Search results for: chitin binding domain

Authors: Mohammed Hakim Jafferali, Balaje Vijayaraghavan, Ricardo A. Figueroa, Ellinor Crafoord, Veronica J. Larsson, Einar Hallberg, Santhosh Gudise

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The nuclear envelope which surrounds the chromatin of eukaryotic cells contains more than a hundred transmembrane proteins. Mutations in some genes encoding nuclear envelope proteins give rise to human diseases including neurological disorders. The function of many nuclear envelope proteins is not well established. This is partly because nuclear envelope proteins and their interactions are difficult to study due to the inherent resistance to extraction of nuclear envelope proteins. We have developed a novel method called MCLIP, to identify interacting partners of nuclear envelope proteins in live cells. Using MCLIP, we found three new binding partners of the inner nuclear membrane protein Samp1: the intermediate filament protein Lamin B1, the LINC complex protein Sun1 and the G-protein Ran. Furthermore, using in vitro studies, we show that Samp1 binds both Emerin and Ran directly. We have also studied the interaction between Samp1 and Ran in detail. The results show that the Samp1 binds stronger to RanGTP than RanGDP. Samp1 is the first transmembrane protein known to bind Ran and it is tempting to speculate that Samp1 may provide local binding sites for RanGTP at membranes.

Keywords: MCLIP, nuclear envelope, ran, Samp1

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Authors: Lydia Novozhilova, Vladimir Urazhdin

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An optimization problem for reinforced thin-walled vessels under uniform external pressure is considered. The conventional approaches to optimization generally start with pre-defined geometric parameters of the vessels, and then employ analytic or numeric calculations and/or experimental testing to verify functionality, such as stability under the projected conditions. The proposed approach consists of two steps. First, the feasibility domain will be identified in the multidimensional parameter space. Every point in the feasibility domain defines a design satisfying both geometric and functional constraints. Second, an objective function defined in this domain is formulated and optimized. The broader applicability of the suggested methodology is maximized by implementing the Support Vector Machines (SVM) classification algorithm of machine learning for identification of the feasible design region. Training data for SVM classifier is obtained using the Simulation package of SOLIDWORKS®. Based on the data, the SVM algorithm produces a curvilinear boundary separating admissible and not admissible sets of design parameters with maximal margins. Then optimization of the vessel parameters in the feasibility domain is performed using the standard algorithms for the constrained optimization. As an example, optimization of a ring-stiffened closed cylindrical thin-walled vessel with semi-spherical caps under high external pressure is implemented. As a functional constraint, von Mises stress criterion is used but any other stability constraint admitting mathematical formulation can be incorporated into the proposed approach. Suggested methodology has a good potential for reducing design time for finding optimal parameters of thin-walled vessels under uniform external pressure.

Keywords: design parameters, feasibility domain, von Mises stress criterion, Support Vector Machine (SVM) classifier

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Authors: Ahmed Ali Asadi, Julio R. Martinez-Alvarado, Claudia V. Camacho-Guevara, J. Jesus Cabrales-Ruvalcaba, Julieta Y. Islas-Limon, Bertha M. Viñas-Velazquez

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The transformation of education in Mexico incorporates human sexuality subjects in its study plans for elementary education level, leaving aside the training of teachers to educate on such topics. The objective of this study was to evaluate the curricular content domain related to human sexuality subjects of public elementary school teachers in Mexico. For this, a transversal descriptive-prospective study with a quantitative focus has been conducted. The population for this study consisted of 109 fifth and sixth-grade teachers from a school zone of the State Education System. It was found in the results that fifth-grade teachers got a low achievement level, sixth-grade teachers got a medium achievement level, while teachers who give classes on both grades obtained a high achievement level on domain of curricular subjects related to sexuality. Likewise, a relation of different variables with the participant’s achievement level is exposed.

Keywords: curricular content, evaluation, sexual education, teacher

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Authors: Sun Li-Ping, Zhu Jian-Xun, Liu Sheng-Nan

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In order to study the performance of dynamic positioning system during S-lay operations, dynamic positioning system is simulated with the hull-stinger-pipe coupling effect. The roller of stinger is simulated by the generalized elastic contact theory. The stinger is composed of Morrison members. Force on pipe is calculated by lumped mass method. Time domain of fully coupled barge model is analyzed combining with PID controller, Kalman filter and allocation of thrust using Sequential Quadratic Programming method. It is also analyzed that the effect of hull wave frequency motion on pipe-stinger coupling force and dynamic positioning system. Besides, it is studied that how S-lay operations affect the dynamic positioning accuracy. The simulation results are proved to be available by checking pipe stress with API criterion. The effect of heave and yaw motion cannot be ignored on hull-stinger-pipe coupling force and dynamic positioning system. It is important to decrease the barge’s pitch motion and lay pipe in head sea in order to improve safety of the S-lay installation and dynamic positioning.

Keywords: S-lay operation, dynamic positioning, coupling motion, time domain, allocation of thrust

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Authors: Shuafeng Yuan, Bojian Zheng

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The RNA-dependent RNA polymerase of influenza a virus comprises conserved and independently folded subdomains with defined functionalities. The N-terminal domain of the PA subunit (PAN) harbors the endonuclease function so that it can serve as a desired target for drug discovery. To identify a class of anti-influenza inhibitors that impedes PAN endonuclease activity, a screening approach that integrated the fluorescence resonance energy transfer based endonuclease inhibitor assay with the DNA gel-based endonuclease inhibitor assay was conducted, followed by the evaluation of antiviral efficacies and potential cytotoxicity of the primary hits in vitro and in vivo. A small-molecule compound ANA-0 was identified as a potent inhibitor against the replication of multiple subtypes of influenza A virus, including H1N1, H3N2, H5N1, H7N7, H7N9 and H9N2, in cell cultures. Combinational treatment of zanamivir and ANA-0 exerted synergistic anti-influenza effect in vitro. Intranasal administration of ANA-0 protected mice from lethal challenge and reduced lung viral loads in H1N1 virus infected BALB/c mice. Docking analyses predicted ANA-0 bound the endonuclease cavity of PAN by interacting with the metal-binding and catalytic residues. In summary, ANA-0 shows potential to be developed to novel anti-influenza agents.

Keywords: anti-influenza, novel compound, inhibition of endonuclease, PA

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Authors: Eashan Hatti

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In software development, programmers often must make a choice between high-level programming and high-performance programs. High-level programming encourages the use of complex, pervasive abstractions. However, the use of these abstractions degrades performance-high performance demands that programs be low-level. In a compiler, the optimizer attempts to let the user have both. The optimizer takes high-level, abstract code as an input and produces low-level, performant code as an output. However, there is a problem with having the optimizer be a built-in part of the compiler. Domain-specific abstractions implemented as libraries are common in high-level languages. As a language’s library ecosystem grows, so does the number of abstractions that programmers will use. If these abstractions are to be performant, the optimizer must be extended with new optimizations to target them, or these abstractions must rely on existing general-purpose optimizations. The latter is often not as effective as needed. The former presents too significant of an effort for the compiler developers, as they are the only ones who can extend the language with new optimizations. Thus, the language becomes more high-level, yet the optimizer – and, in turn, program performance – falls behind. Programmers are again confronted with a choice between high-level programming and high-performance programs. To investigate a potential solution to this problem, we developed Peridot, a prototype programming language. Peridot’s main contribution is that it enables library developers to easily extend the language with new optimizations themselves. This allows the optimization workload to be taken off the compiler developers’ hands and given to a much larger set of people who can specialize in each problem domain. Because of this, optimizations can be much more effective while also being much more numerous. To enable this, Peridot supports metaprogramming designed for implementing program transformations. The language is split into two fragments or “levels”, one for metaprogramming, the other for high-level general-purpose programming. The metaprogramming level supports logic programming. Peridot’s key idea is that optimizations are simply implemented as metaprograms. The meta level supports several specific features which make it particularly suited to implementing optimizers. For instance, metaprograms can automatically deduce equalities between the programs they are optimizing via unification, deal with variable binding declaratively via higher-order abstract syntax, and avoid the phase-ordering problem via non-determinism. We have found that this design centered around logic programming makes optimizers concise and easy to write compared to their equivalents in functional or imperative languages. Overall, implementing Peridot has shown that its design is a viable solution to the problem of writing code which is both high-level and performant.

Keywords: optimization, metaprogramming, logic programming, abstraction

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Authors: Rodrigo Montufar-Chaveznava, Fernando Brambila-Paz, Ivette Caldelas

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In this paper, we present the advances corresponding to the denoising processing of magnetotelluric signals using several filters. In particular, we use the most common spatial domain filters such as median and mean, but we are also using the Fourier and wavelet transform for frequency domain filtering. We employ three datasets obtained at the different sampling rate (128, 4096 and 8192 bps) and evaluate the mean square error, signal-to-noise relation, and peak signal-to-noise relation to compare the kernels and determine the most suitable for each case. The magnetotelluric signals correspond to earth exploration when water is searched. The object is to find a denoising strategy different to the one included in the commercial equipment that is employed in this task.

Keywords: denoising, filtering, magnetotelluric signals, wavelet transform

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Authors: Martin Cermak, Stanislav Sysala

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In this paper we present the efficient parallel implementation of elastoplastic problems based on the TFETI (Total Finite Element Tearing and Interconnecting) domain decomposition method. This approach allow us to use parallel solution and compute this nonlinear problem on the supercomputers and decrease the solution time and compute problems with millions of DOFs. In our approach we consider an associated elastoplastic model with the von Mises plastic criterion and the combination of linear isotropic-kinematic hardening law. This model is discretized by the implicit Euler method in time and by the finite element method in space. We consider the system of nonlinear equations with a strongly semismooth and strongly monotone operator. The semismooth Newton method is applied to solve this nonlinear system. Corresponding linearized problems arising in the Newton iterations are solved in parallel by the above mentioned TFETI. The implementation of this problem is realized in our in-house MatSol packages developed in MATLAB.

Keywords: isotropic-kinematic hardening, TFETI, domain decomposition, parallel solution

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Authors: Abdelrahman Taha, Niloofar Malekghaini, Hamed Ebrahimian, Ramin Motamed

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This paper compares the substructure and direct methods for soil-structure interaction (SSI) analysis in the time domain. In the substructure SSI method, the soil domain is replaced by a set of springs and dashpots, also referred to as the impedance function, derived through the study of the behavior of a massless rigid foundation. The impedance function is inherently frequency dependent, i.e., it varies as a function of the frequency content of the structural response. To use the frequency-dependent impedance function for time-domain SSI analysis, the impedance function is approximated at the fundamental frequency of the structure-soil system. To explore the potential limitations of the substructure modeling process, a two-dimensional reinforced concrete frame structure is modeled using substructure and direct methods in this study. The results show discrepancies between the simulated responses of the substructure and the direct approaches. To isolate the effects of higher modal responses, the same study is repeated using a harmonic input motion, in which a similar discrepancy is still observed between the substructure and direct approaches. It is concluded that the main source of discrepancy between the substructure and direct SSI approaches is likely attributed to the way the impedance functions are calculated, i.e., assuming a massless rigid foundation without considering the presence of the superstructure. Hence, a refined impedance function, considering the presence of the superstructure, shall be developed. This refined impedance function is expected to significantly improve the simulation accuracy of the substructure approach for structural systems whose behavior is dominated by the fundamental mode response.

Keywords: direct approach, impedance function, soil-structure interaction, substructure approach

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Authors: Hernández Yasmín, Ochoa Alberto, Hurtado Diego

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The aim of this study is developing an intelligent tutoring system for electrical operators training with virtual reality systems at the laboratory center of partials discharges LAPEM. The electrical domain requires efficient and well trained personnel, due to the danger involved in the partials discharges field, qualified electricians are required. This paper presents an overview of the intelligent tutor adaptive learning design and user interface with VR. We propose the develop of constructing a model domain of a subset of partial discharges enables adaptive training through a trainee model which represents the affective and knowledge states of trainees. According to the success of the intelligent tutor system with VR, it is also hypothesized that the trainees will able to learn the electrical domain installations of partial discharges and gain knowledge more efficient and well trained than trainees using traditional methods of teaching without running any risk of being in danger, traditional methods makes training lengthily, costly and dangerously.

Keywords: intelligent tutoring system, artificial intelligence, virtual reality, partials discharges, adaptive learning

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Authors: Kyung-Tae Lee, Li Li Wang, Kwang-Woo Jung, Yong-Sun Bahn

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Microtubules are involved in mechanical support, cytoplasmic organization as well as in a number of cellular processes by interacting with diverse microtubule-associated proteins (MAPs), such as plus-end tracking proteins, motor proteins, and tubulin-folding cofactors. A common feature of these proteins is the presence of a cytoskeleton-associated protein-glycine-rich (CAP-Gly) domain, which is evolutionarily conserved and generally considered to bind to α-tubulin to regulate functions of microtubules. However, there has been a dearth of research on CAP-Gly proteins in fungal pathogens, including Cryptococcus neoformans, which causes fatal meningoencephalitis globally. In this study, we identified five CAP-Gly proteins encoding genes in C. neoformans. Among these, Cgp1, encoded by CNAG_06352, has a unique domain structure that has not been reported before in other eukaryotes. Supporting the role of Cpg1 in microtubule-related functions, we demonstrate that deletion or overexpression of CGP1 alters cellular susceptibility to thiabendazole, a microtubule destabilizer, and Cgp1 is co-localized with cytoplasmic microtubules. Related to the cellular functions of microtubules, Cgp1 also governs maintenance of membrane stability and genotoxic stress responses. Furthermore, we demonstrate that Cgp1 uniquely regulates sexual differentiation of C. neoformans with distinct roles in the early and late stage of mating. Our domain analysis reveals that the CAP-Gly domain plays major roles in all the functions of Cgp1. Finally, the cgp1Δ mutant is attenuated in virulence. In conclusion, this novel CAP-Gly protein, Cgp1, has pleotropic roles in regulating growth, stress responses, differentiation and pathogenicity of C. neoformans.

Keywords: human fungal pathogen, CAP-Glycine protein, microtubule, meningoencephalitis

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Authors: Somtop Keawchuer

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This research aims to study (1) the relationship between competency-based learning and learning efficiency of new media communication students at Suan Sunandha University (2) the demographic factor effect on learning efficiency of students at Suan Sunandha University. This research method will use quantitative research; data was collected by questionnaires distributed to students from new media communication in management science faculty of Suan Sunandha Rajabhat University for 1340 sample by purposive sampling method. Data was analyzed by descriptive statistic including percentage, mean, standard deviation and inferential statistic including T-test, ANOVA and Pearson correlation for hypothesis testing. The results showed that the competency-based learning in term of ability to communicate, ability to think and solve the problem, life skills and ability to use technology has a significant relationship with learning efficiency in term of the cognitive domain, psychomotor domain and affective domain at the 0.05 level and which is in harmony with the research hypotheses.

Keywords: competency-based learning, learning efficiency, new media communication students, Suan Sunandha Rajabhat University

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Authors: Michael Karnes, Alper Yilmaz

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This paper presents the application of the omni-modeler towards pedestrian redetection. The pedestrian redetection task creates several challenges when applying deep neural networks (DNN) due to the variety of pedestrian appearance with camera position, the variety of environmental conditions, and the specificity required to recognize one pedestrian from another. DNNs require significant training sets and are not easily adapted for changes in class appearances or changes in the set of classes held in its knowledge domain. Pedestrian redetection requires an algorithm that can actively manage its knowledge domain as individuals move in and out of the scene, as well as learn individual appearances from a few frames of a video. The Omni-Modeler is a dynamically learning few-shot visual recognition algorithm developed for tasks with limited training data availability. The Omni-Modeler adapts the knowledge domain of pre-trained deep neural networks to novel concepts with a calculated localized language encoder. The Omni-Modeler knowledge domain is generated by creating a dynamic dictionary of concept definitions, which are directly updatable as new information becomes available. Query images are identified through nearest neighbor comparison to the learned object definitions. The study presented in this paper evaluates its performance in re-identifying individuals as they move through a scene in both single-camera and multi-camera tracking applications. The results demonstrate that the Omni-Modeler shows potential for across-camera view pedestrian redetection and is highly effective for single-camera redetection with a 93% accuracy across 30 individuals using 64 example images for each individual.

Keywords: dynamic learning, few-shot learning, pedestrian redetection, visual recognition

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Authors: Sahar Maâlej Dammak, Anis Jedidi, Rafik Bouaziz

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With the great mass of pages managed through the world, and especially with the advent of the Web, their manual annotation is impossible. We focus, in this paper, on the semiautomatic annotation of the web pages. We propose an approach and a framework for semantic annotation of web pages entitled “Querying Web”. Our solution is an enhancement of the first result of annotation done by the “Semantic Radar” Plug-in on the web resources, by annotations using an enriched domain ontology. The concepts of the result of Semantic Radar may be connected to several terms of the ontology, but connections may be uncertain. We represent annotations as possibility distributions. We use the hierarchy defined in the ontology to compute degrees of possibilities. We want to achieve an automation of the fuzzy semantic annotation of web resources.

Keywords: fuzzy semantic annotation, semantic web, domain ontologies, querying web

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Authors: M. Rafiur Rahman, M. Mezbah Uddin, Mohammad Irfan Uddin, M. Moinul Islam

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With a rapid development of offshore renewable energy industry, the research activities in regards of harnessing power from offshore wind and wave energy are increasing day by day. Integration of wind turbines and wave energy converters into one combined semi-submersible platform might be a cost-economy and beneficial option. In this paper, the coupled integrated dynamic analysis in the time domain (TD) of a simplified semi-submersible flap type concept (SFC) is accomplished via state-of-the-art numerical code referred as Simo-Riflex-Aerodyn (SRA). This concept is a combined platform consisting of a semi-submersible floater supporting a 5 MW horizontal axis wind turbine (WT) and three elliptical shaped flap type wave energy converters (WECs) on three pontoons. The main focus is to validate the numerical model of SFC with experimental results and perform the frequency domain (FD) and TD response analysis. The numerical analysis is performed using potential flow theory for hydrodynamics and blade element momentum (BEM) theory for aerodynamics. A variety of environmental conditions encompassing the functional & survival conditions for short-term sea (1-hour simulation) are tested to evaluate the sustainability of the SFC. The numerical analysis is performed in full scale. Finally, the time domain analysis of heave, pitch & surge motions is performed numerically using SRA and compared with the experimental results. Due to the simplification of the model, there are some discrepancies which are discussed in brief.

Keywords: coupled integrated dynamic analysis, SFC, time domain analysis, wave energy converters

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Authors: Virendra Nath, Vipin Kumar

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Background: TypeII Diabetes mellitus is a foremost health problem worldwide, predisposing to increased mortality and morbidity. Undesirable effects of the current medications have prompted the researcher to develop more potential drug(s) against the disease. The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptors family and take part in a vital role in the regulation of metabolic equilibrium. They can induce or repress genes associated with adipogenesis, lipid, and glucose metabolism. Aims: Investigation of PPARα/γ agonistic hits were screened by hierarchical virtual screening followed by molecular dynamics simulation and knowledge-based structure-activity relation (SAR) analysis using approved PPAR α/γ dual agonist. Methods: The PPARα/γ agonistic activity of compounds was searched by using Maestro through structure-based virtual screening and molecular dynamics (MD) simulation application. Virtual screening of nuclear-receptor ligands was done, and the binding modes with protein-ligand interactions of newer entity(s) were investigated. Further, binding energy prediction, Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit along with the structural comparative analysis of approved PPARα/γ agonists with screened hit was done for knowledge-based SAR. Results and Discussion: The silicone chip-based approach recognized the most capable nine hits and had better predictive binding energy as compared to the reference drug compound (Tesaglitazar). In this study, the key amino acid residues of binding pockets of both targets PPARα/γ were acknowledged as essential and were found to be associated in the key interactions with the most potential dual hit (ChemDiv-3269-0443). Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit and found root mean square deviation (RMSD) stabile around 2Å and 2.1Å, respectively. Frequency distribution data also revealed that the key residues of both proteins showed maximum contacts with a potent hit during the MD simulation of 20 nanoseconds (ns). The knowledge-based SAR studies of PPARα/γ agonists were studied using 2D structures of approved drugs like aleglitazar, tesaglitazar, etc. for successful designing and synthesis of compounds PPARγ agonistic candidates with anti-hyperlipidimic potential.

Keywords: computational, diabetes, PPAR, simulation

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Authors: Cosmas Pandit Pagwiwoko, Ammar Khaled Abdelaziz Abdelsamia

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Flutter as a phenomenon of flow-induced and self-excited vibration has to be recognized considering its harmful effect on the structure especially in a stage of aircraft design. This phenomenon is also important for a wind energy harvester based on the fluttering surface due to its effective operational velocity range. This multi-physics occurrence can be presented by two governing equations in both fluid and structure simultaneously in respecting certain boundary conditions on the surface of the body. In this work, the equations are resolved separately by two distinct solvers, one-time step of each domain. The modelling and simulation of this flow-structure interaction in ANSYS show the effectiveness of this loosely coupled method in representing flutter phenomenon however the process is time-consuming for design purposes. Therefore, another technique using the same weak coupled aero-structure is proposed by using system dynamics approach. In this technique, the aerodynamic forces were calculated using singularity function for a range of frequencies and certain natural mode shapes are transformed into time domain by employing an approximation model of fraction rational function in Laplace variable. The representation of structure in a multi-degree-of-freedom coupled with a transfer function of aerodynamic forces can then be simulated in time domain on a block-diagram platform such as Simulink MATLAB. The dynamic response of flutter at certain velocity can be evaluated with another established flutter calculation in frequency domain k-method. In this method, a parameter of artificial structural damping is inserted in the equation of motion to assure the energy balance of flow and vibrating structure. The simulation in time domain is particularly interested as it enables to apply the structural non-linear factors accurately. Experimental tests on a fluttering airfoil in the wind tunnel are also conducted to validate the method.

Keywords: flutter, flow-induced vibration, flow-structure interaction, non-linear structure

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Authors: Emmy Pratiwi, Ketut B. Artana, A. A. B. Dinariyana

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Madura Strait is considered as one of the busiest shipping channels in Indonesia. High vessel traffic density in Madura Strait gives serious threat due to navigational safety in this area, i.e. ship collision. This study is necessary as an attempt to enhance the safety of marine traffic. Fuzzy inference system (FIS) is proposed to calculate risk collision of ships. Collision risk is evaluated based on ship domain, Distance to Closest Point of Approach (DCPA), and Time to Closest Point of Approach (TCPA). Data were collected by utilizing Automatic Identification System (AIS). This study considers several ships’ domain models to give the characteristic of marine traffic in the waterways. Each encounter in the ship domain is analyzed to obtain the level of collision risk. Risk level of ships, as the result in this study, can be used as guidance to avoid the accident, providing brief description about safety traffic in Madura Strait and improving the navigational safety in the area.

Keywords: automatic identification system, collision risk, DCPA, fuzzy inference system, TCPA

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Authors: Wael M. Rabeh, Cesar Carrasco-Lopez, Juliana C. Ferreira, Pance Naumov

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Bioluminescence, the emission of light from a biological process, is found in various living organisms including bacteria, fireflies, beetles, fungus and different marine organisms. Luciferase is an enzyme that catalyzes a two steps oxidation of luciferin in the presence of Mg2+ and ATP to produce oxyluciferin and releases energy in the form of light. The luciferase assay is used in biological research and clinical applications for in vivo imaging, cell proliferation, and protein folding and secretion analysis. The luciferase enzyme consists of two domains, a large N-terminal domain (1-436 residues) that is connected to a small C-terminal domain (440-544) by a flexible loop that functions as a hinge for opening and closing the active site. The two domains are separated by a large cleft housing the active site that closes after binding the substrates, luciferin and ATP. Even though all insect luciferases catalyze the same chemical reaction and share 50% to 90% sequence homology and high structural similarity, they emit light of different colors from green at 560nm to red at 640 nm. Currently, the majority of the structural and biochemical studies have been conducted on green-emitting firefly luciferases. To address the color emission mechanism, we expressed and purified two luciferase enzymes with blue-shifted green and red emission from indigenous Brazilian species Amydetes fanestratus and Phrixothrix, respectively. The two enzymes naturally emit light of different colors and they are an excellent system to study the color-emission mechanism of luciferases, as the current proposed mechanisms are based on mutagenesis studies. Using a vapor-diffusion method and a high-throughput approach, we crystallized and solved the crystal structure of both enzymes, at 1.7 Å and 3.1 Å resolution respectively, using X-ray crystallography. The free enzyme adopted two open conformations in the crystallographic unit cell that are different from the previously characterized firefly luciferase. The blue-shifted green luciferase crystalized as a monomer similar to other luciferases reported in literature, while the red luciferases crystalized as an octamer and was also purified as an octomer in solution. The octomer conformation is the first of its kind for any insect’s luciferase, which might be relate to the red color emission. Structurally designed mutations confirmed the importance of the transition between the open and close conformations in the fine-tuning of the color and the characterization of other interesting mutants is underway.

Keywords: bioluminescence, enzymology, structural biology, x-ray crystallography

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

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

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

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Authors: W. S. Thulasitha, N. Umasuthan, G. I. Godahewa, Jehee Lee

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In fish, innate immune defense is the first immune response against microbial pathogens which consists of several antimicrobial components. Galectins are one of the carbohydrate binding lectins that have the ability to identify pathogen by recognition of pathogen associated molecular patterns. Galectins play a vital role in the regulation of innate and adaptive immune responses. Rock bream Oplegnathus fasciatus is one of the most important cultured species in Korea and Japan. Considering the losses due to microbial pathogens, present study was carried out to understand the molecular and functional characteristics of a galectin in normal and pathogenic conditions, which could help to establish an understanding about immunological components of rock bream. Complete cDNA of rock bream galectin like protein B (rbGal like B) was identified from the cDNA library, and the in silico analysis was carried out using bioinformatic tools. Genomic structure was derived from the BAC library by sequencing a specific clone and using Spidey. Full length of rbGal like B (contig14775) cDNA containing 517 nucleotides was identified from the cDNA library which comprised of 435 bp in the open reading frame encoding a deduced protein composed of 145 amino acids. The molecular mass of putative protein was predicted as 16.14 kDa with an isoelectric point of 8.55. A characteristic conserved galactose binding domain was located from 12 to 145 amino acids. Genomic structure of rbGal like B consisted of 4 exons and 3 introns. Moreover, pairwise alignment showed that rock bream rbGal like B shares highest similarity (95.9 %) and identity (91 %) with Takifugu rubripes galectin related protein B like and lowest similarity (55.5 %) and identity (32.4 %) with Homo sapiens. Multiple sequence alignment demonstrated that the galectin related protein B was conserved among vertebrates. A phylogenetic analysis revealed that rbGal like B protein clustered together with other fish homologs in fish clade. It showed closer evolutionary link with Takifugu rubripes. Tissue distribution and expression patterns of rbGal like B upon immune challenges were performed using qRT-PCR assays. Among all tested tissues, level of rbGal like B expression was significantly high in gill tissue followed by kidney, intestine, heart and spleen. Upon immune challenges, it showed an up-regulated pattern of expression with Edwardsiella tarda, rock bream irido virus and poly I:C up to 6 h post injection and up to 24 h with LPS. However, In the presence of Streptococcus iniae rbGal like B showed an up and down pattern of expression with the peak at 6 - 12 h. Results from the present study revealed the phylogenetic position and role of rbGal like B in response to microbial infection in rock bream.

Keywords: galectin like protein B, immune response, Oplegnathus fasciatus, molecular characterization

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Authors: Dechao Meng, Yongqi Dong, Qiyuan Feng, Zhangzhang Cui, Xiang Hu, Haoliang Huang, Genhao Liang, Huanhua Wang, Hua Zhou, Hawoong Hong, Jinghua Guo, Qingyou Lu, Xiaofang Zhai, Yalin Lu

Abstract:

Great efforts have been taken to reveal the intrinsic origins of emerging ferromagnetism (FM) in strained LaCoO₃ (LCO) films. However, some macro magnetic performances of LCO are still not well understood and even controversial, such as magnetic anisotropy. Determining and understanding magnetic anisotropy might help to find the true causes of FM in turn. Perpendicular magnetic anisotropy (PMA) was the first time to be directly observed in high-quality LCO films with different thickness. The in-plane (IP) and out of plane (OOP) remnant magnetic moment ratio of 30 unit cell (u.c.) films is as large as 20. The easy axis lays in the OOP direction with an IP/OOP coercive field ratio of 10. What's more, the PMA could be simply tuned by changing the thickness. With the thickness increases, the IP/OOP magnetic moment ratio remarkably decrease with magnetic easy axis changing from OOP to IP. Such a huge and tunable PMA performance exhibit strong potentials in fundamental researches or applications. What causes PMA is the first concern. More OOP orbitals occupation may be one of the micro reasons of PMA. A cluster-like magnetic domain pattern was found in 30 u.c. with no obvious color contrasts, similar to that of LaAlO₃/SrTiO₃ films. And the nanosize domains could not be totally switched even at a large OOP magnetic field of 23 T. It indicates strong IP characters or none OOP magnetism of some clusters. The IP magnetic domains might influence the magnetic performance and help to form PMA. Meanwhile some possible nonmagnetic clusters might be the reason why the measured moments of LCO films are smaller than the calculated values 2 μB/Co, one of the biggest confusions in LCO films.What tunes PMA seems much more interesting. Totally different magnetic domain patterns were found in 180 u.c. films with cluster magnetic domains surrounded by < 110 > cross-hatch lines. These lines were regarded as structure domain walls (DWs) determined by 3D reciprocal space mapping (RSM). Two groups of in-plane features with fourfold symmetry were observed near the film diffraction peaks in (002) 3D-RSM. One is along < 110 > directions with a larger intensity, which is well match the lines on the surfaces. The other is much weaker and along < 100 > directions, which is from the normal lattice titling of films deposited on cubic substrates. The < 110 > domain features obtained from (103) and (113) 3D-RSMs exhibit similar evolution of the DWs percentages and magnetic behavior. Structure domains and domain walls are believed to tune PMA performances by transform more IP magnetic moments to OOP. Last but not the least, thick films with lots of structure domains exhibit different electrical transport behaviors. A metal-to-insulator transition (MIT) and an angular dependent negative magnetic resistivity were observed near 150 K, higher than FM transition temperature but similar to that of spin-orbital coupling related 1/4 order diffraction peaks.

Keywords: structure domain, magnetic anisotropy, magnetic domain, domain wall, 3D-RSM, strain

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Authors: Shai Sarussi

Abstract:

Let S be an integral domain with field of fractions F and let A be an F-algebra. An S-subalgebra R of A is called S-nice if R∩F = S and the localization of R with respect to S \{0} is A. Denoting by W the set of all S-nice subalgebras of A, and defining a notion of open sets on W, one can view W as a T0-Alexandroff space. Thus, the algebraic structure of W can be viewed from the point of view of topology. It is shown that every nonempty open subset of W has a maximal element in it, which is also a maximal element of W. Moreover, a supremum of an irreducible subset of W always exists. As a notable connection with valuation theory, one considers the case in which S is a valuation domain and A is an algebraic field extension of F; if S is indecomposed in A, then W is an irreducible topological space, and W contains a greatest element.

Keywords: integral domains, Alexandroff topology, prime spectrum of a ring, valuation domains

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Authors: Hassan Youssef Mohamed

Abstract:

In this paper, we show new wave equations, and by using the equations, we concluded that the strong force and the weak force are not fundamental, but they are quantum effects for electromagnetism. This result is different from the current scientific understanding about strong and weak interactions at all. So, we introduce three evidences for our theory. First, we prove the asymptotic freedom phenomenon in the strong force by using our model. Second, we derive the nuclear shell model as an approximation of our model. Third, we prove that the leptons do not participate in the strong interactions, and we prove the short ranges of weak and strong interactions. So, our model is consistent with the current understanding of physics. Finally, we introduce the electron-positron model as the basic ingredients for protons, neutrons, and all matters, so we can study all particles interactions and nuclear interaction as many-body problems of electrons and positrons. Also, we prove the violation of parity conservation in weak interaction as evidence of our theory in the weak interaction. Also, we calculate the average of the binding energy per nucleon.

Keywords: new wave equations, the strong force, the grand unification theory, hydrogen atom, weak force, the nuclear shell model, the asymptotic freedom, electron-positron model, the violation of parity conservation, the binding energy

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Authors: Kinga Mylkie, Pawel Nowak, Marta Z. Borowska

Abstract:

The most important proteins in human serum responsible for drug binding are human serum albumin (HSA) and α1-acid glycoprotein (AGP). The AGP molecule is a glycoconjugate containing a single polypeptide chain composed of 183 amino acids (the core of the protein), and five glycan branched chains (sugar part) covalently linked by an N-glycosidic bond with aspartyl residues (Asp(N) -15, -38, -54, -75, - 85) of polypeptide chain. This protein plays an important role in binding alkaline drugs, a large group of drugs used in psychiatry, some acid drugs (e.g., coumarin anticoagulants), and neutral drugs (steroid hormones). The main goal of the research was to obtain magnetic nanoparticles coated with biopolymers in a chemically modified form, which will have highly reactive functional groups able to effectively immobilize the glycoprotein (acid α1-glycoprotein) without losing the ability to bind active substances. The first phase of the project involved the chemical modification of biopolymer starch. Modification of starch was carried out by methods of organic synthesis, leading to the preparation of a polymer enriched on its surface with aldehyde groups, which in the next step was coupled with 3-aminophenylboronic acid. Magnetite nanoparticles coated with starch were prepared by in situ co-precipitation and then oxidized with a 1 M sodium periodate solution to form a dialdehyde starch coating. Afterward, the reaction between the magnetite nanoparticles coated with dialdehyde starch and 3-aminophenylboronic acid was carried out. The obtained materials consist of a magnetite core surrounded by a layer of modified polymer, which contains on its surface dihydroxyboryl groups of boronic acids which are capable of binding glycoproteins. Magnetic nanoparticles obtained as carriers for plasma protein immobilization were fully characterized by ATR-FTIR, TEM, SEM, and DLS. The glycoprotein was immobilized on the obtained nanoparticles. The amount of mobilized protein was determined by the Bradford method.

Keywords: glycoproteins, immobilization, magnetic nanoparticles, polysaccharides

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Authors: Thomas LaRocca

Abstract:

This study explores the development of a public-school music teacher’s professional identity within three domains: as an educator in the profession at large, as a music teacher in a school, and as a professional musician. An autoethnographic method is employed by calling upon undergraduate student teaching reflections, graduate writing assignments and presentations, cover letters for employment, professional correspondence, and reflective memos. These artifacts provide a reference for phenomenological insights into the values, hopes, and criticisms within each domain over time –all of which provide a window into the overall ontological perspective of one’s professional life at different moments in their career. While the topic of music teacher identity has been examined using autoethnographical methods before, by accessing materials over the course of ten years, the study is able to investigate the ‘how’ of identity development in a temporal context; from undergraduate student to established professional. Additionally, while the field offers a considerable amount of work surrounding the child and adolescent identity development, there are unmined opportunities to examine identity development in the adult years, especially surrounding adult professional life. Employing a postpositivist approach with social constructionism as a backdrop, this study examines adult identity formation and the contradictions, resonances, and priorities within each domain, between each domain, and perceived expectations of the professional community. What is revealed is a journey of self-improvement motivated by failure and success, marked by negotiation and sacrifice; as each domain competes for mental and temporal resources, identity is viewed as not just who one is, but also as what one leaves behind. These insights offer a window into the ontology of identity of a music educator and may provide considerations for differentiating professional development based on what stage educators are at in their careers.

Keywords: identity, longitudinal autoethnography, music teacher education, music teacher ontology

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Authors: Nkosingiphile Mbusozayo Zungu

Abstract:

The purpose of the current study is to adopt informetrics methods to analyse the research on phishing from 2012 to 2021 in three selected databases in order to contribute to global cybersecurity through impactful research. The study follows a quantitative research methodology. We opted for the positivist epistemology and objectivist ontology. The analysis focuses on: (i) the productivity of individual authors, institutions, and countries; (ii) the research contributions, using co-authorship as a measure of collaboration; (iii) the altmetrics of selected research contributions; (iv) the citation patterns and research impact of research on phishing; and (v) research contributions by keywords, to discover the concepts that are related to phishing. The preliminary findings favour developed countries in terms of quantity and quality of research in the domain. There are unique research trends and patterns in the developing countries, including those in Africa, that provide opportunities for research development in the domain in the region. This study explores an important research domain by using unexplored method in the region. The study supports the SDG Agenda 2030, such as ending abuse, exploitation, trafficking, and all other forms of violence and torture of children through the use of cyberspace (SDG 16). Further, the results from this study can inform research, teaching, and learning largely in Africa. Invariably, the study contributes to cybersecurity awareness that will mitigate cybersecurity threats against vulnerable communities.

Keywords: phishing, cybersecurity, informetrics, information security

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Authors: A. V. Patil

Abstract:

The microwave dielectric relaxation study of diethanolamine with triethanolamine binary mixture have been determined over the frequency range of 10 MHz to 20 GHz, at various temperatures using time domain reflectometry (TDR) method for 11 concentrations of the system. The present work reveals molecular interaction between same multi-functional groups [−OH and –NH2] of the alkanolamines (diethanolamine and triethanolamine) using different models such as Debye model, Excess model, and Kirkwood model. The dielectric parameters viz. static dielectric constant (ε0) and relaxation time (τ) have been obtained with Debye equation characterized by a single relaxation time without relaxation time distribution by the least squares fit method.

Keywords: diethanolamine, excess properties, kirkwood properties, time domain reflectometry, triethanolamine

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Authors: Saurabh B. Ganorkar, Atul A. Shirkhedkar

Abstract:

The need for investigations protecting against toxic impurities though seems to be a primary requirement; the impurities which may prove non - toxic can be explored for their therapeutic potential if any to assist advanced drug discovery. The essential role of pharmaceutical analysis can thus be extended effectively to achieve it. The present study successfully achieved these objectives with characterization of major degradation products as impurities for Zileuton which has been used for to treat asthma since years. The forced degradation studies were performed to identify the potential degradation products using Ultra-fine Liquid-chromatography. Liquid-chromatography-Mass spectrometry (Time of Flight) and Proton Nuclear Magnetic Resonance Studies were utilized effectively to characterize the drug along with five major oxidative and hydrolytic degradation products (DP’s). The mass fragments were identified for Zileuton and path for the degradation was investigated. The characterized DP’s were subjected to In-Silico studies as XP Molecular Docking to compare the gain or loss in binding affinity with 5-Lipooxygenase enzyme. One of the impurity of was found to have the binding affinity more than the drug itself indicating for its potential to be more bioactive as better Antiasthmatic. The close structural resemblance has the ability to potentiate or reduce bioactivity and or toxicity. The chances of being active biologically at other sites cannot be denied and the same is achieved to some extent by predictions for probability of being active with Prediction of Activity Spectrum for Substances (PASS) The impurities found to be bio-active as Antineoplastic, Antiallergic, and inhibitors of Complement Factor D. The toxicological abilities as Ames-Mutagenicity, Carcinogenicity, Developmental Toxicity and Skin Irritancy were evaluated using Toxicity Prediction by Komputer Assisted Technology (TOPKAT). Two of the impurities were found to be non-toxic as compared to original drug Zileuton. As the drugs are purposed and repurposed effectively the impurities can also be; as they can have more binding affinity; less toxicity and better ability to be bio-active at other biological targets.

Keywords: UFLC, LC-MS-TOF, NMR, Zileuton, impurities, toxicity, bio-activity

Procedia PDF Downloads 171

Authors: Tanushree Jaitly, Shailendra Gupta, Leila Taher, Gerold Schuler, Julio Vera

Abstract:

Genomics-based personalized medicine is a promising approach to fight aggressive tumors based on patient's specific tumor mutation and expression profiles. A remarkable case is, dendritic cell-based immunotherapy, in which tumor epitopes targeting patient's specific mutations are used to design a vaccine that helps in stimulating cytotoxic T cell mediated anticancer immunity. Here we present a computational pipeline for epitope-based personalized cancer vaccines using patient-specific haplotype and cancer mutation profiles. In the workflow proposed, we analyze Whole Exome Sequencing and RNA Sequencing patient data to detect patient-specific mutations and their expression level. Epitopes including the tumor mutations are computationally predicted using patient's haplotype and filtered based on their expression level, binding affinity, and immunogenicity. We calculate binding energy for each filtered major histocompatibility complex (MHC)-peptide complex using docking studies, and use this feature to select good epitope candidates further.

Keywords: cancer immunotherapy, epitope prediction, NGS data, personalized medicine

Procedia PDF Downloads 230