Search results for: tumor immune response

Authors: Lamis Naddaf, Yuval Tabach

Abstract:

In this research, we identified the missense genetic variants that have the potential to enhance resistance against cancer. Such field has not been widely explored, as researchers tend to investigate mutations that cause diseases, in response to the suffering of patients, rather than those mutations that protect from them. In conjunction with the genomic revolution, and the advances in genetic engineering and synthetic biology, identifying the protective variants will increase the power of genotype-phenotype predictions and can have significant implications on improved risk estimation, diagnostics, prognosis and even for personalized therapy and drug discovery. To approach our goal, we systematically investigated the sites of the coding genomes and picked up the alleles that showed a correlation with the species’ cancer resistance. We predicted 250 protecting variants (PVs) with a 0.01 false discovery rate and more than 20 thousand PVs with a 0.25 false discovery rate. Cancer resistance in Mammals and reptiles was significantly predicted by the number of PVs a species has. Moreover, Genes enriched with the protecting variants are enriched in pathways relevant to tumor suppression like pathways of Hedgehog signaling and silencing, which its improper activation is associated with the most common form of cancer malignancy. We also showed that the PVs are more abundant in healthy people compared to cancer patients within different human races.

Keywords: comparative genomics, machine learning, cancer resistance, cancer-protecting alleles

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Authors: Abdulbaset Mazarzaei

Abstract:

Natural killer (NK) cells are innate immune effectors that play a pivotal role in combating tumors and infected cells. In recent years, the therapeutic potential of NK cells has gained significant attention due to their remarkable cytotoxic ability. This study focuses on investigating the cytotoxic effect of expanded NK cells enriched with interleukin 12 (IL12) and interleukin 15 (IL15), derived from the leukoreduction filter, on the K562 cell line. Firstly, NK cells were isolated from whole blood samples obtained from healthy volunteers. These cells were subsequently expanded ex vivo using a combination of feeder cells, IL12, and IL15. The expanded NK cells were then harvested and assessed for their cytotoxicity against K562, a well-established human chronic myelogenous leukemia cell line. The cytotoxicity was evaluated using flow cytometry assay. Results demonstrate that the expanded NK cells significantly exhibited enhanced cytotoxicity against K562 cells compared to non-expanded NK cells. Interestingly, the expanded NK cells derived specifically from IL12 and IL15-enriched leukoreduction filters showed a robust cytotoxic effect similar to the whole blood-derived NK cells. These findings suggest that IL12 and IL15 in the leukoreduction filter are crucial in promoting NK cell cytotoxicity. Furthermore, the expanded NK cells displayed relatively similar cytotoxicity profiles to whole blood-derived NK cells, indicating their comparable capability in targeting and eliminating tumor cells. This observation is of significant relevance as expanded NK cells from the leukoreduction filter could potentially serve as a readily accessible and efficient source for adoptive immunotherapy. In conclusion, this study highlights the significant cytotoxic effect of expanded NK cells enriched with IL12 and IL15 obtained from the leukoreduction filter on the K562 cell line. Moreover, it emphasizes that these expanded NK cells exhibit comparable cytotoxicity to whole blood-derived NK cells. These findings reinforce the potential clinical utility of using expanded NK cells from the leukoreduction filter as an effective strategy in adoptive immunotherapy for the treatment of cancer. Further studies are warranted to explore the broader implications of this approach in clinical settings.

Keywords: natural killer (NK) cells, Cytotoxicity, Leukoreduction filter, IL-12 and IL-15 Cytokines

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Authors: Radia Chemlal, Salim Mehenni, Dahbia Leila Anes-boulahbal, Mohamed Kherat, Nabil Mameri

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The application of the electric field is considered to be a very promising method in cancer therapy. Indeed, cancer cells are very sensitive to the electric field, although the cellular response is not entirely clear. The tests carried out consisted in subjecting the RD cell line under the effect of the continuous electric field while varying certain parameters (voltage, exposure time, and cell concentration). The response surface methodology (RSM) was used to assess the effect of the chosen parameters, as well as the existence of interactions between them. The results obtained showed that the voltage, the cell concentration as well as the interaction between voltage and exposure time have an influence on the mortality rate of the RD cell line.

Keywords: continuous electric field, RD cancer cell line, RSM, voltage

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Authors: Varsha Singh, Kishan Fuse

Abstract:

This paper presents a study of the grey-Taguchi method to optimize CNC milling parameters of AA6061 T6 aluminium alloy. Grey-Taguchi method combines Taguchi method based design of experiments (DOE) with grey relational analysis (GRA). Multi-response optimization of different quality characteristics as surface roughness, material removal rate, cutting forces is done using grey relational analysis (GRA). The milling parameters considered for experiments include cutting speed, feed per tooth, and depth of cut. Each parameter with three levels is selected. A grey relational grade is used to estimate overall quality characteristics performance. The Taguchi’s L9 orthogonal array is used for design of experiments. MINITAB 17 software is used for optimization. Analysis of variance (ANOVA) is used to identify most influencing parameter. The experimental results show that grey relational analysis is effective method for optimizing multi-response characteristics. Optimum results are finally validated by performing confirmation test.

Keywords: ANOVA, CNC milling, grey relational analysis, multi-response optimization

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Authors: Naif Al-Jomah, Falah H Al-Mohanna, Abdelilah Aboussekhra

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Active breast cancer-associated fibroblasts (CAFs), the most influential cells in breast tumor microenvironment, express/secrete high levels of the proinvasive/metastatic interleukin-6 (IL-6). Therefore, we have tested here the effect of the IL-6 receptor (IL-6R) inhibitor tocilizumab (TCZ; Actemra) on different active breast CAFs. We have shown that TCZ potently and persistently suppresses the expression of various CAF biomarkers, namely α-SMA, SDF-1 as well as the STAT3 pathway and its downstream target AUF1. TCZ also inhibited the proliferation, migration and invasion abilities of active breast CAF cells. Additionally, TCZ repressed the ability of CAF cells in promoting epithelial-to-mesenchymal transition, and enhancing the migratory/invasive and proliferative capacities of breast cancer cells in vitro. Importantly, these findings were confirmed in orthotopic humanized breast tumors in mice. Furthermore, TCZ suppressed the expression of the pro-angiogenic factor VEGF-A and its transactivator HIF-1α in CAF cells, and consequently inhibited the angiogenic-promoting effect of active CAFs both in vitro and in orthotopic tumor xenografts. These results indicate that inhibition of the IL-6/STAT3/AUF1 pathway by TCZ can normalize active breast CAFs and suppress their paracrine pro-carcinogenic effects, which paves the way toward development of specific CAF-targeting therapy, badly needed for more efficient breast cancer treatments.

Keywords: angiogenesis, interleukin-6, paracrine, cancer-associated fibroblasts

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Authors: P. Vosynek, T. Návrat, M. Peč, J. Pořízka, P. Diviš

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Changes of mechanical properties and response behavior of bones is an important external sign of medical problems like osteoporosis, bone remodeling after fracture or surgery, osteointegration, or bone tissue loss of astronauts in space. Measuring of mechanical behavior of bones in physiological and osteoporotic states, quantified by different degrees of protein (collagen) and mineral loss, is thus an important topic in biomechanical research. This contribution deals with the relation between mechanical properties of the turkey long bone–tibia in physiological, demineralized, and deproteinized state. Three methods for comparison were used: densitometry, three point bending and harmonic response analysis. The results help to find correlations between the methods and estimate their possible application in medical practice.

Keywords: bone properties, long bone, osteoporosis, response behavior

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Authors: Wiam El Kheir, Anais Dumais, Maude Beaudoin, Bernard Marcos, Nick Virgilio, Benoit Paquette, Nathalie Faucheux, Marc-Antoine Lauzon

Abstract:

The high infiltrative pattern of glioblastoma multiforme cells (GBM) is the main cause responsible for the actual standard treatments failure. The tumor high heterogeneity, the interstitial fluid flow (IFF) and chemokines guides GBM cells migration in the brain parenchyma resulting in tumor recurrence. Drug delivery systems emerged as an alternative approach to develop effective treatments for the disease. Some recent studies have proposed to harness the effect CXC-lchemokine-ligand-12 to direct and control the cancer cell migration through delivery system. However, the dynamics of the brain environment on the delivery system remains poorly understood. Nanoparticles (NPs) and hydrogels are known as good carriers for the encapsulation of different agents and control their release. We studied the release of CXCL12 (free or loaded into NPs) from an alginate-based hydrogel under static and indirect perfusion (IP) conditions. Under static conditions, the main phenomena driving CXCL12 release from the hydrogel was diffusion with the presence of strong interactions between the positively charged CXCL12 and the negatively charge alginate. CXCL12 release profiles were independent from the initial mass loadings. Afterwards, we demonstrated that the release could tuned by loading CXCL12 into Alginate/Chitosan-Nanoparticles (Alg/Chit-NPs) and embedded them into alginate-hydrogel. The initial burst release was substantially attenuated and the overall cumulative release percentages of 21%, 16% and 7% were observed for initial mass loadings of 0.07, 0.13 and 0.26 µg, respectively, suggesting stronger electrostatic interactions. Results were mathematically modeled based on Fick’s second law of diffusion framework developed previously to estimate the effective diffusion coefficient (Deff) and the mass transfer coefficient. Embedding the CXCL12 into NPs decreased the Deff an order of magnitude, which was coherent with experimental data. Thereafter, we developed an in-vitro 3D model that takes into consideration the convective contribution of the brain IFF to study CXCL12 release in an in-vitro microenvironment that mimics as faithfully as possible the human brain. From is unique design, the model also allowed us to understand the effect of IP on CXCL12 release in respect to time and space. Four flow rates (0.5, 3, 6.5 and 10 µL/min) which may increase CXCL12 release in-vivo depending on the tumor location were assessed. Under IP, cumulative percentages varying between 4.5-7.3%, 23-58.5%, 77.8-92.5% and 89.2-95.9% were released for the three initial mass loadings of 0.08, 0.16 and 0.33 µg, respectively. As the flow rate increase, IP culture conditions resulted in a higher release of CXCL12 compared to static conditions as the convection contribution became the main driving mass transport phenomena. Further, depending on the flow rate, IP had a direct impact on CXCL12 distribution within the simulated brain tissue, which illustrates the importance of developing such 3D in-vitro models to assess the efficiency of a delivery system targeting the brain. In future work, using this very model, we aim to understand the impact of the different phenomenon occurring on GBM cell behaviors in response to the resulting chemokine gradient subjected to various flow while allowing them to express their invasive characteristics in an in-vitro microenvironment that mimics the in-vivo brain parenchyma.

Keywords: 3D culture system, chemokines gradient, glioblastoma multiforme, kinetic release, mathematical modeling

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Authors: Meenakshi Barsaul Chauhan, Aastha Chauhan, Shilpa Hurmade, Rajeev Sen, Jyotsna Sen, Monika Dalal

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Introduction: Ovarian masses are common forms of neoplasm in women and represent 2/3rd of gynaecological malignancies. A pre-operative suggestion of malignancy can guide the gynecologist to refer women with suspected pelvic mass to a gynecological oncologist for appropriate therapy and optimized treatment, which can improve survival. In the younger age group preoperative differentiation into benign or malignant pathology can decide for conservative or radical surgery. Imaging modalities have a definite role in establishing the diagnosis. By using International Ovarian Tumor Analysis (IOTA) classification with sonography, costly radiological methods like Magnetic Resonance Imaging (MRI) / computed tomography (CT) scan can be reduced, especially in developing countries like India. Thus, this study is being undertaken to evaluate the role of clinical methods and sonography for diagnosis of the nature of the ovarian tumor. Material And Methods: This prospective observational study was conducted on 40 patients presenting with ovarian masses, in the Department of Obstetrics and Gynaecology, at a tertiary care center in northern India. Functional cysts were excluded. Ultrasonography and color Doppler were performed on all the cases.IOTA rules were applied, which take into account locularity, size, presence of solid components, acoustic shadow, dopper flow etc . Magnetic Resonance Imaging (MRI) / computed tomography (CT) scans abdomen and pelvis were done in cases where sonography was inconclusive. In inoperable cases, Fine needle aspiration cytology (FNAC) was done. The histopathology report after surgery and cytology report after FNAC was correlated statistically with the pre-operative diagnosis made clinically and sonographically using IOTA rules. Statistical Analysis: Descriptive measures were analyzed by using mean and standard deviation and the Student t-test was applied and the proportion was analyzed by applying the chi-square test. Inferential measures were analyzed by sensitivity, specificity, negative predictive value, and positive predictive value. Results: Provisional diagnosis of the benign tumor was made in 16(42.5%) and of the malignant tumor was made in 24(57.5%) patients on the basis of clinical findings. With IOTA simple rules on sonography, 15(37.5%) were found to be benign, while 23 (57.5%) were found to be malignant and findings were inconclusive in 2 patients (5%). FNAC/Histopathology reported that benign ovarian tumors were 14 (35%) and 26(65%) were malignant, which was taken as the gold standard. The clinical finding alone was found to have a sensitivity of 66.6% and a specificity of 90.9%. USG alone had a sensitivity of 86% and a specificity of 80%. When clinical findings and IOTA simple rules of sonography were combined (excluding inconclusive masses), the sensitivity and specificity were 83.3% and 92.3%, respectively. While including inconclusive masses, sensitivity came out to be 91.6% and specificity was 89.2. Conclusion: IOTA's simple sonography rules are highly sensitive and specific in the prediction of ovarian malignancy and also easy to use and easily reproducible. Thus, combining clinical examination with USG will help in the better management of patients in terms of time, cost and better prognosis. This will also avoid the need for costlier modalities like CT, and MRI.

Keywords: benign, international ovarian tumor analysis classification, malignant, ovarian tumours, sonography

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Authors: Lamis Naddaf, Yuval Tabach

Abstract:

We identified missense genetic variants with the potential to enhance resistance against cancer. Such a field has not been widely explored as researchers tend to investigate the mutations that cause diseases, in response to the suffering of patients, rather than those mutations that protect from them. In conjunction with the genomic revolution and the advances in genetic engineering and synthetic biology, identifying the protective variants will increase the power of genotype-phenotype predictions and have significant implications for improved risk estimation, diagnostics, prognosis, and even personalized therapy and drug discovery. To approach our goal, we systematically investigated the sites of the coding genomes and selected the alleles that showed a correlation with the species’ cancer resistance. Interestingly, we found several amino acids that are more generally preferred (like the Proline) or avoided (like the Cysteine) by the resistant species. Furthermore, Cancer resistance in mammals and reptiles is significantly predicted by the number of the predicted protecting variants (PVs) a species has. Moreover, PVs-enriched-genes are enriched in pathways relevant to tumor suppression. For example, they are enriched in the Hedgehog signaling and silencing pathways, which its improper activation is associated with the most common form of cancer malignancy. We also showed that the PVs are mostly more abundant in healthy people compared to cancer patients within different human races.

Keywords: cancer resistance, protecting variant, naked mole rat, comparative genomics

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Authors: Alan Ruiz-Padilla, Brando Villalobos-Villalobos, Yeniley Ruiz-Noa, Claudia Mendoza-Macías, Claudia Palafox-Sánchez, Miguel Marín-Rosales, Álvaro Cruz, Rubén Rangel-Salazar

Abstract:

Introduction: In patients with rheumatoid arthritis, resistance or poor response to disease modifying antirheumatic drugs (DMARD) may be a reflection of the increase in g-P. The expression of g-P may be important in mediating the effluence of DMARD from the cell. In addition, P-glycoprotein is involved in the transport of cytokines, IL-1, IL-2 and IL-4, from normal lymphocytes activated to the surrounding extracellular matrix, thus influencing the activity of RA. The involvement of P-glycoprotein in the transmembrane transport of cytokines can serve as a modulator of the efficacy of DMARD. It was shown that a number of lymphocytes with glycoprotein P activity is increased in patients with RA; therefore, P-glycoprotein expression could be related to the activity of RA and could be a predictor of poor response to therapy. Objective: To evaluate in RA patients, if the G2677T/A MDR1 polymorphisms is associated with differences in the rate of therapeutic response to disease-modifying antirheumatic agents in patients with rheumatoid arthritis. Material and Methods: A prospective cohort study was conducted. Fifty seven patients with RA were included. They had an active disease according to DAS-28 (score >3.2). We excluded patients receiving biological agents. All the patients were followed during 6 months in order to identify the rate of therapeutic response according to the American College of Rheumatology (ACR) criteria. At the baseline peripheral blood samples were taken in order to identify the G2677T/A MDR1 polymorphisms using PCR- Specific allele. The fragment was identified by electrophoresis in polyacrylamide gels stained with ethidium bromide. For statistical analysis, the genotypic and allelic frequencies of MDR1 gene polymorphism between responders and non-responders were determined. Chi-square tests as well as, relative risks with 95% confidence intervals (95%CI) were computed to identify differences in the risk for achieving therapeutic response. Results: RA patients had a mean age of 47.33 ± 12.52 years, 87.7% were women with a mean for DAS-28 score of 6.45 ± 1.12. At the 6 months, the rate of therapeutic response was 68.7 %. The observed genotype frequencies were: for G/G 40%, T/T 32%, A/A 19%, G/T 7% and for A/A genotype 2%. Patients with G allele developed at 6 months of treatment, higher rate for therapeutic response assessed by ACR20 compared to patients with others alleles (p=0.039). Conclusions: Patients with G allele of the - G2677T/A MDR1 polymorphisms had a higher rate of therapeutic response at 6 months with DMARD. These preliminary data support the requirement for a deep evaluation of these and other genotypes as factors that may influence the therapeutic response in RA.

Keywords: pharmacogenetics, MDR1, P-glycoprotein, therapeutic response, rheumatoid arthritis

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Authors: Sai-Kit Choi

Abstract:

While traditional social services heavily depended on Government funding and support, there were always time lag, and resources mismatch with the fast growing and changing social needs. This study aims at investigating the effectiveness of implementing Circular Economy concept in a social service setting with comparison to Government Policy in response to social needs in 3 areas: response time, suitability, and community participation. To investigate the effectiveness of implementing Circular Economy concept in a social service setting, a real service model, a community resources sharing platform, was set up and statistics of the first 6 months’ operation data were used as comparison with traditional social services. Literature review was conducted as a reference basis of traditional social services under Government Policy. Case studies were conducted to provide the qualitative perspectives of the innovative approach. The results suggest that the Circular Economy model showed extraordinarily high level of community participation. In addition, it could utilize community resources in response precisely to the burning social needs. On the other hand, the available resources were unstable when comparing to those services supported by Government funding. The research team concluded that Circular Economy has high potential in applications in social service, especially in certain areas, such as resources sharing platform. Notwithstanding, it should be aware of the stability of resources when the services targeted to support some crucial needs.

Keywords: circular economy, social innovation, community participation, sharing economy, social response

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Authors: Shreya Thusoo, Karan Modi, Rajesh Kumar, Hitesh Madahar

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Over the years, it has been extensively established that the practice of assuming a structure being fixed at base, leads to gross errors in evaluation of its overall response due to dynamic loadings and overestimations in design. The extent of these errors depends on a number of variables; soil type being one of the major factor. This paper studies the effect of Soil Structure Interaction (SSI) on multi-storey buildings with varying under-laying soil types after proper validation of the effect of SSI. Analysis for soft, stiff and very stiff base soils has been carried out, using a powerful Finite Element Method (FEM) software package ANSYS v14.5. Results lead to some very important conclusions regarding time period, deflection and acceleration responses.

Keywords: dynamic response, multi-storey building, soil-structure interaction, varying soil types

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Authors: Swati Srivastava, Mattia Lauriola, Yuval Gilad, Adi Kimchi, Yosef Yarden

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The glucocorticoid receptor (GR) has been proposed to play important, but incompletely understood roles in cancer. Glucocorticoids (GCs) are widely used as co-medication of various carcinomas, due to their ability to reduce the toxicity of chemotherapy. Furthermore, GR antagonism has proven to be a strategy to treat triple negative breast cancer and castration-resistant prostate cancer. These observations suggest differential GR involvement in cancer subtypes. The goal of our study has been to elaborate the current understanding of GR signaling in tumor progression and metastasis. Our study involves two cellular models, non-tumorigenic breast epithelial cells (MCF10A) and Ewing sarcoma cells (CHLA9). In our breast cell model, the results indicated that the GR agonist dexamethasone inhibits EGF-induced mammary cell migration, and this effect was blocked when cells were stimulated with a GR antagonist, namely RU486. Microarray analysis for gene expression revealed that the mechanism underlying inhibition involves dexamenthasone-mediated repression of well-known activators of EGFR signaling, alongside with enhancement of several EGFR’s negative feedback loops. Because GR mainly acts primarily through composite response elements (GREs), or via a tethering mechanism, our next aim has been to find the transcription factors (TFs) which can interact with GR in MCF10A cells.The TF-binding motif overrepresented at the promoter of dexamethasone-regulated genes was predicted by using bioinformatics. To validate the prediction, we performed high-throughput Protein Complementation Assays (PCA). For this, we utilized the Gaussia Luciferase PCA strategy, which enabled analysis of protein-protein interactions between GR and predicted TFs of mammary cells. A library comprising both nuclear receptors (estrogen receptor, mineralocorticoid receptor, GR) and TFs was fused to fragments of GLuc, namely GLuc(1)-X, X-GLuc(1), and X-GLuc(2), where GLuc(1) and GLuc(2) correspond to the N-terminal and C-terminal fragments of the luciferase gene.The resulting library was screened, in human embryonic kidney 293T (HEK293T) cells, for all possible interactions between nuclear receptors and TFs. By screening all of the combinations between TFs and nuclear receptors, we identified several positive interactions, which were strengthened in response to dexamethasone and abolished in response to RU486. Furthermore, the interactions between GR and the candidate TFs were validated by co-immunoprecipitation in MCF10A and in CHLA9 cells. Currently, the roles played by the uncovered interactions are being evaluated in various cellular processes, such as cellular proliferation, migration, and invasion. In conclusion, our assay provides an unbiased network analysis between nuclear receptors and other TFs, which can lead to important insights into transcriptional regulation by nuclear receptors in various diseases, in this case of cancer.

Keywords: epidermal growth factor, glucocorticoid receptor, protein complementation assay, transcription factor

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Authors: Raj Banerjee, Aniruddha Sengupta

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An earthquake event, associated with a typical fault rupture, initiates at the source, propagates through a rock or soil medium and finally daylights at a surface which might be a populous city. The detrimental effects of an earthquake are often quantified in terms of the responses of superstructures resting on the soil. Hence, there is a need for the estimation of amplification of the bedrock motions due to the influence of local site conditions. In the present study, field borehole log data of Mangalwadi and Walkeswar sites in Mumbai city are considered. The data consists of variation of SPT N-value with the depth of soil. A correlation between shear wave velocity (Vₛ) and SPT N value for various soil profiles of Mumbai city has been developed using various existing correlations which is used further for site response analysis. MATLAB program is developed for studying the ground response analysis by performing two dimensional linear and equivalent linear analysis for some of the typical Mumbai soil sites using pure shear (Multi Point Constraint) boundary condition. The model is validated in linear elastic and equivalent linear domain using the popular commercial program, DEEPSOIL. Three actual earthquake motions are selected based on their frequency contents and durations and scaled to a PGA of 0.16g for the present ground response analyses. The results are presented in terms of peak acceleration time history with depth, peak shear strain time history with depth, Fourier amplitude versus frequency, response spectrum at the surface etc. The peak ground acceleration amplification factors are found to be about 2.374, 3.239 and 2.4245 for Mangalwadi site and 3.42, 3.39, 3.83 for Walkeswar site using 1979 Imperial Valley Earthquake, 1989 Loma Gilroy Earthquake and 1987 Whitter Narrows Earthquake, respectively. In the absence of any site-specific response spectrum for the chosen sites in Mumbai, the generated spectrum at the surface may be utilized for the design of any superstructure at these locations.

Keywords: deepsoil, ground response analysis, multi point constraint, response spectrum

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Authors: Mohammed Ali Hjaji, A.K. El-Senussi, Said H. Eshtewi

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The flexural dynamic response of symmetric laminated composite beams subjected to general transverse harmonic forces is investigated. The dynamic equations of motion and associated boundary conditions based on the first order shear deformation are derived through the use of Hamilton’s principle. The influences of shear deformation, rotary inertia, Poisson’s ratio and fibre orientation are incorporated in the present formulation. The resulting governing flexural equations for symmetric composite Timoshenko beams are exactly solved and the closed form solutions for steady state flexural response are then obtained for cantilever and simply supported boundary conditions. The applicability of the analytical closed-form solution is demonstrated via several examples with various transverse harmonic loads and symmetric cross-ply and angle-ply laminates. Results based on the present solution are assessed and validated against other well established finite element solutions and exact solutions available in the literature.

Keywords: analytical solution, flexural response, harmonic forces, symmetric laminated beams, steady state response

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Authors: Vasu Velagapudi, G. Suresh

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PTFE/HNTs nanocomposites are fabricated with 4%, 6%, and 8% by weight fraction, and the optimization study of wear parameters are performed using response surface methodology (RSM). The experiments are carried out on a pin on disc (POD) wear tester under different operating parameters planned according to Taguchi L27 orthogonal array. The input factors considered are wt% HNTs addition, sliding velocity, load, and distance with three levels for each factor. From ANOVA: The factors load, speed and distance and their interactions have a significant effect on COF. Also for SWR, composition factor and interaction of load and speed are observed to be significant ( < 0.05) Optimum input parameters corresponding to desirability 1 are found to be: COF (0.11) and SWR (17.5)×10⁻⁶ (mm3/N-m) at 6.34 wt% of composition, 5N of load, 2 km of distance and 1 m/sec of velocity.

Keywords: PTFE/HNT, nanocomposites, response surface methodology (RSM), specific wear rate

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Authors: Serges Mendomo Meye, Li Guowei, Shen Zhenzhong

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Earthquake is one of the main loads threatening dam safety. Once the dam is damaged, it will bring huge losses of life and property to the country and people. Therefore, it is very important to research the seismic safety of the dam. Due to the complex foundation conditions, high fortification intensity, and high scientific and technological content, it is necessary to adopt reasonable methods to evaluate the seismic safety performance of concrete arch dams built and under construction in strong earthquake areas. Structural seismic vulnerability analysis can predict the probability of structural failure at all levels under different intensity earthquakes, which can provide a scientific basis for reasonable seismic safety evaluation and decision-making. In this paper, the response surface method (RSM) is applied to the seismic vulnerability analysis of arch dams, which improves the efficiency of vulnerability analysis. Based on the central composite test design method, the material-seismic intensity samples are established. The response surface model (RSM) with arch crown displacement as performance index is obtained by finite element (FE) calculation of the samples, and then the accuracy of the response surface model (RSM) is verified. To obtain the seismic vulnerability curves, the seismic intensity measure ??(?1) is chosen to be 0.1~1.2g, with an interval of 0.1g and a total of 12 intensity levels. For each seismic intensity level, the arch crown displacement corresponding to 100 sets of different material samples can be calculated by algebraic operation of the response surface model (RSM), which avoids 1200 times of nonlinear dynamic calculation of arch dam; thus, the efficiency of vulnerability analysis is improved greatly.

Keywords: high concrete arch dam, performance index, response surface method, seismic vulnerability analysis, vector-valued intensity measure

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Authors: A. M. Khourshid, A. M. El-Kassas, I. Sabry

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The objective of this work was to investigate the mechanical properties in order to demonstrate the feasibility of friction stir welding for joining Al 6061 aluminium alloys. Welding was performed on pipe with different thickness (2, 3 and 4 mm), five rotational speeds (485, 710, 910, 1120 and 1400 rpm) and a traverse speed of 4mm/min. This work focuses on two methods which are artificial neural networks using software and Response Surface Methodology (RSM) to predict the tensile strength, the percentage of elongation and hardness of friction stir welded 6061 aluminium alloy. An Artificial Neural Network (ANN) model was developed for the analysis of the friction stir welding parameters of 6061 pipe. Tensile strength, the percentage of elongation and hardness of weld joints were predicted by taking the parameters tool rotation speed, material thickness and axial force as a function. A comparison was made between measured and predicted data. Response Surface Methodology (RSM) was also developed and the values obtained for the response tensile strength, the percentage of elongation and hardness are compared with measured values. The effect of FSW process parameters on mechanical properties of 6061 aluminium alloy has been analysed in detail.

Keywords: friction stir welding, aluminium alloy, response surface methodology, artificial neural network

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Authors: Salem Alsanusi, Loubna Bentaher

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Response Surface Methods (RSM) provide statistically validated predictive models that can then be manipulated for finding optimal process configurations. Variation transmitted to responses from poorly controlled process factors can be accounted for by the mathematical technique of propagation of error (POE), which facilitates ‘finding the flats’ on the surfaces generated by RSM. The dual response approach to RSM captures the standard deviation of the output as well as the average. It accounts for unknown sources of variation. Dual response plus propagation of error (POE) provides a more useful model of overall response variation. In our case, we implemented this technique in predicting compressive strength of concrete of 28 days in age. Since 28 days is quite time consuming, while it is important to ensure the quality control process. This paper investigates the potential of using design of experiments (DOE-RSM) to predict the compressive strength of concrete at 28th day. Data used for this study was carried out from experiment schemes at university of Benghazi, civil engineering department. A total of 114 sets of data were implemented. ACI mix design method was utilized for the mix design. No admixtures were used, only the main concrete mix constituents such as cement, coarse-aggregate, fine aggregate and water were utilized in all mixes. Different mix proportions of the ingredients and different water cement ratio were used. The proposed mathematical models are capable of predicting the required concrete compressive strength of concrete from early ages.

Keywords: mix proportioning, response surface methodology, compressive strength, optimal design

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Authors: Gonzalez Carlos, Martinez Fransisco

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The creation of a seismic prediction model that considers all the regional variations and perfectly adjusts its results to the response spectra is very complicated. To achieve statistically acceptable results, it is necessary to process a sufficiently robust data set, and even if high efficiencies are achieved, this model will only work properly in this region. However, when using it in other regions, differences are found due to different parameters that have not been calibrated to other regions, such as the site effect. The fact that impedance contrasts, as well as other factors belonging to the site, have a great influence on the local response is well known, which is why this work, using the residual method, is intended to establish a regional calibration of the corresponding parameters site effect for the Spain region in the global GMPM BSSA 14.

Keywords: GMPM, seismic prediction equations, residual method, response spectra, impedance contrast

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Authors: Shepherd Manhokwe, Sheron Shoko, Cuthbert Zvidzai

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In the present study, the interactive effects of temperature and cultured bacteria on the performance of a biological treatment system of yeast processing wastewater were investigated. The main objective of this study was to investigate and optimize the operating parameters that reduce organic load and colour. Experiments were conducted based on a Central Composite Design (CCD) and analysed using Response Surface Methodology (RSM). Three dependent parameters were either directly measured or calculated as response. These parameters were total Chemical Oxygen Demand (COD) removal, colour reduction and total solids. COD removal efficiency of 26 % and decolourization efficiency of 44 % were recorded for the wastewater treatment. The optimized conditions for the biological treatment were found to be at 20 g/l cultured bacteria and 25 °C for COD reduction. For colour reduction optimum conditions were temperature of 30.35°C and bacterial formulation of 20g/l. Biological treatment of baker’s yeast processing effluent is a suitable process for the removal of organic load and colour from wastewater, especially when the operating parameters are optimized.

Keywords: COD reduction, optimisation, response surface methodology, yeast processing wastewater

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Authors: Yaping Zhao, Yimin Zhang

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In the present paper, the stationary random vibration of a uniform cantilever beam is investigated. Two types of damping mechanism, i.e. the external and internal viscous dampings, are taken into account simultaneously. The excitation form is the support motion, and it is ideal white. Because two type of damping mechanism are considered concurrently, the product of the modal damping ratio and the natural frequency is not a constant anymore. As a result, the infinite definite integral encountered in the process of computing the mean square response is more complex than that in the existing literature. One signal progress of this work is to have calculated these definite integrals accurately. The precise solution of the mean square response is thus obtained in the infinite series form finally. Numerical examples are supplied and the numerical outcomes acquired confirm the validity of the theoretical analyses.

Keywords: random vibration, cantilever beam, mean square response, white noise

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Authors: Zerroug Abdelhamid, Danielle Chassoux

Abstract:

Various models are given to simulate homogeneous or heterogeneous cancerous tumors and extract in each case the boundary. The fractal dimension is then estimated by least squares method and compared to some previous methods.

Keywords: simulation, cancerous tumor, Markov fields, fractal dimension, extraction, recovering

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Authors: Sunho Seo, Younghwan Shin, Jong-Hong Park, Sooeun Song, Junsung Kim, Jusik Yun, Yongkyun Kim, Jong-Moon Chung

Abstract:

In order to effectively cope with large and complex disasters, disaster response training is needed. Recently, disaster response training led by the ROK (Republic of Korea) government is being implemented through a 4 year R&D project, which has several similar functions as the HSEEP (Homeland Security Exercise and Evaluation Program) of the United States, but also has several different features as well. Due to the unpredictiveness and diversity of disasters, existing training methods have many limitations in providing experience in the efficient use of disaster incident response and recovery resources. Always, the challenge is to be as efficient and effective as possible using the limited human and material/physical resources available based on the given time and environmental circumstances. To enable repeated training under diverse scenarios, an AR (Augmented Reality) and VR (Virtual Reality) combined simulator is under development. Unlike existing disaster response training, simulator based training (that allows remote login simultaneous multi-user training) enables freedom from limitations in time and space constraints, and can be repeatedly trained with different combinations of functions and disaster situations. There are related systems such as ADMS (Advanced Disaster Management Simulator) developed by ETC simulation and HLS2 (Homeland Security Simulation System) developed by ELBIT system. However, the ROK government needs a simulator custom made to the country's environment and disaster types, and also combines the latest information and communication technologies, which include AR, VR, and MPEG-DASH (Moving Picture Experts Group - Dynamic Adaptive Streaming over HTTP) technology. In this paper, a new disaster response training simulator is proposed to overcome the limitation of existing training systems, and adapted to actual disaster situations in the ROK, where several technical features are described.

Keywords: augmented reality, emergency response training simulator, MPEG-DASH, virtual reality

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Authors: Zhaojun Wang, Zongdi Sun, Zhiyuan Liu

Abstract:

First of all, the carbon trading price and trading volume in Shanghai are transformed by Fourier transform, and the frequency response diagram is obtained. Then, the frequency response diagram is analyzed and the Blackman filter is designed. The Blackman filter is used to filter, and the carbon trading time domain and frequency response diagram are obtained. After wavelet analysis, the carbon trading data were processed; respectively, we got the average value for each 5 days, 10 days, 20 days, 30 days, and 60 days. Finally, the data are used as input of the Back Propagation Neural Network model for prediction.

Keywords: Shanghai carbon trading, carbon trading price, carbon trading volume, wavelet analysis, BP neural network model

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Authors: Sundaresan Sivapatham, B. Prabhu

Abstract:

Cancer results from a multistage, multi-mechanism carcinogenesis process that involves mutagenic, cell death and epigenetic mechanisms, during the three distinguishable but closely allied stages: initiation, promotion, and progression. Chemoprevention is promising in the realm of cancer prevention and it has been shown to reduce the risk of development of carcinoma in highly susceptible individuals such as those with known genetic mutations or high level of risk factors. The present study is aimed at the need of early detection of bladder cancer in order to improve performance in the treatment of this disease. Consumption of certain natural products like DIM is associated with a reduction in cancer incidence in humans. The study showed the protective effects of Diindolylmethane in N-Butyl-N-(4-hydroxybutyl) nitrosamine treated rats. Results of the study had shown the changes in the tumor markers, biomarkers and histopathological alterations in experimental rats when compared to control rats. The protective effects of DIM were shown from the results of cell proliferation, apoptotic markers and histopathological findings when compared with experimental control animals. Hence, our results speculate that the tumor markers, apoptotic markers, histopathological changes and cell proliferation index measured as PCNA serves as an indicator suggestive of protective effects of DIM in BBN induced urinary bladder carcinogenesis.

Keywords: bladder cancer, N-Butyl-N-(4-hydroxybutyl) nitrosamine, diindolylmethane, histopathology

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Authors: Aref Ghafouri, Mohammad javad Mollakazemi, Farhad Asadi

Abstract:

In this paper, model order reduction method is used for approximation in linear and nonlinearity aspects in some experimental data. This method can be used for obtaining offline reduced model for approximation of experimental data and can produce and follow the data and order of system and also it can match to experimental data in some frequency ratios. In this study, the method is compared in different experimental data and influence of choosing of order of the model reduction for obtaining the best and sufficient matching condition for following the data is investigated in format of imaginary and reality part of the frequency response curve and finally the effect and important parameter of number of order reduction in nonlinear experimental data is explained further.

Keywords: frequency response, order of model reduction, frequency matching condition, nonlinear experimental data

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Authors: Yang Yang, Luciana Magalhães Rebelo Alencar, Martha Sahylí Ortega Pijeira, Beatriz da Silva Batista, Alefe Roger Silva França, Erick Rafael Dias Rates, Ruana Cardoso Lima, Sara Gemini-Piperni, Ralph Santos-Oliveira

Abstract:

Radium-²²³ dichloride ([²²³Rₐ]RₐCl₂) is an alpha particle-emitting radiopharmaceutical currently approved for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease. [²²³Rₐ]RₐCl₂ is bone-seeking calcium mimetic that bonds into the newly formed bone stroma, especially osteoblastic or sclerotic metastases, killing the tumor cells by inducing DNA breaks in a potent and localized manner. Nonetheless, the successful therapy of osteosarcoma as primary bone tumors is still a challenge. Nanomicelles are colloidal nanosystems widely used in drug development to improve blood circulation time, bioavailability, and specificity of therapeutic agents, among other applications. In addition, the enhanced permeability and retention effect of the nanosystems, and the renal excretion of the nanomicelles reported in most cases so far, are very attractive to achieve selective and increased accumulation in tumor site as well as to increase the safety of [²²³Rₐ]RₐCl₂ in the clinical routine. In the present work, [²²³Rₐ]RₐCl₂ nanomicelles were produced, characterized, in vitro evaluated, and compared with pure [²²³Rₐ]RₐCl2 solution using SAOS2 osteosarcoma cells. The [²²³Rₐ]RₐCl₂ nanomicelles were prepared using the amphiphilic copolymer Pluronic F127. The dynamic light scattering analysis of freshly produced [²²³Rₐ]RₐCl₂ nanomicelles demonstrated a mean size of 129.4 nm with a polydispersity index (PDI) of 0.303. After one week stored in the refrigerator, the mean size of the [²²³Rₐ]RₐCl₂ nanomicelles increased to 169.4 with a PDI of 0.381. Atomic force microscopy analysis of [223Rₐ]RₐCl₂ nanomicelles exhibited spherical structures whose heights reach 1 µm, suggesting the filling of 127-Pluronic nanomicelles with [²²³Rₐ]RₐCl₂. The viability assay with [²²³Rₐ]RₐCl₂ nanomicelles displayed a dose-dependent response as it was observed using pure [²²³Rₐ]RₐCl2. However, at the same dose, [²²³Rₐ]RₐCl₂ nanomicelles were 20% higher efficient in killing SAOS2 cells when compared with pure [²²³Rₐ]RₐCl₂. These findings demonstrated the effectiveness of the nanosystem validating the application of nanotechnology in targeted alpha therapy with [²²³Ra]RₐCl₂. In addition, the [²²³Rₐ]RaCl₂nanomicelles may be decorated and incorporated with a great variety of agents and compounds (e.g., monoclonal antibodies, aptamers, peptides) to overcome the limited use of [²²³Ra]RₐCl₂.

Keywords: nanomicelles, osteosarcoma, radium dichloride, targeted alpha therapy

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Authors: Ahmed Atef, Mohamed Alhasheem, Eman Beshr

Abstract:

In this paper, an enhanced DC microgrid design is proposed using the DAB converter as a conversion unit in order to harvest the maximum power from the PV array. Each connected DAB converter is controlled with an enhanced control strategy. The controller is based on the artificial intelligence (AI) technique to regulate the terminal PV voltage through the phase shift angle of each DAB converter. In this manner, no need for a Maximum Power Point Tracking (MPPT) unit to set the reference of the PV terminal voltage. This strategy overcomes the stability issues of the DC microgrid as the response of converters is superior compared to the conventional strategies. The proposed PV interface system is modelled and simulated using MATLAB/SIMULINK. The simulation results reveal an accurate and fast response of the proposed design in case of irradiance changes.

Keywords: DC microgrid, DAB converter, parallel operation, artificial intelligence, fast response

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Authors: F. A. F. da Ponte, J. Q. Malveira, I. A. Maciel, M. C. G. Albuquerque

Abstract:

In this work aviation, biofuel production was studied by fatty acids (C6 to C16) esterification. The process variables in heterogeneous catalysis were evaluated using an experimental design. Temperature and reaction time were the studied parameters, and the methyl esters content was the response of the experimental design. An ion exchange resin was used as a heterogeneous catalyst. The process optimization was carried out using response surface methodology (RSM) and polynomial model of second order. Results show that the most influential variables on the linear coefficient of each effect studied were temperature and reaction time. The best result of methyl esters conversion in the experimental design was under the conditions: 10% wt of catalyst; 100 °C and 4 hours of reaction. The best-achieved conversion was 96.5% wt of biofuel.

Keywords: esterification, ion-exchange resins, response surface methodology, biofuel

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