Search results for: post cancer maxillary reconstruction
5647 Malignant Ovarian Cancer Ascites Confers Platinum Chemoresistance to Ovarian Cancer Cells: A Combination Treatment with Crizotinib and 2 Hydroxyestradiol Restore Platinum Sensitivity
Authors: Yifat Koren Carmi, Abed Agbarya, Hazem Khamaisi, Raymond Farah, Yelena Shechtman, Roman Korobochka, Jacob Gopas, Jamal Mahajna
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Ovarian cancer (OC), the second most common form of gynecological malignancy, has a poor prognosis and is frequently identified in its late stages. The recommended treatment for OC typically includes a platinum-based chemotherapy, like carboplatin. Nonetheless, OC treatment has proven challenging due to toxicity and development of acquired resistance to therapy. Chemoresistance is a significant obstacle to a long-lasting response in OC patients, believed to arise from alterations within the cancer cells as well as within the tumor microenvironments (TME). Malignant ascites is a presenting feature in more than one-third of OC patients. It serves as a reservoir for a complex mixture of soluble factors, metabolites, and cellular components, providing a pro-inflammatory and tumor-promoting microenvironment for the OC cells. Malignant ascites is also associated with metastasis and chemoresistance. In an attempt to elucidate the role of TME in chemoresistance of OC, we monitored the ability of soluble factors derived from ascites fluids to affect platinum sensitivity of OC cells. This research, compared ascites fluids from non-malignant cirrhotic patients to those from OC patients in terms of their ability to alter the platinum sensitivity of OC cells. Our findings indicated that exposure to OC ascites induces platinum chemoresistance on OC cells in 11 out of 13 cases (85%). In contrast, 75% of cirrhosis ascites (3 out of 4) failed to confer platinum chemoresistance to OC cells. Cytokine array analysis revealed that IL-6, and to a lesser extent HGF were enriched in OC ascites, whereas IL-22 was enriched in cirrhosis ascites. Pharmaceutical inhibitors that target the IL-6/JAK signaling pathway were mildly effective in overcoming the platinum chemoresistance induced by malignant ascites. In contrast, Crizotinib an HGF/c-MET inhibitor, and 2-hydroxyestradiol (2HE2) were effective in restoring platinum chemoresistance to OC. Our findings demonstrate the importance of OC ascites in supporting platinum chemoresistance as well as the potential of a combination therapy with Crizotinib and the estradiol metabolite 2HE2 to regain OC cells chemosensitivity.Keywords: ovarian cancer, platinum chemoresistance, malignant ascites, tumor microenvironment, IL-6, 2-hydroxyestradiol, HGF, crizotinib
Procedia PDF Downloads 695646 Regulation of Apoptosis in Human Lung Cancer NCI-H226 Cells through Caspase – Dependent Mechanism by Benjakul Extract
Authors: Pintusorn Hansakul, Ruchilak Rattarom, Arunporn Itharat
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Background: Benjakul, a Thai traditional herbal formulation, comprises of five plants: Piper chaba, Piper sarmentosum, Piper interruptum, Plumbago indica, and Zingiber officinale. It has been widely used to treat cancer patients in the context of folk medicine in Thailand. This study aimed to investigate the cytotoxic effect of the ethanol extract of Benjakul against three non-small cell lung cancer (NSCLC) cell lines (NCI-H226, A549, COR-L23), small cell lung cancer (SCLC) cell line NCI-H1688 and normal lung fibroblast cell line MRC-5. The study further examined the molecular mechanisms underlying its cytotoxicity via induction of apoptosis in NCI-H226 cells. Methods: The cytotoxic effect of Benjakul was determined by SRB assay. The effect of Benjakul on cell cycle distribution was assessed by flow cytometric analysis. The apoptotic effects of Benjakul were determined by sub-G1 quantitation and Annexin V-FITC/PI flow cytometric analyses as well as by changes in caspase-3 activity. Results: Benjakul exerted potent cytotoxicity on NCI-H226 and A549 cells but lower cytotoxicity on COR-L23 and NCI-H1688 cells without any cytotoxic effect on normal cells. Molecular studies showed that Benjakul extract induced G2/M phase arrest in human NCI-H226 cells in a dose-dependent manner. The highest concentration of Benjakul (150 μg/ml) led to the highest increase in the G2/M population at 12 h, followed by the highest increase in the sub-G1 population (apoptotic cells) at 60 h. Benjakul extract also induced early apoptosis (AnnexinV +/PI−) in NCI-H226 cells in a dose- and time- dependent manner. Moreover, treatment with 150 μg/ml Benjakul extract for 36 h markedly increased caspase-3 activity by 3.5-fold, and pretreatment with the general caspase inhibitor z-VAD-fmk completely abolished such activity. Conclusions: This study reveals for the first time the regulation of apoptosis in human lung cancer NCI-H226 cells through caspase-dependent mechanism by Benjakul extract.Keywords: apoptosis, Benjakul, caspase activation, cytotoxicity
Procedia PDF Downloads 4435645 Functionalization of Carboxylated Single-Walled Carbon Nanotubes with 2-En 4-Hydroxy Cyclo 1-Octanon and Toxicity Investigation
Authors: D. ChobfroushKhoei, S. K. Heidari , Sh. Dariadel
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Carbon nanotubes were used in medical sciences especially in drug delivery system and cancer therapy. In this study, we functionalized carboxylated single-wall carbon nanotubes (SWNT-COOH) with 2-en 4-hydroxy cyclo 1-octanon. Synthesized sample was characterized by FT-IR, Raman spectroscopy, SEM, TGA and cellular investigations. The results showed well formation of SWNT-Ester. Cell viability assay results and microscopic observations demonstrated that cancerous cells were killed in the sample. The synthesized sample can be used as a toxic material for cancer therapy.Keywords: MWNT-COOH, functionalization, phenylisocyanate, phenylisothiocyanate, 1, 4-phenylendiamine, toxicity investigation
Procedia PDF Downloads 4535644 Health Post A Sustainable Prototype for the Third World
Authors: Chizzoniti Domenico, Beggiora Klizia, Cattani Letizia, Moscatelli Monica
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This paper concerns the study of sustainable construction materials applied on the "Health Post", a prototype for the primary health care situated in alienated areas of the world. It's suitable for social and climatic Sub-Saharan context; however, it could be moved in other countries of the world with similar urgent needs. The idea is to create a Health Post with local construction materials that have a low environmental impact and promote the local workforce allowing reuse of traditional building techniques lowering production costs and transport. The aim of Primary Health Care Centre is to be a flexible and expandable structure identifying a modular form that can be repeated several times to expand its existing functions. In this way it could be not only a health care centre but also a socio-cultural facility.Keywords: low costs building, sustainable construction materials, green construction system, prototype, health care, emergency
Procedia PDF Downloads 4805643 The Use of Medical Biotechnology to Treat Genetic Disease
Authors: Rachel Matar, Maxime Merheb
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Chemical drugs have been used for many centuries as the only way to cure diseases until the novel gene therapy has been created in 1960. Gene therapy is based on the insertion, correction, or inactivation of genes to treat people with genetic illness (1). Gene therapy has made wonders in Parkison’s, Alzheimer and multiple sclerosis. In addition to great promises in the healing of deadly diseases like many types of cancer and autoimmune diseases (2). This method implies the use of recombinant DNA technology with the help of different viral and non-viral vectors (3). It is nowadays used in somatic cells as well as embryos and gametes. Beside all the benefits of gene therapy, this technique is deemed by some opponents as an ethically unacceptable treatment as it implies playing with the genes of living organisms.Keywords: gene therapy, genetic disease, cancer, multiple sclerosis
Procedia PDF Downloads 5415642 The Initiator Matters in Service Co-Recovery: Investigation on Attribution and Satisfaction
Authors: Chia-Ching Tsai
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In the literature, the positive effect of service co-recovery has been evidenced, and which customers’ attribution is the key successful factor has also been indicated. There is also literature investigating on initiation of co-recovery for finding out the superior way to co-recovery, and indicating co-recovery initiated by employees causes better effect of co-recovery. This research postulates the consequences of co-recovery by different initiators affect customers’ attribution and the resultant results. Thus, this research uses a 3x2 factorial design to investigate the impact of initiator of co-recovery and consequence of co-recovery on customers’ attribution and post-recovery satisfaction. The results show initiation of co-recovery has a significant influence on internal attribution, and the employee initiator causes the highest internal attribution. The consequences of co-recovery interact with initiators of co-recovery on internal attribution significantly. Moreover, internal attribution significantly affects post-recovery satisfaction.Keywords: service co-recovery, initiation of co-recovery, attribution, post-recovery satisfaction
Procedia PDF Downloads 2635641 Retrospective Reconstruction of Time Series Data for Integrated Waste Management
Authors: A. Buruzs, M. F. Hatwágner, A. Torma, L. T. Kóczy
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The development, operation and maintenance of Integrated Waste Management Systems (IWMS) affects essentially the sustainable concern of every region. The features of such systems have great influence on all of the components of sustainability. In order to reach the optimal way of processes, a comprehensive mapping of the variables affecting the future efficiency of the system is needed such as analysis of the interconnections among the components and modelling of their interactions. The planning of a IWMS is based fundamentally on technical and economical opportunities and the legal framework. Modelling the sustainability and operation effectiveness of a certain IWMS is not in the scope of the present research. The complexity of the systems and the large number of the variables require the utilization of a complex approach to model the outcomes and future risks. This complex method should be able to evaluate the logical framework of the factors composing the system and the interconnections between them. The authors of this paper studied the usability of the Fuzzy Cognitive Map (FCM) approach modelling the future operation of IWMS’s. The approach requires two input data set. One is the connection matrix containing all the factors affecting the system in focus with all the interconnections. The other input data set is the time series, a retrospective reconstruction of the weights and roles of the factors. This paper introduces a novel method to develop time series by content analysis.Keywords: content analysis, factors, integrated waste management system, time series
Procedia PDF Downloads 3265640 Computational Fluid Dynamic Modeling of Mixing Enhancement by Stimulation of Ferrofluid under Magnetic Field
Authors: Neda Azimi, Masoud Rahimi, Faezeh Mohammadi
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Computational fluid dynamics (CFD) simulation was performed to investigate the effect of ferrofluid stimulation on hydrodynamic and mass transfer characteristics of two immiscible liquid phases in a Y-micromixer. The main purpose of this work was to develop a numerical model that is able to simulate hydrodynamic of the ferrofluid flow under magnetic field and determine its effect on mass transfer characteristics. A uniform external magnetic field was applied perpendicular to the flow direction. The volume of fluid (VOF) approach was used for simulating the multiphase flow of ferrofluid and two-immiscible liquid flows. The geometric reconstruction scheme (Geo-Reconstruct) based on piecewise linear interpolation (PLIC) was used for reconstruction of the interface in the VOF approach. The mass transfer rate was defined via an equation as a function of mass concentration gradient of the transported species and added into the phase interaction panel using the user-defined function (UDF). The magnetic field was solved numerically by Fluent MHD module based on solving the magnetic induction equation method. CFD results were validated by experimental data and good agreements have been achieved, which maximum relative error for extraction efficiency was about 7.52 %. It was showed that ferrofluid actuation by a magnetic field can be considered as an efficient mixing agent for liquid-liquid two-phase mass transfer in microdevices.Keywords: CFD modeling, hydrodynamic, micromixer, ferrofluid, mixing
Procedia PDF Downloads 1965639 Challenges of Technical and Engineering Students in the Application of Scientific Cancer Knowledge to Preserve the Future Generation in Sub-Saharan Africa
Authors: K. Shaloom Mbambu, M. Pascal Tshimbalanga, K. Ruth Mutala, K. Roger Kabuya, N. Dieudonné Kabeya, Y. L. Kabeya Mukeba
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In this article, the authors examine the even more worrying situation of girls in sub-Saharan Africa. Two-girls on five are private of Global Education, which represents a real loss to the development of communities and countries. Cultural traditions, poverty, violence, early and forced marriages, early pregnancies, and many other gender inequalities were the causes of this cancer development. Namely, "it is no more efficient development tool that is educating girls." The non-schooling of girls and their lack of supervision by liberal professions have serious consequences for the life of each of them. To improve the conditions of their inferior status, girls to men introduce poverty and health risks. Raising awareness among parents and communities on the importance of girls' education, improving children's access to school, girl-boy equality with their rights, creating income, and generating activities for girls, girls, and girls learning of liberal trades to make them self-sufficient. Organizations such as the United Nations Organization can save the children. ASEAD and the AEDA group are predicting the impact of this cancer on the development of a nation's future generation must be preserved.Keywords: young girl, Sub-Saharan Africa, higher and vocational education, development, society, environment
Procedia PDF Downloads 2545638 Predictors of Post-marketing Regulatory Actions Concerning Hepatotoxicity
Authors: Salwa M. Almomen, Mona A. Almaghrabi, Saja M. Alhabardi, Adel A. Alrwisan
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Background: Hepatotoxicity is a major reason for medication withdrawal from the markets. Unfortunately, serious adverse hepatic effects can occur after marketing with limited indicators during clinical development. Therefore, finding possible predictors for hepatotoxicity might guide the monitoring program of various stakeholders. Methods: We examined the clinical review documents for drugs approved in the US from 2011 to 2016 to evaluate their hepatic safety profile. Predictors: we assessed whether these medications meet Hy’s Law with hepatotoxicity grade ≥ 3, labeled hepatic adverse effects at approval, or accelerated approval status. Outcome: post-marketing regulatory action related to hepatotoxicity, including product withdrawal or updates to warning, precaution, or adverse effects sections. Statistical analysis: drugs were included in the analysis from the time of approval until the end of 2019 or the first post-marketing regulatory action related to hepatotoxicity, whichever occurred first. The hazard ratio (HR) was estimated using Cox-regression analysis. Results: We included 192 medications in the study. We classified 48 drugs as having grade ≥ 3 hepatotoxicities, 43 had accelerated approval status, and 74 had labeled information about hepatotoxicity prior to marketing. The adjusted HRs for post-marketing regulatory action for products with grade ≥ 3 hepatotoxicity was 0.61 (95% confidence interval [CI], 0.17-2.23), 0.92 (95%CI, 0.29-2.93) for a drug approved via accelerated approval program, and was 0.91 (95%CI, 0.33-2.56) for drugs with labeled hepatotoxicity information at approval time. Conclusion: This study does not provide conclusive evidence on the association between post-marketing regulatory action and grade ≥ 3 hepatotoxicity, accelerated approval status, or availability of labeled information at approval due to sampling size and channeling bias.Keywords: accelerated approvals, hepatic adverse effects, drug-induced liver injury, hepatotoxicity predictors, post-marketing withdrawal
Procedia PDF Downloads 1525637 The Prognostic Prediction Value of Positive Lymph Nodes Numbers for the Hypopharyngeal Squamous Cell Carcinoma
Authors: Wendu Pang, Yaxin Luo, Junhong Li, Yu Zhao, Danni Cheng, Yufang Rao, Minzi Mao, Ke Qiu, Yijun Dong, Fei Chen, Jun Liu, Jian Zou, Haiyang Wang, Wei Xu, Jianjun Ren
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We aimed to compare the prognostic prediction value of positive lymph node number (PLNN) to the American Joint Committee on Cancer (AJCC) tumor, lymph node, and metastasis (TNM) staging system for patients with hypopharyngeal squamous cell carcinoma (HPSCC). A total of 826 patients with HPSCC from the Surveillance, Epidemiology, and End Results database (2004–2015) were identified and split into two independent cohorts: training (n=461) and validation (n=365). Univariate and multivariate Cox regression analyses were used to evaluate the prognostic effects of PLNN in patients with HPSCC. We further applied six Cox regression models to compare the survival predictive values of the PLNN and AJCC TNM staging system. PLNN showed a significant association with overall survival (OS) and cancer-specific survival (CSS) (P < 0.001) in both univariate and multivariable analyses, and was divided into three groups (PLNN 0, PLNN 1-5, and PLNN>5). In the training cohort, multivariate analysis revealed that the increased PLNN of HPSCC gave rise to significantly poor OS and CSS after adjusting for age, sex, tumor size, and cancer stage; this trend was also verified by the validation cohort. Additionally, the survival model incorporating a composite of PLNN and TNM classification (C-index, 0.705, 0.734) performed better than the PLNN and AJCC TNM models. PLNN can serve as a powerful survival predictor for patients with HPSCC and is a surrogate supplement for cancer staging systems.Keywords: hypopharyngeal squamous cell carcinoma, positive lymph nodes number, prognosis, prediction models, survival predictive values
Procedia PDF Downloads 1545636 Absence of Malignancy in Oral Epithelial Cells from Individuals Occupationally Exposed to Organic Solvents Working in the Shoe Industry
Authors: B. González-Yebra, B. Flores-Nieto, P. Aguilar-Salinas, M. Preciado Puga, A. L. González Yebra
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The monitoring of populations occupationally exposed to organic solvents has been an important issue for several shoe factories for years since the International Agency for Research on Cancer (IARC) has advised on the potential carcinogenic risk of chemicals related to occupations. In order to detect if exposition to organic solvents used in some Mexican shoe factories contributes to oral carcinogenesis, we performed monitoring in three factories. Occupational exposure was determined by using monitors 3M. Organic solvents were assessed by gas chromatography. Then, we recruited 30 shoe workers (30.2 ± 8.4 years) and 10 unexposed subjects (43.3 ± 11.2 years) for the micronuclei (MN) test and immunodetection of some cancer biomarkers (ki-67, p16, caspase-3) in scraped oral epithelial cells. Monitored solvents detected were acetone, benzene, hexane, methyl ethyl ketone, and toluene in acceptable levels according to Official Mexican Norm. We found by MN test higher incidence of nuclear abnormalities (karyorrhexis, pycnosis, karyolysis, condensed chromatin, and macronuclei) in the exposed group than the non-exposed group. On the other hand, we found, a negative expression for Ki-67 and p16 in exfoliated epithelial cells from exposed and non-exposed to organic solvents subjects. Only caspase-3 shown positive patter of expression in 9/30 (30%) exposed subjects, and we detected high karyolysis incidence in caspase-3 subjects (p = 0.021). The absence of expression of proliferation markers p16 and ki-67 and presence of apoptosis marker caspase-3 are indicating the absence of malignancy in oral epithelial cells and low risk for oral cancer. It is a fact that the MN test is a very effective method to detect nuclear abnormalities in exfoliated buccal cells from subjects that have been exposed to organic solvents in the shoe industry. However, in order to improve this tool and predict cancer risk is it is mandatory to implement complementary tests as other biomarkers that can help to detect malignancy in individuals occupationally exposed.Keywords: biomarkers, oral cancer, organic solvents, shoe industries
Procedia PDF Downloads 1365635 Cardenolides from the Egyptian Cultivar: Acokanthera spectabilis Leaves Inducing Apoptosis through Arresting Hepatocellular Carcinoma Growth at G2/M
Authors: Maha Soltan, Amal Z. Hassan, Howaida I. Abd-Alla, Atef G. Hanna
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Two naturally known cardenolides; acovenoside A and acobioside A were isolated from the Egyptian cultivar; Acokanthera spectabilis leaves. It is an ornamental and poisonous plant that has been traditionally claimed for their medicinal properties against infectious microbes, killing worms and curing some inflammations at little amounts. We examined the growth inhibition effects of both cardenolides against four types of human cancer cell lines using Sulphorhodamine B assay. In addition, the clonogenic assay was also performed for testing the growth inhibiting power of the isolated compounds. An in vitro mechanistic investigation was further accomplished against hepatocellular carcinoma HepG2 cell line. Microscopic examination, colorimetric ELISA and flow cytometry techniques were our tools of proving at least part of the anticancer pathway of the tested compounds. Both compounds were able to inhibit the growth of 4 human cancer cell lines at less than 100 nM. In addition, they were able to activate the executioner Caspase-3 and apoptosis was then induced as a consequence of cell growth arrest at G2/M. An attention must be payed to those bioactive agents particularly when giving their activity against cancer cells at considerable small values while presenting safe therapeutic margins as indicated by literature.Keywords: anticancer, cardenolides, Caspase-3, apoptosis
Procedia PDF Downloads 1475634 TP53 Mutations in Molecular Subtypes of Breast Cancer in Young Pakistani Patients
Authors: Nadia Naseem, Farwa Batool, Nasir Mehmood, AbdulHannan Nagi
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Background: The incidence and mortality of breast cancer vary significantly in geographically distinct populations. In Pakistan, breast cancer has shown an increase in incidence in young females and is characterized by more aggressive behavior. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. This study investigated the TP53 mutations in molecular subtypes of both nodes negative and positive breast cancer in young Pakistani patients. Material and Methods: p53, Estrogen Receptor (ER), Progesterone Receptor (PR), Her-2 neu and Ki 67 expressions were analyzed immunohistochemically in a series of 75 node negative (A) and 75 node positive (B) young (aged: 19-40 years) breast cancer patients diagnosed between 2014 to 2017 at two leading hospitals of Punjab, Pakistan. Tumor tissue specimens and peripheral blood samples were examined for TP53 mutations by direct sequencing of the gene (exons 4-9). The relation of TP53 mutations to these markers and clinicopathological data was investigated. Results: Mean age of the patients was 32.4 + 9.1 SD. Invasive breast carcinoma was the most frequent histological variant (A=92%, B=94.6%). Grade 3 carcinoma was the commonest grade (A=72%, B=81.3%). Triple negative cases (ER-, PR-, Her-2) formed most of the molecular subtypes (A=44%, B=50.6%). A total of 17.2% (A: 6.6%, B: 10.6%) patients showed TP53 mutations. Mutations were significantly more frequent in triple negative cases (A: 74.8%, B: 62.2%) compared to HER2-positive patients (P < 0.0001). In the multivariate analysis of the whole patient group, the independent prognosticator were triple negative cases (P=0.021), TP53 overexpression by IHC (P=0.001) and advanced-stage disease (P=0.007). No statistically significant correlation between TP53 mutations and clinicopathological parameters was found (P < 0.05). Conclusions: It is concluded that TP53 mutations are infrequently present in breast carcinoma of young Pakistani population and there was no significant correlation between p53 mutation and early onset disease. Immunohistochemically detected TP53 expression in our resource-constrained to set up can be beneficial in predicting mutations at the younger age in our population.Keywords: immunohistochemistry (IHC), invasive breast carcinoma (IBC), Pakistan, TP53
Procedia PDF Downloads 1585633 Synthetic, Characterization and Biological Studies of Bis(Tetrathiomolybdate) Compounds of Pt (II), Pd (II) and Ni (II)
Authors: V. K. Srivastava
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The chemistry of compounds containing transition metals bound to sulfur containing ligands has been actively studied. Interest in these compounds arises from the identification of the biological importance of iron-sulfur containing proteins as well as the unusual behaviour of several types of synthetic metal-sulfur complexes. Metal complexes (C₆H₅)₄P)₂ Pt(Mos₄)₂, (C₆H₅)₄P)₂ Pd(MoS₄)₂, (C₆H₅)₄P)₂ Ni(MoS₄)₂ of bioinorganic relevance were investigated. The complexes [M(M'S₄)₂]²⁻ were prepared with high yield and purity as salts of the variety of organic cations. The diamagnetism and spectroscopic properties of these complexes confirmed that their structures are essentially equivalent with two bidentate M'S₄²⁻ ligands coordinated to the central d⁸ metal in a square planer geometry. The interaction of the complexes with CT-DNA was studied. Results showed that metal complexes increased DNA's relative viscosity and quench the fluorescence intensity of EB bound to DNA. In antimicrobial activities, all complexes showed good antimicrobial activity higher than ligand against gram positive, gram negative bacteria and fungi. The antitumor properties have been tested in vitro against two tumor human cell lines, Hela (derived from cervical cancer) and MCF-7 (derived from breast cancer) using metabolic activity tests. Result showed that the complexes are promising chemotherapeutic alternatives in the search of anticancer agents.Keywords: anti cancer, biocidal, DNA binding, spectra
Procedia PDF Downloads 1595632 Automated Building Internal Layout Design Incorporating Post-Earthquake Evacuation Considerations
Authors: Sajjad Hassanpour, Vicente A. González, Yang Zou, Jiamou Liu
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Earthquakes pose a significant threat to both structural and non-structural elements in buildings, putting human lives at risk. Effective post-earthquake evacuation is critical for ensuring the safety of building occupants. However, current design practices often neglect the integration of post-earthquake evacuation considerations into the early-stage architectural design process. To address this gap, this paper presents a novel automated internal architectural layout generation tool that optimizes post-earthquake evacuation performance. The tool takes an initial plain floor plan as input, along with specific requirements from the user/architect, such as minimum room dimensions, corridor width, and exit lengths. Based on these inputs, firstly, the tool randomly generates different architectural layouts. Secondly, the human post-earthquake evacuation behaviour will be thoroughly assessed for each generated layout using the advanced Agent-Based Building Earthquake Evacuation Simulation (AB2E2S) model. The AB2E2S prototype is a post-earthquake evacuation simulation tool that incorporates variables related to earthquake intensity, architectural layout, and human factors. It leverages a hierarchical agent-based simulation approach, incorporating reinforcement learning to mimic human behaviour during evacuation. The model evaluates different layout options and provides feedback on evacuation flow, time, and possible casualties due to earthquake non-structural damage. By integrating the AB2E2S model into the automated layout generation tool, architects and designers can obtain optimized architectural layouts that prioritize post-earthquake evacuation performance. Through the use of the tool, architects and designers can explore various design alternatives, considering different minimum room requirements, corridor widths, and exit lengths. This approach ensures that evacuation considerations are embedded in the early stages of the design process. In conclusion, this research presents an innovative automated internal architectural layout generation tool that integrates post-earthquake evacuation simulation. By incorporating evacuation considerations into the early-stage design process, architects and designers can optimize building layouts for improved post-earthquake evacuation performance. This tool empowers professionals to create resilient designs that prioritize the safety of building occupants in the face of seismic events.Keywords: agent-based simulation, automation in design, architectural layout, post-earthquake evacuation behavior
Procedia PDF Downloads 1045631 Anticancer Lantadene Derivatives: Synthesis, Cytotoxic and Docking Studies
Authors: A. Monika, Manu Sharma, Hong Boo Lee, Richa Dhingra, Neelima Dhingra
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Nuclear factor-κappa B serve as a molecular lynchpin that links persistent infections and chronic inflammation to increased cancer risk. Inflammation has been recognized as a hallmark and cause of cancer. Natural products present a privileged source of inspiration for chemical probe and drug design. Herbal remedies were the first medicines used by humans due to the many pharmacologically active secondary metabolites produced by plants. Some of the metabolites like Lantadene (pentacyclic triterpenoids) from the weed Lantana camara has been known to inhibit cell division and showed anti-antitumor potential. The C-3 aromatic esters of lantadenes were synthesized, characterized and evaluated for cytotoxicity and inhibitory potential against Tumor necrosis factor alpha-induced activation of Nuclear factor-κappa B in lung cancer cell line A549. The 3-methoxybenzoyloxy substituted lead analogue inhibited kinase activity of the inhibitor of nuclear factor-kappa B kinase in a single-digit micromolar concentration. At the same time, the lead compound showed promising cytotoxicity against A549 lung cancer cells with IC50 ( half maximal inhibitory concentration) of 0.98l µM. Further, molecular docking of 3-methoxybenzoyloxy substituted analogue against Inhibitor of nuclear factor-kappa B kinase (Protein data bank ID: 3QA8) showed hydrogen bonding interaction involving oxygen atom of 3-methoxybenzoyloxy with the Arginine-31 and Glutamine-110. Encouraging results indicate the Lantadene’s potential to be developed as anticancer agents.Keywords: anticancer, lantadenes, pentacyclic triterpenoids, weed
Procedia PDF Downloads 1565630 Tumor Cell Detection, Isolation and Monitoring Using Bi-Layer Magnetic Microfluidic Chip
Authors: Amir Seyfoori, Ehsan Samiei, Mohsen Akbari
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The use of microtechnology for detection and high yield isolation of circulating tumor cells (CTCs) has shown enormous promise as an indication of clinical metastasis prognosis and cancer treatment monitoring. The Immunomagnetic assay has been also coupled to microtechnology to improve the selectivity and efficiency of the current methods of cancer biomarker isolation. In this way, generation and configuration of the local high gradient magnetic field play essential roles in such assay. Additionally, considering the intrinsic heterogeneity of cancer cells, real-time analysis of isolated cells is necessary to characterize their responses to therapy. Totally, on-chip isolation and monitoring of the specific tumor cells is considered as a pressing need in the way of modified cancer therapy. To address these challenges, we have developed a bi-layer magnetic-based microfluidic chip for enhanced CTC detection and capturing. Micromagnet arrays at the bottom layer of the chip were fabricated using a new method of magnetic nanoparticle paste deposition so that they were arranged at the center of the chain microchannel with the lowest fluid velocity zone. Breast cancer cells labelled with EPCAM-conjugated smart microgels were immobilized on the tip of the micromagnets with greater localized magnetic field and stronger cell-micromagnet interaction. Considering different magnetic nano-powder usage (MnFe2O4 & gamma-Fe2O3) and micromagnet shapes (ellipsoidal & arrow), the capture efficiency of the systems was adjusted while the higher CTC capture efficiency was acquired for MnFe2O4 arrow micromagnet as around 95.5%. As a proof of concept of on-chip tumor cell monitoring, magnetic smart microgels made of thermo-responsive poly N-isopropylacrylamide-co-acrylic acid (PNIPAM-AA) composition were used for both purposes of targeted cell capturing as well as cell monitoring using antibody conjugation and fluorescent dye loading at the same time. In this regard, magnetic microgels were successfully used as cell tracker after isolation process so that by raising the temperature up to 37⁰ C, they released the contained dye and stained the targeted cell just after capturing. This microfluidic device was able to provide a platform for detection, isolation and efficient real-time analysis of specific CTCs in the liquid biopsy of breast cancer patients.Keywords: circulating tumor cells, microfluidic, immunomagnetic, cell isolation
Procedia PDF Downloads 1435629 Efficacy and Safety of Updated Target Therapies for Treatment of Platinum-Resistant Recurrent Ovarian Cancer
Authors: John Hang Leung, Shyh-Yau Wang, Hei-Tung Yip, Fion, Ho Tsung-chin, Agnes LF Chan
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Objectives: Platinum-resistant ovarian cancer has a short overall survival of 9–12 months and limited treatment options. The combination of immunotherapy and targeted therapy appears to be a promising treatment option for patients with ovarian cancer, particularly to patients with platinum-resistant recurrent ovarian cancer (PRrOC). However, there are no direct head-to-head clinical trials comparing their efficacy and toxicity. We, therefore, used a network to directly and indirectly compare seven newer immunotherapies or targeted therapies combined with chemotherapy in platinum-resistant relapsed ovarian cancer, including antibody-drug conjugates, PD-1 (Programmed death-1) and PD-L1 (Programmed death-ligand 1), PARP (Poly ADP-ribose polymerase) inhibitors, TKIs (Tyrosine kinase inhibitors), and antiangiogenic agents. Methods: We searched PubMed (Public/Publisher MEDLINE), EMBASE (Excerpta Medica Database), and the Cochrane Library electronic databases for phase II and III trials involving PRrOC patients treated with immunotherapy or targeted therapy plus chemotherapy. The quality of included trials was assessed using the GRADE method. The primary outcomes compared were progression-free survival, the secondary outcomes were overall survival and safety. Results: Seven randomized controlled trials involving a total of 2058 PRrOC patients were included in this analysis. Bevacizumab plus chemotherapy showed statistically significant differences in PFS (Progression-free survival) but not OS (Overall survival) for all interested targets and immunotherapy regimens; however, according to the heatmap analysis, bevacizumab plus chemotherapy had a statistically significant risk of ≥grade 3 SAEs (Severe adverse effects), particularly hematological severe adverse events (neutropenia, anemia, leukopenia, and thrombocytopenia). Conclusions: Bevacizumab plus chemotherapy resulted in better PFS as compared with all interested regimens for the treatment of PRrOC. However, statistical differences in SAEs as bevacizumab plus chemotherapy is associated with a greater risk for hematological SAE.Keywords: platinum-resistant recurrent ovarian cancer, network meta-analysis, immune checkpoint inhibitors, target therapy, antiangiogenic agents
Procedia PDF Downloads 795628 An Alternative Nano Design Strategy by Neutralized AMPS and Soy Bean Lecithin to Form Nanoparticles
Authors: Esra Cansever Mutlu, Muge Sennaroglu Bostan, Fatemeh Bahadori, Ebru Toksoy Oner, Mehmet S. Eroglu
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Paclitaxel is used in treatment of different cancer types mainly breast, ovarian, lung and Kaposi’s sarcoma. It is poorly soluble in water; therefore, currently used formulations tremendously show side-effects and high toxicity. Encapsulation of the drug in a nano drug carrier which causes both reducing side effects and increasing drug activity is a desired new approach for the nano-medicine to target the site of cancer. In this study, synthesis of a novel nano paclitaxel formulation made of a new amphiphilic monomer was followed by the investigation of its pharmacological properties. UV radical polymerization was carried out by using the monomer Lecithin-2-Acrylamido-2-methylpropane (L-AMPS) and the drug-spacer, to obtain sterically high stabilized, biocompatible and biodegradable phospholipid nanoparticles, in which the drug paclitaxel (Pxl) was encapsulated (NanoPxl). Particles showed high drug loading capacity (68%) and also hydrodynamic size less than 200 nm with slight negative surface charge. The drug release profile was obtained and in vitro cytotoxicity test was performed on MCF-7 cell line. Consequently, these data indicated that paclitaxel loaded Lecithin-AMPS/PCL-MAC nanoparticles can be considered as a new, safe and effective nanocarrier for the treatment of breast cancer.Keywords: paclitaxel, nanoparticle, drug delivery, L-AMPS
Procedia PDF Downloads 3205627 SOCS3 Reverses Multidrug Resistance by Inhibiting MDR1 in Mammary Cell Carcinoma
Authors: S. Pradhan, D. Pradhan, G. Tripathy, T. Dasmohapatra
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Suppressors of cytokine signalling (SOCS3), a newly indentified anti-apoptotic molecule is a downstream effecter of the receptor tyrosine kinase-Ras signalling pathway. Current study has uncovered that SOCS3 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS3 on MDR, we analyzed the expression of P-gp and SOCS3 by immune-histochemistry and found there was positive correlation between them. At that point we effectively interfered with RNA translation by the contamination of siRNA of SOCS3 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flowcytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS3 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.Keywords: SOCS3gene, breast cancer, multidrug resistance, MDR1 gene, RNA interference
Procedia PDF Downloads 3375626 Impact of Hormone Replacement Therapy on Body Composition Analysis of Women during Perimenopause: A Framework for Action
Authors: Varsha Chorsiya, Pooja Aneja, Dhananjay Kaushik, Abhinav Yadav
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Intoduction: Women’s Health Initiatives (WHI) focuses on defining the risks and benefits of strategies that could potentially reduce the incidence of obesity, heart disease, breast cancer and colorectal cancer, and fractures in menopause women. The utility of the present research work determines to find the role of Hormone Replacement Therapy (HRT) in changing the different component of body composition during perimenopause period. Methods: A comparative cross-sectional study included 30 subjects, aged between 40 and 50 years which were assigned into 2 groups i.e. 15 subjects in HRT (Group A) and 15 subjects in non-HRT (Group B). The subjects were taken from the hospitals and clinics of Faridabad undergoing HRT in supervision of the consultant gynecologist. The informed consents were signed before including the participants in the study. The body composition and lipid profile were evaluated for all the subjects. Result and Discussion: The BMI, body density, percent body fats and fat mass in both groups showed statistically significant differences i.e. p < 0.05. Our study did not reveal any statistically significant difference between non-HRT and HRT for lipid profile composition of HDL, LDL, VLDL, ratio, triglycerides and total cholesterol although these indicators (LDL, VLDL, ratio, triglycerides and total cholesterol) showed difference clinically with a higher mean values for non-HRT as compared to HRT group. The mean value for HDL was higher for HRT group in contrast to non-HRT group. The result clearly showed that HRT group has a good lipid profile composition. Conclusion: In conclusion, our data show that HRT has statistically significant role in determining BMI, fat percent mass and fat mass. The lipid profile including LDL, HDL, VLDL, ratio, triglycerides and total cholesterol found to be clinically better in HRT group as compared to the non-HRT group. The rationale for non-significant lipid profile probably lie in the fact that hormonal changes need a particular time period and might become significant in post-menopausal period.Keywords: body composition, hormone replacement therapy, perimenopause, women health
Procedia PDF Downloads 2935625 Formulation and Evaluation of Silibilin Loaded PLGA Nanoparticles for Cancer Therapy
Authors: Priya Patel, Paresh Patel, Mihir Raval
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Silibinin, a flavanone as an antimicrotubular agent used in the treatment of cancer, was encapsulated in nanoparticles (NPs) of poly (lactide-co-glycolide) (PLGA) polymer using the spray-drying technique. The effects of various experimental parameters were optimized by box-behnken experimental design. Production yield, encapsulation efficiency and dissolution study along with characterization by scanning electron microscopy, DSC, FTIR followed by bioavailability study. Particle size and zeta potential were evaluated by using zetatrac particle size analyzer. Experimental design it was evaluated that inlet temperature and polymer concentration influence on the drug release. Feed flow rate impact on particle size. Results showed that spray drying technique yield 149 nm indicate nanosize range. The small size of the nanoparticle resulted in an enhanced cellular entry and greater bioavailability. Entrapment efficiency was found between 89.35% and 98.36%. Zeta potential shows good stability index of nanoparticle formulation. The in vitro release studies indicated the silibinin loaded PLGA nanoparticles provide controlled drug release over a period of 32 h. Pharmacokinetic studies demonstrated that after oral administration of silibinin-loaded PLGA nanoparticles to rats at a dose of 10 mg/kg, relative bioavailability was enhanced about 8.85-fold, compared to silibinin suspension as control hence, this investigation demonstrated the potential of the experimental design in understanding the effect of the formulation variables on the quality of silibinin loaded PLGA nanoparticles. These results describe an effective strategy of silibinin loaded PLGA nanoparticles and might provide a promising approach against the cancer.Keywords: silibinin, cancer, nanoparticles, PLGA, bioavailability
Procedia PDF Downloads 4295624 Effect of TPA and HTLV-1 Tax on BRCA-1 and ERE Controlled Genes Expression
Authors: Azhar Jabareen, Mahmoud Huleihel
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BRCA-1 is a multifunctional tumor suppressor, whose expression is activated by the estrogen (E2)-liganded ERα receptor. The activated ERα is a transcriptional factor which activates various genes either by direct binding to the DNA at E2-responsive elements (EREs) and indirectly associated with a range of alternative non-ERE elements. Interference with BRCA-1 expression and/or functions leads to high risk of breast or/and ovarian cancer. Our lab investigated the involvement of Human T-cell leukemia Virus Type 1 (HTLV-1) in breast cancer, since HTLV-1 Tax was found to strongly inhibit BRCA-1 expression. In addition, long exposure of 12-O-tetradecanoylphorbol-13-acetate (TPA), which is one of the stress-inducing agents activated the HTLV-1 promoter. So here the involvement of TPA in breast cancer had been examined by testing the effect of TPA on BRCA-1 and ERE expression. The results showed that TPA activated both BRCA-1 and ERE expression. In the 12 hours TPA activated the tow promoters more than others time, and after 24 hours the level of the tow promoters was decreased. Tax inhibited BRCA-1 expression but did not succeed to inhibit the effect of TPA. Then the activation of the two promoters was not through ERα pathway because TPA had no effect on ERα binding to the two promoters of the BRCA-1 and ERE. Also, the activation was not via nuclear factor kappa B (NF-κB) pathway because when the inhibitory of NF-κB had been added to the TPA, it still activated the tow promoters. However, it seems that 53BP1 may be involved in TPA activation of these promoters because ectopic high expression of 53BP1 significantly reduced the TPA activity. In addition, in the presence of Bisindolylmaleimide-I (BI)- the inhibitor of Protein Kinase C (PKC)- there was no activation for the two promoters, so the PKC is agonized BRCA-1 and ERE activation.Keywords: BRCA-1, ERE, HTLV-1, TPA
Procedia PDF Downloads 2485623 'It’s a Very, Very New Old South Africa…': Exploring Some Race, Corruption and Protest Issues in Zakes Mda’s 'Our Lady of Benoni'
Authors: Bongani Clearance Thela
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It seems that theatre remains a practical method for mobilising people and their ideologies; and South African literature has strengthened over the years as a result of the events which took place during both the Apartheid and Post-Apartheid eras. Hence, the problem noted in this study is that, generally, many people seem to believe that the issues which were a concern during Apartheid times in South Africa no longer exist in Post-Apartheid South Africa, whereas, it is seems that they still do. Post-Apartheid playwrights such as Zakes Mda among others, explore these issues in their works. There are common themes between the two periods, for this reason, distinction can only be drawn in terms of the context. Therefore, this study explores solutions offered by the themes of protest, corruption and race in Zakes Mda’s Our Lady of Benoni. The study uses real events and Mda’s play to reveal that there is a reinvention of Apartheid times’ issues into Post-Apartheid times’ issues. Moreover, the theme of race is explored with reference to class issues. Also, the study aims at highlighting some distinctions between the Apartheid period and Post-Apartheid period as shown by the playwright, Zakes Mda’s fictitious version as seen in some of his characters in the play. Theatre in general has always protested, it is either against an issue or for an issue; therefore, this paper will also explore the various ways in which the theme of protest is undertaken in the study of theatre. Respectively, the paper looks in the literal protest found in Mda’s Our Lady of Benoni in order to provide critical understanding with regard to the notion undertaken in this study. The paper goes on to provide an alternative discussion of the theme of protest; it critically evaluates issues such as corruption and race in terms of class that the playwright, Mda addresses in his play. In conclusion, this paper will use other relevant examples other than Mda’s drama, Our Lady of Benoni, in order to prove that there is a reinvention of Apartheid issues in Post-Apartheid issues in South Africa.Keywords: protest, corruption, race, class
Procedia PDF Downloads 3235622 Idiopathic Gingival Fibromatosis
Authors: Bandana Koirala, Shivalal Sharma
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Introduction: Gingival enlargements are quite common and may be either inflammatory, non-inflammatory or a combination of both. Idiopathic gingival enlargement is a rare condition with a proliferative fibrous lesion of the gingival tissue that causes esthetic and functional problems. It is of undetermined etiology. Case Description: This case report addresses the diagnosis and treatment of a case of idiopathic gingival enlargement in a 9-year-old male patient. The patient presented with a generalized diffuse gingival enlargement involving the entire maxillary and the mandibular arch with extension on occlusal, buccal, lingual, and palatal surfaces with just parts of occlusal surfaces of few upper and lower molars visible resulting in open mouth, difficulty in mastication and speech. Biopsy report confirmed the diagnosis of fibromatosis gingivae. Gingivectomy was carried out in all four quadrants by using external bevel incision. Conclusion: Though total esthetics could not be restored due to unusual bony enlargement, the general appearance improved satisfactorily. Treatment after complete excision however, improved the masticatory competence to a great extent.Keywords: idiopathic gingival fibromatosis, gingival enlargement, gingivectomy, medical and health sciences
Procedia PDF Downloads 3295621 Financial Literacy and Entrepreneurship-Business Startup for Effective Post-retirement Life Management Among Pre-retirees in Universities in Edo State, Nigeria
Authors: Obose Angela Oriazowanlan
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The role of entrepreneurship in preventing poverty and mitigating other post-retirement challenges has been acknowledged to be crucial for effective post-retirement life management, but financial constraints could constitute a bane to pre-retirees’ entrepreneurial intentions. Therefore, the study determined the financial knowledge that could spur their intentions and readiness for a business start that could enable them to surmount post-retirement life challenges. Two research questions guided the study. The descriptive survey research design was adopted and the population comprised all the pre-retirees in universities in Edo State. 250 respondents were randomly selected using the simple random sampling technique from three purposive selected universities. Primary data were gathered through the use of a structured questionnaire, which was validated and tested to have a reliability coefficient value of 0.84. The descriptive statistics of mean and standard deviation were used to answer the research questions and test the respondents’ homogeneity. The findings revealed, among others, that the respondents perceived the benefits of entrepreneurship-business startups to ensure their effective post-retirement life management but intended to rely totally on their retirement savings benefits with the Contributory Pension Scheme (CPS) for business startups. Based on the findings, it was recommended, among others, that pre-retirees should make contingency savings plans and that the employers and government should provide them with financial education in order to acquaint them with relevant financial knowledge to access other forms of business financing such as loans, bank overdraft, angel investors, venture capital and government grants among others prior to final disengagement.Keywords: financial knowledge, entrepreneurial intentions, availability of business funds, business investment and fulfilled post-retirement living.
Procedia PDF Downloads 545620 Banks' Financial Performance in Pakistan from 2012-2015
Authors: Saima Akbar
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The global financial crisis severely and adversely impacted the Pakistanis’ financial setups with far-reaching consequences for its victims. This study aimed to analyze the various determinants of the banks’ financial performance in Pakistan. The stepwise multiple regression analysis and pre-post analysis were carried out in this regard by using SPSS ver 22. The study found that the assets quality is the most influential determinant of return over assets followed by bank size and solvency. Advances, liquidity, investments, and size have positive while poor assets quality and deposits have a negative impact on the return over assets. The comparison of the pre-crisis and post-crisis coefficient values of the independent variables revealed that the global financial crisis had exerted a significant impact on the relative ability of the financial performance determinants to explain variations in return over assets.Keywords: pre-crisis, post-crisis, coefficient values, determinants
Procedia PDF Downloads 2775619 The Influence of Concrete Pictorial Abstract Teaching Approach on Students' Concepts Understanding and Retention in Mathematics in Rwandan Lower Secondary Schools
Authors: Emmanuel Iyamuremye, Irenee Ndayambaje
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This study investigated the influence of Concrete Pictorial Abstract (CPA) teaching approach on mathematics achievement based on a sample of eighth-grade students (N = 10,345) from the Rwandan Lower Secondary School quasi-experimental study with pre-test and post-test control group of 2019 (RLSQES19). Key aspects studied included mathematics concept understanding and mathematics concept retention and how these are influenced by teacher's teaching approach. Specifically, the study aimed to a.) investigate students' concept understanding and concept retention in mathematics when exposed to CPA approach and to those exposed to non-CPA approach before and after the intervention, and b.) ascertain the significant difference between the performance of the students exposed to CPA approach and those exposed to non-CPA approach in terms of post-test scores and retention test scores. Two groups (control and experimental) undergone pre-test, post-test, and retention test. The assignment of control and experimental group among senior two classes from 10 schools was done randomly. The materials used to determine the performance of the students is a teacher-made test. Descriptive statistics and ANCOVA were used for the analysis of the study. For determining the improvement in concept understanding of mathematics, Hakes methods of calculating gain were used to analyze the pre-test and post test score. The level of performance of the two groups in the pre-test is below average level. During the post-test and retention test, the performance of students in non-CPA group is on average level, and students in CPA group are on above average level. Hakes methods of calculating gain revealed higher significant performance in the post-test and retention test of CPA group of students than non-CPA group of students.Keywords: concept understanding, concept retention, performance, teaching approach
Procedia PDF Downloads 1255618 Pre and Post Mordant Effect of Alum on Gamma Rays Assisted Cotton Fabric by Using Ipomoea indica Leaves Extract
Authors: Abdul Hafeez, Shahid Adeel, Ayesha Hussain
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There are number of plants species in the universe which give the protections from different diseases and give colour for the foods and textiles. The environmental condition of the universe suggested toward the ecofriendly textiles. The aim of the paper is to analyze the influence of pre & post mordanting of alum on radiated cotton fabric with Gamma Radiation of different doses by using Ipomoea indica leaves extract. Alum used as mordant with the concentration of 2, 4, 6, 8 and 10% as pre and post mordanting to observe the effect of light and colour fastness of radiated cotton. 6% of alum concentration in pre mordanting gave good colour strength 117.82 with darker in shade toward the greenish tone and in post mordanting 6% concentration gave good colour strength 102.19. The lab values show that the colour is darker in tone and gave bluish effect. Further results showed that alum gave good light and rubbing fastness on gamma radiated cotton fabric.Keywords: Ipomoea indica, gamma radiation, alum, light fastness
Procedia PDF Downloads 171