method. The path calculation can be studied in two ways, one way is to label, and the other is computational. Labeling is a part of the representation of objects, and generating functions can provide many different ways of representing share price paths. In this paper, the recent works on graphical theoretical construction of individual share price path via matroid is presented. Firstly, a study is done on the knowledge of matroid, relationship between lattice path matroid and Tutte polynomials and ways to connect points in the lattice path matroid and Tutte polynomials is suggested. Secondly, It is found that a general binary tree can be validly constructed from a connected lattice path matroid rather than general lattice path matroid. Lastly, it is suggested that there is a way to represent share price paths via a general binary tree, and an algorithm is developed to construct share price paths from general binary trees. A relationship is also provided between lattice integer points and Tutte polynomials of a transversal matroid. Use this way of connection together with the algorithm, a share price path can be constructed from a given connected lattice path matroid.

Keywords: combinatorial construction, graphical representation, matroid, path calculation, share price, Tutte polynomial

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Authors: Pierre-Louis Lucas, Corinne Loutelier-Bourhis, Narimane Mati-Baouche, Philippe Chan Tchi-Song, Patrice Lerouge, Elodie Mathieu-Rivet, Muriel Bardor

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N-glycosylation is a post-translational modification taking place in the Endoplasmic Reticulum and the Golgi apparatus where defined glycan features are added on protein in a very specific sequence Asn-X-Thr/Ser/Cys were X can be any amino acid except proline. Because it is well-established that those N-glycans play a critical role in protein biological activity, protein half-life and that a different N-glycan structure may induce an immune response, they are very important in Biopharmaceuticals which are mainly glycoproteins bearing N-glycans. From now, most of the biopharmaceuticals are produced by mammalian cells like Chinese Hamster Ovary cells (CHO) for their N-glycosylation similar to the human, but due to the high production costs, several other species are investigated as the possible alternative system. In this purpose, the green microalgae Chlamydomonas reinhardtii was investigated as the potential production system for Biopharmaceuticals. This choice was influenced by the facts that C. reinhardtii is a well-study microalgae which is growing fast with a lot of molecular biology tools available. This organism is also producing N-glycan on its endogenous proteins. However, the analysis of the N-glycan structure of this microalgae has revealed some differences as compared to the human. Rather than in Human where the glycans are processed by key enzymes called N-acetylglucosaminyltransferase I and II (GnTI and GnTII) adding GlcNAc residue to form a GlcNAc₂Man₃GlcNAc₂ core N-glycan, C. reinhardtii lacks those two enzymes and possess a GnTI independent glycosylation pathway. Moreover, some enzymes like xylosyltransferases and methyltransferases not present in human are supposed to act on the glycans of C. reinhardtii. Furthermore, the recent structural study by mass spectrometry shows that the N-glycosylation precursor supposed to be conserved in almost all eukaryotic cells results in a linear Man₅GlcNAc₂ rather than a branched one in C. reinhardtii. In this work, we will discuss the new released MS information upon C. reinhardtii N-glycan structure and their impact on our attempt to modify the glycan in a Human manner. Two strategies will be discussed. The first one consisted in the study of Xylosyltransferase insertional mutants from the CLIP library in order to remove xyloses from the N-glycans. The second will go further in the humanization by transforming the microalgae with the exogenous gene from Toxoplasma gondii having an activity similar to GnTI and GnTII with the aim to synthesize GlcNAc₂Man₃GlcNAc₂ in C. reinhardtii.

Keywords: Chlamydomonas reinhardtii, N-glycosylation, glycosyltransferase, mass spectrometry, humanization

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Authors: Pawthawala Nancy Manish, Syed Alay Hashim

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A hybrid rocket is a rocket engine which uses propellants in two different states of matter- one is in solid and the other either gas or liquid. A hybrid rocket exhibit advantages over both liquid rockets and solid rockets especially in terms of simplicity, stop-start-restart capabilities, safety and cost. This paper deals the design and development of a hybrid rocket having paraffin wax as solid fuel and liquid oxygen as oxidizer. Due to variation of pressure in combustion chamber there is significantly change in mass flow rate, burning rate and uneven regression along the length of the grain. This project describes the working model of a hybrid propellant rocket motor. We have designed a hybrid rocket thrust chamber based on the predetermined combustion chamber pressure and the properties of hybrid propellant. This project is all ready in working condition with normal oxygen injector. Now we have planned to modify the injector design to improve the combustion property. We will use spray type injector for injecting the oxidizer. This idea will increase the performance followed by the regression rate of the solid fuel. By employing mass conservation law, oxygen mass flux, oxidizer/fuel ratio and regression rate the thrust coefficient can be obtained for our current design. CATIA V5 R20 is our design software for the complete setup. This project is fully based on experimental evaluation and the collection of combustion and flow parameters. The thrust chamber is made of stainless steel and the duration of test is around 15-20 seconds (Maximum). These experiments indicates that paraffin based fuel provides the opportunity to satisfy a broad range of mission requirements for the next generation of the hybrid rocket system.

Keywords: burning rate, liquid oxygen, mass flow rate, paraffin wax and sugar

Procedia PDF Downloads 335

Authors: Frederic Schenker, Jonathan J. Hendriks, Gianluca Nicchiotti

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In a product industrialization perspective, the end-product shall always be at the peak of technological advancement and developed in the shortest time possible. Thus, the constant growth of complexity and a shorter time-to-market calls for important changes on both the technical and business level. Undeniably, the common understanding of the system is beclouded by its complexity which leads to the communication gap between the engineers and the sale department. This communication link is therefore important to maintain and increase the information exchange between departments to ensure a punctual and flawless delivery to the end customer. This evolution brings engineers to reason with more hindsight and plan ahead. In this sense, they use new viewpoints to represent the data and to express the model deliverables in an understandable way that the different stakeholder may identify their needs and ideas. This article focuses on the usage of Model-Based System Engineering (MBSE) in a perspective of system industrialization and reconnect the engineering with the sales team. The modeling method used and presented in this paper concentrates on displaying as closely as possible the needs of the customer. Firstly, by providing a technical solution to the sales team to help them elaborate commercial offers without omitting technicalities. Secondly, the model simulates between a vast number of possibilities across a wide range of components. It becomes a dynamic tool for powerful analysis and optimizations. Thus, the model is no longer a technical tool for the engineers, but a way to maintain and solidify the communication between departments using different views of the model. The MBSE contribution to cost optimization during New Product Introduction (NPI) activities is made explicit through the illustration of a case study describing the support provided by system models to architectural choices during the industrialization of a novel optical sensor.

Keywords: analytical model, architecture comparison, MBSE, product industrialization, SysML, system thinking

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Authors: Vivek Kumar Gupta, Kripi Vohra, Monika Gupta

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Pulses have been a vital ingredient of the balanced human diet in India. Lentil (Lens culinaris Medikus or Lens esculenta Moench.) is a common legume known since biblical times. Lentil seeds, with or without hulls, are cooked as dhal and this has been the main dish for millennia in the South Asian region. Oxidative stress can damage lipids, proteins, enzymes, carbohydrates and DNA in cells and tissues, resulting in membrane damage, fragmentation or random cross linking of molecules like DNA, enzymes and structural proteins and even lead to cell death induced by DNA fragmentation and lipid peroxidation. These consequences of oxidative stress construct the molecular basis in the development of cancer, neurodegenerative disorders, cardiovascular diseases, diabetes and autoimmune. The aim of the present work is to assess the antioxidant potential of the peteroleum ether, acetone, methanol and water extract of the Lens esculenta seeds. In vitro antioxidant assessment of the extracts was carried out using 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging activity, hydroxyl radical scavenging activity, reducing power assay. The quantitative estimation of total phenolic content, total flavonoid content in extracts and in plant material, total saponin content, total alkaloid content, crude fibre content, total volatile content, fat content and mucilage content in drug material was also carried out. Though all the extracts exhibited dose dependent reducing power activity the acetone extract was found to possess significant hydrogen donating ability in DPPH (45.83%-93.13%) and hydroxyl radical scavenging system (28.7%-46.41%) than the peteroleum ether, methanol and water extracts. Total phenolic content in the acetone and methanol extract was found to be 608 and 188 mg gallic acid equivalent of phenol/g of sample respectively. Total flavonoid content of acetone and methanol extract was found to be 128 and 30.6 mg quercetin equivalent/g of sample respectively. It is evident that acetone extract of Lentil seeds possess high levels of polyphenolics and flavonoids that could be utilized as antioxidants and neutraceuticals.

Keywords: antioxidant, flavanoids, Lens esculenta, polyphenols

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Authors: Narges Razmjoo, Hamid Sefidari, Michael Strand

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Biomass combustion is a growing technique for heat and power production due to the increasing stringent regulations with CO2 emissions. Grate-fired systems have been regarded as a common and popular combustion technology for burning woody biomass. However, some grate furnaces are not well optimized and may emit significant amount of unwanted compounds such as dust, NOx, CO, and unburned gaseous components. The combustion characteristics inside the fuel bed are of practical interest, as they are directly related to the release of volatiles and affect the stability and the efficiency of the fuel bed combustion. Although numerous studies have been presented on the grate firing of biomass, to the author’s knowledge, none of them have conducted a detailed experimental study within the fuel bed. It is difficult to conduct measurements of temperature and gas species inside the burning bed of the fuel in full-scale boilers. Results from such inside bed measurements can also be applied by the numerical experts for modeling the fuel bed combustion. The current work presents an experimental investigation into the combustion behavior of wet woody biomass (53 %) in a 4 MW reciprocating grate boiler, by focusing on the gas species distribution along the height of the fuel bed. The local concentrations of gases (CO, CO2, CH4, NO, and O2) inside the fuel bed were measured through a glass port situated on the side wall of the furnace. The measurements were carried out at five different heights of the fuel bed, by means of a bent stainless steel probe containing a type-k thermocouple. The sample gas extracted from the fuel bed, through the probe, was filtered and dried and then was analyzed using two infrared spectrometers. Temperatures of about 200-1100 °C were measured close to the grate, indicating that char combustion is occurring at the bottom of the fuel bed and propagates upward. The CO and CO2 concentration varied in the range of 15-35 vol % and 3-16 vol %, respectively, and NO concentration varied between 10-140 ppm. The profile of the gas concentrations distribution along the bed height provided a good overview of the combustion sub-processes in the fuel bed.

Keywords: experimental, fuel bed, grate firing, wood combustion

Procedia PDF Downloads 326

Authors: Ali Javaid, Rizwan Latif, Syed Adnan Qasim, Imran Shafi

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To control combustion inside a direct injection diesel engine, fuel atomization is the best tool. Controlling combustion helps in reducing emissions and improves efficiency. Cavitation is one of the most important factors that significantly affect the nature of spray before it injects into combustion chamber. Typical fuel injector nozzles are small and operate at a very high pressure, which limits the study of internal nozzle behavior especially in case of diesel engine. Simulating cavitation in a fuel injector will help in understanding the phenomenon and will assist in further development. There is a parametric variation between high speed and high torque low speed diesel engines. The objective of this study is to simulate internal spray characteristics for a low speed high torque diesel engine. In-nozzle cavitation has strong effects on the parameters e.g. mass flow rate, fuel velocity, and momentum flux of fuel that is to be injected into the combustion chamber. The external spray dynamics and subsequently the air – fuel mixing depends on a lot of the parameters of fuel injecting the nozzle. The approach used to model turbulence induced in – nozzle cavitation for high-torque low-speed diesel engine, is homogeneous equilibrium model. The governing equations were modeled using Matlab. Complete Model in question was extensively evaluated by performing 3-D time-dependent simulations on Open FOAM, which is an open source flow solver and implemented in CFD (Computational Fluid Dynamics). Results thus obtained will be analyzed for better evaporation in the near-nozzle region. The proposed analyses will further help in better engine efficiency, low emission, and improved fuel economy.

Keywords: cavitation, HEM model, nozzle flow, open foam, turbulence

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Authors: Sabin Aslam, Sultan Habibullah Khan, James G. Thomson, Abhaya M. Dandekar

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Losses due to viral diseases are posing a serious threat to crop production. A quick breakdown of resistance to viruses like Cotton Leaf Curl Virus (CLCuV) demands the application of a proficient technology to engineer durable resistance. Gene stacking has recently emerged as a potential approach for integrating multiple genes in crop plants. In the present study, recombinase technology has been used for site-specific gene stacking. A target vector (pG-Rec) was designed for engineering a predetermined specific site in the plant genome whereby genes can be stacked repeatedly. Using Agrobacterium-mediated transformation, the pG-Rec was transformed into Coker-312 along with Nicotiana tabacum L. cv. Xanthi and Nicotiana benthamiana. The transgene analysis of target lines was conducted through junction PCR. The transgene positive target lines were used for further transformations to site-specifically stack two genes of interest using Bxb1 and PhiC31 recombinases. In the first instance, Cas9 driven by multiplex gRNAs (for Rep gene of CLCuV) was site-specifically integrated into the target lines and determined by the junction PCR and real-time PCR. The resulting plants were subsequently used to stack the second gene of interest (AVP3 gene from Arabidopsis for enhancing cotton plant growth). The addition of the genes is simultaneously achieved with the removal of marker genes for recycling with the next round of gene stacking. Consequently, transgenic marker-free plants were produced with two genes stacked at the specific site. These transgenic plants can be potential germplasm to introduce resistance against various strains of cotton leaf curl virus (CLCuV) and abiotic stresses. The results of the research demonstrate gene stacking in crop plants, a technology that can be used to introduce multiple genes sequentially at predefined genomic sites. The current climate change scenario highlights the use of such technologies so that gigantic environmental issues can be tackled by several traits in a single step. After evaluating virus resistance in the resulting plants, the lines can be a primer to initiate stacking of further genes in Cotton for other traits as well as molecular breeding with elite cotton lines.

Keywords: cotton, CRISPR/Cas9, gene stacking, genome editing, recombinases

Procedia PDF Downloads 155

Authors: Redvan Ghasemlounia, Elham Ansari, Hikmet Kerem Cigizoglu

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Hydrological modeling in arid and semi-arid regions is very important. Iran has many regions with these climate conditions such as Chaharmahal and Bakhtiari province that needs lots of attention with an appropriate management. Forecasting of hydrological parameters and estimation of hydrological events of catchments, provide important information that used for design, management and operation of water resources such as river systems, and dams, widely. Discharge in rivers is one of these parameters. This study presents the application and comparison of some estimation methods such as Feed-Forward Back Propagation Neural Network (FFBPNN), Multi Linear Regression (MLR), Gene Expression Programming (GEP) and Bayesian Network (BN) to predict the daily flow discharge of the Soolegan River, located at Chaharmahal and Bakhtiari province, in Iran. In this study, Soolegan, station was considered. This Station is located in Soolegan River at 51° 14՜ Latitude 31° 38՜ longitude at North Karoon basin. The Soolegan station is 2086 meters higher than sea level. The data used in this study are daily discharge and daily precipitation of Soolegan station. Feed Forward Back Propagation Neural Network(FFBPNN), Multi Linear Regression (MLR), Gene Expression Programming (GEP) and Bayesian Network (BN) models were developed using the same input parameters for Soolegan's daily discharge estimation. The results of estimation models were compared with observed discharge values to evaluate performance of the developed models. Results of all methods were compared and shown in tables and charts.

Keywords: ANN, multi linear regression, Bayesian network, forecasting, discharge, gene expression programming

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Authors: Louise H. Gracioso, Marcela P.G. Baltazar, Ingrid R. Avanzi, Bruno Karolski, Luciana J. Gimenes, Claudio O. Nascimento, Elen A. Perpetuo

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Introduction: Higher copper concentrations promote a selection pressure on organisms such as plants, fungi and bacteria, which allows surviving only the resistant organisms to the contaminated site. This selective pressure keeps only the organisms most resistant to a specific condition and subsequently increases their bioremediation potential. Despite the bacteria importance for biosphere maintenance, it is estimated that only a small fraction living microbial species has been described and characterized. Due to the molecular biology development, tools based on analysis 16S ribosomal RNA or another specific gene are making a new scenario for the characterization studies and identification of microorganisms in the environment. News identification of microorganisms methods have also emerged like Biotyper (MALDI / TOF), this method mass spectrometry is subject to the recognition of spectroscopic patterns of conserved and features proteins for different microbial species. In view of this, this study aimed to isolate bacteria resistant to copper present in a Copper Processing Area (Sossego Mine, Canaan, PA) and identifies them in two different methods: Recent (spectrometry mass) and conventional. This work aimed to use them for a future bioremediation of this Mining. Material and Methods: Samples were collected at fifteen different sites of five periods of times. Microorganisms were isolated from mining wastes by culture enrichment technique; this procedure was repeated 4 times. The isolates were inoculated into MJS medium containing different concentrations of chloride copper (1mM, 2.5mM, 5mM, 7.5mM and 10 mM) and incubated in plates for 72 h at 28 ºC. These isolates were subjected to mass spectrometry identification methods (Biotyper – MALDI/TOF) and 16S gene sequencing. Results: A total of 105 strains were isolated in this area, bacterial identification by mass spectrometry method (MALDI/TOF) achieved 74% agreement with the conventional identification method (16S), 31% have been unsuccessful in MALDI-TOF and 2% did not obtain identification sequence the 16S. These results show that Biotyper can be a very useful tool in the identification of bacteria isolated from environmental samples, since it has a better value for money (cheap and simple sample preparation and MALDI plates are reusable). Furthermore, this technique is more rentable because it saves time and has a high performance (the mass spectra are compared to the database and it takes less than 2 minutes per sample).

Keywords: copper mining area, bioremediation, microorganisms, identification, MALDI/TOF, RNA 16S

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Authors: Hang Yang, Jichao Li, Kewei Yang, Tianyang Lei

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Multivariate time series anomaly detection is a significant research topic in the field of data mining, encompassing a wide range of applications across various industrial sectors such as traffic roads, financial logistics, and corporate production. The inherent spatial dependencies and temporal characteristics present in multivariate time series introduce challenges to the anomaly detection task. Previous studies have typically been based on the assumption that all variables belong to the same spatial hierarchy, neglecting the multi-level spatial relationships. To address this challenge, this paper proposes a multi-scale spatial and unified temporal feature fusion network, denoted as MSUT-Net, for multivariate time series anomaly detection. The proposed model employs a multi-level modeling approach, incorporating both temporal and spatial modules. The spatial module is designed to capture the spatial characteristics of multivariate time series data, utilizing an adaptive graph structure learning model to identify the multi-level spatial relationships between data variables and their attributes. The temporal module consists of a unified temporal processing module, which is tasked with capturing the temporal features of multivariate time series. This module is capable of simultaneously identifying temporal dependencies among different variables. Extensive testing on multiple publicly available datasets confirms that MSUT-Net achieves superior performance on the majority of datasets. Our method is able to model and accurately detect systems data with multi-level spatial relationships from a spatial-temporal perspective, providing a novel perspective for anomaly detection analysis.

Keywords: data mining, industrial system, multivariate time series, anomaly detection

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Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

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The drug discovery and development process is generally known to be a very lengthy and labor-intensive process. Therefore, in order to be able to deliver prompt and effective responses to cure certain diseases, there is an urgent need to reduce the time and resources needed to design, develop, and optimize potential drugs. Computer-aided drug design (CADD) is able to alleviate this issue by applying computational power in order to streamline the whole drug discovery process, starting from target identification to lead optimization. This drug design approach can be predominantly applied to diseases that cause major public health concerns, such as tuberculosis. Hitherto, there has been no concrete cure for this disease, especially with the continuing emergence of drug resistant strains. In this study, CADD is employed for tuberculosis by first identifying a key enzyme in the mycobacterium’s metabolic pathway that would make a good drug target. One such potential target is the lipoate protein ligase B enzyme (LipB), which is a key enzyme in the M. tuberculosis metabolic pathway involved in the biosynthesis of the lipoic acid cofactor. Its expression is considerably up-regulated in patients with multi-drug resistant tuberculosis (MDR-TB) and it has no known back-up mechanism that can take over its function when inhibited, making it an extremely attractive target. Using cutting-edge computational methods, compounds from AnalytiCon Discovery Natural Derivatives database were screened and docked against the LipB enzyme in order to rank them based on their binding affinities. Compounds which have better binding affinities than LipB’s known inhibitor, decanoic acid, were subjected to in silico toxicity evaluation using the ADMET and TOPKAT protocols. Out of the 31,692 compounds in the database, 112 of these showed better binding energies than decanoic acid. Furthermore, 12 out of the 112 compounds showed highly promising ADMET and TOPKAT properties. Future studies involving in vitro or in vivo bioassays may be done to further confirm the therapeutic efficacy of these 12 compounds, which eventually may then lead to a novel class of anti-tuberculosis drugs.

Keywords: pharmacophore, molecular docking, lipoate protein ligase B (LipB), ADMET, TOPKAT

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Authors: Leandra Prempeh, Emily Malugen

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Prenatal drug exposure can have a molecular impact on the hypothalamic and reward genes that regulate feeding behavior. This can impact feeding regulation, resulting in feeding difficulties and growth failure. This was potentially seen in “McKayla,” a 19- month old girl with a history of in-utero drug exposure, patent ductus arteriosus, and gastroesophageal reflux disease who presented for intensive day treatment feeding therapy. She was diagnosed with Avoidant Restrictive Food Intake Disorder, described as total food refusal and meeting 100% of her caloric needs from a gastrostomy tube. The primary goals during intensive feeding therapy were to increase her oral intake and decrease her reliance on supplementation with formula. Several behavioral antecedent manipulations were implemented to establish consistent responding and make progress towards treatment goals. This included multiple modified bolus placements (using underloaded and Nuk brush), reinforcement contingencies, and variety fading before stability was finally achieved. Following, increasing retention of bites then increasing volume and variety were goals targeted. From treatment onset to the last 3 days of treatment, McKayla's rate of rapid acceptance of bite presentations increased significantly from 33.33% to 93.13%, rapid swallowing went from 0.00% to 92.32%, and her percentage of inappropriate mealtime behavior and expels decreased from 58.33% and 100% to 2.31% and 7.68%, respectively. Overall, the treatment team successfully introduced and increased the bite size of 7 pureed foods, generalize the treatment to caregivers with high integrity, and began facilitating tube weaning. She was receiving about 33.42% of her needs by mouth at the time of discharge. Other nutritional concerns addressed during treatment included drinking a nutritionally complete drink out of an open cup and age appropriate growth. McKayla continued to have emesis almost daily, as was her baseline before starting treatment; however, the frequency during mealtime decreased. Overall, McKayla responded well to treatment. She had a very slow response to treatment and required a lot of antecedent manipulations to establish consistent responding. As the literature suggests, [drug]-exposed neonates, like McKayla, may be at increased risk for nutritional and growth challenges that may persist throughout development. This supports the need for longterm follow-up of infant growth.

Keywords: behavioral intervention, feeding problems, in-utero drug exposure, intensive multidisciplinary intervention

Procedia PDF Downloads 66