Search results for: single cell
6382 Comparative Parametric Analysis on the Dynamic Response of Fibre Composite Beams with Debonding
Authors: Indunil Jayatilake, Warna Karunasena
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Fiber Reinforced Polymer (FRP) composites enjoy an array of applications ranging from aerospace, marine and military to automobile, recreational and civil industry due to their outstanding properties. A structural glass fiber reinforced polymer (GFRP) composite sandwich panel made from E-glass fiber skin and a modified phenolic core has been manufactured in Australia for civil engineering applications. One of the major mechanisms of damage in FRP composites is skin-core debonding. The presence of debonding is of great concern not only because it severely affects the strength but also it modifies the dynamic characteristics of the structure, including natural frequency and vibration modes. This paper deals with the investigation of the dynamic characteristics of a GFRP beam with single and multiple debonding by finite element based numerical simulations and analyses using the STRAND7 finite element (FE) software package. Three-dimensional computer models have been developed and numerical simulations were done to assess the dynamic behavior. The FE model developed has been validated with published experimental, analytical and numerical results for fully bonded as well as debonded beams. A comparative analysis is carried out based on a comprehensive parametric investigation. It is observed that the reduction in natural frequency is more affected by single debonding than the equally sized multiple debonding regions located symmetrically to the single debonding position. Thus it is revealed that a large single debonding area leads to more damage in terms of natural frequency reduction than isolated small debonding zones of equivalent area, appearing in the GFRP beam. Furthermore, the extents of natural frequency shifts seem mode-dependent and do not seem to have a monotonous trend of increasing with the mode numbers.Keywords: debonding, dynamic response, finite element modelling, novel FRP beams
Procedia PDF Downloads 1206381 Functioning of a Temporarily Single Parent Family System Due to Migration from the Perspective of Adolescents with Cerebral Palsy
Authors: A. Gagat-Matuła
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There is a definite lack – in Poland, as well as around the world – of empirical studies of families raising handicapped child, in which one parent migrates. In diagnostics of the functioning of such families emphasis should be placed not only on the difficulties, but most of all it should be indicated what possibilities are there for the family and how it overcomes the difficulties. Migration of a parent on the one hand is a chance to improve the family’s material situation. In certain circumstances this may only be an “escape” into work from the issues associated with the upbringing and rehabilitation of a handicapped child. The aim of the study was to learn the functioning of a temporarily single parent family system as a result of migration of a parent from the perspective of adolescents with cerebral palsy. The study was conducted in the year 2013 in the area of Eastern Poland. It involved an analysis of 70 persons (with cerebral palsy in an intellectual capacity) from families in which at least one of the parents migrates. The study incorporated the diagnostic survey method. These tools were used: Family Evaluation Scales (SOR) adapted for Poland by Andrzej Margasiński. The explorations in this study indicate, that 47% of studied temporarily single parent families are balanced models. This is evidence of the resources at the disposal of the family which, despite the disability of the child and temporary separation, is able to function properly. The conducted studies show, that 37% of temporarily single parent families are imbalanced models in the perception of adolescents with cerebral palsy. These families experience functional difficulties and require psychological and pedagogical support. There is a need for building skills related to effective coping with family stress. Especially considering, that families of an imbalanced type do not use the internal and external resources of the family system. Such a situation may deepen the disarrangement of family life. In intermediate families (16%) there are also temporary difficulties in functioning. Separation anxiety experienced by mothers may disrupt relations and introduce additional stress factors. For that reason it is important to provide support for women with difficulties coping with the emotions associated with raising handicapped adolescents and migratory separation.Keywords: child with cerebral palsy, family, migration, parents
Procedia PDF Downloads 4206380 On a Single Server Queue with Arrivals in Batches of Variable Size, Generalized Coxian-2 Service and Compulsory Server Vacations
Authors: Kailash C. Madan
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We study the steady state behaviour of a batch arrival single server queue in which the first service with general service times is compulsory and the second service with general service times is optional. We term such a two phase service as generalized Coxian-2 service. Just after completion of a service the server must take a vacation of random length of time with general vacation times. We obtain steady state probability generating functions for the queue size as well as the steady state mean queue size at a random epoch of time in explicit and closed forms. Some particular cases of interest including some known results have been derived.Keywords: batch arrivals, compound Poisson process, generalized Coxian-2 service, steady state
Procedia PDF Downloads 4586379 In vitro Modulation of Cytokine Expression by an Aqueous Licorice Extract in Canine
Authors: A. Watson, G. Telford, D. I. Pritchard
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Objective: We investigated the immunomodulatory ability of licorice (Glycyrrhiza glabra). Such activities could have value for the management of common immunological diseases in dogs, such as environmental allergy. This study investigated the potential of a Licorice root extract (LRE) to influence the relative expression of Th-1, Th-2, and Th-17 cytokines in canine peripheral blood mononuclear cells (PBMC). Methods: A LRE was prepared using an alcoholic-aqueous-based solvent method. The extract was tested in three in vitro assays using canine leukocytes to determine its toxicity and immunoregulatory profile. Extract toxicity was assessed using the human T-lymphocyte cell line, Jurkat E6.1. The impact of the extract on the proliferation of concanavalin-activated canine PBMC was also determined. Finally, the extract was assessed for its ability to influence cytokine release in activated PBMC, measuring culture medium concentrations of interleukin-17, interferon gamma, and interleukin-4. One-way ANOVA followed by Dunnett’s post-test was used for statistics using concanavalin positive control as reference (p ≤ 0.05). Results: There was evidence that the LRE had specific immunomodulatory properties, causing significant inhibition of IL4 expression over a non-toxic/non-cytostatic concentration range (p < 0.001). In the same cell incubations, there was no significant impact on IL17 nor IFNg over the same non-toxic/non-cytostatic concentration range. Conclusion: The study provides in vitro evidence that LRE preferentially reduces the expression of a Th-2-type cytokine, IL4. The dog population, as with humans, is prone to conditions associated with a Th-2 bias of the immune system, such as environmental allergy. Based on these results, licorice merits further evaluation as a useful immune modulator for such allergic diseases.Keywords: cytokine, Glycyrrhiza glabra, peripheral blood mononuclear cells, T-cell activation
Procedia PDF Downloads 1266378 Human Mesenchymal Stem Cells as a Potential Source for Cell Therapy in Liver Disorders
Authors: Laila Montaser, Hala Gabr, Maha El-Bassuony, Gehan Tawfeek
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Orthotropic liver transplantation (OLT) is the final procedure of both end stage and metabolic liver diseases. Hepatocyte transplantation is an alternative for OLT, but the sources of hepatocytes are limited. Bone marrow mesenchymal stem cells (BM-MSCs) can differentiate into hepatocyte-like cells and are a potential alternative source for hepatocytes. The MSCs from bone marrow are a promising target population as they are capable of differentiating along multiple lineages and, at least in vitro, have significant expansion capability. MSCs from bone marrow may have the potential to differentiate in vitro and in vivo into hepatocytes. Our study examined whether mesenchymal stem cells (MSCs), which are stem cells originated from human bone marrow, are able to differentiate into functional hepatocyte-like cells in vitro. Our aim was to investigate the differentiation potential of BM-MSCs into hepatocyte-like cells. Adult stem cell therapy could solve the problem of degenerative disorders, including liver disease.Keywords: bone marrow, differentiation, hepatocyte, stem cells
Procedia PDF Downloads 5216377 Immunolabeling of TGF-β during Muscle Regeneration
Authors: K. Nikovics, D. Riccobono, M. Oger, H. Morin, L. Barbier, T. Poyot, X. Holy, A. Bendahmane, M. Drouet, A. L. Favier
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Muscle regeneration after injury (as irradiation) is of great importance. However, the molecular and cellular mechanisms are still unclear. Cytokines are believed to play fundamental role in the different stages of muscle regeneration. They are secreted by many cell populations, but the predominant producers are macrophages and helper T cells. On the other hand, it has been shown that adipose tissue derived stromal/stem cell (ASC) injection could improve muscle regeneration. Stem cells probably induce the coordinated modulations of gene expression in different macrophage cells. Therefore, we investigated the patterns and timing of changes in gene expression of different cytokines occurring upon stem cells loading. Muscle regeneration was studied in an irradiated muscle of minipig animal model in presence or absence of ASC treatment (irradiated and treated with ASCs, IRR+ASC; irradiated not-treated with ASCs, IRR; and non-irradiated no-IRR). We characterized macrophage populations by immunolabeling in the different conditions. In our study, we found mostly M2 and a few M1 macrophages in the IRR+ASC samples. However, only few M2b macrophages were noticed in the IRR muscles. In addition, we found intensive fibrosis in the IRR samples. With in situ hybridization and immunolabeling, we analyzed the cytokine expression of the different macrophages and we showed that M2d macrophage are the most abundant in the IRR+ASC samples. By in situ hybridization, strong expression of the transforming growth factor β (TGF-β) was observed in the IRR+ASC but very week in the IRR samples. But when we analyzed TGF-β level with immunolabeling the expression was very different: many M2 macrophages showed week expression in IRR+ASC and few cells expressing stronger level in IRR muscles. Therefore, we investigated the MMP expressions in the different muscles. Our data showed that the M2 macrophages of the IRR+ASC muscle expressed MMP2 proteins. Our working hypothesis is that MMP2 expression of the M2 macrophages can decrease fibrosis in the IRR+ASC muscle by capturing TGF-β.Keywords: adipose tissue derived stromal/stem cell, cytokine, macrophage, muscle regeneration
Procedia PDF Downloads 2346376 Thermal Properties of Polyhedral Oligomeric Silsesquioxanes/Polyimide Nanocomposite
Authors: Seyfullah Madakbas, Hatice Birtane, Memet Vezir Kahraman
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In this study, we aimed to synthesize and characterize polyhedral oligomeric silsesquioxanes containing polyimide nanocomposite. Polyimide nanocomposites widely have been used in membranes in fuel cell, solar cell, gas filtration, sensors, aerospace components, printed circuit boards. Firstly, polyamic acid was synthesized and characterized by Fourier Transform Infrared. Then, polyhedral oligomeric silsesquioxanes containing polyimide nanocomposite was prepared with thermal imidization method. The obtained polyimide nanocomposite was characterized by Fourier Transform Infrared, Scanning Electron Microscope, Thermal Gravimetric Analysis and Differential Scanning Calorimetry. Thermal stability of polyimide nanocomposite was evaluated by thermal gravimetric analysis and differential scanning calorimetry. Surface morphology of composite samples was investigated by scanning electron microscope. The obtained results prove that successfully prepared polyhedral oligomeric silsesquioxanes are containing polyimide nanocomposite. The obtained nanocomposite can be used in many industries such as electronics, automotive, aerospace, etc.Keywords: polyimide, nanocomposite, polyhedral oligomeric silsesquioxanes
Procedia PDF Downloads 1816375 Aberrant Genome‐Wide DNA Methylation Profiles of Peripheral Blood Mononuclear Cells from Patients Hospitalized with COVID-19
Authors: Inam Ridha, Christine L. Kuryla, Madhuranga Thilakasiri Madugoda Ralalage Don, Norman J. Kleiman, Yunro Chung, Jin Park, Vel Murugan, Joshua LaBaer
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To date, more than 275 million people worldwide have been diagnosed with COVID-19 and the rapid spread of the omicron variant suggests many millions more will soon become infected. Many infections are asymptomatic, while others result in mild to moderate illness. Unfortunately, some infected individuals exhibit more serious symptoms including respiratory distress, thrombosis, cardiovascular disease, multi-organ failure, cognitive difficulties, and, in roughly 2% of cases, death. Studies indicate other coronaviruses can alter the host cell's epigenetic profile and lead to alterations in the immune response. To better understand the mechanism(s) by which SARS-CoV-2 infection causes serious illness, DNA methylation profiles in peripheral blood mononuclear cells (PBMCs) from 90 hospitalized severely ill COVID-19 patients were compared to profiles from uninfected control subjects. Exploratory epigenome-wide DNA methylation analyses were performed using multiplexed methylated DNA immunoprecipitation (MeDIP) followed by pathway enrichment analysis. The findings demonstrated significant DNA methylation changes in infected individuals as compared to uninfected controls. Pathway analysis indicated that apoptosis, cell cycle control, Toll-like receptors (TLR), cytokine interactions, and T cell differentiation were among the most affected metabolic processes. In addition, changes in specific gene methylation were compared to SARS-CoV-2 induced changes in RNA expression using published RNA-seq data from 3 patients with severe COVID-19. These findings demonstrate significant correlations between differentially methylated and differentially expressed genes in a number of critical pathways.Keywords: COVID19, epigenetics, DNA mathylation, viral infection
Procedia PDF Downloads 1826374 In vitro and vivo Studies for Assessing the Anti-Proliferative, Anti-Migration and Apoptotic Activity of A. squamosa L. Leaves Extract
Authors: Rawan Al-Nemari, Abdulrahman Al-Senaidy, Abdelhabib Semlali
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Background and objectives: The most common cause of death in women worldwide is breast cancer. Regarding all chemotherapy disadvantages and side effects, it’s becoming necessary to identify natural products that target cancer cells with lesser harmful side effects on non-targeted cells and biological environment. Different parts of A. squamosa L., commonly known as custard apple, show varied therapeutic effects. The objective of this study is to investigate in vitro and in vivo, the anti-cancer activity of A. squamosa leaves extract. Methods: The physiological responses using MTT, nucleus staining, and LDH assays were used to evaluate cell survival and proliferation in both ER+ and ER- cells when they were exposed to extract. Monolayer wound repair assay was used to investigate the effect of extracts on cell migration. Apoptotic gene’s expression was investigated by real-time polymerase chain reaction. To study the effect of the extract on the size of tumor, breast cancer induced rats were used. Results: A. squamosa leaves extract showed high anti-proliferative and cytotoxicity effects against different breast cancer cell lines with high concentration, 100 ug/ml. The extracts have reduced the cells wound closure. Polymerase chain reaction revealed downregulation of Bcl-2 and upregulation of Bax. In breast cancer model animal developed in our laboratory, after 4 weeks treatment, treated groups have shown smaller tumor size in comparison with control group (n=4). Conclusion: These results suggest that A. squamosa leaves extract has anti-cancer activity against breast cancer in both in vitro and in vivo, and it may be developed as a potential novel agent to treat breast cancer.Keywords: apoptosis, breast cancer, migration, proliferation
Procedia PDF Downloads 1496373 Effect of Rotation Rate on Chemical Segregation during Phase Change
Authors: Nouri Sabrina, Benzeghiba Mohamed, Ghezal Abderrahmane
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Numerical parametric study is conducted to study the effects of ampoule rotation on the flows and the dopant segregation in vertical Bridgman (VB) crystal growth. Calculations were performed in unsteady state. The extended Darcy model, which includes the time derivative and Coriolis terms, has been employed in the momentum equation. It was found that the convection, and dopant segregation can be affected significantly by ampoule rotation, and the effect is similar to that by an axial magnetic field. Ampoule rotation decreases the intensity of convection and stretches the flow cell axially. When the convection is weak, the flow can be suppressed almost completely by moderate ampoule rotation and the dopant segregation becomes diffusion-controlled. For stronger convection, the elongated flow cell by ampoule rotation may bring dopant mixing into the bulk melt reducing axial segregation at the early stage of the growth. However, if the cellular flow cannot be suppressed completely, ampoule rotation may induce larger radial segregation due to poor mixing.Keywords: numerical simulation, heat and mass transfer, vertical solidification, chemical segregation
Procedia PDF Downloads 3526372 Using Single Decision Tree to Assess the Impact of Cutting Conditions on Vibration
Authors: S. Ghorbani, N. I. Polushin
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Vibration during machining process is crucial since it affects cutting tool, machine, and workpiece leading to a tool wear, tool breakage, and an unacceptable surface roughness. This paper applies a nonparametric statistical method, single decision tree (SDT), to identify factors affecting on vibration in machining process. Workpiece material (AISI 1045 Steel, AA2024 Aluminum alloy, A48-class30 Gray Cast Iron), cutting tool (conventional, cutting tool with holes in toolholder, cutting tool filled up with epoxy-granite), tool overhang (41-65 mm), spindle speed (630-1000 rpm), feed rate (0.05-0.075 mm/rev) and depth of cut (0.05-0.15 mm) were used as input variables, while vibration was the output parameter. It is concluded that workpiece material is the most important parameters for natural frequency followed by cutting tool and overhang.Keywords: cutting condition, vibration, natural frequency, decision tree, CART algorithm
Procedia PDF Downloads 3386371 Removal of Problematic Organic Compounds from Water and Wastewater Using the Arvia™ Process
Authors: Akmez Nabeerasool, Michaelis Massaros, Nigel Brown, David Sanderson, David Parocki, Charlotte Thompson, Mike Lodge, Mikael Khan
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The provision of clean and safe drinking water is of paramount importance and is a basic human need. Water scarcity coupled with tightening of regulations and the inability of current treatment technologies to deal with emerging contaminants and Pharmaceuticals and personal care products means that alternative treatment technologies that are viable and cost effective are required in order to meet demand and regulations for clean water supplies. Logistically, the application of water treatment in rural areas presents unique challenges due to the decentralisation of abstraction points arising from low population density and the resultant lack of infrastructure as well as the need to treat water at the site of use. This makes it costly to centralise treatment facilities and hence provide potable water direct to the consumer. Furthermore, across the UK there are segments of the population that rely on a private water supply which means that the owner or user(s) of these supplies, which can serve one household to hundreds, are responsible for the maintenance. The treatment of these private water supply falls on the private owners, and it is imperative that a chemical free technological solution that can operate unattended and does not produce any waste is employed. Arvia’s patented advanced oxidation technology combines the advantages of adsorption and electrochemical regeneration within a single unit; the Organics Destruction Cell (ODC). The ODC uniquely uses a combination of adsorption and electrochemical regeneration to destroy organics. Key to this innovative process is an alternative approach to adsorption. The conventional approach is to use high capacity adsorbents (e.g. activated carbons with high porosities and surface areas) that are excellent adsorbents, but require complex and costly regeneration. Arvia’s technology uses a patent protected adsorbent, Nyex™, which is a non-porous, highly conductive, graphite based adsorbent material that enables it to act as both the adsorbent and as a 3D electrode. Adsorbed organics are oxidised and the surface of the Nyex™ is regenerated in-situ for further adsorption without interruption or replacement. Treated water flows from the bottom of the cell where it can either be re-used or safely discharged. Arvia™ Technology Ltd. has trialled the application of its tertiary water treatment technology in treating reservoir water abstracted near Glasgow, Scotland, with promising results. Several other pilot plants have also been successfully deployed at various locations in the UK showing the suitability and effectiveness of the technology in removing recalcitrant organics (including pharmaceuticals, steroids and hormones), COD and colour.Keywords: Arvia™ process, adsorption, water treatment, electrochemical oxidation
Procedia PDF Downloads 2656370 Enhancement of Performance Utilizing Low Complexity Switched Beam Antenna
Authors: P. Chaipanya, R. Keawchai, W. Sombatsanongkhun, S. Jantaramporn
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To manage the demand of wireless communication that has been dramatically increased, switched beam antenna in smart antenna system is focused. Implementation of switched beam antennas at mobile terminals such as notebook or mobile handset is a preferable choice to increase the performance of the wireless communication systems. This paper proposes the low complexity switched beam antenna using single element of antenna which is suitable to implement at mobile terminal. Main beam direction is switched by changing the positions of short circuit on the radiating patch. There are four cases of switching that provide four different directions of main beam. Moreover, the performance in terms of Signal to Interference Ratio when utilizing the proposed antenna is compared with the one using omni-directional antenna to confirm the performance improvable.Keywords: switched beam, shorted circuit, single element, signal to interference ratio
Procedia PDF Downloads 1736369 Detection Kit of Type 1 Diabetes Mellitus with Autoimmune Marker GAD65 (Glutamic Acid Decarboxylase)
Authors: Aulanni’am Aulanni’am
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Incidence of Diabetes Mellitus (DM) progressively increasing it became a serious problem in Indonesia and it is a disease that government is priority to be addressed. The longer a person is suffering from diabetes the more likely to develop complications particularly diabetic patients who are not well maintained. Therefore, Incidence of Diabetes Mellitus needs to be done in the early diagnosis of pre-phase of the disease. In this pre-phase disease, already happening destruction of pancreatic beta cells and declining in beta cell function and the sign autoimmunity reactions associated with beta cell destruction. Type 1 DM is a multifactorial disease triggered by genetic and environmental factors, which leads to the destruction of pancreatic beta cells. Early marker of "beta cell autoreactivity" is the synthesis of autoantibodies against 65-kDa protein, which can be a molecule that can be detected early in the disease pathomechanism. The importance of early diagnosis of diabetic patients held in the phase of pre-disease is to determine the progression towards the onset of pancreatic beta cell destruction and take precautions. However, the price for this examination is very expensive ($ 150/ test), the anti-GAD65 abs examination cannot be carried out routinely in most or even in all laboratories in Indonesia. Therefore, production-based Rapid Test Recombinant Human Protein GAD65 with "Reverse Flow Immunchromatography Technique" in Indonesia is believed to reduce costs and improve the quality of care of patients with diabetes in Indonesia. Rapid Test Product innovation is very simple and suitable for screening and routine inspection of GAD65 autoantibodies. In the blood serum of patients with diabetes caused by autoimmunity, autoantibody-GAD65 is a major serologic marker to detect autoimmune reaction because their concentration level of stability.GAD65 autoantibodies can be found 10 years before clinical symptoms of diabetes. Early diagnosis is more focused to detect the presence autontibodi-GAD65 given specification and high sensitivity. Autoantibodies- GAD65 that circulates in the blood is a major indicator of the destruction of the islet cells of the pancreas. Results of research in collaboration with Biofarma has produced GAD65 autoantibodies based Rapid Test had conducted the soft launch of products and has been tested with the results of a sensitivity of 100 percent and a specificity between 90 and 96% compared with the gold standard (import product) which worked based on ELISA method.Keywords: diabetes mellitus, GAD65 autoantibodies, rapid test, sensitivity, specificity
Procedia PDF Downloads 2706368 Design and Simulation of Low Cost Boost-Half- Bridge Microinverter with Grid Connection
Authors: P. Bhavya, P. R. Jayasree
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This paper presents a low cost transformer isolated boost half bridge micro-inverter for single phase grid connected PV system. Since the output voltage of a single PV panel is as low as 20~50V, a high voltage gain inverter is required for the PV panel to connect to the single-phase grid. The micro-inverter has two stages, an isolated dc-dc converter stage and an inverter stage with a dc link. To achieve MPPT and to step up the PV voltage to the dc link voltage, a transformer isolated boost half bridge dc-dc converter is used. To output the synchronised sinusoidal current with unity power factor to the grid, a pulse width modulated full bridge inverter with LCL filter is used. Variable step size Maximum Power Point Tracking (MPPT) method is adopted such that fast tracking and high MPPT efficiency are both obtained. AC voltage as per grid requirement is obtained at the output of the inverter. High power factor (>0.99) is obtained at both heavy and light loads. This paper gives the results of computer simulation program of a grid connected solar PV system using MATLAB/Simulink and SIM Power System tool.Keywords: boost-half-bridge, micro-inverter, maximum power point tracking, grid connection, MATLAB/Simulink
Procedia PDF Downloads 3426367 3D Printing of Cold Atmospheric Plasma Treated Poly(ɛ-Caprolactone) for Bone Tissue Engineering
Authors: Dong Nyoung Heo, Il Keun Kwon
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Three-dimensional (3D) technology is a promising method for bone tissue engineering. In order to enhance bone tissue regeneration, it is important to have ideal 3D constructs with biomimetic mechanical strength, structure interconnectivity, roughened surface, and the presence of chemical functionality. In this respect, a 3D printing system combined with cold atmospheric plasma (CAP) was developed to fabricate a 3D construct that has a rough surface with polar functional chemical groups. The CAP-etching process leads to oxidation of chemical groups existing on the polycaprolactone (PCL) surface without conformational change. The surface morphology, chemical composition, mean roughness of the CAP-treated PCL surfaces were evaluated. 3D printed constructs composed of CAP-treated PCL showed an effective increment in the hydrophilicity and roughness of the PCL surface. Also, an in vitro study revealed that CAP-treated 3D PCL constructs had higher cellular behaviors such as cell adhesion, cell proliferation, and osteogenic differentiation. Therefore, a 3D printing system with CAP can be a highly useful fabrication method for bone tissue regeneration.Keywords: bone tissue engineering, cold atmospheric plasma, PCL, 3D printing
Procedia PDF Downloads 1156366 Rationally Designed Dual PARP-HDAC Inhibitor Elicits Striking Anti-leukemic Effects
Authors: Amandeep Thakur, Yi-Hsuan Chu, Chun-Hsu Pan, Kunal Nepali
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The transfer of ADP-ribose residues onto target substrates from nicotinamide adenine dinucleotide (NAD) (PARylation) is catalyzed by Poly (ADP-ribose) polymerases (PARPs). Amongst the PARP family members, the DNA damage response in cancer is majorly regulated by PARP1 and PARP2. The blockade of DNA repair by PARP inhibitors leads to the progression of DNA single-strand breaks (induced by some triggering factors) to double-strand breaks. Notably, PARP inhibitors are remarkably effective in cancers with defective homologous recombination repair (HRR). In particular, cancer cells with BRCA mutations are responsive to therapy with PARP inhibitors. The aforementioned requirement for PARP inhibitors to be effective confers a narrow activity spectrum to PARP inhibitors, which hinders their clinical applicability. Thus, the quest to expand the application horizons of PARP inhibitors beyond BRCA mutations is the need of the hour. Literature precedents reveal that HDAC inhibition induces BRCAness in cancer cells and can broaden the therapeutic scope of PARP inhibitors. Driven by such disclosures, dual inhibitors targeting both PARP and HDAC enzymes were designed by our research group to extend the efficacy of PARP inhibitors beyond BRCA-mutated cancers to cancers with induced BRCAness. The design strategy involved the installation of Veliparib, an investigational PARP inhibitor, as a surface recognition part in the HDAC inhibitor pharmacophore model. The chemical architecture of veliparib was deemed appropriate as a starting point for the generation of dual inhibitors by virtue of its size and structural flexibility. A validatory docking study was conducted at the outset to predict the binding mode of the designed dual modulatory chemical architectures. Subsequently, the designed chemical architectures were synthesized via a multistep synthetic route and evaluated for antitumor efficacy. Delightfully, one compound manifested impressive anti-leukemic effects (HL-60 cell lines) mediated via dual inhibition of PARP and class I HDACs. The outcome of the western blot analysis revealed that the compound could downregulate the expression levels of PARP1 and PARP2 and the HDAC isoforms (HDAC1, 2, and 3). Also, the dual PARP-HDAC inhibitor upregulated the protein expression of the acetyl histone H3, confirming its abrogation potential for class I HDACs. In addition, the dual modulator could arrest the cell cycle at the G0/G1 phase and induce autophagy. Further, polymer-based nanoformulation of the dual inhibitor was furnished to afford targeted delivery of the dual inhibitor at the cancer site. Transmission electron microscopy (TEM) results indicate that the nanoparticles were monodispersed and spherical. Moreover, the polymeric nanoformulation exhibited an appropriate particle size. Delightfully, pH-sensitive behavior was manifested by the polymeric nanoformulation that led to selective antitumor effects towards the HL-60 cell lines. In light of the magnificent anti-leukemic profile of the identified dual PARP-HDAC inhibitor, in-vivo studies (pharmacokinetics and pharmacodynamics) are currently being conducted. Notably, the optimistic findings of the aforementioned study have spurred our research group to initiate several medicinal chemistry campaigns to create bifunctional small molecule inhibitors addressing PARP as the primary target.Keywords: PARP inhibitors, HDAC inhibitors, BRCA mutations, leukemia
Procedia PDF Downloads 276365 Optimization of Surface Coating on Magnetic Nanoparticles for Biomedical Applications
Authors: Xiao-Li Liu, Ling-Yun Zhao, Xing-Jie Liang, Hai-Ming Fan
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Owing to their unique properties, magnetic nanoparticles have been used as diagnostic and therapeutic agents for biomedical applications. Highly monodispersed magnetic nanoparticles with controlled particle size and surface coating have been successfully synthesized as a model system to investigate the effect of surface coating on the T2 relaxivity and specific absorption rate (SAR) under an alternating magnetic field, respectively. Amongst, by using mPEG-g-PEI to solubilize oleic-acid capped 6 nm magnetic nanoparticles, the T2 relaxivity could be significantly increased by up to 4-fold as compared to PEG coated nanoparticles. Moreover, it largely enhances the cell uptake with a T2 relaxivity of 92.6 mM-1s-1 for in vitro cell MRI. As for hyperthermia agent, SAR value increase with the decreased thickness of PEG surface coating. By elaborate optimization of surface coating and particle size, a significant increase of SAR (up to 74%) could be achieved with a minimal variation on the saturation magnetization (<5%). The 19 nm magnetic nanoparticles with 2000 Da PEG exhibited the highest SAR of 930 W•g-1 among the samples, which can be maintained in various simulated physiological conditions. This systematic work provides a general strategy for the optimization of surface coating of magnetic core for high performance MRI contrast agent and hyperthermia agent.Keywords: magnetic nanoparticles, magnetic hyperthermia, magnetic resonance imaging, surface modification
Procedia PDF Downloads 5116364 Defective Autophagy Disturbs Neural Migration and Network Activity in hiPSC-Derived Cockayne Syndrome B Disease Models
Authors: Julia Kapr, Andrea Rossi, Haribaskar Ramachandran, Marius Pollet, Ilka Egger, Selina Dangeleit, Katharina Koch, Jean Krutmann, Ellen Fritsche
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It is widely acknowledged that animal models do not always represent human disease. Especially human brain development is difficult to model in animals due to a variety of structural and functional species-specificities. This causes significant discrepancies between predicted and apparent drug efficacies in clinical trials and their subsequent failure. Emerging alternatives based on 3D in vitro approaches, such as human brain spheres or organoids, may in the future reduce and ultimately replace animal models. Here, we present a human induced pluripotent stem cell (hiPSC)-based 3D neural in a vitro disease model for the Cockayne Syndrome B (CSB). CSB is a rare hereditary disease and is accompanied by severe neurologic defects, such as microcephaly, ataxia and intellectual disability, with currently no treatment options. Therefore, the aim of this study is to investigate the molecular and cellular defects found in neural hiPSC-derived CSB models. Understanding the underlying pathology of CSB enables the development of treatment options. The two CSB models used in this study comprise a patient-derived hiPSC line and its isogenic control as well as a CSB-deficient cell line based on a healthy hiPSC line (IMR90-4) background thereby excluding genetic background-related effects. Neurally induced and differentiated brain sphere cultures were characterized via RNA Sequencing, western blot (WB), immunocytochemistry (ICC) and multielectrode arrays (MEAs). CSB-deficiency leads to an altered gene expression of markers for autophagy, focal adhesion and neural network formation. Cell migration was significantly reduced and electrical activity was significantly increased in the disease cell lines. These data hint that the cellular pathologies is possibly underlying CSB. By induction of autophagy, the migration phenotype could be partially rescued, suggesting a crucial role of disturbed autophagy in defective neural migration of the disease lines. Altered autophagy may also lead to inefficient mitophagy. Accordingly, disease cell lines were shown to have a lower mitochondrial base activity and a higher susceptibility to mitochondrial stress induced by rotenone. Since mitochondria play an important role in neurotransmitter cycling, we suggest that defective mitochondria may lead to altered electrical activity in the disease cell lines. Failure to clear the defective mitochondria by mitophagy and thus missing initiation cues for new mitochondrial production could potentiate this problem. With our data, we aim at establishing a disease adverse outcome pathway (AOP), thereby adding to the in-depth understanding of this multi-faced disorder and subsequently contributing to alternative drug development.Keywords: autophagy, disease modeling, in vitro, pluripotent stem cells
Procedia PDF Downloads 1216363 Novel Coprocessor for DNA Sequence Alignment in Resequencing Applications
Authors: Atef Ibrahim, Hamed Elsimary, Abdullah Aljumah, Fayez Gebali
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This paper presents a novel semi-systolic array architecture for an optimized parallel sequence alignment algorithm. This architecture has the advantage that it can be modified to be reused for multiple pass processing in order to increase the number of processing elements that can be packed into a single FPGA and to increase the number of sequences that can be aligned in parallel in a single FPGA. This resolves the potential problem of many FPGA resources left unused for designs that have large values of short read length. When using the previously published conventional hardware design. FPGA implementation results show that, for large values of short read lengths (M>128), the proposed design has a slightly higher speed up and FPGA utilization over the the conventional one.Keywords: bioinformatics, genome sequence alignment, re-sequencing applications, systolic array
Procedia PDF Downloads 5326362 Nano-Plasmonic Diagnostic Sensor Using Ultraflat Single-Crystalline Au Nanoplate and Cysteine-Tagged Protein G
Authors: Hwang Ahreum, Kang Taejoon, Kim Bongsoo
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Nanosensors for high sensitive detection of diseases have been widely studied to improve the quality of life. Here, we suggest robust nano-plasmonic diagnostic sensor using cysteine tagged protein G (Cys3-protein G) and ultraflat, ultraclean and single-crystalline Au nanoplates. Protein G formed on an ultraflat Au surface provides ideal background for dense and uniform immobilization of antibodies. The Au is highly stable in diverse biochemical environment and can immobilize antibodies easily through Au-S bonding, having been widely used for various biosensing applications. Especially, atomically smooth single-crystalline Au nanomaterials synthesized using chemical vapor transport (CVT) method are very suitable to fabricate reproducible sensitive sensors. As the C-reactive protein (CRP) is a nonspecific biomarker of inflammation and infection, it can be used as a predictive or prognostic marker for various cardiovascular diseases. Cys3-protein G immobilized uniformly on the Au nanoplate enable CRP antibody (anti-CRP) to be ordered in a correct orientation, making their binding capacity be maximized for CRP detection. Immobilization condition for the Cys3-protein G and anti-CRP on the Au nanoplate is optimized visually by AFM analysis. Au nanoparticle - Au nanoplate (NPs-on-Au nanoplate) assembly fabricated from sandwich immunoassay for CRP can reduce zero-signal extremely caused by nonspecific bindings, providing a distinct surface-enhanced Raman scattering (SERS) enhancement still in 10-18 M of CRP concentration. Moreover, the NP-on-Au nanoplate sensor shows an excellent selectivity against non-target proteins with high concentration. In addition, comparing with control experiments employing a Au film fabricated by e-beam assisted deposition and linker molecule, we validate clearly contribution of the Au nanoplate for the attomolar sensitive detection of CRP. We expect that the devised platform employing the complex of single-crystalline Au nanoplates and Cys3-protein G can be applied for detection of many other cancer biomarkers.Keywords: Au nanoplate, biomarker, diagnostic sensor, protein G, SERS
Procedia PDF Downloads 2596361 Comparison of Polyphonic Profile of a Berry from Two Different Sources, Using an Optimized Extraction Method
Authors: G. Torabian, A. Fathi, P. Valtchev, F. Dehghani
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The superior polyphenol content of Sambucus nigra berries has high health potentials for the production of nutraceutical products. Numerous factors influence the polyphenol content of the final products including the berries’ source and the subsequent processing production steps. The aim of this study is to compare the polyphenol content of berries from two different sources and also to optimise the polyphenol extraction process from elderberries. Berries from source B obtained more acceptable physical properties than source A; a single berry from source B was double in size and weight (both wet and dry weight) compared with a source A berry. Despite the appropriate physical characteristics of source B berries, their polyphenolic profile was inferior; as source A berries had 2.3 fold higher total anthocyanin content, and nearly two times greater total phenolic content and total flavonoid content compared to source B. Moreover, the result of this study showed that almost 50 percent of the phenolic content of berries are entrapped within their skin and pulp that potentially cannot be extracted by press juicing. To address this challenge and to increase the total polyphenol yield of the extract, we used cold-shock blade grinding method to break the cell walls. The result of this study showed that using cultivars with higher phenolic content as well as using the whole fruit including juice, skin and pulp can increase polyphenol yield significantly; and thus, may boost the potential of using elderberries as therapeutic products.Keywords: different sources, elderberry, grinding, juicing, polyphenols
Procedia PDF Downloads 2966360 Experimental Verification of On-Board Power Generation System for Vehicle Application
Authors: Manish Kumar, Krupa Shah
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The usage of renewable energy sources is increased day by day to overcome the dependency on fossil fuels. The wind energy is considered as a prominent source of renewable energy. This paper presents an approach for utilizing wind energy obtained from moving the vehicle for cell-phone charging. The selection of wind turbine, blades, generator, etc. is done to have the most efficient system. The calculation procedure for power generated and drag force is shown to know the effectiveness of the proposal. The location of the turbine is selected such that the system remains symmetric, stable and has the maximum induced wind. The calculation of the generated power at different velocity is presented. The charging is achieved for the speed 30 km/h and the system works well till 60 km/h. The model proposed seems very useful for the people traveling long distances in the absence of mobile electricity. The model is very economical and easy to fabricate. It has very less weight and area that makes it portable and comfortable to carry along. The practical results are shown by implementing the portable wind turbine system on two-wheeler.Keywords: cell-phone charging, on-board power generation, wind energy, vehicle
Procedia PDF Downloads 2976359 Hemocompatible Thin-Film Materials Recreating the Structure of the Cell Niches with High Potential for Endothelialization
Authors: Roman Major, Klaudia Trembecka- Wojciga, Juergen Markus Lackner, Boguslaw Major
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The future and the development of science is therefore seen in interdisciplinary areas such as bio medical engineering. Self-assembled structures, similar to stem cell niches would inhibit fast division process and subsequently capture the stem cells from the blood flow. By means of surface topography and the stiffness as well as micro structure progenitor cells should be differentiated towards the formation of endothelial cells monolayer which effectively will inhibit activation of the coagulation cascade. The idea of the material surface development met the interest of the clinical institutions, which support the development of science in this area and are waiting for scientific solutions that could contribute to the development of heart assist systems. This would improve the efficiency of the treatment of patients with myocardial failure, supported with artificial heart assist systems. Innovative materials would enable the redesign, in the post project activity, construction of ventricular heart assist.Keywords: bio-inspired materials, electron microscopy, haemocompatibility, niche-like structures, thin coatings
Procedia PDF Downloads 4796358 PIV Measurements of the Instantaneous Velocities for Single and Two-Phase Flows in an Annular Duct
Authors: Marlon M. Hernández Cely, Victor E. C. Baptistella, Oscar M. H. Rodríguez
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Particle Image Velocimetry (PIV) is a well-established technique in the field of fluid flow measurement and provides instantaneous velocity fields over global domains. It has been applied to external and internal flows and in single and two-phase flows. Regarding internal flow, works about the application of PIV in annular ducts are scanty. An experimental work is presented, where flow of water is studied in an annular duct of inner diameter of 60 mm and outer diameter of 155 mm and 10.5-m length, with the goal of obtaining detailed velocity measurements. Depending on the flow rates of water, it can be laminar, transitional or turbulent. In this study, the water flow rate was kept at three different values for the annular duct, allowing the analysis of one laminar and two turbulent flows. Velocity fields and statistic quantities of the turbulent flow were calculated.Keywords: PIV, annular duct, laminar, turbulence, velocity profile
Procedia PDF Downloads 3556357 Municipal Sewage Sludge as Co-Substrate in Anaerobic Digestion of Vegetable Waste and Biogas Yield
Authors: J. V. Thanikal, M. Torrijos, Philipe Sousbie, S. M. Rizwan, R. Senthil Kumar, Hatem Yezdi
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Co-digestion is one of the advantages of anaerobic digestion process because; several wastes having complimentary characteristics can be treated in a single process. The anaerobic co-digestion process, which can be defined as the simultaneous treatment of two –or more – organic biodegradable waste streams by anaerobic digestion offers great potential for the proper disposal of the organic fraction of solid waste coming from source or separate collection systems. The results of biogas production for sewage sludge, when used as a single substrate, were low (350ml/d), and also the biodegradation rate was slow. Sewage sludge as a co-substrate did not show much effect on biogas yield. The vegetable substrates (Potato, Carrot, Spinach) with a total charge of 27–36 g VS, with a HRT starting from 3 days and ending with 1 day, shown a considerable increase in biogas yield 3.5-5 l/d.Keywords: anaerobic digestion, co-digestion, vegetable substrate, sewage sludge
Procedia PDF Downloads 5736356 Numerical Simulation of the Rotating Vertical Bridgman Growth
Authors: Nouri Sabrina
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Numerical parametric study is conducted to study the effects of ampoule rotation on the flows and the dopant segregation in Vertical Bridgman (VB) crystal growth. Calculations were performed in unsteady state. The extended darcy model, whıch includes the time derivative and coriolis terms, has been employed in the momentum equation. It is found that the convection, and dopant segregation can be affected significantly by ampoule rotation, and the effect is similar to that by an axial magnetıc field. Ampoule rotation decreases the intensity of convection and stretches the flow cell axıally. When the convectıon is weak, the flow can be suppressed almost completely by moderate ampoule rotation and the dopant segregation becomes diffusion-controlled. For stronger convection, the elongated flow cell by ampoule rotation may bring dopant mixing into the bulk melt reducing axial segregation at the early stage of the growth. However, if the cellular flow cannot be suppressed completely, ampoule rotation may induce larger radial segregation due to poor mixing.Keywords: rotating vertical solidification, Finite Volume Method, heat and mass transfer, porous medium, phase change
Procedia PDF Downloads 4346355 Chemical and Physical Properties and Biocompatibility of Ti–6Al–4V Produced by Electron Beam Rapid Manufacturing and Selective Laser Melting for Biomedical Applications
Authors: Bing–Jing Zhao, Chang-Kui Liu, Hong Wang, Min Hu
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Electron beam rapid manufacturing (EBRM) or Selective laser melting is an additive manufacturing process that uses 3D CAD data as a digital information source and energy in the form of a high-power laser beam or electron beam to create three-dimensional metal parts by fusing fine metallic powders together.Object:The present study was conducted to evaluate the mechanical properties ,the phase transformation,the corrosivity and the biocompatibility of Ti-6Al-4V by EBRM,SLM and forging technique.Method: Ti-6Al-4V alloy standard test pieces were manufactured by EBRM, SLM and forging technique according to AMS4999,GB/T228 and ISO 10993.The mechanical properties were analyzed by universal test machine. The phase transformation was analyzed by X-ray diffraction and scanning electron microscopy. The corrosivity was analyzed by electrochemical method. The biocompatibility was analyzed by co-culturing with mesenchymal stem cell and analyzed by scanning electron microscopy (SEM) and alkaline phosphatase assay (ALP) to evaluate cell adhesion and differentiation, respectively. Results: The mechanical properties, the phase transformation, the corrosivity and the biocompatibility of Ti-6Al-4V by EBRM、SLM were similar to forging and meet the mechanical property requirements of AMS4999 standard. aphase microstructure for the EBM production contrast to the a’phase microstructure of the SLM product. Mesenchymal stem cell adhesion and differentiation were well. Conclusion: The property of the Ti-6Al-4V alloy manufactured by EBRM and SLM technique can meet the medical standard from this study. But some further study should be proceeded in order to applying well in clinical practice.Keywords: 3D printing, Electron Beam Rapid Manufacturing (EBRM), Selective Laser Melting (SLM), Computer Aided Design (CAD)
Procedia PDF Downloads 4566354 Enhancing Anode Performance in Li-S Batteries via Coating with Waste Battery-Derived Materials
Authors: Mohsen Hajian Foroushani, Samane Maroufi, Rasoul Khayyam Nekouei, Veena Sahajwalla
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Lithium (Li) metal possesses outstanding characteristics, with the highest specific capacity (3860 mAh g-1) and the lowest electrochemical potential (-3.04 V vs. SHE) among available metal anodes. The collaborative impact of Li and sulfur, featuring a specific capacity of 1670 mAh g-1, positions Li–S batteries (LSBs) as highly promising contenders for the next generation of high-energy-density batteries. However, the comprehensive commercialization of LSBs relies on addressing various challenges inherent to these batteries. One of the most formidable hurdles is the widespread issue of Li dendrite nucleation and growth on the anode surface, stemming from the inherent instability of the solid electrolyte interphase (SEI) layer. In this study, we employed a Zn-based coating derived from waste materials, significantly enhancing the performance of the symmetrical cell across various current densities. The applied coating not only improved the cyclability of the cell by more than fourfold but also reduced the charge transfer resistance from over 300 to less than 10 before cycling. Examination through SEM micrographs of both samples revealed the successful suppression of Li dendrites by the applied coating.Keywords: Li-S batteries, Li dendrite, sustainability, Li anode
Procedia PDF Downloads 746353 The Comparative Study of the Characteristics of Chinese and Foreign Excellent Woman’s Single Players’ Serve, Receive Tactic Author
Authors: Zhai Yuan, Wu Xueqing
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This article statistics the technology which used by Chinese and foreign excellent players in the game, including types and serves areas,receive technology and effect and utilization ratio receiving and losing points. The sample is che videos which is world's top matches of excellent badminton athletes of che single, including Chinese players’ 43 games and foreign players’ 38 games. Conclusion: For the serving, Chinese and foreign single players are to give priority to forehand short-low serve and the long-high serve. And Chinese and foreign players in using forehand short-low serve and drive server exist significant differences; For the serves areas, Chinese and foreign players serve area is concentrated in area 1,5,6. Area 6 has the highest rate of all the district areas, following by the area 1and area 5. Among the 2ed serve area Sino-foreign player, there exist significant differences; In the receiver, when returning the frontcourt shutter, players is given priority to net lift and push. When returning the backcourt shutter, receiver's the best ball is smash, followed by clear and drop shot. Foreign players have higher utilization rate in smash than Chinese players in the backcourt; In the receiver result, Chinese players give priority to actively and equally situation than foreign players, but in negatively receiving is just opposite.Keywords: badminton, woman’s singles, technique and tactics, comparative analysis
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