Search results for: wheatstone bridge load cell
Commenced in January 2007
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Paper Count: 6989

Search results for: wheatstone bridge load cell

4979 Anti-proliferative Activity and HER2 Receptor Expression Analysis of MCF-7 (Breast Cancer Cell) Cells by Plant Extract Coleus Barbatus (Andrew)

Authors: Anupalli Roja Rani, Pavithra Dasari

Abstract:

Background: Among several, breast cancer has emerged as the most common female cancer in developing countries. It is the most common cause of cancer-related deaths worldwide among women. It is a molecularly and clinically heterogeneous disease. Moreover, it is a hormone–dependent tumor in which estrogens can regulate the growth of breast cells by binding with estrogen receptors (ERs). Moreover, the use of natural products in cancer therapeutics is due to their properties of biocompatibility and less toxicity. Plants are the vast reservoirs for various bioactive compounds. Coleus barbatus (Lamiaceae) contains anticancer properties against several cancer cell lines. Method: In the present study, an attempt is being made to enrich the knowledge of the anticancer activity of pure compounds extracted from Coleus barbatus (Andrew). On human breast cancer cell lines MCF-7. Here in, we are assessing the antiproliferative activity of Coleus barbatus (Andrew) plant extracts against MCF 7 and also evaluating their toxicity in normal human mammary cell lines such as Human Mammary Epithelial Cells (HMEC). The active fraction of plant extract was further purified with the help of Flash chromatography, Medium Pressure Liquid Chromatography (MPLC) and preparative High-Performance Liquid Chromatography (HPLC). The structure of pure compounds will be elucidated by using modern spectroscopic methods like Nuclear magnetic resonance (NMR), Electrospray Ionisation Mass Spectrometry (ESI-MS) methods. Later, the growth inhibition morphological assessment of cancer cells and cell cycle analysis of purified compounds were assessed using FACS. The growth and progression of signaling molecules HER2, GRP78 was studied by secretion assay using ELISA and expression analysis by flow cytometry. Result: Cytotoxic effect against MCF-7 with IC50 values were derived from dose response curves, using six concentrations of twofold serially diluted samples, by SOFTMax Pro software (Molecular device) and respectively Ellipticine and 0.5% DMSO were used as a positive and negative control. Conclusion: The present study shows the significance of various bioactive compounds extracted from Coleus barbatus (Andrew) root material. It acts as an anti-proliferative and shows cytotoxic effects on human breast cancer cell lines MCF7. The plant extracts play an important role pharmacologically. The whole plant has been used in traditional medicine for decades and the studies done have authenticated the practice. Earlier, as described, the plant has been used in the ayurveda and homeopathy medicine. However, more clinical and pathological studies must be conducted to investigate the unexploited potential of the plant. These studies will be very useful for drug designing in the future.

Keywords: coleus barbatus, HPLC, MPLC, NMR, MCF7, flash chromatograph, ESI-MS, FACS, ELISA.

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4978 Mesenchymal Stem Cells on Fibrin Assemblies with Growth Factors

Authors: Elena Filova, Ondrej Kaplan, Marie Markova, Helena Dragounova, Roman Matejka, Eduard Brynda, Lucie Bacakova

Abstract:

Decellularized vessels have been evaluated as small-diameter vascular prostheses. Reseeding autologous cells onto decellularized tissue prior implantation should prolong prostheses function and make them living tissues. Suitable cell types for reseeding are both endothelial cells and bone marrow-derived stem cells, with a capacity for differentiation into smooth muscle cells upon mechanical loading. Endothelial cells assure antithrombogenicity of the vessels and MSCs produce growth factors and, after their differentiation into smooth muscle cells, they are contractile and produce extracellular matrix proteins as well. Fibrin is a natural scaffold, which allows direct cell adhesion based on integrin receptors. It can be prepared autologous. Fibrin can be modified with bound growth factors, such as basic fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF). These modifications in turn make the scaffold more attractive for cells ingrowth into the biological scaffold. The aim of the study was to prepare thin surface-attached fibrin assemblies with bound FGF-2 and VEGF, and to evaluate growth and differentiation of bone marrow-derived mesenchymal stem cells on the fibrin (Fb) assemblies. Following thin surface-attached fibrin assemblies were prepared: Fb, Fb+VEGF, Fb+FGF2, Fb+heparin, Fb+heparin+VEGF, Fb+heparin+FGF2, Fb+heparin+FGF2+VEGF. Cell culture poly-styrene and glass coverslips were used as controls. Human MSCs (passage 3) were seeded at the density of 8800 cells/1.5 mL alpha-MEM medium with 2.5% FS and 200 U/mL aprotinin per well of a 24-well cell culture. The cells have been cultured on the samples for 6 days. Cell densities on day 1, 3, and 6 were analyzed after staining with LIVE/DEAD cytotoxicity/viability assay kit. The differentiation of MSCs is being analyzed using qPCR. On day 1, the highest density of MSCs was observed on Fb+VEGF and Fb+FGF2. On days 3 and 6, there were similar densities on all samples. On day 1, cell morphology was polygonal and spread on all sample. On day 3 and 6, MSCs growing on Fb assemblies with FGF2 became apparently elongated. The evaluation of expression of genes for von Willebrand factor and CD31 (endothelial cells), for alpha-actin (smooth muscle cells), and for alkaline phosphatase (osteoblasts) is in progress. We prepared fibrin assemblies with bound VEGF and FGF-2 that supported attachment and growth of mesenchymal stem cells. The layers are promising for improving the ingrowth of MSCs into the biological scaffold. Supported by the Technology Agency of the Czech Republic TA04011345, and Ministry of Health NT11270-4/2010, and BIOCEV – Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University” project (CZ.1.05/1.1.00/02.0109), funded by the European Regional Development Fund for their financial supports.

Keywords: fibrin assemblies, FGF-2, mesenchymal stem cells, VEGF

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4977 Effect of Capsule Storage on Viability of Lactobacillus bulgaricus and Streptococcus thermophilus in Yogurt Powder

Authors: Kanchana Sitlaothaworn

Abstract:

Yogurt capsule was made by mixing 14% w/v of reconstitution of skim milk with 2% FOS. The mixture was fermented by commercial yogurt starter comprising Lactobacillus bulgaricus and Streptococcus thermophilus. These yogurts were made as yogurt powder by freeze-dried. Yogurt powder was put into capsule then stored for 28 days at 4oc. 8ml of commercial yogurt was found to be the most suitable inoculum size in yogurt production. After freeze-dried, the viability of L. bulgaricus and S. thermophilus reduced from 109 to 107 cfu/g. The precence of sucrose cannot help to protect cell from ice crystal formation in freeze-dried process, high (20%) sucrose reduced L. bulgaricus and S. thermophilus growth during fermentation of yogurt. The addition of FOS had reduced slowly the viability of both L. bulgaricus and S. thermophilus similar to control (without FOS) during 28 days of capsule storage. The viable cell exhibited satisfactory viability level in capsule storage (6.7x106cfu/g) during 21 days at 4oC.

Keywords: yogurt capsule, Lactobacillus bulgaricus, Streptococcus thermophilus, freeze-drying, sucrose

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4976 In Vivo Response of Scaffolds of Bioactive Glass-Ceramic

Authors: Ana Claudia Muniz Rennó, Karina Nogueira

Abstract:

This study aimed to investigate the in vivo tissue response of the introduction of the bioactive mesh (BM) scaffolds using a model of tibial bone defect implants in rats. Although a previous in vivo study demonstrated a highly positive response of particulate bioactive materials in the morphological and biomechanical properties of the bone callus, the effects of material with superior bioactivity, present in form of meshes have not been studied yet. Eighty male Wistar rats with 3 mm tibial defects were used. Animals were divided into four groups: intact group (IG) – tibia without any injury; bone defect day zero (0dD) – bone defects, sacrificed immediately after injury; bone defect control group (CG) – bone defects without any filler and bone defect filled with BM scaffold. The animals of BM and CG groups were sacrificed 15, 30 and 45 days post-injury to compare the temporal-special effects of the scaffolds on bone healing. The histological analysis revealed an organized newly formed bone at 30 and 45 days post-surgery in the BM. Also, this group presented an increased COX-2 expression on days 15 and 30 post-surgery. Furthermore, the immunohistochemistry analysis revealed that, BM presented a positive immunoexpression of RUNX-2 during all periods evaluated. The biomechanical analysis revealed that at 15 day after surgery, no significant statistically difference was observed between BM and CG and both groups had significantly higher values of maximal load compared to 0dG and significantly lower values than IG. On days 30 and 45 post-surgery, BM presented statistically lower values of maximal load compared to the CG. Nevertheless, at the same periods, BM did not show statistically significant difference compared to the IG maximal load values (p > 0, 05). Our results revealed that the implantation of the BM scaffolds was effective in stimulating newly bone formation.

Keywords: bone, biomaterials, scaffolds, cartilage

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4975 Experimenting the Influence of Input Modality on Involvement Load Hypothesis

Authors: Mohammad Hassanzadeh

Abstract:

As far as incidental vocabulary learning is concerned, the basic contention of the Involvement Load Hypothesis (ILH) is that retention of unfamiliar words is, generally, conditional upon the degree of involvement in processing them. This study examined input modality and incidental vocabulary uptake in a task-induced setting whereby three variously loaded task types (marginal glosses, fill-in-task, and sentence-writing) were alternately assigned to one group of students at Allameh Tabataba’i University (n=2l) during six classroom sessions. While one round of exposure was comprised of the audiovisual medium (TV talk shows), the second round consisted of textual materials with approximately similar subject matter (reading texts). In both conditions, however, the tasks were equivalent to one another. Taken together, the study pursued the dual objectives of establishing a litmus test for the ILH and its proposed values of ‘need’, ‘search’ and ‘evaluation’ in the first place. Secondly, it sought to bring to light the superiority issue of exposure to audiovisual input versus the written input as far as the incorporation of tasks is concerned. At the end of each treatment session, a vocabulary active recall test was administered to measure their incidental gains. Running a one-way analysis of variance revealed that the audiovisual intervention yielded higher gains than the written version even when differing tasks were included. Meanwhile, task 'three' (sentence-writing) turned out the most efficient in tapping learners' active recall of the target vocabulary items. In addition to shedding light on the superiority of audiovisual input over the written input when circumstances are relatively held constant, this study for the most part, did support the underlying tenets of ILH.

Keywords: Keywords— Evaluation, incidental vocabulary learning, input mode, Involvement Load Hypothesis, need, search.

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4974 Finite Element Analysis of Oil-Lubricated Elliptical Journal Bearings

Authors: Marco Tulio C. Faria

Abstract:

Fixed-geometry hydrodynamic journal bearings are one of the best supporting systems for several applications of rotating machinery. Cylindrical journal bearings present excellent load-carrying capacity and low manufacturing costs, but they are subjected to the oil-film instability at high speeds. An attempt of overcoming this instability problem has been the development of non-circular journal bearings. This work deals with an analysis of oil-lubricated elliptical journal bearings using the finite element method. Steady-state and dynamic performance characteristics of elliptical bearings are rendered by zeroth- and first-order lubrication equations obtained through a linearized perturbation method applied on the classical Reynolds equation. Four-node isoparametric rectangular finite elements are employed to model the bearing thin film flow. Curves of elliptical bearing load capacity and dynamic force coefficients are rendered at several operating conditions. The results presented in this work demonstrate the influence of the bearing ellipticity on its performance at different loading conditions.

Keywords: elliptical journal bearings, non-circular journal bearings, hydrodynamic bearings, finite element method

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4973 Smart Coating for Enhanced Corneal Healing via Delivering Progranulin

Authors: Dan Yan, Yunuo Zhang, Yuhan Huang, Weijie Ouyang

Abstract:

The cornea serves as a vital protective barrier for the eye; however, it is prone to injury and damage that can disrupt corneal epithelium and nerves, triggering inflammation. Therefore, understanding the biological effects and molecular mechanisms involved in corneal wound healing and identifying drugs targeting these pathways is crucial for researchers in this field. This study aimed to investigate the therapeutic potential of progranulin (PGRN) in treating corneal injuries. Our findings demonstrated that PGRN significantly enhanced corneal wound repair by accelerating corneal re-epithelialization and re-innervation. In vitro experiments with cultured epithelial cells and trigeminal ganglion cells further revealed that PGRN stimulated corneal epithelial cell proliferation and promoted axon growth in trigeminal ganglion cells. Through RNA-sequencing (RNA-seq) analysis and other experimental techniques, we discovered that PGRN exerted its healing effects by modulating the Wnt signaling pathway, which played a critical role in repairing epithelial cells and promoting axon regeneration in trigeminal neurons. Importantly, our study highlighted the anti-inflammatory properties of PGRN by inhibiting the NF-κB signaling pathway, leading to decreased infiltration of macrophages. In conclusion, our findings underscored the potential of PGRN in facilitating corneal wound healing by promoting corneal epithelial cell proliferation, trigeminal ganglion cell axon regeneration, and suppressing ocular inflammation. These results suggest that PGRN could potentially expedite the healing process and improve visual outcomes in patients with corneal injuries.

Keywords: cornea, wound healing, progranulin, corneal epithelial cells, trigeminal ganglion cells

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4972 Compact Dual-Band Bandpass Filter Based on Quarter Wavelength Stepped Impedance Resonators

Authors: Yu-Fu Chen, Zih-Jyun Dai, Chen-Te Chiu, Shiue-Chen Chiou, Yung-Wei Chen, Yu-Ming Lin, Kuan-Yu Chen, Hung-Wei Wu, Hsin-Ying Lee, Yan-Kuin Su, Shoou-Jinn Chang

Abstract:

This paper presents a compact dual-band bandpass filter that involves using the quarter wavelength stepped impedance resonators (SIRs) for achieving simultaneously compact circuit size and good dual-band performance. The filter is designed at 2.4 / 3.5 GHz and constructed by two pairs of quarter wavelength SIRs and source-load lines. By properly tuning the impedance ratio, length ratio and radius of via hole of the SIRs, dual-passbands performance can be easily determined. To improve the passband selectivity, the use of source-load lines is to increase coupling energy between the resonators. The filter is showing simple configuration, effective design method and small circuit size. The measured results are in good agreement with the simulation results.

Keywords: dual-band, bandpass filter, stepped impedance resonators, SIR

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4971 Integration of a Microbial Electrolysis Cell and an Oxy-Combustion Boiler

Authors: Ruth Diego, Luis M. Romeo, Antonio Morán

Abstract:

In the present work, a study of the coupling of a Bioelectrochemical System together with an oxy-combustion boiler is carried out; specifically, it proposes to connect the combustion gas outlet of a boiler with a microbial electrolysis cell (MEC) where the CO2 from the gases are transformed into methane in the cathode chamber, and the oxygen produced in the anode chamber is recirculated to the oxy-combustion boiler. The MEC mainly consists of two electrodes (anode and cathode) immersed in an aqueous electrolyte; these electrodes are separated by a proton exchange membrane (PEM). In this case, the anode is abiotic (where oxygen is produced), and it is at the cathode that an electroactive biofilm is formed with microorganisms that catalyze the CO2 reduction reactions. Real data from an oxy-combustion process in a boiler of around 20 thermal MW have been used for this study and are combined with data obtained on a smaller scale (laboratory-pilot scale) to determine the yields that could be obtained considering the system as environmentally sustainable energy storage. In this way, an attempt is made to integrate a relatively conventional energy production system (oxy-combustion) with a biological system (microbial electrolysis cell), which is a challenge to be addressed in this type of new hybrid scheme. In this way, a novel concept is presented with the basic dimensioning of the necessary equipment and the efficiency of the global process. In this work, it has been calculated that the efficiency of this power-to-gas system based on MEC cells when coupled to industrial processes is of the same order of magnitude as the most promising equivalent routes. The proposed process has two main limitations, the overpotentials in the electrodes that penalize the overall efficiency and the need for storage tanks for the process gases. The results of the calculations carried out in this work show that certain real potentials achieve an acceptable performance. Regarding the tanks, with adequate dimensioning, it is possible to achieve complete autonomy. The proposed system called OxyMES provides energy storage without energetically penalizing the process when compared to an oxy-combustion plant with conventional CO2 capture. According to the results obtained, this system can be applied as a measure to decarbonize an industry, changing the original fuel of the oxy-combustion boiler to the biogas generated in the MEC cell. It could also be used to neutralize CO2 emissions from industry by converting it to methane and then injecting it into the natural gas grid.

Keywords: microbial electrolysis cells, oxy-combustion, co2, power-to-gas

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4970 Cryotopic Macroporous Polymeric Matrices for Regenerative Medicine and Tissue Engineering Applications

Authors: Archana Sharma, Vijayashree Nayak, Ashok Kumar

Abstract:

Three-dimensional matrices were fabricated from blend of natural-natural polymers like carrageenan-gelatin and synthetic -natural polymers such as PEG- gelatin (PEG of different molecular weights (2,000 and 6,000) using two different crosslinkers; glutaraldehyde and EDC-NHS by cryogelation technique. Blends represented a feasible approach to design 3-D scaffolds with controllable mechanical, physical and biochemical properties without compromising biocompatibility and biodegradability. These matrices possessed interconnected porous structure, good mechanical strength, biodegradable nature, constant swelling kinetics, ability to withstand high temperature and visco-elastic behavior. Hemocompatibility of cryogel matrices was determined by coagulation assays and hemolytic activity assay which demonstrated that these cryogels have negligible effects on coagulation time and have excellent blood compatibility. In vitro biocompatibility (cell-matrix interaction) inferred good cell adhesion, proliferation, and secretion of ECM on matrices. These matrices provide a microenvironment for the growth, proliferation, differentiation and secretion of ECM of different cell types such as IMR-32, C2C12, Cos-7, rat bone marrow derived MSCs and human bone marrow MSCs. Hoechst 33342 and PI staining also confirmed that the cells were uniformly distributed, adhered and proliferated properly on the cryogel matrix. An ideal scaffold used for tissue engineering application should allow the cells to adhere, proliferate and maintain their functionality. Neurotransmitter analysis has been done which indicated that IMR-32 cells adhered, proliferated and secreted neurotransmitters when they interacted with these matrices which showed restoration of their functionality. The cell-matrix interaction up to molecular level was also evaluated so to check genotoxicity and protein expression profile which indicated that these cryogel matrices are non-genotoxic and maintained biofunctionality of cells growing on these matrices. All these cryogels, when implanted subcutaneously in balb/c mice, showed no adverse systemic or local toxicity effects at implantation site. There was no significant increase in inflammatory cell count has otherwise been observed after scaffold implantation. These cryogels are supermacroporous and this porous structure allows cell infiltration and proliferation of host cells. This showed the integration and presence of infiltrated cells into the cryogel implants. Histological analysis confirmed that the implanted cryogels do not have any adverse effect in spite of host immune system recognition at the site of implantation, on its surrounding tissues and other vital host organs. In vivo biocompatibility study after in vitro biocompatibility analysis has also concluded that these synthesized cryogels act as important biological substitutes, more adaptable and appropriate for transplantation. Thus, these cryogels showed their potential for soft tissue engineering applications.

Keywords: cryogelation, hemocompatibility, in vitro biocompatibility, in vivo biocompatibility, soft tissue engineering applications

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4969 Reduction of the Microbial Load of Biocontaminated Bovine Milk Using Grounding with Copper Wire

Authors: Claudivan Costa de Lima, Angelo da Silva Monteiro

Abstract:

With the aim of evaluating the effects of grounding with copper wire on the reduction of the microbial load of biocontaminated milk samples and on their acidification over time, two complementary experiments were carried out. In the first, the treatments consisted of: i) raw milk sample (control), ii) slow pasteurization, iii) grounding with copper wire and, iv) contact with copper ring. Analyzes of total, thermoresistant and mesophilic coliforms were performed 30 minutes after the application of these treatments. In the second experiment, under the same conditions as the first, measurements of pH and Dornic acidity were performed at 0, 0.5, 2, 4, 8, 12, and 24 h from the installation of the experiment. Pasteurization eliminated almost all groups of bacteria present in the milk samples while grounding only allowed reductions in the population of thermotolerant coliforms and mesophiles, both greater than 95%, maintaining, however, unchanged the amounts of total coliforms. The copper ring, in turn, had no effect on the microbiological parameters studied. The reduction in the population of mesophiles in grounded milk samples, contrary to what happened with pasteurized milk, was not enough to inhibit the acidification process over the experimental period.

Keywords: pasteurization, low frequency electric current, thermotolerant coliforms, mesophiles in bovine milk

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4968 Curcumin Nanomedicine: A Breakthrough Approach for Enhanced Lung Cancer Therapy

Authors: Shiva Shakori Poshteh

Abstract:

Lung cancer is a highly prevalent and devastating disease, representing a significant global health concern with profound implications for healthcare systems and society. Its high incidence, mortality rates, and late-stage diagnosis contribute to its formidable nature. To address these challenges, nanoparticle-based drug delivery has emerged as a promising therapeutic strategy. Curcumin (CUR), a natural compound derived from turmeric, has garnered attention as a potential nanomedicine for lung cancer treatment. Nanoparticle formulations of CUR offer several advantages, including improved drug delivery efficiency, enhanced stability, controlled release kinetics, and targeted delivery to lung cancer cells. CUR exhibits a diverse array of effects on cancer cells. It induces apoptosis by upregulating pro-apoptotic proteins, such as Bax and Bak, and downregulating anti-apoptotic proteins, such as Bcl-2. Additionally, CUR inhibits cell proliferation by modulating key signaling pathways involved in cancer progression. It suppresses the PI3K/Akt pathway, crucial for cell survival and growth, and attenuates the mTOR pathway, which regulates protein synthesis and cell proliferation. CUR also interferes with the MAPK pathway, which controls cell proliferation and survival, and modulates the Wnt/β-catenin pathway, which plays a role in cell proliferation and tumor development. Moreover, CUR exhibits potent antioxidant activity, reducing oxidative stress and protecting cells from DNA damage. Utilizing CUR as a standalone treatment is limited by poor bioavailability, lack of targeting, and degradation susceptibility. Nanoparticle-based delivery systems can overcome these challenges. They enhance CUR’s bioavailability, protect it from degradation, and improve absorption. Further, Nanoparticles enable targeted delivery to lung cancer cells through surface modifications or ligand-based targeting, ensuring sustained release of CUR to prolong therapeutic effects, reduce administration frequency, and facilitate penetration through the tumor microenvironment, thereby enhancing CUR’s access to cancer cells. Thus, nanoparticle-based CUR delivery systems promise to improve lung cancer treatment outcomes. This article provides an overview of lung cancer, explores CUR nanoparticles as a treatment approach, discusses the benefits and challenges of nanoparticle-based drug delivery, and highlights prospects for CUR nanoparticles in lung cancer treatment. Future research aims to optimize these delivery systems for improved efficacy and patient prognosis in lung cancer.

Keywords: lung cancer, curcumin, nanomedicine, nanoparticle-based drug delivery

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4967 Endometriosis-Associated Ovarian Cancer: Clinical and Pathological Pattern

Authors: I. Ramalho, S. Campos, M. Dias

Abstract:

Introduction: Endometriosis may play a role in the pathogenesis of ovarian cancer (OC), however, the risk and prognosis have not been well established. The association between these two pathologies could have an important impact on prevention and early diagnosis of OC. Objective: To analyze the prevalence of endometriosis associated ovarian cancer and related clinical, epidemiological and histopathological issues. Design: We conducted a retrospective case series analysis of patients diagnosed with endometriosis and ovarian cancer in the Gynecology Department of Coimbra University Hospital Center since 2006 to 2015. Methods: We collected data from women diagnosed with ovarian cancer, with anatomopathology records reporting findings of endometriosis in ovarian cancer patients. Patients were retrieved from the pathological records and appropriate medical records were retrospectively reviewed. Statistical analysis was performed using SPSS 22.0. Results: Histological evidence of endometriosis was found in 17 out of 261 patients diagnosed with ovarian cancer (OC) (6.51%). The most usual symptoms were pelvic pain, abdominal distension, asthenia, ascites, weight loss and nausea. Mean age at diagnosis was 61.2 ± 15.1, 41-86 years old, 33.3% were pre-menopausal patients and cancer stage distribution was predominantly stage I (31.3%) and stage III (56.3%). OC occurred unilaterally in 14 patients and 2 patients were diagnosed with a synchronous ovarian and endometrial cancer. Regarding histological type, 10 OC were classified as clear cell carcinoma (CCC), 4 endometrioid carcinomas (EC) and 3 mixed type (clear cell and endometrioid). Four ovarian carcinomas presumably arose from endometriomas: 3 CCC and 1 EC. Conclusions: In accordance with previous studies, clear cell was the most common pathological type in endometriotic patients, followed by endometrioid carcinomas, and two rare synchronous ovarian and endometrial carcinomas were registered. Although endometriosis association to OC is uncommon, endometriosis should be managed with special care in order to early diagnosis.

Keywords: endometriosis, histology, observational study, ovarian cancer

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4966 Induction of G1 Arrest and Apoptosis in Human Cancer Cells by Panaxydol

Authors: Dong-Gyu Leem, Ji-Sun Shin, Sang Yoon Choi, Kyung-Tae Lee

Abstract:

In this study, we focused on the anti-proliferative effects of panaxydol, a C17 polyacetylenic compound derived from Panax ginseng roots, against various human cancer cells. We treated with panaxydol to various cancer cells and panaxydol treatment was found to significantly inhibit the proliferation of human lung cancer cells (A549) and human pancreatic cancer cells (AsPC-1 and MIA PaCa-2), of which AsPC-1 cells were most sensitive to its treatment. DNA flow cytometric analysis indicated that panaxydol blocked cell cycle progression at the G1 phase in A549 cells, which accompanied by a parallel reduction of protein expression of cyclin-dependent kinase (CDK) 2, CDK4, CDK6, cyclin D1 and cyclin E. CDK inhibitors (CDKIs), such as p21CIP1/WAF1 and p27KIP1, were gradually upregulated after panaxydol treatment at the protein levels. Furthermore, panaxydol induced the activation of p53 in A549 cells. In addition, panaxydol also induced apoptosis of AsPC-1 and MIA PaCa-2 cells, as shown by accumulation of subG1 and apoptotic cell populations. Panaxydol triggered the activation of caspase-3, -8, -9 and the cleavage of poly (ADP-ribose) polymerase (PARP). Reduction of mitochondrial transmembrane potential by panaxydol was determined by staining with dihexyloxacarbocyanine iodide. Furthermore, panaxydol suppressed the levels of anti-apoptotic proteins, XIAP and Bcl-2, and increased the levels of proapoptotic proteins, Bax and Bad. In addition, panaxydol inhibited the activation of Akt and extracellular signal-regulated kinase (ERK) and activated the p38 mitogen-activated protein kinase kinase (MAPK). Our results suggest that panaxydol is an anti-tumor compound that causes p53-mediated cell cycle arrest and apoptosis via mitochondrial apoptotic pathway in various cancer cells.

Keywords: apoptosis, cancer, G1 arrest, panaxydol

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4965 An Activatable Theranostic for Targeted Cancer Therapy and Imaging

Authors: Sankarprasad Bhuniya, Sukhendu Maiti, Eun-Joong Kim, Hyunseung Lee, Jonathan L. Sessler, Kwan Soo Hong, Jong Seung Kim

Abstract:

A new theranostic strategy is described. It is based on the use of an “all in one” prodrug, namely the biotinylated piperazine-rhodol conjugate 4a. This conjugate, which incorporates the anticancer drug SN-38, undergoes self-immolative cleavage when exposed to biological thiols. This leads to the tumor-targeted release of the active SN-38 payload along with fluorophore 1a. This release is made selective as the result of the biotin functionality. Fluorophore 1a is 32-fold more fluorescent than prodrug 4a. It permits the delivery and release of the SN-38 payload to be monitored easily in vitro and in vivo, as inferred from cell studies and ex vivo analyses of mice xenografts derived HeLa cells, respectively. Prodrug 4a also displays anticancer activity in the HeLa cell murine xenograft tumor model. On the basis of these findings we suggest that the present strategy, which combines within a single agent the key functions of targeting, release, imaging, and treatment, may have a role to play in cancer diagnosis and therapy.

Keywords: theranostic, prodrug, cancer therapy, fluorescence

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4964 Multiple Winding Multiphase Motor for Electric Drive System

Authors: Zhao Tianxu, Cui Shumei

Abstract:

This paper proposes a novel multiphase motor structure. The armature winding consists of several independent multiphase windings that have different rating rotate speed and power. Compared to conventional motor, the novel motor structure has more operation mode and fault tolerance mode, which makes it adapt to high-reliability requirement situation such as electric vehicle, aircraft and ship. Performance of novel motor structure varies with winding match. In order to find optimum control strategy, motor torque character, efficiency performance and fault tolerance ability under different operation mode are analyzed in this paper, and torque distribution strategy for efficiency optimization is proposed. Simulation analyze is taken and the result shows that proposed structure has the same efficiency on heavy load and higher efficiency on light load operation points, which expands high efficiency area of motor and cruise range of vehicle. The proposed structure can improve motor highest speed.

Keywords: multiphase motor, armature winding match, torque distribution strategy, efficiency

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4963 Biosynthesis of Titanium Dioxide Nanoparticles and Their Antibacterial Property

Authors: Prachi Singh

Abstract:

This paper presents a low-cost, eco-friendly and reproducible microbe mediated biosynthesis of TiO2 nanoparticles. TiO2 nanoparticles synthesized using the bacterium, Bacillus subtilis, from titanium as a precursor, were confirmed by TEM analysis. The morphological characteristics state spherical shape, with the size of individual or aggregate nanoparticles, around 30-40 nm. Microbial resistance represents a challenge for the scientific community to develop new bioactive compounds. Here, the antibacterial effect of TiO2 nanoparticles on Escherichia coli was investigated, which was confirmed by CFU (Colony-forming unit). Further, growth curve study of E. coli Hb101 in the presence and absence of TiO2 nanoparticles was done. Optical density decrease was observed with the increase in the concentration of TiO2. It could be attributed to the inactivation of cellular enzymes and DNA by binding to electron-donating groups such as carboxylates, amides, indoles, hydroxyls, thiols, etc. which cause little pores in bacterial cell walls, leading to increased permeability and cell death. This justifies that TiO2 nanoparticles have efficient antibacterial effect and have potential to be used as an antibacterial agent for different purposes.

Keywords: antibacterial effect, CFU, Escherichia coli Hb101, growth curve, TEM, TiO2 nanoparticle, Toxicity, UV-Vis

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4962 Capture of Co₂ From Natural Gas Using Modified Imidazolium Ionic Liquids

Authors: Alaa A. Ghanem, S. E. M. Desouky

Abstract:

Natural gas (NG) is considered one of the most essential global energy sources. NG fields are often far away from the market, and a long-distance transporting pipeline usually is required. Production of NG with high content of CO₂ leads to severe problems such as equipment corrosion along with the production line until refinery.in addition to a high level of toxicity and decreasing in calorific value of the NG. So it is recommended to remove or decrease the CO₂ percent to meet transport specifications. This can be reached using different removal techniques such as physical and chemical absorption, pressure swing adsorption, membrane separation, or low-temperature separation. Many solvents and chemicals are being used to capture carbon dioxide on a large scale; among them, Ionic liquids have great potential due to their tunable properties; low vapour pressure, low melting point, and sensible thermal stability. In this research, three modifiedimidazolium ionic liquids will be synthesized and characterized using different tools of analysis such as FT-IR, 1H NMR. Thermal stability and surface activity will be studied. The synthesized compounds will be evaluated as selective solvents for CO₂ removal from natural gas using PVT cell.

Keywords: natural gas, CO₂ capture, imidazolium ionic liquid, PVT cell

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4961 Adomian’s Decomposition Method to Generalized Magneto-Thermoelasticity

Authors: Hamdy M. Youssef, Eman A. Al-Lehaibi

Abstract:

Due to many applications and problems in the fields of plasma physics, geophysics, and other many topics, the interaction between the strain field and the magnetic field has to be considered. Adomian introduced the decomposition method for solving linear and nonlinear functional equations. This method leads to accurate, computable, approximately convergent solutions of linear and nonlinear partial and ordinary differential equations even the equations with variable coefficients. This paper is dealing with a mathematical model of generalized thermoelasticity of a half-space conducting medium. A magnetic field with constant intensity acts normal to the bounding plane has been assumed. Adomian’s decomposition method has been used to solve the model when the bounding plane is taken to be traction free and thermally loaded by harmonic heating. The numerical results for the temperature increment, the stress, the strain, the displacement, the induced magnetic, and the electric fields have been represented in figures. The magnetic field, the relaxation time, and the angular thermal load have significant effects on all the studied fields.

Keywords: Adomian’s decomposition method, magneto-thermoelasticity, finite conductivity, iteration method, thermal load

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4960 Electrochemistry and Performance of Bryophylum pinnatum Leaf (BPL) Electrochemical Cell

Authors: M. A. Mamun, M. I. Khan, M. H. Sarker, K. A. Khan, M. Shajahan

Abstract:

The study was carried out to investigate on an innovative invention, Pathor Kuchi Leaf (PKL) cell, which is fueled with PKL sap of widely available plant called Bryophyllum pinnatum as an energy source for use in PKL battery to generate electricity. This battery, a primary source of electricity, has several order of magnitude longer shelf-lives than the traditional Galvanic cell battery, is still under investigation. In this regard, we have conducted some experiments using various instruments including Atomic Absorption Spectrophotometer (AAS), Ultra-Violet Visible spectrophotometer (UV-Vis), pH meter, Ampere-Volt-Ohm Meter (AVO Meter), etc. The AAS, UV-Vis, and pH-metric analysis data provided that the potential and current were produced as the Zn electrode itself acts as reductant while Cu2+ and H+ ions are behaving as the oxidant. The significant influence of secondary salt on current and potential leads to the dissociation of weak organic acids in PKL juice, and subsequent enrichment to the reactant ions by the secondary salt effects. However, the liquid junction potential was not as great as minimized with the opposite transference of organic acid anions and H+ ions as their dissimilar ionic mobilities. Moreover, the large value of the equilibrium constant (K) implies the big change in Gibbs free energy (∆G), the more electromotive force works in electron transfer during the forward electrochemical reaction which coincides with the fast reduction of the weight of zinc plate, revealed the additional electrical work in the presence of PKL sap. This easily fabricated high-performance PKL battery can show an excellent promise during the off-peak across the countryside.

Keywords: Atomic Absorption Spectrophotometer (AAS), Bryophylum Pinnatum Leaf (BPL), electricity, electrochemistry, organic acids

Procedia PDF Downloads 329
4959 The Dynamic Cone Penetration Test: A Review of Its Correlations and Applications

Authors: Abdulrahman M. Hamid

Abstract:

Dynamic Cone Penetration Test (DCPT) is widely used for field quality assessment of soils. Its application to predict the engineering properties of soil is globally promoted by the fact that it is difficult to obtain undisturbed soil samples, especially when loose or submerged sandy soil is encountered. Detailed discussion will be presented on the current development of DCPT correlations with resilient modulus, relative density, California Bearing Ratio (CBR), unconfined compressive strength and shear strength that have been developed for different materials in both the laboratory and field, as well as on the usage of DCPT in quality control of compaction of earth fills and performance evaluation of pavement layers. In addition, the relationship of the DCPT with other instruments such as falling weight deflectometer, nuclear gauge, soil stiffens gauge, and plate load test will be reported. Lastely, the application of DCPT in Saudi Arabia in recent years will be addressed in this manuscript.

Keywords: dynamic cone penetration test, falling weight deflectometer, nuclear gauge, soil stiffens gauge, plate load test, automated dynamic cone penetration

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4958 Influence of Stress Relaxation and Hysteresis Effect for Pressure Garment Design

Authors: Chia-Wen Yeh, Ting-Sheng Lin, Chih-Han Chang

Abstract:

Pressure garment has been used to prevent and treat the hypertrophic scars following serious burns since 1970s. The use of pressure garment is believed to hasten the maturation process and decrease the highness of scars. Pressure garment is custom made by reducing circumferential measurement of the patient by 10%~20%, called Reduction Factor. However the exact reducing value used depends on the subjective judgment of the therapist and the feeling of patients throughout the try and error process. The Laplace Law can be applied to calculate the pressure from the dimension of the pressure garment by the circumferential measurements of the patients and the tension profile of the fabrics. The tension profile currently obtained neglects the stress relaxation and hysteresis effect within most elastic fabrics. The purpose of this study was to investigate the influence of the tension attenuation, from stress relaxation and hysteresis effect of the fabrics. Samples of pressure garment were obtained from Sunshine Foundation Organization, a nonprofit organization for burn patients in Taiwan. The wall tension profile of pressure garments were measured on a material testing system. Specimens were extended to 10% of the original length, held for 1 hour for the influence of the stress relaxation effect to take place. Then, specimens were extended to 15% of the original length for 10 seconds, then reduced to 10% to simulate donning movement for the influence of the hysteresis effect to take place. The load history was recorded. The stress relaxation effect is obvious from the load curves. The wall tension is decreased by 8.5%~10% after 60mins of holding. The hysteresis effect is obvious from the load curves. The wall tension is increased slightly, then decreased by 1.5%~2.5% and lower than stress relaxation results after 60mins of holding. The wall tension attenuation of the fabric exists due to stress relaxation and hysteresis effect. The influence of hysteresis is more than stress relaxation. These effect should be considered in order to design and evaluate the pressure of pressure garment more accurately.

Keywords: hypertrophic scars, hysteresis, pressure garment, stress relaxation

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4957 Quality Assessment of Hollow Sandcrete Blocks in Minna, Nigeria

Authors: M. Abdullahi, S. Sadiku, Bashar S. Mohammed, J. I. Aguwa

Abstract:

The properties of hollow sandcrete blocks produced in Minna, Nigeria are presented. Sandcrete block is made of cement, water and sand bound together in certain mix proportions. For the purpose of this work, fifty (50) commercial sandcrete block industries were visited in Minna, Nigeria to obtain block samples and aggregates used for the manufacture, and to also take inventory of the mix composition and the production process. Sieve analysis tests were conduction on the soil sample from various block industries to ascertain their quality to be used for block making. The mix ratios were also investigated. Five (5) nine inches (9’’ or 225mm) blocks were obtained from each block industry and tested for dimensional compliance and compressive strength. The result of test shows that the grading of the sand falls within the limit required by BS 882: 1990. The sand particles generally satisfy the grading requirement of overall grading and also fall in at least one of the classification of coarse grading, medium grading or fine grading. This clearly indicates that the quality of the aggregates used for the production of sandcrete blocks in Minna, Nigeria are of good quality in terms of grading and workable mix can easily be achieved to obtain high quality product. Physical examinations of the block sizes show slight deviation from the standard requirement in NIS 87:2000. Compressive strength of hollow sandcrete blocks in range of 0.12 N/mm2 to 0.54 N/mm2 was obtained which is below the recommendable value of 3.45 N/mm2 for load bearing hollow sandcrete blocks. This indicates that these blocks are below the standard for load-bearing sandcrete blocks and cannot be used as load bearing walling units. The mix composition also indicated low cement content resulting in low compressive strength. Most of the commercial block industries visited do not take curing very serious. Water were only sprinkled ones or twice before the blocks were stacked and made readily available for sale. It is recommended that a mix ratio of 1:4 to 1:6 should be used for the production of sandcrete blocks and proper curing practice should be adhered to. Blocks should also be cured for 14 days before making them available for consumers.

Keywords: compressive strength, dimensions, mix proportions, sandcrete blocks

Procedia PDF Downloads 392
4956 Effect of Stress Relief of the Footbath Using Bio-Marker in Japan

Authors: Harumi Katayama, Mina Suzuki, Taeko Muramatsu, Yui Shimogawa, Yoshimi Mizushima, Mitsuo Hiramatsu, Kimitsugu Nakamura, Takeshi Suzue

Abstract:

Purpose: There are very often footbaths in the hot-spring area as culture from old days in Japan. This culture moderately supported mental and physical health among people. In Japanese hospitals, nurses provide footbath for severe patients to mental comfortable. However, there are only a few evidences effect of footbath for mental comfortable. In this presentation, we show the effect of stress relief of the footbath using biomarker among 35 college students in volunteer. Methods: The experiment was designed in two groups of the footbath group and the simple relaxation group randomly. As mental load, Kraepelin test was given to the students beforehand. Ultra-weak chemiluminescence (UCL) in saliva and self-administered liner scale measurable emotional state were measured on four times concurrently; there is before and after the mental load, after the stress relief, and 30 minutes after the stress relief. The scale that measured emotional state was consisted of 7 factors; there is excitement, relaxation, vigorous, fatigue, tension, calm, and sleepiness with 22 items. ANOVA was calculated effect of the footbath for stress relief. Results: The level of UCL (photons/100sec) was significantly increased in response on both groups after mental load. After the two types of stress relief, UCL (photons/100sec) of footbath group was significantly decreased compared to simple relaxation group. Score of sleepiness and relaxation were significantly increased after the stress relief in the footbath group than the simple relaxation group. However, score of excitement, vigorous, tension, and calm were exhibit the same degree of decrease after the stress relief on both group. Conclusion: It was suggested that salivary UCL may be a sensitive biomarker for mild stress relief as nursing care. In the future, we will measure using UCL to evaluate as stress relief for inpatients, outpatients, or general public as the subjects.

Keywords: bio-marker, footbath, Japan, stress relief

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4955 Identification and Application of Biocontrol Agents against Cotton Leaf Curl Virus Disease in Gossypium hirsutum under Green House Conditions

Authors: Memoona Ramzan, Bushra Tabassum, Anwar Khan, Muhammad Tariq, Mudassar Fareed Awan, Idrees Ahmad Nasir, Zahida Qamar, Naila Shahid, Tayyab Husnain

Abstract:

Biological control is a novel approach being used in crop protection nowadays. Bacteria like Bacillus and Pseudomonas are reported for this purpose and few of their products are commercially available too. Rhizosphere and phyllosphere of healthy cotton plants were used as a source to isolate bacteria capable of exhibiting properties worthy for selection as biocontrol agent. For this purpose all isolated strains were screened for the activities like phosphate solubilization, Indole acetic acid (IAA) production and biocontrol against fungi. Two strains S1HL3 and S1HL4 showed phosphate solubilization and IAA production simultaneously while two other JS2HR4 and JS3HR2 were good inhibitors of fungal pathogens. Through biochemical and molecular characterization these bacteria were identified as P. aeruginosa, Burkholderia and Bacillus respectively. In green house trials of these isolates against Cotton leaf curl virus (CLCuV), seven treatments including individual bacterial isolate and consortia were included. Treated plants were healthy as compared to control plants in which upto 74% CLCuV symptomatic plants exist. Maximum inhibition of CLCuV was observed in T7 treated plants where viral load was only 0.4% as compared to control where viral load was upto 74%. This treatment consortium included Bacillus and Pseudomonas isolates; S1HL3, S1HL4, JS2HR4 and JS3HR2. Principal Component Biplot depicted highly significant correlation between percentage viral load and the disease incidence.

Keywords: cotton leaf curl virus, biological control, bacillus, pseudomonas

Procedia PDF Downloads 388
4954 Neuron Point-of-Care Stem Cell Therapy: Intrathecal Transplant of Autologous Bone Marrow-Derived Stem Cells in Patients with Cerebral Palsy

Authors: F. Ruiz-Navarro, M. Matzner, G. Kobinia

Abstract:

Background: Cerebral palsy (CP) encompasses the largest group of childhood movement disorders, the patterns and severity varies widely. Today, the management focuses only on a rehabilitation therapy that tries to secure the functions remained and prevents complications. However the treatments are not aimed to cure the disease. Stem cells (SCs) transplant via intrathecal is a new approach to the disease. Method: Our aim was to performed a pilot study under the condition of unproven treatment on clinical practice to assessed the safety and efficacy of Neuron Point-of-care Stem cell Therapy (N-POCST), an ambulatory procedure of autologous bone marrow derived SCs (BM-SCs) harvested from the posterior superior iliac crest undergo an on-site cell separation for intrathecal infusion via lumbar puncture. Results: 82 patients were treated in a period of 28 months, with a follow-up after 6 months. They had a mean age of 6,2 years old and male predominance (65,9%). Our preliminary results show that: A. No patient had any major side effects, B. Only 20% presented mild headache due to LP, C. 53% of the patients had an improvement in spasticity, D. 61% improved the coordination abilities, 23% improved the motor function, 15% improved the speech, 23% reduced the number of convulsive events with the same doses or less doses of anti-convulsive medication and 94% of the patients report a subjective general improvement. Conclusions: These results support previous worldwide publications that described the safety and effectiveness of autologous BM-SCs transplant for patients wit CP.

Keywords: autologous transplant, cerebral palsy, point of care, childhood movement disorders

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4953 Nanomechanical Characterization of Healthy and Tumor Lung Tissues at Cell and Extracellular Matrix Level

Authors: Valeria Panzetta, Ida Musella, Sabato Fusco, Paolo Antonio Netti

Abstract:

The study of the biophysics of living cells drew attention to the pivotal role of the cytoskeleton in many cell functions, such as mechanics, adhesion, proliferation, migration, differentiation and neoplastic transformation. In particular, during the complex process of malignant transformation and invasion cell cytoskeleton devolves from a rigid and organized structure to a more compliant state, which confers to the cancer cells a great ability to migrate and adapt to the extracellular environment. In order to better understand the malignant transformation process from a mechanical point of view, it is necessary to evaluate the direct crosstalk between the cells and their surrounding extracellular matrix (ECM) in a context which is close to in vivo conditions. In this study, human biopsy tissues of lung adenocarcinoma were analyzed in order to define their mechanical phenotype at cell and ECM level, by using particle tracking microrheology (PTM) technique. Polystyrene beads (500 nm) were introduced into the sample slice. The motion of beads was obtained by tracking their displacements across cell cytoskeleton and ECM structures and mean squared displacements (MSDs) were calculated from bead trajectories. It has been already demonstrated that the amplitude of MSD is inversely related to the mechanical properties of intracellular and extracellular microenvironment. For this reason, MSDs of particles introduced in cytoplasm and ECM of healthy and tumor tissues were compared. PTM analyses showed that cancerous transformation compromises mechanical integrity of cells and extracellular matrix. In particular, the MSD amplitudes in cells of adenocarcinoma were greater as compared to cells of normal tissues. The increased motion is probably associated to a less structured cytoskeleton and consequently to an increase of deformability of cells. Further, cancer transformation is also accompanied by extracellular matrix stiffening, as confirmed by the decrease of MSDs of matrix in tumor tissue, a process that promotes tumor proliferation and invasiveness, by activating typical oncogenic signaling pathways. In addition, a clear correlation between MSDs of cells and tumor grade was found. MSDs increase when tumor grade passes from 2 to 3, indicating that cells undergo to a trans-differentiation process during tumor progression. ECM stiffening is not dependent on tumor grade, but the tumor stage resulted to be strictly correlated with both cells and ECM mechanical properties. In fact, a greater stage is assigned to tumor spread to regional lymph nodes and characterized by an up-regulation of different ECM proteins, such as collagen I fibers. These results indicate that PTM can be used to get nanomechanical characterization at different scale levels in an interpretative and diagnostic context.

Keywords: cytoskeleton, extracellular matrix, mechanical properties, particle tracking microrheology, tumor

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4952 Cloud Monitoring and Performance Optimization Ensuring High Availability

Authors: Inayat Ur Rehman, Georgia Sakellari

Abstract:

Cloud computing has evolved into a vital technology for businesses, offering scalability, flexibility, and cost-effectiveness. However, maintaining high availability and optimal performance in the cloud is crucial for reliable services. This paper explores the significance of cloud monitoring and performance optimization in sustaining the high availability of cloud-based systems. It discusses diverse monitoring tools, techniques, and best practices for continually assessing the health and performance of cloud resources. The paper also delves into performance optimization strategies, including resource allocation, load balancing, and auto-scaling, to ensure efficient resource utilization and responsiveness. Addressing potential challenges in cloud monitoring and optimization, the paper offers insights into data security and privacy considerations. Through this thorough analysis, the paper aims to underscore the importance of cloud monitoring and performance optimization for ensuring a seamless and highly available cloud computing environment.

Keywords: cloud computing, cloud monitoring, performance optimization, high availability, scalability, resource allocation, load balancing, auto-scaling, data security, data privacy

Procedia PDF Downloads 63
4951 Comparison of the Performance of a Brake Energy Regeneration System in Hybrid Vehicles

Authors: Miguel Arlenzo Duran Sarmiento, Luis Alfonso Del Portillo Valdés, Carlos Borras Pinilla

Abstract:

Brake energy regeneration systems have the capacity to transform part of the vehicle's kinetic energy during deceleration into useful energy. These systems can be implemented in hybrid vehicles, which can be electric or hydraulic in type, and contribute to reducing the energy required to propel the vehicle thanks to the accumulation of energy. This paper presents the modeling and simulation of a braking energy regeneration system applied in hydraulic hybrid vehicles configured in parallel, the modeling and simulation were performed in Simulink of Matlab, where a performance comparison of the regenerated torque as a function of vehicle load, the displacement of the hydraulic regeneration device and the vehicle speed profile. The speed profiles used in the simulation are standard profiles such as the NEDC and WLTP profiles. The vehicle loads range from 1500 kg to 12000 kg. The results show the comparison of the torque required by the vehicle, the torque regenerated by the system subjected to the different speed and load conditions.

Keywords: braking energy, energy regeneration, hybrid vehicles, kinetic energy, torque

Procedia PDF Downloads 128
4950 Molecular Docking Analysis of Flavonoids Reveal Potential of Eriodictyol for Breast Cancer Treatment

Authors: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery

Abstract:

Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.

Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking

Procedia PDF Downloads 93