Search results for: MCF-7 human breast cancer cell line
13616 Product Line Design with Customization in the Presence of Demand Uncertainty
Authors: Parisa Bagheri Tookanlou
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In this paper, we analyze a product line design problem faced by a manufacturing firm where the product line consists of a customized product in addition to a standard product and is offered in a market in which customers are heterogeneous on aesthetic attributes of the product. The customization level of a product is defined by the fraction of aesthetic attributes of the product that the manufacturer chooses to customize. In contrast to the existing literature on product line design that predominantly assumes deterministic demand, we consider the presence of demand uncertainty and frame the product line design problem in a single period (news vendor) setting. We examine the effect of demand uncertainty on product line decisions. Furthermore, we also examine how product line decisions are influenced by channel structure. While we use the centralized channel as a benchmark, we consider the decentralized dual channel where the customized product is sold through an online channel owned by the manufacturer and the standard product is sold through a retailer. We introduce a supply contract between the manufacturer and the retailer for improving channel efficiency and coordinate the distribution channel.Keywords: product line design, demand uncertainty, customization level, distribution channel
Procedia PDF Downloads 18313615 Ancelim: Health System Restoration Protocol for Cancer Patients
Authors: Mark Berry
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A number of studies have identified several factors involved in the malignant progression of cancer cells. The Primary modulator in driving inflammation to these transformed cells has been identified as the transcription factor known as nuclear factor-κB. This essential regulator of inflammation and the development of cancer, combined with a microenvironment of inflammation and signaling molecules, plays a major role in the malignant progression of cancer, and this progression is the result of the mutagenic predisposition of persistent substances that combat infection at tumor sites and other areas of chronic inflammation. Inflammation-induced tumors, and their inflammatory cells and regulators may be the primary source of metastasis of tumor cells through angiogenesis. Previous research on cytokines and chemokines, including their downstream targets, has been the focus of the cancer/inflammation connection. The identification of the biological mechanisms of other proteins vital to the inflammation cascade and their interactions are crucial to novel and effective therapeutic protocols for the treatment of inflammation-induced cancers. The Ancelim HSRP Protocol is just such a therapeutic intervention.Keywords: ancelim, cancer, inflammation, tumor
Procedia PDF Downloads 54313614 The Role of Genetic Markers in Prostate Cancer Diagnosis and Treatment
Authors: Farman Ali, Asif Mahmood
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The utilization of genetic markers in prostate cancer management represents a significant advance in personalized medicine, offering the potential for more precise diagnosis and tailored treatment strategies. This paper explores the pivotal role of genetic markers in the diagnosis and treatment of prostate cancer, emphasizing their contribution to the identification of individual risk profiles, tumor aggressiveness, and response to therapy. By integrating current research findings, we discuss the application of genetic markers in developing targeted therapies and the implications for patient outcomes. Despite the promising advancements, challenges such as accessibility, cost, and the need for further validation in diverse populations remain. The paper concludes with an outlook on future directions, underscoring the importance of genetic markers in revolutionizing prostate cancer care.Keywords: prostate cancer, genetic markers, personalized medicine, BRCA1 and BRCA2
Procedia PDF Downloads 6013613 Histopathological Characterization of Prostate Cancer in Saudi Patients
Authors: Nadeem A. Kizilbash
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The study aimed to compare the histopathological characterization of prostate cancer using the conventional and 2005 ISUP modified Gleason system. It employed samples from 40 prostate cancer patients employing resection, biopsies and RP. The majority of cases (95%) comprised adenocarcinoma of the prostate. The results showed that there is migration or upgrading of scores to higher values on using the 2005 ISUP modified Gleason system and an increase in a score of 7 in more than 45% of the cases.Keywords: prostate cancer, conventional gleason grading, 2005 ISUP modified gleason system, histopathology
Procedia PDF Downloads 42513612 Retrospective Study on the Prognosis of Patients with New-Onset Atrial Fibrillation to Evaluate the Risk of Developing Occult Cancer in Absence of Concurrent Chronic Inflammatory Disease
Authors: Helen Huang, Francisco Javier Quesada Ocet, Blanca Quesada Oce, Javier Jimenez Bello, Victor Palanca Gil, Alba Cervero Rubio, Ana Paya Chaume, Alejandro Herreros-Pomares, Fernando Vidal-Vanaclocha, Rafael Paya Serrano, Aurelio Quesada Dorador, Monica Soliman
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Background: Cancer favors both the pro-inflammatory state and autonomic dysfunction, two important mechanisms in the genesis of AF. Atrial remodeling might be caused as a result of paraneoplastic conditions or the result of direct expression of neoplasia. Here, we hypothesize that cancer, through inflammatory mediators, may favor the appearance of AF and patients with the first episode of AF could have a higher risk of developing cancer. Method: Data was collected from patients who attended the emergency department of our hospital for the first episode of AF, diagnosed electrocardiographically, between 2010-2015 (n = 712). The minimum follow-up was 2 years, recording the appearance of cancer, total mortality, recurrences of AF and other events. Patients who developed cancer and those who did not during the 2 years after the onset of AF were compared, as well as with the incidence of cancer in Spain in 2012. Results: After 2 years, 35 patients (4.91%) were diagnosed with cancer, with an annual incidence of 2.45%. Hematological neoplasms were the most frequent (34.28%). The cancer group was older (76.68 +/-12.75 years vs 74.16 +/-12.71; p <0.05) and had fewer typical symptoms (palpitations) (33.38% vs 14.28% , p <0.05). The incidence of cancer in Spain during 2012 was 0.46%, much lower than our sample. When comparing the incidence by age, these differences were maintained both in those over 65 years of age and in those under 65 years of age (2.17% vs. 0.28%; 0.28% vs. 0.18% respectively). Discussion: Therefore, a high incidence of cancer in patients with the first episode of AF was observed (the annual incidence of 2.45% after the onset of AF is 6.1 times that of the general population). After the evaluation of patients with AF in their first detected episode, surveillance of the appearance of cancer should be considered in clinical practice.Keywords: cancer, cardiovascular outcomes, atrial fibrillation, inflammation
Procedia PDF Downloads 14713611 Postoperative Radiotherapy in Cancers of the Larynx: Experience of the Emir Abdelkader Cancer Center of Oran, about 89 Cases
Authors: Taleb Lotfi, Benarbia Maheidine, Allam Hamza, Boutira Fatima, Boukerche Abdelbaki
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Introduction and purpose of the study: This is a retrospective single-center study with an analytical aim to determine the prognostic factors for relapse in patients treated with radiotherapy after total laryngectomy with lymph node dissection for laryngeal cancer at the Emir Abdelkader cancer center in Oran (Algeria). Material and methods: During the study period from January 2014 to December 2018, eighty-nine patients (n=89) with squamous cell carcinoma of the larynx were treated with postoperative radiotherapy. Relapse-free survival was studied in the univariate analysis according to pre-treatment criteria using Kaplan-Meier survival curves. We performed a univariate analysis to identify relapse factors. Statistically significant factors have been studied in the multifactorial analysis according to the Cox model. Results and statistical analysis: The average age was 62.7 years (40-86 years). It was a squamous cell carcinoma in all cases. Postoperatively, the tumor was classified as pT3 and pT4 in 93.3% of patients. Histological lymph node involvement was found in 36 cases (40.4%), with capsule rupture in 39% of cases, while the limits of surgical excision were microscopically infiltrated in 11 patients (12.3%). Chemotherapy concomitant with radiotherapy was used in 67.4% of patients. With a median follow-up of 57 months (23 to 104 months), the probabilities of relapse-free survival and five-year overall survival are 71.2% and 72.4%, respectively. The factors correlated with a high risk of relapse were locally advanced tumor stage pT4 (p=0.001), tumor site in case of subglottic extension (p=0.0003), infiltrated surgical limits R1 (p=0.001), l lymph node involvement (p=0.002), particularly in the event of lymph node capsular rupture (p=0.0003) as well as the time between surgery and adjuvant radiotherapy (p=0.001). However, in the subgroup analysis, the major prognostic factors for disease-free survival were subglottic tumor extension (p=0.001) and time from surgery to adjuvant radiotherapy (p=0.005). Conclusion: Combined surgery and postoperative radiation therapy are effective treatment modalities in the management of laryngeal cancer. Close cooperation of the entire cervicofacial oncology team is essential, expressed during a multidisciplinary consultation meeting, with the need to respect the time between surgery and radiotherapy.Keywords: laryngeal cancer, laryngectomy, postoperative radiotherapy, survival
Procedia PDF Downloads 10213610 A Mathematical Description of a Growing Cell Colony Based on the Mechanical Bidomain Model
Authors: Debabrata Auddya, Bradley J. Roth
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The mechanical bidomain model is used to describe a colony of cells growing on a substrate. Analytical expressions are derived for the intracellular and extracellular displacements. Mechanotransduction events are driven by the difference between the displacements in the two spaces, corresponding to the force acting on integrins. The equation for the displacement consists of two terms: one proportional to the radius that is the same in the intracellular and extracellular spaces (the monodomain term) and one that is proportional to a modified Bessel function that is responsible for mechanotransduction (the bidomain term). The model predicts that mechanotransduction occurs within a few length constants of the colony’s edge, and an expression for the length constant contains the intracellular and extracellular shear moduli and the spring constant of the integrins coupling the two spaces. The model predictions are qualitatively consistent with experiments on human embryonic stem cell colonies, in which differentiation is localized near the edge.Keywords: cell colony, integrin, mechanical bidomain model, stem cell, stress-strain, traction force
Procedia PDF Downloads 23713609 Identification of Bioactive Metabolites from Ficus carica and Their Neuroprotective Effects of Alzheimer's Disease
Authors: Hanan Khojah, RuAngelie Edrada-Ebel
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Neurodegenerative disease including Alzheimer’s disease is a major cause of long-term disability. Oxidative stress is frequently implicated as one of the key contributing factors to neurodegenerative diseases. Protection against neuronal damage remains a great challenge for researchers. Ficus carica (commonly known as fig) is a species of great antioxidant nutritional value comprising a protective mechanism against innumerable health disorders related to oxidative stress as well as Alzheimer’s disease. The purpose of this work was to characterize the non-polar active metabolites in Ficus carica endocarp, mesocarp, and exocarp. Crude extracts were prepared using several extraction solvents, which included 1:1 water: ethylacetate, acetone and methanol. The dried extracts were then solvent partitioned between equivalent amounts of water and ethylacetate. Purification and fractionation were accomplished by high-throughput chromatography. The isolated metabolites were tested on their effect on human neuroblastoma cell line by cell viability test and cell cytotoxicity assay with acrolein. Molecular weights of the active metabolites were determined via LC–HRESIMS and GC-EIMS. Metabolomic profiling was performed to identify the active metabolites by using differential expression analysis software (Mzmine) and SIMCA for multivariate analysis. Structural elucidation and identification of the interested active metabolites were studied by 1-D and 2-D NMR. Significant differences in bioactivity against a concentration-dependent assay on acrolein radicals were observed between the three fruit parts. However, metabolites obtained from mesocarp and the endocarp demonstrated bioactivity to scavenge ROS radical. NMR profiling demonstrated that aliphatic compounds such as γ-sitosterol tend to induce neuronal bioactivity and exhibited bioactivity on the cell viability assay. γ-Sitosterol was found in higher concentrations in the mesocarp and was considered as one of the major phytosterol in Ficus carica.Keywords: alzheimer, Ficus carica, γ-Sitosterol, metabolomics
Procedia PDF Downloads 34213608 Expanding the Therapeutic Utility of Curcumin
Authors: Azza H. El-Medany, Hanan H. Hagar, Omnia A. Nayel, Jamila H. El-Medany
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In search for drugs that can target cancer cell micro-environment in as much as being able to halt malignant cellular transformation, the natural dietary phytochemical curcumin was currently assessed in DMH-induced colorectal cancer rat model. The study enrolled 50 animals divided into a control group (n=10) and DMH-induced colorectal cancer control group (n=20) (20mg/kg-body weight for 28 weeks) versus curcumin-treated group (n=20) (160 mg/kg suspension daily oral for further 8 weeks). Treatment by curcumin succeeded to significantly decrease the percent of ACF and tended to normalize back the histological changes retrieved in adenomatous and stromal cells induced by DMH. The drug also significantly elevated GSH and significantly reduced most of the accompanying biochemical elevations (namely MDA, TNF-α, TGF-β and COX2) observed in colonic carcinomatous tissue, induced by DMH, thus succeeding to revert that of MDA, COX2 and TGF-β back to near normal as justified by being non-significantly altered as compared to normal controls. The only exception was PAF that was insignificantly altered by the drug. When taken together, it could be concluded that curcumin possess the potentiality to halt some of the orchestrated cross-talk between cancerous transformation and its micro-environmental niche that contributes to cancer initiation, progression and metastasis in this experimental cancer colon model. Envisioning these merits to a drug with already known safety preferentiality, awaits final results of current ongoing clinical trials, before curcumin can be added to the new therapeutic armamentarium of anticancer therapy.Keywords: curcumin, dimethyl hydralazine, aberrant crypt foci, malondialdehyde, reduced glutathione, cyclooxygenase-2, tumour necrosis factor-alpha, transforming growth factor-beta, platelet activating factor
Procedia PDF Downloads 29413607 Transforming Butterworth Low Pass Filter into Microstrip Line Form at LC-Band Applications
Authors: Liew Hui Fang, Syed Idris Syed Hassan, Mohd Fareq Abd. Malek, Yufridin Wahab, Norshafinash Saudin
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The paper implementation new approach method applied into transforming lumped element circuit into microstrip line form for Butterworth low pass filter which is operating at LC band. The filter’s lumped element circuits and microstrip line form were first designed and simulated using Advanced Design Software (ADS) to obtain the best filter characteristic based on S-parameter and implemented on FR4 substrate for order N=3,4,5,6,7,8 and 9. The importance of a new approach of transforming method as a correction factor has been considered into designed microstrip line. From ADS simulation results proved that the response of microstrip line circuit of Butterworth low pass filter with fringing correction factor has an excellent agreement with its lumped circuit. This shows that the new approach of transforming lumped element circuit into microstrip line is able to solve the conventional design of complexity size of circuit of Butterworth low pass filter (LPF) into microstrip line.Keywords: Butterworth low pass filter, number of order, microstrip line, microwave filter, maximally flat
Procedia PDF Downloads 33213606 Synthesis and Application of Oligosaccharides Representing Plant Cell Wall Polysaccharides
Authors: Mads H. Clausen
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Plant cell walls are structurally complex and contain a larger number of diverse carbohydrate polymers. These plant fibers are a highly valuable bio-resource and the focus of food, energy and health research. We are interested in studying the interplay of plant cell wall carbohydrates with proteins such as enzymes, cell surface lectins and antibodies. However, detailed molecular level investigations of such interactions are hampered by the heterogeneity and diversity of the polymers of interest. To circumvent this, we target well-defined oligosaccharides with representative structures that can be used for characterizing protein-carbohydrate binding. The presentation will highlight chemical syntheses of plant cell wall oligosaccharides from our group and provide examples from studies of their interactions with proteins.Keywords: oligosaccharides, carbohydrate chemistry, plant cell walls, carbohydrate-acting enzymes
Procedia PDF Downloads 30813605 Title: Real World Evidence a Tool to Overcome the Lack of a Comparative Arm in Drug Evaluation in the Context of Rare Diseases
Authors: Mohamed Wahba
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Objective: To build a comparative arm for product (X) in specific gene mutated advanced gastrointestinal cancer using real world evidence to fulfill HTA requirements in drug evaluation. Methods: Data for product (X) were collected from phase II clinical trial while real world data for (Y) and (Z) were collected from US database. Real-world (RW) cohorts were matched to clinical trial base line characteristics using weighting by odds method. Outcomes included progression-free survival (PFS) and overall survival (OS) rates. Study location and participants: Internationally (product X, n=80) and from USA (Product Y and Z, n=73) Results: Two comparisons were made: trial cohort 1 (X) versus real-world cohort 1 (Z), trial cohort 2 (X) versus real-world cohort 2 (Y). For first line, the median OS was 9.7 months (95% CI 8.6- 11.5) and the median PFS was 5.2 months (95% CI 4.7- not reached) for real-world cohort 1. For second line, the median OS was 10.6 months (95% CI 4.7- 27.3) for real-world cohort 2 and the median PFS was 5.0 months (95% CI 2.1- 29.3). For OS analysis, results were statistically significant but not for PFS analysis. Conclusion: This study provided the clinical comparative outcomes needed for HTA evaluation.Keywords: real world evidence, pharmacoeconomics, HTA agencies, oncology
Procedia PDF Downloads 8913604 Therapeutic Potential of Cannabis in Cancer: Advances in Clinical Research and Pharmacogenomic Aspects
Authors: Bouchaïb Gazzaz, Hamid El Amri, Hind Dehbi, Abderraouf Hilali
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Medical cannabis has been cultivated and used in many countries around the world. The story of the use of cannabis as a therapeutic agent is difficult to trace, in particular, because the laws regulating its production, distribution, possession, and consumption are relatively recent. Nowadays, in countries where it is authorized, medical cannabis is used in a very wide variety of illnesses and pathologies, particularly in cancer cures. Presently, cannabinoid receptor agonists (like nabilone and dronabinol) are used for reducing chemotherapy induced vomiting. This review aims to discuss a recent finding on the use of therapeutic cannabis in patients with cancer. First, this work addresses the progress made in the use of cannabinoids as therapeutic agent and their application in the treatment of different types of cancer. Secondly, a detailed analysis of the pharmacogenetic aspect of cannabis will be discussed.Keywords: cannabinoids, endocannabinoids system, cancer treatment, cannabinoid receptors, genetic polymorphism, pharmacogenomics
Procedia PDF Downloads 14213603 Inducible Trans-Encapsidation System for Temporal Separation of Hepatitis C Virus Life Cycle
Authors: Ovidiu Vlaicu, Leontina Banica, Dan Otelea, Andrei-Jose Petrescu, Costin-Ioan Popescu
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Hepatitis C Virus (HCV) infects 170 million peoples worldwide. Major advances have been made recently in HCV standard of care with interferon-free therapy being already approved. Despite major progress in HCV therapy, the genotype associated treatment efficacy and toxicity still represent issues to address. To identify endogenous factors involved in different stages of HCV life cycle, we have developed a trans-packaging system for HCV subgenomic replicons lacking core protein gene. Huh7 cells were used to generate a packaging cell line expressing the core protein in an inducible manner. The core packaging cell line was able to trans-complemented various subgenomic replicons to secret infectious trans-complemented HCV particles (HCV-TCP). Further, we constructed subgenomic replicons with foreign epitopes suitable for immunoaffinity purification or fluorescence microscopy studies. We have shown that the insertion has not effects on the efficacy of trans-complementation yielding similar titers to the control subgenomic replicon. This system will be a valuable tool in studying pre- and post-assembly events in HCV life cycle and for the fast identification of HCV assembly inhibitors.Keywords: assembly inhibitors, core protein, HCV, trans-complementation
Procedia PDF Downloads 29113602 Structural Evaluation of Cell-Filled Pavement
Authors: Subrat Roy
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This paper describes the findings of a study carried out for evaluating the performance of cell-filled pavement for low volume roads. Details of laboratory investigations and the methodology adopted for construction of cell-filled pavement are presented. The aim of this study is to evaluate the structural behaviour of cement concrete filled cell pavement laid over three different types of subbases (water bound macadam, soil-cement and moorum). A formwork of cells of a thin plastic sheet was used to construct the cell-filled pavements to form flexible, interlocked block pavements. Surface deflections were measured using falling weight deflectometer and benkelman beam methods. Resilient moduli of pavement layers were estimated from the measured deflections. A comparison of deflections obtained from both the methodology is also presented.Keywords: cell-filled pavement, WBM, FWD, Moorum
Procedia PDF Downloads 29613601 The Mediating Role of Resilience in the Association Between Stigma and Psychosocial Adjustment: A Cross-sectional Study Among Young and Middle-Aged Patients With Lung Cancer
Authors: Ziyun Li, Jiudi Zhong, June Zhang
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Background: The diagnosis and treatment of lung cancer lead to varying degrees of psychological and social maladjustment among patients with lung cancer. Understanding psychosocial adjustment (PA) and its influencing factors in young and middle-aged lung cancer patients is essential to help them return to society and lead a normal life. Objectives: This study aims to examine the mediating role of resilience in the association between stigma and psychosocial adjustment among young and middle-aged patients with lung cancer. Methods: A total of 235 patients with lung cancer were recruited from a tertiary grade A cancer center in southern China and investigated using a self-designed general information questionnaire, Psychosocial Adjustment to Illness Scale Self-Report, Social Impact Scale, and Conner-Davidson Resilience Scale. Results: The mean score of PA was (32.61±14.75), and its influencing factors included treatment modalities, stigma, and resilience. The total effect of stigma on PA was significant (total effect=0.418, SE=0.045, 95%CI [0.310-0.497]), and a positive indirect effect was identified for stigma on PA via resilience (indirect effect=0.143, SE=0.041, 95% CI [0.075-0.236]). Conclusion: Stigma and resilience are significantly associated with PA, and resilience is also a mediating variable between stigma and PA. This study suggests that individualized interventions can be made to improve the PA by alleviating their stigma, or by enhancing their resilience in young and middle-aged lung cancer patients.Keywords: psychosocial adjustment, lung cancer, cancer caring, nursing, young and middle-aged
Procedia PDF Downloads 8913600 First Experimental Evidence on Feasibility of Molecular Magnetic Particle Imaging of Tumor Marker Alpha-1-Fetoprotein Using Antibody Conjugated Nanoparticles
Authors: Kolja Them, Priyal Chikhaliwala, Sudeshna Chandra
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Purpose: The purpose of this work is to examine possibilities for noninvasive imaging and identification of tumor markers for cancer diagnosis. The proposed method uses antibody conjugated iron oxide nanoparticles and multicolor Magnetic Particle Imaging (mMPI). The method has the potential for radiation exposure free real-time estimation of local tumor marker concentrations in vivo. In this study, the method is applied to human Alpha-1-Fetoprotein. Materials and Methods: As tracer material AFP antibody-conjugated Dendrimer-Fe3O4 nanoparticles were used. The nanoparticle bioconjugates were then incubated with bovine serum albumin (BSA) to block any possible nonspecific binding sites. Parts of the resulting solution were then incubated with AFP antigen. MPI measurements were done using the preclinical MPI scanner (Bruker Biospin MRI GmbH) and the multicolor method was used for image reconstruction. Results: In multicolor MPI images the nanoparticles incubated only with BSA were clearly distinguished from nanoparticles incubated with BSA and AFP antigens. Conclusion: Tomographic imaging of human tumor marker Alpha-1-Fetoprotein is possible using AFP antibody conjugated iron oxide nanoparticles in presence of BSA. This opens interesting perspectives for cancer diagnosis.Keywords: noninvasive imaging, tumor antigens, antibody conjugated iron oxide nanoparticles, multicolor magnetic particle imaging, cancer diagnosis
Procedia PDF Downloads 30213599 Parental Monitoring of Learners’ Cell Phone Use in the Eastern Cape, South Africa
Authors: Melikhaya Skhephe, Robert Mawuli Kwasi Boadzo, Zanoxolo Berington Gobingca
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This research study sought to examine parental monitoring of learners’ cell phone use in the Eastern Cape, South Africa. To this end, the researchers employed a quantitative approach. Data were obtained through questionnaires, with a sample of 15 parents having been purposively selected. The findings revealed that parents are unaware that they have to monitor the learner’s cell phone. Another finding was that parents in the 21-century did not support the use of mobile phones in education. The researchers recommend that parent’s discussion forums be created to educate parents on how a cell phone can be used in education. Cellphone companies need to be encouraged to educate parents on how they monitor cell phones used by learners. Another recommendation was that network providers need to restrict access to searching on the internet according to age.Keywords: parental monitoring, app blocking services, learner’s cell phone use, cell phone
Procedia PDF Downloads 15913598 Design and Implementation of a Control System for a Walking Robot with Color Sensing and Line following Using PIC and ATMEL Microcontrollers
Authors: Ibraheem K. Ibraheem
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The aim of this research is to design and implement line-tracking mobile robot. The robot must follow a line drawn on the floor with different color, avoids hitting moving object like another moving robot or walking people and achieves color sensing. The control system reacts by controlling each of the motors to keep the tracking sensor over the middle of the line. Proximity sensors used to avoid hitting moving objects that may pass in front of the robot. The programs have been written using micro c instructions, then converted into PIC16F887 ATmega48/88/168 microcontrollers counterparts. Practical simulations show that the walking robot accurately achieves line following action and exactly recognizes the colors and avoids any obstacle in front of it.Keywords: color sensing, H-bridge, line following, mobile robot, PIC microcontroller, obstacle avoidance, phototransistor
Procedia PDF Downloads 39513597 A Serum- And Feeder-Free Culture System for the Robust Generation of Human Stem Cell-Derived CD19+ B Cells and Antibody-Secreting Cells
Authors: Kirsten Wilson, Patrick M. Brauer, Sandra Babic, Diana Golubeva, Jessica Van Eyk, Tinya Wang, Avanti Karkhanis, Tim A. Le Fevre, Andy I. Kokaji, Allen C. Eaves, Sharon A. Louis, , Nooshin Tabatabaei-Zavareh
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Long-lived plasma cells are rare, non-proliferative B cells generated from antibody-secreting cells (ASCs) following an immune response to protect the host against pathogen re-exposure. Despite their therapeutic potential, the lack of in vitro protocols in the field makes it challenging to use B cells as a cellular therapeutic tool. As a result, there is a need to establish robust and reproducible methods for the generation of B cells. To address this, we have developed a culture system for generating B cells from hematopoietic stem and/or progenitor cells (HSPCs) derived from human umbilical cord blood (CB) or pluripotent stem cells (PSCs). HSPCs isolated from CB were cultured using the StemSpan™ B Cell Generation Kit and produced CD19+ B cells at a frequency of 23.2 ± 1.5% and 59.6 ± 2.3%, with a yield of 91 ± 11 and 196 ± 37 CD19+ cells per input CD34+ cell on culture days 28 and 35, respectively (n = 50 - 59). CD19+IgM+ cells were detected at a frequency of 31.2 ± 2.6% and were produced at a yield of 113 ± 26 cells per input CD34+ cell on culture day 35 (n = 50 - 59). The B cell receptor loci of CB-derived B cells were sequenced to confirm V(D)J gene rearrangement. ELISpot analysis revealed that ASCs were generated at a frequency of 570 ± 57 per 10,000 day 35 cells, with an average IgM+ ASC yield of 16 ± 2 cells per input CD34+ cell (n = 33 - 42). PSC-derived HSPCs were generated using the STEMdiff™ Hematopoietic - EB reagents and differentiated to CD10+CD19+ B cells with a frequency of 4 ± 0.8% after 28 days of culture (n = 37, 1 embryonic and 3 induced pluripotent stem cell lines tested). Subsequent culture of PSC-derived HSPCs increased CD19+ frequency and generated ASCs from 1 - 2 iPSC lines. This method is the first report of a serum- and feeder-free system for the generation of B cells from CB and PSCs, enabling further B lineage-specific research for potential future clinical applications.Keywords: stem cells, B cells, immunology, hematopoiesis, PSC, differentiation
Procedia PDF Downloads 5713596 Identification of miRNA-miRNA Interactions between Virus and Host in Human Cytomegalovirus Infection
Authors: Kai-Yao Huang, Tzong-Yi Lee, Pin-Hao Ho, Tzu-Hao Chang, Cheng-Wei Chang
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Background: Human cytomegalovirus (HCMV) infects much people around the world, and there were many researches mention that many diseases were caused by HCMV. To understand the mechanism of HCMV lead to diseases during infection. We observe a microRNA (miRNA) – miRNA interaction between HCMV and host during infection. We found HCMV miRNA sequence component complementary with host miRNA precursors, and we also found that the host miRNA abundances were decrease in HCMV infection. Hence, we focus on the host miRNA which may target by the other HCMV miRNA to find theirs target mRNAs expression and analysis these mRNAs affect what kind of signaling pathway. Interestingly, we found the affected mRNA play an important role in some diseases related pathways, and these diseases had been annotated by HCMV infection. Results: From our analysis procedure, we found 464 human miRNAs might be targeted by 26 HCMV miRNAs and there were 291 human miRNAs shows the concordant decrease trend during HCMV infection. For case study, we found hcmv-miR-US22-5p may regulate hsa-mir-877 and we analysis the KEGG pathway which built by hsa-mir-877 validate target mRNA. Additionally, through survey KEGG Disease database found that these mRNA co-regulate some disease related pathway for instance cancer, nerve disease. However, there were studies annotated that HCMV infection casuse cancer and Alzheimer. Conclusions: This work supply a different scenario of miRNA target interactions(MTIs). In previous study assume miRNA only target to other mRNA. Here we wonder there is possibility that miRNAs might regulate non-mRNA targets, like other miRNAs. In this study, we not only consider the sequence similarity with HCMV miRNAs and human miRNA precursors but also the expression trend of these miRNAs. Then we analysis the human miRNAs validate target mRNAs and its associated KEGG pathway. Finally, we survey related works to validate our investigation.Keywords: human cytomegalovirus, HCMV, microRNA, miRNA
Procedia PDF Downloads 43313595 Developing Motorized Spectroscopy System for Tissue Scanning
Authors: Tuba Denkceken, Ayse Nur Sarı, Volkan Ihsan Tore, Mahmut Denkceken
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The aim of the presented study was to develop a newly motorized spectroscopy system. Our system is composed of probe and motor parts. The probe part consists of bioimpedance and fiber optic components that include two platinum wires (each 25 micrometer in diameter) and two fiber cables (each 50 micrometers in diameter) respectively. Probe was examined on tissue phantom (polystyrene microspheres with different diameters). In the bioimpedance part of the probe current was transferred to the phantom and conductivity information was obtained. Adjacent two fiber cables were used in the fiber optic part of the system. Light was transferred to the phantom by fiber that was connected to the light source and backscattered light was collected with the other adjacent fiber for analysis. It is known that the nucleus expands and the nucleus-cytoplasm ratio increases during the cancer progression in the cell and this situation is one of the most important criteria for evaluating the tissue for pathologists. The sensitivity of the probe to particle (nucleus) size in phantom was tested during the study. Spectroscopic data obtained from our system on phantom was evaluated by multivariate statistical analysis. Thus the information about the particle size in the phantom was obtained. Bioimpedance and fiber optic experiments results which were obtained from polystyrene microspheres showed that the impedance value and the oscillation amplitude were increasing while the size of particle was enlarging. These results were compatible with the previous studies. In order to motorize the system within the motor part, three driver electronic circuits were designed primarily. In this part, supply capacitors were placed symmetrically near to the supply inputs which were used for balancing the oscillation. Female capacitors were connected to the control pin. Optic and mechanic switches were made. Drivers were structurally designed as they could command highly calibrated motors. It was considered important to keep the drivers’ dimension as small as we could (4.4x4.4x1.4 cm). Then three miniature step motors were connected to each other along with three drivers. Since spectroscopic techniques are quantitative methods, they yield more objective results than traditional ones. In the future part of this study, it is planning to get spectroscopic data that have optic and impedance information from the cell culture which is normal, low metastatic and high metastatic breast cancer. In case of getting high sensitivity in differentiated cells, it might be possible to scan large surface tissue areas in a short time with small steps. By means of motorize feature of the system, any region of the tissue will not be missed, in this manner we are going to be able to diagnose cancerous parts of the tissue meticulously. This work is supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK) through 3001 project (115E662).Keywords: motorized spectroscopy, phantom, scanning system, tissue scanning
Procedia PDF Downloads 19013594 Mathematical Modeling of Cell Volume Alterations under Different Osmotic Conditions
Authors: Juliana A. Knocikova, Yann Bouret, Médéric Argentina, Laurent Counillon
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Cell volume, together with membrane potential and intracellular hydrogen ion concentration, is an essential biophysical parameter for normal cellular activity. Cell volumes can be altered by osmotically active compounds and extracellular tonicity. In this study, a simple mathematical model of osmotically induced cell swelling and shrinking is presented. Emphasis is given to water diffusion across the membrane. The mathematical description of the cellular behavior consists in a system of coupled ordinary differential equations. We compare experimental data of cell volume alterations driven by differences in osmotic pressure with mathematical simulations under hypotonic and hypertonic conditions. Implications for a future model are also discussed.Keywords: eukaryotic cell, mathematical modeling, osmosis, volume alterations
Procedia PDF Downloads 46113593 Contact Address Levels and Human Health Risk of Metals In Milk and Milk Products Bought from Abeokuta, Southwestern Nigeria
Authors: Olukayode Bamgbose, Feyisola Agboola, Adewale M. Taiwo, Olanrewaju Olujimi Oluwole Terebo, Azeez Soyingbe, Akeem Bamgbade
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The present study evaluated the contents and health risk assessment of metals determined in milk and milk product samples collected from the Abeokuta market. Forty-five milk and milk product (yoghurt) samples were digested and analysed for selected metals using Atomic Absorption Spectrophotometric method. Health risk assessment was evaluated for hazard quotient (HQ), hazard index (HI), and cancer risk (CR). Data were subjected to descriptive and inferential statistics. The concentrations of Zn, which ranged from 3.24±0.59 to 4.35±0.59 mg/kg, were the highest in the samples. Cr and Cd were measured below the detection limit of the analytical instrument, while the Pb level was higher than the Codex Alimentarius Commission value of 0.02 mg/kg, indicating unsafe for consumption. However, the HQ of Pb and other metals in milk and milk product samples was less than 1.0, thereby establishing no adverse health effects for Pb and other metals. The distribution pattern of metals in milk and milk product samples followed the decreasing order of Zn > Fe > Ni > Co > Cu > Mn > Pb > Cd/Cr. The CR levels of meals were also less than the permissible limit of 1.0 x 10-4, establishing no possible development of cancer. Keywords: adverse effects, cancer, metals, milk, milk product, the permissible limit.Keywords: adverse effects, cancer, metals, milk, milk product, permissible limit
Procedia PDF Downloads 7813592 Cancer Patients' Quality of Life and Fatigue: A Correlational Study
Authors: Abdul-Monim Batiha
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Aim: The aim of this study were to correlate Jordanian cancer patients’ quality of life and fatigue with selected variables (age, sex, religion, marital status, level of education, type of cancer, number of people living in the same household, type of radiotherapy, dose of radiotherapy, and hemoglobin level). Background: Radiotherapy and chemotherapy remain devastating agents that altered patients’ normal lives. Methods: A correlational design was used in this study to 80 cancer patients and required radiotherapy treatment using a convenience sampling procedure. Results: No significant differences were found in the relationship between quality of life scores and selected variables. A significant negative relationship was found between quality of life scores and the side effects of radiotherapy treatment. Significant positive relationships were found between fatigue scores measured by Piper Fatigue Scale and cancer complications, and radiotherapy side effects. Conclusion: Cancer patients’ quality of life and fatigue are affected by radiotherapy’s side effects and cancer complications. Implications for Nursing: Nurses should try to prevent and manage the negative side effects of radiotherapy and complications of cancer. Such an initiative would serve to design specific nursing interventions that have the potential to help patients enjoy their lives and perform their activities.Keywords: cancer patients, piper fatigue scale, fatigue, quality of life, radiotherapy
Procedia PDF Downloads 53613591 An Unbiased Profiling of Immune Repertoire via Sequencing and Analyzing T-Cell Receptor Genes
Authors: Yi-Lin Chen, Sheng-Jou Hung, Tsunglin Liu
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Adaptive immune system recognizes a wide range of antigens via expressing a large number of structurally distinct T cell and B cell receptor genes. The distinct receptor genes arise from complex rearrangements called V(D)J recombination, and constitute the immune repertoire. A common method of profiling immune repertoire is via amplifying recombined receptor genes using multiple primers and high-throughput sequencing. This multiplex-PCR approach is efficient; however, the resulting repertoire can be distorted because of primer bias. To eliminate primer bias, 5’ RACE is an alternative amplification approach. However, the application of RACE approach is limited by its low efficiency (i.e., the majority of data are non-regular receptor sequences, e.g., containing intronic segments) and lack of the convenient tool for analysis. We propose a computational tool that can correctly identify non-regular receptor sequences in RACE data via aligning receptor sequences against the whole gene instead of only the exon regions as done in all other tools. Using our tool, the remaining regular data allow for an accurate profiling of immune repertoire. In addition, a RACE approach is improved to yield a higher fraction of regular T-cell receptor sequences. Finally, we quantify the degree of primer bias of a multiplex-PCR approach via comparing it to the RACE approach. The results reveal significant differences in frequency of VJ combination by the two approaches. Together, we provide a new experimental and computation pipeline for an unbiased profiling of immune repertoire. As immune repertoire profiling has many applications, e.g., tracing bacterial and viral infection, detection of T cell lymphoma and minimal residual disease, monitoring cancer immunotherapy, etc., our work should benefit scientists who are interested in the applications.Keywords: immune repertoire, T-cell receptor, 5' RACE, high-throughput sequencing, sequence alignment
Procedia PDF Downloads 19213590 Basal Cell Carcinoma: Epidemiological Analysis of a 5-Year Period in a Brazilian City with a High Level of Solar Radiation
Authors: Maria E. V. Amarante, Carolina L. Cerdeira, Julia V. Cortes, Fiorita G. L. Mundim
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Basal cell carcinoma (BCC) is the most prevalent type of skin cancer in humans. It arises from the basal cells of the epidermis and cutaneous appendages. The role of sunlight exposure as a risk factor for BCC is very well defined due to its power to influence genetic mutations, in addition to having a suppressor effect on the skin immune system. Despite showing low metastasis and mortality rates, the tumor is locally infiltrative, aggressive, and destructive. Considering the high prevalence rate of this carcinoma and the importance of early detection, a retrospective study was carried out in order to correlate the clinical data available on BBC, characterize it epidemiologically, and thus enable effective prevention measures for the population. Data on the period from January 2015 to December 2019 were collected from the medical records of patients registered at one pathology service located in the southeast region of Brazil, known as SVO, which delivers skin biopsy results. The study was aimed at correlating the variables, sex, age, and subtypes found. Data analysis was performed using the chi-square test at a nominal significance level of 5% in order to verify the independence between the variables of interest. Fisher's exact test was applied in cases where the absolute frequency in the cells of the contingency table was less than or equal to five. The statistical analysis was performed using the R® software. Ninety-three basal cell carcinoma were analyzed, and its frequency in the 31-to 45-year-old age group was 5.8 times higher in men than in women, whereas, from 46 to 59 years, the frequency was found 2.4 times higher in women than in men. Between the ages of 46 to 59 years, it should be noted that the sclerodermiform subtype appears more than the solid one, with a difference of 7.26 percentage points. Reversely, the solid form appears more frequently in individuals aged 60 years or more, with a difference of 8.57 percentage points. Among women, the frequency of the solid subtype was 9.93 percentage points higher than the sclerodermiform frequency. In males, the same percentage difference is observed, but sclerodermiform is the most prevalent subtype. It is concluded in this study that, in general, there is a predominance of basal cell carcinoma in females and in individuals aged 60 years and over, which demonstrates the tendency of this tumor. However, when rarely found in younger individuals, the male gender prevailed. The most prevalent subtype was the solid one. It is worth mentioning that the sclerodermiform subtype, which is more aggressive, was seen more frequently in males and in the 46-to 59-year-old range.Keywords: basal cell carcinoma, epidemiology, sclerodermiform basal cell carcinoma, skin cancer, solar radiation, solid basal cell carcinoma
Procedia PDF Downloads 13813589 Characterization of Transmembrane Proteins with Five Alpha-Helical Regions
Authors: Misty Attwood, Helgi Schioth
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Transmembrane proteins are important components in many essential cell processes such as signal transduction, cell-cell signalling, transport of solutes, structural adhesion activities, and protein trafficking. Due to their involvement in diverse critical activities, transmembrane proteins are implicated in different disease pathways and hence are the focus of intense interest in understanding functional activities, their pathogenesis in disease, and their potential as pharmaceutical targets. Further, as the structure and function of proteins are correlated, investigating a group of proteins with the same tertiary structure, i.e., the same number of transmembrane regions, may give understanding about their functional roles and potential as therapeutic targets. In this in silico bioinformatics analysis, we identify and comprehensively characterize the previously unstudied group of proteins with five transmembrane-spanning regions (5TM). We classify nearly 60 5TM proteins in which 31 are members of ten families that contain two or more family members and all members are predicted to contain the 5TM architecture. Furthermore, nine singlet proteins that contain the 5TM architecture without paralogues detected in humans were also identifying, indicating the evolution of single unique proteins with the 5TM structure. Interestingly, more than half of these proteins function in localization activities through movement or tethering of cell components and more than one-third are involved in transport activities, particularly in the mitochondria. Surprisingly, no receptor activity was identified within this family in sharp contrast with other TM families. Three major 5TM families were identified and include the Tweety family, which are pore-forming subunits of the swelling-dependent volume regulated anion channel in astrocytes; the sidoreflexin family that acts as mitochondrial amino acid transporters; and the Yip1 domain family engaged in vesicle budding and intra-Golgi transport. About 30% of the proteins have enhanced expression in the brain, liver, or testis. Importantly, 60% of these proteins are identified as cancer prognostic markers, where they are associated with clinical outcomes of various tumour types, indicating further investigation into the function and expression of these proteins is important. This study provides the first comprehensive analysis of proteins with 5TM regions and provides details of the unique characteristics and application in pharmaceutical development.Keywords: 5TM, cancer prognostic marker, drug targets, transmembrane protein
Procedia PDF Downloads 10813588 Dynamic Thermal Modelling of a PEMFC-Type Fuel Cell
Authors: Marco Avila Lopez, Hasnae Ait-Douchi, Silvia De Los Santos, Badr Eddine Lebrouhi, Pamela Ramírez Vidal
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In the context of the energy transition, fuel cell technology has emerged as a solution for harnessing hydrogen energy and mitigating greenhouse gas emissions. An in-depth study was conducted on a PEMFC-type fuel cell, with an initiation of an analysis of its operational principles and constituent components. Subsequently, the modelling of the fuel cell was undertaken using the Python programming language, encompassing both steady-state and transient regimes. In the case of the steady-state regime, the physical and electrochemical phenomena occurring within the fuel cell were modelled, with the assumption of uniform temperature throughout all cell compartments. Parametric identification was carried out, resulting in a remarkable mean error of only 1.62% when the model results were compared to experimental data documented in the literature. The dynamic model that was developed enabled the scrutiny of the fuel cell's response in terms of temperature and voltage under varying current conditions.Keywords: fuel cell, modelling, dynamic, thermal model, PEMFC
Procedia PDF Downloads 8013587 Alternative General Formula to Estimate and Test Influences of Early Diagnosis on Cancer Survival
Authors: Li Yin, Xiaoqin Wang
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Background and purpose: Cancer diagnosis is part of a complex stochastic process, in which patients' personal and social characteristics influence the choice of diagnosing methods, diagnosing methods, in turn, influence the initial assessment of cancer stage, the initial assessment, in turn, influences the choice of treating methods, and treating methods in turn influence cancer outcomes such as cancer survival. To evaluate diagnosing methods, one needs to estimate and test the causal effect of a regime of cancer diagnosis and treatments. Recently, Wang and Yin (Annals of statistics, 2020) derived a new general formula, which expresses these causal effects in terms of the point effects of treatments in single-point causal inference. As a result, it is possible to estimate and test these causal effects via point effects. The purpose of the work is to estimate and test causal effects under various regimes of cancer diagnosis and treatments via point effects. Challenges and solutions: The cancer stage has influences from earlier diagnosis as well as on subsequent treatments. As a consequence, it is highly difficult to estimate and test the causal effects via standard parameters, that is, the conditional survival given all stationary covariates, diagnosing methods, cancer stage and prognosis factors, treating methods. Instead of standard parameters, we use the point effects of cancer diagnosis and treatments to estimate and test causal effects under various regimes of cancer diagnosis and treatments. We are able to use familiar methods in the framework of single-point causal inference to accomplish the task. Achievements: we have applied this method to stomach cancer survival from a clinical study in Sweden. We have studied causal effects under various regimes, including the optimal regime of diagnosis and treatments and the effect moderation of the causal effect by age and gender.Keywords: cancer diagnosis, causal effect, point effect, G-formula, sequential causal effect
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