Search results for: Neutron Activation Analysis
28154 Rauvolfine B Isolated from the Bark of Rauvolfia reflexa (Apocynaceae) Induces Apoptosis through Activation of Caspase-9 Coupled with S Phase Cell Cycle Arrest
Authors: Mehran Fadaeinasab, Hamed Karimian, Najihah Mohd Hashim, Hapipah Mohd Ali
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In this study, three indole alkaloids namely; rauvolfine B, macusine B, and isoreserpiline have been isolated from the dichloromethane crude extract of Rauvolfia reflexa bark (Apocynaceae). The structural elucidation of the isolated compounds has been performed using spectral methods such as UV, IR, MS, 1D, and 2D NMR. Rauvolfine B showed anti proliferation activity on HCT-116 cancer cell line, its cytotoxicity induction was observed using MTT assay in eight different cell lines. Annexin-V is serving as a marker for apoptotic cells and the Annexin-V-FITC assay was carried out to observe the detection of cell-surface Phosphatidylserine (PS). Apoptosis was confirmed by using caspase-8 and -9 assays. Cell cycle arrest was also investigated using flowcytometric analysis. rauvolfine B had exhibited significantly higher cytotoxicity against HCT-116 cell line. The treatment significantly arrested HCT-116 cells in the S phase. Together, the results presented in this study demonstrated that rauvolfine B inhibited the proliferation of HCT-116 cells and programmed cell death followed by cell cycle arrest.Keywords: apocynacea, indole alkaloid, apoptosis, cell cycle arrest
Procedia PDF Downloads 33428153 Microscopic and Mesoscopic Deformation Behaviors of Mg-2Gd Alloy with or without Li Addition
Authors: Jing Li, Li Jin, Fulin Wang, Jie Dong, Wenjiang Ding
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Mg-Li dual-phase alloy exhibits better combination of yield strength and elongation than the Mg single-phase alloy. To exploit its deformation behavior, the deformation mechanisms of Mg-2Gd alloy with or without Li addition, i.e., Mg-6Li-2Gd and Mg-2Gd alloy, have been studied at both microscale and mesoscale. EBSD-assisted slip trace, twin trace, and texture evolution analysis show that the α-Mg phase of Mg-6Li-2Gd alloy exhibits different microscopic deformation mechanisms with the Mg-2Gd alloy, i.e., mainly prismatic slip in the former one, while basal slip, prismatic slip and extension twin in the latter one. Further Schmid factor analysis results attribute this different intra-phase deformation mechanisms to the higher critical resolved shear stress (CRSS) value of extension twin and lower ratio of CRSSprismatic /CRSSbasal in the α-Mg phase of Mg-6Li-2Gd alloy. Additionally, Li addition can induce dual-phase microstructure in the Mg-6Li-2Gd alloy, leading to the formation of hetero-deformation induced (HDI) stress at the mesoscale. This can be evidenced by the hysteresis loops appearing during the loading-unloading-reloading (LUR) tensile tests and the activation of multiple slip activity in the α-Mg phase neighboring β-Li phase. The Mg-6Li-2Gd alloy shows higher yield strength is due to the harder α-Mg phase arising from solid solution hardening of Li addition, as well asthe strengthening of soft β-Li phase by the HDI stress during yield stage. Since the strain hardening rate of Mg-6Li-2Gd alloy is lower than that of Mg-2Gd alloy after ~2% strain, which is partly due to the weak contribution of HDI stress, Mg-6Li-2Gd alloy shows no obvious increase of uniform elongation than the Mg-2Gd alloy.But since the β-Li phase is effective in blunting the crack tips, the Mg-6Li-2Gd alloy shows ununiform elongation, which, thus, leads to the higher total elongation than the Mg-2Gd alloy.Keywords: Mg-Li-Gd dual-phase alloy, phase boundary, HDI stress, dislocation slip activity, mechanical properties
Procedia PDF Downloads 20228152 Feature Extractions of EMG Signals during a Constant Workload Pedaling Exercise
Authors: Bing-Wen Chen, Alvin W. Y. Su, Yu-Lin Wang
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Electromyography (EMG) is one of the important indicators during exercise, as it is closely related to the level of muscle activations. This work quantifies the muscle conditions of the lower limbs in a constant workload exercise. Surface EMG signals of the vastus laterals (VL), vastus medialis (VM), rectus femoris (RF), gastrocnemius medianus (GM), gastrocnemius lateral (GL) and Soleus (SOL) were recorded from fourteen healthy males. The EMG signals were segmented in two phases: activation segment (AS) and relaxation segment (RS). Period entropy (PE), peak count (PC), zero crossing (ZC), wave length (WL), mean power frequency (MPF), median frequency (MDF) and root mean square (RMS) are calculated to provide the quantitative information of the measured EMG segments. The outcomes reveal that the PE, PC, ZC and RMS have significantly changed (p<.001); WL presents moderately changed (p<.01); MPF and MDF show no changed (p>.05) during exercise. The results also suggest that the RS is also preferred for performance evaluation, while the results of the extracted features in AS are usually affected directly by the amplitudes. It is further found that the VL exhibits the most significant changes within six muscles during pedaling exercise. The proposed work could be applied to quantify the stamina analysis and to predict the instant muscle status in athletes.Keywords: electromyographic feature extraction, muscle status, pedaling exercise, relaxation segment
Procedia PDF Downloads 30228151 Moved by Music: The Impact of Music on Fatigue, Arousal and Motivation During Conditioning for High to Elite Level Female Artistic Gymnasts
Authors: Chante J. De Klerk
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The potential of music to facilitate superior performance during high to elite level gymnastics conditioning instigated this research. A team of seven gymnasts completed a fixed conditioning programme eight times, alternating the two variable conditions. Four sessions of each condition were conducted: without music (session 1), with music (session 2), without music (3), with music (4), without music (5), and so forth. Quantitative data were collected in both conditions through physiological monitoring of the gymnasts, and administration of the Situational Motivation Scale (SIMS). Statistical analysis of the physiological data made it possible to quantify the presence as well as the magnitude of the musical intervention’s impact on various aspects of the gymnasts' physiological functioning during conditioning. The SIMS questionnaire results were used to evaluate if their motivation towards conditioning was altered by the intervention. Thematic analysis of qualitative data collected through semi-structured interviews revealed themes reflecting the gymnasts’ sentiments towards the data collection process. Gymnast-specific descriptions and experiences of the team as a whole were integrated with the quantitative data to facilitate greater dimension in establishing the impact of the intervention. The results showed positive physiological, motivational, and emotional effects. In the presence of music, superior sympathetic nervous activation, and energy efficiency, with more economic breathing, dominated the physiological data. Fatigue and arousal levels (emotional and physiological) were also conducive to improved conditioning outcomes compared to conventional conditioning (without music). Greater levels of positive affect and motivation emerged in analysis of both the SIMS and interview data sets. Overall, the intervention was found to promote psychophysiological coherence during the physical activity. In conclusion, a strategically constructed musical intervention, designed to accompany a gymnastics conditioning session for high to elite level gymnasts, has ergogenic potential.Keywords: arousal, fatigue, gymnastics conditioning, motivation, musical intervention, psychophysiological coherence
Procedia PDF Downloads 9428150 Anticancer Study of Copper and Zinc Complexes with Doxorubicin
Authors: Grzegorz Swiderski, Agata Jablonska-Trypuc, Natalia Popow, Renata Swislocka, Wlodzimierz Lewandowski
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Doxorubicin belongs to the group of anthracycline antitumor antibiotics. Because of the wide spectrum of actions, it is one of the most widely used anthracycline antibiotics, including the treatment of breast, ovary, bladder, lung cancers as well as neuroblastoma, lymphoma, leukemia and myeloid leukemia. Antitumor activity of doxorubicin is based on the same mechanisms as for most anthracyclines. Like the metal ions affect the nucleic acids on many biological processes, so the environment of the metal chelates of antibiotics can have a significant effect on the pharmacological properties of drugs. Complexation of anthracyclines with metal ions may contribute to the production of less toxic compounds. In the framework of this study, the composition of complexes obtained in aqueous solutions of doxorubicin with metal ions (Cu2+ and Zn2+). Complexation was analyzed by spectrophotometric titration in aqueous solution at pH 7.0. The pH was adjusted with 0.02M Tris-HCl buffer. The composition of the complexes found was Cu: doxorubicin (1: 2) and a Zn: doxorubicin (1: 1). The effect of Dox, Dox-Cu and Dox-Zn was examined in MCF-7 breast cancer cell line, which were obtained from American Type Culture Collection (ATCC). The compounds were added to the cultured cells for a final concentration in the range of 0,01µM to 0,5µM. The number of MCF-7 cells with division into living and dead, was determined by direct counts of cells with the use of trypan blue dye using LUNA Logos Biosystems cell counter. ApoTox-Glo Triplex Assay (Promega, Madison, Wisconsin, USA) was used according to the manufacturer’s instructions to measure the MCF-7 cells’ viability, cytotoxicity and apoptosis. We observed a decrease in cells proliferation in a dose-dependent manner. An increase in cytotoxicity and decrease in viability in the ApoTox Triplex assay was also showed for all tested compounds. Apoptosis, showed as caspase 3/7 activation, was observed only in Dox treatment. In Dox-Zn and Dox-Cu caspase 3/7 activation was not observed. This work was financially supported by National Science Centre, Poland, under the research project number 2014/13/B/NZ7/02 352.Keywords: anticancer properties, anthracycline antibiotic, doxorubicine, metal complexes
Procedia PDF Downloads 28028149 Preliminary dosimetric Evaluation of a New Therapeutic 177LU Complex for Human Based on Biodistribution Data in Rats
Authors: H. Yousefnia, S. Zolghadri, A. Golabi Dezfuli
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Tris (1,10-phenanthroline) lanthanum(III)] trithiocyanate is a new compound that has shown to stop DNA synthesis in CCRF-CEM and Ehrlich ascites cells leading to a cell cycle arrest in G0/G1. One other important property of the phenanthroline nucleus is its ability to act as a triplet-state photosensitizer especially in complexes with lanthanides. In Nowadays, the radiation dose assessment resource (RADAR) method is known as the most common method for absorbed dose calculation. 177Lu was produced by irradiation of a natural Lu2O3 target at a thermal neutron flux of approximately 4 × 1013 n/cm2•s. 177Lu-PL3 was prepared in the optimized condition. The radiochemical yield was checked by ITLC method. The biodistribution of the complex was investigated by intravenously injection to wild-type rats via their tail veins. In this study, the absorbed dose of 177Lu-PL3 to human organs was estimated by RADAR method. 177Lu was prepared with a specific activity of 2.6-3 GBq.mg-1 and radionuclide purity of 99.98 %. The 177Lu-PL3 complex can prepare with high radiochemical yield (> 99 %) at optimized conditions. The results show that liver and spleen have received the highest absorbed dose of 1.051 and 0.441 mSv/MBq, respectivley. The absorbed dose values for these two dose-limiting tissues suggest more biological studies special in tumor-bearing animals.Keywords: internal dosimetry, Lutetium-177, radar, animals
Procedia PDF Downloads 37228148 Study of Tribological Behavior of Zirconium Alloy Against SS-410 at High Temperature
Authors: Bharat Kumar, Deepak Kumar, Vijay Chaudhry
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Zirconium alloys exhibit low neutron absorption cross-section and excellent mechanical properties. Due to these unique characteristics, these materials are widely used in designing core components of pressurized heavy water reactors (PHWRs). Another material that is widely used in the design of reactor core is stainless steel. Under operating conditions of the reactor, there are possibilities for mechanical and tribological interaction between the components made of zirconium alloy (Zr-2.5 Nb) and stainless steel (SS-410). This may result in wear of the material. To study the tribological characteristics of Zr-2.5 Nb and SS-410, low amplitude reciprocating wear tests are conducted at room temperature and at high temperatures (260 degrees Celsius). The tests are conducted at frequencies ranging from 5 Hz to 25 Hz. The displacement amplitude is varied from 200 µm to 600 µm. The responses are recorded, analyzed and correlated with damage observed using scanning electron microscopy (SEM) and an optical profilometer. Energy dispersive spectroscopy (EDS) is used to study the damage mechanism prevailing at the contact interface. A higher coefficient of friction (COF) is observed at higher temperatures as compared to the one at room temperature. Tests carried out at high temperature reveals adhesive wear as the dominant mechanism resulting in significant material transfer.Keywords: PHWRs, Zr-2.5Nb, SS-410, wear
Procedia PDF Downloads 9228147 Production, Quality Control, and Biodistribution Studies of 141ce-Edtmp as a Potential Bone Pain Palliation Agent
Authors: Fatemeh Soltani, Simindokht Shirvani Arani, Ali Bahrami Samani, Mahdi Sadeghi, Kamal Yavari
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Cerium-141 [T1/2 = 32.501 days, Eβ (max) = 0.580 (29.8%) and 0.435(70.2%) MeV, Eγ=145.44 (48.2%) keV] possesses radionuclidic properties suitable for use in palliative therapy of bone metastases. 141Ce also has gamma energy of 145.44 keV, which resembles that of 99mTc. Therefore, the energy window is adjustable on the Tc-99m energy because of imaging studies. 141Ce can be produced through a relatively easy route that involves thermal neutron bombardment on natural CeO2 in medium flux research reactors (4–5×1013 neutrons/cm2•s). The requirement for an enriched target does not arise. Ethylenediamine tetramethylene phosphonic acid (EDTMP) was synthesized and radiolabeled with 141Ce. Complexation parameters were optimized to achieve maximum yields (>99%). The radiochemical purity of 141Ce-EDTMP was evaluated by radio-thin layer chromatography. The stability of the prepared formulation was monitored for one week at room temperature, and results showed that the preparation was stable during this period (>99%). Biodistribution studies of the complexes carried out in wild-type rats exhibited significant bone uptake with rapid clearance from blood. The properties of produced 141Ce-EDTMP suggest applying a new efficient bone pain palliative therapeutic agent to overcome metastatic bone pains.Keywords: bone pain palliative, cerium-141, EDTMP, radiopharmaceutical
Procedia PDF Downloads 48928146 Molecular Migration in Polyvinyl Acetate Matrix: Impact of Compatibility, Number of Migrants and Stress on Surface and Internal Microstructure
Authors: O. Squillace, R. L. Thompson
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Migration of small molecules to, and across the surface of polymer matrices is a little-studied problem with important industrial applications. Tackifiers in adhesives, flavors in foods and binding agents in paints all present situations where the function of a product depends on the ability of small molecules to migrate through a polymer matrix to achieve the desired properties such as softness, dispersion of fillers, and to deliver an effect that is felt (or tasted) on a surface. It’s been shown that the chemical and molecular structure, surface free energies, phase behavior, close environment and compatibility of the system, influence the migrants’ motion. When differences in behavior, such as occurrence of segregation to the surface or not, are observed it is then of crucial importance to identify and get a better understanding of the driving forces involved in the process of molecular migration. In this aim, experience is meant to be allied with theory in order to deliver a validated theoretical and computational toolkit to describe and predict these phenomena. The systems that have been chosen for this study aim to address the effect of polarity mismatch between the migrants and the polymer matrix and that of a second migrant over the first one. As a non-polar resin polymer, polyvinyl acetate is used as the material to which more or less polar migrants (sorbitol, carvone, octanoic acid (OA), triacetin) are to be added. Through contact angle measurement a surface excess is seen for sorbitol (polar) mixed with PVAc as the surface energy is lowered compare to the one of pure PVAc. This effect is increased upon the addition of carvon or triacetin (non-polars). Surface micro-structures are also evidenced by atomic force microscopy (AFM). Ion beam analysis (Nuclear Reaction Analysis), supplemented by neutron reflectometry can accurately characterize the self-organization of surfactants, oligomers, aromatic molecules in polymer films in order to relate the macroscopic behavior to the length scales that are amenable to simulation. The nuclear reaction analysis (NRA) data for deuterated OA 20% shows the evidence of a surface excess which is enhanced after annealing. The addition of 10% triacetin, as a second migrant, results in the formation of an underlying layer enriched in triacetin below the surface excess of OA. The results show that molecules in polarity mismatch with the matrix tend to segregate to the surface, and this is favored by the addition of a second migrant of the same polarity than the matrix. As studies have been restricted to materials that are model supported films under static conditions in a first step, it is also wished to address the more challenging conditions of materials under controlled stress or strain. To achieve this, a simple rig and PDMS cell have been designed to stretch the material to a defined strain and to probe these mechanical effects by ion beam analysis and atomic force microscopy. This will make a significant step towards exploring the influence of extensional strain on surface segregation, flavor release in cross-linked rubbers.Keywords: polymers, surface segregation, thin films, molecular migration
Procedia PDF Downloads 13228145 Properties of Bio-Phenol Formaldehyde Composites Filled with Empty Fruit Bunch Fiber
Authors: Sharifah Nabihah Syed Jaafar, Umar Adli Amran, Rasidi Roslan, Chia Chin Hua, Sarani Zakaria
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Bio-composites derived from plant fiber and bio-derived polymer, are likely more ecofriendly and demonstrate competitive performance with petroleum based. In this research, the green phenolic resin was used as a matrix and oil palm empty fruit bunch fiber (EFB) was used as filler. The matrix was synthesized from soda lignin, phenol and hydrochloric acid as a catalyst. The phenolic resin was synthesized via liquefaction and condensation to enhance the combination of phenol during the process. Later, the phenolic resin was mixed with EFB by using mechanical stirrer and was molded with hot press at 180 oC. In this research, the composites were prepared with EFB content of 5%, 10%, 15% and 20%. The samples that viewed under scanning electron microscopy (SEM) showed that the EFB filler remained embedded in the resin. From impact and hardness testing, samples 10% of EFB showed the optimum properties meanwhile sample 15% showed the optimum properties for flexural testing. Thermal stability of the composites was investigated using thermogravimetric (TGA) analysis and found that the weight loss and the activation energy (Ea) of the composites samples were decreased as the filler content increased.Keywords: EFB, liquefaction, phenol formaldehyde, lignin
Procedia PDF Downloads 58928144 Evidence of the Effect of the Structure of Social Representations on Group Identification
Authors: Eric Bonetto, Anthony Piermatteo, Fabien Girandola, Gregory Lo Monaco
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The present contribution focuses on the effect of the structure of social representations on group identification. A social representation (SR) is defined as an organized and structured set of cognitions, produced and shared by members of a same group about a same social object. Within this framework, the central core theory establishes a structural distinction between central cognitions – or 'core' – and peripheral ones: the former are theoretically considered as more connected than the later to group members’ social identity and may play a greater role in SRs’ ability to allow group identification by means of a common vision of the object of representation. Indeed, the central core provides a reference point for the in-group as it constitutes a consensual vision that gives meaning to a social object particularly important to individuals and to the group. However, while numerous contributions clearly refer to the underlying role of SRs in group identification, there are only few empirical evidences of this aspect. Thus, we hypothesize an effect of the structure of SRs on group identification. More precisely, central cognitions (vs. peripheral ones) will lead to a stronger group identification. In addition, we hypothesize that the refutation of a cognition will lead to a stronger group identification than its activation. The SR mobilized here is that of 'studying' among a population of first-year undergraduate psychology students. Thus, a pretest (N = 82), using an Attribute-Challenge Technique, was designed in order to identify the central and the peripheral cognitions to use in the primings of our main study. The results of this pretest are in line with previous studies. Then, the main study (online; N = 184), using a social priming methodology, was based on a 2 (Structural status of the cognitions belonging to the prime: central vs. peripheral) x 2 (Type of prime: activation vs. refutation) experimental design in order to test our hypotheses. Results revealed, as expected, the main effect of the structure of the SR on group identification. Indeed, central cognitions trigger a higher level of identification than the peripheral ones. However, we observe neither effect of the type of prime, nor interaction effect. These results experimentally demonstrate for the first time the effect of the structure of SRs on group identification and indicate that central cognitions are more connected than peripheral ones to group members’ social identity. These results will be discussed considering the importance of understanding identity as a function of SRs and on their ability to potentially solve the lack of consideration of the definition of the group in Social Representations Theory.Keywords: group identification, social identity, social representations, structural approach
Procedia PDF Downloads 19128143 Improved Performance of Mn Substituted Ceria Nanospheres for Water Gas Shift Reaction: Influence of Preparation Conditions
Authors: Bhairi Lakshminarayana, Surajit Sarker, Ch. Subrahmanyam
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The present study reports the development of noble metal free nano catalysts for low-temperature CO oxidation and water gas shift reaction. Mn-substituted CeO2 solid solution catalysts were synthesized by co-precipitation, combustion and hydrothermal methods. The formation of solid solution was confirmed by XRD with Rietveld refinement and the percentage of carbon and nitrogen doping was ensured by CHNS analyzer. Raman spectroscopic confirmed the oxygen vacancies. The surface area, pore volume and pore size distribution confirmed by N2 physisorption analysis, whereas, UV-visible diffuse reflectance spectroscopy and XPS data confirmed the oxidation state of the Mn ion. The particle size and morphology (spherical shape) of the material was confirmed using FESEM and HRTEM analysis. Ce0.8Mn0.2O2-δ was calcined at 400 °C, 600 °C and 800 °C. Raman spectroscopy confirmed that the catalyst calcined at 400 °C has the best redox properties. The activity of the designed catalysts for CO oxidation (0.2 vol%), carried out with GHSV of 21,000 h-1 and it has been observed that co-precipitation favored the best active catalyst towards CO oxidation and water gas shift reaction, due to the high surface area, improved reducibility, oxygen mobility and highest quantity of surface oxygen species. The activation energy of low temperature CO oxidation on Ce0.8Mn0.2O2- δ (combustion) was 5.5 kcal.K-1.mole-1. The designed catalysts were tested for water gas shift reaction. The present study demonstrates that Mn ion substituted ceria at 400 °C calcination temperature prepared by co-precipitation method promise to revive a green sustainable energy production approach.Keywords: Ce0.8Mn0.2O2-ð, CO oxidation, physicochemical characterization, water gas shift reaction (WGS)
Procedia PDF Downloads 23728142 Ordinary Differentiation Equations (ODE) Reconstruction of High-Dimensional Genetic Networks through Game Theory with Application to Dissecting Tree Salt Tolerance
Authors: Libo Jiang, Huan Li, Rongling Wu
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Ordinary differentiation equations (ODE) have proven to be powerful for reconstructing precise and informative gene regulatory networks (GRNs) from dynamic gene expression data. However, joint modeling and analysis of all genes, essential for the systematical characterization of genetic interactions, are challenging due to high dimensionality and a complex pattern of genetic regulation including activation, repression, and antitermination. Here, we address these challenges by unifying variable selection and game theory through ODE. Each gene within a GRN is co-expressed with its partner genes in a way like a game of multiple players, each of which tends to choose an optimal strategy to maximize its “fitness” across the whole network. Based on this unifying theory, we designed and conducted a real experiment to infer salt tolerance-related GRNs for Euphrates poplar, a hero tree that can grow in the saline desert. The pattern and magnitude of interactions between several hub genes within these GRNs were found to determine the capacity of Euphrates poplar to resist to saline stress.Keywords: gene regulatory network, ordinary differential equation, game theory, LASSO, saline resistance
Procedia PDF Downloads 63928141 The Effect of Physical Exercise to Level of Nuclear Factor Kappa B on Serum, Macrophages and Myocytes
Authors: Eryati Darwin, Eka Fithra Elfi, Indria Hafizah
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Background: Physical exercise induces a pattern of hormonal and immunological responses that prevent endothelial dysfunction by maintaining the availability of nitric oxide (NO). Regular and moderate exercise stimulates NO release, that can be considered as protective factor of cardiovascular diseases, while strenuous exercise induces increased levels in a number of pro-inflammatory and anti-inflammatory cytokines. Pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) triggers endothelial activation which results in an increased vascular permeability. Nuclear gene factor kappa B (NF-κB) activates biological effect of TNF-α. Aim of Study: To determine the effect of physical exercise on the endothelial and skeletal muscle, we measured the level of NF-κB on rats’ serum, macrophages, and myocytes after strenuous physical exercise. Methods: 30 male Rattus norvegicus in the age of eight weeks were randomly divided into five groups (each containing six), and there were treated groups (T) and control group (C). The treated groups obtain strenuous physical exercise by ran on treadmill at 32 m/minutes for 1 hour or until exhaustion. Blood samples, myocytes of gastrocnemius muscle, and intraperitoneal macrophages were collected sequentially. There were investigated immediately, 2 hours, 6 hours, and 24 hours (T1, T2, T3, and T4) after sacrifice. The levels of NF-κB were measured by ELISA methods. Results: From our study, we found that the levels of NF-κB on myocytes in treated group from which its specimen was taken immediately (T1), 2 hours after treadmill (T2), and 6 hours after treadmill (T3) were significantly higher than control group (p<0.05), while the group from which its specimen was taken 24 hours after treadmill, was no significantly different (p>0.05). Also on macrophages, NF-κB in treated groups T1, T2, and T3 was significantly higher than control group (p<0.05), but there was no difference between T4 and control group (p>0.05). The level of serum NF-κB was not significantly different between treatment group as well as compared to control group (p>0.05). Serum NF-κB was significantly higher than the level on macrophages and myocytes (p<0.05). Conclusion: This study demonstrated that strenuous physical exercise stimulates the activation of NF-κB that plays a role in vascular inflammation and muscular damage, and may be recovered after resting period.Keywords: endothelial function, inflammation, NFkB, physical exercise
Procedia PDF Downloads 25928140 Ultra-High Molecular Weight Polyethylene (UHMWPE) for Radiation Dosimetry Applications
Authors: Malik Sajjad Mehmood, Aisha Ali, Hamna Khan, Tariq Yasin, Masroor Ikram
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Ultra-high molecular weight polyethylene (UHMWPE) is one of the polymers belongs to polyethylene (PE) family having monomer –CH2– and average molecular weight is approximately 3-6 million g/mol. Due its chemical, mechanical, physical and biocompatible properties, it has been extensively used in the field of electrical insulation, medicine, orthopedic, microelectronics, engineering, chemistry and the food industry etc. In order to alter/modify the properties of UHMWPE for particular application of interest, certain various procedures are in practice e.g. treating the material with high energy irradiations like gamma ray, e-beam, and ion bombardment. Radiation treatment of UHMWPE induces free radicals within its matrix, and these free radicals are the precursors of chain scission, chain accumulation, formation of double bonds, molecular emission, crosslinking etc. All the aforementioned physical and chemical processes are mainly responsible for the modification of polymers properties to use them in any particular application of our interest e.g. to fabricate LEDs, optical sensors, antireflective coatings, polymeric optical fibers, and most importantly for radiation dosimetry applications. It is therefore, to check the feasibility of using UHMWPE for radiation dosimetery applications, the compressed sheets of UHMWPE were irradiated at room temperature (~25°C) for total dose values of 30 kGy and 100 kGy, respectively while one were kept un-irradiated as reference. Transmittance data (from 400 nm to 800 nm) of e-beam irradiated UHMWPE and its hybrids were measured by using Muller matrix spectro-polarimeter. As a result significant changes occur in the absorption behavior of irradiated samples. To analyze these (radiation induced) changes in polymer matrix Urbach edge method and modified Tauc’s equation has been used. The results reveal that optical activation energy decreases with irradiation. The values of activation energies are 2.85 meV, 2.48 meV, and 2.40 meV for control, 30 kGy, and 100 kGy samples, respectively. Direct and indirect energy band gaps were also found to decrease with irradiation due to variation of C=C unsaturation in clusters. We believe that the reported results would open new horizons for radiation dosimetery applications.Keywords: electron beam, radiation dosimetry, Tauc’s equation, UHMWPE, Urbach method
Procedia PDF Downloads 40628139 Estimation of Forces Applied to Forearm Using EMG Signal Features to Control of Powered Human Arm Prostheses
Authors: Faruk Ortes, Derya Karabulut, Yunus Ziya Arslan
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Myoelectric features gathering from musculature environment are considered on a preferential basis to perceive muscle activation and control human arm prostheses according to recent experimental researches. EMG (electromyography) signal based human arm prostheses have shown a promising performance in terms of providing basic functional requirements of motions for the amputated people in recent years. However, these assistive devices for neurorehabilitation still have important limitations in enabling amputated people to perform rather sophisticated or functional movements. Surface electromyogram (EMG) is used as the control signal to command such devices. This kind of control consists of activating a motion in prosthetic arm using muscle activation for the same particular motion. Extraction of clear and certain neural information from EMG signals plays a major role especially in fine control of hand prosthesis movements. Many signal processing methods have been utilized for feature extraction from EMG signals. The specific objective of this study was to compare widely used time domain features of EMG signal including integrated EMG(IEMG), root mean square (RMS) and waveform length(WL) for prediction of externally applied forces to human hands. Obtained features were classified using artificial neural networks (ANN) to predict the forces. EMG signals supplied to process were recorded during only type of muscle contraction which is isometric and isotonic one. Experiments were performed by three healthy subjects who are right-handed and in a range of 25-35 year-old aging. EMG signals were collected from muscles of the proximal part of the upper body consisting of: biceps brachii, triceps brachii, pectorialis major and trapezius. The force prediction results obtained from the ANN were statistically analyzed and merits and pitfalls of the extracted features were discussed with detail. The obtained results are anticipated to contribute classification process of EMG signal and motion control of powered human arm prosthetics control.Keywords: assistive devices for neurorehabilitation, electromyography, feature extraction, force estimation, human arm prosthesis
Procedia PDF Downloads 36728138 Microanalysis of a New Cementitious System Containing High Calcium Fly Ash and Waste Material by Scanning Electron Microscopy (SEM)
Authors: Anmar Dulaimi, Hassan Al Nageim, Felicite Ruddock, Linda Seton
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Fast-curing cold bituminous emulsion mixture (CBEM) including active filler from high calcium fly ash (HCFA) and waste material (LJMU-A2) has been developed in this study. This will overcome the difficulties related with the use of hot mix asphalt such as greenhouse gases emissions and problems in keeping the temperature when transporting long distance. The aim of this study is to employ petrographic examinations using scanning electron microscopy (SEM) for characterizing the hydrates microstructure, in a new binary blended cement filler (BBCF) system. The new BBCF has been used as a replacement to traditional mineral filler in cold bituminous emulsion mixtures (CBEMs), comprises supplementary cementitious materials containing high calcium fly ash (HCFA) and a waste material (LJMU-A2). SEM analysis demonstrated the formation of hydrates after varying curing ages within the BBCF. The accelerated activation of HCFA by LJMU-A2 within the BBCF was revealed and as a consequence early and later stiffness was developed in novel CBEM.Keywords: cold bituminous emulsion mixtures, indirect tensile stiffness modulus, scanning electron microscopy (SEM), and high calcium fly ash
Procedia PDF Downloads 27628137 The Realization of a System’s State Space Based on Markov Parameters by Using Flexible Neural Networks
Authors: Ali Isapour, Ramin Nateghi
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— Markov parameters are unique parameters of the system and remain unchanged under similarity transformations. Markov parameters from a power series that is convergent only if the system matrix’s eigenvalues are inside the unity circle. Therefore, Markov parameters of a stable discrete-time system are convergent. In this study, we aim to realize the system based on Markov parameters by using Artificial Neural Networks (ANN), and this end, we use Flexible Neural Networks. Realization means determining the elements of matrices A, B, C, and D.Keywords: Markov parameters, realization, activation function, flexible neural network
Procedia PDF Downloads 19428136 Effects of Renin Angiotensin Pathway Inhibition on Efficacy of Anti-PD-1/PD-L1 Treatment in Metastatic Cancer
Authors: Philip Friedlander, John Rutledge, Jason Suh
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Inhibition of programmed death-1 (PD-1) or its ligand PD-L1 confers therapeutic efficacy in a wide range of solid tumor malignancies. Primary or acquired resistance can develop through activation of immunosuppressive immune cells such as tumor-associated macrophages. The renin angiotensin system (RAS) systemically regulates fluid and sodium hemodynamics, but components are expressed on and regulate the activity of immune cells, particularly of myeloid lineage. We hypothesized that inhibition of RAS would improve the efficacy of PD-1/PD-L-1 treatment. A retrospective analysis was performed through a chart review of patients with solid metastatic malignancies treated with a PD-1/PD-L1 inhibitor between 1/2013 and 6/2019 at Valley Hospital, a community hospital in New Jersey, USA. Efficacy was determined by medical oncologist documentation of clinical benefit in visit notes and by the duration of time on immunotherapy treatment. The primary endpoint was the determination of efficacy differences in patients treated with an inhibitor of RAS ( ace inhibitor, ACEi, or angiotensin blocker, ARB) compared to patients not treated with these inhibitors. To control for broader antihypertensive effects, efficacy as a function of treatment with beta blockers was assessed. 173 patients treated with PD-1/PD-L-1 inhibitors were identified of whom 52 were also treated with an ACEi or ARB. Chi-square testing revealed a statistically significant relationship between being on an ACEi or ARB and efficacy to PD-1/PD-L-1 therapy (p=0.001). No statistically significant relationship was seen between patients taking or not taking beta blocker antihypertensives (p= 0.33). Kaplan-Meier analysis showed statistically significant improvement in the duration of therapy favoring patients concomitantly treated with ACEi or ARB compared to patients not exposed to antihypertensives and to those treated with beta blockers. Logistic regression analysis revealed that age, gender, and cancer type did not have significant effects on the odds of experiencing clinical benefit (p=0.74, p=0.75, and p=0.81, respectively). We conclude that retrospective analysis of the treatment of patients with solid metastatic tumors with anti-PD-1/PD-L1 in a community setting demonstrates greater clinical benefit in the context of concomitant ACEi or ARB inhibition, irrespective of gender or age. This data supports the development of prospective assessment through randomized clinical trials.Keywords: angiotensin, cancer, immunotherapy, PD-1, efficacy
Procedia PDF Downloads 7628135 Treating Voxels as Words: Word-to-Vector Methods for fMRI Meta-Analyses
Authors: Matthew Baucum
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With the increasing popularity of fMRI as an experimental method, psychology and neuroscience can greatly benefit from advanced techniques for summarizing and synthesizing large amounts of data from brain imaging studies. One promising avenue is automated meta-analyses, in which natural language processing methods are used to identify the brain regions consistently associated with certain semantic concepts (e.g. “social”, “reward’) across large corpora of studies. This study builds on this approach by demonstrating how, in fMRI meta-analyses, individual voxels can be treated as vectors in a semantic space and evaluated for their “proximity” to terms of interest. In this technique, a low-dimensional semantic space is built from brain imaging study texts, allowing words in each text to be represented as vectors (where words that frequently appear together are near each other in the semantic space). Consequently, each voxel in a brain mask can be represented as a normalized vector sum of all of the words in the studies that showed activation in that voxel. The entire brain mask can then be visualized in terms of each voxel’s proximity to a given term of interest (e.g., “vision”, “decision making”) or collection of terms (e.g., “theory of mind”, “social”, “agent”), as measured by the cosine similarity between the voxel’s vector and the term vector (or the average of multiple term vectors). Analysis can also proceed in the opposite direction, allowing word cloud visualizations of the nearest semantic neighbors for a given brain region. This approach allows for continuous, fine-grained metrics of voxel-term associations, and relies on state-of-the-art “open vocabulary” methods that go beyond mere word-counts. An analysis of over 11,000 neuroimaging studies from an existing meta-analytic fMRI database demonstrates that this technique can be used to recover known neural bases for multiple psychological functions, suggesting this method’s utility for efficient, high-level meta-analyses of localized brain function. While automated text analytic methods are no replacement for deliberate, manual meta-analyses, they seem to show promise for the efficient aggregation of large bodies of scientific knowledge, at least on a relatively general level.Keywords: FMRI, machine learning, meta-analysis, text analysis
Procedia PDF Downloads 44828134 A Study on Energy-Saving Modular Housing Units Considering Environmental and Aesthetic Aspects
Authors: Jae Hee Chung, Tae Uk Kang, Byung Seo Kim
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This study aims to propose design technologies for the energy-saving modular housing units considering environmental and aesthetic aspects. Modular houses are environmentally friendly based on 3R (Reduce, Reuse, Recycle) because they can dramatically reduce carbon dioxide and construction wastes generated during the construction, use, and disposal process by the pre-fabrication at the factory and the recyclability of the unit, compared to the existing construction methods. The existing modular housing, however, tends to focus on quantitative aspects of energy reduction, such as windows, insulation, and introduction of renewable energy, and there is not much research on energy-saving type units considering the environmental aspects such as daylighting and ventilation, and the design that goes beyond the standardized appearance. Therefore, this study conducts theoretical investigation and analytical case studies on the energy-saving methods through various architectural planning elements as well as materials like insulation considering the environmental and aesthetic aspects in the modular housing. Then, comparative analysis on the energy efficiency through the energy simulation is conducted. As a conclusion, the energy-saving modular housing units considering environmental and aesthetics aspects are proposed. It is expected that this study will contribute to the supply and activation of modular housing through deriving design technologies for the energy-saving modular housing units that consider not only quantitative aspects but also qualitative aspects.Keywords: aesthetic aspects, energy-saving, environmental, modular housing
Procedia PDF Downloads 35728133 New Quinazoline Derivative Exhibit Cytotoxic Effect agaisnt MCF-7 Human Breast Cancer Cell
Authors: Maryam Zahedifard, Fadhil Lafta Faraj, Nazia Abdul Majid, Hapipah Mohd Ali, Mahmood Ameen Abdulla
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The new quinazoline Schiff bases have been synthesized through condensation reaction of 2-aminobenzhydrazide with 5-bromosalicylaldehyde and 3-methoxy-5-bromosalicylaldehyde. The compound was investigated for anticancer activity against MCF-7 human breast cancer cell line. It demonstrated a remarkable antiproliferative effect, with an IC50 value of 3.41±0.34, after 72 hours of treatment. Most apoptosis morphological features in treated MCF-7 cells were observed by AO/PI staining. The results of cell cycle analysis indicate that compounds did not induce S and M phase arrest in cell after 24 hours of treatment. Furthermore, MCF-7 cells treated with compound subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome C release as well as increase in ROS generation. We also found activation of caspases 3/7 and -9. Moreover, acute toxicity results demonstrated the nontoxic nature of the compounds in mice. Our results showed the selected compound significantly induce apoptosis in MCF-7 cells via intrinsic pathway, which might be considered as a potential candidate for further in vivo and clinical breast cancer studies.Keywords: quinazoline Schiff base, apoptosis, MCF-7, caspase, cell cycle, acute toxicity
Procedia PDF Downloads 44128132 Social Media as a ‘Service’ for Value Co-Creation by Integrating Sponsoring Companies, Sports Entities and Fans
Authors: Harri Jalonen
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Social media has changed the ways we communicate, collaborate and connect with each other. It has also influenced our habits of consuming sports. Social media has allowed direct interaction between sponsoring companies, athletes/players and fans. Drawing on the service dominant logic of value co-creation, the conceptual paper identifies three operant resources which are beneficial for value co-creation: i) social identity and sense of community, ii) congruence and brand personality, and iii) participatory culture and fan activation. The paper contributes to the theoretical discussion on how social can be media used for value co-creation purposes in the sports industry.Keywords: sports, value co-creation, social media, service
Procedia PDF Downloads 27828131 Implications of Fuel Reloading in Heterogeneous Thorium-Based Fuel Designs for Improved Fuel Cycle Characteristics
Authors: Hendrik Bernard Van Der Walt, Frik Van Niekerk
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Fuel models render a reduction in BOL when thorium is added to a reactor core. Thorium emulates the role of a fertile poison, and is beneficial for reducing beginning of cycle (BOC) excess reactivity. In spite of the build-up of 233U over the duration of a fuel cycle, the effects of fuel reloading have a significant impact on fuel viability, especially in the case of heterogeneous thorium-based fuels. The most common practice of compensating for the reduction of BOC reactivity is the addition of fissile isotopes (uranium fuel with increased enrichment or plutonium). This study introduces a heterogeneous thorium-based fuel with minimal fissile isotope additions. A pseudo reloading scheme was developed for numerical simulations of an infinite reactor based on the North-Anna 1 reactor operating in Virginia, USA. Use of this reloading pattern allows new thorium-based fuel to be loaded into the reactor model as part of a phasing in strategy at the end of any conventional reactor cycle. Results demonstrate the effects of thorium-based fuel on fuel cycle characteristics such as fuel cycle length, neutron economy and material matrix. Application of the above mentioned approach delivered promising results and presents a heterogeneous thorium-based fuel which could replace conventional fuel of typical, currently operating (or future) reactors without the need for expensive reactor redesign or fuel recycling strategies.Keywords: nuclear fuel, nuclear characteristics, nuclear fuel cycle, thorium-based fuel, heterogeneous design, fuel reloading
Procedia PDF Downloads 13528130 Sulforaphane Alleviates Muscular Dystrophy in Mdx Mice by Activation of Nrf2
Authors: Chengcao Sun, Cuili Yang, Shujun Li, Ruilin Xue, Liang Wang, Yongyong Xi, Dejia Li
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Backgrounds: Sulforaphane, one of the most important isothiocyanates in the human diet, is known to have chemopreventive and antioxidant activities in different tissues via activation of NF-E2-related factor 2 (Nrf2)-mediated induction of antioxidant/phase II enzymes, such as heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). However, its effects on muscular dystrophy remain unknown. This work was undertaken to evaluate the effects of Sulforaphane on Duchenne muscular dystrophy (DMD). Methods: 4-week-old mdx mice were treated with SFN by gavage (2 mg/kg body weight per day) for 8 weeks. Blood was collected from eye socket every week, and tibial anterior, extensor digitorum longus, gastrocnemius, soleus, triceps brachii muscles and heart samples were collected after 8-week gavage. Force measurements and mice exercise capacity assays were detected. GSH/GSSG ratio, TBARS, CK and LDH levels were analyzed by spectrophotometric methods. H&E staining was used to analyze histological and morphometric of skeletal muscles of mdx mice, and Evas blue dye staining was made to detect sarcolemmal integrity of mdx mice. Further, the role of Sulforaphane on Nrf2/ARE signaling pathway was analyzed by ELISA, western blot and qRT-PCR. Results: Our results demonstrated that SFN treatment increased the expression and activity of muscle phase II enzymes NQO1 and HO-1 with Nrf2 dependent manner. SFN significantly increased skeletal muscle mass, muscle force (~30%), running distance (~20%) and GSH/GSSG ratio (~3.2 folds) of mdx mice, and decreased the activities of plasma creatine phosphokinase (CK) (~45%) and lactate dehydrogenase (LDH) (~40%), gastrocnemius hypertrophy (~25%), myocardial hypertrophy (~20%) and MDA levels (~60%). Further, SFN treatment also reduced the central nucleation (~40%), fiber size variability, inflammation and improved the sarcolemmal integrity of mdx mice. Conclusions: Collectively, these results show that SFN can improve muscle function, pathology and protect dystrophic muscle from oxidative damage in mdx mice through Nrf2 signaling pathway, which indicate Nrf2 may have clinical implications for the treatment of patients with muscular dystrophy.Keywords: sulforaphane, duchenne muscular dystrophy, Nrf2, oxidative stress
Procedia PDF Downloads 32228129 Theoretical Study of Acetylation of P-Methylaniline Catalyzed by Cu²⁺ Ions
Authors: Silvana Caglieri
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Theoretical study of acetylation of p-methylaniline catalyzed by Cu2+ ions from the analysis of intermediate of the reaction was carried out. The study of acetylation of amines is of great interest by the utility of its products of reaction and is one of the most frequently used transformations in organic synthesis as it provides an efficient and inexpensive means for protecting amino groups in a multistep synthetic process. Acetylation of amine is a nucleophilic substitution reaction. This reaction can be catalyzed by Lewis acid, metallic ion. In reaction mechanism, the metallic ion formed a complex with the oxygen of the acetic anhydride carbonyl, facilitating the polarization of the same and the successive addition of amine at the position to form a tetrahedral intermediate, determining step of the rate of the reaction. Experimental work agreed that this reaction takes place with the formation of a tetrahedral intermediate. In the present theoretical work were investigated the structure and energy of the tetrahedral intermediate of the reaction catalyzed by Cu2+ ions. Geometries of all species involved in the acetylation were made and identified. All of the geometry optimizations were performed by the method at the DFT/B3LYP level of theory and the method MP2. Were adopted the 6-31+G* basis sets. Energies were calculated using the Mechanics-UFF method. Following the same procedure it was identified the geometric parameters and energy of reaction intermediate. The calculations show 61.35 kcal/mol of energy for the tetrahedral intermediate and the energy of activation for the reaction was 15.55 kcal/mol.Keywords: amides, amines, DFT, MP2
Procedia PDF Downloads 28228128 Pregnancy - The Unique Immunological Paradigm
Authors: Husham Bayazed
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Purpose of presentation: Pregnancy represents the most important period for the conservation of the species. The immune system is one of the most important systems protecting the mother against the environment and preventing damage to the fetus. This presentation aims to review and discuss the role of the immune system during pregnancy, the evolutionary inflammatory process through pregnancy, infectious and environmental exposure influences on the mother and the fetus, and the impacts of sexual dimorphism of the placenta on offspring susceptibility to different disorders. Recent Findings: In 1960, Peter Medawar (Nobel Prize Winner) proposed that the fetus, a semi-allograft, is similar to a tissue graft that escapes rejection through a mechanism involving systemic immune suppression (Graft –Host response). However, recent researchers and studies have documented that implantation means inflammation, and the inflammatory process is considered a breach of tolerance in pregnancy with immune induction, which is necessary for the protection of the mother and the fetus against infections and environmental triggers. This inflammatory process should be maintained during different pregnancy phases till parturition, and any block at any phase will be associated with pregnancy complications, including pregnancy failure or loss, miscarriage, and preterm birth subsequently. Maternal immune activation following any trigger can have a positive effect on the fetus. The old concept of the placenta being asexual is inaccurate, and being with sexual dimorphism with clear differences in susceptibility to different factors that stimulate maternal immunity. Summary: The presence of different immune cells ((i.e., T cells, B cells, NK cells, etc.) at the implantation site is considered proof of a strong maternal immune response to the fetus. Therefore, human pregnancy is considered a unique immunological paradigm requiring maternal immune modulation rather than suppression. So Medawar's postulation of maternal systemic immunosuppression is wrong. Maternal immune system activation triggered by infections, stress, diet, and pollution can have a positive effect on the fetus, with the development of fetal-trained immunity necessary for survival. The sexual dimorphism of the placenta seems to have an impact on the differences in sex susceptible to the environment maternal risk stimuli. This link to why the incidence of autism is increasing more among boys than girls.Keywords: pregnancy, maternal immunity, implantation and inflammation, placenta sexual dimorphism
Procedia PDF Downloads 9328127 Cloning and Expression of Human Interleukin 15: A Promising Candidate for Cytokine Immunotherapy
Authors: Sadaf Ilyas
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Recombinant cytokines have been employed successfully as potential therapeutic agent. Some cytokine therapies are already used as a part of clinical practice, ranging from early exploratory trials to well established therapies that have already received approval. Interleukin 15 is a pleiotropic cytokine having multiple roles in peripheral innate and adaptive immune cell function. It regulates the activation, proliferation and maturation of NK cells, T-cells, monocytes/macrophages and granulocytes, and the interactions between them thus acting as a bridge between innate and adaptive immune responses. Unraveling the biology of IL-15 has revealed some interesting surprises that may point toward some of the first therapeutic applications for this cytokine. In this study, the human interleukin 15 gene was isolated, amplified and ligated to a TA vector which was then transfected to a bacterial host, E. coli Top10F’. The sequence of cloned gene was confirmed and it showed 100% homology with the reported sequence. The confirmed gene was then subcloned in pET Expression system to study the IPTG induced expression of IL-15 gene. Positive expression was obtained for number of clones that showed 15 kd band of IL-15 in SDS-PAGE analysis, indicating the successful strain development that can be studied further to assess the potential therapeutic intervention of this cytokine in relevance to human diseases.Keywords: Interleukin 15, pET expression system, immune therapy, protein purification
Procedia PDF Downloads 41328126 Non-Steroidal Microtubule Disrupting Analogues Induce Programmed Cell Death in Breast and Lung Cancer Cell Lines
Authors: Marcel Verwey, Anna M. Joubert, Elsie M. Nolte, Wolfgang Dohle, Barry V. L. Potter, Anne E. Theron
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A tetrahydroisoquinolinone (THIQ) core can be used to mimic the A,B-ring of colchicine site-binding microtubule disruptors such as 2-methoxyestradiol in the design of anti-cancer agents. Steroidomimeric microtubule disruptors were synthesized by introducing C'2 and C'3 of the steroidal A-ring to C'6 and C'7 of the THIQ core and by introducing a decorated hydrogen bond acceptor motif projecting from the steroidal D-ring to N'2. For this in vitro study, four non-steroidal THIQ-based analogues were investigated and comparative studies were done between the non-sulphamoylated compound STX 3450 and the sulphamoylated compounds STX 2895, STX 3329 and STX 3451. The objective of this study was to investigate the modes of cell death induced by these four THIQ-based analogues in A549 lung carcinoma epithelial cells and metastatic breast adenocarcinoma MDA-MB-231 cells. Cytotoxicity studies to determine the half maximal growth inhibitory concentrations were done using spectrophotometric quantification via crystal violet staining and lactate dehydrogenase (LDH) assays. Microtubule integrity and morphologic changes of exposed cells were investigated using polarization-optical transmitted light differential interference contrast microscopy, transmission electron microscopy and confocal microscopy. Flow cytometric quantification was used to determine apoptosis induction and the effect that THIQ-based analogues have on cell cycle progression. Signal transduction pathways were elucidated by quantification of the mitochondrial membrane integrity, cytochrome c release and caspase 3, -6 and -8 activation. Induction of autophagic cell death by the THIQ-based analogues was investigated by morphological assessment of fluorescent monodansylcadaverine (MDC) staining of acidic vacuoles and by quantifying aggresome formation via flow cytometry. Results revealed that these non-steroidal microtubule disrupting analogues inhibited 50% of cell growth at nanomolar concentrations. Immunofluorescence microscopy indicated microtubule depolarization and the resultant mitotic arrest was further confirmed through cell cycle analysis. Apoptosis induction via the intrinsic pathway was observed due to depolarization of the mitochondrial membrane, induction of cytochrome c release as well as, caspase 3 activation. Potential involvement of programmed cell death type II was observed due to the presence of acidic vacuoles and aggresome formation. Necrotic cell death did not contribute significantly, indicated by stable LDH levels. This in vitro study revealed the induction of the intrinsic apoptotic pathway as well as possible involvement of autophagy after exposure to these THIQ-based analogues in both MDA-MB-231- and A549 cells. Further investigation of this series of anticancer drugs still needs to be conducted to elucidate the temporal, mechanistic and functional crosstalk mechanisms between the two observed programmed cell deaths pathways.Keywords: apoptosis, autophagy, cancer, microtubule disruptor
Procedia PDF Downloads 25328125 Conformation Prediction of Human Plasmin and Docking on Gold Nanoparticle
Authors: Wen-Shyong Tzou, Chih-Ching Huang, Chin-Hwa Hu, Ying-Tsang Lo, Tun-Wen Pai, Chia-Yin Chiang, Chung-Hao Li, Hong-Jyuan Jian
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Plasmin plays an important role in the human circulatory system owing to its catalytic ability of fibrinolysis. The immediate injection of plasmin in patients of strokes has intrigued many scientists to design vectors that can transport plasmin to the desired location in human body. Here we predict the structure of human plasmin and investigate the interaction of plasmin with the gold-nanoparticle. Because the crystal structure of plasminogen has been solved, we deleted N-terminal domain (Pan-apple domain) of plasminogen and generate a mimic of the active form of this enzyme (plasmin). We conducted a simulated annealing process on plasmin and discovered a very large conformation occurs. Kringle domains 1, 4 and 5 had been observed to leave its original location relative to the main body of the enzyme and the original doughnut shape of this enzyme has been transformed to a V-shaped by opening its two arms. This observation of conformational change is consistent with the experimental results of neutron scattering and centrifugation. We subsequently docked the plasmin on the simulated gold surface to predict their interaction. The V-shaped plasmin could utilize its Kringle domain and catalytic domain to contact the gold surface. Our findings not only reveal the flexibility of plasmin structure but also provide a guide for the design of a plasmin-gold nanoparticle.Keywords: docking, gold nanoparticle, molecular simulation, plasmin
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