Search results for: binding stability

Authors: Grienggrai Rajchakit

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This paper is concerned with the exponential stability of switched linear systems with interval time-varying delays. The time delay is any continuous function belonging to a given interval, in which the lower bound of delay is not restricted to zero. By constructing a suitable augmented Lyapunov-Krasovskii functional combined with Leibniz-Newton's formula, a switching rule for the exponential stability of switched linear systems with interval time-varying delays and new delay-dependent sufficient conditions for the exponential stability of the systems are first established in terms of LMIs. Finally, some examples are exploited to illustrate the effectiveness of the proposed schemes.

Keywords: exponential stability, hybrid systems, time-varying delays, lyapunov-krasovskii functional, leibniz-newton's formula

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Authors: P. Singh, S. Mittal

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Stability of slope in Chamoli Distt. near River Alaknanda in Uttarakhand is essential to safeguard the infrastructure of the slope where a dam is proposed to be built near this slope. Every year the areas near the slope have been facing severe landslides (small or big) due to intensive precipitation inflicting substantial damages as per Geological Survey of India records. The stability analysis of the slope under static and pseudo static conditions are presented in this study by using FEM software PHASE2. As per the earthquake zonation map of India, the slope is found in zone V, and hence, pseudo static stability of slope has been performed considering pseudo static analysis. For analysing the slope Mohr-Coulomb shear strength criteria is adopted for soil material and self-drilling anchors are modelled as bolts with parameters like modulus of elasticity, diameter of anchors and peak pull-out resistance of the anchors with the soil present there. The slope is found to be unstable under pseudo static conditions with computed factor of safety= 0.93. Stability is provided to the slope by using Self Drilling Anchors (SDA) which gives factor of safety= 1.15 under pseudo static condition.

Keywords: FEM, pseudo static, self-drilling anchors, slope stability

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Authors: Nigar Kantarci Carsibasi

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Coarse-grained elastic network models, namely Gaussian network model (GNM) and Anisotropic network model (ANM), are utilized in order to investigate the fluctuation dynamics of Murine Double Minute 2 (MDM2), which is the native inhibitor of p53. Conformational dynamics of MDM2 are elucidated in unbound, p53 bound, and non-peptide small molecule inhibitor bound forms. With this, it is aimed to gain insights about the alterations brought to global dynamics of MDM2 by native peptide inhibitor p53, and two small molecule inhibitors (HDM201 and NVP-CGM097) that are undergoing clinical stages in cancer studies. MDM2 undergoes significant conformational changes upon inhibitor binding, carrying pieces of evidence of induced-fit mechanism. Small molecule inhibitors examined in this work exhibit similar fluctuation dynamics and characteristic mode shapes with p53 when complexed with MDM2, which would shed light on the design of novel small molecule inhibitors for cancer therapy. The results showed that residues Phe 19, Trp 23, Leu 26 reside in the minima of slowest modes of p53, pointing to the accepted three-finger binding model. Pro 27 displays the most significant hinge present in p53 and comes out to be another functionally important residue. Three distinct regions are identified in MDM2, for which significant conformational changes are observed upon binding. Regions I (residues 50-77) and III (residues 90-105) correspond to the binding interface of MDM2, including (α2, L2, and α4), which are stabilized during complex formation. Region II (residues 77-90) exhibits a large amplitude motion, being highly flexible, both in the absence and presence of p53 or other inhibitors. MDM2 exhibits a scattered profile in the fastest modes of motion, while binding of p53 and inhibitors puts restraints on MDM2 domains, clearly distinguishing the kinetically hot regions. Mode shape analysis revealed that the α4 domain controls the size of the cleft by keeping the cleft narrow in unbound MDM2; and open in the bound states for proper penetration and binding of p53 and inhibitors, which points to the induced-fit mechanism of p53 binding. P53 interacts with α2 and α4 in a synchronized manner. Collective modes are shifted upon inhibitor binding, i.e., second mode characteristic motion in MDM2-p53 complex is observed in the first mode of apo MDM2; however, apo and bound MDM2 exhibits similar features in the softest modes pointing to pre-existing modes facilitating the ligand binding. Although much higher amplitude motions are attained in the presence of non-peptide small molecule inhibitor molecules as compared to p53, they demonstrate close similarity. Hence, NVP-CGM097 and HDM201 succeed in mimicking the p53 behavior well. Elucidating how drug candidates alter the MDM2 global and conformational dynamics would shed light on the rational design of novel anticancer drugs.

Keywords: cancer, drug design, elastic network model, MDM2

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Authors: Ratchaneewan Maneemaroj, Paveena Noisuwan, Chonlada Lakhonphon

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The smoking is one of the major risk factors in Non-Communicable Disease. Free radicals from cigarette smoke can cause oxidative stress. The oxidative insults can lead to red blood cell (RBC) senescence and are involved in the clearance of red blood cells. The objective of the present study is to assess the association between smoke, oxidative stress evaluated with serum Malondialdehyde (MDA) level and phosphatidylserine (PS) externalization (biomarker of RBC senescence) evaluated with annexin V binding. A total of sixty-four male volunteers aged 25-60 years old were recruited in this study. MDA was measured by colorimetric method. Annexin V binding was detected by flow cytometry. Our results show that there was a significant increase in MDA levels in cigarette smokers as compared to non-smokers (p < 0.001). However, there was no significant different between annexin V binding (% gate) in cigarette smokers and non-smokers (p = 0.978). These results provide evidence of free radical from smoking is associated with oxidative damage to erythrocytes. However, our results suggest that PS externalization is unlikely to have a role in RBC senescence pathway of stressed erythrocytes from cigarette smoke. The other biomarker of RBC senescence should be determined on cigarette smoker erythrocytes.

Keywords: malondialdehyde, phosphatidylserine, RBC senescence, annexin V

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Authors: Bercem Kiran-Yildirim, Volker Gaukel

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Ice recrystallization (IR) which occurs especially during frozen storage is an undesired process due to the possible influence on the quality of products. As a result of recrystallization, the total volume of ice remains constant, but the size, number, and shape of ice crystals change. For instance, as indicated in the literature, the size of ice crystals in ice cream increases due to recrystallization. This results in texture deterioration. Therefore, the inhibition of ice recrystallization is of great importance, not only for food industry but also for several other areas where sensitive products are stored frozen, like pharmaceutical products or organs and blood in medicine. Ice-binding proteins (IBPs) have the unique ability to inhibit ice growth and in consequence inhibit recrystallization. This effect is based on their ice binding affinity. In the presence of IBP in a solution, ice crystal growth is inhibited during temperature decrease until a certain temperature is reached. The melting during temperature increase is not influenced. The gap between melting and freezing points is known as thermal hysteresis (TH). In literature, the TH activity is usually investigated under laboratory conditions in IBP buffer solutions. In product applications (e.g., food) there are many other solutes present which may influence the TH activity. In this study, a subset of IBPs, so-called antifreeze proteins (AFPs), is used for the investigation of the influence of sucrose solution concentration on the TH activity. For the investigation, a polarization microscope (Nikon Eclipse LV100ND) equipped with a digital camera (Nikon DS-Ri1) and a cold stage (Linkam LTS420) was used. In a first step, the equipment was established and validated concerning the accuracy of TH measurements based on literature data.

Keywords: ice binding proteins, ice crystals, sucrose solution, thermal hysteresis

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Authors: N. Chérif, T. Allaoui, M. Benasla, H. Chaib

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Industrialization and population growth are the prime factors for which the consumption of electricity is steadily increasing. Thus, to have a balance between production and consumption, it is necessary at first to increase the number of power plants, lines and transformers, which implies an increase in cost and environmental degradation. As a result, it is now important to have mesh networks and working close to the limits of stability in order to meet these new requirements. The transient stability studies involve large disturbances such as short circuits, loss of work or production group. The consequence of these defects can be very serious, and can even lead to the complete collapse of the network. This work focuses on the regulation means that networks can help to keep their stability when submitted to strong disturbances. The magnetic energy storage-based superconductor (SMES) comprises a superconducting coil short-circuited on it self. When such a system is connected to a power grid is able to inject or absorb the active and reactive power. This system can be used to improve the stability of power systems.

Keywords: short-circuit, power oscillations, multiband PSS, power system, SMES, transient stability

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Authors: Phillip Kearney, Constantina Lekakou, Stephen Belcher, Alessandro Sordon

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The focus in the automotive industry is to reduce human operator and machine interaction, so manufacturing becomes more automated and safer. The aim is to lower part cost and construction time as well as defects in the parts, sometimes occurring due to the physical limitations of human operators. A move to automate the layup of reinforcement material in composites manufacturing has resulted in the use of tapes that are placed in position by a robotic deposition head, also described as Automated Fibre Placement (AFP). The process of AFP is limited with respect to the finite amount of material that can be loaded into the machine at any one time. Joining two batches of tape material together involves a splice to secure the ends of the finishing tape to the starting edge of the new tape. The splicing method of choice for the majority of prepreg applications is a hand stich method, and as the name suggests requires human input to achieve. This investigation explores three methods for automated splicing, namely, adhesive, binding and stitching. The adhesive technique uses an additional adhesive placed on the tape ends to be joined. Binding uses the binding agent that is already impregnated onto the tape through the application of heat. The stitching method is used as a baseline to compare the new splicing methods to the traditional technique currently in use. As the methods will be used within a High Speed Automated Fibre Placement (HSAFP) process, this meant the parameters of the splices have to meet certain specifications: (a) the splice must be able to endure a load of 50 N in tension applied at a rate of 1 mm/s; (b) the splice must be created in less than 6 seconds, dictated by the capacity of the tape accumulator within the system. The samples for experimentation were manufactured with controlled overlaps, alignment and splicing parameters, these were then tested in tension using a tensile testing machine. Initial analysis explored the use of the impregnated binding agent present on the tape, as in the binding splicing technique. It analysed the effect of temperature and overlap on the strength of the splice. It was found that the optimum splicing temperature was at the higher end of the activation range of the binding agent, 100 °C. The optimum overlap was found to be 25 mm; it was found that there was no improvement in bond strength from 25 mm to 30 mm overlap. The final analysis compared the different splicing methods to the baseline of a stitched bond. It was found that the addition of an adhesive was the best splicing method, achieving a maximum load of over 500 N compared to the 26 N load achieved by a stitching splice and 94 N by the binding method.

Keywords: analysis, automated fibre placement, high speed, splicing

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Authors: Jui-Pin Hung, Qiao-Wen Chang, Kung-Da Wu, Yong-Run Chen

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This study was aimed to investigate the machining stability of a spindle tool with different preloaded amount. To this end, the vibration tests were conducted on the spindle unit with different preload to assess the dynamic characteristics and machining stability of the spindle unit. Current results demonstrate that the tool tip frequency response characteristics and the machining stabilities in X and Y direction are affected to change for spindle with different preload. As can be found from the results, a high preloaded spindle tool shows higher limited cutting depth at mid position, while a spindle with low preload shows a higher limited depth. This implies that the machining stability of spindle tool system is affected to vary by the machine frame structure. Besides, such an effect is quite different and varied with the preload of the spindle.

Keywords: bearing preload, dynamic compliance, machining stability, spindle

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Authors: Hainan Chen, Jina Qing, Xiao Zhu, Ling Gao, Ampadu O. Jackson, Min Zhang, Kai Yin

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Objective: Editing macrophage activation to dampen inflammatory diseases by promoting the repolarization of inflammatory (M1) macrophages to anti-inflammatory (M2) macrophages is highly associated with mitochondrial respiration. Recent studies have suggested that mitochondrial apolipoprotein A-1 binding protein (APOA1BP) was essential for the cellular metabolite NADHX repair to NADH, which is necessary for the mitochondrial function. The exact role of APOA1BP in the repolarization of M1 to M2, however, is uncertain. Material and method: THP-1-derived macrophages were incubated with LPS (10 ng/ml) or/and IL-4 (100 U/ml) for 24 hours. Biochemical parameters of oxidative phosphorylation and M1/M2 markers were analyzed after overexpression of APOA1BP in cells. Results: Compared with control and IL-4-exposed M2 cells, APOA1BP was downregulated in M1 macrophages. APOA1BP restored the decline in mitochondrial function to improve metabolic and phenotypic reprogramming of M1 to M2 macrophages. Blocking oxidative phosphorylation by oligomycin blunts the effects of APOA1BP on M1 to M2 repolarization. Mechanistically, LPS triggered the hydration of NADH and increased its hydrate NADHX which inhibit cellular NADH dehydrogenases, a key component of electron transport chain for oxidative phosphorylation. APOA1BP decreased the level of NADHX via converting R-NADHX to biologically useful S-NADHX. The mutant of APOA1BP aspartate188, the binding site of NADHX, fail to repair oxidative phosphorylation, thereby preventing repolarization. Conclusions: Restoring mitochondrial function by increasing mitochondrial APOA1BP might be useful to improve the reprogramming of inflammatory macrophages into anti-inflammatory cells to control inflammatory diseases.

Keywords: inflammatory diseases, macrophage repolarization, mitochondrial respiration, apolipoprotein A-1 binding protein, NADHX, NADH

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Authors: Natalina, Hwai Chyuan Onga, W. T. Chonga

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Oxidation stability of biodiesel is very important in fuel handling especially for remote location of biodiesel application. Variety of feedstocks and biodiesel production process resulted many variation of biodiesel oxidation stability. The current study relates to investigation of the impact of fatty acid composition that caused by natural and production process of calophyllum inophyllum palm oil methyl ester that correlated with improvement of biodiesel oxidation stability. Firstly, biodiesel was produced from crude oil of palm oil, calophyllum inophyllum and mixing of calophyllum inophyllum and palm oil. The production process of calophyllum inophyllum palm oil methyl ester (CIPOME) was divided by including washing process and without washing. Secondly, the oxidation stability was measured from the palm oil methyl ester (POME), calophyllum inophyllum methyl ester (CIME), CIPOME with washing process and CIPOME without washing process. Then, in order to find the differences of fatty acid compositions all of the biodiesels were measured by gas chromatography analysis. It was found that mixing calophyllum inophyllum into palm oil increased the oxidation stability. Washing process influenced the CIPOME fatty acid composition, and reduction of washing process during the production process gave significant oxidation stability number of CIPOME (38 h to 114 h).

Keywords: biodiesel, oxidation stability, calophyllum inophyllum, water content

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Authors: C. S. Bianca Sabrina, N. Egidio Raimundo, L. Alexandre Baratella, C. H. João Paulo

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This paper aims to present a study, with the theoretical concepts and applications of the Quadcopter, using the MATLAB simulator. In order to use this tool, the study of the stability of the drone through a Proportional - Integral - Derivative (PID) controller will be presented. After the stability study, some tests are done on the simulator and its results will be presented. From the mathematical model, it is possible to find the Newton-Euler angles, so that it is possible to stabilize the quadcopter in a certain position in the air, starting from the ground. In order to understand the impact of the controllers gain values on the stabilization of the Euler-Newton angles, three conditions will be tested with different controller gain values.

Keywords: controllers, drones, quadcopter, stability

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Authors: Danish Idrees, Vijay Kumar, Samudrala Gourinath

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by misfolding and aggregation of Cu, Zn superoxide dismutase (SOD1). The use of small molecules has been shown to stabilize the SOD1 dimer and preventing its dissociation and aggregation. In this study, we employed molecular docking, molecular dynamics simulation and surface plasmon resonance (SPR) to study the interactions between SOD1 and natural polyphenolic compounds. In order to explore the noncovalent interaction between SOD1 and natural polyphenolic compounds, molecular docking and molecular dynamic (MD) simulations were employed to gain insights into the binding modes and free energies of SOD1-polyphenolic compounds. MM/PBSA methods were used to calculate free energies from obtained MD trajectories. The compounds, Hesperidin, Ergosterol, and Rutin showed the excellent binding affinity in micromolar range with SOD1. Ergosterol and Hesperidin have the strongest binding affinity to SOD1 and was subjected to further characterization. Biophysical experiments using Circular Dichroism and Thioflavin T fluorescence spectroscopy results show that the binding of these two compounds can stabilize SOD1 dimer and inhibit the aggregation of SOD1. Molecular simulation results also suggest that these compounds reduce the dissociation of SOD1 dimers through direct interaction with the dimer interface. This study will be helpful to develop other drug-like molecules which may have the effect to reduce the aggregation of SOD1.

Keywords: amyotrophic lateral sclerosis, molecular dynamics simulation, surface plasmon resonance, superoxide dismutase

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Authors: Mohamed Amarouayache, Badia Amrouche, Gharbi Akila, Boukadoume Mohamed

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This work is devoted to the modeling of DC-DC converter (boost) used for MPPT applications to set conditions of stability. For this, we establish a linear mathematical model of the DC-DC converter with an average small signal model. This model has allowed us to apply conventional linear methods of automation. A mathematical relationship between the duty cycle and the voltage of the panel has been set up. With this relationship we specify the conditions of the stability in closed-loop depending on the system parameters (the elements of storage capacity and inductance, PWM control).

Keywords: MPPT, PWM, stability, criterion of Routh, average small signal model

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Authors: F. Rahimi Dehgolan, S. E. Khadem, S. Bab, M. Najafee

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Nowadays, using rotating systems like shafts and disks in industrial machines have been increased constantly. Dynamic stability is one of the most important factors in designing rotating systems. In this study, linear frequencies and stability of a coupled continuous flexible rotor-disk-blades system are studied. The Euler-Bernoulli beam theory is utilized to model the blade and shaft. The equations of motion are extracted using the extended Hamilton principle. The equations of motion have been simplified using the Coleman and complex transformations method. The natural frequencies of the linear part of the system are extracted, and the effects of various system parameters on the natural frequencies and decay rates (stability condition) are clarified. It can be seen that the centrifugal stiffening effect applied to the blades is the most important parameter for stability of the considered rotating system. This result highlights the importance of considering this stiffing effect in blades equation.

Keywords: rotating shaft, flexible blades, centrifugal stiffness, stability

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Authors: E. Popov, N. Yorino, Y. Zoka, Y. Sasaki, H. Sugihara

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This paper discusses the performance of critical trajectory method (CTrj) for power system transient stability analysis under various loading settings and heavy fault condition. The method obtains Controlling Unstable Equilibrium Point (CUEP) which is essential for estimation of power system stability margins. The CUEP is computed by applying the CTrjto the boundary controlling unstable equilibrium point (BCU) method. The Proposed method computes a trajectory on the stability boundary that starts from the exit point and reaches CUEP under certain assumptions. The robustness and effectiveness of the method are demonstrated via six power system models and five loading conditions. As benchmark is used conventional simulation method whereas the performance is compared with and BCU Shadowing method.

Keywords: power system, transient stability, critical trajectory method, energy function method

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Authors: Burak Yildirim, Muhsin Tunay Gençoğlu

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A microgrid (MG) is a small power grid composed of localized medium or low level power generation, storage systems, and loads. In this paper, the effects of a MG on power systems voltage stability are shown. The MG model, designed to demonstrate the effects of the MG, was applied to the IEEE 14 bus power system which is widely used in power system stability studies. Eigenvalue and modal analysis methods were used in simulation studies. In the study results, it is seen that MGs affect system voltage stability positively by increasing system voltage instability limit value for buses of a power system in which MG are placed.

Keywords: eigenvalue analysis, microgrid, modal analysis, voltage stability

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Authors: Jui-Pui Hung, Yong-Run Chen, Wei-Cheng Shih, Shen-He Tsui, Kung-Da Wu

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This paper presents the effect on the tooling conditions on the machining stabilities of a milling machine tool. The machining stability was evaluated in different feeding direction in the X-Y plane, which was referred as the orientation-dependent machining stability. According to the machining mechanics, the machining stability was determined by the frequency response function of the cutter. Thus, we first conducted the vibration tests on the spindle tool of the milling machine to assess the tool tip frequency response functions along the principal direction of the machine tool. Then, basing on the orientation dependent stability analysis model proposed in this study, we evaluated the variation of the dynamic characteristics of the spindle tool and the corresponding machining stabilities at a specific feeding direction. Current results demonstrate that the stability boundaries and limited axial cutting depth of a specific cutter were affected to vary when it was fixed in the tool holder with different overhang length. The flute of the cutter also affects the stability boundary. When a two flute cutter was used, the critical cutting depth can be increased by 47 % as compared with the four flute cutter. The results presented in study provide valuable references for the selection of the tooling conditions for achieving high milling performance.

Keywords: tooling condition, machining stability, milling machine, chatter

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Authors: Abid Fida Masih

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Forced degradation study of Rifaximin was conducted to determine the stability indicating potential of HPLC testing method for detection of Rifaximin in formulated tablets to be employed for quality control and stability testing. The questioned method applied with mobile phase methanol: water (70:30), 5µm, 250 x 4.6mm, C18 column, wavelength 293nm and flow rate of 1.0 ml/min. Forced degradation study was performed under oxidative, acidic, basic, thermal and photolytic conditions. The applied method successfully determined the degradation products after acidic and basic degradation without interfering with Rifaximin detection. Therefore, the method was said to be stability indicating and can be applied for quality control and stability testing of Rifaxmin tablets during its shelf life.

Keywords: forced degradation, high-performance liquid chromatography, method validation, rifaximin, stability indicating method

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Authors: S. Limpattayanate, M. Hunsom

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A comparison of activity and stability of the as-formed Pt/C, Pt-Co, and Pt-Pd/C electrocatalysts, prepared by a combined approach of impregnation and seeding, was performed. According to the activity test in a single proton exchange membrane (PEM) fuel cell, the oxygen reduction reaction (ORR) activity of the Pt-M/C electro catalyst was slightly lower than that of Pt/C. The j0.9 V and E10 mA/cm2 of the as-prepared electrocatalysts increased in the order of Pt/C>Pt-Co/C>Pt-Pd/C. However, in the medium-to-high current density region, Pt-Pd/C exhibited the best performance. With regard to their stability in a 0.5 M H2SO4 electrolyte solution, the electro chemical surface area decreased as the number of rounds of repetitive potential cycling increased due to the dissolution of the metals within the catalyst structure. For long-term measurement, Pt-Pd/C was the most stable than the other three electrocatalysts.

Keywords: ORR activity, stability, Pt-based electrocatalysts, PEM fuel cell

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Authors: Xiao Zhou, Jianlin Cheng

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A single amino acid mutation can have a significant impact on the stability of protein structure. Thus, the prediction of protein stability change induced by single site mutations is critical and useful for studying protein function and structure. Here, we presented a deep learning network with the dropout technique for predicting protein stability changes upon single amino acid substitution. While using only protein sequence as input, the overall prediction accuracy of the method on a standard benchmark is >85%, which is higher than existing sequence-based methods and is comparable to the methods that use not only protein sequence but also tertiary structure, pH value and temperature. The results demonstrate that deep learning is a promising technique for protein stability prediction. The good performance of this sequence-based method makes it a valuable tool for predicting the impact of mutations on most proteins whose experimental structures are not available. Both the downloadable software package and the user-friendly web server (DNpro) that implement the method for predicting protein stability changes induced by amino acid mutations are freely available for the community to use.

Keywords: bioinformatics, deep learning, protein stability prediction, biological data mining

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Authors: Abdulrahman Abdulrahman, Abir Abdulrahman

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The stability of slopes of earthen embankments is usually examined by Swedish slip circle method or the slices method. The factor of safety against sliding using Fellenius procedure depends upon the angle formed by the arc of sliding at the center ψ and the radius of the slip circle r. The values of both mentioned parameters ψ and r aren't precisely predicted because they are measured from the drawing. In this paper, analytical formulae were derived for finding the exact values of both ψ and r. Also this paper presents the different conditions of intersections the slip circle with the body of an earthen dam and the coordinate of intersection points. Numerical examples are chosen for demonstration the proposed solution

Keywords: earthen dams stability, , earthen embankments stability, , Fellenius method, hydraulic structures, , side slopes stability, , slices method, Swedish slip circle

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Authors: Imran Muhammad

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The main cause of infectious disease in the modern world is Mycobacterium Tuberculosis (MT). To combat tuberculosis, new and efficient drugs are an urgent need in the modern world. Schif bases are potent for their biological pharmacophore activity. Thus we selected different Vanillin-based Schiff bases for their binding activity against target enzymes of Mycobacterium tuberculosis that is (DprE1 (decaprenyl phosphoryl-β-D-ribose 2′-epimerase), and DNA gyrase subunit-A), using molecular docking. We evaluate the inhibition potential, interaction, and binding mode of these compounds with the target enzymes.

Keywords: schiff bases, tuberculosis, DNA gyrase, DprE1, docking

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Authors: Syed Asif Hassan, Tabrej Khan

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Tuberculosis (TB) caused by bacillus Mycobacterium tuberculosis (Mtb) continues to take a disturbing toll on human life and healthcare facility worldwide. The global burden of TB remains enormous. The alarming rise of multi-drug resistant strains of Mycobacterium tuberculosis calls for an increase in research efforts towards the development of new target specific therapeutics against diverse strains of M. tuberculosis. Therefore, the discovery of new molecular scaffolds targeting new drug sites should be a priority for a workable plan for fighting resistance in Mycobacterium tuberculosis (Mtb). Mtb non-acylated lipoprotein LprG (Rv1411c) has a Toll-like receptor 2 (TLR2) agonist actions that depend on its association with triacylated glycolipids binding specifically with the hydrophobic pocket of Mtb LprG lipoprotein. The detection of a glycolipid carrier function has important implications for the role of LprG in Mycobacterial physiology and virulence. Therefore, considering the pivotal role of glycolipids in mycobacterial physiology and host-pathogen interactions, designing competitive antagonist (chemotherapeutics) ligands that competitively bind to glycolipid binding domain in LprG lipoprotein, will lead to inhibition of tuberculosis infection in humans. In this study, a unified approach involving ligand-based virtual screening protocol USRCAT (Ultra Shape Recognition) software and molecular docking studies using Auto Dock Vina 1.1.2 using the X-ray crystal structure of Mtb LprG protein was implemented. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the Ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has the higher hypothetical affinity, also has greater negative value. Based on the USRCAT, Lipinski’s values and molecular docking results, [(2R)-2,3-di(hexadecanoyl oxy)propyl][(2S,3S,5S,6R)-3,4,5-trihydroxy-2,6-bis[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6 (hydroxymethyl)tetrahydropyran-2-yl]oxy]cyclohexyl] phosphate (XPX) was confirmed as a promising drug-like lead compound (antagonist) binding specifically to the hydrophobic domain of LprG protein with affinity greater than that of PIM2 (agonist of LprG protein) with a free binding energy of -9.98e+006 Kcal/mol and binding affinity of -132 Kcal/mol, respectively. A further, in vitro assay of this compound is required to establish its potency in inhibiting molecular evasion mechanism of MTB within the infected host macrophages. These results will certainly be helpful in future anti-TB drug discovery efforts against Multidrug-Resistance Tuberculosis (MDR-TB).

Keywords: antagonist, agonist, binding affinity, chemotherapeutics, drug-like, multi drug resistance tuberculosis (MDR-TB), RV1411c protein, toll-like receptor (TLR2)

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Authors: Mohamed Abd Esselem Dems, Souhila Laib, Nadjia Latelli, Nadia Ouddai

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In this work, we have developed QSAR model for Relative Binding Affinity (RBA) of a large diverse set of estradiol among these derivatives, the organometallic derivatives. By dividing the dataset into a training set of 24 compounds and a test set of 6 compounds. The DFT method was used to calculate quantum chemical descriptors and physicochemical descriptors (MR and MLOGP) were performed using E-Dragon. All the validations indicated that the QSAR model built was robust and satisfactory (R2 = 90.12, Q2LOO = 86.61, RMSE = 0.272, F = 60.6473, Q2ext =86.07). We have therefore apply this model to predict the RBA, for two isomers β and α wherein Mn(CO)3 complex with the aromatic ring of estradiol, and the two isomers show little appreciation for the estrogenic receptor (RBAβ = 1.812 and RBAα = 1.741).

Keywords: DFT, estradiol, haptotropic rearrangement, QSAR, relative binding affinity

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Authors: Ridzuan Ramli, Zianor Azrina Zianon Abdin, Mohammad Dalour Beg, Rosli M. Yunus

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Nanocrystalline cellulose (NCC) were produced by using the ultrasound assisted acid hydrolysis from oil palm empty fruit bunch (EFB) pulp with different hydrolysis time then were analyzed by using FESEM and TGA as in comparison with EFB fiber and EFB pulp. Based on the FESEM analysis, it was found that NCC has a rod like shaped under the acid hydrolysis with an assistant of ultrasound. According to thermal stability, the NCC obtained show remarkable sign of high thermal stability compared to EFB fiber and EFB pulp. However, as the hydrolysis time increase, the thermal stability of NCC was deceased. As in conclusion, the NCC can be prepared by using ultrasound assisted acid hydrolysis. The NCC obtained have good thermal stability and have a great potential as the reinforcement in composite materials.

Keywords: Nanocrystalline cellulose, ultrasound assisted acid hydrolysis, thermal stability, morphology, empty fruit bunch (EFB)

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Authors: Abdulrahman M. Alsuhaibani, Martin Maken

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FACTS devices have great influence on the grid stability and power markets price. Recently, there is intent to integrate a large scale of renewable energy sources to the power system which in turn push the power system to operate closer to the security limits. This paper discusses the power system stability and reliability improvement that could be achieved by using FACTS. There is a comparison between FACTS devices to evaluate their performance for different functions. A case study has also been made about its effect on reducing generation cost and minimizing transmission losses which have good impact on efficient and economic operation of electricity markets

Keywords: FACTS, grid stability, spot price, OPF

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Authors: Nisha Budhwar, Sunita Daniel

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In this paper, we analyse the stability of the SEIR model of malaria with infective immigrants which was recently formulated by the authors. The model consists of an SEIR model for the human population and SI Model for the mosquitoes. Susceptible humans become infected after they are bitten by infectious mosquitoes and move on to the Exposed, Infected and Recovered classes respectively. The susceptible mosquito becomes infected after biting an infected person and remains infected till death. We calculate the reproduction number R0 using the next generation method and then discuss about the stability of the equilibrium points. We use the Lyapunov function to show the global stability of the equilibrium points.

Keywords: equilibrium points, exposed, global stability, infective immigrants, Lyapunov function, recovered, reproduction number, susceptible

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Authors: Sabri Arik

Abstract:

In this paper, we study the global asymptotic robust stability of delayed neural networks with norm-bounded uncertainties. By employing the Lyapunov stability theory and Homeomorphic mapping theorem, we derive some new types of sufficient conditions ensuring the existence, uniqueness and global asymptotic stability of the equilibrium point for the class of neural networks with discrete time delays under parameter uncertainties and with respect to continuous and slopebounded activation functions. An important aspect of our results is their low computational complexity as the reported results can be verified by checking some properties symmetric matrices associated with the uncertainty sets of network parameters. The obtained results are shown to be generalization of some of the previously published corresponding results. Some comparative numerical examples are also constructed to compare our results with some closely related existing literature results.

Keywords: neural networks, delayed systems, lyapunov functionals, stability analysis

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Authors: Xiaolin Li, Terence Turney, John Forsythe, Bryce Feltis, Paul Wright, Vinh Truong, Will Gates

Abstract:

Clay-hydrogel nanocomposites have attracted great attention recently, mainly because of their enhanced mechanical properties and ease of fabrication. Moreover, the unique platelet structure of clay nanoparticles enables the incorporation of bioactive molecules, such as proteins or drugs, through ion exchange, adsorption or intercalation. This study seeks to improve the mechanical and rheological properties of a novel hydrogel system, copolymerized from a tetrapodal polyethylene glycol (PEG) thiol and a linear, triblock PEG-PPG-PEG (PPG: polypropylene glycol) α,ω-bispropynoate polymer, with the simultaneous incorporation of various amounts of Na-saturated, montmorillonite clay (MMT) platelets (av. lateral dimension = 200 nm), to form a bioactive three-dimensional network. Although the parent hydrogel has controlled swelling ability and its PEG groups have good affinity for the clay platelets, it suffers from poor mechanical stability and is currently unsuitable for potential applications. Nanocomposite hydrogels containing 4wt% MMT showed a twelve-fold enhancement in compressive strength, reaching 0.75MPa, and also a three-fold acceleration in gelation time, when compared with the parent hydrogel. Interestingly, clay nanoplatelet incorporation into the hydrogel slowed down the rate of its dehydration in air. Preliminary results showed that protein binding by the MMT varied with the nature of the protein, as horseradish peroxidase (HRP) was more strongly bound than bovine serum albumin. The HRP was no longer active when bound, presumably as a result of extensive structural refolding. Further work is being undertaken to assess protein binding behaviour within the nanocomposite hydrogel for potential diabetic wound healing applications.

Keywords: hydrogel, nanocomposite, small molecule, wound healing

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Authors: Mohamad Ammar Ayass, Natalya Griko, Victor Pashkov, Wanying Cao, Kevin Zhu, Jin Zhang, Lina Abi Mosleh

Abstract:

Respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for coronavirus disease 2019 (COVID-19). Early evidence pointed at the angiotensin-converting enzyme 2 (ACE-2) expressed on the epithelial cells of the lung as the main entry point of SARS-CoV-2 into the cells. The viral entry is mediated by the binding of the Receptor Binding Domain (RBD) of the spike protein that is expressed on the surface of the virus to the ACE-2 receptor. As the number of SARS-CoV-2 variants continues to increase, mutations arising in the RBD of SARS-CoV-2 may lead to the ineffectiveness of RBD targeted neutralizing antibodies. To address this limitation, the objective of this study is to develop a combination of aptamers that target different regions of the RBD, preventing the binding of the spike protein to ACE-2 receptor and subsequent viral entry and replication. A safe and innovative biomedical tool was developed to inhibit viral infection and reduce the harms of COVID-19. In the present study, DNA aptamers were developed against a recombinant trimer S protein using the Systematic Evolution of Ligands by Exponential enrichment (SELEX). Negative selection was introduced at round number 7 to select for aptamers that bind specifically to the RBD domain. A series of 9 aptamers (ADI2010, ADI2011, ADI201L, ADI203L, ADI205L, ADIR68, ADIR74, ADIR80, ADIR83) were selected and characterized with high binding affinity and specificity to the RBD of the spike protein. Aptamers (ADI25, ADI2009, ADI203L) were able to bind and pull down endogenous spike protein expressed on the surface of SARS-CoV-2 virus in COVID-19 positive patient samples and determined by liquid chromatography- tandem mass spectrometry analysis (LC-MS/MS). LC-MS/MS data confirmed that aptamers can bind to the RBD of the spike protein. Furthermore, results indicated that the combination of the 9 best aptamers inhibited the binding of the purified trimer spike protein to the ACE-2 receptor found on the surface of Vero E6 cells. In the same experiment, the combined aptamers displayed a better neutralizing effect than antibodies. The data suggests that the selected aptamers could be used in therapy to neutralize the effect of the SARS-CoV-2 virus by inhibiting the interaction between the RBD and ACE-2 receptor, preventing viral entry into target cells and therefore blocking viral replication.

Keywords: aptamer, ACE-2 receptor, binding inhibitor, COVID-19, spike protein, SARS-CoV-2, treatment

Procedia PDF Downloads 183