Search results for: nuclear factor kappa B (NF-κB) pathway

Authors: Alan Luo, Hunter N. B. Moseley

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Many macromolecular structure entries in the Protein Data Bank (PDB) have a range of regional (localized) quality issues, be it derived from x-ray crystallography, Nuclear Magnetic Resonance (NMR) spectroscopy, or other experimental approaches. However, most PDB entries are judged by global quality metrics like R-factor, R-free, and resolution for x-ray crystallography or backbone phi-psi distribution statistics and average restraint violations for NMR. Regional quality is often ignored when PDB entries are re-used for a variety of structurally based analyses. The binding of ligands, especially ligands involved in energy metabolism, is of particular interest in many structurally focused protein studies. Using a regional quality metric that provides chemically interpretable information from electron density maps, a significant number of outliers in regional structural quality was detected across x-ray crystallographic PDB entries for proteins bound to biochemically critical ligands. In this study, a series of analyses was performed to evaluate both specific and general potential factors that could promote these outliers. In particular, these potential factors were the minimum distance to a metal ion, the minimum distance to a crystal contact, and the isotropic atomic b-factor. To evaluate these potential factors, Fisher’s exact tests were performed, using regional quality criteria of outlier (top 1%, 2.5%, 5%, or 10%) versus non-outlier compared to a potential factor metric above versus below a certain outlier cutoff. The results revealed a consistent general effect from region-specific normalized b-factors but no specific effect from metal ion contact distances and only a very weak effect from crystal contact distance as compared to the b-factor results. These findings indicate that no single specific potential factor explains a majority of the outlier ligand-bound regions, implying that human error is likely as important as these other factors. Thus, all factors, including human error, should be considered when regions of low structural quality are detected. Also, the downstream re-use of protein structures for studying ligand-bound conformations should screen the regional quality of the binding sites. Doing so prevents misinterpretation due to the presence of structural uncertainty or flaws in regions of interest.

Keywords: biomacromolecular structure, coenzyme, electron density discrepancy analysis, x-ray crystallography

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Authors: Denise Levy, Anna Lucia C. H. Villavicencio

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In a rapid-changing world, science teachers face considerable challenges. In addition to the basic curriculum, there must be included several transversal themes, which demand creative and innovative strategies to be arranged and integrated to traditional disciplines. In Brazil, nuclear science is still a controversial theme, and teachers themselves seem to be unaware of the issue, most often perpetuating prejudice, errors and misconceptions. This article presents the authors’ experience in the development of an interdisciplinary pedagogical proposal to include nuclear science in the basic curriculum, in a transversal and integrating way. The methodology applied was based on the analysis of several normative documents that define the requirements of essential learning, competences and skills of basic education for all schools in Brazil. The didactic materials and resources were developed according to the best practices to improve learning processes privileging constructivist educational techniques, with emphasis on active learning process, collaborative learning and learning through research. The material consists of an illustrated book for students, a book for teachers and a manual with activities that can articulate nuclear science to different disciplines: Portuguese, mathematics, science, art, English, history and geography. The content counts on high scientific rigor and articulate nuclear technology with topics of interest to society in the most diverse spheres, such as food supply, public health, food safety and foreign trade. Moreover, this pedagogical proposal takes advantage of the potential value of digital technologies, implementing QR codes that excite and challenge students of all ages, improving interaction and engagement. The expected results include the education of the educators for nuclear science communication in a transversal and integrating way, demystifying nuclear technology in a contextualized and significant approach. It is expected that the interdisciplinary pedagogical proposal contributes to improving attitudes towards knowledge construction, privileging reconstructive questioning, fostering a culture of systematic curiosity and encouraging critical thinking skills.

Keywords: science education, interdisciplinary learning, nuclear science, scientific literacy

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Authors: Subzar Ahmad Bhat, Saraswati Setia, V. K.Sehgal

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During the past earthquakes, open ground storey buildings have performed poorly due to the soft storey defect. Indian Standard IS 1893:2002 allows analysis of open ground storey buildings without considering infill stiffness but with a multiplication factor 2.5 in compensation for the stiffness discontinuity. Therefore, the aim of this paper is to check the applicability of the multiplication factor of 2.5 and study behaviour of the structure after the application of the multiplication factor. For this purpose, study is performed on models considering infill stiffness using SAP 2000 (Version 14) by linear static analysis and response spectrum analysis. Total seven models are analysed and designed for the range of multiplication factor ranging from 1.25 to 2.5. The value of multiplication factor equal to 2.5 has been found on the higher side, resulting in increased dimension and percentage of reinforcement without significant enhancement beyond a certain multiplication factor. When the building with OGS is designed for values of MF higher than 1.25 considering infill stiffness soft storey effect shifts from ground storey to first storey. For the analysis of the OGS structure best way to analysis the structure is to analyse it as the frame with stiffness and strength of the infill taken into account. The provision of infill walls in the upper storeys enhances the performance of the structure in terms of displacement and storey drift controls.

Keywords: open ground storey, multiplication factor, IS 1893:2002 provisions, static analysis, response spectrum analysis, infill stiffness, equivalent strut

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Authors: Jodie Stevenson, Lisa-Marie Emerson, Abigail Millings

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Mindfulness has been conceptualized as a dispositional trait, which is different across individuals. Previous research has independently identified both adult attachment orientations and emotion regulation abilities as correlates of dispositional mindfulness. Research has also presented a two-factor model of the relationship between these three constructs. The present study aimed to further develop this model and investigated theses relationships in a sample of 186 participants. Participants completed the Five Factor Mindfulness Questionnaire Short Form (FFMQ-SF), the Experiences in Close Relationships Scale for global attachment (ECR), the Emotion Regulation Questionnaire (ERC), and the Adult Disorganized Attachment scale (ADA). Exploratory factor analysis revealed a 3-factor solution accounting for 59% of the variance across scores on these measures. The first factor accounted for 32% of the variance and loaded highly on attachment and mindfulness subscales. The second factor accounted for 15% of the variance with strong loadings on emotion regulation subscales. The third factor accounted for 12% of the variance with strong loadings on disorganized attachment, and the mindfulness observes subscale. The results further confirm the relationship between attachment, mindfulness, and emotion regulation along with the unique addition of disorganized attachment. The extracted factors will then be used to predict well-being outcomes for an undergraduate student population.

Keywords: adult attachment, emotion regulation, mindfulness, well-being

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Authors: Shu-Pin Huang, Pai-Chi Teng, Hao-Han Chang, Chia-Hsin Liu, Yung-Lun Lin, Shu-Chi Wang, Hsin-Chih Yeh, Chih-Pin Chuu, Jiun-Hung Geng, Li-Hsin Chang, Wei-Chung Cheng, Chia-Yang Li

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The emergence of immune checkpoint inhibitors (ICIs) targeting proteins like PD-1 and PD-L1 has changed the treatment paradigm of bladder cancer. However, not all patients benefit from ICIs, with some experiencing early death. There's a significant need for biomarkers associated with the PD-1 pathway in bladder cancer. Current biomarkers focus on tumor PD-L1 expression, but a more comprehensive understanding of PD-1-related biology is needed. Our study has developed a seven-gene risk score panel, employing a comprehensive bioinformatics strategy, which could serve as a potential prognostic and predictive biomarker for bladder cancer. This panel incorporates the FYN, GRAP2, TRIB3, MAP3K8, AKT3, CD274, and CD80 genes. Additionally, we examined the relationship between this panel and immune cell function, utilizing validated tools such as ESTIMATE, TIDE, and CIBERSORT. Our seven-genes panel has been found to be significantly associated with bladder cancer survival in two independent cohorts. The panel was also significantly correlated with tumor infiltration lymphocytes, immune scores, and tumor purity. These factors have been previously reported to have clinical implications on ICIs. The findings suggest the potential of a PD-1 pathway-based transcriptomic panel as a prognostic and predictive biomarker in bladder cancer, which could help optimize treatment strategies and improve patient outcomes.

Keywords: bladder cancer, programmed cell death protein 1, prognostic biomarker, immune checkpoint inhibitors, predictive biomarker

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Authors: Seyed Abolhassan Naeini, Azam Kouhpeyma

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Reduction of water level at which a slope is submerged with it is called drawdown. Draw down can took place rapidly or slowly and in both situations, it can affect slope stability. Using coupled analysis (seepage and stability analysis) causes more accurate results. In this study, the stability of homogeneous embankment is investigated numerically. Slope safety factor changes due to changes in three factors of height, slope and drawdown rate have been investigated and compared. It was found that with increasing height and slope, the safety factor decreases, and with increasing the discharge rate, the safety factor increases.

Keywords: drawdown, slope stability, coupled seepage and stability analysis

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Authors: Sachin K. Samuchiwal, Barbara Balestrieri, Amanda Paskavitz, Hannah Raff, Joshua A. Boyce

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IL-33, a recently discovered member of the IL-1 cytokine family, binds to the TLR/IL1R super family receptor ST2 and induces type 2 immune responses. IL-33 is constitutively expressed in structural cells at barrier sites such as skin, lung, and intestine, and also inducibly expressed by hematopoietic cells including macrophages. Stimulation of macrophages by Lipopolysaccharide (LPS) can induce de novo IL-33 expression, and also causes the production of prostaglandin-E2 (PGE2) via cyclooxygenase (COX)-2 and microsomal PGE2 synthase-1 (mPGES-1). Because PGE2 can regulate macrophage functions through both autocrine and paracrine mechanisms, the potential interplay of endogenous PGE2 on IL-33 production was explored. Bone-marrow derived murine macrophages (bmMF) that lack either mPGES-1 or EP2 receptor expression were stimulated with LPS in the absence or presence of exogenous PGE2 along with pharmacological agonists and antagonists. The study results demonstrate that endogenous PGE2 markedly enhances LPS-induced IL-33 production by bmMFs via EP2 receptors. Moreover, exogenous PGE2 can amplify LPS-induced IL-33 expression dominantly by EP2 and partly by EP4 receptors by a pathway involving cAMP and exchange protein activated by cAMP (EPAC), but not protein kinase A (PKA). Though both IL-33 production and PGE2 generation in response to LPS require activation of both p38 MAPK and NF-κB, PGE2 did not influence this activation. In conclusion, it is demonstrated that endogenous PGE2 signaling through EP2 and EP4 receptors is a prerequisite for LPS-induced IL-33 production in bmMFs and the underlying cAMP mediated pathway involves EPAC. Since IL-33 is a critical pro-inflammatory cytokine in various pathological disorders, this PGE2-EP2/EP4-cAMP mediated pathway can be exploited to intervene in IL-33 driven pathologies.

Keywords: bone marrow macrophages, EPAC, IL-33, PGE2

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Authors: Khalid Almarri

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The UAE is currently developing a peaceful nuclear energy program as part of its low Carbon energy strategy to meet future energy demands. Research of nuclear energy technologies is required to support nuclear energy generation projects and maximize their performance. Research of this type will require building an operating a research reactor (RR), a costly undertaking in most circumstances. Collaboration between government and private parties through public, private partnerships (PPP) can maximize the benefits expected from the adoption of an RR project. The aim of this research is to establish the critical success factors (CSF) for developing an RR project for newcomer countries, with the UAE taken as a case study, through the utilization of public, private partnerships (PPP). The results of this study were arrived at through the use of semi-structured interviews conducted with ten experts in the field of research reactors, using grounded theory method. Underutilization was identified as the main stumbling block that impairs the success of research reactors.

Keywords: public private partnerships, research reactors, grounded theory, critical success factors

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Authors: Leo Carlo B. Rondina

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Self-image is an important factor to improve the self-esteem of the personnel. The purpose of the study is to determine the self-image of the police. The respondents were the 503 policemen assigned in different Police Station in Davao City, and they were chosen with the used of random sampling. With the used of Exploratory Factor Analysis (EFA), latent construct variables of police image were identified as follows; professionalism, obedience, morality and justice and fairness. Further, ordinal regression indicates statistical characteristics on ages 21-40 which means the age of the respondent statistically improves self-image.

Keywords: police image, exploratory factor analysis, ordinal regression, Galatea effect

Procedia PDF Downloads 257

Authors: Andressa dos Santos Nicolau, João P. da S.C Algusto, Claudio Márcio do N. A. Pereira, Roberto Schirru

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In case of abnormal situations, the nuclear power plant (NPP) operators must follow written procedures to check the condition of the plant and to classify the type of emergency. In this paper, we proposed a Real Time Expert System in order to improve operator’s performance in case of transient or accident with reactor shutdown. The expert system’s knowledge is based on the sequence of events (SoE) of known accident and two emergency procedures of the Brazilian Pressurized Water Reactor (PWR) NPP and uses two kinds of knowledge representation: rule and logic trees. The results show that the system was able to classify the response of the automatic protection systems, as well as to evaluate the conditions of the plant, diagnosing the type of occurrence, recovery procedure to be followed, indicating the shutdown root cause, and classifying the emergency level.

Keywords: emergence procedure, expert system, operator support, PWR nuclear power plant

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Authors: Huimin Zhao, Xiaoquan Liu, Haochen Liu

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The major challenge facing Alzheimer's Disease (AD) drug development is how to effectively improve cognitive function in clinical practice. Growing evidence indicates that stimulating hippocampal neurogenesis is a strategy for restoring cognition in animal models of AD. The mitogen-activated protein kinase (MAPK) pathway is a crucial factor in neurogenesis, which is negatively regulated by Dual-specificity phosphatase 16 (DUSP16). Transcriptome analysis of post-mortem brain tissue revealed up-regulation of DUSP16 expression in AD patients. Additionally, DUSP16 was involved in regulating the proliferation and neural differentiation of neural progenitor cells (NPCs). Nevertheless, whether the effect of DUSP16 on ameliorating cognitive disorders by influencing NPCs differentiation in AD mice remains unclear. Our study demonstrates an association between DUSP16 SNPs and clinical progression in individuals with mild cognitive impairment (MCI). Besides, we found that increased DUSP16 expression in both 3×Tg and SAMP8 models of AD led to NPC differentiation impairments. By silencing DUSP16, cognitive benefits, the induction of AHN and synaptic plasticity, were observed in AD mice. Furthermore, we found that DUSP16 is involved in the process of NPC differentiation by regulating c-Jun N-terminal kinase (JNK) phosphorylation. Moreover, the increased DUSP16 may be regulated by the ETS transcription factor (ELK1), which binds to the promoter region of DUSP16. Loss of ELK1 resulted in decreased DUSP16 mRNA and protein levels. Our data uncover a potential regulatory role for DUSP16 in adult hippocampal neurogenesis and provide a possibility to find the target of AD intervention.

Keywords: alzheimer's disease, cognitive function, DUSP16, hippocampal neurogenesis

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Authors: Rahaba Marima, Clement Penny

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The Health-related quality of life (HRQoL) for HIV positive patients has improved since the introduction of the highly active antiretroviral treatment (HAART). However, in the present HAART era, HIV co-morbidities such as lung cancer, a non-AIDS (NAIDS) defining cancer have been documented to be on the rise. Under normal physiological conditions, cells grow, repair and proliferate through the cell-cycle as cellular homeostasis is important in the maintenance and proper regulation of tissues and organs. Contrarily, the deregulation of the cell-cycle is a hallmark of cancer, including lung cancer. The association between lung cancer and the use of HAART components such as Efavirenz (EFV) is poorly understood. This study aimed at elucidating the effects of EFV on the cell-cycle genes’ expression in lung cancer. For this purpose, the human cell-cycle gene array composed of 84 genes was evaluated on both normal lung fibroblasts (MRC-5) cells and adenocarcinoma (A549) lung cells, in response to 13µM EFV or 0.01% vehicle. The ±2 up or down fold change was used as a basis of target selection, with p < 0.05. Additionally, RT-qPCR was done to validate the gene array results. Next, In-silico bio-informatics tools, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Reactome, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Ingenuity Pathway Analysis (IPA) were used for gene/gene interaction studies as well as to map the molecular and biological pathways influenced by the identified targets. Interestingly, the DNA damage response (DDR) pathway genes such as p53, Ataxia telangiectasia mutated and Rad3 related (ATR), Growth arrest and DNA damage inducible alpha (GADD45A), HUS1 checkpoint homolog (HUS1) and Role of radiation (RAD) genes were shown to be upregulated following EFV treatment, as revealed by STRING analysis. Additionally, functional enrichment analysis by the KEGG pathway revealed that most of the differentially expressed gene targets function at the cell-cycle checkpoint such as p21, Aurora kinase B (AURKB) and Mitotic Arrest Deficient-Like 2 (MAD2L2). Core analysis by IPA revealed that p53 downstream targets such as survivin, Bcl2, and cyclin/cyclin dependent kinases (CDKs) complexes are down-regulated, following exposure to EFV. Furthermore, Reactome analysis showed a significant increase in cellular response to stress genes, DNA repair genes, and apoptosis genes, as observed in both normal and cancerous cells. These findings implicate the genotoxic effects of EFV on lung cells, provoking the DDR pathway. Notably, the constitutive expression of this pathway (DDR) often leads to uncontrolled cell proliferation and eventually tumourigenesis, which could be the attribute of HAART components’ (such as EFV) effect on human cancers. Targeting the cell-cycle and its regulation holds a promising therapeutic intervention to the potential HAART associated carcinogenesis, particularly lung cancer.

Keywords: cell-cycle, DNA damage response, Efavirenz, lung cancer

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Authors: Kishor Chandra Kandpal, Amit Kumar

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The Indian Himalaya region harbours approximately 1748 plants of medicinal importance, and as per International Union for Conservation of Nature (IUCN), the 112 plant species among these are threatened and endangered. To ease the pressure on these plants, the government of India is encouraging its in-situ cultivation. The Saussurea costus, Valeriana jatamansi, and Picrorhiza kurroa have also been prioritized for large scale cultivation owing to their market demand, conservation value and medicinal properties. These species are found from 1000 m to 4000 m elevation ranges in the Indian Himalaya. Identification of these plants in the field requires taxonomic skills, which is one of the major bottleneck in the conservation and management of these plants. In recent years, Hyperspectral remote sensing techniques have been precisely used for the discrimination of plant species with the help of their unique spectral signatures. In this background, a spectral library of the above 03 medicinal plants was prepared by collecting the spectral data using a handheld spectroradiometer (325 to 1075 nm) from farmer’s fields of Himachal Pradesh and Uttarakhand states of Indian Himalaya. The Random forest (RF) model was implied on the spectral data for the classification of the medicinal plants. The 80:20 standard split ratio was followed for training and validation of the RF model, which resulted in training accuracy of 84.39 % (kappa coefficient = 0.72) and testing accuracy of 85.29 % (kappa coefficient = 0.77). This RF classifier has identified green (555 to 598 nm), red (605 nm), and near-infrared (725 to 840 nm) wavelength regions suitable for the discrimination of these species. The findings of this study have provided a technique for rapid and onsite identification of the above medicinal plants in the field. This will also be a key input for the classification of hyperspectral remote sensing images for mapping of these species in farmer’s field on a regional scale. This is a pioneer study in the Indian Himalaya region for medicinal plants in which the applicability of hyperspectral remote sensing has been explored.

Keywords: himalaya, hyperspectral remote sensing, machine learning; medicinal plants, random forests

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Authors: E. A. Krasikov

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As a main barrier against radioactivity outlet reactor pressure vessel (RPV) is a key component in terms of NPP safety. Therefore, present-day demands in RPV reliability enhance have to be met by all possible actions for RPV in-service embrittlement mitigation. Annealing treatment is known to be the effective measure to restore the RPV metal properties deteriorated by neutron irradiation. There are two approaches to annealing. The first one is so-called ‘dry’ high temperature (~475°C) annealing. It allows obtaining practically complete recovery, but requires the removal of the reactor core and internals. External heat source (furnace) is required to carry out RPV heat treatment. The alternative approach is to anneal RPV at a maximum coolant temperature which can be obtained using the reactor core or primary circuit pumps while operating within the RPV design limits. This low temperature «wet» annealing, although it cannot be expected to produce complete recovery, is more attractive from the practical point of view especially in cases when the removal of the internals is impossible. The first RPV «wet» annealing was done using nuclear heat (US Army SM-1A reactor). The second one was done by means of primary pumps heat (Belgian BR-3 reactor). As a rule, there is no recovery effect up to annealing and irradiation temperature difference of 70°C. It is known, however, that along with radiation embrittlement neutron irradiation may mitigate the radiation damage in metals. Therefore, we have tried to test the possibility to use the effect of radiation-induced ductilization in ‘wet’ annealing technology by means of nuclear heat utilization as heat and neutron irradiation sources at once. In support of the above-mentioned conception the 3-year duration reactor experiment on 15Cr3NiMoV type steel with preliminary irradiation at operating PWR at 270°C and following extra irradiation (87 h at 330°C) at IR-8 test reactor was fulfilled. In fact, embrittlement was partly suppressed up to value equivalent to 1,5 fold neutron fluence decrease. The degree of recovery in case of radiation enhanced annealing is equal to 27% whereas furnace annealing results in zero effect under existing conditions. Mechanism of the radiation-induced damage mitigation is proposed. It is hoped that «wet » annealing technology will help provide a better management of the RPV degradation as a factor affecting the lifetime of nuclear power plants which, together with associated management methods, will help facilitate safe and economic long-term operation of PWRs.

Keywords: controlling, embrittlement, radiation, steel, wet annealing

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Authors: Moon Byung Woo, Seok Chang-Sung, Koo Jae-Mean, Kim Sang-Young, Choi Jae Gu, Huh Nam-Su

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Recently, the occurrence of the earthquake has increased sharply and many of the casualties have occurred worldwide, due to the influence of earthquakes. Especially, the Fukushima nuclear power plant accident which was caused by the earthquake in 2011 has significantly increased the fear of people and the demand for the safety of the nuclear power plant. Thus, in order to prevent the earthquake accident at nuclear power plant, it is important to evaluate the fracture toughness considering the seismic loading rate. To obtain fracture toughness for the safety evaluation of nuclear power plant, it is desirable to perform experiments with a real scale pipe which is expensive and hard to perform. Therefore, many researchers have proposed various test specimens to replicate the fracture toughness of a real scale pipe. Since such specimens have several problems, the equivalent stress gradient (ESG) specimen has been recently suggested. In this study, in order to consider the effects of the dynamic loading speed on fracture toughness, the experiment was conducted by applying five different kinds of test speeds using an ESG specimen. In addition, after we performed the fracture toughness test under dynamic loading with different speeds using an ESG specimen and a standard specimen, we compared them with the test results under static loading.

Keywords: dynamic loading speed, fracture toughness, load-ratio-method, equivalent stress gradient (ESG) specimen

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Authors: Shreya Sara Ittycheria, K. C. Sivakumar, Shijulal Nelson Sathi, Priya Srinivas

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hCG, a heterodimer composed of α and β subunits, is a peptide hormone having numerous biological functions. Although hCG is expressed by placenta during pregnancy, ectopic β-hCG secretion is observed in many non-trophoblastic tumors including that of breast. In-vitro and in-vivo studies done in the lab, have proved that BRCA1 defective cancers express β-hCG and when β-hCG is expressed or supplemented, it promotes tumor progression and exhibits resistance to carboplatin and ABT888, in such cancers but not in BRCA1 wild type cancers. In cancer cells, instead of binding to its regular receptor, LH-CGR, β-hCG binds with Transforming Growth Factor Receptor 2 (TGFβRII) and phosphorylates it resulting in faster tumor progression through the Smad signaling pathway. Targeting β-hCG could be a potential therapeutic strategy for managing BRCA1 defective cancers. Here, molecular docking and dynamic simulation studies were done to identify potential small molecule inhibitors against β-hCG as there are currently no such inhibitors reported. The binding sites of TGFβRII on β-hCG were identified from the top 10 predicted complexes from Z Dock. Virtual screening of selected commercially available small molecules from various libraries such as ZINC, NCI and Life Chemicals amounting to a total of 50,025 molecules were done. Four potential small molecule inhibitors were identified, RgcbPs-1, RgcbPs-2, RgcbPs-3 and RgcbPs-4 with binding affinities -60.778 kcal/mol, -45.447 kcal/mol, -65.2268 kcal/mol and -82.040 kcal/mol respectively. Further, 100ns Molecular Dynamics (MD) simulation showed that these molecules form stable complexes with β-hCG. RgcbPs-1 maintains hydrogen bonds with Q54, L52, Q46, C100, G36, C57, C38 residues, RgcbPs-2 maintains hydrogen bonds with A83 residue, RgcbPs-3 maintains hydrogen bonds with C57, Y58, R94, G101 residues and RgcbPs-4 maintains hydrogen bonds with G36, C38, T40, C57, D99, C100, G101 and L104 residues of β-hCG all of which coincide with the TGFβRII binding site on β-hCG. These results show that these two inhibitors could be used either singly or in combination for inhibiting β-hCG from binding to TGFβRII and thereby directly inhibiting the tumorigenesis pathway.

Keywords: β-hCG, breast cancer, dynamic simulations, molecular docking, small molecule inhibitors, virtual screening.

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Authors: Dong Wook Lee

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This paper presents a method to analyze the stiffness of the expansion joint with structural support using a hybrid method combining computational and analytical methods. Many expansion joints found in tubes and ducts of mechanical structures are designed to absorb thermal expansion mismatch between their structural members and deal with misalignments introduced from the assembly/manufacturing processes. One of the important design perspectives is the system’s vibrational characteristics. We calculate the stiffness as a characterization parameter for structural joint systems using a combined Finite Element Analysis (FEA) and an analytical method. We apply the methods to two sample applications: external configurations of aircraft engines and nuclear power plant structures.

Keywords: expansion joint, expansion joint stiffness, finite element analysis, nuclear power plants, aircraft engine external configurations

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Authors: Mohamed El-Bady

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The Northern Egyptian Lagoons are (from east to west) Bardawil Lagoon, Manzala Lagoon, Burullus Lagoon, Edku Lagoons and Mariute Lagoon. These lagoons have been received the bulk of drainage water from the lands of Delta and from the other coastal areas. Where, the heavy metals can occur in Lagoons environments through a variety of sources, including industries, wastewaters and domestic effluents. The potential ecological risk index (RI) calculation of the bottom sediments of the northern lagoons depends on contamination factor (CF), potential ecological risk factor and proposed toxic response factor (Tr). Each lagoon with special indices according to its conditions.

Keywords: Northern Lagoons, Nile Delta, ecological risk index, contamination factor

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Authors: A. O. Ogunkeyede, D. Amuchi, A. A. Adebayo

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Heavy metal contaminations in soil have received great attention. Anthropogenic activities such as vehicular emission, industrial activities and constructions have resulted in elevated concentration of heavy metals in the surface soils. The metal particles can be free from the surface soil when they are disturbed and re-entrained in air, which necessitated the need to investigate surface soil at market environment where adults and children are present on daily basis. This study assesses concentration of heavy metal pollution, ecological and health risk factors in surface soil at Effurun market. 8 samples were collected at household material (EMH), fish (EMFs), fish and commodities (EMF-C), Abattoir (EMA 1 & 2), fruit sections (EMF 1 & 2) and lastly main road (EMMR). The samples were digested and analyzed in triplicate for contents of Lead (Pb), Nickel (Ni), Cadmium (Cd) and Copper (Cu). The mean concentration of the Pb mg/kg (112.27 ± 1.12) and Cu mg/kg (156.14 ± 1.10) were highest in the abattoir section (EMA 1). The mean concentrations of the heavy metal were then used to calculate the ecological and health risk for people within the market. Pb contamination at EMMR, EMF 2, EMFs were moderately while Pb shows considerable contamination at EMH, EMA 1, EMA 2 and EMF-C sections of the Effurun market. The ecological risk factor varies between low to moderate pollution for Pb and EMA 1 has the highest potential ecological risk that falls within moderate pollution. The hazard quotient results show that dermal exposure pathway is the possible means of heavy metal exposure to the traders while ingestion is the least sources of exposure to adult. The ingestion suggested that children around the EMA 1 have the highest possible exposure to children due to hand-to-mouth and object-to-mouth behaviour. The results further show that adults at the EMA1 will have the highest exposure to Pb due to inhalation during burning of cow with tyre that contained Pb and Cu. The carcinogenic risk values of most sections were higher than acceptable values, while Ni at EMMR, EMF 1 & 2, EMFs and EMF-C sections that were below the acceptable values. The cancer risk for inhalation exposure pathway for Pb (1.01E+17) shows a significant level of contamination than all the other sections of the market. It suggested that the people working at the Abattoir were very prone to cancer risk.

Keywords: carcinogenic, ecological, heavy metal, risk

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Authors: Michela Terlizzi, Chiara Colarusso, Aldo Pinto, Rosalinda Sorrentino

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Sphingosine-1-phosphate (S1P) is a membrane-derived bioactive phospholipid exerting a multitude of effects on respiratory cell physiology and pathology through five S1P receptors (S1PR1-5). Higher levels of S1P have been registered in a broad range of respiratory diseases, including inflammatory disorders and cancer, although its exact role is still elusive. Based on our previous study in which we found that S1P/S1PR3 is involved in an inflammatory pattern via the activation of Toll-like Receptor 9 (TLR9), highly expressed on lung cancer cells, the main goal of the current study was to better understand the involvement of S1P/S1PR3 pathway/signaling during lung carcinogenesis, taking advantage of a mouse model of first-hand smoke exposure and of carcinogen-induced lung cancer. We used human samples of Non-Small Cell Lung Cancer (NSCLC), a mouse model of first-hand smoking, and of Benzo(a)pyrene (BaP)-induced tumor-bearing mice and A549 lung adenocarcinoma cells. We found that the intranuclear, but not the membrane, localization of S1PR3 was associated to the proliferation of lung adenocarcinoma cells, the mechanism that was correlated to human and mouse samples of smoke-exposure and carcinogen-induced lung cancer, which were characterized by higher utilization of S1P. Indeed, the inhibition of the membrane S1PR3 did not alter tumor cell proliferation after TLR9 activation. Instead, according to the nuclear localization of sphingosine kinase (SPHK) II, the enzyme responsible for the catalysis of the S1P last step synthesis, the inhibition of the kinase completely blocked the endogenous S1P-induced tumor cell proliferation. These results prove that the endogenous TLR9-induced S1P can on one side favor pro-inflammatory mechanisms in the tumor microenvironment via the activation of cell surface receptors, but on the other tumor progression via the nuclear S1PR3/SPHK II axis, highlighting a novel molecular mechanism that identifies S1P as one of the crucial mediators for lung carcinogenesis-associated inflammatory processes and that could provide differential therapeutic approaches especially in non-responsive lung cancer patients.

Keywords: sphingosine-1-phosphate (S1P), S1P Receptor 3 (S1PR3), smoking-mice, lung inflammation, lung cancer

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Authors: Dongheon Shin, Kyungnam Ko, Jongchul Huh

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The investigation on wind turbine degradation was carried out using the nacelle wind data. The three Vestas V80-2MW wind turbines of Sungsan wind farm in Jeju Island, South Korea were selected for this work. The SCADA data of the wind farm for five years were analyzed to draw power curve of the turbines. It is assumed that the wind distribution is the Rayleigh distribution to calculate the normalized capacity factor based on the drawn power curve of the three wind turbines for each year. The result showed that the reduction of power output from the three wind turbines occurred every year and the normalized capacity factor decreased to 0.12%/year on average.

Keywords: wind energy, power curve, capacity factor, annual energy production

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Authors: S. W. Chen, W. K. Lin, J. R. Wang, C. Shih, H. T. Lin, H. C. Chang, W. Y. Li

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Kuosheng nuclear power plant (NPP) is a BWR/6 type NPP and located on the northern coast of Taiwan. First, Kuosheng NPP TRACE model were developed in this research. In order to assess the system response of Kuosheng NPP TRACE model, startup tests data were used to evaluate Kuosheng NPP TRACE model. Second, the over pressurization transient analysis of Kuosheng NPP TRACE model was performed. Besides, in order to confirm the mechanical property and integrity of fuel rods, FRAPTRAN analysis was also performed in this study.

Keywords: TRACE, safety analysis, BWR/6, FRAPTRA

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Authors: Fang Yao, Minglei Chen

Abstract:

City shrinkage is one of the thorny problems that many European cities have to face with nowadays. It is mainly expressed as the decrease of population in these cities. Eastern Germany is one of the pioneers of European shrinking cities with long shrinking history. Selecting one representative shrinking city Halle(Saale) in eastern Germany as research objective, collecting and investigating nearly 20 years (1993-2010) municipal data after the reunification of Germany. These data based on five dimensions, which are demographic, economic, social, spatial and environmental and total 16 eligible variables. Using Factor Analysis to dealing with these variables in order to assess the most important factors affecting shrinking Halle. The Factor Analysis shows that there are three main factors determine the shrinkage of Halle, namely demographical and economical factor, social stability factor, and city vitality factor. Three factors acts at different period of Halle’s shrinkage: from 1993 to 1997 the demographical and economical factor played an important role; from 1997 to 2004 the social stability is significant to city shrinkage; since 2005 city vitality factors determines the shrinkage of Halle. In recent years, the shrinkage in Halle mitigates that shows the sign of growing population. Thus the city Halle should focus on attaching more importance on the city vitality factor to prevent the city from shrinkage. Meanwhile, the city should possess a positive perspective that to shift the growth-oriented development to tap the potential of shrinking cities. This method is expected to apply to further research and other shrinking cities.

Keywords: demography, factor analysis, Halle, shrinking cities

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Authors: K. E. Daryani, H. Mohamad

Abstract:

Uncertainties in the geo-structure analysis and design have a significant impact on the safety of slopes. Traditionally, uncertainties in the geotechnical design are addressed by incorporating a conservative factor of safety in the analytical model. In this paper, a risk-based approach is adopted to assess the influence of the geotechnical variable uncertainties on the stability of infinite slopes in cohesionless soils using the “partial factor of safety on shear strength” approach as stated in Eurocode 7. Analyses conducted using Monte Carlo simulation show that the same partial factor can have very different levels of risk depending on the degree of uncertainty of the mean values of the soil friction angle and void ratio.

Keywords: Safety, Probability of Failure, Reliability, Infinite Slopes, Sand.

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Authors: Azza A. Ali, Mona G. Khalil, Hemat A. Elariny, Shereen S. El Shaer

Abstract:

Background: Aluminium (Al) is very abundant metal in the earth’s crust. It is a constituent of cooking utensils, medicines, cosmetics, some foods and food additives. Salts of Al are widely used in the treatment of drinking water for purification purposes. Excessive and prolonged exposure to Al causes oxidative stress and impairment of many physiological functions. Its accumulation in liver and kidney causes hepatotoxicity and nephrotoxicity. Social isolation (SI) or Protein malnutrition (PM) also increases oxidative stress and may enhance the toxicity of Al as well as the degeneration in liver and kidney. Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea and has strong antioxidant as well as anti-inflammatory activities and can protect against oxidative stress-induced degenerations. Objective: To study the influence of stress or PM on Al-induced nephrotoxicity and hepatotoxicity in rats, as well as on the potential role of EGCG in providing protection. Methods: Rats received daily AlCl3 (70 mg/kg, IP) for three weeks (Al-toxicity groups) except one normal control group received saline. Al-toxicity groups were divided into four treated and four untreated groups; treated rats received EGCG (10 mg/kg, IP) together with AlCl3. One group of both treated and untreated rats served as control for each of them, and the others were subjected to either stress (mild using isolation or high using electric shock) or to PM (10% casein diet). Specimens of liver and kidney were used for assessment of levels of inflammatory mediators as TNF-α, IL6β, nuclear factor kappa B (NF-κB), oxidative stress (MDA, SOD, TAC, NO), Caspase-3 and for DNA fragmentation as well as for histopathological examinations. Biochemical changes were also measured in the serum as total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea as well as the level of Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lactate deshydrogenase (LDH). Results: Nephrotoxicity and hepatotoxicity induced by Al were enhanced in rats exposed to stress and to PM. The influence of stress was more pronounced than PM. Al-toxicity was indicated by the increase in liver and kidney MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3, DNA fragmentation and in ALT, AST, ALP, LDH and total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea levels, together with the decrease in total proteins, SOD, TAC. EGCG provided protection against hazards of Al as indicated by the decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation as well as in levels of ALT, AST, ALP, LDH and total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea in liver and kidney, together with the increase in total proteins, SOD, TAC and confirmed by histopathological examinations. It provided more pronounced protection in high stressful conditions than in mild one than in PM. Conclusion: Stress have a bad impact on Al-induced nephrotoxicity and hepatotoxicity more than PM. Thus it can clarify and maximize the role of EGCG in providing protection. Consequently, administration of EGCG is advised with excessive Al-exposure to avoid nephrotoxicity and hepatotoxicity especially in populations more subjected to stress or PM.

Keywords: aluminum, stress, protein malnutrition, nephrotoxicity, hepatotoxicity, epigallocatechin-3-gallate, rats

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Authors: Betty Anson

Abstract:

Researchers have found that mature sperm cells are not only devoid of mature MTDNA (mitochondrial DNA) but also lack a particular protein essential for DNA maintenance, known as mitochondrial transcription factor A, or TFAM (transcription factor A mitochondria). As a result, children get the DNA of certain important body functions only from their mothers. More experiments show that TFAM appears to burn out when it is used as a source of energy for sperm movement. This study investigates alternative sources of energy for sperm movement that could sustain the existence of TFAM.

Keywords: mItochondria, DNA, TFAM, sperm

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Authors: Ali Bahri Lubis

Abstract:

The study of dioxygenase enzymatic mechanism on tryptophan oxidation has been a wide interest since the reaction is rate-limiting step of kynurenine pathway. In this research, observation of tryptophan oxidation through h-IDO enzyme along with synthesis of enzyme products was conducted in order to comprehend how the enzyme works on distinct substrates. UV-vis spectrophotometry, LC-MS, H-NMR and HSQC measurement were carried out to characterise enzyme product. It is found that while tryptophan was oxidised to form Nformylkynurenine (NFK) as a major product and hydroxypyrroloindole amine carboxylic acid (HPIC) in cis and trans confirmed in HSQC, N-methyl tryptophan substrate was converted to NFK and trans HPIC only. Other intriguing results showed that 5-hydroxy- tryptophan and Stryptophan was degraded to become NFK and epoxide cyclic respectively. The formation of NFK was considered through dioxygenation pathway, however HPIC was formed via monooxygenation. The epoxide cyclic—considered as intermediate compound in the mechanism— from S-tryptophan was not able to cleave the epoxide ring since bond energy of epoxide was probably much stronger. This validates the enzymatic mechanism where the intermediate compound in the enzymatic mechanism is epoxide cyclic.

Keywords: tryptophan oxidation, heme-dioxygenases, N-formylkynurenine, hydroxypyrrroloindoleamine, monooxidation

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Authors: Ahmed Elsebaay, Maged A. Abu Adma, Mahmoud Ramadan

Abstract:

This study presents a technique clarifying the effect of ambient air temperature and loads power factor changing from standard values on electric generator power rating. The study introduces an optimized technique for selecting the correct electric generator power rating for certain application and operating site ambient temperature. The de-rating factors due to the previous effects will be calculated to be applied on a generator to select its power rating accurately to avoid unsafe operation and save its lifetime. The information in this paper provides a simple, accurate, and general method for synchronous generator selection and eliminates common errors.

Keywords: ambient temperature, de-rating factor, electric generator, power factor

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Authors: Alexey V. Klyuev, Arkady V. Yakimov, Mikhail I. Ryzhkin, Andrey V. Klyuev

Abstract:

Fluctuations of Schottky diode parameters in a structure of the mixer are investigated. These fluctuations are manifested in two ways. At the first, they lead to fluctuations in the transfer factor that is lead to the amplitude fluctuations in the signal of intermediate frequency. On the basis of the measurement data of 1/f noise of the diode at forward current, the estimation of a spectrum of relative fluctuations in transfer factor of the mixer is executed. Current dependence of the spectrum of relative fluctuations in transfer factor of the mixer and dependence of the spectrum of relative fluctuations in transfer factor of the mixer on the amplitude of the heterodyne signal are investigated. At the second, fluctuations in parameters of the diode lead to the occurrence of 1/f noise in the output signal of the mixer. This noise limits the sensitivity of the mixer to the value of received signal.

Keywords: current-voltage characteristic, fluctuations, mixer, Schottky diode, 1/f noise

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Authors: Muna Al-Kalbani, Thuwayba Al Barwani, Otherine Neisler, Hussain Alkharusi, David Clayton, Humaira Al-Sulaimani, Mohammad Khan, Hamad Al-Yahmadi

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This study describes the psychometric properties and factor structure of the University Readiness Survey (URS). Survey data were collected from sample of 2652 students from Sultan Qaboos University. Exploratory factor analysis identified ten significant factors underlining the structure. The results of Confirmatory factor analysis showed a good fit to the data where the indices for the revised model were χ2(df = 1669) = 6093.4; CFI = 0.900; GFI =0.926; PCLOSE = 1.00 and RMSAE = 0.030 where each of these indices were above threshold. The overall value of Cronbach’s alpha was 0.899 indicating that the instrument score was reliable. Results imply that the URS is a valid measure describing the college readiness pattern among Sultan Qaboos University students and the Arabic version could be used by university counselors to identify students’ readiness factors. Nevertheless, further validation of the of the USR is recommended.

Keywords: college readiness, confirmatory factor analysis, reliability, validity

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