Search results for: TNBC: triple negative breast cancer

Authors: Sara Przetocka, Krzysztof Żak, Grzegorz Dubin, Tadeusz Holak

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Toll-like receptors (TLRs) play central role in the innate immune response and inflammation by recognizing pathogen-associated molecular patterns (PAMPs). A fundamental basis of TLR signalling is dependent upon the recruitment and association of adaptor molecules that contain the structurally conserved Toll/interleukin-1 receptor (TIR) domain. MyD88 (myeloid differentiation primary response gene 88) is the universal adaptor for TLRs and cooperates with Mal (MyD88 adapter-like protein, also known as TIRAP) in TLR4 response which is predominantly used in inflammation, host defence and carcinogenesis. Up to date two possible models of MyD88, Mal and TLR4 interactions have been proposed. The aim of our studies is to confirm or abolish presented models and accomplish the full structural characterisation of TIR domains interaction. Using molecular cloning methods we obtained several construct of MyD88 and Mal TIR domain with GST or 6xHis tag. Gel filtration method as well as pull-down analysis confirmed that recombinant TIR domains from MyD88 and Mal are binding in complexes. To examine whether obtained complexes are homo- or heterodimers we carried out cross-linking reaction of TIR domains with BS3 compound combined with mass spectrometry. To investigate which amino acid residues are involved in this interaction the NMR titration experiments were performed. 15N MyD88-TIR solution was complemented with non-labelled Mal-TIR. The results undoubtedly indicate that MyD88-TIR interact with Mal-TIR. Moreover 2D spectra demonstrated that simultaneously Mal-TIR self-dimerization occurs which is necessary to create proper scaffold for Mal-TIR and MyD88-TIR interaction. Final step of this study will be crystallization of MyD88 and Mal TIR domains complex. This crystal structure and characterisation of its interface will have an impact in understanding the TLR signalling pathway and possibly will be used in development of new anti-cancer treatment.

Keywords: cancer, MyD88, TIR domains, Toll-like receptors

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Authors: Jodie Bradnam, Mark Edwards, Bruce Watt

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Mobile technologies have emerged as tools to create and sustain social and romantic relationships. The integration of technologies in close relationships has been of particular research interest with findings supporting the positive role of mobile phones in nurturing feelings of closeness and connection. More recently, the use of text messaging to manage conflict has become a focus of research attention. Four hundred and eleven adults in committed romantic relationships completed a series of questionnaires measuring attachment orientation, relationship quality, texting frequencies, attitudes, and response expectations. Attachment orientation, relationship length, texting for connection and disconnection were significant predictors of relationship quality, specifically relationship intimacy. Text frequency varied as a function of attachment orientation, with high attachment anxiety associated with high texting frequencies and with low relationship quality. Sending text messages of love and support was related to higher intimacy and relationship satisfaction scores, while sending critical or impersonal texts was associated with significantly lower intimacy and relationship satisfaction scores. The use of texting to manage relational conflict was a stronger negative predictor of relationship satisfaction than was the use of texting to express love and affection. Consistent with research on face-to-face communication in couples, the expression of negative sentiments via text were related to lower relationship quality, and these negative sentiments had a stronger and more enduring impact on relationship quality than did the expression of positive sentiments. Attachment orientation, relationship length and relationship status emerged as variables of interest in understanding the use of mobile technologies in romantic relationships.

Keywords: attachment, destructive conflict, intimacy, mobile communication, relationship quality, relationship satisfaction, texting

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Authors: Hussain-Abdulah Arjmand, Nikki S. Rickard

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The response to stress can be highly heterogenous, and may be influenced by methodological factors. The integrity of data will be optimized by measuring both positive and negative affective responses to an event, by measuring responses in real time as close to the stressful event as possible, and by utilizing data collection methods that do not interfere with naturalistic behaviours. The aim of the current study was to explore short term prototypical responses to major stressor events on outcome measures encompassing both positive and negative indicators of psychological functioning. A novel mobile experience sampling methodology (m-ESM) was utilized to monitor both effective responses to stressors in real time. A smartphone mental health app (‘Moodprism’) which prompts users daily to report both their positive and negative mood, as well as whether any significant event had occurred in the past 24 hours, was developed for this purpose. A sample of 142 participants was recruited as part of the promotion of this app. Participants’ daily reported experience of stressor events, levels of depressive symptoms and positive affect were collected across a 30 day period as they used the app. For each participant, major stressor events were identified on the subjective severity of the event rated by the user. Depression and positive affect ratings were extracted for the three days following the event. Responses to the event were scaled relative to their general reactivity across the remainder of the 30 day period. Participants were first clustered into groups based on initial reactivity and subsequent recovery following a stressor event. This revealed distinct patterns of responding along depressive symptomatology and positive affect. Participants were then grouped based on allocations to clusters in each outcome variable. A highly individualised nature in which participants respond to stressor events, in symptoms of depression and levels of positive affect, was observed. A complete description of the novel profiles identified will be presented at the conference. These findings suggest that real-time measurement of both positive and negative functioning to stressors yields a more complex set of responses than previously observed with retrospective reporting. The use of smartphone technology to measure individualized responding also proved to shed significant insight.

Keywords: depression, experience sampling methodology, positive functioning, resilience

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Authors: R. Vigneswaran, S. Thilakanathan

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Variable time-stepping algorithms for solving dynamical systems performed poorly for long time computations which pass close to a fixed point. To overcome this difficulty, several authors considered phase space error controls for numerical simulation of dynamical systems. In one generalized phase space error control, a step-size selection scheme was proposed, which allows this error control to be incorporated into the standard adaptive algorithm as an extra constraint at negligible extra computational cost. For this generalized error control, it was already analyzed the forward Euler method applied to the linear system whose coefficient matrix has real and negative eigenvalues. In this paper, this result was extended to the linear system whose coefficient matrix has complex eigenvalues with negative real parts. Some theoretical results were obtained and numerical experiments were carried out to support the theoretical results.

Keywords: adaptivity, fixed point, long time simulations, stability, linear system

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Authors: Nizar Ghali, Bernard Fortin, Guy Lacroix

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In Quebec, colonoscopies volumes have continued to rise in recent years in the absence of effective monitoring mechanism for the appropriateness and the quality of these exams. In 2010, November, Quebec Government introduced the colorectal cancer-screening program in the objective to control for volume and cost imperfection. This program is based on clinical standards and was initiated for first group of institutions. One year later, Government adds financial incentives for participants institutions. In this analysis, we want to assess for the causal effect of the two components of this program: clinical pathways and financial incentives. Especially we assess for the reform effect on healthcare quality and population health in the context that medical remuneration is not directly dependent on this additional funding offered by the program. We have data on admissions episodes and deaths for 8 years. We use multistate model analog to difference in difference approach to estimate reform effect on the transition probability between different states for each patient. Our results show that the reform reduced length of stay without deterioration in hospital mortality or readmission rate. In the other hand, the program contributed to decrease the hospitalization rate and a less invasive treatment approach for colorectal surgeries. This is a sign of healthcare quality and population health improvement. We demonstrate in this analysis that physicians’ behavior can be affected by both clinical standards and financial incentives even if offered to facilities.

Keywords: multi-state and multi-episode transition model, healthcare quality, length of stay, transition probability, difference in difference

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Authors: Mohammad Maruf Hasan

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Foreign Direct Investment (FDI) has been increased at a remarkable position around the globe in which emerging economies are getting more FDI compared to industrialized economies. This study aims to examine the determinants of inward FDI flows in Bangladesh. To estimate the long and short-run impact of the FDI determinants for 1996-2020, we employed the Autoregressive-Distributed Lag (ARDL) model. Results show that: (1) macroeconomic determinants, such as economic growth, infrastructure, and market size, have a significant and strong positive effect.(2) Inflation exchange rate shows insignificant effects, while trade openness has mixed (short-run negative, long-run positive) effects on FDI inflows in both the long and short run. (3) Current institutional determinants rule of law has a positive effect on FDI inflows but is statistically insignificant, political stability has a negative, and the rule of law has a considerable beneficial impact on inflows of FDI. (4) The macroeconomic factors have been determined to impact Bangladesh's FDI inflows. Finally, a stable macroeconomic climate is more effective at luring FDI, as this study confirms. From a policy perspective, this study will help the government and policymakers to make a new investment policy.

Keywords: determinants, FDI, ARDL, Bangladesh

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Authors: Surajit Das Barman, Rakibuzzaman Shah, Apurv Kumar

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Bushfire is known as one of the ascendant factors to create pyrocumulus thundercloud that causes the ignition of new fires by pyrocumulonimbus (pyroCb) lightning strikes and creates major losses of lives and property worldwide. A conceptual model-based risk planning would be beneficial to predict the lightning striking zones on the surface of the earth underneath the pyroCb thundercloud. PyroCb thundercloud can generate both positive cloud-to-ground (+CG) and negative cloud-to-ground (-CG) lightning in which +CG tends to ignite more bushfires and cause massive damage to nature and infrastructure. In this paper, a simple line charge structured thundercloud model is constructed in 2-D coordinates using the method of image charge to predict the probable +CG lightning striking zones on the earth’s surface for two conceptual thundercloud charge configurations: titled dipole and conventional tripole structure with excessive lower positive charge regions that lead to producing +CG lightning. The electric potential and surface charge density along the earth’s surface for both structures via continuously adjusting the position and the charge density of their charge regions is investigated. Simulation results for tilted dipole structure confirm the down-shear extension of the upper positive charge region in the direction of the cloud’s forward flank by 4 to 8 km, resulting in negative surface density, and would expect +CG lightning to strike within 7.8 km to 20 km around the earth periphery in the direction of the cloud’s forward flank. On the other hand, the conceptual tripole charge structure with enhanced lower positive charge region develops negative surface charge density on the earth’s surface in the range |x| < 6.5 km beneath the thundercloud and highly favors producing +CG lightning strikes.

Keywords: pyrocumulonimbus, cloud-to-ground lightning, charge structure, surface charge density, forward flank

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Authors: Maddalena Arigoni, Maria Luisa Ratto, Raffaele A. Calogero, Luca Alessandri

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The presence of tumor heterogeneity, where distinct cancer cells exhibit diverse morphological and phenotypic profiles, including gene expression, metabolism, and proliferation, poses challenges for molecular prognostic markers and patient classification for targeted therapies. Understanding the causes and progression of cancer requires research efforts aimed at characterizing heterogeneity, which can be facilitated by evolving single-cell sequencing technologies. However, analyzing single-cell data necessitates computational methods that often lack objective validation. Therefore, the establishment of benchmarking datasets is necessary to provide a controlled environment for validating bioinformatics tools in the field of single-cell oncology. Benchmarking bioinformatics tools for single-cell experiments can be costly due to the high expense involved. Therefore, datasets used for benchmarking are typically sourced from publicly available experiments, which often lack a comprehensive cell annotation. This limitation can affect the accuracy and effectiveness of such experiments as benchmarking tools. To address this issue, we introduce omics benchmark experiments designed to evaluate bioinformatics tools to depict the heterogeneity in single-cell tumor experiments. We conducted single-cell RNA sequencing on six lung cancer tumor cell lines that display resistant clones upon treatment of EGFR mutated tumors and are characterized by driver genes, namely ROS1, ALK, HER2, MET, KRAS, and BRAF. These driver genes are associated with downstream networks controlled by EGFR mutations, such as JAK-STAT, PI3K-AKT-mTOR, and MEK-ERK. The experiment also featured an EGFR-mutated cell line. Using 10XGenomics platform with cellplex technology, we analyzed the seven cell lines together with a pseudo-immunological microenvironment consisting of PBMC cells labeled with the Biolegend TotalSeq™-B Human Universal Cocktail (CITEseq). This technology allowed for independent labeling of each cell line and single-cell analysis of the pooled seven cell lines and the pseudo-microenvironment. The data generated from the aforementioned experiments are available as part of an online tool, which allows users to define cell heterogeneity and generates count tables as an output. The tool provides the cell line derivation for each cell and cell annotations for the pseudo-microenvironment based on CITEseq data by an experienced immunologist. Additionally, we created a range of pseudo-tumor tissues using different ratios of the aforementioned cells embedded in matrigel. These tissues were analyzed using 10XGenomics (FFPE samples) and Curio Bioscience (fresh frozen samples) platforms for spatial transcriptomics, further expanding the scope of our benchmark experiments. The benchmark experiments we conducted provide a unique opportunity to evaluate the performance of bioinformatics tools for detecting and characterizing tumor heterogeneity at the single-cell level. Overall, our experiments provide a controlled and standardized environment for assessing the accuracy and robustness of bioinformatics tools for studying tumor heterogeneity at the single-cell level, which can ultimately lead to more precise and effective cancer diagnosis and treatment.

Keywords: single cell omics, benchmark, spatial transcriptomics, CITEseq

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Authors: Lavinia Flueckiger, Roselind Lieb, Andrea H. Meyer, Cornelia Witthauer, Jutta Mata

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Objective: Health behaviors tend to show a high variability over time within the same person. However, most existing research can only assess a snapshot of a person’s behavior and not capture this natural daily variability. Two intensive longitudinal studies examine the variability in health behavior over one academic year and their implications for other aspects of daily life such as affect and academic performance. Can already a single day of increased physical activity, snacking, or improved sleep have beneficial effects? Methods: In two intensive longitudinal studies with up to 65 assessment days over an entire academic year, university students (Study 1: N = 292; Study 2: N = 304) reported sleep quality, physical activity, snacking, positive and negative affect, and learning goal achievement. Results: Multilevel structural equation models showed that on days on which participants reported better sleep quality or more physical activity than usual, they also reported increased positive affect, decreased negative affect, and better learning goal achievement. Higher day-to-day snacking was only associated with increased positive affect. Both, increased day-to-day sleep quality and physical activity were indirectly associated with better learning goal achievement through changes in positive and negative affect; results for snacking were mixed. Importantly, day-to-day sleep quality was a stronger predictor for affect and learning goal achievement than physical activity or snacking. Conclusion: One day of better sleep or more physical activity than usual is associated with improved affect and academic performance. These findings have important implications for low-threshold interventions targeting the improvement of daily functioning.

Keywords: sleep quality, physical activity, snacking, affect, academic performance, multilevel structural equation model

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Authors: Mounia El Hafyani, Khalid El Himdi

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Precipitation is one of the key variables in water resource planning. The importance of modeling wet and dry durations is a crucial pointer in engineering hydrology. The objective of this study is to model and analyze the distribution of wet and dry durations. For this purpose, the daily rainfall data from 1967 to 2017 of the Moroccan city of Kenitra’s station are used. Three models are implemented for the distribution of wet and dry durations, namely the first-order Markov chain, the second-order Markov chain, and the truncated negative binomial law. The adherence of the data to the proposed models is evaluated using Chi-square and Kolmogorov-Smirnov tests. The Akaike information criterion is applied to assess the most effective model distribution. We go further and study the law of the number of wet and dry days among k consecutive days. The calculation of this law is done through an algorithm that we have implemented based on conditional laws. We complete our work by comparing the observed moments of the numbers of wet/dry days among k consecutive days to the calculated moment of the three estimated models. The study shows the effectiveness of our approach in modeling wet and dry durations of daily precipitation.

Keywords: Markov chain, rainfall, truncated negative binomial law, wet and dry durations

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Authors: Chi-Ching Lee, Po-Jung Huang, Kuo-Yang Huang, Petrus Tang

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Background: Recent advances in high-throughput research technologies such as new-generation sequencing and multi-dimensional liquid chromatography makes it possible to dissect the complete transcriptome and proteome in a single run for the first time. However, it is almost impossible for many laboratories to handle and analysis these “BIG” data without the support from a bioinformatics team. We aimed to provide a web-based analysis platform for users with only limited knowledge on bio-computing to study the functional genomics and proteomics. Method: We use NCI-60 as an example dataset to demonstrate the power of the web-based analysis platform and data delivering system: C-eXpress takes a simple text file that contain the standard NCBI gene or protein ID and expression levels (rpkm or fold) as input file to generate a distribution map of gene/protein expression levels in a heatmap diagram organized by color gradients. The diagram is hyper-linked to a dynamic html table that allows the users to filter the datasets based on various gene features. A dynamic summary chart is generated automatically after each filtering process. Results: We implemented an integrated database that contain pre-defined annotations such as gene/protein properties (ID, name, length, MW, pI); pathways based on KEGG and GO biological process; subcellular localization based on GO cellular component; functional classification based on GO molecular function, kinase, peptidase and transporter. Multiple ways of sorting of column and rows is also provided for comparative analysis and visualization of multiple samples.

Keywords: cancer, visualization, database, functional annotation

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Authors: Elisa Santana-Monagas, Juan L. Núñez, Jaime León, Samuel Falcón, Celia Fernández, Rocío P. Solís

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Students’ emotional experiences have been a widely discussed theme among researchers, proving a central role on students’ outcomes. Yet, up to now, far too little attention has been paid to teaching practices that negatively relate with students’ negative emotions in the higher education. The present work aims to examine the relationship between teachers’ teaching practices (i.e., students’ evaluations of teaching and autonomy support), the students’ feelings of boredom and agentic engagement and motivation in the higher education context. To do so, the present study incorporates one of the most popular tools in natural processing language to address students’ evaluations of teaching: sentiment analysis. Whereas most research has focused on the creation of SA models and assessing students’ satisfaction regarding teachers and courses to the author’s best knowledge, no research before has included results from SA into an explanatory model. A total of 225 university students (Mean age = 26.16, SD = 7.4, 78.7 % women) participated in the study. Students were enrolled in degree and masters’ studies at the faculty of Education of a public university of Spain. Data was collected using an online questionnaire students could access through a QR code they completed during a teaching period where the assessed teacher was not present. To assess students’ sentiments towards their teachers’ teaching, we asked them the following open-ended question: “If you had to explain a peer who doesn't know your teacher how he or she communicates in class, what would you tell them?”. Sentiment analysis was performed with Microsoft's pre-trained model. For this study, we relied on the probability of the students answer belonging to the negative category. To assess the reliability of the measure, inter-rater agreement between this NLP tool and one of the researchers, who independently coded all answers, was examined. The average pairwise percent agreement and the Cohen’s kappa were calculated with ReCal2. The agreement reached was of 90.8% and Cohen’s kappa .68, both considered satisfactory. To test the hypothesis relations a structural equation model (SEM) was estimated. Results showed that the model fit indices displayed a good fit to the data; χ² (134) = 351.129, p < .001, RMSEA = .07, SRMR = .09, TLI = .91, CFI = .92. Specifically, results show that boredom was negatively predicted by autonomy support practices (β = -.47[-.61, -.33]), whereas for the negative sentiment extracted from SET, this relation was positive (β = .23[.16, .30]). In other words, when students’ opinion towards their instructors’ teaching practices was negative, it was more likely for them to feel bored. Regarding the relations among boredom and student outcomes, results showed a negative predictive value of boredom on students’ motivation to study (β = -.46[-.63, -.29]) and agentic engagement (β = -.24[-.33, -.15]). Altogether, results show a promising future for sentiment analysis techniques in the field of education as they proved the usefulness of this tool when evaluating relations among teaching practices and student outcomes.

Keywords: sentiment analysis, boredom, motivation, agentic engagement

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Authors: Ekaterina Zvorykina

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Nowadays, Arctic and Antarctic regions are distinguished to be one of the most important strategic resources for global development. Nonetheless, living conditions in Arctic regions still demand certain improvements. As soon as the region is rarely populated, one of the main points of interest is health accommodation of the people, who migrate to Arctic region for permanent and shift work. At Arctic and Antarctic latitudes, personnel face polar day and polar night conditions during the time of the year. It means that they are deprived of natural sunlight in winter season and have continuous daylight in summer. Firstly, the change in light intensity during 24-hours period due to migration affects circadian rhythms. Moreover, the controlled artificial light in winter is also an issue. The results of the recent studies on night shift medical professionals, who were exposed to permanent artificial light, have already demonstrated higher risks in cancer, depression, Alzheimer disease. Moreover, people exposed to frequent time zones change are also subjected to higher risks of heart attack and cancer. Thus, our main goals are to understand how high latitude work and living conditions can affect human health and how it can be prevented. In our study, we analyze molecular and cellular factors, which play important role in circadian rhythm change and distinguish main risk groups in people, migrating to high latitudes. The main well-studied index of circadian timing is melatonin or its metabolite 6-sulfatoxymelatonin. In low light intensity melatonin synthesis is disturbed and as a result human organism requires more time for sleep, which is still disregarded when it comes to working time organization. Lack of melatonin also causes shortage in serotonin production, which leads to higher depression risk. Melatonin is also known to inhibit oncogenes and increase apoptosis level in cells, the main factors for tumor growth, as well as circadian clock genes (for example Per2). Thus, people who work in high latitudes can be distinguished as a risk group for cancer diseases and demand more attention. Clock/Clock genes, known to be one of the main circadian clock regulators, decrease sensitivity of hypothalamus to estrogen and decrease glucose sensibility, which leads to premature aging and oestrous cycle disruption. Permanent light exposure also leads to accumulation superoxide dismutase and oxidative stress, which is one of the main factors for early dementia and Alzheimer disease. We propose a new screening system adjusted for people, migrating from middle to high latitudes and accommodation therapy. Screening is focused on melatonin and estrogen levels, sleep deprivation and neural disorders, depression level, cancer risks and heart and vascular disorders. Accommodation therapy includes different types artificial light exposure, additional melatonin and neuroprotectors. Preventive procedures can lead to increase of migration intensity to high latitudes and, as a result, the prosperity of Arctic region.

Keywords: circadian rhythm, high latitudes, melatonin, neuroprotectors

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Authors: Ricardo Alberto Chiong Zevallos, Eduardo Moraes Rego Reis

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Pancreatic adenocarcinoma (PDAC) patients have a less than 10% 5-year survival rate. PDAC has no defined diagnostic and prognostic biomarkers. Gemcitabine is the first-line drug in PDAC and several other cancers. Long non-coding RNAs (lncRNAs) contribute to the tumorigenesis and are potential biomarkers for PDAC. Although lncRNAs aren’t translated into proteins, they have important functions. LncRNAs can decoy or recruit proteins from the epigenetic machinery, act as microRNA sponges, participate in protein translocation through different cellular compartments, and even promote chemoresistance. The chromatin remodeling enzyme EZH2 is a histone methyltransferase that catalyzes the methylation of histone 3 at lysine 27, silencing local expression. EZH2 is ambivalent, it can also activate gene expression independently of its histone methyltransferase activity. EZH2 is overexpressed in several cancers and interacts with lncRNAs, being recruited to a specific locus. EZH2 can be recruited to activate an oncogene or silence a tumor suppressor. The lncRNAs misregulation in cancer can result in the differential recruitment of EZH2 and in a distinct epigenetic landscape, promoting chemoresistance. The relevance of the EZH2-lncRNAs interaction to chemoresistant PDAC was assessed by Real Time quantitative PCR (RT-qPCR) and RNA Immunoprecipitation (RIP) experiments with naïve and gemcitabine-resistant PDAC cells. The expression of several lncRNAs and EZH2 gene targets was evaluated contrasting naïve and resistant cells. Selection of candidate genes was made by bioinformatic analysis and literature curation. Indeed, the resistant cell line showed higher expression of chemoresistant-associated lncRNAs and protein coding genes. RIP detected lncRNAs interacting with EZH2 with varying intensity levels in the cell lines. During RIP, the nuclear fraction of the cells was incubated with an antibody for EZH2 and with magnetic beads. The RNA precipitated with the beads-antibody-EZH2 complex was isolated and reverse transcribed. The presence of candidate lncRNAs was detected by RT-qPCR, and the enrichment was calculated relative to INPUT (total lysate control sample collected before RIP). The enrichment levels varied across the several lncRNAs and cell lines. The EZH2-lncRNA interaction might be responsible for the regulation of chemoresistance-associated genes in multiple cancers. The relevance of the lncRNA-EZH2 interaction to PDAC was assessed by siRNA knockdown of a lncRNA, followed by the analysis of the EZH2 target expression by RT-qPCR. The chromatin immunoprecipitation (ChIP) of EZH2 and H3K27me3 followed by RT-qPCR with primers for EZH2 targets also assess the specificity of the EZH2 recruitment by the lncRNA. This is the first report of the interaction of EZH2 and lncRNAs HOTTIP and PVT1 in chemoresistant PDAC. HOTTIP and PVT1 were described as promoting chemoresistance in several cancers, but the role of EZH2 is not clarified. For the first time, the lncRNA LINC01133 was detected in a chemoresistant cancer. The interaction of EZH2 with LINC02577, LINC00920, LINC00941, and LINC01559 have never been reported in any context. The novel lncRNAs-EZH2 interactions regulate chemoresistant-associated genes in PDAC and might be relevant to other cancers. Therapies targeting EZH2 alone weren’t successful, and a combinatorial approach also targeting the lncRNAs interacting with it might be key to overcome chemoresistance in several cancers.

Keywords: epigenetics, chemoresistance, long non-coding RNAs, pancreatic cancer, histone modification

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Authors: Palak V. Patel, Jessica Pixley, Steven R. Feldman

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Introduction: Basal cell carcinoma (BCC) is the most common skin cancer worldwide and requires substantial resources to treat. When choosing between indicated therapies, providers consider their associated adverse effects, efficacy, cosmesis, and function preservation. The patient’s tumor burden, infiltrative risk, and risk of tumor recurrence are also considered. Treatment cost is often left out of these discussions. This can lead to financial toxicity, which describes the harm and quality of life reductions inflicted by high care costs. Methods: We studied the guidelines set forth by the American Academy of Dermatology for the treatment of BCC. A PubMed literature search was conducted to identify the costs of each recommended therapy. We discuss costs alongside treatment efficacy and side-effect profile. Results: Surgical treatment for BCC can be cost-effective if the appropriate treatment is selected for the presenting tumor. Curettage and electrodesiccation can be used in low-grade, low-recurrence tumors in aesthetically unimportant areas. The benefits of cost-conscious care are not likely to be outweighed by the risks of poor cosmesis or tumor return ($471 BCC of the cheek). When tumor burden is limited, MMS offers better cure rates and lower recurrence rates than surgical excision, and with comparable costs (MMS $1263; SE $949). Surgical excision with permanent sections may be indicated when tumor burden is more extensive or if molecular testing is necessary. The utility of surgical excision with frozen sections, which costs substantially more than MMS without comparable outcomes, is less clear (SE with frozen sections $2334-$3085). Less data exists on non-surgical treatments for BCC. These techniques cost less, but recurrence-risk is high. Side-effects of nonsurgical treatment are limited to local skin reactions, and cosmesis is good. Cryotherapy, 5-FU, and MAL-PDT are all more affordable than surgery, but high recurrence rates increase risk of secondary financial and psychosocial burden (recurrence rates 21-39%; cost $100-270). Radiation therapy offers better clearance rates than other nonsurgical treatments but is associated with similar recurrence rates and a significantly larger financial burden ($2591-$3460 BCC of the cheek). Treatments for advanced or metastatic BCC are extremely costly, but few patients require their use, and the societal cost burden remains low. Vismodegib and sonidegib have good response rates but substantial side effects, and therapy should be combined with multidisciplinary care and palliative measures. Expert-review has found sonidegib to be the less expensive and more efficacious option (vismodegib $128,358; sonidegib $122,579). Platinum therapy, while not FDA-approved, is also effective but expensive (~91,435). Immunotherapy offers a new line of treatment in patients intolerant of hedgehog inhibitors ($683,061). Conclusion: Dermatologists working within resource-compressed practices and with resource-limited patients must prudently manage the healthcare dollar. Surgical therapies for BCC offer the lowest risk of recurrence at the most reasonable cost. Non-surgical therapies are more affordable, but high recurrence rates increase the risk of secondary financial and psychosocial burdens. Treatments for advanced BCC are incredibly costly, but the low incidence means the overall cost to the system is low.

Keywords: nonmelanoma skin cancer, basal cell skin cancer, squamous cell skin cancer, cost of care

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Authors: Elnaz Entezar, Reza Ezzati

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In recent decades, trade flows, capital, workforce, technology and information have increased between international borders and the globalization has turned to an undeniable process in international economics. Meanwhile, despite the positive aspects of globalization, the critics of globalization opine that the risks and costs of globalization for developing vulnerable economies and the world's impoverished people are high and significant. In this regard, this study by using the data of KOF Economic Institute and the World Bank for 113 different countries during the period 2002-2012, by taking advantage of panel smooth transition regression, and by taking the gross domestic product as transmission variables discuss the nonlinear relationship between research variables. The results have revealed that globalization in low regime (countries with low GDP) has negative impact whereas in high regime (countries with high GDP) has a positive impact. In spite of the fact that in the early stages of growth, control of corruption has a positive impact on economic growth, after a threshold has a negative impact on economic growth.

Keywords: globalization, corruption, panel smooth transition model, economic growth, threshold, economic convergence

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Authors: Alejandra Sierra, Maria de los Angeles Covarrubias, Guillermo Julian Gonzalez, Noe Alfaro

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The objective of this study was to identify the cultural dimensions of the terms unplanned pregnancy and unwanted pregnancy built by adolescent women, through the focus of the social representations. Two associative methods were used: free listings and the paired comparison. 72 female students between the ages of 15 and 19 were interviewed, from the downtown area of Leon Guanajuato, Mexico. Words related to inducer terms were classified into five thematic categories: facilitators, consequences, reactions, expectations, and lexicon. The results showed that the social representations of unplanned pregnancy highlighted elements related to economic difficulties and negative emotional aspects, while unwanted pregnancy was associated with negative emotional aspects such as anger, anxiety, and sadness. The meanings each person attributes to terms related to pregnancy are culturally constructed and differ between populations; therefore, more attention should be paid to understanding the cultural meanings and attitudes of people in fertility decision-making, including also the views of adolescent men and other types of population, stratified by age groups and social conditions.

Keywords: adolescent, qualitative research, unplanned pregnancy, unwanted pregnancy

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Authors: Redrisse Djoumessi Fobasso, Baidyanath Sahu, Andre M. Strydom

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The R₂TX₃ (R = rare-earth, T = transition, and X = s and p block element) series of compounds are interesting owing to their fascinating structural and magnetic properties. In this present work, we have studied the magnetic and physical properties of the new Gd₂AgSi₃ polycrystalline compound. The sample was synthesized by the arc-melting method and confirmed to crystallize in the tetragonal α-ThSi₂-type crystal structure with space group I4/amd. Dc– and ac–magnetic susceptibility, specific heat, electrical resistivity, and magnetoresistance measurements were performed on the new compound. The structure provides a unique position in the unit cell for the magnetic trivalent Gd ion. Two magnetic phase transitions were consistently found in dc- and ac-magnetic susceptibility, heat capacity, and electrical resistivity at temperatures Tₙ₁ = 11 K and Tₙ₂ = 20 K, which is an indication of the complex magnetic behavior in this compound. The compound is found to be metamagnetic over a range of temperatures below and above Tₙ₁. From field-dependent electrical resistivity, it is confirmed that the compound shows unusual negative magnetoresistance in the antiferromagnetically ordered region. These results contribute to a better understanding of this class of materials.

Keywords: complex magnetic behavior, metamagnetic, negative magnetoresistance, two magnetic phase transitions

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Authors: Uma Krishnamoorthy, Vivienne Beavers, Janet Marshall

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Introduction: Cervical cytology showing features raising the suspicion of non cervical glandular neoplasia are reported as code 0 under the United Kingdom National Health Service Cervical screening programme ( NHSCSP). As the suspicion is regarding non cervical neoplasia, smear is reported as normal and patient informed that cervical screening result is normal. GP receives copy of results where it states further referral is indicated in small font within text of report. Background: There were several incidents of delayed diagnosis of endometrial cancer in Lancashire which prompted this Northwest Regional review to enable an understanding of underlying pathology outcome of code zero smears to raise awareness and also to review whether further action on wording of smear results was indicated to prevent such delay. Methodology: All Smears reported at the Manchester cytology centre who process cytology for Lancashire population from March 2013 to March 2014 were reviewed and histological diagnosis outcome of women in whom smear was reported as code zero was reviewed retrospectively . Results: Total smears reported by the cytology centre during this period was approximately 109400. Reports issued with result code 0 among this during this time period was 49.Results revealed that among three fourth (37) of women with code zero smear (N=49), evidence of underlying pathology of non cervical origin was confirmed. Of this, 73 % (36) were due to endometrial pathology with 49 % (24) endometrial carcinoma, 12 % (6)polyp, 4 % atypical endometrial hyperplasia (2), 6 % endometrial hyperplasia without atypia (3), and 2 % adenomyosis (1 case) and 2 % ( 1 case) due to ovarian adenocarcinoma. Conclusion: This review demonstrated that more than half (51 %) of women with a code 0 smear report were diagnosed with underlying carcinoma and 75 % had a confirmed underlying pathology contributory to code 0 smear findings. Recommendations and Action Plan: A local rapid access referral and management pathway for this group of women was implemented as a result of this in our unit. The findings and Pathway were shared with other regional units served by the cytology centre through the Pan Lancashire cervical screening board and through the Cytology centre. Locally, the smear report wording was updated to include a rubber stamp/ print in "Red Bold letters" stating that " URGENT REFERRAL TO GYNAECOLOGY IS INDICATED". Findings were also shared through the Pan Lancashire board with National cervical screening programme board, and revisions to wording of code zero smear reports to highlight the need for Urgent referral has now been agreed at National level to be implemented.

Keywords: code zero smears, endometrial cancer, non cervical glandular neoplasia, ovarian cancer

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Authors: Eyad H. R. Fadda, Jawaher K. Al Rashdieah, Aysha H. Al Rashdieh

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Urban Sprawl is a phenomenon that many regions in the Sultanate of Oman suffer from in general and in Welayat Barka in particular. It is considered a human phenomenon that causes many negative effects as it has increased in the last time clearly, and this study aims to diagnose the current status of urban growth taking place in Walayat Barka. The objective of this study is to monitor and follow up on the most prominent changes and developments taking place in Barka in the period from 2002 to 2019 and provide suggestions to the decision-makers to reduce the negative effects of the phenomenon. The study methodology depends on the descriptive and analytical approach to describe the phenomenon and its analysis and knowledge of the factors that helped in urban expansion in the Barka, using a number of studies and interviews with the specialists, both in governmental and private institutions, as well as with individuals who own land, real estate, and others. Geographic Information Systems (GIS) and Remote Sensing (ERDAS software) have been used to analyze the satellite images that helped in obtaining results that reflect the changes Barka, in addition to knowing the natural and human determinants that stand on Urban Sprawl Expansion. The study concluded that the geographical location of Barka has a significant role in its urban expansion, as it is the closest state to the capital Muscat, as this expansion continues toward the southern and south-western directions, as this expansion has significant negative effects represented in the low number of agricultural lands due to the continuous change in land use. In addition, it was found that there are two types of natural determinants of urban expansion in Barka, which are consumed land from the Sea of Oman and from the western sands.

Keywords: GIS applications, remote sensing, urbanization, urban sprawl expansion trends

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Authors: Warachate Khobjai, Suriyan Sukati, Khemjira Jarmkom, Pattaranut Eakwaropas, Surachai Techaoei

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The propose of this study was to investigate in vitro thrombolytic activity of Zingiber cassumunar Roxb. and Prasaplai, a Thai herbal formulation of Z. cassumunar Roxb. Herbs were extracted with boiling water and concentrated by lyophilization. To observe their thrombolytic potential, an in vitro clot lysis method was applied where streptokinase and sterile distilled water were used as positive and negative controls, respectively. Crude aqueous extracts from Z. cassumunar Roxb. and Prasaplai formula showed significant thrombolytic activity by clot lysis of 17.90% and 25.21%, respectively, compared to the negative control water (5.16%) while the standard streptokinase revealed 64.78% clot lysis. These findings suggest that Z. cassumunar Roxb. exhibits moderate thrombolytic activity and cloud play an important role in the thrombolytic properties of Prasaplai formula. However, further study should be done to observe in vivo clot dissolving potential and to isolate active component(s) of these extracts.

Keywords: thrombolytic activity, clot lysis, Zingiber cassumunar Roxb., Prasaplai formula, aqueous extract

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Authors: Liang Ning, Chung Hau Yin

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Angiogenesis is the process of new blood vessel development. It has been recognized as a therapeutic target for blocking cancer growth four decades ago. Vascular sprouting is initiated by pro-angiogenic factors. Vascular endothelial cell growth factor (VEGF) plays a central role in angiogenic initiation, many patients with cancer or ocular neovascularization have been benefited from anti-VEGF therapy. Emerging approaches impacting in the later stages of vessel remodeling and maturation are expected to improve clinical efficacy. TIE receptor as well as the corresponding angiopoietin ligands, were identified as another endothelial cell specific receptor tyrosine kinase signaling system. Much efforts were made to reduce the activity of angiopoietin-TIE receptor axis. Two eudesmane-type sesquiterpenes from laggera alata, namely, 15-dihydrocostic acid and ilicic acid were found with strong anti-angiogenic properties in zebrafish model. Meanwhile, the mRNA expression levels of VEGFR2 and TIE2 pathway related genes were down-regulated in the sesquiterpenes treated zebrafish embryos. Besides, in human umbilical vein endothelial cells (HUVECs), the sesquiterpenes have the ability to inhibit VEGF-induced HUVECs proliferation and migration at non-toxic concentration. Moreover, angiopoietin-2 induced TIE2 phosphorylation was inhibited by the sesquiterpenes, the inhibitory effect was detected in angiopoietin-1 induced HUVECs proliferation as well. Thus, we hypothesized the anti-angiogenic activity of the compounds may via the inhibition of VEGF and TIE2 related pathways. How the compounds come into play as the pathways inhibitors need to be evaluated in the future.

Keywords: Laggera alata, eudesmane-type sesquiterpene, anti-angiogenesis, VEGF, angiopoietin, TIE2

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Authors: Atheer Al-Nuaimi, Harry Evdorides

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Every day many people die or get disabled or injured on roads around the world, which necessitates more specific treatments for transportation safety issues. International road assessment program (iRAP) model is one of the comprehensive road safety models which accounting for many factors that affect road safety in a cost-effective way in low and middle income countries. In iRAP model road safety has been divided into five star ratings from 1 star (the lowest level) to 5 star (the highest level). These star ratings are based on star rating score which is calculated by iRAP methodology depending on road attributes, traffic volumes and operating speeds. The outcome of iRAP methodology are the treatments that can be used to improve road safety and reduce fatalities and serious injuries (FSI) numbers. These countermeasures can be used separately as a single countermeasure or mix as multiple countermeasures for a location. There is general agreement that the adequacy of a countermeasure is liable to consistent losses when it is utilized as a part of mix with different countermeasures. That is, accident diminishment appraisals of individual countermeasures cannot be easily added together. The iRAP model philosophy makes utilization of a multiple countermeasure adjustment factors to predict diminishments in the effectiveness of road safety countermeasures when more than one countermeasure is chosen. A multiple countermeasure correction factors are figured for every 100-meter segment and for every accident type. However, restrictions of this methodology incorporate a presumable over-estimation in the predicted crash reduction. This study aims to adjust this correction factor by developing new models to calculate the effect of using multiple countermeasures on the number of fatalities for a location or an entire road. Regression models have been used to establish relationships between crash frequencies and the factors that affect their rates. Multiple linear regression, negative binomial regression, and Poisson regression techniques were used to develop models that can address the effectiveness of using multiple countermeasures. Analyses are conducted using The R Project for Statistical Computing showed that a model developed by negative binomial regression technique could give more reliable results of the predicted number of fatalities after the implementation of road safety multiple countermeasures than the results from iRAP model. The results also showed that the negative binomial regression approach gives more precise results in comparison with multiple linear and Poisson regression techniques because of the overdispersion and standard error issues.

Keywords: international road assessment program, negative binomial, road multiple countermeasures, road safety

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Authors: Chinedu Ifedi Okeke

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The behavioural orientations of fathers, which resonate in the way they relate to members of their families and other community members, appear to have a variety of implications for the early development of children. In this paper, a conceptual map of fathers’ lifestyles is adopted to provide an interconnected network of father lifestyles. Empirical evidence from a qualitative case study of 25 Black fathers, who had been purposively selected from a suburb in one rural Eastern Cape municipality in South Africa, is reported in this paper. Semi-structured in-depth interviews were used to obtain data, which was analysed thematically. Findings identify and provide evidence of father lifestyles that are incongruent with the kind of parental behaviour needed to support the healthy early development of children. Findings suggest that these negative lifestyles appear to incapacitate fathers who fail to make a positive contribution to their children’s early development. To ensure that fathers make the expected contributions to their children’s early development, policies aimed at rehabilitating fathers who are involved in the negative lifestyles reported in this paper should be put in place.

Keywords: childhood development, fathering, fathers, intervention strategies, lifestyles, South Africa

Procedia PDF Downloads 135

Authors: Valentina V. Zhurikhina, Mihail I. Petrov, Alexandra A. Rtischeva, Mark Dussauze, Thierry Cardinal, Andrey A. Lipovskii

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Polarization of glass, often referred to as thermal poling, is a well-known method to modify the glass physical and chemical properties, that manifest themselves in loosing central symmetry of the medium, glass structure and refractive index modification. The usage of the poling for second optical harmonic generation, fabrication of optical waveguides and electrooptic modulators was also reported. Nevertheless, the detailed description of the poling of glasses, containing multiple charge carriers is still under discussion. In particular, the role of possible migration of electrons in the space charge formation usually remains out of the question. In this work, we performed the numerical simulation of thermal poling of a silicate glass, containing Na, K, Mg, and Ca. We took into consideration the contribution of electrons in the polarization process. The possible explanation of migration of electrons can be the break of non-bridging oxygen bonds. It was found, that the modeled depth of the space charge region is about 10 times higher if the migration of the negative charges is taken under consideration. The simulated profiles of cations, participating in the polarization process, are in a good agreement with the experimental data, obtained by glow discharge spectroscopy.

Keywords: glass poling, charge transport, modeling, concentration profiles

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Authors: Wilailak Siripornadulsil, Siriyanapat Tasaku, Jutamas Buahorm, Surasak Siripornadulsil

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The objectives of this study were to isolate LAB from various sources, dietary supplement, Thai traditional fermented food, and freshwater fish and to characterize their potential as probiotic cultures. Out of 1,558 isolates, 730 were identified as LAB based on isolation on MRS agar supplemented with a bromocresol purple indicator and CaCO3 and gram-positive, catalase and oxidase negative characteristics. Eight isolates showed the potential probiotic properties including tolerance to acid, bile salt and heat, proteolytic, amylolytic and lipolytic activities and oxalate-degrading capability. They all showed the antimicrobial activity against some Gram-negative and Gram-positive pathogenic bacteria. Based on 16S rDNA sequence analysis, they were identified as Enterococcus faecalis BT2 and MG30, Leconostoc mesenteroides SW64 and Pediococcus pentosaceous BD33, CF32, NP6, PS34 and SW5. The health beneficial effects and food safety will be further investigated and developed as a probiotic or protective culture used in Nile tilapia belly flap meat fermentation.

Keywords: probiotic, lactic acid bacteria, pathogen, protective culture

Procedia PDF Downloads 382

Authors: M. Abdullah Al Faruque, Ram Balachandar

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An experimental study with four different types of bed conditions was carried out to understand the effect of roughness in open channel flow at two different Reynolds numbers. The bed conditions include a smooth surface and three different roughness conditions which were generated using sand grains with a median diameter of 2.46 mm. The three rough conditions include a surface with distributed roughness, a surface with continuously distributed roughness and a sand bed with a permeable interface. A commercial two-component fibre-optic LDA system was used to conduct the velocity measurements. The variables of interest include the mean velocity, turbulence intensity, the correlation between the streamwise and the wall normal turbulence, Reynolds shear stress and velocity triple products. Quadrant decomposition was used to extract the magnitude of the Reynolds shear stress of the turbulent bursting events. The effect of roughness was evident throughout the flow depth. The results show that distributed roughness has the greatest roughness effect followed by the sand bed and the continuous roughness. Compared to the smooth bed, the streamwise turbulence intensity reduces but the vertical turbulence intensity increases at a location very close to the bed due to the introduction of roughness. Although the same sand grain is used to create the three different rough bed conditions, the difference in the turbulence intensity is an indication that the specific geometry of the roughness has an influence on turbulence structure.

Keywords: open channel flow, smooth and rough bed, Reynolds number, turbulence

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Authors: P. B. Sob, T. B. Tengen, A. A. Alugongo

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Mechanical behavior of 6082T6 aluminum is investigated at different temperatures. The strain rate sensitivity is investigated at different temperatures on the grain size variants. The sensitivity of the measured grain size variants on 3-D grain is discussed. It is shown that the strain rate sensitivities are negative for the grain size variants during the deformation of nanostructured materials. It is also observed that the strain rate sensitivities vary in different ways with the equivalent radius, semi minor axis radius, semi major axis radius and major axis radius. From the obtained results, it is shown that the variation of strain rate sensitivity with temperature suggests that the strain rate sensitivity at the low and the high temperature ends of the 6082T6 aluminum range is different. The obtained results revealed transition at different temperature from negative strain rate sensitivity as temperature increased on the grain size variants.

Keywords: nanostructured materials, grain size variants, temperature, yield stress, strain rate sensitivity

Procedia PDF Downloads 287

Authors: M'Hamed Boulakroune, Mouloud Challal, Hassiba Louazene, Saida Fentiz

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This paper presents a new ultra wideband (UWB) microstrip bandpass filter (BPF) at microwave frequencies. The first one is based on multiple-mode resonator (MMR) and rectangular-shaped defected ground structure (DGS). This filter, which is compact size of 25.2 x 3.8 mm2, provides in the pass band an insertion loss of 0.57 dB and a return loss greater than 12 dB. The second structure is a tunable bandpass filters using planar patch resonators based on diode varactor. This filter is formed by a triple mode circular patch resonator with two pairs of slots, in which the varactors are connected. Indeed, this filter is initially centered at 2.4 GHz, the center frequency of the tunable patch filter could be tuned up to 1.8 GHz simultaneously with the bandwidth, reaching high tuning ranges. Lossless simulations were compared to those considering the substrate dielectric, conductor losses, and the equivalent electrical circuit model of the tuning element in order to assess their effects. Within these variations, simulation results showed insertion loss better than 2 dB and return loss better than 10 dB over the passband. The proposed filters presents good performances and the simulation results are in satisfactory agreement with the experimentation ones reported elsewhere.

Keywords: defected ground structure, diode varactor, microstrip bandpass filter, multiple-mode resonator

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Authors: Soumya S., Manju Nidagodu Jayakumar, Vellore Kannan Gopinath

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Dental pulp inflammation resulting from dental caries often leads to a pathologic condition known as irreversible pulpitis and the currently managed by root canal treatment. Extirpation of the entire pulp tissue is done during this procedure, and the canal space is filled with synthetic materials. Recent studies in the stem cell biology state that some portion of the irreversibly inflamed pulp tissue could be viable with progenitor cells, having the properties similar to that of Mesenchymal stem cells. Hence, we aim to isolate Dental Pulp Stem Cells (DPSCs) from patients diagnosed with severe irreversible pulpitis and characterize the cells for the MSC specific markers. The pulp tissue was collected from the dental clinic and subjected to collagenase/dispase digestion. The isolated cells were expanded in culture, and the phenotypic characterization was done using flow cytometry. MSC specific markers such as CD-90, CD-73, and CD-105 were analysed along with negative markers such as CD-14 and CD-45. The isolated cells expressed positive expression for CD markers with CD90 and CD105 ( > 95%) and CD73 (19%). The cells did not express the negative markers CD-14 and CD-45. The commercially available DPSCs from vital extracted teeth, preferably molar/wisdom teeth with large pulp cavity or incomplete root growth in young patients (aged 15-30 years) showed more than 90% expression for all the CD markers such as CD-90, 73 and 105, whereas negative for CD-14 and CD-45. The DPSCs isolated from inflamed pulp tissue showed a less expression for CD-73 compared to the commercially available DPSCs whereas, as the other two markers were found to show similar percentage of positive expression. This could be attributed to the fact that the pulp population is very heterogeneous and we used the pooled tissue from different patients. Hence the phenotypic characterization and comparison with the commercially available DPSCs proved that the inflamed pulp tissue is a good source of MSC like cells which can be utilized further for regenerative application.

Keywords: collagenase/dispase, dental pulp stem cells, flow cytometry, irreversible pulpitis

Procedia PDF Downloads 251