Search results for: cell wall

Authors: Husham Bayazed

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Immune responses following surgical trauma play a pivotal role in predicting postoperative outcomes from healing and recovery to postoperative complications. Postoperative complications, including infections and protracted recovery, occur in a significant number of about 300 million surgeries performed annually worldwide. Complications cause personal suffering along with a significant economic burden on the healthcare system in any community. The accurate prediction of postoperative complications and patient-targeted interventions for their prevention remain major clinical provocations. Recent Findings: Recent studies are focusing on immune dysregulation mechanisms that occur in response to surgical trauma as a key determinant of postoperative complications. Antecedent studies mainly were plunging into the detection of inflammatory plasma markers, which facilitate in providing important clues regarding their pathogenesis. However, recent Single-cell technologies, such as mass cytometry or single-cell RNA sequencing, have markedly enhanced our ability to understand the immunological basis of postoperative immunological trauma complications and to identify their prognostic biological signatures. Summary: The advent of proteomic technologies has significantly advanced our ability to predict the risk of postoperative complications. Multiomic modeling of patients' immune states holds promise for the discovery of preoperative predictive biomarkers and providing patients and surgeons with information to improve surgical outcomes. However, more studies are required to accurately predict the risk of postoperative complications in individual patients.

Keywords: immune dysregulation, postoperative complications, surgical trauma, flow cytometry

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Authors: Viriyavudh Sim, WooYoung Jung

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Window system in high rise building is occasionally subjected to an excessive wind intensity, particularly during typhoon. The failure of window system did not affect overall safety of structural performance; however, it could endanger the safety of the residents. In this paper, comparison of fragility curves for window system of two residential buildings was studied. The probability of failure for individual window was determined with Monte Carlo Simulation method. Then, lognormal cumulative distribution function was used to represent the fragility. The results showed that windows located on the edge of leeward wall were more susceptible to wind load and the probability of failure for each window panel increased at higher floors.

Keywords: wind fragility, window system, high rise building, wind disaster

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Authors: Edison Bicudo

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Cell and gene therapies (CGTs) result from the intense manipulation of cells or the use of techniques such as gene editing. They have been increasingly used to tackle rare diseases or conditions of genetic origin, such as cancer. One might expect such a complex scientific field to be dominated by scientific findings and evidence-based explanations. However, people engaged in scientific argumentation also mobilize a range of cognitive operations of which they are not fully aware, in addition to drawing on widely available oral traditions. This paper analyses how experts discussing the potentialities and challenges of CGTs have recourse to a particular kind of prototypical myth. This sociology study, conducted at the University of Sussex (UK), involved interviews with scientists, regulators, and entrepreneurs involved in the development or governance of CGTs. It was observed that these professionals, when voicing their views, sometimes have recourse to narratives where CGTs appear as promising tools for alleviating or curing diseases. This is said to involve much personal, scientific, and financial sacrifice. In his study of traditional narratives, Hogan identified three prototypes: the romantic narrative, moved by the ideal of romantic union; the heroic narrative, moved by the desire for political power; and the sacrificial narrative, where the ideal is plenty, well-being, and health. It is argued here that discourses around CGTs often involve some narratives – or myths – that have a sacrificial nature. In this sense, the development of innovative therapies is depicted as a huge sacrificial endeavor involving biomedical scientists, biotech and pharma companies, and decision-makers. These sacrificial accounts draw on oral traditions and benefit from an emotional intensification that can be easily achieved in stories of serious diseases and physical suffering. Furthermore, these accounts draw on metaphorical understandings where diseases and vectors of diseases are considered enemies or invaders while therapies are framed as shields or protections. In this way, this paper aims to unravel the cognitive underpinnings of contemporary science – and, more specifically, biomedicine – revealing how myths, prototypes, and metaphors are highly operative even when complex reasoning is at stake. At the same time, this paper demonstrates how such hidden cognitive operations underpin the construction of powerful ideological discourses aimed at defending certain ways of developing, disseminating, and governing technologies and therapies.

Keywords: cell and gene therapies, myths, prototypes, metaphors

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Authors: Brahim Mahfoud, Ali Bendjaghlouli

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Natural convection is simulated in a truncated cone filled with nanofluid. Inclined and top walls have constant temperature where the heat source is located on the bottom wall of the conical container which is thermally insulated. A finite volume approach is used to solve the governing equations using the SIMPLE algorithm for different parameters such as Rayleigh number, inclination angle of inclined walls of the enclosure and heat source length. The results showed an enhancement in cooling system by using a nanofluid, when conduction regime is assisted. The inclination angle of inclined sidewall and heat source length affect the heat transfer rate and the maximum temperature.

Keywords: heat source, truncated cone, nanofluid, natural convection

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Authors: Jameela Ali, Hamid A. Jalab, Loay E. George, Abdul Rahim Ahmad, Azizah Suliman, Karim Al-Jashamy

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Red blood cells (RBC) are the most common types of blood cells and are the most intensively studied in cell biology. The lack of RBCs is a condition in which the amount of hemoglobin level is lower than normal and is referred to as “anemia”. Abnormalities in RBCs will affect the exchange of oxygen. This paper presents a comparative study for various techniques for classifyig the red blood cells as normal, or abnormal (anemic) using WEKA. WEKA is an open source consists of different machine learning algorithms for data mining applications. The algorithm tested are Radial Basis Function neural network, Support vector machine, and K-Nearest Neighbors algorithm. Two sets of combined features were utilized for classification of blood cells images. The first set, exclusively consist of geometrical features, was used to identify whether the tested blood cell has a spherical shape or non-spherical cells. While the second set, consist mainly of textural features was used to recognize the types of the spherical cells. We have provided an evaluation based on applying these classification methods to our RBCs image dataset which were obtained from Serdang Hospital-Malaysia, and measuring the accuracy of test results. The best achieved classification rates are 97%, 98%, and 79% for Support vector machines, Radial Basis Function neural network, and K-Nearest Neighbors algorithm respectively

Keywords: red blood cells, classification, radial basis function neural networks, suport vector machine, k-nearest neighbors algorithm

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Authors: W. Meron Mebrahtu, R. Absi

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Velocity distribution in turbulent open-channel flows is organized in a complex manner. This is due to the large spatial and temporal variability of fluid motion resulting from the free-surface turbulent flow condition. This phenomenon is complicated further due to the complex geometry of channels and the presence of solids transported. Thus, several efforts were made to understand the phenomenon and obtain accurate mathematical models that are suitable for engineering applications. However, predictions are inaccurate because oversimplified assumptions are involved in modeling this complex phenomenon. Therefore, the aim of this work is to study velocity distribution profiles and obtain simple, more accurate, and predictive mathematical models. Particular focus will be made on the acceptable simplification of the general transport equations and an accurate representation of eddy viscosity. Wide rectangular open-channel seems suitable to begin the study; other assumptions are smooth-wall, and sediment-free flow under steady and uniform flow conditions. These assumptions will allow examining the effect of the bottom wall and the free surface only, which is a necessary step before dealing with more complex flow scenarios. For this flow condition, two ordinary differential equations are obtained for velocity profiles; from the Reynolds-averaged Navier-Stokes (RANS) equation and equilibrium consideration between turbulent kinetic energy (TKE) production and dissipation. Then different analytic models for eddy viscosity, TKE, and mixing length were assessed. Computation results for velocity profiles were compared to experimental data for different flow conditions and the well-known linear, log, and log-wake laws. Results show that the model based on the RANS equation provides more accurate velocity profiles. In the viscous sublayer and buffer layer, the method based on Prandtl’s eddy viscosity model and Van Driest mixing length give a more precise result. For the log layer and outer region, a mixing length equation derived from Von Karman’s similarity hypothesis provides the best agreement with measured data except near the free surface where an additional correction based on a damping function for eddy viscosity is used. This method allows more accurate velocity profiles with the same value of the damping coefficient that is valid under different flow conditions. This work continues with investigating narrow channels, complex geometries, and the effect of solids transported in sewers.

Keywords: accuracy, eddy viscosity, sewers, velocity profile

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Authors: Ozan Ozkan, Hilal Turkoglu Sasmazel

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Natural polymers are widely used in tissue engineering applications, because of their biocompatibility, biodegradability and solubility in the physiological medium. On the other hand, synthetic polymers are also widely utilized in tissue engineering applications, because they carry no risk of infectious diseases and do not cause immune system reaction. However, the disadvantages of both polymer types block their individual usages as tissue scaffolds efficiently. Therefore, the idea of usage of natural and synthetic polymers together as a single 3D hybrid scaffold which has the advantages of both and the disadvantages of none has been entered to the literature. On the other hand, even though these hybrid structures support the cell adhesion and/or proliferation, various surface modification techniques applied to the surfaces of them to create topographical changes on the surfaces and to obtain reactive functional groups required for the immobilization of biomolecules, especially on the surfaces of synthetic polymers in order to improve cell adhesion and proliferation. In a study presented here, to improve the surface functionality and topography of the layer by layer electrospun 3D poly-epsilon-caprolactone/chitosan/poly-epsilon-caprolactone hybrid tissue scaffolds by using atmospheric pressure plasma method, thus to improve cell adhesion and proliferation of these tissue scaffolds were aimed. The formation/creation of the functional hydroxyl and amine groups and topographical changes on the surfaces of scaffolds were realized by using two different atmospheric pressure plasma systems (nozzle type and dielectric barrier discharge (DBD) type) carried out under different gas medium (air, Ar+O2, Ar+N2). The plasma modification time and distance for the nozzle type plasma system as well as the plasma modification time and the gas flow rate for DBD type plasma system were optimized with monitoring the changes in surface hydrophilicity by using contact angle measurements. The topographical and chemical characterizations of these modified biomaterials’ surfaces were carried out with SEM and ESCA, respectively. The results showed that the atmospheric pressure plasma modifications carried out with both nozzle type plasma and DBD plasma caused topographical and functionality changes on the surfaces of the layer by layer electrospun tissue scaffolds. However, the shelf life studies indicated that the hydrophilicity introduced to the surfaces was mainly because of the functionality changes. Therefore, according to the optimized results, samples treated with nozzle type air plasma modification applied for 9 minutes from a distance of 17 cm and Ar+O2 DBD plasma modification applied for 1 minute under 70 cm3/min O2 flow rate were found to have the highest hydrophilicity compared to pristine samples.

Keywords: biomaterial, chitosan, hybrid, plasma

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Authors: Roham Rafiee, Hadi Hesamsadat

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In this study, a parametric finite element modeling is developed to analyze failure modes of FRP pipes subjected to internal pressure. First-ply failure pressure and functional failure pressure was determined by a progressive damage modeling and then it is validated using experimental observations. The influence of both winding angle and fiber volume fraction is studied on the functional failure of FRP pipes and it corresponding pressure. It is observed that despite the fact that increasing fiber volume fraction will enhance the mechanical properties, it will be resulted in lower values for functional failure pressure. This shortcoming can be compensated by modifying the winding angle in angle plies of pipe wall structure.

Keywords: composite pipe, functional failure, progressive modeling, winding angle

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Authors: Samuel Akinlabi Ola, Emeka Segun Nnochiri, Stephen Kayode Aderomose, Paul Ayesemhe Edoh

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Fadama soils of Northern Nigeria are generally a problem soil for highway and geotechnical engineers. There has been no consistent conclusion on the effect of the strain rate on the shear strength of soils, thus necessitating the need to clarify this issue with various types of soil. Consolidated undrained tests with pore pressure measurements were conducted at optimum moisture content and maximum dry density using standard proctor compaction. Back pressures were applied to saturate the soil. The shear strength parameters were determined. Analyzing the results and model studies using the Rate Process Theory, functional relationships between the deviator stress and strain rate were determined and expressed mathematically as deviator stress = β0+ β1 log(strain rate) at each cell pressure where β0 and β1 are constants. Also, functional relationships between the pore pressure coefficient Āf and the time to failure were determined and expressed mathematically as pore pressure coefficient, Āf = ψ0+ѱ1log (time to failure) where ψ0 and ѱ1 are constants. For cell pressure between 69 – 310 kN/m2 (10 - 45psi) the constants found for Fadama soil in this study are ψ0=0.17 and ѱ1=0.18. The study also shows the dependence of the angle of friction (ø’) on the rate of strain as it increases from 22o to 25o for an increase in the rate of strain from 0.08%/min to 1.0%/min. Conclusively, the study also shows that within the strain rate utilized in the research, the deviator strength increased with the strain rate while the excess pore water pressure decreased with an increase in the rate of strain.

Keywords: deviator stress, Fadama soils, pore pressure coefficient, rate process

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Authors: Adedoyin Akintunde Adedayo, Onilude Abiodun Anthony

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The continuous usage of synthetic antibiotics in livestock production has led to the resistance of microbial pathogens. This has prompted research to find alternative sources. This study aims to compare the growth and intestinal health of broilers fed scent leaf meal (SLM) as an alternative to synthetic antibiotics. The study used a completely randomized design (CRD) with 300 one-week-old Arbor Acres broiler chicks. The chicks were divided into six treatments with five replicates of ten birds each. The feeding trial lasted 49 days, including a one-week acclimatization period. Commercial broiler diets were used. The diets included a negative control (no leaf meal or antibiotics), a positive control (0.10% oxy-tetracycline), and four diets with different levels of SLM (0.5%, 1.0%, 1.5%, and 2.0%). The supplementation of both oxy-tetracycline and SLM improved feed intake during the finisher phase. Birds fed SLM at a 1% inclusion level showed significantly (P<0.05) improved average body weight gain (ABWG), lowered feed-to-gain ratio, and cost per kilogram of weight gain compared to other diets. The mortality (2.0%) rate was significantly higher in the negative control group. White blood cell levels varied significantly (P<0.05) in birds fed SLM-supplemented diets, and the use of 2% SLM led to an increase in liver weight. However, welfare indices were not compromised.

Keywords: Arbor Acres, phyto-biotic, synthetic antibiotic, white blood cell, liver weight

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Authors: Junya Kouwa, Shinsuke Matsuno, Chihiro Inoue, Takehiro Himeno, Toshinori Watanabe

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Bi-propellant thrusters use impinging jet atomization to atomize liquid fuel and oxidizer. Atomized propellants are mixed and combusted due to auto-ignitions. Therefore, it is important for a prediction of thruster’s performance to simulate the primary atomization phenomenon; especially, the local mixture ratio can be used as indicator of thrust performance, so it is useful to evaluate it from numerical simulations. In this research, we propose a numerical method for considering bi-liquid and the mixture and install it to CIP-LSM which is a two-phase flow simulation solver with level-set and MARS method as an interfacial tracking method and can predict local mixture ratio distribution downstream from an impingement point. A new parameter, beta, which is defined as the volume fraction of one liquid in the mixed liquid within a cell is introduced and the solver calculates the advection of beta, inflow and outflow flux of beta to a cell. By validating this solver, we conducted a simple experiment and the same simulation by using the solver. From the result, the solver can predict the penetrating length of a liquid jet correctly and it is confirmed that the solver can simulate the mixing of liquids. Then we apply this solver to the numerical simulation of impinging jet atomization. From the result, the inclination angle of fan after the impingement in the bi-liquid condition reasonably agrees with the theoretical value. Also, it is seen that the mixture of liquids can be simulated in this result. Furthermore, simulation results clarify that the injecting condition affects the atomization process and local mixture ratio distribution downstream drastically.

Keywords: bi-propellant thrusters, CIP-LSM, free-surface flow simulation, impinging jet atomization

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Authors: Kirill D. Kapustin, Mikhail B. Krasilnikov, Anatoly A. Kudryavtsev

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Physical formation mechanisms of differential electron fluxes is high pressure positive column gas discharge are discussed. It is shown that the spatial differential fluxes of the electrons are directed both inward and outward depending on the energy relaxation law. In some cases the direction of energy differential flux at intermediate energies (5-10eV) in whole volume, except region near the wall, appeared to be down directed, so electron in this region dissipate more energy than gain from axial electric field. Paradoxical behaviour of electron flux in spatial-energy space is presented.

Keywords: plasma kinetics, electron distribution function, excitation and radiation rates, local and nonlocal EDF

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Authors: Jayahar Sivasubramanian

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Understanding laminar-turbulent transition process in hyper-sonic boundary layers is crucial for designing viable high speed flight vehicles. The study of transition becomes particularly important in the high speed regime due to the effect of transition on aerodynamic performance and heat transfer. However, even after many years of research, the transition process in hyper-sonic boundary layers is still not understood. This lack of understanding of the physics of the transition process is a major impediment to the development of reliable transition prediction methods. Towards this end, spatial Direct Numerical Simulations are conducted to investigate the instability waves generated by a localized disturbance in a hyper-sonic flat plate boundary layer. In order to model a natural transition scenario, the boundary layer was forced by a short duration (localized) pulse through a hole on the surface of the flat plate. The pulse disturbance developed into a three-dimensional instability wave packet which consisted of a wide range of disturbance frequencies and wave numbers. First, the linear development of the wave packet was studied by forcing the flow with low amplitude (0.001% of the free-stream velocity). The dominant waves within the resulting wave packet were identified as two-dimensional second mode disturbance waves. Hence the wall-pressure disturbance spectrum exhibited a maximum at the span wise mode number k = 0. The spectrum broadened in downstream direction and the lower frequency first mode oblique waves were also identified in the spectrum. However, the peak amplitude remained at k = 0 which shifted to lower frequencies in the downstream direction. In order to investigate the nonlinear transition regime, the flow was forced with a higher amplitude disturbance (5% of the free-stream velocity). The developing wave packet grows linearly at first before reaching the nonlinear regime. The wall pressure disturbance spectrum confirmed that the wave packet developed linearly at first. The response of the flow to the high amplitude pulse disturbance indicated the presence of a fundamental resonance mechanism. Lower amplitude secondary peaks were also identified in the disturbance wave spectrum at approximately half the frequency of the high amplitude frequency band, which would be an indication of a sub-harmonic resonance mechanism. The disturbance spectrum indicates, however, that fundamental resonance is much stronger than sub-harmonic resonance.

Keywords: boundary layer, DNS, hyper sonic flow, instability waves, wave packet

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Authors: Huajuan Shi

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Background: The biopsy of the preimplantation embryo may increase the potential risk and concern of embryo viability. Clinically discarded spent embryo medium (SEM) has entered the view of researchers, sparking an interest in noninvasive embryo screening. However, one of the major restrictions is the extremelty low quantity of cf-RNA, which is difficult to efficiently and unbiased amplify cf-RNA using traditional methods. Hence, there is urgently need to an efficient and low bias amplification method which can comprehensively and accurately obtain cf-RNA information to truly reveal the state of SEM cf-RNA. Result: In this present study, we established an agarose PCR amplification system, and has significantly improved the amplification sensitivity and efficiency by ~90 fold and 9.29 %, respectively. We applied agarose to sequencing library preparation (named AG-seq) to quantify and characterize cf-RNA in SEM. The number of detected cf-RNAs (3533 vs 598) and coverage of 3' end were significantly increased, and the noise of low abundance gene detection was reduced. The increasing percentage 5' end adenine and alternative splicing (AS) events of short fragments (< 400 bp) were discovered by AG-seq. Further, the profiles and characterizations of cf-RNA in spent cleavage medium (SCM) and spent blastocyst medium (SBM) indicated that 4‐mer end motifs of cf-RNA fragments could remarkably differentiate different embryo development stages. Significance: This study established an efficient and low-cost SEM amplification and library preparation method. Not only that, we successfully described the characterizations of SEM cf-RNA of preimplantation embryo by using AG-seq, including abundance features fragment lengths. AG-seq facilitates the study of cf-RNA as a noninvasive embryo screening biomarker and opens up potential clinical utilities of trace samples.

Keywords: cell-free RNA, agarose, spent embryo medium, RNA sequencing, non-invasive detection

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

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

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

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Authors: Regina R. Gunawan, Indwiani Astuti, H. Raden Danarto

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Cancer is the leading cause of death worldwide. Cancer is caused by mutations that alter the function of normal human genes and give rise to cancer genes. MicroRNA (miRNA) is a small non-coding RNA that regulates the gen through complementary bond towards mRNA target and cause mRNA degradation. miRNA works by either promoting or suppressing cell proliferation. miRNA level expression in cancer may offer another value of miRNA as a biomarker in cancer diagnostic. miRNA-21 is believed to have a role in carcinogenesis by enhancing proliferation, anti-apoptosis, cell cycle progression and invasion of tumor cells. Hsa-miR-21-5p marker has been identified in Prostate Cancer (PCa) and Benign Prostatic Hyperplasia (BPH) patient’s urine. This research planned to explore the diagnostic performance of miR-21 to differentiate PCa and BPH patients. In this study, urine samples were collected from 20 PCa patients and 20 BPH patients. miR-21 relative expression against the reference gene was analyzed and compared between the two. miRNA expression was analyzed using the comparative quantification method to find the fold change. miR-21 validity in identifying PCa patients was performed by quantifying the sensitivity and specificity with the contingency table. miR-21 relative expression against miR-16 in PCa patient and in BPH patient has 12,98 differences in fold change. From a contingency table of Cq expression of miR-21 in identifying PCa patients from BPH patient, Cq miR-21 has 100% sensitivity and 75% specificity. miR-21 relative expression can be used in discriminating PCa from BPH by using a urine sample. Furthermore, the expression of miR-21 has higher sensitivity compared to PSA (Prostate specific antigen), therefore miR-21 has a high potential to be analyzed and developed more.

Keywords: benign prostate hyperplasia, biomarker, miRNA-21, prostate cancer

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Authors: Mustafa Al-Yaseen, Haider Mohammed Mahdi, Haider Ali Al–Zahid, Nazar S. Haddad

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Background: Early diagnosis of musculoskeletal infections is of vital importance to avoid devastating complications. There is no single laboratory marker which is sensitive and specific in diagnosing these infections accurately. White blood cell count, erythrocyte sedimentation rate, and C-reactive protein are not specific as they can also be elevated in conditions other than bacterial infections. Materials Culture and sensitivity is not a true gold standard due to its varied positivity rates. Serum Procalcitonin is one of the new laboratory markers for pyogenic infections. The objective of this study is to assess the value of PCT in the diagnosis of soft tissue, bone, and joint infections. Patients and Methods: Patients of all age groups (seventy-four patients) with a diagnosis of musculoskeletal infection are prospectively included in this study. All patients were subjected to White blood cell count, erythrocyte sedimentation rate, C-reactive protein, and serum Procalcitonin measurements. A healthy non infected outpatient group (twenty-two patients) taken as a control group and underwent the same evaluation steps as the study group. Results: The study group showed mean Procalcitonin levels of 1.3 ng/ml. Procalcitonin, at 0.5 ng/ml, was (42.6%) sensitive and (95.5%) specific in diagnosing of musculoskeletal infections with (positive predictive value of 87.5% and negative predictive value of 48.3%) and (positive likelihood ratio of 9.3 and negative likelihood ratio of 0.6). Conclusion: Serum Procalcitonin, at a cut – off of 0.5 ng/ml, is a specific but not sensitive marker in the diagnosis of musculoskeletal infections, and it can be used effectively to rule in the diagnosis of infection but not to rule out it.

Keywords: procalcitonin, infection, labratory markers, musculoskeletal

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Authors: M. Markova, E. Filova, O. Kaplan, R. Matejka, L. Bacakova

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The porcine pericardium is used as a material for cardiac and aortic valves substitutes. Current biological aortic heart valve prosthesis have a limited lifetime period because they undergo degeneration. In order to make them more biocompatible and prolong their lifetime it is necessary to reseed the decellularized prostheses with endothelial cells and with valve interstitial cells. The endothelialization of the prosthesis-surface may be supported by suitable chemical surface modification of the prosthesis. The aim of this study is to prepare bioactive fibrin layers which would both support endothelialization of porcine pericardium and enhance differentiation and maturation of the endothelial cells seeded. As a material for surface adjustments we used layers of fibrin with/without heparin and some of them with adsorbed or chemically bound FGF2, VEGF or their combination. Fibrin assemblies were prepared in 24-well cell culture plate and were seeded with HSVEC (Human Saphenous Vein Endothelial Cells) at a density of 20,000 cells per well in EGM-2 medium with 0.5% FS and without heparin, without FGF2 and without VEGF; medium was supplemented with aprotinin (200 U/mL). As a control, surface polystyrene (PS) was used. Fibrin was also used as homogeneous impregnation of the decellularized porcine pericardium throughout the scaffolds. Morphology, density, and viability of the seeded endothelial cells were observed from micrographs after staining the samples by LIVE/DEAD cytotoxicity/viability assay kit on the days 1, 3, and 7. Endothelial cells were immunocytochemically stained for proteins involved in cell adhesion, i.e. alphaV integrin, vinculin, and VE-cadherin, markers of endothelial cells differentiation and maturation, i.e. von Willebrand factor and CD31, and for extracellular matrix proteins typically produced by endothelial cells, i.e. type IV collagen and laminin. The staining intensities were subsequently quantified using a software. HSVEC cells grew on each of the prepared surfaces better than on control surface. They reached confluency. The highest cell densities were obtained on the surface of fibrin with heparin and both grow factors used together. Intensity of alphaV integrins staining was highest on samples with remained fibrin layer, i.e. on layers with lower cell densities, i.e. on fibrin without heparin. Vinculin staining was apparent, but was rather diffuse, on fibrin with both FGF2 and VEGF and on control PS. Endothelial cells on all samples were positively stained for von Willebrand factor and CD31. VE-cadherin receptors clusters were best developed on fibrin with heparin and growth factors. Significantly stronger staining of type IV collagen was observed on fibrin with heparin and both growth factors. Endothelial cells on all samples produced laminin-1. Decellularized pericardium was homogeneously filled with fibrin structures. These fibrin-modified pericardium samples will be further seeded with cells and cultured in a bioreactor. Fibrin layers with/without heparin and with adsorbed or chemically bound FGF2, VEGF or their combination are good surfaces for endothelialization of cardiovascular prostheses or porcine pericardium based heart valves. Supported by the Ministry of Health, grants No15-29153A and 15-32497A, and the Grant Agency of the Czech Republic, project No. P108/12/G108.

Keywords: aortic valves prosthesis, FGF2, heparin, HSVEC cells, VEGF

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Authors: Inas Raafat, Azza El Bassiouny, Waldemar L. Olszewsky, Nagui E. Mikhail, Mona Nossier, Nora E. I. El-Bassiouni, Mona Zoheiry, Houda Abou Taleb, Noha Abd El-Aal, Ali Baioumy, Shimaa Attia

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Background: Orthotopic liver transplantation is an established treatment for patients with severe acute and end-stage chronic liver disease. The shortage of donor organs continues to be the rate-limiting factor for liver transplantation throughout the world. Hepatocyte transplantation is a promising treatment for several liver diseases and can, also, be used as a "bridge" to liver transplantation in cases of liver failure. Aim of the work: This study was designed to develop a highly efficient protocol for isolation and transplantation of hepatocytes in experimental Lewis rat model to provide satisfactory guidelines for future application on humans.Materials and Methods: Hepatocytes were isolated from the liver by double perfusion technique and bone marrow cells were isolated by centrifugation of shafts of tibia and femur of donor Lewis rats. Recipient rats were subjected to sub-lethal dose of irradiation 2 days before transplantation. In a laparotomy operation the spleen was injected by freshly isolated hepatocytes and bone marrow cells were injected intravenously. The animals were sacrificed 45 day latter and splenic sections were prepared and stained with H & E, PAS AFP and Prox1. Results: The data obtained from this study showed that the double perfusion technique is successful in separation of hepatocytes regarding cell number and viability. Also the method used for bone marrow cells separation gave excellent results regarding cell number and viability. Intrasplenic engraftment of hepatocytes and live tissue formation within the splenic tissue were found in 70% of cases. Hematoxylin and eosin stained splenic sections from 7 rats showed sheets and clusters of cells among the splenic tissues. Periodic Acid Schiff stained splenic sections from 7 rats showed clusters of hepatocytes with intensely stained pink cytoplasmic granules denoting the presence of glycogen. Splenic sections from 7 rats stained with anti-α-fetoprotein antibody showed brownish cytoplasmic staining of the hepatocytes denoting positive expression of AFP. Splenic sections from 7 rats stained with anti-Prox1 showed brownish nuclear staining of the hepatocytes denoting positive expression of Prox1 gene on these cells. Also, positive expression of Prox1 gene was detected on lymphocytes aggregations in the spleens. Conclusions: Isolation of liver cells by double perfusion technique using collagenase buffer is a reliable method that has a very satisfactory yield regarding cell number and viability. The intrasplenic route of transplantation of the freshly isolated liver cells in an immunocompromised model was found to give good results regarding cell engraftment and tissue formation. Further studies are needed to assess function of engrafted hepatocytes by measuring prothrombin time, serum albumin and bilirubin levels.

Keywords: Lewis rats, hepatocytes, BMCs, transplantation, AFP, Prox1

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Authors: Seung Ju Yeon, Seul Ki Min, Jun Sang Park, Yeo Seon Kwon, Hoo Cheol Lee, Hyun Jung Shim, Il-Doo Kim, Ja Kyeong Lee, Hwa Sung Shin

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In brain injury, depleting oxidative stress is the most effective way to reduce the brain infarct size. C-phycocyanin (C-Pc) is a well-known antioxidant protein that has neuroprotective effects obtained from green microalgae. Astrocyte is glial cell that supports the nerve cell such as neuron, which account for a large portion of the brain. In brain injury, such as ischemia and reperfusion, astrocyte has an important rule that overcomes the oxidative stress and protect from brain reactive oxygen species (ROS) injury. However little is known about how C-Pc regulates the anti-oxidants effects of astrocyte. In this study, when the C-Pc was treated in oxidized astrocyte, we confirmed that inflammatory factors Interleukin-6 and Interleukin-3 were increased and antioxidants enzyme, Superoxide dismutase (SOD) and catalase was upregulated, and neurotrophic factors, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) was alleviated. Also, it was confirmed to reduce infarct size of the brain in ischemia and reperfusion because C-Pc has anti-oxidant effects in middle cerebral artery occlusion (MCAO) animal model. These results show that C-Pc can help astrocytes lead neuroprotective activities in the oxidative stressed environment of the brain. In summary, the C-PC protects astrocytes from oxidative stress and has anti-oxidative, anti-inflammatory, neurotrophic effects under ischemic situations.

Keywords: c-phycocyanin, astrocyte, reactive oxygen species, ischemia and reperfusion, neuroprotective effect

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Authors: Dipranjan Laha, Parimal Karmakar

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Metal oxide nanoparticles are well known to generate oxidative stress and deregulate normal cellular activities. Among these, transition metals copper oxide nanoparticles (CuO NPs) are more compelling than others and able to modulate different cellular responses. In this work, we have synthesized and characterized CuO NPs by various biophysical methods. These CuO NPs (~30 nm) induce autophagy in human breast cancer cell line, MCF7 in a time and dose-dependent manner. Cellular autophagy was tested by MDC staining, induction of green fluorescent protein light chain 3 (GFP-LC3B) foci by confocal microscopy, transfection of pBABE-puro mCherry-EGFP-LC3B plasmid and western blotting of autophagy marker proteins LC3B, beclin1, and ATG5. Further, inhibition of autophagy by 3-Methyladenine (3-MA) decreased LD50 doses of CuO NPs. Such cell death was associated with the induction of apoptosis as revealed by FACS analysis, cleavage of PARP, dephosphorylation of Bad and increased cleavage product of caspase3. siRNA-mediated inhibition of autophagy-related gene beclin1 also demonstrated similar results. Finally, induction of apoptosis by 3-MA in CuO NPs treated cells were observed by TEM. This study indicates that CuO NPs are a potent inducer of autophagy which may be a cellular defense against the CuO NPs mediated toxicity and inhibition of autophagy switches the cellular response into apoptosis. A combination of CuO NPs with the autophagy inhibitor is essential to induce apoptosis in breast cancer cells. Acknowledgments: The authors would like to acknowledge for financial support for this research work to the Department of Biotechnology (No. BT/PR14661/NNT/28/494/2010), Government of India.

Keywords: nanoparticle, autophagy, apoptosis, siRNA-mediated inhibition

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Authors: D. Pradhan, G. Tripathy, S. Pradhan

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Objectives: Imperviousness gainst estrogen treatments is a noteworthy reason for infection backslide and mortality in estrogen receptor alpha (ERα)- positive breast diseases. Tamoxifen or estrogen withdrawal builds the reliance of breast malignancy cells on INT3 flagging. Here, we researched the commitment of Quercetin and INT3 motioning in endocrine-safe breast tumor cells. Methods: We utilized two models of endocrine treatments safe (ETR) breast tumor: Tamoxifen-safe (TamR) and long haul estrogen-denied (LTED) MCF7 cells. We assessed the transitory and intrusive limit of these cells by Transwell cells. Articulation of epithelial to mesenchymal move (EMT) controllers and in addition INT3 receptors and targets were assessed by constant PCR and western smudge investigation. Besides, we tried in-vitro hostile to Quercetin monoclonal Antibodies (mAbs) and Gamma Secretase Inhibitors (GSIs) as potential EMT inversion remedial specialists. At last, we created stable Quercetin overexpressing MCF7 cells and assessed their EMT components and reaction to Tamoxifen. Results: We found that ETR cells procured an Epithelial to Mesenchymal move (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we distinguished more elevated amount of INT3 however lower levels of INT1 and INT3 proposing a change to motioning through distinctive INT3 receptors after obtaining of resistance. Against Quercetin monoclonal antibodies and the GSI PF03084014 were powerful in obstructing the Quercetin/INT3 pivot and in part repressing the EMT process. As a consequence of this, cell relocation and attack were weakened and the immature microorganism like populace was essentially decreased. Hereditary hushing of Quercetin and INT3 prompted proportionate impacts. At long last, stable overexpression of Quercetin was adequate to make MCF7 lethargic to Tamoxifen by INT3 initiation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives intrusive conduct. Hostile to Quercetin mAbs and GSI PF03084014 lessen articulation of EMT particles decreasing cell obtrusiveness. Quercetin overexpression instigates Tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and INT3 warrants further clinical Correlation as substantial restorative methodologies in endocrine-safe breast.

Keywords: endocrine, epithelial, mesenchymal, INT3, quercetin, MCF7

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Authors: Vitheejongjaroen P., Jaisin Y., Pachekrepapol U., Taweechotipatr M.

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Lactic acid bacteria (LAB) are the most common type of microorganisms that had been used as probiotics also known for many beneficial health effects. The antioxidant activity of LAB is associated with numerous health-protective effects. This research aimed to investigate the antioxidant activity of lactic acid bacteria isolated from Thai sour pork sausage for their application in fermented milk products. Antioxidant activity determined by DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay showed that the isolate FN33-7, as 1 of 8 isolated exhibited scavenging activity in intact cell 5-7%, and supernatant 13-16%, intracellular cell free extract 42-48% respectively. This isolate was identified using 16S ribosomal DNA sequence analysis as Lactobacillus plantarum. The effect of milk fermented with L. plantarum FN33-7 on microbial count, pH and syneresis was assessed during refrigerated storage period of 28 days. The strain showed increased viability, pH level decreased, while syneresis increased. These results are similar to dairy products fermented with commercial starter cultures. Additionally, microstructure analysis of fermented milk by fluorescent microscopy showed that curd structure appeared to be dense and less porous in this fermented milk than commercial yogurt. The results of this study indicated that L. plantarum FN33-7 was a good probiotic candidate to be used in cultured milk products to reduce the risk of diseases caused by oxidative stress.

Keywords: Lactobacillus plantarum, probiotics, free radical, antioxidant, oxidative stress, fermented milk products

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Authors: Lesly Y Carmona-Sarabia, Luisa Barraza-Vergara, Vilmalí López-Mejías, Wandaliz Torres-García, Maribella Domenech-Garcia, Madeline Torres-Lugo

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Biosensors are used in many applications providing real-time monitoring to treat long-term conditions. Thus, understanding the physicochemical properties and biological side effects on the skin of polymers (e. g., poly(methyl methacrylate), PMMA) employed in the fabrication of wearable biosensors is crucial for the selection of manufacturing materials within this field. The PMMA (hydrophobic and thermoplastic polymer) is commonly employed as a coating material or substrate in the fabrication of wearable devices. The cytotoxicityof PMMA (including residual monomers or degradation products) on the skin, in terms of cells and tissue, is required to prevent possible adverse effects (cell death, skin reactions, sensitization) on human health. Within this work, accelerated aging of PMMA (Mw ~ 15000) through thermal and photochemical degradation was under-taken. The accelerated aging of PMMA was carried out by thermal (200°C, 1h) and photochemical degradation (UV-Vis, 8-15d) adapted employing ISO protocols (ISO-10993-12, ISO-4892-1:2016, ISO-877-1:2009, ISO-188: 2011). In addition, in vitro cytotoxicity evaluation of PMMA degradation products was performed using NIH3T3 fibroblast cells to assess the response of skin tissues (in terms of cell viability) exposed with polymers utilized to manufacture wearable biosensors, such as PMMA. The PMMA (Mw ~ 15000) before and after accelerated aging experiments was characterized by thermal gravimetric analysis (TGA), differential scanning calorimetric (DSC), powder X-ray diffractogram (PXRD), and scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) to determine and verify the successful degradation of this polymer under the specific conditions previously mention. The degradation products were characterized through nuclear magnetic resonance (NMR) to identify possible byproducts generated after the accelerated aging. Results demonstrated a percentage (%) weight loss between 1.5-2.2% (TGA thermographs) for PMMA after accelerated aging. The EDS elemental analysis reveals a 1.32 wt.% loss of carbon for PMMA after thermal degradation. These results might be associated with the amount (%) of PMMA degrade after the accelerated aging experiments. Furthermore, from the thermal degradation products was detected the presence of the monomer and methyl formate (low concentrations) and a low molecular weight radical (·COOCH3) in higher concentrations by NMR. In the photodegradation products, methyl formate was detected in higher concentrations. These results agree with the proposed thermal or photochemical degradation mechanisms found in the literature.1,2 Finally, significant cytotoxicity on the NIH3T3 cells was obtained for the thermal and photochemical degradation products. A decrease in cell viability by > 90% (stock solutions) was observed. It is proposed that the presence of byproducts (e.g. methyl formate or radicals such as ·COOCH₃) from the PMMA degradation might be responsible for the cytotoxicity observed in the NIH3T3 fibroblast cells. Additionally, experiments using skin models will be employed to compare with the NIH3T3 fibroblast cells model.

Keywords: biosensors, polymer, skin irritation, degradation products, cell viability

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Authors: T. Mushiri, K. Tengende, C. Mbohwa, T. Garikayi

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This paper introduces finite element analysis of Run off Mine (ROM) silo subjected to dynamic loading. The proposed procedure is based on the use of theoretical equations to come up with pressure and forces exerted by Platinum Group Metals (PGMs) ore to the silo wall. Finite Element Analysis of the silo involves the use of CAD software (AutoCAD) for3D creation and CAE software (T-FLEX) for the simulation work with an optimization routine to minimize the mass and also ensure structural stiffness and stability. In this research an efficient way to design and analysis of a silo in 3D T-FLEX (CAD) program was created the silo to stay within the constrains and so as to know the points of failure due dynamic loading.

Keywords: reinforced concrete silo, finite element analysis, T-FLEX software, AutoCAD

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Authors: Mahmoodreza Tahamtan

Abstract:

Background: Malignant surface epithelial ovarian tumors (SEOT) account for approximately 90% of primary ovarian cancer. Wilms tumor gene (WT1) product was defined as a tumor suppressor gene, but today it is considered capable of performing oncogenic functions. There seems to be differences in WT1 expression patterns among SEOT subtypes. We evaluate the immunohistochemical expression of WT1 protein among different histologic subtypes of SEOT. Materials and Methods: Immunohistochemistry for WT1 was done on 35 serous cystadenocarcinomas, 9 borderline serous tumors, 3 mucinous cystadenocarcinomas, 10 borderline mucinous tumors, 7 endometrioid ovarian carcinomas, 3 clear cell carcinomas, 1 malignant Brenner tumor, 2 metastatic adenocarcinomas, and 6 endometrial adenocarcinomas. A tumor was considered negative if < 1% of tumor cells were stained.Positive reactions were graded as follows:1+,1%-24%; 2+,25%-49%; 3+,50%-74%; 4+,75%-100%. Results: Of the 35 cases of ovarian serous cystadenocarcinoma, 30(85.7%) were diffusely positive (3+,4+),4 showed reactivity of < 50% of the tumor cells (1+,2+), and one were negative. All 9 borderline serous tumors showed immunoreactivity with WT1. All the mucinous tumors(n:13), endometrioid carcinomas (n: 7), clear cell carcinomas (n: 3), metastatic adenocarcinomas (n: 2) and primary endometrial carcinomas (n:6) were negative. The single malignant Brenner tumor showed a positive reaction for WT1(4+) Conclusion: WT1 is a good marker to distinguish primary ovarian serous carcinomas from other surface epithelial tumors (especially endometrioid subtype) and metastatic carcinomas (especially endometrial serous carcinoma), other than malignant mesothelioma. We cannot rely to the degree of expression inorder to separate high grade borderline serous tumors from low grade ones.

Keywords: WT1, ovary, epithelial tumors, malignant

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Authors: N. Prabavathy, R. Balasundaraprabhu, S. Shalini, Dhayalan Velauthapillai, S. Prasanna, N. Muthukumarasamy

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Dye sensitized solar cell (DSSC) has become a significant research area due to their fundamental and scientific importance in the area of energy conversion. Synthetic dyes as sensitizer in DSSC are efficient and durable but they are costlier, toxic and have the tendency to degrade. Natural sensitizers contain plant pigments such as anthocyanin, carotenoid, flavonoid, and chlorophyll which promote light absorption as well as injection of charges to the conduction band of TiO2 through the sensitizer. But, the efficiency of natural dyes is not up to the mark mainly due to instability of the pigment such as anthocyanin. The stability issues in vitro are mainly due to the effect of solvents on extraction of anthocyanins and their respective pH. Taking this factor into consideration, in the present work, the anthocyanins were extracted from the flower Caesalpinia pulcherrima (C. pulcherrimma) with various solvents and their respective stability and pH values are discussed. The usage of citric acid as solvent to extract anthocyanin has shown good stability than other solvents. It also helps in enhancing the sensitization properties of anthocyanins with Titanium dioxide (TiO2) nanorods. The IPCE spectra show higher photovoltaic performance for dye sensitized TiO2nanorods using citric acid as solvent. The natural DSSC using citric acid as solvent shows a higher efficiency compared to other solvents. Hence citric acid performs to be a safe solvent for natural DSSC in boosting the photovoltaic performance and maintaining the stability of anthocyanins.

Keywords: Caesalpinia pulcherrima, citric acid, dye sensitized solar cells, TiO₂ nanorods

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Authors: Satya Eswari Jujjavarapu, Swast Dhagat

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Contagious diseases enact severe public health problems and have upsetting consequences. The cyclic lipopeptides explained by bacteria Bacillus, Paenibacillus, Pseudomonas, Streptomyces, Serratia, Propionibacterium and fungus Fusarium are very critical in confining the pathogens. As the degree of drug resistance upsurges in unparalleled manner, the perseverance of searching novel cyclic lipopeptides is being professed. The intense study has shown the implication of these bioactive compounds extending beyond antibacterial and antifungal. Lipopeptides, composed of single units of peptide and fatty acyl moiety, show broad spectrum antimicrobial effects. Among the surplus of cyclic lipopeptides, only few have materialized as strong antibiotics. For their functional vigor, polymyxin, daptomycin, surfactin, iturin and bacillomycin have been integrated in mainstream healthcare. In our work daptomycin has been a major part of antimicrobial resource since the past decade. Daptomycin, a cyclic lipopeptide consists of 13-member amino acid with a decanoyl side-chain. This structure of daptomycin confers it the mechanism of action through which it forms pore in the bacterial cell membrane resulting in the death of cell. Daptomycin is produced by Streptococccus roseoporus and acts against Streptococcus pneumonia (PSRP), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The PDB structure and ligands of daptomycin are available online. The molecular docking studies of these ligands with the lipopeptides were performed and their docking score and glide energy were recorded.

Keywords: daptomycin, molecular docking, structure-based drug design, lipopeptide

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Authors: Elhamalsadat Ghaffari, Moghan Amirhosseinian, Amir Khaleghipour

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Multifunctional bioactive glasses (BGs) are designed with a focus on the provision of bactericidal and biological properties desired for angiogenesis, osteogenesis, and ultimately potential applications in bone tissue engineering. To achieve these, six sol-gel copper/magnesium substituted derivatives of 58S-BG, i.e. a mol% series of 60SiO₂-4P₂O₅-5CuO-(31-x) CaO/xMgO (where x=0, 1, 3, 5, 8, and 10), were synthesized. Afterwards, the effect of MgO/CaO substitution on the in vitro formation of nano-hydroxyapatite (HA), osteoblast-like cell responses and BGs antibacterial performance were studied. During the BGs synthesis, the elimination of nitrates was achieved at 700 °C that prevented the BGs crystallization and stabilized the obtained dried gels. The structural and morphological evaluations were performed with X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). These characterizations revealed that Cu-substituted 58S-BG consisting of 5 mol% MgO (BG-5/5) slightly had retarded the formation of HA. In addition, Cu-substituted 58S-BGs consisting 8 mol% and 10 mol% MgO (BG-5/8 and BG-5/10) displayed lower bioactivity probably due to the lower ion release rate of Ca–Si into the simulated body fluid (SBF). The determination of 3-(4, 5 dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and alkaline phosphate (ALP) activities proved that the highest values of both differentiation and proliferation of MC3T3-E1 cells can be obtained from a 5 mol% MgO substituted BG, while the over addition of MgO (8 mol% and 10 mol%) decreased the bioactivity. Furthermore, these novel Cu/Mg-substituted 58S-BGs displayed antibacterial effect against methicillin-resistant Staphylococcus aureus bacteria. Taken together, the results suggest the equally-substituted BG-5/5 (i.e. the one consists of 5 mol% of both CuO and MgO) as a promising candidate for bone tissue engineering, among all newly designed BGs in this work, owing to its desirable cell proliferation, ALP activity and antibacterial properties.

Keywords: apatite, bioactivity, biomedical applications, sol-gel processes

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Authors: Inês N. Peça , A. Bicho, Rui Gardner, M. Margarida Cardoso

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Inorganic/organic nanocomplexes offer tremendous scope for future biomedical applications, including imaging, disease diagnosis and drug delivery. The combination of Fe3O4 with biocompatible polymers to produce smart drug delivery systems for use in pharmaceutical formulation present a powerful tool to target anti-cancer drugs to specific tumor sites through the application of an external magnetic field. In the present study, we focused on the evaluation of the effect of the magnetic field application time on the rate of drug release from iron oxide polymeric nanoparticles. Doxorubicin, an anticancer drug, was selected as the model drug loaded into the nanoparticles. Nanoparticles composed of poly(d-lactide-co-glycolide (PLGA), a biocompatible polymer already approved by FDA, containing iron oxide nanoparticles (MNP) for magnetic targeting and doxorubicin (DOX) were synthesized by the o/w solvent extraction/evaporation method and characterized by scanning electron microscopy (SEM), by dynamic light scattering (DLS), by inductively coupled plasma-atomic emission spectrometry and by Fourier transformed infrared spectroscopy. The produced particles yielded smooth surfaces and spherical shapes exhibiting a size between 400 and 600 nm. The effect of the magnetic doxorubicin loaded PLGA nanoparticles produced on cell viability was investigated in mammalian CHO cell cultures. The results showed that unloaded magnetic PLGA nanoparticles were nontoxic while the magnetic particles without polymeric coating show a high level of toxicity. Concerning the therapeutic activity doxorubicin loaded magnetic particles cause a remarkable enhancement of the cell inhibition rates compared to their non-magnetic counterpart. In vitro drug release studies performed under a non-permanent magnetic field show that the application time and the on/off cycle duration have a great influence with respect to the final amount and to the rate of drug release. In order to determine the mechanism of drug release, the data obtained from the release curves were fitted to the semi-empirical equation of the the Korsmeyer-Peppas model that may be used to describe the Fickian and non-Fickian release behaviour. Doxorubicin release mechanism has shown to be governed mainly by Fickian diffusion. The results obtained show that the rate of drug release from the produced magnetic nanoparticles can be modulated through the magnetic field time application.

Keywords: drug delivery, magnetic nanoparticles, PLGA nanoparticles, controlled release rate

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