Search results for: binding constant

Authors: Daohong Yang, Xiang Zhang, Lei Li, Wanting Zhou

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Visual Simultaneous Localization and Mapping (VSLAM) is a technology that obtains information in the environment for self-positioning and mapping. It is widely used in computer vision, robotics and other fields. Many visual SLAM systems, such as OBSLAM3, employ a constant-speed motion model that provides the initial pose of the current frame to improve the speed and accuracy of feature matching. However, in actual situations, the constant velocity motion model is often difficult to be satisfied, which may lead to a large deviation between the obtained initial pose and the real value, and may lead to errors in nonlinear optimization results. Therefore, this paper proposed a motion model based on acceleration, which can be applied on most SLAM systems. In order to better describe the acceleration of the camera pose, we decoupled the pose transformation matrix, and calculated the rotation matrix and the translation vector respectively, where the rotation matrix is represented by rotation vector. We assume that, in a short period of time, the changes of rotating angular velocity and translation vector remain the same. Based on this assumption, the initial pose of the current frame is estimated. In addition, the error of constant velocity model was analyzed theoretically. Finally, we applied our proposed approach to the ORBSLAM3 system and evaluated two sets of sequences on the TUM dataset. The results showed that our proposed method had a more accurate initial pose estimation and the accuracy of ORBSLAM3 system is improved by 6.61% and 6.46% respectively on the two test sequences.

Keywords: error estimation, constant acceleration motion model, pose estimation, visual SLAM

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Authors: Lavinia Ruta, Ileana Farcasanu

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The yeast surface display (YSD) technique enables the expression of proteins on yeast cell surfaces, facilitating the identification and isolation of proteins with targeted binding properties, such as nanobodies. Nanobodies, derived from camelid species, are single-domain antibody fragments renowned for their high affinity and specificity towards target proteins, making them valuable in research and potentially in therapeutics. Their advantages include a compact size (~15 kDa), robust stability, and the ability to target challenging epitopes. The project endeavors to establish and validate a platform for producing Green Fluorescent Protein (GFP) and mCherry nanobodies using the yeast surface display method. mCherry, a prevalent red fluorescent protein sourced from coral species, is commonly utilized as a genetic marker in biological studies due to its vibrant red fluorescence. The GFP-nanobody, a single variable domain of heavy-chain antibodies (VHH), exhibits specific binding to GFP, offering a potent means for isolating and engineering fluorescent protein fusions across various biological research domains. Both GFP and mCherry nanobodies find specific utility in cellular imaging and protein analysis applications.

Keywords: YSD, nanobodies, GFP, Saccharomyces cerevisiae

Procedia PDF Downloads 35

Authors: Mona Alharbi

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Melioidosis has emerged as a lethal disease. Unfortunately, the molecular mechanisms of virulence and pathogenicity of Burkholderia pseudomallei remain unknown. However, proteomics research has selected putative targets in B. pseudomallei that might play roles in the B. pseudomallei virulence. BPSL 2418 putative protein has been predicted as a free methionine sulfoxide reductase and interestingly there is a link between the level of the methionine sulfoxide in pathogen tissues and its virulence. Therefore in this work, we describe the cloning expression, purification, and crystallization of BPSL 2418 and the solution of its 3D structure using X-ray crystallography. Also, we aimed to identify the substrate binding and reduced forms of the enzyme to understand the role of BPSL 2418. The gene encoding BPSL2418 from B. pseudomallei was amplified by PCR and reclone in pETBlue-1 vector and transformed into E. coli Tuner DE3 pLacI. BPSL2418 was overexpressed using E. coli Tuner DE3 pLacI and induced by 300μM IPTG for 4h at 37°C. Then BPS2418 purified to better than 95% purity. The pure BPSL2418 was crystallized with PEG 4000 and PEG 6000 as precipitants in several conditions. Diffraction data were collected to 1.2Å resolution. The crystals belonged to space group P2 21 21 with unit-cell parameters a = 42.24Å, b = 53.48Å, c = 60.54Å, α=γ=β= 90Å. The BPSL2418 binding MES was solved by molecular replacement with the known structure 3ksf using PHASER program. The structure is composed of six antiparallel β-strands and four α-helices and two loops. BPSL2418 shows high homology with the GAF domain fRMsrs enzymes which suggest that BPSL2418 might act as methionine sulfoxide reductase. The amino acids alignment between the fRmsrs including BPSL 2418 shows that the three cysteines that thought to catalyze the reduction are fully conserved. BPSL 2418 contains the three conserved cysteines (Cys⁷⁵, Cys⁸⁵ and Cys¹⁰⁹). The active site contains the six antiparallel β-strands and two loops where the disulfide bond formed between Cys⁷⁵ and Cys¹⁰⁹. X-ray structure of free methionine sulfoxide binding and native forms of BPSL2418 were solved to increase the understanding of the BPSL2418 catalytic mechanism.

Keywords: X-Ray Crystallography, BPSL2418, Burkholderia pseudomallei, Melioidosis

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Authors: E. Taslak, C. Kocatepe, O. Arıkan, C. F. Kumru

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In insulation and cooling of power transformers various liquids are used. Mineral oils have wide availability and low cost. However, they have a poor biodegradability potential and lower fire point in comparison with other insulating liquids. Use of a liquid having high biodegradability is important due to environmental consideration. This paper investigates edible corn oil as an alternative to mineral oil. Various properties of mineral and corn oil like breakdown voltage, dissipation factor, relative dielectric constant, power loss and resistivity were measured according to different standards.

Keywords: breakdown voltage, corn oil, dissipation factor, mineral oil, power loss, relative dielectric constant, resistivity

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Authors: Saurabh B. Ganorkar, Atul A. Shirkhedkar

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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 176

Authors: Strahinja Kovačević, Sanja Podunavac-Kuzmanović, Lidija Jevrić, Milica Karadžić

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The present study is based on the quantitative structure-activity relationship (QSAR) analysis of eighteen compounds with anti-prion activity. The structures and anti-prion activities (expressed in response units, RU%) of the analyzed compounds are taken from CHEMBL database. In the first step of analysis 85 molecular descriptors were calculated and based on them the hierarchical cluster analysis (HCA) and principal component analysis (PCA) were carried out in order to detect potential significant similarities or dissimilarities among the studied compounds. The calculated molecular descriptors were physicochemical, lipophilicity and ADMET (absorption, distribution, metabolism, excretion and toxicity) descriptors. The first stage of the QSAR analysis was simple linear regression modeling. It resulted in one acceptable model that correlates Henry's law constant with RU% units. The obtained 2D-QSAR model was validated by cross-validation as an internal validation method. The validation procedure confirmed the model’s quality and therefore it can be used for prediction of anti-prion activity. The next stage of the analysis of anti-prion activity will include 3D-QSAR and molecular docking approaches in order to select the most promising compounds in treatment of prion diseases. These results are the part of the project No. 114-451-268/2016-02 financially supported by the Provincial Secretariat for Science and Technological Development of AP Vojvodina.

Keywords: anti-prion activity, chemometrics, molecular modeling, QSAR

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

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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

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Authors: Lina Wu, Jia Liu, Ye Li

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The goal of this project is to investigate constant properties (called the Liouville-type Problem) for a p-stable map as a local or global minimum of a p-energy functional where the domain is a Euclidean space and the target space is a closed half-ellipsoid. The First and Second Variation Formulas for a p-energy functional has been applied in the Calculus Variation Method as computation techniques. Stokes’ Theorem, Cauchy-Schwarz Inequality, Hardy-Sobolev type Inequalities, and the Bochner Formula as estimation techniques have been used to estimate the lower bound and the upper bound of the derived p-Harmonic Stability Inequality. One challenging point in this project is to construct a family of variation maps such that the images of variation maps must be guaranteed in a closed half-ellipsoid. The other challenging point is to find a contradiction between the lower bound and the upper bound in an analysis of p-Harmonic Stability Inequality when a p-energy minimizing map is not constant. Therefore, the possibility of a non-constant p-energy minimizing map has been ruled out and the constant property for a p-energy minimizing map has been obtained. Our research finding is to explore the constant property for a p-stable map from a Euclidean space into a closed half-ellipsoid in a certain range of p. The certain range of p is determined by the dimension values of a Euclidean space (the domain) and an ellipsoid (the target space). The certain range of p is also bounded by the curvature values on an ellipsoid (that is, the ratio of the longest axis to the shortest axis). Regarding Liouville-type results for a p-stable map, our research finding on an ellipsoid is a generalization of mathematicians’ results on a sphere. Our result is also an extension of mathematicians’ Liouville-type results from a special ellipsoid with only one parameter to any ellipsoid with (n+1) parameters in the general setting.

Keywords: Bochner formula, Calculus Stokes' Theorem, Cauchy-Schwarz Inequality, first and second variation formulas, Liouville-type problem, p-harmonic map

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Authors: Byoung-Hee Lee

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Wireless battery charger with adaptive rapid charging algorithm is proposed. The proposed wireless charger adopts voltage regulation technique to reduce the number of power conversion steps. Moreover, based on battery models, an adaptive rapid charging algorithm for Li-ion batteries is obtained. Rapid-charging performance with the proposed wireless battery charger and the proposed rapid charging algorithm has been experimentally verified to show more than 70% charging time reduction compared to conventional constant-current constant-voltage (CC-CV) charging without the degradation of battery lifetime.

Keywords: wireless, battery charger, adaptive, rapid-charging

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Authors: Hamid Hossein Khezri, Afsaneh Javdani-Mallak

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Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors. Cannabidiol (CBD) is one of the members of cannabinoid compounds found in cannabis. CBD and Cannabinol (CBN), as the other extract of plant Cannabis were able to reduce myofascial pain in rats with immunosuppressive and anti-inflammatory activities. In this study, we accomplished protein-protein BLAST, and the sequence was found to be for Gamma-aminobutyric acid receptor subunit alpha-1 (GBRA1) chain A and its 3D structure was subsequently downloaded from Protein Data Bank. The structures of the ligands, cannabinol, and cannabidiol, were obtained from PubChem. After the necessary process of the obtained files, AutoDock Vina was used to perform molecular docking. Docking between the ligands and GBRA1 chain A revealed that cannabinol has a higher affinity to GBRA1 (binding energy = -7.5 kcal/mol) compared to cannabidiol (binding energy = -6.5 kcal/mol). Furthermore, cannabinol seems to be able to interact with 10 residues of the protein, out of which 3 are in the neurotransmitter-gated ion-channel transmembrane domain of GBRA1, whereas cannabidiol interacts with two other residues. Although the results of this project do not indicate the activating /or inhibitory capability of the studied compounds, it suggests that cannabinol can act as a relatively strong ligand for GBRA1.

Keywords: protein-ligand docking, cannabinol, cannabidiol, GBRA1

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Authors: Mariam Mojally, Randa Abdou, Wisal Bokhari, Sultan Sab, Mohammed Dawoud, Amjad Albohy

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Secondary metabolites produced by endophytes are an excellent source of biologically active compounds. In our current study, we evaluated terezine E and 14-hydroxyterezine D for binding to the active site of histone deacetylase (PDB ID: 4CBT) and matrix metalloproteinase 9 (PDB ID: 4H3X) by molecular docking using AutoDock Vina software after having tested their cytotoxic activities on three cell lines (human ductal breast epithelial tumor cells (T47D)-HCC1937), human hepatocarcinoma cell line (HepG2)-HB8065), and human colorectal carcinoma cells (HCT-116)-TCP1006, purchased from ATCC, USA)). Additionally, their antimicrobial activities were investigated, and their minimum inhibitory concentration (MIC) values were determined against P. notatum and S. aureus by the broth microdilution method. Higher cytotoxicity was observed for terezine E against all tested cell lines compared to 14-hydroxyterezine D. Molecular docking results supported the high cytotoxicity of terezine E and showed higher binding affinity with 4CBT with an energy score of 9 kcal/mol. Terezine E showed higher antibacterial and antifungal activities than 14-hydroxyrerezine D: MIC values were 15.45 and 21.73 mg/mL against S. aureus and 8.61 and 11.54 mg/mL against P. notatum, respectively

Keywords: Terezine E, 14-Hydroxyterezine D, cytotoxicity, antimicrobial activity, molecular docking

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Authors: Abdul Matin, Salik Nawaz, Suk-Yul Jung

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Balamuthia mandrillaris is well known to cause fatal Balamuthia amoebic encephalitis (BAE). Amoebic transmission into the central nervous system (CNS), haematogenous spread is thought to be the prime step, followed by blood-brain barrier (BBB) dissemination. Macrophages are considered to be the foremost line of defense and present in excessive numbers during amoebic infections. The aim of the present investigation was to evaluate the effects of macrophages alone or primed with cytokines on the biological characteristics of Balamuthia in vitro. Using human brain microvascular endothelial cells (HBMEC), which constitutes the BBB, we have shown that Balamuthia demonstrated > 90% binding and > 70% cytotoxicity to host cells. However, macrophages further increased amoebic binding and Balamuthia-mediated cell cytotoxicity. Furthermore, macrophages exhibited no amoebicidal effect against Balamuthia. Zymography assay demonstrated that macrophages exhibited no inhibitory effect on proteolytic activity of Balamuthia. Overall, to our best knowledge, we have shown for the first time macrophages has no inhibitory effects on the biological properties of Balamuthia in vitro. This also strengthened the concept that how and why Balamuthia can cause infections in both immuno-competent and immuno-compromised individuals.

Keywords: Balamuthia mandrillaris, macrophages, cytokines, human brain microvascular endothelial cells, Balamuthia amoebic encephalitis

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Authors: Aidan Battison, Neliswa Mama

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Environmental pollution by ionic species has been identified as one of the biggest challenges to the sustainable development of communities. The widespread use of organic and inorganic chemical products and the release of toxic chemical species from industrial waste have resulted in a need for advanced monitoring technologies for environment protection, remediation and restoration. Some of the disadvantages of conventional sensing methods include expensive instrumentation, well-controlled experimental conditions, time-consuming procedures and sometimes complicated sample preparation. On the contrary, the development of fluorescent chemosensors for biological and environmental detection of metal ions has attracted a great deal of attention due to their simplicity, high selectivity, eidetic recognition, rapid response and real-life monitoring. Coumarin derivatives S1 and S2 (Scheme 1) containing 1,2,3-triazole moieties at position -3- have been designed and synthesized from azide and alkyne derivatives by CuAAC “click” reactions for the detection of metal ions. These compounds displayed a strong preference for Fe3+ ions with complexation resulting in fluorescent quenching through photo-induced electron transfer (PET) by the “sphere of action” static quenching model. The tested metal ions included Cd2+, Pb2+, Ag+, Na+, Ca2+, Cr3+, Fe3+, Al3+, Cd2+, Ba2+, Cu2+, Co2+, Hg2+, Zn2+ and Ni2+. The detection limits of S1 and S2 were determined to be 4.1 and 5.1 uM, respectively. Compound S1 displayed the greatest selectivity towards Fe3+ in the presence of competing for metal cations. S1 could also be used for the detection of Fe3+ in a mixture of CH3CN/H¬2¬O. Binding stoichiometry between S1 and Fe3+ was determined by using both Jobs-plot and Benesi-Hildebrand analysis. The binding was shown to occur in a 1:1 ratio between the sensor and a metal cation. Reversibility studies between S1 and Fe3+ were conducted by using EDTA. The binding site of Fe3+ to S1 was determined by using 13 C NMR and Molecular Modelling studies. Complexation was suggested to occur between the lone-pair of electrons from the coumarin-carbonyl and the triazole-carbon double bond.

Keywords: chemosensor, "click" chemistry, coumarin, fluorescence, static quenching, triazole

Procedia PDF Downloads 138

Authors: Hamid Hossein Khezri, Afsaneh Javdani-Mallak

Abstract:

Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors. Cannabidiol (CBD) is one of the members of cannabinoid compounds found in cannabis. CBD and Cannabinol (CBN), as the other extract of plant Cannabis, were able to reduce myofascial pain in rats with immunosuppressive and anti-inflammatory activities. In this study, we accomplished protein-protein BLAST and the sequence was found to be for Gamma-aminobutyric acid receptor subunit alpha-1 (GBRA1) chain A and its 3D structure was subsequently downloaded from Protein Data Bank. The structures of the ligands cannabinol and cannabidiol were obtained from PubChem. After a necessary process of the obtained files, AutoDock Vina was used to performing molecular docking. Docking between the ligands and GBRA1 chain A revealed that cannabinol has a higher affinity to GBRA1 (binding energy = -7.5 kcal/mol) compared to cannabidiol (binding energy = -6.5 kcal/mol). Furthermore, cannabinol seems to be able to interact with 10 residues of the protein, out of which 3 are in the neurotransmitter-gated ion-channel transmembrane domain of GBRA1, whereas cannabidiol interacts with two other residues. Although the results of this project do not indicate the activating /or inhibitory capability of the studied compounds, it suggests that cannabinol can act as a relatively strong ligand for GBRA1.

Keywords: protein-ligand docking, cannabinol, cannabidiol, GBRA1

Procedia PDF Downloads 98

Authors: Azhar Jabareen, Mahmoud Huleihel

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BRCA-1 is a multifunctional tumor suppressor, whose expression is activated by the estrogen (E2)-liganded ERα receptor. The activated ERα is a transcriptional factor which activates various genes either by direct binding to the DNA at E2-responsive elements (EREs) and indirectly associated with a range of alternative non-ERE elements. Interference with BRCA-1 expression and/or functions leads to high risk of breast or/and ovarian cancer. Our lab investigated the involvement of Human T-cell leukemia Virus Type 1 (HTLV-1) in breast cancer, since HTLV-1 Tax was found to strongly inhibit BRCA-1 expression. In addition, long exposure of 12-O-tetradecanoylphorbol-13-acetate (TPA), which is one of the stress-inducing agents activated the HTLV-1 promoter. So here the involvement of TPA in breast cancer had been examined by testing the effect of TPA on BRCA-1 and ERE expression. The results showed that TPA activated both BRCA-1 and ERE expression. In the 12 hours TPA activated the tow promoters more than others time, and after 24 hours the level of the tow promoters was decreased. Tax inhibited BRCA-1 expression but did not succeed to inhibit the effect of TPA. Then the activation of the two promoters was not through ERα pathway because TPA had no effect on ERα binding to the two promoters of the BRCA-1 and ERE. Also, the activation was not via nuclear factor kappa B (NF-κB) pathway because when the inhibitory of NF-κB had been added to the TPA, it still activated the tow promoters. However, it seems that 53BP1 may be involved in TPA activation of these promoters because ectopic high expression of 53BP1 significantly reduced the TPA activity. In addition, in the presence of Bisindolylmaleimide-I (BI)- the inhibitor of Protein Kinase C (PKC)- there was no activation for the two promoters, so the PKC is agonized BRCA-1 and ERE activation.

Keywords: BRCA-1, ERE, HTLV-1, TPA

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Authors: William Thomas Worster

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This paper will highlight the failure of international adjudication to prevent a state from evading an order of provisional measures by simply issuing a diplomatic assurance to the court. This practice changes the positions of the litigants as equals before a court, prevents the court from inquiring into the reliability of the political pledge as it would with assurances from a state to an individual, and diminishes the court’s ability to control its own proceedings in the face of concerns over sovereignty. Both the European Court of Human Rights (ECtHR) and International Court of Justice (ICJ) will entertain these kinds of unilateral pledges, but they consider them differently when the declaration is made between states or between a state and an individual, and when made directly to the court. In short, diplomatic assurances issued between states or to individuals are usually considered not to be legally binding and are essentially questions of fact, but unilateral assurances issued directly to an international court are questions of law, and usually legally binding. At the same time, orders for provisional measures are now understood also to be legally binding, yet international courts will sometimes permit a state to substitute an assurance in place of an order for provisional measures. This emerging practice has brought the nature of a state as a sovereign capable of creating legal obligations into the forum of adjudication where the parties should have equality of arms and permitted states to create legal obligations that escape inquiry into the reliability of the outcome. While most recent practice has occurred at the ICJ in state-to-state litigation, there is some practice potentially extending the practice to human rights courts. Especially where the litigants are factually unequal – a state and an individual – this practice is problematic since states could more easily overcome factual failings in their pledges and evade the control of the court. Consider, for example, the potential for evading non-refoulement obligations by extending the current diplomatic assurances practice from the state-to-state context to the state-to-court context. The dual nature of assurances, as both legal and factual instruments, should be considered as addressed to distinct questions, each with its own considerations, and that we need to be more demanding about their precise legal and factual effects.

Keywords: unilateral, diplomacy, assurances, undertakings, provisional measures, interim measures

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Authors: Ceren Vardar Acar, Mine Caglar

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In finance, the price of a volatile asset can be modeled using fractional Brownian motion (fBm) with Hurst parameter H>1/2. The Black-Scholes model for the values of returns of an asset using fBm is given as, 〖Y_t=Y_0 e^((r+μ)t+σB)〗_t^H, 0≤t≤T where Y_0 is the initial value, r is constant interest rate, μ is constant drift and σ is constant diffusion coefficient of fBm, which is denoted by B_t^H where t≥0. Black-Scholes model can be constructed with some Markov processes such as Brownian motion. The advantage of modeling with fBm to Markov processes is its capability of exposing the dependence between returns. The real life data for a volatile asset display long-range dependence property. For this reason, using fBm is a more realistic model compared to Markov processes. Investors would be interested in any kind of information on the risk in order to manage it or hedge it. The maximum possible loss is one way to measure highest possible risk. Therefore, it is an important variable for investors. In our study, we give some theoretical bounds on the distribution of maximum possible loss of fBm. We provide both asymptotical and strong estimates for the tail probability of maximum loss of standard fBm and fBm with drift and diffusion coefficients. In the investment point of view, these results explain, how large values of possible loss behave and its bounds.

Keywords: maximum drawdown, maximum loss, fractional brownian motion, large deviation, Gaussian process

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Authors: Yu-Jen Shih, Juan-Zhang Lou

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Nitrogenous compounds, such as NH4+/NH3 and NO3-, have become important contaminants in water resources. Excessive concentration of NH3 leads to eutrophication, which poses a threat to aquatic organisms in the environment. Electrochemical oxidation emerged as a promising water treatment technology, offering advantages such as simplicity, small-scale operation, and minimal reliance on additional chemicals. In this study, a nickel-based metal-organic framework (Ni-MOF) was synthesized using 2-amino terephthalic acid (BDC-NH2) and nickel nitrate. The Ni-MOF was further carbonized as derived nickel oxide and nitrogen-carbon composite, Ni/NiOx/NC. The nickel oxide within the 2D porous carbon texture served as active sites for ammonia oxidation. Results of characterization showed that the Ni-MOF was a hexagonal and flaky nanoparticle. With increasing carbonization temperature, the nickel ions in the organic framework re-crystallized as NiO clusters on the surfaces of the 2D carbon. The electrochemical surface area of Ni/NiOx/NC significantly increased as to improve the efficiency of ammonia oxidation. The phase transition of Ni(OH)2⇌NiOOH at around +0.8 V was the primary mediator of electron transfer. Batch electrolysis was conducted under constant current and constant potential modes. The electrolysis parameters included pyrolysis temperatures, pH, current density, initial feed concentration, and electrode potential. The constant current batch experiments indicated that via carbonization at 800 °C, Ni/NiOx/NC(800) was able to decrease the ammonium nitrogen of 50 mg-N/L to below 1 ppm within 4 hours at a current density of 3 mA/cm2 and pH 11 with negligible oxygenated nitrogen formation. The constant potential experiments confirmed that N2 nitrogen selectivity was enhanced up to 90% at +0.8 V.

Keywords: electrochemical oxidation, nickel oxyhydroxide, metal-organic framework, ammonium, nitrate

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Authors: Son Nguyen, Thanh Van, Ly Le

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Ca2+ - dependent calmodulin kinase IIa (CaMKIIa) has recently been found to associate with protein tau missorting and polymerization in Alzheimer’s Disease (AD). However, there has yet inhibitors targeting CaMKIIa to investigate the correlation between CaMKIIa activity and protein tau polymer formation. Combining virtual screening and our statistics in binding contribution scoring function (BCSF), we rationally identified potential compounds that bind to specific CaMKIIa active site and specificity-affinity distribution of the ligand within the active site. Using molecular dynamics simulation, we identified structural stability of CaMKIIa and potent inhibitors, and site-directed bonding, separating non-specific and specific molecular interaction features. Despite of variation in confirmation of simulation time, interactions of the potent inhibitors were found to be strongly associated with the unique chemical features extracted from molecular binding poses. In addition, competitive inhibitors within CaMKIIa showed an important molecular recognition pattern toward specific ligand features. Our approach combining virtual screening with BCSF may provide an universally applicable method for precise identification in the discovery of compounds.

Keywords: Alzheimer’s disease, Ca 2+ -dependent calmodulin kinase IIa, protein tau, molecular docking

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Authors: Endris Yibru Hanurry, Wei-Hsin Hsu, Hsieh-Chih Tsai

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In recent years, the discovery of small interfering RNAs (siRNAs) has got great attention for the treatment of cancer and other diseases. However, the therapeutic efficacy of siRNAs has been faced with many drawbacks because of short half-life in blood circulation, poor membrane penetration, weak endosomal escape and inadequate release into the cytosol. To overcome these drawbacks, we designed a non-viral vector by conjugating polyamidoamine generation 4.5 dendrimer (PDG4.5) with diethylenetriamine (DETA)- and tetraethylenepentamine (TEPA) followed by binding with siRNA to form polyplexes through electrostatic interaction. The result of 1H nuclear magnetic resonance (NMR), 13C NMR, correlation spectroscopy, heteronuclear single–quantum correlation spectroscopy, and Fourier transform infrared spectroscopy confirmed the successful conjugation of DETA and TEPA with PDG4.5. Then, the size, surface charge, morphology, binding ability, stability, release assay, toxicity and cellular internalization were analyzed to explore the physicochemical and biological properties of PDG4.5-DETA and PDG4.5-TEPA polyplexes at specific N/P ratios. The polyplexes (N/P = 8) exhibited spherical nanosized (125 and 85 nm) particles with optimum surface charge (13 and 26 mV), showed strong siRNA binding ability, protected the siRNA against enzyme digestion and accepted biocompatibility to the HeLa cells. Qualitatively, the fluorescence microscopy image revealed the delocalization (Manders’ coefficient 0.63 and 0.53 for PDG4.5-DETA and PDG4.5-TEPA, respectively) of polyplexes and the translocation of the siRNA throughout the cytosol to show a decent cellular internalization and intracellular biodistribution of polyplexes in HeLa cells. Quantitatively, the flow cytometry result indicated that a significant (P < 0.05) amount of siRNA was internalized by cells treated with PDG4.5-DETA (68.5%) and PDG4.5-TEPA (73%) polyplexes. Generally, PDG4.5-DETA and PDG4.5-TEPA were ideal nanocarriers of siRNA in vitro and might be used as promising candidates for in vivo study and future pharmaceutical applications.

Keywords: non-viral carrier, oligoalkylamine, poly(amidoamine) dendrimer, polyplexes, siRNA

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Authors: Owonikoko Abayomi Dele

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Epilepsy is an unresolved disease that needs urgent attention. It is a brain disorder that affects over sixty-five (65) million people around the globe. Despite the availability of commercial anti-epileptic drugs, the war against this unmet condition is yet to be resolved. Most epilepsy patients are resistant to available anti-epileptic medications thus the need for affordable novel therapy against epilepsy is a necessity. Numerous phytochemicals have been reported for their potency, efficacy and safety as therapeutic agents against many diseases. This study investigated 99 isolated phytochemicals from Chasmanthera dependens and Carissa edulis against carbonic anhydrase (ii) drug target. The absorption, distribution, metabolism, excretion and toxicity (ADMET) of the isolated compounds were examined using admet SAR-2 web server while Swiss ADME was used to analyze the oral bioavailability, drug-likeness and lead-likeness properties of the selected leads. PASS web server was used to predict the biological activities of selected leads while other important physicochemical properties and interactions of the selected leads with the active site of the target after successful molecular docking simulation with the pyrx virtual screening tool were also examined. The results of these study identified seven lead compounds; C49- alpha-carissanol (-7.6 kcal/mol), C13- Catechin (-7.4 kcal/mol), C45- Salicin (-7.4 kcal/mol), C6- Bisnorargemonine (-7.3 kcal/mol), C36- Pallidine (-7.1 kcal/mol), S4- Lacosamide (-7.1 kcal/mol), and S7- Acetazolamide (-6.4 kcal/mol) for CA II (3HS4 receptor). These leads compounds are probable inhibitors of this drug target due to the observed good binding affinities and favourable interactions with the active site of the drug target, excellent ADMET profiles, PASS Properties, drug-likeness, lead-likeness and oral bioavailability properties. The identified leads have better binding energies as compared to the binding energies of the two standards. Thus, seven identified lead compounds can be developed further towards the development of new anti-epileptic medications.

Keywords: drug-likeness, phytochemicals, carbonic anhydrases, metalloeazymes, active site, ADMET

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Authors: M. Insiat Islam Rabby, M. Mahbubur Rahman, Eshanul Islam, A. K. M. Sadrul Islam

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The numerical and simulative analysis of laminar heat exchange convection of aluminum oxide (Al₂O₃) - water nanofluid for the developed region through two parallel plates is presented in this present work. The second order single phase energy equation, mass and momentum equation are solved by using finite volume method with the ANSYS FLUENT 16 software. The distance between two parallel plates is 4 mm and length is 600 mm. Aluminum oxide (Al₂O₃) is used as nanoparticle and water is used as the base/working fluid for the investigation. At the time of simulation 1% to 5% volume concentrations of the Al₂O₃ nanoparticles are used for mixing with water to produce nanofluid and a wide range of interval of Reynolds number from 500 to 1100 at constant heat flux 500 W/m² at the channel wall has also been introduced. The result reveals that for increasing the Reynolds number the Nusselt number and heat transfer coefficient are increased linearly and friction factor decreased linearly in the developed region for both water and Al₂O₃-H₂O nanofluid. By increasing the volume fraction of Al₂O₃-H₂O nanofluid from 1% to 5% the value of Nusselt number increased rapidly from 0.7 to 7.32%, heat transfer coefficient increased 7.14% to 31.5% and friction factor increased very little from 0.1% to 4% for constant Reynolds number compared to pure water. At constant heat transfer coefficient 700 W/m2-K the pumping power advantages have been achieved 20% for 1% volume concentration and 62% for 3% volume concentration of nanofluid compared to pure water.

Keywords: convective heat transfer, pumping power, constant heat flux, nanofluid, nanoparticles, volume concentration, thermal conductivity

Procedia PDF Downloads 146

Authors: Rawa Delshada, Sanaa G. Hamab, Rastee D. Koyeec

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Eighty patients with suspected ischemic heart disease were enrolled in the present study. They were classified into two groups: patients with positive exercise stress test results (n=40) and control group with negative exercise stress test results (n=40). Serum concentration of troponin I, Heart-type Fatty Acid Binding Protein (H-FABP) and Ischemia Modified Albumin (IMA) were measured one hour after performing stress test. Enzyme Linked Immunosorbent Assay was used to measure both troponin I, H-FABP levels, while IMA levels were measured by albumin cobalt binding test. There was no statistically significant difference in the mean concentration of troponin I between two groups (0.75±0.55ng/ml) for patients with positive test result vs. (0.71±0.55ng/ml) for negative test result group with P>0.05. Contrary to our expectation, mean IMA level was slightly higher among control group (70.88±39.76U/ml) compared to (62.7±51.9U/ml) in positive test result group, but still with no statistically significant difference (P>0.05). Median H-FABP level was also higher among negative exercise stress testing group compared the positive one (2ng/ml vs. 1.9ng/ml respectively), but failed to reach statistically significant difference (P>0.05). When quartiles model used to explore the possible association between each study biomarkers with the others; serum H-FABP level was lowest (1.7ng/ml) in highest quartile of IMA and lowest H-FABP (1.8ng/ml) in highest quartile of troponin I but with no statistically significant association (P>0.05). Myocardial ischemia, more likely occurred after exercise stress test, is not capable of causing troponin I release. Furthermore, an increase in H-FABP and IMA levels after stress test are not reflecting myocardial ischemia. Moreover, the combination of troponin I, H-FABP and IMA after measuring their post exercise levels does not improve the diagnostic utility of exercise stress test enormously.

Keywords: cardiac biomarkers, ischemic heart disease, troponin I, ischemia modified albumin, heart-type fatty acid binding protein, exercise stress testing

Procedia PDF Downloads 234

Authors: Ria Forner

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Introduction: Due to increases in the SNR at 7T and above, it becomes more favourable to make use of X-nuclear imaging. Integrated body coils tuned to 120MHz for 31P, 79MHz for 23Na, and 75 MHz for 13C at 7T were simulated with a human male, female, or child body model to assess strategies of use for metabolic MR imaging in the body. Methods: B1 and SAR efficiencies in the heart, liver, spleen, and kidneys were assessed using numerical simulations over the three frequencies with phase shimming. Results: B1+ efficiency is highly variable over the different organs, particularly for the highest frequency; however, local SAR efficiency remains relatively constant over the frequencies in all subjects. Although the optimal phase settings vary, one generic phase setting can be identified for each frequency at which the penalty in B1+ is at a max of 10%. Discussion: The simulations provide practical strategies for power optimization, B1 management, and maintaining safety. As expected, the B1 field is similar at 75MHz and 79MHz, but reduced at 120MHz. However, the B1 remains relatively constant when normalised by the square root of the peak local SAR. This is in contradiction to generalized SAR considerations of 1H MRI at different field strengths, which is defined by global SAR instead. Conclusion: Although the B1 decreases with frequency, SAR efficiency remains constant throughout the investigated frequency range. It is possible to shim the body coil to obtain a maximum of 10% extra B1+ in a specific organ in a body when compared to a generic setting.

Keywords: birdcage, multi-nuclear, B1 shimming, 7 Tesla MRI, liver, kidneys, heart, spleen

Procedia PDF Downloads 38

Authors: Seyed Amin Vakili, Sahar Sadat Vakili, Seyed Ehsan Vakili, Nader Abdoli Yazdi

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The main purpose of this paper is to present the Modified Newmark Method of buckling analysis frame considering the effect of the axial load. The discussion will be restricted to plane frameworks containing a constant cross-section for each element. In addition, it is assumed that the frames are prevented from out-of-plane deflection. In this method, stiffness matrix of the structure is considered to be constant. The most important advantage of such a method is that it obtains both upper and lower critical loads. The advanced of the present method is fast convergence, ability to use computer simulations, and ability to model structures with semi-rigid support conditions using linear and rotational spring.

Keywords: buckling, stability, frame, modified newmark method

Procedia PDF Downloads 389

Authors: Sina Ranjbar, Masakiyo Tsunoda, Mikihiko Oogane, Yasuo Ando

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We systematically investigated the exchange anisotropy for ferromagnetic Co70Fe30 and antiferromagnetic PtMn bilayer films. We focused on the relevance between the exchange bias and the composition of the Ptₓ Mn₁₋ₓ (14 < x < 22 and 45 < x < 56 at %) films, and we successfully optimized the composition. The crystal structure of the Ptₓ Mn₁₋ₓ films was FCC for 14 < x < 22 at % and FCT for 45 < x < 56 at % after annealing at 370 ◦C for 6 hours. The unidirectional anisotropy constant (Jₖ) for fcc-Pt₁₅Mn₈₅ (20 nm) and fct-Pt₄₈Mn₅₂ (20 nm) prepared under optimum conditions in composition were 0.16 and 0.20 erg/cm², respectively. Both Pt₁₅Mn₈₅ and Pt₄₈Mn₅₂ films showed a larger unidirectional anisotropy constant (Jₖ) than in other reports. They also showed a flatter surface than that of other antiferromagnetic materials. The obtained PtMn films with a large exchange anisotropy and slight roughness are useful as an antiferromagnetic layer in spintronic applications.

Keywords: antiferromagnetic material, PtMn thin film, exchange anisotropy, composition dependence

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Authors: Uzma Saqib, Mirza S. Baig

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Myeloid differentiation primary response protein 88 (MYD88) has long been considered a central player in the inflammatory pathway. Recent studies clearly suggest that it is an important therapeutic target in inflammation. On the other hand, a recent study on the interaction between the orphan nuclear receptor (Nur77) and p38α, leading to increased lipopolysaccharide-induced hyperinflammatory response, suggests this binary complex as a therapeutic target. In this study, we have designed inhibitors that can inhibit both MYD88 and Nur77 at the same time. Since both MYD88 and Nur77 are an integral part of the pathways involving lipopolysaccharide-induced activation of NF-κB-mediated inflammation, we tried to target both proteins with the same library in order to retrieve compounds having dual inhibitory properties. To perform this, we developed a homodimeric model of MYD88 and, along with the crystal structure of Nur77, screened a virtual library of compounds from the traditional Chinese medicine database containing ~61,000 compounds. We analyzed the resulting hits for their efficacy for dual binding and probed them for developing a common pharmacophore model that could be used as a prototype to screen compound libraries as well as to guide combinatorial library design to search for ideal dual-target inhibitors. Thus, our study explores the identification of novel leads having dual inhibiting effects due to binding to both MYD88 and Nur77 targets.

Keywords: drug design, Nur77, MYD88, inflammation

Procedia PDF Downloads 287

Authors: S. M. Mahdi Niktabara, K. Seshagiri Raob, Amit Kumar Shrivastavac, Jiří Ščučkaa

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The presence of the discontinuity in the form of joints is one of the most significant factors causing instability in the rock mass. On the other hand, dynamic loads, including earthquake and blasting induce cyclic shear loads along the joints in rock masses; therefore, failure of rock mass exacerbates along the joints due to changing shear resistance. Joints are under constant normal load (CNL) and constant normal stiffness (CNS) conditions. Normal stiffness increases on the joints with increasing depth, and it can affect shear resistance. For correct assessment of joint shear resistance under varying normal stiffness and number of cycles, advanced laboratory shear machine is essential for the shear test. Conventional direct shear equipment has limitations such as boundary conditions, working under monotonic movements only, or cyclic shear loads with constant frequency and amplitude of shear loads. Hence, a large-scale servo-controlled direct shear testing machine was designed and fabricated to perform shear test under the both CNL and CNS conditions with varying normal stiffness at different frequencies and amplitudes of shear loads. In this study, laboratory cyclic shear tests were conducted on non-planar joints under varying normal stiffness. In addition, the effects of different frequencies and amplitudes of shear loads were investigated. The test results indicate that shear resistance increases with increasing normal stiffness at the first cycle, but the influence of normal stiffness significantly decreases with an increase in the number of shear cycles. The frequency of shear load influences on shear resistance, i.e. shear resistance increases with increasing frequency. However, at low shear amplitude the number of cycles does not affect shear resistance on the joints, but it decreases with higher amplitude.

Keywords: cyclic shear load, frequency of load, amplitude of displacement, normal stiffness

Procedia PDF Downloads 124

Authors: R. H. Bustos, L. Martinez, J. García, F. Suárez

Abstract:

MRP1 (Multi-drug resistance associated protein 1) and MRP2 (Multi-drug resistance associated protein 2) are two proteins belonging to the transporters of ABC (ATP-Binding Cassette). These transporter proteins are involved in the efflux of several biological drugs and xenobiotic and also in multiple physiological, pathological and pharmacological processes. Evidence has been found that there is a correlation among different polymorphisms found and their clinical implication in the resistance to antiepileptic, chemotherapy and anti-infectious drugs. In our study, exonic regions of MRP1/ABCC1 y MRP2/ABCC2 were studied in the Colombian population, specifically in the region of the central Savannah (Cundinamarca) to determinate SNP (Single Nucleotide Polymorphisms) and determinate its allele frequency and its genomics frequency. Results showed that for our population, SNP are found that have been previously reported for MRP1/ABCC1 (rs200647436, rs200624910, rs150214567) as well as for MRP2/ABCC2 (rs2273697, rs3740066, rs142573385, rs17216212). In addition, 13 new SNP were identified. Evidences show an important clinic correlation for polymorphisms rs3740066 and rs2273697. The study object population displays genetic variability as compared to the one reported in other populations.

Keywords: ATP-binding cassette (ABCC), Colombian population, multidrug-resistance protein (MRP), pharmacogenetic, single nucleotide polymorphism (SNP)

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Authors: Djamel Djeghader, Bachir Redjel

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The composite materials of glass fibers can be used as a repair material for damage elements under repeated stresses, and in various environments. A cyclic bending characterization of a glass/polyester composite material was carried out with consideration of the period of immersion in water. These tests describe the behavior of materials and identify the mechanical fatigue characteristics using the Wohler Curve for different immersion time: 0, 90, 180 and 270 days in water. These curves are characterized by a dispersion in the lifetimes were modeled by straight whose intercepts are very similar and comparable to the static strength. This material deteriorates fatigue at a constant rate, which increases with increasing immersion time in water at a constant speed. The endurance limit seems to be independent of the immersion time in the water.

Keywords: fatigue, composite, glass, polyester, immersion, wohler

Procedia PDF Downloads 293