Search results for: expression success
3275 Evolving Credit Scoring Models using Genetic Programming and Language Integrated Query Expression Trees
Authors: Alexandru-Ion Marinescu
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There exist a plethora of methods in the scientific literature which tackle the well-established task of credit score evaluation. In its most abstract form, a credit scoring algorithm takes as input several credit applicant properties, such as age, marital status, employment status, loan duration, etc. and must output a binary response variable (i.e. “GOOD” or “BAD”) stating whether the client is susceptible to payment return delays. Data imbalance is a common occurrence among financial institution databases, with the majority being classified as “GOOD” clients (clients that respect the loan return calendar) alongside a small percentage of “BAD” clients. But it is the “BAD” clients we are interested in since accurately predicting their behavior is crucial in preventing unwanted loss for loan providers. We add to this whole context the constraint that the algorithm must yield an actual, tractable mathematical formula, which is friendlier towards financial analysts. To this end, we have turned to genetic algorithms and genetic programming, aiming to evolve actual mathematical expressions using specially tailored mutation and crossover operators. As far as data representation is concerned, we employ a very flexible mechanism – LINQ expression trees, readily available in the C# programming language, enabling us to construct executable pieces of code at runtime. As the title implies, they model trees, with intermediate nodes being operators (addition, subtraction, multiplication, division) or mathematical functions (sin, cos, abs, round, etc.) and leaf nodes storing either constants or variables. There is a one-to-one correspondence between the client properties and the formula variables. The mutation and crossover operators work on a flattened version of the tree, obtained via a pre-order traversal. A consequence of our chosen technique is that we can identify and discard client properties which do not take part in the final score evaluation, effectively acting as a dimensionality reduction scheme. We compare ourselves with state of the art approaches, such as support vector machines, Bayesian networks, and extreme learning machines, to name a few. The data sets we benchmark against amount to a total of 8, of which we mention the well-known Australian credit and German credit data sets, and the performance indicators are the following: percentage correctly classified, area under curve, partial Gini index, H-measure, Brier score and Kolmogorov-Smirnov statistic, respectively. Finally, we obtain encouraging results, which, although placing us in the lower half of the hierarchy, drive us to further refine the algorithm.Keywords: expression trees, financial credit scoring, genetic algorithm, genetic programming, symbolic evolution
Procedia PDF Downloads 1173274 Cellular Senescence and Neuroinflammation Following Controlled Cortical Impact Traumatic Brain Injury in Juvenile Mice
Authors: Zahra F. Al-Khateeb, Shenel Shekerzade, Hasna Boumenar, Siân M. Henson, Jordi L. Tremoleda, A. T. Michael-Titus
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Traumatic brain injury (TBI) is the leading cause of disability and death in young adults and also increases the risk ofneurodegeneration. The mechanisms linking moderate to severe TBI to neurodegeneration are not known. It has been proposed that cellular senescence inductionpost-injury could amplify neuroinflammation and induce long-term changes. The impact of these processes after injury to an immature brain has not been characterised yet. We carried out a controlled cortical impact injury (CCI) in juvenile 1 month-old male CD1 mice. Animals were anesthetised and received a unilateral CCI injury. The sham group received anaesthesia and had a craniotomy. A naïve group had no intervention. The brain tissue was analysed at 5 days and 35 days post-injury using immunohistochemistry and markers for microglia, astrocytes, and senescence. Compared tonaïve animals, injured mice showed an increased microglial and astrocytic reaction early post-injury, as reflected in Iba1 and GFAP markers, respectively; the GFAP increase persisted in the later phase. The senescence analysis showed a significant increase inγH2AX-53BP1 nuclear foci, 8-oxoguanine, p19ARF, p16INK4a, and p53 expression in naïve vs. sham groups and naïve vs. CCI groups, at 5 dpi. At 35 days, the difference was no longer statistically significant in all markers. The injury induced a decrease p21 expression vs. the naïve group, at 35 dpi. These results indicate the induction of a complex senescence response after immature brain injury. Some changes occur early and may reflect the activation/proliferation of non-neuronal cells post-injury that had been hindered, whereas changes such as p21 downregulation may reflect a delayed response and pro-repair processes.Keywords: cellular senescence, traumatic brain injury, brain injury, controlled cortical impact
Procedia PDF Downloads 1393273 Hesperidin through Acting on Proliferating Cell Nuclear Antigen and Follicle Stimulating Hormone Receptor Expression Decreased Ovarian Toxicity Induced by Malathion
Authors: Mahnaz Zarein, Hamed Shoorei
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Background: Malathion is one of the most toxic agents widely used in agriculture throughout the world. This agent has adverse effects on the functions of multiple organs such as the reproductive system in both male and female genders. On the one hand, daily use of antioxidant supplementations such as hesperidin is capable to neutralize the deleterious impacts of malathion. Therefore, in this experimental study, the protective effects of hesperidin against ovarian toxicity induced by malathion were investigated. Material & Methods: Balb/c adult mice (n=32) were randomly divided into 4 groups including 1) the control group, treated with normal saline, 2) the Mal group, treated with 30mg/kg malathion, daily for 1 month, 3) Mal + Hes group, treated with 20 mg/kg malathion and 20 mg/kg hesperidin, daily for 1 month, and 5) Hes group, treated with 20 mg/kg hesperidin. At the end of the experimental period, mice were anesthetized and their drops of blood were collected to the assessment of some hormones such as LH, FSH, E2, and P4. Also, the right ovaries were used to H&E staining, and the left ovaries were used for IHC staining (PCNA and FSHR). Results: Histopathological assessments showed that the number of follicles, i.e. primordial, primary, and secondary, significantly decreased, while the atretic follicle counts remarkably increased compared to the control group (p<0.05). Hormonal levels revealed that the production of all mentioned hormones decreased in the Mal group in comparison with the control group (p<0.05). The expression of PCNA, as a proliferative marker, and FHSR, as a marker showing maturation, decreased when mice received malathion compared to the control group (p<0.05). Interestingly, treatment with hesperidin significantly neutralized the adverse effects of malathion on all mentioned parameters. Conclusion: Daily use of antioxidant supplementations such as hesperidin could alleviate the ovarian toxicity induced by malathion.Keywords: malathion, ovary, antioxidant hesperidin, FSHR PCNA, ovary
Procedia PDF Downloads 753272 Axillary Evaluation with Targeted Axillary Dissection Using Ultrasound-Visible Clips after Neoadjuvant Chemotherapy for Patients with Node-Positive Breast Cancer
Authors: Naomi Sakamoto, Eisuke Fukuma, Mika Nashimoto, Yoshitomo Koshida
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Background: Selective localization of the metastatic lymph node with clip and removal of clipped nodes with sentinel lymph node (SLN), known as targeted axillary dissection (TAD), reduced false-negative rates (FNR) of SLN biopsy (SLNB) after neoadjuvant chemotherapy (NAC). For the patients who achieved nodal pathologic complete response (pCR), accurate staging of axilla by TAD lead to omit axillary lymph node dissection (ALND), decreasing postoperative arm morbidity without a negative effect on overall survival. This study aimed to investigate the ultrasound (US) identification rate and success removal rate of two kinds of ultrasound-visible clips placed in metastatic lymph nodes during TAD procedure. Methods: This prospective study was conducted using patients with clinically T1-3, N1, 2, M0 breast cancer undergoing NAC followed by surgery. A US-visible clip was placed in the suspicious lymph node under US guidance before neoadjuvant chemotherapy. Before surgery, US examination was performed to evaluate the detection rate of clipped node. During the surgery, the clipped node was removed using several localization techniques, including hook-wire localization, dye-injection, or fluorescence technique, followed by a dual-technique SLNB and resection of palpable nodes if present. For the fluorescence technique, after injection of 0.1-0.2 mL of indocyanine green dye (ICG) into the clipped node, ICG fluorescent imaging was performed using the Photodynamic Eye infrared camera (Hamamatsu Photonics k. k., Shizuoka, Japan). For the dye injection method, 0.1-0.2 mL of pyoktanin blue dye was injected into the clipped node. Results: A total of 29 patients were enrolled. Hydromark™ breast biopsy site markers (Hydromark, T3 shape; Devicor Medical Japan, Tokyo, Japan) was used in 15patients, whereas a UltraCor™ Twirl™ breast marker (Twirl; C.R. Bard, Inc, NJ, USA) was placed in 14 patients. US identified the clipped node marked with the UltraCore Twirl in 100% (14/14) and with the Hydromark in 93.3% (14/15, p = ns). Success removal of clipped node marked with the UltraCore Twirl was achieved in 100% (14/14), whereas the node marked with the Hydromark was removed in 80% (12/15) (p = ns). Conclusions: The ultrasound identification rate differed between the two types of ultrasound-visible clips, which also affected the success removal rate of clipped nodes. Labelling the positive node with a US-highly-visible clip allowed successful TAD.Keywords: breast cancer, neoadjuvant chemotherapy, targeted axillary dissection, breast tissue marker, clip
Procedia PDF Downloads 663271 Aquaporin-1 as a Differential Marker in Toxicant-Induced Lung Injury
Authors: Ekta Yadav, Sukanta Bhattacharya, Brijesh Yadav, Ariel Hus, Jagjit Yadav
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Background and Significance: Respiratory exposure to toxicants (chemicals or particulates) causes disruption of lung homeostasis leading to lung toxicity/injury manifested as pulmonary inflammation, edema, and/or other effects depending on the type and extent of exposure. This emphasizes the need for investigating toxicant type-specific mechanisms to understand therapeutic targets. Aquaporins, aka water channels, are known to play a role in lung homeostasis. Particularly, the two major lung aquaporins AQP5 and AQP1 expressed in alveolar epithelial and vasculature endothelia respectively allow for movement of the fluid between the alveolar air space and the associated vasculature. In view of this, the current study is focused on understanding the regulation of lung aquaporins and other targets during inhalation exposure to toxic chemicals (Cigarette smoke chemicals) versus toxic particles (Carbon nanoparticles) or co-exposures to understand their relevance as markers of injury and intervention. Methodologies: C57BL/6 mice (5-7 weeks old) were used in this study following an approved protocol by the University of Cincinnati Institutional Animal Care and Use Committee (IACUC). The mice were exposed via oropharyngeal aspiration to multiwall carbon nanotube (MWCNT) particles suspension once (33 ugs/mouse) followed by housing for four weeks or to Cigarette smoke Extract (CSE) using a daily dose of 30µl/mouse for four weeks, or to co-exposure using the combined regime. Control groups received vehicles following the same dosing schedule. Lung toxicity/injury was assessed in terms of homeostasis changes in the lung tissue and lumen. Exposed lungs were analyzed for transcriptional expression of specific targets (AQPs, surfactant protein A, Mucin 5b) in relation to tissue homeostasis. Total RNA from lungs extracted using TRIreagent kit was analyzed using qRT-PCR based on gene-specific primers. Total protein in bronchoalveolar lavage (BAL) fluid was determined by the DC protein estimation kit (BioRad). GraphPad Prism 5.0 (La Jolla, CA, USA) was used for all analyses. Major findings: CNT exposure alone or as co-exposure with CSE increased the total protein content in the BAL fluid (lung lumen rinse), implying compromised membrane integrity and cellular infiltration in the lung alveoli. In contrast, CSE showed no significant effect. AQP1, required for water transport across membranes of endothelial cells in lungs, was significantly upregulated in CNT exposure but downregulated in CSE exposure and showed an intermediate level of expression for the co-exposure group. Both CNT and CSE exposures had significant downregulating effects on Muc5b, and SP-A expression and the co-exposure showed either no significant effect (Muc5b) or significant downregulating effect (SP-A), suggesting an increased propensity for infection in the exposed lungs. Conclusions: The current study based on the lung toxicity mouse model showed that both toxicant types, particles (CNT) versus chemicals (CSE), cause similar downregulation of lung innate defense targets (SP-A, Muc5b) and mostly a summative effect when presented as co-exposure. However, the two toxicant types show differential induction of aquaporin-1 coinciding with the corresponding differential damage to alveolar integrity (vascular permeability). Interestingly, this implies the potential of AQP1 as a differential marker of toxicant type-specific lung injury.Keywords: aquaporin, gene expression, lung injury, toxicant exposure
Procedia PDF Downloads 1843270 Tumour Radionuclides Therapy: in vitro and in vivo Dose Distribution Study
Authors: Rekaya A. Shabbir, Marco Mingarelli, Glenn Flux, Ananya Choudhury, Tim A. D. Smith
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Introduction: Heterogeneity of dose distributions across a tumour is problematic for targeted radiotherapy. Gold nanoparticles (AuNPs) enhance dose-distributions of targeted radionuclides. The aim of this study is to demonstrate if tumour dose-distribution of targeted AuNPs radiolabelled with either of two radioisotopes (¹⁷⁷Lu and ⁹⁰Y) in breast cancer cells produced homogeneous dose distributions. Moreover, in vitro and in vivo studies were conducted to study the importance of receptor level on cytotoxicity of EGFR-targeted AuNPs in breast and colorectal cancer cells. Methods: AuNPs were functionalised with DOTA and OPPS-PEG-SVA to optimise labelling with radionuclide tracers and targeting with Erbitux. Radionuclides were chelated with DOTA, and the uptake of the radiolabelled AuNPs and targeted activity in vitro in both cell lines measured using liquid scintillation counting. Cells with medium (HCT8) and high (MDA-MB-468) EGFR expression were incubated with targeted ¹⁷⁷Lu-AuNPs for 4h, then washed and allowed to form colonies. Nude mice bearing tumours were used to study the biodistribution by injecting ¹⁷⁷Lu-AuNPs or ⁹⁰Y-AuNPs via the tail vein. Heterogeneity of dose-distribution in tumours was determined using autoradiography. Results: Colony formation (% control) was 81 ± 4.7% (HCT8) and 32 ± 9% (MDA-MB-468). High uptake was observed in the liver and spleen, indicating hepatobiliary excretion. Imaging showed heterogeneity in dose-distributions for both radionuclides across the tumours. Conclusion: The cytotoxic effect of EGFR-targeted AuNPs is greater in cells with higher EGFR expression. Dose-distributions for individual radiolabelled nanoparticles were heterogeneous across tumours. Further strategies are required to improve the uniformity of dose distribution prior to clinical trials.Keywords: cancer cells, dose distributions, radionuclide therapy, targeted gold nanoparticles
Procedia PDF Downloads 1143269 An Empty Canvas is Full
Authors: Joonha Park
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This essay examines the Soviet Artist Pavel Korin’s artistic pursuit towards his life-long project, “Requiem/Passing of the Rus,” framing the funeral of Tikhon, the last great defender of the Russian orthodox Church during the Great purge, as the final moment of “Rus,” which is the identity of the Russian people that built up in the 1000 year of history behind Russian Orthodoxy. Korin’s project remains in the form of a series of 29 man-sized portraits and a monumental blank canvas. Born in a family dedicated to iconography, Korin witnessed the historic drama during Stalin’s terror; therefore, he tried to convey the nation’s mourning for the disappearance of “Rus” and disapproval of the Soviet notion of atheism. Yet, due to Korin’s success as a state artist, many believed that the political pressure led Korin to give up his belief and controversy arose over the fact that Korin left the canvas blank. The empty 40-square-meter canvas, which remains untouched in his studio since 1930, supports this theory to an extent. However, resources such as Korin’s notes, primary accounts from his fellow Soviet Artists, and testimonies from his wife suggested that this assumption is incorrect. Moreover, Korin’s uninterrupted relationship with the church and the religious attributes in his commissioned works were brought up as evidence of Korin’s continued belief. The empty canvas not only represents Korin’s discontentment towards the repression and the hardships that the Orthodox Church experienced, but also depicts the identity that coexisted with the Church in order to bequeath this idea to future generations. The faultless canvas surrounded by the striking 29 portraits is a symbol of the highest spirit, similar to that of the iconography paintings placed in every Russian house that unites the Russian people till this day, therefore one can deduce that the legacy of “Requiem” is still relevant to the Russian people even under freedom of religious expression. Consequently, “Requiem” was on display at the Tretyakov Gallery for the first time in public in 2013 even though Korin started creating this piece in 1925, extolling Korin not only as an artist but also as a historian; by recording the turmoil of the Great Oppression, Korin exhibited the social responsibility universal to artists across time and space. In this essay, the legacy Korin left behind, both to his contemporaries and his posterity is reevaluated through the lens of his works, unfinished as they were.Keywords: Pavel Korin, Art History, Art, Russia, Soviet Union, Requiem, Russian orthodox church, Treytyakov gallery, contemporary art, socialist realism, Maxim Gorky
Procedia PDF Downloads 4173268 Breast Cancer: The Potential of miRNA for Diagnosis and Treatment
Authors: Abbas Pourreza
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MicroRNAs (miRNAs) are small single-stranded non-coding RNAs. They are almost 18-25 nucleotides long and very conservative through evolution. They are involved in adjusting the expression of numerous genes due to the existence of a complementary region, generally in the 3' untranslated regions (UTR) of target genes, against particular mRNAs in the cell. Also, miRNAs have been proven to be involved in cell development, differentiation, proliferation, and apoptosis. More than 2000 miRNAs have been recognized in human cells, and these miRNAs adjust approximately one-third of all genes in human cells. Dysregulation of miRNA originated from abnormal DNA methylation patterns of the locus, cause to down-regulated or overexpression of miRNAs, and it may affect tumor formation or development of it. Breast cancer (BC) is the most commonly identified cancer, the most prevalent cancer (23%), and the second-leading (14%) mortality in all types of cancer in females. BC can be classified based on the status (+/−) of the hormone receptors, including estrogen receptor (ER), progesterone receptor (PR), and the Receptor tyrosine-protein kinase erbB-2 (ERBB2 or HER2). Currently, there are four main molecular subtypes of BC: luminal A, approximately 50–60 % of BCs; luminal B, 10–20 %; HER2 positive, 15–20 %, and 10–20 % considered Basal (triple-negative breast cancer (TNBC)) subtype. Aberrant expression of miR-145, miR-21, miR-10b, miR-125a, and miR-206 was detected by Stem-loop real-time RT-PCR in BC cases. Breast tumor formation and development may result from down-regulation of a tumor suppressor miRNA such as miR-145, miR-125a, and miR-206 and/or overexpression of an oncogenic miRNA such as miR-21 and miR-10b. MiR-125a, miR-206, miR-145, miR-21, and miR-10b are hugely predicted to be new tumor markers for the diagnosis and prognosis of BC. MiR-21 and miR-125a could play a part in the treatment of HER-2-positive breast cancer cells, while miR-145 and miR-206 could speed up the evolution of cure techniques for TNBC. To conclude, miRNAs will be presented as hopeful molecules to be used in the primary diagnosis, prognosis, and treatment of BC and battle as opposed to its developed drug resistance.Keywords: breast cancer, HER2 positive, miRNA, TNBC
Procedia PDF Downloads 963267 Interwoven Realms: The Relationship Between Textiles, Fashion, and Architecture
Authors: Toktam mehrabani
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Textiles, fashion, and architecture, though seemingly disparate fields, share a deep and evolving relationship. This paper explores the intersection of these disciplines, examining how the tactile, structural, and aesthetic qualities of textiles have influenced both fashion and architecture over time. By investigating historical and contemporary examples, this paper seeks to unravel the ways in which textiles and fashion have not only shaped architectural design but have also acted as a bridge between functionality, art, and human experience in the built environment.Textiles have been integral to human culture since the dawn of civilization. Their presence transcends mere functionality, serving as a medium for artistic expression, cultural identity, and social commentary. Fashion, derived from textiles, has long been associated with personal identity and societal trends, while architecture reflects human needs, environmental context, and cultural values. This paper posits that the relationship between textiles, fashion, and architecture is more interconnected than often perceived, with each influencing and inspiring the other across time. Textiles in Architectural Design: From ancient draperies in temples to tapestries in castles, textiles have adorned structures, softening rigid spaces and adding layers of warmth and luxury. Fabric screens and curtains have also served functional purposes, such as controlling light, acoustics, and temperature. Fashion as Architectural Expression: Renaissance and Baroque fashion used exaggerated forms, corsetry, and layers to mirror the grandiosity of architectural styles of the time. Clothing acted as wearable architecture, with structured garments mirroring the strong lines and curves of buildings..Structural Textiles in Architecture: In the 21st century, textiles are no longer just decorative; they have become integral to architectural innovation. Materials like tensile fabrics and smart textiles are used in creating flexible, lightweight structures. Iconic examples include Frei Otto’s work with tensile membranes, seen in the Munich Olympic Stadium.Technological advancements have drastically transformed the relationship between textiles, fashion, and architecture. Digital tools like 3D printing and laser cutting allow designers in both fields to push the limits of form and structure. Smart textiles that react to environmental stimuli are being explored for use in both wearable technology and adaptable architecture, such as facades that change in response to weather conditions. Textiles, fashion, and architecture are inextricably linked through their shared exploration of form, structure, and expression. This interdisciplinary relationship continues to evolve, driven by technological advancements and a growing emphasis on sustainability. As fashion becomes more architectural in its construction and architecture more fluid in its forms, the lines between these disciplines blur, offering new possibilities for creativity and functionality in both wearable and built environments.Keywords: textiles in architecture, fashion and architecture, textile architecture, structural textiles, wearable architecture, architectural fashion
Procedia PDF Downloads 293266 Transcriptional Evidence for the Involvement of MyD88 in Flagellin Recognition: Genomic Identification of Rock Bream MyD88 and Comparative Analysis
Authors: N. Umasuthan, S. D. N. K. Bathige, W. S. Thulasitha, I. Whang, J. Lee
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The MyD88 is an evolutionarily conserved host-expressed adaptor protein that is essential for proper TLR/ IL1R immune-response signaling. A previously identified complete cDNA (1626 bp) of OfMyD88 comprised an ORF of 867 bp encoding a protein of 288 amino acids (32.9 kDa). The gDNA (3761 bp) of OfMyD88 revealed a quinquepartite genome organization composed of 5 exons (with the sizes of 310, 132, 178, 92 and 155 bp) separated by 4 introns. All the introns displayed splice signals consistent with the consensus GT/AG rule. A bipartite domain structure with two domains namely death domain (24-103) coded by 1st exon, and TIR domain (151-288) coded by last 3 exons were identified through in silico analysis. Moreover, homology modeling of these two domains revealed a similar quaternary folding nature between human and rock bream homologs. A comprehensive comparison of vertebrate MyD88 genes showed that they possess a 5-exonic structure. In this structure, the last three exons were strongly conserved, and this suggests that a rigid structure has been maintained during vertebrate evolution. A cluster of TATA box-like sequences were found 0.25 kb upstream of cDNA starting position. In addition, putative 5'-flanking region of OfMyD88 was predicted to have TFBS implicated with TLR signaling, including copies of NFB1, APRF/ STAT3, Sp1, IRF1 and 2 and Stat1/2. Using qPCR technique, a ubiquitous mRNA expression was detected in liver and blood. Furthermore, a significantly up-regulated transcriptional expression of OfMyD88 was detected in head kidney (12-24 h; >2-fold), spleen (6 h; 1.5-fold), liver (3 h; 1.9-fold) and intestine (24 h; ~2-fold) post-Fla challenge. These data suggest a crucial role for MyD88 in antibacterial immunity of teleosts.Keywords: MyD88, innate immunity, flagellin, genomic analysis
Procedia PDF Downloads 4163265 Competency and Strategy Formulation in Automobile Industry
Authors: Chandan Deep Singh
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In present days, companies are facing the rapid competition in terms of customer requirements to be satisfied, new technologies to be integrated into future products, new safety regulations to be followed, new computer-based tools to be introduced into design activities that becomes more scientific. In today’s highly competitive market, survival focuses on various factors such as quality, innovation, adherence to standards, and rapid response as the basis for competitive advantage. For competitive advantage, companies have to produce various competencies: for improving the capability of suppliers and for strengthening the process of integrating technology. For more competitiveness, organizations should operate in a strategy driven way and have a strategic architecture for developing core competencies. Traditional ways to take such experience and develop competencies tend to take a lot of time and they are expensive. A new learning environment, which is built around a gaming engine, supports the development of competences in specific subject areas. Technology competencies have a significant role in firm innovation and competitiveness; they interact with the competitive environment. Technological competencies vary according to the type of competitive environment, thus enhancing firm innovativeness. Technological competency is gained through extensive experimentation and learning in its research, development and employment in manufacturing. This is a review paper based on competency and strategic success of automobile industry. The aim here is to study strategy formulation and competency tools in the industry. This work is a review of literature related to competency and strategy in automobile industry. This study involves review of 34 papers related to competency and strategy.Keywords: manufacturing competency, strategic success, competitiveness, strategy formulation
Procedia PDF Downloads 3113264 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 4353263 Mobile Communication Technologies, Romantic Attachment and Relationship Quality: An Exploration of Partner Attunement
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
Procedia PDF Downloads 3853262 Rapid Classification of Soft Rot Enterobacteriaceae Phyto-Pathogens Pectobacterium and Dickeya Spp. Using Infrared Spectroscopy and Machine Learning
Authors: George Abu-Aqil, Leah Tsror, Elad Shufan, Shaul Mordechai, Mahmoud Huleihel, Ahmad Salman
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Pectobacterium and Dickeya spp which negatively affect a wide range of crops are the main causes of the aggressive diseases of agricultural crops. These aggressive diseases are responsible for a huge economic loss in agriculture including a severe decrease in the quality of the stored vegetables and fruits. Therefore, it is important to detect these pathogenic bacteria at their early stages of infection to control their spread and consequently reduce the economic losses. In addition, early detection is vital for producing non-infected propagative material for future generations. The currently used molecular techniques for the identification of these bacteria at the strain level are expensive and laborious. Other techniques require a long time of ~48 h for detection. Thus, there is a clear need for rapid, non-expensive, accurate and reliable techniques for early detection of these bacteria. In this study, infrared spectroscopy, which is a well-known technique with all its features, was used for rapid detection of Pectobacterium and Dickeya spp. at the strain level. The bacteria were isolated from potato plants and tubers with soft rot symptoms and measured by infrared spectroscopy. The obtained spectra were analyzed using different machine learning algorithms. The performances of our approach for taxonomic classification among the bacterial samples were evaluated in terms of success rates. The success rates for the correct classification of the genus, species and strain levels were ~100%, 95.2% and 92.6% respectively.Keywords: soft rot enterobacteriaceae (SRE), pectobacterium, dickeya, plant infections, potato, solanum tuberosum, infrared spectroscopy, machine learning
Procedia PDF Downloads 1003261 First Cracking Moments of Hybrid Fiber Reinforced Polymer-Steel Reinforced Concrete Beams
Authors: Saruhan Kartal, Ilker Kalkan
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The present paper reports the cracking moment estimates of a set of steel-reinforced, Fiber Reinforced Polymer (FRP)-reinforced and hybrid steel-FRP reinforced concrete beams, calculated from different analytical formulations in the codes, together with the experimental cracking load values. A total of three steel-reinforced, four FRP-reinforced, 12 hybrid FRP-steel over-reinforced and five hybrid FRP-steel under-reinforced concrete beam tests were analyzed within the scope of the study. Glass FRP (GFRP) and Basalt FRP (BFRP) bars were used in the beams as FRP bars. In under-reinforced hybrid beams, rupture of the FRP bars preceded crushing of concrete, while concrete crushing preceded FRP rupture in over-reinforced beams. In both types, steel yielding took place long before the FRP rupture and concrete crushing. The cracking moment mainly depends on two quantities, namely the moment of inertia of the section at the initiation of cracking and the flexural tensile strength of concrete, i.e. the modulus of rupture. In the present study, two different definitions of uncracked moment of inertia, i.e. the gross and the uncracked transformed moments of inertia, were adopted. Two analytical equations for the modulus of rupture (ACI 318M and Eurocode 2) were utilized in the calculations as well as the experimental tensile strength of concrete from prismatic specimen tests. The ACI 318M modulus of rupture expression produced cracking moment estimates closer to the experimental cracking moments of FRP-reinforced and hybrid FRP-steel reinforced concrete beams when used in combination with the uncracked transformed moment of inertia, yet the Eurocode 2 modulus of rupture expression gave more accurate cracking moment estimates in steel-reinforced concrete beams. All of the analytical definitions produced analytical values considerably different from the experimental cracking load values of the solely FRP-reinforced concrete beam specimens.Keywords: polymer reinforcement, four-point bending, hybrid use of reinforcement, cracking moment
Procedia PDF Downloads 1403260 AI-Assisted Business Chinese Writing: Comparing the Textual Performances Between Independent Writing and Collaborative Writing
Authors: Stephanie Liu Lu
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With the proliferation of artificial intelligence tools in the field of education, it is crucial to explore their impact on language learning outcomes. This paper examines the use of AI tools, such as ChatGPT, in practical writing within business Chinese teaching to investigate how AI can enhance practical writing skills and teaching effectiveness. The study involved third and fourth-year university students majoring in accounting and finance from a university in Hong Kong within the context of a business correspondence writing class. Students were randomly assigned to a control group, who completed business letter writing independently, and an experimental group, who completed the writing with the assistance of AI. In the latter, the AI-assisted business letters were initially drafted by the students issuing commands and interacting with the AI tool, followed by the students' revisions of the draft. The paper assesses the performance of both groups in terms of grammatical expression, communicative effect, and situational awareness. Additionally, the study collected dialogue texts from interactions between students and the AI tool to explore factors that affect text generation and the potential impact of AI on enhancing students' communicative and identity awareness. By collecting and comparing textual performances, it was found that students assisted by AI showed better situational awareness, as well as more skilled organization and grammar. However, the research also revealed that AI-generated articles frequently lacked a proper balance of identity and writing purpose due to limitations in students' communicative awareness and expression during the instruction and interaction process. Furthermore, the revision of drafts also tested the students' linguistic foundation, logical thinking abilities, and practical workplace experience. Therefore, integrating AI tools and related teaching into the curriculum is key to the future of business Chinese teaching.Keywords: AI-assistance, business Chinese, textual analysis, language education
Procedia PDF Downloads 573259 The Importance of Parental Projective Care in Perceived Parenting Effectiveness in African American Upper Middle Class Families
Authors: Susan D. Toliver
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Within the professional research literature on parenting in the United States, there is a paucity of research on parenting within the African American or Black community. Research on parenting focused on African Americans within the upper middle class, who constitute a critical and growing sector within the African American population, is all but non-existent. Research to address this void is needed. Despite the progress that has been made toward eliminating the long-standing racial divides in U.S. society, these divides persist and continue to affect different experiences and opportunity structures for White Americans versus Black Americans, including those in the upper middle class. Achievement of middle and upper middle class status of adult heads of families has generally been seen as the route to greater success and well-being for their children. While higher family class status is positively correlated with these factors, the strength of the relationship between higher social class and success and well-being is weaker for Black American families as compared to White American families. In light of the realities of racial inequality, African American parents, including those who have achieved higher status, have unique concerns for their children. African American parents, on the basis of their own experiences and their sense of the world as being highly racialized, anticipate the kinds of experiences that their children are likely to encounter as they grow and mature from childhood to adulthood and beyond. Racial discrimination and macro and micro racial aggressions are continued sources of concern for these parents. On the basis of in-depth personal interviews with upper middle class African American parents, findings suggest that the parenting goals and strategies of African American parents are influenced by the continuing significance of race as a social divide, including in higher socio-economic strata, in the United States. Black American families' parenting practices differ from those of White American families and are inclusive of the unique factors that threaten the well-being of African American children. Specifically, parenting practices are shaped by parents' fears about the racial experiences that they anticipate that their children will encounter. Parents' perceptions of parental effectiveness are linked to their ability to prepare their children for success in confronting, understanding, and contextualizing racial inequalities and aggressions. Theories of Parental Projective Care are useful in understanding the special considerations and unique parenting goals and behaviors of higher status African Americans.Keywords: African American parenting, parental projective care, parenting effectiveness, racial socialization, upper middle class parenting
Procedia PDF Downloads 1413258 Growth and Differentiation of Mesenchymal Stem Cells on Titanium Alloy Ti6Al4V and Novel Beta Titanium Alloy Ti36Nb6Ta
Authors: Eva Filová, Jana Daňková, Věra Sovková, Matej Daniel
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Titanium alloys are biocompatible metals that are widely used in clinical practice as load bearing implants. The chemical modification may influence cell adhesion, proliferation, and differentiation as well as stiffness of the material. The aim of the study was to evaluate the adhesion, growth and differentiation of pig mesenchymal stem cells on the novel beta titanium alloy Ti36Nb6Ta compared to standard medical titanium alloy Ti6Al4V. Discs of Ti36Nb6Ta and Ti6Al4V alloy were sterilized by ethanol, put in 48-well plates, and seeded by pig mesenchymal stem cells at the density of 60×103/cm2 and cultured in Minimum essential medium (Sigma) supplemented with 10% fetal bovine serum and penicillin/streptomycin. Cell viability was evaluated using MTS assay (CellTiter 96® AQueous One Solution Cell Proliferation Assay;Promega), cell proliferation using Quant-iT™ ds DNA Assay Kit (Life Technologies). Cells were stained immunohistochemically using monoclonal antibody beta-actin, and secondary antibody conjugated with AlexaFluor®488 and subsequently the spread area of cells was measured. Cell differentiation was evaluated by alkaline phosphatase assay using p-nitrophenyl phosphate (pNPP) as a substrate; the reaction was stopped by NaOH, and the absorbance was measured at 405 nm. Osteocalcin, specific bone marker was stained immunohistochemically and subsequently visualized using confocal microscopy; the fluorescence intensity was analyzed and quantified. Moreover, gene expression of osteogenic markers osteocalcin and type I collagen was evaluated by real-time reverse transcription-PCR (qRT-PCR). For statistical evaluation, One-way ANOVA followed by Student-Newman-Keuls Method was used. For qRT-PCR, the nonparametric Kruskal-Wallis Test and Dunn's Multiple Comparison Test were used. The absorbance in MTS assay was significantly higher on titanium alloy Ti6Al4V compared to beta titanium alloy Ti36Nb6Ta on days 7 and 14. Mesenchymal stem cells were well spread on both alloys, but no difference in spread area was found. No differences in alkaline phosphatase assay, fluorescence intensity of osteocalcin as well as the expression of type I collagen, and osteocalcin genes were observed. Higher expression of type I collagen compared to osteocalcin was observed for cells on both alloys. Both beta titanium alloy Ti36Nb6Ta and titanium alloy Ti6Al4V Ti36Nb6Ta supported mesenchymal stem cellsˈ adhesion, proliferation and osteogenic differentiation. Novel beta titanium alloys Ti36Nb6Ta is a promising material for bone implantation. The project was supported by the Czech Science Foundation: grant No. 16-14758S, the Grant Agency of the Charles University, grant No. 1246314 and by the Ministry of Education, Youth and Sports NPU I: LO1309.Keywords: beta titanium, cell growth, mesenchymal stem cells, titanium alloy, implant
Procedia PDF Downloads 3163257 The Molecular Mechanism of Vacuolar Function in Yeast Cell Homeostasis
Authors: Chang-Hui Shen, Paulina Konarzewska
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Cell homeostasis is regulated by vacuolar activity and it has been shown that lipid composition of the vacuole plays an important role in vacuolar function. The major phosphoinositide species present in the vacuolar membrane include phosphatidylinositol 3,5-biphosphate (PI(3,5)P₂) which is generated from PI(3)P controlled by Fab1p. Deletion of FAB1 gene reduce the synthesis of PI(3,5)P₂ and thus result in enlarged or fragmented vacuoles, with neutral vacuolar pH due to reduced vacuolar H⁺-ATPase activity. These mutants also exhibited poor growth at high extracellular pH and in the presence of CaCl₂. Conversely, VPS34 regulates the synthesis of PI(3)P from phosphatidylinositol (PI), and the lack of Vps34p results in the reduction of vacuolar activity. Although the cellular observations are clear, it is still unknown about the molecular mechanism between the phospholipid biosynthesis pathway and vacuolar activity. Since both VPS34 and FAB1 are important in vacuolar activity, we hypothesize that the molecular mechanism of vacuolar function might be regulated by the transcriptional regulators of phospholipid biosynthesis. In this study, we study the role of the major phospholipid biosynthesis transcription factor, INO2, in the regulation of vacuolar activity. We first performed qRT-PCR to examine the effect of Ino2p on the expression of VPS34 and FAB1. Our results showed that VPS34 was upregulated in the presence of inositol for both WT and ino2Δ cells. However, FAB1 was only upregulated significantly in ino2Δ cells. This indicated that Ino2p might be the negative regulator for FAB1 expression. Next, growth sensitivity experiment showed that WT, vma3Δ, and ino2Δ grew well in growth medium buffered to pH 5.5 containing 10 mM CaCl₂. As cells were switched to growth medium buffered to pH 7 containing CaCl₂ WT, ino2Δ and opi1Δ showed growth reduction, whereas vma3Δ was completely nonviable. As the concentration of CaCl₂ was increased to 60 mM, ino2Δ cells showed moderate growth reduction compared to WT. This result suggests that ino2Δ cells have better vacuolar activity. Microscopic analysis and vacuolar acidification were employed to further elucidate the importance of INO2 in vacuolar homeostasis. Analysis of vacuolar morphology indicated that WT and vma3Δ cells displayed vacuoles that occupied a small area of the cell when grown in media buffered to pH 5.5. Whereas, ino2Δ displayed fragmented vacuoles. On the other hand, all strains grown in media buffered to pH 7, exhibited enlarged vacuoles that occupied most of the cell’s surface. This indicated that the presence of INO2 may play negative effect in vacuolar morphology when cells are grown in media buffered to pH 5.5. Furthermore, vacuolar acidification assay showed that only vma3Δ cells displayed notably less acidic vacuoles as cells were grown in media buffered to pH 5.5 and pH 7. Whereas, ino2Δ cells displayed more acidic pH compared to WT at pH7. Taken together, our results demonstrated the molecular mechanism of the vacuolar activity regulated by the phospholipid biosynthesis transcription factors Ino2p. Ino2p negatively regulates vacuolar activity through the expression of FAB1.Keywords: vacuole, phospholipid, homeostasis, Ino2p, FAB1
Procedia PDF Downloads 1273256 Organizational Culture and Its Internalization of Change in the Manufacturing and Service Sector Industries in India
Authors: Rashmi Uchil, A. H. Sequeira
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Post-liberalization era in India has seen an unprecedented growth of mergers, both domestic as well as cross-border deals. Indian organizations have slowly begun appreciating this inorganic method of growth. However, all is not well as is evidenced in the lowering value creation of organizations after mergers. Several studies have identified that organizational culture is one of the key factors that affects the success of mergers. But very few studies have been attempted in this realm in India. The current study attempts to identify the factors in the organizational culture variable that may be unique to India. It also focuses on the difference in the impact of organizational culture on merger of organizations in the manufacturing and service sectors in India. The study uses a mixed research approach. An exploratory research approach is adopted to identify the variables that constitute organizational culture specifically in the Indian scenario. A few hypotheses were developed from the identified variables and tested to arrive at the Grounded Theory. The Grounded Theory approach used in the study, attempts to integrate the variables related to organizational culture. Descriptive approach is used to validate the developed grounded theory with a new empirical data set and thus test the relationship between the organizational culture variables and the success of mergers. Empirical data is captured from merged organizations situated in major cities of India. These organizations represent significant proportions of the total number of organizations which have adopted mergers. The mix of industries included software, banking, manufacturing, pharmaceutical and financial services. Mixed sampling approach was adopted for this study. The first phase of sampling was conducted using the probability method of stratified random sampling. The study further used the non-probability method of judgmental sampling. Adequate sample size was identified for the study which represents the top, middle and junior management levels of the organizations that had adopted mergers. Validity and reliability of the research instrument was ensured with appropriate tests. Statistical tools like regression analysis, correlation analysis and factor analysis were used for data analysis. The results of the study revealed a strong relationship between organizational culture and its impact on the success of mergers. The study also revealed that the results were unique to the extent that they highlighted a marked difference in the manner of internalization of change of organizational culture after merger by the organizations in the manufacturing sector. Further, the study reveals that the organizations in the service sector internalized the changes at a slower rate. The study also portrays the industries in the manufacturing sector as more proactive and can contribute to a change in the perception of the said organizations.Keywords: manufacturing industries, mergers, organizational culture, service industries
Procedia PDF Downloads 2973255 Serum MicroRNA and Inflammatory Mediators: Diagnostic Biomarkers for Endometritis in Arabian Mares
Authors: Sally Ibrahim, Mohamed Hedia, Mohamed Taqi, Mohamed Derbala, Karima Mahmoud, Youssef Ahmed, Sayed Ismail, Mohamed El-Belely
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The identification and quantification of serum microRNA (miRNA) from mares with endometritis might serve as useful and implementable clinical biomarkers for the early diagnosis of endometiritis. Aims of the current study were (I) to study the expression pattern of eca-miR-155, eca-miR-223, eca-miR-17, eca-miR-200a, and eca-miR-205, and (II) to determine the levels of interleukin 6 (IL-6), prostaglandins (PGF₂α and PGE₂), in the serum of Arabian mares with healthy and abnormal uterine status (endometritis). This study was conducted on 80 Arabian mares (4-14 years old). Mares were divided into 48 sub-fertile mares suspected of endometritis and 32 fertile at stud farms. The criteria for mares to be enrolled in the endometritis group were that they had been bred three or more times unsuccessfully in the breeding season or had a history of more than one year of reproductive failure. In addition, two or more of the following criteria on a checklist were present: abnormal clinical findings, transrectal ultrasonographic uterine examination showed abnormal fluid in the uterus (echogenic or ≥2 cm in diameter), positive endometrial cytology; and bacterial and/or fungal growth. Serum samples were collected for measuring IL-6, PGF₂α, and PGE₂ concentrations, as well as serum miRNA isolation and quantitative real-time PCR. Serum concentrations of IL-6, PGE₂, and PGF₂α were higher (P ≤ 0.001) in mares with endometritis compared to the control healthy ones. The expression profile of eca-miR-155, eca-miR-223, eca-miR-17, eca-miR-200a, and eca-miR-205 increased (P≤0.001) in mares with endometritis compared to the control ones. To the best of our knowledge, this is the first study that revealed that serum miRNA and serum inflammatory mediators (IL-6, PGE₂, and PGF₂α) could be used as non-invasive gold standard biomarkers, and therefore might be served as an important additional diagnostic tool for endometritis in Arabian mares. Moreover, estimation of the serum concentrations of serum miRNA, IL-6, PGE₂, and PGF₂α is a promising recommended tool during the breeding soundness examination in mares.Keywords: Arabian Mares, endometritis, inflammatory mediators, serum miRNA
Procedia PDF Downloads 1803254 Epstein, Barr Virus Alters ATM-Dependent DNA Damage Responses in Germinal Centre B-Cells during Early Infection
Authors: Esther N. Maina, Anna Skowronska, Sridhar Chaganti, Malcolm A. Taylor, Paul G. Murray, Tatjana Stankovic
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Epstein-Barr virus (EBV) has been implicated in the pathogenesis of human tumours of B-cell origin. The demonstration that a proportion of Hodgkin lymphomas and all Burkitt’s lymphomas harbour EBV suggests that the virus contributes to the development of these malignancies. However, the mechanisms of lymphomagenesis remain largely unknown. To determine whether EBV causes DNA damage and alters DNA damage response in cells of EBV-driven lymphoma origin, Germinal Centre (GC) B cells were infected with EBV and DNA damage responses to gamma ionising radiation (IR) assessed at early time points (12hr – 72hr) after infection and prior to establishment of lymphoblastoid (LCL) cell lines. In the presence of EBV, we observed induction of spontaneous DNA DSBs and downregulation of ATM-dependent phosphorylation in response to IR. This downregulation coincided with reduced ability of infected cells to repair IR-induced DNA double-strand breaks, as measured by the kinetics of gamma H2AX, a marker of double-strand breaks, and by the tail moment of the comet assay. Furthermore, we found that alteration of DNA damage responses coincided with the expression of LMP-1 protein. The presence of the EBV virus did not affect the localization of the ATM-dependent DNA repair proteins to sites of damage but instead lead to an increased expression of PP5, a phosphatase that regulates ATM function. The impact of the virus on DNA repair was most prominent 24h after infection, suggesting that this time point is crucial for the viral establishment in B cells. Our results suggest that during an early infection EBV virus dampens crucial cellular responses to DNA double-strand breaks which facilitate successful viral infection, but at the same time might provide the mechanism for tumor development.Keywords: EBV, ATM, DNA damage, germinal center cells
Procedia PDF Downloads 3493253 Use of an Insecticidal-Iridovirus Kinase towards the Development of Aphid-Resistant Plants
Authors: Saranya Ganapathy, Megha N. Parajulee, Michael San Francisco, Hong Zhang
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Insect pests are a serious threat to agricultural productivity. Use of chemical pesticides, the predominant control method thus far, has resulted in environmental damage, pest resurgence, and negative effects on non-target species. Genetically modified (GM) crops offer a promising alternative, and Bacillus thuringiensis endotoxin genes have played a major role in this respect. However, to overcome insect tolerance issues and to broaden the target range, it is critical to identify alternative-insecticidal toxins working through novel mechanisms. Our research group has identified a kinase from Chilo iridescent virus (CIV; Family Iridoviridae) that has insecticidal activity and designated it as ISTK (Iridovirus Serine/Threonine Kinase). A 35 kDa truncated form of ISTK, designated iridoptin, was obtained during expression and purification of ISTK in the yeast system. This yeast-expressed CIV toxin induced 50% mortality in cotton aphids and 100% mortality in green peach aphids (GPA). Optimized viral genes (o-ISTK and o-IRI) were stably transformed into the model plant, Arabidopsis. PCR analysis of genomic DNA confirmed the presence of the gene insert (oISTK/oIRI) in selected transgenic lines. The further screening was performed to identify the PCR positive lines that showed expression of respective toxins at the polypeptide level using Western blot analysis. The stable lines expressing either of these two toxins induced moderate to very high mortality in GPAs and significantly affected GPA development and fecundity. The aphicidal potential of these transgenic Arabidopsis lines will be presented.Keywords: Chilo iridescent virus, insecticidal toxin, iridoviruses, plant-incorporated protectants, serine/threonine kinase
Procedia PDF Downloads 2863252 Effects of Anti-FGL2 Monoclonal Antibody SPF89 on Vascular Inflammation
Authors: Ying Sun, Biao Cheng, Qing Lu, Xuefei Tao, Xiaoyu Lai, Cheng Guo, Dan Wang
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Fibrinogen-like protein 2 (FGL2) has recently been identified to play an important role in inflammatory diseases such as atherosclerosis through a thrombin-dependent manner. Here, a murine monoclonal antibody was raised against the critical residue Ser(89) of FGL2, and the effects of the anti-FGL2 mAb (SPF89) were analyzed in human umbilical vein endothelial cells (HUVECs) and THP-1 cells. Firstly, it was proved that SPF89, which belongs to the IgG1 subtype with a KD value of 44.5 pM, could specifically show the expression levels of protein FGL2 in different cell lines of known target gene status. The lipopolysaccharide (LPS)-mediated endothelial cell proliferation was significantly inhibited with a decline of phosphorylation nuclear factor-κB (NF-κB) in a dose-dependent manner after SPF89 treatment. Furthermore, SPF89 reduced LPS-induced expression of adhesion molecules and inflammatory cytokines such as vascular cell adhesion molecule-1, tumor necrosis factor-α, Matrix metalloproteinase MMP-2, Integrin αvβ3, and interleukin-6 in HUVECs. In macrophage-like THP-1 cells, SPF89 effectively inhibited LPS and low-density lipoprotein-induced foam cell formation. However, these anti-inflammatory and anti-atherosclerotic effects of anti-FGL2 mAb in HUVECs and THP-1 cells were significantly reduced after treatment with an NF-κB inhibitor PDTC. All the above suggest, by efficiently inhibiting LPS-induced pro-inflammatory effects in vascular endothelial cells by attenuating NF-κB dependent pathway, the new anti-FGL2 mAb SPF89 could to be a potential therapeutic candidate for protecting the vascular endothelium against inflammatory diseases such as atherosclerosis. This work was supported by the Program of Sichuan Science and Technology Department (2017FZ0069) and Collaborative Innovation Program of Sichuan for Elderly Care and Health(YLZBZ1511).Keywords: monoclonal antibody, fibrinogen like protein 2, inflammation, endothelial cells
Procedia PDF Downloads 2713251 The Multiple Sclerosis condition and the Role of Varicella-zoster virus in its Progression
Authors: Sina Mahdavi, Mahdi Asghari Ozma
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Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human Varicella-zoster virus (VZV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on VZV retrovirus infection in MS disease progression. For this study, the keywords "Multiple sclerosis", " Human Varicella-zoster virus ", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched and 14 articles were chosen, studied, and analyzed. Analysis of the amino acid sequences of HNRNPA1 with VZV proteins has shown a 62% amino acid sequence similarity between VZV gE and the PrLD/M9 epitope region (TNPO1 binding domain) of mutant HNRNPA1. A heterogeneous nuclear ribonucleoprotein (hnRNP), which is produced by HNRNPA1, is involved in the processing and transfer of mRNA and pre-mRNA. Mutant HNRNPA1 mimics gE of VZV as an antigen that leads to autoantibody production. Mutant HnRNPA1 translocates to the cytoplasm, after aggregation is presented by MHC class I, followed by CD8 + cells. Of these, antibodies and immune cells against the gE epitopes of VZV remain due to the memory immune response, causing neurodegeneration and the development of MS in genetically predisposed individuals. VZV expression during the course of MS is present in genetically predisposed individuals with HNRNPA1 mutation, suggesting a link between VZV and MS, and that this virus may play a role in the development of MS by inducing an inflammatory state. Therefore, measures to modulate VZV expression may be effective in reducing inflammatory processes in demyelinated areas of MS patients in genetically predisposed individuals.Keywords: multiple sclerosis, varicella-zoster virus, central nervous system, autoimmunity
Procedia PDF Downloads 763250 Dys-Regulation of Immune and Inflammatory Response in in vitro Fertilization Implantation Failure Patients under Ovarian Stimulation
Authors: Amruta D. S. Pathare, Indira Hinduja, Kusum Zaveri
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Implantation failure (IF) even after the good-quality embryo transfer (ET) in the physiologically normal endometrium is the main obstacle in in vitro fertilization (IVF). Various microarray studies have been performed worldwide to elucidate the genes requisite for endometrial receptivity. These studies have included the population based on different phases of menstrual cycle during natural cycle and stimulated cycle in normal fertile women. Additionally, the literature is also available in recurrent implantation failure patients versus oocyte donors in natural cycle. However, for the first time, we aim to study the genomics of endometrial receptivity in IF patients under controlled ovarian stimulation (COS) during which ET is generally practised in IVF. Endometrial gene expression profiling in IF patients (n=10) and oocyte donors (n=8) were compared during window of implantation under COS by whole genome microarray (using Illumina platform). Enrichment analysis of microarray data was performed to determine dys-regulated biological functions and pathways using Database for Annotation, Visualization and Integrated Discovery, v6.8 (DAVID). The enrichment mapping was performed with the help of Cytoscape software. Microarray results were validated by real-time PCR. Localization of genes related to immune response (Progestagen-Associated Endometrial Protein (PAEP), Leukaemia Inhibitory Factor (LIF), Interleukin-6 Signal Transducer (IL6ST) was detected by immunohistochemistry. The study revealed 418 genes downregulated and 519 genes upregulated in IF patients compared to healthy fertile controls. The gene ontology, pathway analysis and enrichment mapping revealed significant downregulation in activation and regulation of immune and inflammation response in IF patients under COS. The lower expression of Progestagen Associated Endometrial Protein (PAEP), Leukemia Inhibitory Factor (LIF) and Interleukin 6 Signal Transducer (IL6ST) in cases compared to controls by real time and immunohistochemistry suggests the functional importance of these genes. The study was proved useful to uncover the probable reason of implantation failure being imbalance of immune and inflammatory regulation in our group of subjects. Based on the present study findings, a panel of significant dysregulated genes related to immune and inflammatory pathways needs to be further substantiated in larger cohort in natural as well as stimulated cycle. Upon which these genes could be screened in IF patients during window of implantation (WOI) before going for embryo transfer or any other immunological treatment. This would help to estimate the regulation of specific immune response during WOI in a patient. The appropriate treatment of either activation of immune response or suppression of immune response can be then attempted in IF patients to enhance the receptivity of endometrium.Keywords: endometrial receptivity, immune and inflammatory response, gene expression microarray, window of implantation
Procedia PDF Downloads 1553249 Collagen Deposition in Lung Parenchyma Driven by Depletion of LYVE-1+ Macrophages Protects Emphysema and Loss of Airway Function
Authors: Yinebeb Mezgebu Dagnachew, Hwee Ying Lim, Liao Wupeng, Sheau Yng Lim, Lim Sheng Jie Natalie, Veronique Angeli
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Collagen is essential for maintaining lung structure and function, and its remodeling has been associated with respiratory diseases, including chronic obstructive pulmonary disease (COPD). However, the cellular mechanisms driving collagen remodeling and the functional implications of this process in the pathophysiology of pulmonary diseases remain poorly understood. Using a mouse model of Lyve-1 expressing macrophage depletion, we found that the absence of this subpopulation of tissue-resident macrophage led to the preferential deposition of type I collagen fibers around the alveoli and bronchi in the steady state. Further analysis by polarized light microscopy revealed that the collagen fibers accumulating in the lungs depleted of Lyve-1+ macrophages were thicker and crosslinked. A decrease in MMP-9 gene expression and proteolytic activity, together with an increase in Col1a1, Timp-3 and Lox gene expression, accompanied the collagen alterations. Next, we investigated the effect of the collagen remodeling on the pathophysiology of COPD and airway function in mouse lacking Lyve-1+ macrophage exposed chronically to cigarette smoke (CS), a well-established animal model of COPD. We showed that the deposition of collagen protected mouse against the destruction of alveoli (emphysema) and bronchi thickening after CS exposure and prevented loss of airway function. Thus, we demonstrate that interstitial Lyve-1+ macrophages regulate the composition, amount, and architecture of the collagen network in the lungs and that such collagen remodeling functionally impacts the development of COPD. This study further supports the potential of targeting collagen as a promising approach to treating respiratory diseases.Keywords: lung, extracellular matrix, chronic obstructive pulmonary disease, matrix metalloproteinases, collagen
Procedia PDF Downloads 373248 Drawings Reveal Beliefs of Japanese University Students
Authors: Sakae Suzuki
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Although Japanese students study English for six years in secondary schools, they demonstrate little success with it when they enter higher education. Learners’ beliefs can predict the future behavior of students, so it may be effective to investigate how learners’ beliefs limit their success and how beliefs might be nudged in a positive direction. While many researchers still depend on a questionnaire called BALLI to reveal explicit beliefs, alternative approaches, especially those designed to reveal implicit beliefs, might be helpful for promoting learning. The present study seeks to identify beliefs with a discursive approach using visual metaphors and narratives. Employing a sociocultural framework, this study investigates how students’ beliefs are revealed by drawings of themselves and their surrounding environments and artifacts while they are engaged in language learning. Research questions are: (1) Can we identify beliefs through an analysis of students’ visual narratives? (2) What environments and artifacts can be found in students’ drawings, and what do they mean? (3) To what extent do students see language learning as a solitary, rather than a social, activity? Participants are university students majoring in science and technology in Japan. The questionnaire was administered to 70 entering students in April, 2014. Data included students drawings of themselves as learners of English as well as written descriptions of students’ backgrounds, English-learning experiences, and analogies and metaphors that they used in written descriptions of themselves as learners. Data will be analyzed qualitatively and quantitatively. Anticipated results include students’ perceptions of themselves as language learners, including their sense of agency, awareness of artifacts, and social contexts of language learning. Comments will be made on implications for teaching, as well as the use of visual narratives as research tools, and recommended further research.Keywords: drawings, learners' beliefs, metaphors, BALLI
Procedia PDF Downloads 4923247 AMF activates PDH 45 and G-proteins Genes to Alleviate Abiotic Stress in Tomato Plants
Authors: Deepak Bhardwaj, Narendra Tuteja
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Global climate change is impacting large agrarian societies, especially those in countries located near the equator. Agriculture, and consequently, plant-based food, is the hardest hit in tropical and sub-tropical countries such as India due to an increased incidence of drought as well as an increase in soil salinity. One method that holds promise is AMF-rich biofertilizers which assist in activating proteins which in turn help alleviate abiotic stress in plants. In the present study, we identified two important species of (arbuscular mycorrhizal fungus) AMF belonging to Glomus and Gigaspora from the rhizosphere of the important medicinal plant Justicia adathoda. These two species have been found to be responsible for the abundance of Justicia adathoda in the semi-arid areas of the Jammu valley located in northern India, namely, the Union Territory of Jammu and Kashmir. We isolated the species of Glomus and Gigaspora from the rhizosphere of Justicia adathoda and used them as biofertilizers for the tomato plant. Significant improvements in the growth parameters were observed in the tomato plants inoculated with Glomus sp. and Gigaspora sp. in comparison with the tomato plants that were grown without AMF treatments. Tomato plants grown along with Glomus sp. and Gigaspora sp. have been observed to withstand 200 mM of salinity and 25% PEG stress. AMF also resulted in an increased concentration of proline and antioxidant enzymes in tomato plants. We also examined the expression levels of salinity and drought stress-inducible genes such as pea DNA helicase 45 (PDH 45) and genes of G-protein subunits of the tomato plants inoculated with and without AMF under stress and normal conditions. All the stress-inducible genes showed a significant increase in their gene expression under stress and AMF inoculation, while their levels were found to be normal under AMF inoculation without stress. We propose a model of abiotic stress alleviation in tomato plants with the help of external factors such as AMF and internally with the help of proteins like PDH 45 and G-proteins.Keywords: AMF, abiotic stress, g-proteins, PDH-45
Procedia PDF Downloads 1763246 The Involvement of the Homing Receptors CCR7 and CD62L in the Pathogenesis of Graft-Versus-Host Disease
Authors: Federico Herrera, Valle Gomez García de Soria, Itxaso Portero Sainz, Carlos Fernández Arandojo, Mercedes Royg, Ana Marcos Jimenez, Anna Kreutzman, Cecilia MuñozCalleja
Abstract:
Introduction: Graft-versus-host disease (GVHD) still remains the major complication associated with allogeneic stem cell transplantation (SCT). The pathogenesis involves migration of donor naïve T-cells into recipient secondary lymphoid organs. Two molecules are important in this process: CD62L and CCR7, which are characteristically expressed in naïve/central memory T-cells. With this background, we aimed to study the influence of CCR7 and CD62L on donor lymphocytes in the development and severity of GVHD. Material and methods: This single center study included 98 donor-recipient pairs. Samples were collected prospectively from the apheresis product and phenotyped by flow cytometry. CCR7 and CD62L expression in CD4+ and CD8+ T-cells were compared between patients who developed acute (n=40) or chronic GVHD (n=33) and those who did not (n=38). Results: The patients who developed acute GVHD were transplanted with a higher percentage of CCR7+CD4+ T-cells (p = 0.05) compared to the no GVHD group. These results were confirmed when these patients were divided in degrees according to the severity of the disease; the more severe disease, the higher percentage of CCR7+CD4+ T-cells. Conversely, chronic GVHD patients received a higher percentage of CCR7+CD8+ T-cells (p=0.02) in comparison to those who did not develop the complication. These data were also confirmed when patients were subdivided in degrees of the disease severity. A multivariable analysis confirmed that percentage of CCR7+CD4+ T-cells is a predictive factor of acute GVHD whereas the percentage of CCR7+CD8+ T-cells is a predictive factor of chronic GVHD. In vitro functional assays (migration and activation assays) supported the idea of CCR7+ T-cells were involved in the development of GVHD. As low levels of CD62L expression were detected in all apheresis products, we tested the hypothesis that CD62L was shed during apheresis procedure. Comparing CD62L surface levels in T-cells from the same donor immediately before collecting the apheresis product, and the final apheresis product we found that this process down-regulated CD62L in both CD4+ and CD8+ T cells (p=0.008). Interestingly, when CD62L levels were analysed in days 30 or 60 after engraftment, they recovered to baseline (p=0.008). However, to investigate the relation between CD62L expression and the development of GVHD in the recipient samples after the engraftment, no differences were observed comparing patients with GVHD to those who did not develop the disease. Discussion: Our prospective study indicates that the CCR7+ T-cells from the donor, which include naïve and central memory T-cells, contain the alloreactive cells with a high ability to mediate GVHD (in the case of both migration and activation). Therefore we suggest that the proportion and functional properties of CCR7+CD4+ and CCR7+CD8+ T-cells in the apheresis could act as a predictive biomarker to both acute and chronic GVHD respectively. Importantly, our study precludes that CD62L is lost in the apheresis and therefore it is not a reliable biomarker for the development of GVHD.Keywords: CCR7, CD62L, GVHD, SCT
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