Search results for: candidate cell
4204 Preparation of Gramine Nanosuspension and Protective Effect of Gramine on Human Oral Cell Lines by Induction of Apoptosis
Authors: K. Suresh, R. Arunkumar
Abstract:
The objective of this study is to investigate the preparation of gramine nano suspension and protective effect of Gramine on the apoptosis of laryngeal cancer cells cell line (HEp-2 and KB). The growth inhibition rate of Hep-2 and KB cells in vitro were measured by MTT assay and apoptosis by, levels of reactive oxygen species, mitochondrial membrane potential, morphological changes and flowcytometry. Based on the results, we determined the effective doses of gramine as 127.23µm/ml for 24 hr and 119.81 µm/ml for 48hr in hep-2 cell line and 147.58 µm ml for 24 hr and 123.74µm µm/ml for 48hr in KB cell line. cytotoxicity effects of gramine were confirmed by treatment of HEp-2 cell and KB cell with IC50 concentration of gramine resulted in sequences of events marked by the enhance the apoptosis accompanied by loss of cell viability, modulation of reactive oxygen species and cell cycle arrest through the induction of G0/G1 phase arrest on HEp-2 cells. Our study suggests that the nanosuspension of gramine possesses the more cytotoxic effect of cancer cells and a novel candidate for cancer chemoprevention.Keywords: apoptosis, HEp-2 cell line, KB cell line mitochondria, gramine, nanosuspension
Procedia PDF Downloads 4474203 Induction of HIV-1 Resistance: The New Approaches Based on Gene Modification and Stem Cell Engineering
Authors: Alieh Farshbaf
Abstract:
Introduction: Current anti-retroviral drugs have some restrictions for treatment of HIV-1 infection. The efficacy of retroviral drugs is not same in different infected patients and the virus rebound from latent reservoirs after stopping them. Recently, the engineering of stem cells and gene therapy provide new approaches to eliminate some drug problems by induction of resistance to HIV-1. Literature review: Up to now, AIDS-restriction genes (ARGs) were suitable candidate for gene and cell therapies, such as cc-chemokine receptor-5 (CCR5). In this manner, CCR5 provide effective cure in Berlin and Boston patients by inducing of HIV-1 resistance with allogeneic stem cell transplantation. It is showed that Zinc Finger Nuclease (ZFN) could induce HIV-1 resistance in stem cells of infected patients by homologous recombination or non-end joining mechanism and eliminate virus loading after returning the modified cells. Then, gene modification by HIV restriction factors, as TRIM5, introduced another gene candidate for HIV by interfering in infection process. These gene modifications/editing provided by stem cell futures that improve treatment in refractory disease such as HIV-1. Conclusion: Although stem cell transplantation has some complications, but in compare to retro-viral drugs demonstrated effective cure by elimination of virus loading. On the other hand, gene therapy is cost-effective for an infected patient than retroviral drugs payment in a person life-long. The results of umbilical cord blood stem cell transplantation showed that gene and cell therapy will be applied easier than previous treatment of AIDS with high efficacy.Keywords: stem cell, AIDS, gene modification, cell engineering
Procedia PDF Downloads 2974202 Vaccine Development for Newcastle Disease Virus in Poultry
Authors: Muhammad Asif Rasheed
Abstract:
Newcastle disease virus (NDV), an avian orthoavulavirus, is a causative agent of Newcastle disease named (NDV) and can cause even the epidemics when the disease is not treated. Previously several vaccines based on attenuated and inactivated viruses have been reported, which are rendered useless with the passage of time due to versatile changes in viral genome. Therefore, we aimed to develop an effective multi-epitope vaccine against the haemagglutinin neuraminidase (HN) protein of 26 NDV strains from Pakistan through a modern immunoinformatic approaches. As a result, a vaccine chimaera was constructed by combining T-cell and B-cell epitopes with the appropriate linkers and adjuvant. The designed vaccine was highly immunogenic, non-allergen, and antigenic; therefore, the potential 3D-structureof multi epitope vaccine was constructed, refined, and validated. A molecular docking study of a multiepitope vaccine candidate with the chicken Toll-like receptor-4 indicated successful binding. An In silico immunological simulation was used to evaluate the candidate vaccine's ability to elicit an effective immune response. According to the computational studies, the proposed multiepitope vaccine is physically stable and may induce immune responses, whichsuggested it a strong candidate against 26 Newcastle disease virus strains from Pakistan. A wet lab study is under process to confirm the results.Keywords: epitopes, newcastle disease virus, paramyxovirus virus, vaccine
Procedia PDF Downloads 1144201 Design and in Slico Study of the Truncated Spike-M-N SARS-CoV-2 as a Novel Effective Vaccine Candidate
Authors: Aghasadeghi MR., Bahramali G., Sadat SM., Sadeghi SA., Yousefi M., Khodaei K., Ghorbani M., Sadat Larijani M.
Abstract:
Background:The emerging COVID-19 pandemic is a serious concernfor the public health worldwide. Despite the many mutations in the virus genome, it is important to find an effective vaccine against viral mutations. Therefore, in current study, we aimed at immunoinformatic evaluation of the virus proteins immunogenicity to design a preventive vaccine candidate, which could elicit humoral and cellular immune responses as well. Methods:Three antigenic regions are included;Spike, Membrane, and Nucleocapsid amino acid sequences were obtained, and possible fusion proteins were assessed andcompared by immunogenicity, structural features, and population coverage. The best fusion protein was also evaluated for MHC-I and MHC-II T-cell epitopes and the linear and conformational B-cell epitopes. Results: Among the four predicted models, the truncated Spike protein in fusion with M and N proteins is composed of 24 highly immunogenic human MHC class I and 29 MHC class II, along with 14 B-cell linear and 61 discontinues epitopes. Also, the selected protein has high antigenicity and acceptable population coverage of 82.95% in Iran and 92.51% in Europe. Conclusion: The data indicate that the truncated Spike-M-N SARS-CoV-2form which could be potential targets of neutralizing antibodies. The protein also has the ability to stimulate humoral and cellular immunity. The in silico study provided the fusion protein as a potential preventive vaccine candidate for further in vivo evaluation.Keywords: SARS-CoV-2, immunoinformatic, protein, vaccine
Procedia PDF Downloads 2164200 Association of Major Histocompatibility Complex with Cell Mediated Immunity
Authors: Atefeh Esmailnejad, Gholamreza Nikbakht Brujeni
Abstract:
Major histocompatibility complex (MHC) is one of the best characterized genetic regions associated with immune responses and controlling disease resistance in chicken. Association of the MHC with a wide range of immune responses makes it a valuable predictive factor for the disease pathogenesis and outcome. In this study, the association of MHC with cell-mediated immune responses was analyzed in commercial broiler chicken. The tandem repeat LEI0258 was applied to investigate the MHC polymorphism. Cell-mediated immune response was evaluated by peripheral blood lymphocyte proliferation assay using MTT method. Association study revealed a significant influence of MHC alleles on cellular immune responses in this population. Alleles 385 and 448 bp were associated with elevated cell-mediated immunity. Haplotypes associated with improved immune responses could be considered as candidate markers for disease resistance and applied to breeding strategies.Keywords: MHC, cell-mediated immunity, broiler, chicken
Procedia PDF Downloads 1404199 Mobile Traffic Management in Congested Cells using Fuzzy Logic
Authors: A. A. Balkhi, G. M. Mir, Javid A. Sheikh
Abstract:
To cater the demands of increasing traffic with new applications the cellular mobile networks face new changes in deployment in infrastructure for making cellular networks heterogeneous. To reduce overhead processing the densely deployed cells require smart behavior with self-organizing capabilities with high adaptation to the neighborhood. We propose self-organization of unused resources usually excessive unused channels of neighbouring cells with densely populated cells to reduce handover failure rates. The neighboring cells share unused channels after fulfilling some conditional candidature criterion using threshold values so that they are not suffered themselves for starvation of channels in case of any abrupt change in traffic pattern. The cells are classified as ‘red’, ‘yellow’, or ‘green’, as per the available channels in cell which is governed by traffic pattern and thresholds. To combat the deficiency of channels in red cell, migration of unused channels from under-loaded cells, hierarchically from the qualified candidate neighboring cells is explored. The resources are returned back when the congested cell is capable of self-contained traffic management. In either of the cases conditional sharing of resources is executed for enhanced traffic management so that User Equipment (UE) is provided uninterrupted services with high Quality of Service (QoS). The fuzzy logic-based simulation results show that the proposed algorithm is efficiently in coincidence with improved successful handoffs.Keywords: candidate cell, channel sharing, fuzzy logic, handover, small cells
Procedia PDF Downloads 1134198 Device Modelling and Analysis of Eco-friendly Inverted Solar Cell Structure Using Valency Ordered Inorganic Double Perovskite Material
Authors: Sindhu S Nair, Atul Thakur, Preeti Thakur, Trukhanov Alex
Abstract:
Perovskite-based absorbing materials that are organic, inorganic, or hybrid have gained interest as an appealing candidate for the development of solar cell devices. Lead-based perovskites are among the most promising materials, but their application is plagued with toxicity and stability concerns. Most of the perovskite solar cell consists of conventional (n-i-p) structure with organic or inorganic charge transport materials. The commercial application of such device is limited due to higher J-V hysteresis and the need for high temperature during fabrication. This numerical analysis primarily directs to investigate the performance of various inorganic lead-free valency ordered double perovskite absorber materials and to develop an inverted perovskite solar cell device structure. Simulation efforts using SCAPS-1D was carried out with various organic and inorganic charge transport materials with absorber layer materials, and their performance has been evaluated for various factors of thickness, absorber thickness, absorber defect density, and interface defect density to achieve the optimized structure.Keywords: perovskite materials, solar cell, inverted solar cell, inorganic perovskite solar cell materials, cell efficiency
Procedia PDF Downloads 744197 Immunoinformatic Design and Evaluation of an Epitope-Based Tetravalent Vaccine against Human Hand, Foot, and Mouth Disease
Authors: Aliyu Maje Bello, Yaowaluck Maprang Roshorm
Abstract:
Hand, foot, and mouth disease (HFMD) is a highly contagious viral infection affecting mostly infants and children. Although the Enterovirus A71 (EV71) is usually the major causative agent of HFMD, other enteroviruses such as coxsackievirus A16, A10, and A6 are also found in some of the recent outbreaks. The commercially available vaccines have demonstrated their effectiveness against only EV71 infection but no protection against other enteroviruses. To address the limitation of the monovalent EV71 vaccine, the present study thus designed a tetravalent vaccine against the four major enteroviruses causing HFMD and primarily evaluated the designed vaccine using an immunoinformatics approach. The immunogen was designed to contain the EV71 VP1 protein and multiple reported epitopes from all four distinct enteroviruses and thus designated a tetravalent vaccine. The 3D structure of the designed tetravalent vaccine was modeled, refined, and validated. Epitope screening showed the presence of B-cell, CTL, CD4 T cell, and IFN epitopes with vast application among the Asian population. Docking analysis confirmed the stable and strong binding interactions between the immunogen and immune receptor B-cell receptor (BCR). In silico cloning and immune simulation analyses guaranteed high efficiency and sufficient expression of the vaccine candidate in humans. Overall, the promising results obtained from the in-silico studies of the proposed tetravalent vaccine make it a potential candidate worth further experimental validation.Keywords: enteroviruses, coxsackieviruses, hand foot and mouth disease, immunoinformatics, tetravalent vaccine
Procedia PDF Downloads 644196 Establishment of a Thermostable Newcastle Disease Vaccine Candidate Strain and Its Adaptation to Vero Cells
Authors: Humayun Kabir, Amirul Hasan, Yu Miyaoka, Makiko Yamaguchi, Chisaki Kadota, Kazuaki Takehara
Abstract:
From field isolates of Newcastle disease virus (NDV) in Japan, one avirulent strain, APMV/northern pintail/Japan/Aomori/2003 (dk-Aomori/03, NDV 261), was selected for its excellent thermostability, and the strain was heat-treated at 56℃ temperatures for 30 min with each passage into Vero cells to maintain thermostability and to adapt Vero cells. After serial 20 passages in Vero cells, it was named NDV Vero20. When growth curves were tested in Vero cells, NDV Vero20 grew well to compare the original NDV261. The HN gene was sequenced, and found motifs that show thermostability. The intracerebral pathogenicity index (ICPI) test score was 0. The thermostability of the virus was confirmed by storing it at different temperatures, including at 37°C. When susceptible chicks were inoculated with NDV Vero20 through eye drops, induced adequate levels of antibody were measured using a serum neutralization test. The results showed that NDV Vero20, a vaccine candidate strain is thermostable, Vero cell adapted, and has immunogenic potential, which would make as an alternative to the traditional embryonated chicken eggs-based vaccine.Keywords: Newcastle disease virus, thermostability, vaccine, Vero cell adaptability
Procedia PDF Downloads 1324195 Cell Patterns and Tissue Metamorphoses Based on Cell Surface Mechanism
Authors: Reyhane Hamed Kamran
Abstract:
Early stage morphogenesis requires the execution of complex systems that direct the nearby conduct of gatherings of cells. The organization of such instruments has been, for the most part, deciphered through the recognizable proof of moderated groups of flagging pathways that spatially and transiently control cell conduct. In any case, how this data is handled to control cell shape and cell elements is an open territory of examination. The structure that rises up out of differing controls, for example, cell science, material science, and formative science, focuses to bond and cortical actin arranges as controllers of cell surface mechanics. In this specific circumstance, a scope of formative marvels can be clarified by the guideline of cell surface pressure.Keywords: cell, tissue damage, morphogenesis, cell conduct
Procedia PDF Downloads 914194 Cell Patterns and Tissue Metamorphoses Based on Cell Surface Mechanics
Authors: Narin Salehiyan
Abstract:
Early stage morphogenesis requires the execution of complex systems that direct the nearby conduct of gatherings of cells. The organization of such instruments has been, for the most part, deciphered through the recognizable proof of moderated groups of flagging pathways that spatially and transiently control cell conduct. In any case, how this data is handled to control cell shape and cell elements is an open territory of examination. The structure that rises up out of differing controls, for example, cell science, material science and formative science, focuses to bond and cortical actin arranges as controllers of cell surface mechanics. In this specific circumstance, a scope of formative marvels can be clarified by the guideline of cell surface pressure.Keywords: cell, tissue damage, morphogenesis, cell conduct
Procedia PDF Downloads 754193 An Ab Initio Study of Delafossite Transparent Conductive Oxides Cu(In, Ga)O2 and Absorbers Films Cu(In, Ga)S2 in Solar-Cell
Authors: Mokdad Sakhri, Youcef Bouhadda
Abstract:
Thin film chalcopyrite technology is thus nowadays a solid candidate for photovoltaic cells. The currently used window layer for the solar cell Cu(In,Ga)S2 is our interest point in this work. For this purpose, we have performed a first-principles study of structural, electronic and optical properties for both delafossite transparent conductive oxides Cu (In, Ga)O2 and absorbers films Cu(In,Ga)S2. The calculations have been carried out within the local density functional (LDA) and generalized gradient approximations (GGA) combined with the hubbard potential using norm-conserving pseudopotentials and a plane-wave basis with ABINIT code. We have found the energy gap is :1.6, 2.53, 3.6, 3.8 eV for CuInS2, CuGaS2, CuInO2 and CuGaO2 respectively. The results are in good agreement with experimental results.Keywords: ABINIT code, DFT, electronic and optical properties, solar-cell absorbers, delafossite transparent conductive oxides
Procedia PDF Downloads 5624192 Neighbour Cell List Reduction in Multi-Tier Heterogeneous Networks
Authors: Mohanad Alhabo, Naveed Nawaz
Abstract:
The ongoing call or data session must be maintained to ensure a good quality of service. This can be accomplished by performing the handover procedure while the user is on the move. However, the dense deployment of small cells in 5G networks is a challenging issue due to the extensive number of handovers. In this paper, a neighbour cell list method is proposed to reduce the number of target small cells and hence minimizing the number of handovers. The neighbour cell list is built by omitting cells that could cause an unnecessary handover and handover failure because of short time of stay of the user in these cells. A multi-attribute decision making technique, simple additive weighting, is then applied to the optimized neighbour cell list. Multi-tier small cells network is considered in this work. The performance of the proposed method is analysed and compared with that of the existing methods. Results disclose that our method has decreased the candidate small cell list, unnecessary handovers, handover failure, and short time of stay cells compared to the competitive method.Keywords: handover, HetNets, multi-attribute decision making, small cells
Procedia PDF Downloads 1144191 New Quinazoline Derivative Exhibit Cytotoxic Effect agaisnt MCF-7 Human Breast Cancer Cell
Authors: Maryam Zahedifard, Fadhil Lafta Faraj, Nazia Abdul Majid, Hapipah Mohd Ali, Mahmood Ameen Abdulla
Abstract:
The new quinazoline Schiff bases have been synthesized through condensation reaction of 2-aminobenzhydrazide with 5-bromosalicylaldehyde and 3-methoxy-5-bromosalicylaldehyde. The compound was investigated for anticancer activity against MCF-7 human breast cancer cell line. It demonstrated a remarkable antiproliferative effect, with an IC50 value of 3.41±0.34, after 72 hours of treatment. Most apoptosis morphological features in treated MCF-7 cells were observed by AO/PI staining. The results of cell cycle analysis indicate that compounds did not induce S and M phase arrest in cell after 24 hours of treatment. Furthermore, MCF-7 cells treated with compound subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome C release as well as increase in ROS generation. We also found activation of caspases 3/7 and -9. Moreover, acute toxicity results demonstrated the nontoxic nature of the compounds in mice. Our results showed the selected compound significantly induce apoptosis in MCF-7 cells via intrinsic pathway, which might be considered as a potential candidate for further in vivo and clinical breast cancer studies.Keywords: quinazoline Schiff base, apoptosis, MCF-7, caspase, cell cycle, acute toxicity
Procedia PDF Downloads 4334190 hsa-miR-1204 and hsa-miR-639 Prominent Role in Tamoxifen's Molecular Mechanisms on the EMT Phenomenon in Breast Cancer Patients
Authors: Mahsa Taghavi
Abstract:
In the treatment of breast cancer, tamoxifen is a regularly prescribed medication. The effect of tamoxifen on breast cancer patients' EMT pathways was studied. In this study to see if it had any effect on the cancer cells' resistance to tamoxifen and to look for specific miRNAs associated with EMT. In this work, we used continuous and integrated bioinformatics analysis to choose the optimal GEO datasets. Once we had sorted the gene expression profile, we looked at the mechanism of signaling, the ontology of genes, and the protein interaction of each gene. In the end, we used the GEPIA database to confirm the candidate genes. after that, I investigated critical miRNAs related to candidate genes. There were two gene expression profiles that were categorized into two distinct groups. Using the expression profile of genes that were lowered in the EMT pathway, the first group was examined. The second group represented the polar opposite of the first. A total of 253 genes from the first group and 302 genes from the second group were found to be common. Several genes in the first category were linked to cell death, focal adhesion, and cellular aging. Two genes in the second group were linked to cell death, focal adhesion, and cellular aging. distinct cell cycle stages were observed. Finally, proteins such as MYLK, SOCS3, and STAT5B from the first group and BIRC5, PLK1, and RAPGAP1 from the second group were selected as potential candidates linked to tamoxifen's influence on the EMT pathway. hsa-miR-1204 and hsa-miR-639 have a very close relationship with the candidates genes according to the node degrees and betweenness index. With this, the action of tamoxifen on the EMT pathway was better understood. It's important to learn more about how tamoxifen's target genes and proteins work so that we can better understand the drug.Keywords: tamoxifen, breast cancer, bioinformatics analysis, EMT, miRNAs
Procedia PDF Downloads 1264189 Anion Exchange Nanocomposite Membrane Doped with ZnO-Nanoparticles for Direct Methanol Alkaline Fuel Cell
Authors: Phumlani Msomi, Patrick Nonjola, Patrick Ndungu, James Ramontja
Abstract:
A series of quaternized poly (2.6 dimethyl – 1.4 phenylene oxide)/ polysulfone (QPPO/PSF) blend anion exchange membrane (AEM) were successfully fabricated and characterized for methanol alkaline fuel cell application. Zinc Oxide (ZnO) nanoparticles were introduced in the polymer matrix to enhance the intrinsic properties of the AEM. To confirm successful fabrication, FT-IR spectroscopy and nuclear magnetic resonance (¹H NMR and HMBC ¹⁵N NMR) were used. The membrane properties were enhanced by the addition of ZnO nanoparticles. The addition of ZnO nanoparticles resulted to a higher ion exchange capacity (IEC) of 3.72 mmol.g⁻¹and a 30-fold ion conductivity (IC) increase of the nanocomposite due to no (zero (0)) methanol permeability at 30 °C and increased water uptake. The QPPO/PSF/2% ZnO composite retained over 80 % of its initial IC when evaluated for alkaline stability at room temperature. The maximum power output reached for the membrane electrode assembly (MEA) constructed with QPPO/PSF/2%ZnO is 69 mW.cm⁻², which is about three times more than the parent QPPO membrane. The above results indicate that QPPO/PSF-ZnO is a good candidate as an anion exchange membrane for fuel cell application.Keywords: anion exchange membrane, fuel cell, zinc oxide, nanocomposite
Procedia PDF Downloads 2674188 Global Analysis of HIV Virus Models with Cell-to-Cell
Authors: Hossein Pourbashash
Abstract:
Recent experimental studies have shown that HIV can be transmitted directly from cell to cell when structures called virological synapses form during interactions between T cells. In this article, we describe a new within-host model of HIV infection that incorporates two mechanisms: infection by free virions and the direct cell-to-cell transmission. We conduct the local and global stability analysis of the model. We show that if the basic reproduction number R0 1, the virus is cleared and the disease dies out; if R0 > 1, the virus persists in the host. We also prove that the unique positive equilibrium attracts all positive solutions under additional assumptions on the parameters.Keywords: HIV virus model, cell-to-cell transmission, global stability, Lyapunov function, second compound matrices
Procedia PDF Downloads 5084187 The Effect of Combined Doxorubicin and Dioscorea esculenta on Apoptosis Induction in Human Breast Cancer Cells
Authors: Dina Fatmawati, Sofia Mubarika, Mae Sri Wahyuningsih
Abstract:
Chemotherapy for breast cancer is largely ineffective, but innovative combinations of chemotherapeutic agents and natural compounds represent a promising strategy. In our previous study, the combination of Doxorubicin (Dox) and ethanolic extract of Dioscorea esculenta tuber ((EED) was found to have a synergistic effect on T47D human breast cancer cell line. In this study, we investigated the apoptotic effect of the combination on T47D human breast cancer cells and normal fibroblasts cell line and its effects on the expression of Caspase-3 and cleaved poly (ADP-Ribose) Polymerase-1 (cPARP-1) protein. T47D cell lines and fibroblasts cells were treated with the combination of Dox and EED. Apoptotic effect of the combination was determined using flow cytrometry assay. Protein expressions were determined by immunocytochemistry staining. The percentage of apoptotic cells were significantly higher in T47D cell lines (75%) than that of in fibroblast cells (23%). The expression of Caspase 3 (84.53%) and cPARP-1 (83.36%) were significantly higher in the cancer cell lines than those of normal cells. These results indicate that the combination of doxorubicin and Dioscorea esculenta is a promising candidate for the treatment of breast cancer cells.Keywords: Dioscorea esculenta, Doxorubicin, apoptosis, immunocytochemistry, cancer cells
Procedia PDF Downloads 4464186 Leukocyte Detection Using Image Stitching and Color Overlapping Windows
Authors: Lina, Arlends Chris, Bagus Mulyawan, Agus B. Dharmawan
Abstract:
Blood cell analysis plays a significant role in the diagnosis of human health. As an alternative to the traditional technique conducted by laboratory technicians, this paper presents an automatic white blood cell (leukocyte) detection system using Image Stitching and Color Overlapping Windows. The advantage of this method is to present a detection technique of white blood cells that are robust to imperfect shapes of blood cells with various image qualities. The input for this application is images from a microscope-slide translation video. The preprocessing stage is performed by stitching the input images. First, the overlapping parts of the images are determined, then stitching and blending processes of two input images are performed. Next, the Color Overlapping Windows is performed for white blood cell detection which consists of color filtering, window candidate checking, window marking, finds window overlaps, and window cropping processes. Experimental results show that this method could achieve an average of 82.12% detection accuracy of the leukocyte images.Keywords: color overlapping windows, image stitching, leukocyte detection, white blood cell detection
Procedia PDF Downloads 3044185 Human Metabolism of the Drug Candidate PBTZ169
Authors: Vadim Makarov, Stewart T.Cole
Abstract:
PBTZ169 is novel drug candidate with high efficacy in animals models, and its combination treatment of PBTZ169 with BDQ and pyrazinamide was shown to be more efficacious than the standard treatment for tuberculosis in a mouse model. The target of PBTZ169 is famous DprE1, an essential enzyme in cell wall biosynthesis. The crystal structure of the DprE1-PBTZ169 complex reveals formation of a semimercaptal adduct with Cys387 in the active site and explains the irreversible inactivation of the enzyme. Furthermore, this drug candidate demonstrated during preclinical research ‘drug like’ properties what made it an attractive drug candidate to treat tuberculosis in humans. During first clinical trials several cohorts of the healthy volunteers were treated by the single doses of PBTZ169 as well as two weeks repeated treatment was chosen for two maximal doses. As expected PBTZ169 was well tolerated, and no significant toxicity effects were observed during the trials. The study of the metabolism shown that human metabolism of PBTZ169 is very different from microbial or animals compound transformation. So main pathway of microbial, mice and less rats metabolism connected with reduction processes, but human metabolism mainly connected with oxidation processes. Due to this difference we observed several metabolites of PBTZ169 in humans with antitubercular activity, and now we can conclude that animal antituberculosis activity of PBTZ169 is a result not only activity of the drug itself, but it is a result of the sum activity of the drug and its metabolites. Direct antimicrobial plasma activity was studied, and such activity was observed for 24 hours after human treatment for some doses. This data gets high chance for good efficacy of PBTZ169 in human for treatment TB infection. Second phase of clinical trials was started summer of 2017 and continues to the present day. Available data will be presented.Keywords: clinical trials, DprE1, PBTZ169, metabolism
Procedia PDF Downloads 1584184 Evaluation of Iron Oxide-Functionalized Multiwall Carbon Nanotube Self-Standing Electrode for Symmetric Supercapacitor Application
Authors: B. V. Bhaskara Rao, Rodrigo Espinoza
Abstract:
The rapid development of renewable energy sources has drawn great attention to energy storage devices, especially supercapacitors, because of their high power density and rate performance. This work focus on Fe₃O₄ nanoparticles synthesized by reverse co-precipitation and MWCNTs functionalized by –COOH acid functionalization. The results show that Optimized 25wt% Fe₃O₄@FMWCNT show high specific capacitance 100 mF/cm² at one mA/cm² whereas 15wt% Fe₃O₄@FMWCNT showed high stability (80% retention capacity) over 5000 cycles. The electrolyte used in the coin cell is LiPF6 and the thickness of the electrode is 30 microns. The optimized Fe₃O₄@FMWCNT bucky papers coin cell electrochemical studies suggest that 25wt% Fe₃O₄@FMWCNT could be a good candidate for high-capacity supercapacitor devices. This could be further tested for flexible and planar supercapacitor device application with gel electrolytes.Keywords: self-standing electrode, Fe₃O4@FMWCNT, supercapacitor, symmetric coin-cell
Procedia PDF Downloads 1524183 Single-Cell Visualization with Minimum Volume Embedding
Authors: Zhenqiu Liu
Abstract:
Visualizing the heterogeneity within cell-populations for single-cell RNA-seq data is crucial for studying the functional diversity of a cell. However, because of the high level of noises, outlier, and dropouts, it is very challenging to measure the cell-to-cell similarity (distance), visualize and cluster the data in a low-dimension. Minimum volume embedding (MVE) projects the data into a lower-dimensional space and is a promising tool for data visualization. However, it is computationally inefficient to solve a semi-definite programming (SDP) when the sample size is large. Therefore, it is not applicable to single-cell RNA-seq data with thousands of samples. In this paper, we develop an efficient algorithm with an accelerated proximal gradient method and visualize the single-cell RNA-seq data efficiently. We demonstrate that the proposed approach separates known subpopulations more accurately in single-cell data sets than other existing dimension reduction methods.Keywords: single-cell RNA-seq, minimum volume embedding, visualization, accelerated proximal gradient method
Procedia PDF Downloads 2224182 Biomolecules Based Microarray for Screening Human Endothelial Cells Behavior
Authors: Adel Dalilottojari, Bahman Delalat, Frances J. Harding, Michaelia P. Cockshell, Claudine S. Bonder, Nicolas H. Voelcker
Abstract:
Endothelial Progenitor Cell (EPC) based therapies continue to be of interest to treat ischemic events based on their proven role to promote blood vessel formation and thus tissue re-vascularisation. Current strategies for the production of clinical-grade EPCs requires the in vitro isolation of EPCs from peripheral blood followed by cell expansion to provide sufficient quantities EPCs for cell therapy. This study aims to examine the use of different biomolecules to significantly improve the current strategy of EPC capture and expansion on collagen type I (Col I). In this study, four different biomolecules were immobilised on a surface and then investigated for their capacity to support EPC capture and proliferation. First, a cell microarray platform was fabricated by coating a glass surface with epoxy functional allyl glycidyl ether plasma polymer (AGEpp) to mediate biomolecule binding. The four candidate biomolecules tested were Col I, collagen type II (Col II), collagen type IV (Col IV) and vascular endothelial growth factor A (VEGF-A), which were arrayed on the epoxy-functionalised surface using a non-contact printer. The surrounding area between the printed biomolecules was passivated with polyethylene glycol-bisamine (A-PEG) to prevent non-specific cell attachment. EPCs were seeded onto the microarray platform and cell numbers quantified after 1 h (to determine capture) and 72 h (to determine proliferation). All of the extracellular matrix (ECM) biomolecules printed demonstrated an ability to capture EPCs within 1 h of cell seeding with Col II exhibiting the highest level of attachment when compared to the other biomolecules. Interestingly, Col IV exhibited the highest increase in EPC expansion after 72 h when compared to Col I, Col II and VEGF-A. These results provide information for significant improvement in the capture and expansion of human EPC for further application.Keywords: biomolecules, cell microarray platform, cell therapy, endothelial progenitor cells, high throughput screening
Procedia PDF Downloads 2834181 Talent-to-Vec: Using Network Graphs to Validate Models with Data Sparsity
Authors: Shaan Khosla, Jon Krohn
Abstract:
In a recruiting context, machine learning models are valuable for recommendations: to predict the best candidates for a vacancy, to match the best vacancies for a candidate, and compile a set of similar candidates for any given candidate. While useful to create these models, validating their accuracy in a recommendation context is difficult due to a sparsity of data. In this report, we use network graph data to generate useful representations for candidates and vacancies. We use candidates and vacancies as network nodes and designate a bi-directional link between them based on the candidate interviewing for the vacancy. After using node2vec, the embeddings are used to construct a validation dataset with a ranked order, which will help validate new recommender systems.Keywords: AI, machine learning, NLP, recruiting
Procedia PDF Downloads 814180 Cratoxy Formosum (Jack) Dyer Leaf Extract-Induced Human Breast and Liver Cancer Cells Death
Authors: Benjaporn Buranrat, Nootchanat Mairuae
Abstract:
Cratoxylum formosum (Jack) Dyer (CF) has been used for the traditional medicines in South East Asian and Thailand. Normally, northeast Thai vegetables have proven cytotoxic to many cancer cells. Therefore, the present study aims to explore the molecular mechanisms underlying CF-induced cancer cell death and apoptosis on breast and liver cancer cells. The cytotoxicity and antiproliferative effects of CF on the human breast MCF-7 and liver HepG2 cancer cell lines were evaluated using sulforhodamine B assay and colony formation assay. Cell migration assay was measured using wound healing assay. The apoptosis induction mechanisms were investigated through reactive oxygen species formation, caspase 3 activity, and JC-1 activity. Gene expression by real-time PCR and apoptosis related protein levels by Western blot analysis. CF induced MCF-7 and HepG2 cell death by time- and dose-dependent manner. Furthermore, CF had the greater cytotoxic potency on MCF-7 more than HepG2 cells with IC50 values of 85.70+4.52 μM and 219.03±9.96 μM respectively, at 24 h. Treatment with CF also caused a dose-dependent decrease in colony forming ability and cell migration, especially on MCF-7 cells. CF induced ROS formation, increased caspase 3 activities, and decreased the mitochondrial membrane potential, and causing apoptotic body production and DNA fragmentation. CF significantly decreased expression of the cell cycle regulatory protein RAC1 and downstream proteins, cdk6. Additionally, CF enhanced p21 and reduced cyclin D1 protein levels. CF leaf extract induced cell death, apoptosis, antimigration in both of MCF-7 and HepG2 cells. CF could be useful for developing to anticancer drug candidate for breast and liver cancer therapy.Keywords: cratoxylum formosum (jack) dyer, breast cancer, liver cancer, cell death
Procedia PDF Downloads 2044179 New Quinazoline Derivative Induce Cytotoxic Effect against Mcf-7 Human Breast Cancer Cell
Authors: Maryam Zahedi Fard, Nazia Abdul Majid, Hapipah Mohd Ali, Mahmood Ameen Abdulla
Abstract:
New quinazoline schiff base 3-(5-bromo-2-hydroxy-3-methoxybenzylideneamino)-2-(5-bromo-2-hydroxy-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one was investigated for anticancer activity against MCF-7 human breast cancer cell line with involved mechanism of apoptosis. The compound demonstrated a remarkable antiproliferative effect, with an IC50 value of 3.41 ± 0.34, after 72 hours of treatment. Morphological apoptotic features in treated MCF-7 cells were observed by AO/PI staining. Furthermore, treated MCF-7 cells subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome c release as well as increase in ROS generation. We also found activation of caspases 3/7 and -9. Moreover, acute toxicity test demonstrated the nontoxic nature of the compound in mice. Our results showed the selected compound significantly induce apoptosis in MCF-7 cells via intrinsic pathway, which might be considered as a potent candidate for further in vivo and clinical breast cancer studies.Keywords: antiproliferative effect, MCF-7 human breast cancer cell line, apoptosis, caspases
Procedia PDF Downloads 5244178 Up-Regulation of SCUBE2 Expression in Co-Cultures of Human Mesenchymal Stem Cell and Breast Cancer Cells
Authors: Hirowati Ali, Aisyah Ellyanti, Dewi Rusnita, Septelia Inawati Wanandi
Abstract:
Stem cell has been known for its potency to be differentiated in many cells. Recently stem cell has been used for many treatment of degenerative medicine. It is still controversy whether stem cell can be used for therapy or these cells can activate cancer stem cell. SCUBE2 is a novel secreted and membrane-anchored protein which has been reported to its role in better prognosis and inhibition of cancer cell proliferation. Our study aims to observe whether stem cell can up-regulate SCUBE2 gene in MCF7 breast cancer cell line. We used in vitro study using MCF-7 cell treated with stem cell derived from placenta Wharton's jelly which has been known for its stemness and widely used. Our results showed that MCF-7 cell line grows up rapidly in 6-well culture dish. Stem cell was cultured in 6-well dish. After 50%-60% MCF-7 confluence, we co-cultured these cells with stem cells for 24 hours and 48 hours. We hypothesize SCUBE2 gene which is previously known for its higher expression in better prognosis of breast cancer, is up-regulated after stem cells addition in MCF7 culture dishes.Keywords: breast cancer cells, inhibition of cancer cells, mesenchymal stem cells, SCUBE2
Procedia PDF Downloads 3314177 The Winning Possibility of Female Candidate in Korea
Authors: Minjeoung Kim
Abstract:
The majority of Korean female members of parliament(MPs) had been elected from the proportional representation till the 19th assemblies but in the 20th general election women MPs of the district representation is slightly more than women MPs of the proportional representation. The chance of women candidates to win is not as low as we assume. Therefore this study aims to reveal which factors influence the election of women candidates, other factors except the political party, because the effect of political party is already well known. Gangnam Eul is selected because female candidate was elected in spite of the low percentage of vote won by her political party. According to the survey, the female candidate was elected thanks to her policies and election pledges. Therefore, women candidates can be elected when they are nominated as candidates by their party in a safe constituency but also they can be elected with their good policies and election pledges in an unsafe constituency. And also the degree of the education, the age and the profession of voters influenced the support of female candidate.Keywords: women candidates, 20th general election, winning in the district representation, policies and election pledges
Procedia PDF Downloads 2454176 The Characteristics of Porcine Immune Synapse via Flow Cytometry and Transmission Electron Microscope
Authors: Ann Ying-An Chen, Yi-Lun Tsai, Hso-Chi Chaung
Abstract:
An understanding of pathogens and the immune system has played an utmost important role in agricultural research for the development of vaccinations. The immunological synapse, cell to cell interaction play a crucial role in triggering the body's immune system, such as activation between antigen-presenting cells (APCs) and different subsets of T-cell. If these interactions are regulated appropriately, the host has the ability to defend itself against a wide spectrum of infectious pathogens. The aim of this study is to establish and to characterize a porcine immune synapse system by co-culturing T cell/APC. In this study, blood samples were collected from specific-pathogen-free piglets, and peripheral blood mononuclear cells (PBMC) were separated by using Ficoll-Pague. The PBMC were then stained with CD4 (FITC) and CD25 (PE) antibodies. Different subsets of T cells sorted by fluorescence-activated cell sorting flow cytometer were co-cultured for 24 hrs with alveolar macrophages, and the profiles of cytokine secretion and mRNA transcription levels of Toll-like receptors were examined after. Results showed that the three stages of immune synapse were clearly visible and identified under both transmission and scanning electron microscope (TEM and SEM). The significant interaction differences in toll-like receptor expressions within the co-cultured cell system were observed. The TLR7 mRNA expressions in CD4+CD25- cells were lower than those in CD4+CD25+ and CD4 -CD25+. Interestingly, the IL-10 production levels in CD4+CD25- cells (7.732 pg/mL) were significantly higher than those of CD4+CD25+ (2.636 pg/mL) and CD4 -CD25+ (2.48 pg/mL). These findings demonstrated that a clear understanding of the porcine immune synapse system can contribute greatly for further investigations on the mechanism of T-cell activation, which can benefit in the discovery of potential adjuvant candidate or effective antigen epitopes in the development of vaccinations with high efficacy.Keywords: antigen-presenting cells, immune synapse, pig, T subsets, toll-like receptor
Procedia PDF Downloads 1114175 Efficient Pre-Processing of Single-Cell Assay for Transposase Accessible Chromatin with High-Throughput Sequencing Data
Authors: Fan Gao, Lior Pachter
Abstract:
The primary tool currently used to pre-process 10X Chromium single-cell ATAC-seq data is Cell Ranger, which can take very long to run on standard datasets. To facilitate rapid pre-processing that enables reproducible workflows, we present a suite of tools called scATAK for pre-processing single-cell ATAC-seq data that is 15 to 18 times faster than Cell Ranger on mouse and human samples. Our tool can also calculate chromatin interaction potential matrices, and generate open chromatin signal and interaction traces for cell groups. We use scATAK tool to explore the chromatin regulatory landscape of a healthy adult human brain and unveil cell-type specific features, and show that it provides a convenient and computational efficient approach for pre-processing single-cell ATAC-seq data.Keywords: single-cell, ATAC-seq, bioinformatics, open chromatin landscape, chromatin interactome
Procedia PDF Downloads 151