Search results for: pathway analyses

Authors: Andrés Quiroz, Emilio Hormazabal, Ana Mutis, Fernando Ortega, Manuel Chacón-Fuentes, Leonardo Parra

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Red clover (Trifolium pratense L.) is an important forage species in temperate regions of the world. The main limitation of this species worldwide is a lack of persistence related to the high mortality of plants due to a complex of biotic and abiotic factors, determining a life span of two or three seasons. Because of the importance of red clover in Chile, a red clover breeding program was started at INIA Carillanca Research Center in 1989, with the main objective of improving the survival of plants, forage yield, and persistence. The main selection criteria for selecting new varieties have been based on agronomical parameters and biotic factors. The main biotic factor associated with red clover mortality in Chile is Hylastinus obscurus (Coleoptera: Curculionidae). Both larval and adults feed on the roots, causing weakening and subsequent death of clover plants. Pesticides have not been successful for controlling infestations of this root borer. Therefore, alternative strategies for controlling this pest are a high priority for red clover producers. Currently, the role of semiochemical in the interaction between H. obscurus and red clover plants has been widely studied for our group. Specifically, from the red clover foliage has been identified limonene is eliciting repellency from the root borer. Limonene is generated in the plant from two independent biosynthetic pathways, the mevalonic acid, and deoxyxylulose pathway. Mevalonate pathway enzymes are localized in the cytosol, whereas the deoxyxylulose phosphate pathway enzymes are found in plastids. In summary, limonene can be determinated by enzymatic bioassay using GPP as substrate and by limonene synthase expression. Therefore, the main objective of this work was to study genetic variation of limonene in material provided by INIA´s Red Clover breeding program. Protein extraction was carried out homogenizing 250 mg of leave tissue and suspended in 6 mL of extraction buffer (PEG 1500, PVP-30, 20 mM MgCl2 and antioxidants) and stirred on ice for 20 min. After centrifugation, aliquots of 2.5 mL were desalted on PD-10 columns, resulting in a final volume of 3.5 mL. Protein determination was performed according to Bradford with BSA as a standard. Monoterpene synthase assays were performed with 50 µL of protein extracts transferred into gas-tight 2 mL crimp seal vials after addition of 4 µL MgCl₂ and 41 µL assay buffer. The assay was started by adding 5 µL of a GPP solution. The mixture was incubated for 30 min at 40 °C. Biosynthesized limonene was quantified in a GC equipped with a chiral column and using synthetic R and S-limonene standards. The enzymatic the production of R and S-limonene from different Superqueli-Carillanca genotypes is shown in this work. Preliminary results showed significant differences in limonene content among the genotypes analyzed. These results constitute an important base for selecting genotypes with a high content of this repellent monoterpene towards H. obscurus.

Keywords: head space, limonene enzymatic determination, red clover, Hylastinus obscurus

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Authors: Mahya Naghipoor

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Purpose: Non-small cell lung cancer (NSCLC) is the most common lung cancer type. Epidermal growth factor receptor (EGFR) mutation is the main reason which causes NSCLC. Computed tomography (CT) is used for diagnosis and prognosis of lung cancers because of low price and little invasion. Semantic analyses of qualitative CT features are based on visual evaluation by radiologist. However, the naked eye ability may not assess all image features. On the other hand, radiomics provides the opportunity of quantitative analyses for CT images features. The aim of this review study was comparing accuracy of semantic and radiomics features in prognosis of EGFR mutation in NSCLC. Methods: For this purpose, the keywords including: non-small cell lung cancer, epidermal growth factor receptor mutation, semantic, radiomics, feature, receiver operating characteristics curve (ROC) and area under curve (AUC) were searched in PubMed and Google Scholar. Totally 29 papers were reviewed and the AUC of ROC analyses for semantic and radiomics features were compared. Results: The results showed that the reported AUC amounts for semantic features (ground glass opacity, shape, margins, lesion density and presence or absence of air bronchogram, emphysema and pleural effusion) were %41-%79. For radiomics features (kurtosis, skewness, entropy, texture, standard deviation (SD) and wavelet) the AUC values were found %50-%86. Conclusions: In conclusion, the accuracy of radiomics analysis is a little higher than semantic in prognosis of EGFR mutation in NSCLC.

Keywords: lung cancer, radiomics, computer tomography, mutation

Procedia PDF Downloads 139

Authors: Kan Yu, Khui Hung Lee, Eben Afrifa-Yamoah, Jing Guo, Katrina Harrison, Jack Goldblatt, Nicholas Pachter, Jitian Xiao, Guicheng Brad Zhang

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Background and Significance of the Study: Congenital Heart Defects (CHDs) are the most common malformation at birth and one of the leading causes of infant death. Although the exact etiology remains a significant challenge, epigenetic modifications, such as DNA methylation, are thought to contribute to the pathogenesis of congenital heart defects. At present, no existing DNA methylation biomarkers are used for early detection of CHDs. The existing CHD diagnostic techniques are time-consuming and costly and can only be used to diagnose CHDs after an infant was born. The present study employed a machine learning technique to analyse genome-wide methylation data in children with and without CHDs with the aim to find methylation biomarkers for CHDs. Methods: The Illumina Human Methylation EPIC BeadChip was used to screen the genome‐wide DNA methylation profiles of 24 infants diagnosed with congenital heart defects and 24 healthy infants without congenital heart defects. Primary pre-processing was conducted by using RnBeads and limma packages. The methylation levels of top 600 genes with the lowest p-value were selected and further investigated by using a random forest approach. ROC curves were used to analyse the sensitivity and specificity of each biomarker in both training and test sample sets. The functionalities of selected genes with high sensitivity and specificity were then assessed in molecular processes. Major Findings of the Study: Three genes (MIR663, FGF3, and FAM64A) were identified from both training and validating data by random forests with an average sensitivity and specificity of 85% and 95%. GO analyses for the top 600 genes showed that these putative differentially methylated genes were primarily associated with regulation of lipid metabolic process, protein-containing complex localization, and Notch signalling pathway. The present findings highlight that aberrant DNA methylation may play a significant role in the pathogenesis of congenital heart defects.

Keywords: biomarker, congenital heart defects, DNA methylation, random forest

Procedia PDF Downloads 139

Authors: Johnson Okoduwa Imumbhon, Mohammad Didarul Alam, Yiding Cao

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Structural analyses are commonly employed to test the integrity of aircraft component systems in the design stage to demonstrate the capability of the structural components to withstand what it was designed for, as well as to predict potential failure of the components. The analyses are also essential for weight minimization and selecting the most resilient materials that will provide optimal outcomes. This research focuses on testing the structural nature of a high-lift low Reynolds number airfoil profile design, the Selig S1223, under certain loading conditions for a drone model application. The wing (ribs, spars, and skin) of the drone model was made of carbon fiber-reinforced polymer and designed in SolidWorks, while the finite element analysis was carried out in ANSYS mechanical in conjunction with the lift and drag forces that were derived from the aerodynamic airfoil analysis. Additionally, modal analysis was performed to calculate the natural frequencies and the mode shapes of the wing structure. The structural strain and stress determined the minimal deformations under the wing loading conditions, and the modal analysis showed the prominent modes that were excited by the given forces. The research findings from the structural analysis of the S1223 high-lift airfoil indicated that it is applicable for use in an unmanned aerial vehicle as well as a novel reciprocating-airfoil-driven vertical take-off and landing (VTOL) drone model.

Keywords: CFRP, finite element analysis, high-lift, S1223, strain, stress, VTOL

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Authors: M. Amelsakhi, A. Sohrabi-Bidar, A. Shareghi

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One of the most important issues about the structural damages caused by earthquake is the evaluating of the spectral response of the site on which the construction is built. This fact has demonstrated during many earlier earthquakes and many researchers’ reports have concerned with it. According to these reports, features of the site materials and geometry of the ground surface are considered the main factors. This study concentrates on the specific form of topographies like hills. Assessing of spectral responses of different points on the hills and beside demonstrates considerable differences between 1D and 2D methods of geotechnical analyses. A general trend of amplifications on the top of the hills and de-amplifications near the toe of the hills has been appeared within the acceleration, velocity and displacement response spectrums of horizontal motion. Evaluating of spectral responses of different sizes of the hills revealed that as much as the hill-size enlarges differences between spectral responses of 1D and 2D analyses transfers to longer range of periods and becomes wider.

Keywords: topography effect, amplification ratio, response spectrum, earth resources engineering

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Authors: Hala Raslan, Noha Eltaweel, Hanaa Rasmi, Solaf Kamel, May Magdy, Sherif Ismail, Khalda Amr

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Introduction: Rheumatoid arthritis (RA) is an inflammatory, autoimmune disorder with progressive joint damage. Osteoarthritis (OA) is a degenerative disease of the articular cartilage that shows multiple clinical manifestations or symptoms resembling those of RA. Genetic predisposition is believed to be a principal etiological factor for RA and OA. In this study, we aimed to measure the expression of the top deregulated miRNAs that might be the cause of pathogenesis in both diseases, according to our latest NGS analysis. Six of the deregulated miRNAs were selected as they had multiple target genes in the RA pathway, so they are more likely to affect the RA pathogenesis.Methods: Eighty cases were recruited in this study; 45 rheumatoid arthiritis (RA), 30 osteoarthiritis (OA) patients, as well as 20 healthy controls. The selection of the miRNAs from our latest NGS study was done using miRwalk according to the number of their target genes that are members in the KEGG RA pathway. Total RNA was isolated from plasma of all recruited cases. The cDNA was generated by the miRcury RT Kit then used as a template for real-time PCR with miRcury Primer Assays and the miRcury SYBR Green PCR Kit. Fold changes were calculated from CT values using the ΔΔCT method of relative quantification. Results were compared RA vs Controls and OA vs Controls. Target gene prediction and functional annotation of the deregulated miRNAs was done using Mienturnet. Results: Six miRNAs were selected. They were miR-15b-3p, -128-3p, -194-3p, -328-3p, -542-3p and -3180-5p. In RA samples, three of the measured miRNAs were upregulated (miR-194, -542, and -3180; mean Rq= 2.6, 3.8 and 8.05; P-value= 0.07, 0.05 and 0.01; respectively) while the remaining 3 were downregulated (miR-15b, -128 and -328; mean Rq= 0.21, 0.39 and 0.6; P-value= <0.0001, <0.0001 and 0.02; respectively) all with high statistical significance except miR-194. While in OA samples, two of the measured miRNAs were upregulated (miR-194 and -3180; mean Rq= 2.6 and 7.7; P-value= 0.1 and 0.03; respectively) while the remaining 4 were downregulated (miR-15b, -128, -328 and -542; mean Rq= 0.5, 0.03, 0.08 and 0.5; P-value= 0.0008, 0.003, 0.006 and 0.4; respectively) with statistical significance compared to controls except miR-194 and miR-542. The functional enrichment of the selected top deregulated miRNAs revealed the highly enriched KEGG pathways and GO terms. Conclusion: Five of the studied miRNAs were greatly deregulated in RA and OA, they might be highly involved in the disease pathogenesis and so might be future therapeutic targets. Further functional studies are crucial to assess their roles and actual target genes.

Keywords: MiRNAs, expression, rheumatoid arthritis, osteoarthritis

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Authors: Shalini Arora, Sri Sivakumar

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The deep removal of high molecular weight sulphur compounds (e.g., 4,6, dimethyl dibenzothiophene) is challenging due to their steric hindrance. Hydrogenation desulfurization (HYD) pathway is the main pathway to remove these sulfur compounds, and it is mainly governed by the number of type 2 sites. The formation of type 2 sites can be enhanced by modulating the pore structure and the interaction between the active metal and support. To this end, we report the enhanced HDS catalytic activity of ultrasmall NiMo supported on amorphous alumina (A-Al₂O₃) catalysts by one pot colloidal synthesis method followed by calcination and sulfidation. The amorphous alumina (A-Al₂O₃) was chosen as the support due to its lower surface energy, better physicochemical properties, and enhanced acidic sites (due to the dominance of tetra and penta coordinated [Al] sites) than crystalline alumina phase. At 20% metal oxide composition, NiMo supported on A-Al₂O₃ catalyst showed 1.4 and 1.2 times more reaction rate constant and turn over frequency (TOF) respectively than the conventional catalyst (wet impregnated NiMo catalysts) for HDS reaction of dibenzothiophene reactant molecule. A-Al₂O₃ supported catalysts represented enhanced type 2 sites formation (because this catalystpossesses higher sulfidation degree (80%) and NiMoS sites (19.3 x 10¹⁷ sites/mg) with desired optimum stacking degree (2.5) than wet impregnated catalyst at same metal oxide composition 20%) along with higher active metal dispersion, Mo edge site fraction. The experimental observations were also supported by DFT simulations. Lower heat of adsorption (< 4.2 ev for MoS2 interaction and < 3.15 ev for Ni doped MoS2 interaction) values for A-Al₂O₃ confirmed the presence of weaker metal-support interaction in A-Al₂O₃ in contrast to crystalline ℽ-Al₂O3. The weak metal-support interaction for prepared catalysts clearly suggests the higher formation of type 2 sites which leads to higher catalytic activity for HDS reaction.

Keywords: amorphous alumina, colloidal, desulfurization, metal-support interaction

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Authors: Pouya Kaafi, Gholamreza Ghodrati Amiri

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Abnormal loads due to natural events, implementation errors and some other issues can lead to occurrence of progressive collapse in structures. Most of the past researches consist of 2- Dimensional (2D) models of steel frames without consideration of the floor system effects, which reduces the accuracy of the modeling. While employing a 3-Dimensional (3D) model and modeling the concrete slab system for the floors have a crucial role in the progressive collapse evaluation. In this research, a 3D finite element model of a 5-story steel building is modeled by the ABAQUS software once with modeling the slabs, and the next time without considering them. Then, the progressive collapse potential is evaluated. The results of the analyses indicate that the lack of the consideration of the slabs during the analyses, can lead to inaccuracy in assessing the progressive failure potential of the structure.

Keywords: abnormal loads, composite floor system, intermediate steel moment resisting frame system, progressive collapse

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Authors: Henrique C. C. Andrade, Ana Beatriz C. G. Silva, Fernando Luiz B. Ribeiro, Samir Maghous, Jose Claudio F. Telles, Eduardo M. R. Fairbairn

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The present paper aims at developing a parallel computational model for numerical simulation of poromechanics analyses of heterogeneous reservoirs. In the context of macroscopic poroelastoplasticity, the hydromechanical coupling between the skeleton deformation and the fluid pressure is addressed by means of two constitutive equations. The first state equation relates the stress to skeleton strain and pore pressure, while the second state equation relates the Lagrangian porosity change to skeleton volume strain and pore pressure. A specific algorithm for local plastic integration using a tangent operator is devised. A modified Cam-clay type yield surface with associated plastic flow rule is adopted to account for both contractive and dilative behavior.

Keywords: finite element method, poromechanics, poroplasticity, reservoir analysis

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Authors: Rahele Hasani, Iraj Mehregan, Kambiz Larijani, Taher Nejadsattari, Romain Scalone

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Essential oils of Heracleum persicum (Apiaceae) have been widely used from many years ago, but the difference of its properties among different populations have not been identified up to now. Hydrodistilation Clevenger type was used to obtaining the fruit essential oils of four populations of H. persicum from different localities in Iran, then they were characterized by GC-FID and GC-MS analyses. Some ecological factors were also measured. The oils of four populations were compared to determine the similarities and differences and the relationships between these factors and ecological factors. Based on the result, 18-32 different components were identified in four populations, while the percentage of the main components was higher in population with lower number of components. According to the statistical analyses of chemical components and ecological factors, it can be concluded that some ecological factors such as altitude, less humidity, high difference between day and night temperature and salty soil would lead to lower number of components in essential oil, whereas they consist the higher percentage.

Keywords: Chemotaxonomy, Persian hogweed, Ecological factors, Apiaceae.

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Authors: Salma A. El-Marasy, Rehab F. Abdel-Rahman, Reham M. Abd-Elsalam

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The burden of stroke is intensely increasing worldwide. Brain injury following transient or permanent focal cerebral ischemia develops ischemic stroke as a consequence of a complex series of pathophysiological events. The aim of this study is to evaluate the possible neuroprotective effect of a dipeptidyl peptidase-4 inhibitor, vildagliptin, independent on its insulinotropic properties in non-diabetic rats subjected to cerebral ischemia. Anaesthetized Wistar rats were subjected to either left middle cerebral artery occlusion (MCAO) or sham operation followed by reperfusion after 30 min of MCAO. The other three groups were orally administered vildagliptin at 3 dose levels (2.5, 5, 10 mg/kg) for 3 successive weeks before subjected to left focal cerebral ischemia/reperfusion and till the end of the study. Neurological deficit scores and motor activity were assessed 24h following reperfusion. 48h following reperfusion, rats were euthanized and their left brain hemispheres were harvested and used in the biochemical, histopathological, and immunohistochemical investigations. Vildagliptin pretreatment improved neurological score deficit, locomotor activity and motor coordination in MCAO rats. Moreover, vildagliptin reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), phosphotylinosital 3 kinase (PI3K), phosphorylated of protein kinase B (p-AKT), and mechanistic target of rapamycin (mTOR) brain contents in addition to reducing protein expression of caspase-3. Also, vildagliptin showed a dose-dependent attenuation in neuronal cell loss and histopathological alterations in MCAO rats. This study proves that vildagliptin exerted the neuroprotective effect in a dose-dependent manner as shown in amelioration of neuronal cell loss and histopathological damage in MCAO rats, which may be mediated by attenuating neuronal and motor deficits, it’s anti-oxidant property, activation of PI3K/AKT/mTOR pathway and its anti-apoptotic effect.

Keywords: caspase-3, cerebral ischemia, dipeptidyl peptidase-4 inhibitor, oxidative stress, PI3K/AKT/mTOR pathway, rats, vildagliptin

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Authors: Iman Atighi, Jalal Soleimannejad, Ahmad Akbarinasab, Saeid Moradpour

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In the past, we could increase profit by increasing product prices. But in the new decade, a competitive market does not let us to increase profit with increase prices. Therefore, the only way to increase profit will be reduce costs. A significant percentage of production costs are the maintenance costs, and analysis of these costs could achieve more profit. Most maintenance strategies such as RCM (Reliability-Center-Maintenance), TPM (Total Productivity Maintenance), PM (Preventive Maintenance) etc., are trying to reduce maintenance costs. In this paper, decreasing the maintenance costs of Concentration Plant of Golgohar Company (GEG) was examined by using of MTBF (Mean Time between Failures) and MTTR (Mean Time to Repair) analyses. These analyses showed that instead of buying new machines and increasing costs in order to promote capacity, the improving of MTBF and MTTR indexes would solve capacity problems in the best way and decrease costs.

Keywords: Golgohar Iron Ore Mining and Industrial Company, maintainability, maintenance costs, reliability-center-maintenance

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Authors: Diyar Yousif Ali

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Braced frames, besides other structural systems, such as shear walls or moment resisting frames, have been a valuable and effective technique to increase structures against seismic loads. In wind or seismic excitations, diagonal members react as truss web elements which would afford tension or compression stresses. This study proposes to consider the effect of bracing diagonal configuration on values of base shear and displacement of building. Two models were created, and nonlinear pushover analysis was implemented. Results show that bracing members enhance the lateral load performance of the Concentric Braced Frame (CBF) considerably. The purpose of this article is to study the nonlinear response of reinforced concrete structures which contain hollow pipe steel braces as the major structural elements against earthquake loads. A five-storey reinforced concrete structure was selected in this study; two different reinforced concrete frames were considered. The first system was an un-braced frame, while the last one was a braced frame with diagonal bracing. Analytical modelings of the bare frame and braced frame were realized by means of SAP 2000. The performances of all structures were evaluated using nonlinear static analyses. From these analyses, the base shear and displacements were compared. Results are plotted in diagrams and discussed extensively, and the results of the analyses showed that the braced frame was seemed to capable of more lateral load carrying and had a high value for stiffness and lower roof displacement in comparison with the bare frame.

Keywords: reinforced concrete structures, pushover analysis, base shear, steel bracing

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Authors: Bennabhaktula Lavanya

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The study of women, their societal roles, and their importance has been a subject of intense discussion and scholarly inquiry. Researchers have diligently endeavoured to understand the influence of women in the domains of society, economy, culture, and politics, as well as the broader ramifications for society. Women's history aims to improve existing historical accounts by analyzing political institutions, economic events, social frameworks, cultural trends, and primary sources that have historically underprivileged women. The extensive research undertaken has resulted in the formation and recognition of women's history as a valid and unique subject of study within history. The Present paper analyses the academic discipline of Women's History and investigates its changing patterns. Tries to address the challenge of transforming the prevailing historical tradition by using innovative methods and frameworks and analyses the interests, experiences, and achievements of women in order to recreate their perceptions and priorities. The paper also examines the principles of Women's History, Gender Studies, and Feminist History and varying perspectives on women.

Keywords: history, perspectives, research, women

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Authors: Donatello Cardone

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Bilinear hysteresis models are usually used to describe the cyclic behavior of high damping rubber bearings. However, they neglect a number of phenomena (such as the interaction between axial load and shear force, buckling and post-buckling behavior, cavitation, scragging effects, etc.) that can significantly influence the dynamic behavior of such isolation devices. In this work, an advanced hysteresis model is examined and properly calibrated using consolidated procedures. Results of preliminary numerical analyses, performed in OpenSees, are shown and compared with the results of experimental tests on high damping rubber bearings and simulation analyses using alternative nonlinear models. The findings of this study can provide an useful tool for the accurate evaluation of the seismic response of structures with rubber-based isolation systems.

Keywords: seismic isolation, high damping rubber bearings, numerical modeling, axial-shear force interaction

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Authors: Lingyu Ding, Hongxia Hua, Hanfei Zhu, Jinling Lu, Qin Xu

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Background: Postoperative pain is a prevalent problem leading to many adverse outcomes in surgical patients. Virtual reality (VR) is an emerging non-pharmacological method of postoperative pain relief, but the effects of it are not clear. This review aimed to explore the effects of VR on relieving postoperative pain. Methods: We searched PubMed, Embase, Web of Science, and other databases from inception to November 2019 to get the eligible studies. Meta-analyses were conducted to compare VR and usual care for relieving postoperative pain. Subgroup analyses and sensitivity analyses were performed to explain the heterogeneity. Results: Overall, 8 randomized control trials (RCTs) enrolling 723 participants were included. Our results demonstrated that the patients receiving the VR intervention had lower postoperative pain scores than those receiving the usual care. One subgroup analysis revealed that VR could relieve postoperative pain both in minor surgery and major surgery. Another subgroup analysis demonstrated a significant reduction in postoperative pain among patients receiving VR during the intraoperative and the postoperative periods. However, there was no significant postoperative pain relief when receiving VR during the preoperative period. Additionally, significant improvements in postoperative satisfaction were reported in two studies. However, another two studies included found that VR could not affect physiological parameters related to pain. Conclusion: Applying VR can relieve postoperative pain effectively. The type of surgery and timing of using VR are the main sources of heterogeneity. More rigorous studies about the relationship between VR and postoperative pain relief will be needed.

Keywords: meta-analysis, postoperative pain, systematic review, virtual reality

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Authors: Fadia Gafri, Kathryn Mckintosh, Louise Young, Alan Harvey, Simon Mackay, Andrew Paul, Robin Plevin

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Nuclear factor-kappa B (NF-κB) is a ubiquitous transcription factor found originally to play a key role in regulating inflammation. However considerable evidence links this pathway to the suppression of apoptosis, cellular transformation, proliferation and invasion (Aggarwal et al., 2006). Moreover, recent studies have also linked inflammation to cancer progression making NF-κB overall a promising therapeutic target for drug discovery (Dobrovolskaia & Kozlov, 2005). In this study we examined the effect of the natural product canthin-6-one (SU182) as part of a CRUK small molecule drug discovery programme for effects upon the NF-κB pathway. Initial studies demonstrated that SU182 was found to have good potency against the inhibitory kappa B kinases (IKKs) at 30M in vitro. However, at concentrations up to 30M, SU182 had no effect upon TNFα stimulated loss in cellular IκBα or p65 phosphorylation in the keratinocyte cell line NCTC2544. Nevertheless, 30M SU182 reduced TNF-α / PMA-induced NF-κB-linked luciferase reporter activity to (22.9 ± 5%) and (34.6± 3 %, P<0.001) respectively, suggesting an action downstream of IKK signalling. Indeed, SU182 neither decreased NF-κB-DNA binding as assayed by EMSA nor prevented the translocation of p65 (NF-κB) to the nucleus assessed by immunofluorescence and subcellular fractionation. In addition to the inhibition of transcriptional activity of TNFα-induced NF-κB reporter activity SU182 significantly reduced PMA-induced AP-1-linked luciferase reporter activity to about (48± 9% at 30M, P<0.001) . This mode of inhibition was not sufficient to prevent the activation of NF-κB dependent induction of other proteins such as COX-2 and iNOS, or activated MAP kinases (p38, JNK and ERK1/2) in LPS stimulated RAW 264.7 macrophages. Taken together these data indicate the potential for SU182 to interfere with the transcription factors NF-κB and AP-1 at transcriptional level. However, no potential anti-inflammatory effect was indicated, further investigation for other NF-κB dependent proteins linked to survival are also required to identify the exact mechanism of action.

Keywords: Canthin-6-one, NF-κB, AP-1, phosphorylation, Nuclear translocation, DNA-binding activity, inflammatory proteins.

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Authors: Christina Williams, Mehari Weldemariam, Ann M. Farese, Thomas J. MacVittie, Maureen A. Kane

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Radiation exposure results in dose-dependent and time-dependent multi-organ damage. Drug development of medical countermeasures (MCM) for radiation-induced injury occurs under the FDA Animal Rule because human efficacy studies are not ethical or feasible. The FDA Animal Rule requires the representation of both sexes and describes several uses for biomarkers in MCM drug development studies. Currently, MCMs are limited and there is no FDA-approved biomarker for any radiation injury. Sex as a variable is essential to identifying biomarkers and developing effective MCMs for acute radiation exposure (ARS) and delayed effects of acute radiation exposure (DEARE). These studies aim to address the death of information on sex differences that have not been determined by studies that included only male, single-sex cohorts. Studies have reported differences in radiosensitivity according to sex. As such, biomarker discovery for radiation-induced damage must consider sex as a variable. This study evaluated the plasma proteomic profile of Rhesus macaque non-human primates after different exposures and doses, as well as time points after radiation. Exposures and doses included total body irradiation between 5-7.5 Gy and partial body irradiation with 5% bone marrow sparing at 9, 9.5 and 10 Gy. Timepoints after irradiation included days 1, 3, 60, and 180, which encompassed both acute radiation syndromes and delayed effects of acute radiation exposure. Bottom-up proteomic analyses of plasma included equal numbers of males and females. In the control animals, few proteomic differences are observed between the sexes. In the irradiated animals, there are a few sex differences, with changes mostly consisting of proteins upregulated in the female animals. Multiple canonical pathways were upregulated in irradiated animals relative to the control animals when subjected to pathway analysis, but differential responses between the sexes are limited. These data provide critical baseline differences according to sex and establish sex differences in non-human primate models relevant to drug development of MCM under the FDA Animal Rule.

Keywords: ionizing radiation, sex differences, plasma proteomics, biomarker discovery

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Authors: Natina Yaduma, Allan Williams, Sangwon Park, Andrew Lockwood

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This paper analyses flexible working, and the employment of migrants, as determinants of productivity in hotels. Controlling for the institutional environment, by focussing on a single firm, it analyses data on actual hours worked and outputs, on a weekly basis, over an 8 year period. The unusually disaggregated data allows the paper to examine not only inter-establishment, but also intra-establishment (departmental) variations in productivity, and to compare financial versus physical measures. The findings emphasise the complexity of productivity findings, sometimes contrasting evidence for establishments versus departments, and the positive but scale and measure-specific contributions of both the employment of migrants and flexible working, especially the utilisation of zero hours contracts.

Keywords: labour productivity, physical productivity, financial productivity, numerical flexibility, functional flexibility, migrant employment, cero-contract employment

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Authors: M. Yoneda

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In this paper, a lateral walking design force per person is proposed and compared with Imperial College test results. Numerical simulations considering the proposed walking design force which is incorporated into the neural-oscillator model are carried out placing much emphasis on the synchronization (the lock-in phenomenon) for a pedestrian bridge model with the span length of 50 m. Numerical analyses are also conducted for an existing pedestrian suspension bridge. As compared with full scale measurements for this suspension bridge, it is confirmed that the analytical method based on the neural-oscillator model might be one of the useful ways to explain the synchronization (the lock-in phenomenon) of pedestrians being on the bridge.

Keywords: pedestrian bridge, human-induced lateral vibration, neural-oscillator, full scale measurement, dynamic response analysis

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Authors: Harika Atmaca, Emir Bozkurt, Latife Merve Oktay, Selim Uzunoglu, Ruchan Uslu, Burçak Karaca

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Microarrays have been developed for highly parallel enzyme-linked immunosorbent assay (ELISA) applications. The most common protein arrays are produced by using multiple monoclonal antibodies, since they are robust molecules which can be easily handled and immobilized by standard procedures without loss of activity. Protein expression profiling with protein array technology allows simultaneous analysis of the protein expression pattern of a large number of proteins. Trabectedin, a tetrahydroisoquinoline alkaloid derived from a Caribbean tunicate, Ecteinascidia turbinata, has been shown to have antitumor effects. Here, we used a novel proteomic approach to explore the mechanism of action of trabectedin in prostate cancer cell line PC-3 by apoptosis antibody microarray. XTT cell proliferation kit and Cell Death Detection Elisa Plus Kit (Roche) was used for measuring cytotoxicity and apoptosis. Human Apoptosis Protein Array (R&D Systems) which consists of 35 apoptosis related proteins was used to assess the omic protein expression pattern. Trabectedin induced cytotoxicity and apoptosis in prostate cancer cells in a time and concentration-dependent manner. The expression levels of the death receptor pathway molecules, TRAIL-R1/DR4, TRAIL R2/DR5, TNF R1/TNFRSF1A, FADD were significantly increased by 4.0-, 21.0-, 4.20- and 11.5-fold by trabectedin treatment in PC-3 cells. Moreover, mitochondrial pathway related pro-apoptotic proteins Bax, Bad, Cytochrome c, and Cleaved Caspase-3 expressions were induced by 2.68-, 2.07-, 2.8-, and 4.5-fold and the expression levels of anti-apoptotic proteins Bcl-2 and Bcl-XL were reduced by 3.5- and 5.2-fold in PC-3 cells. Proteomic (antibody microarray) analysis suggests that the mechanism of action of trabectedin may be exerted via the induction of both intrinsic and extrinsic apoptotic pathways. The antibody microarray platform can be utilised to explore the molecular mechanism of action of novel anticancer agents.

Keywords: trabectedin, prostate cancer, omic protein expression profile, apoptosis

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Authors: Ouabo Emmanuel Romaric, Amougou Armathe

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Background and aim: The study of impacts of floods and landslides at a small scale, specifically in the urban areas of developing countries is done to provide tools and actors for a better management of risks in such areas, which are now being affected by climate change. The main objective of this study is to assess the hydrometeorological vulnerabilities associated with flooding and urban landslides to propose adaptation measures. Methods: Climatic data analyses were done by calculation of indices of climate change within 50 years (1960-2012). Analyses of field data to determine causes, the level of risk and its consequences on the area of study was carried out using SPSS 18 software. The cartographic analysis and GIS were used to refine the work in space. Then, spatial and terrain analyses were carried out to determine the morphology of field in relation with floods and landslide, and the diffusion on the field. Results: The interannual changes in precipitation has highlighted the surplus years (21), the deficit years (24) and normal years (7). Barakat method bring out evolution of precipitation by jerks and jumps. Floods and landslides are correlated to high precipitation during surplus and normal years. Data field analyses show that populations are conscious (78%) of the risks with 74% of them exposed, but their capacities of adaptation is very low (51%). Floods are the main risk. The soils are classed as feralitic (80%), hydromorphic (15%) and raw mineral (5%). Slope variation (5% to 15%) of small hills and deep valley with anarchic construction favor flood and landslide during heavy precipitation. Mismanagement of waste produce blocks free circulation of river and accentuate floods. Conclusion: Vulnerability of population to hydrometeorological risks in Yaoundé VI is the combination of variation of parameters like precipitation, temperature due to climate change, and the bad planning of construction in urban areas. Because of lack of channels for water to circulate due to saturation of soils, the increase of heavy precipitation and mismanagement of waste, the result are floods and landslides which causes many damages on goods and people.

Keywords: climate change, floods, hydrometeorological, vulnerability

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Authors: Thyagi Ponnamperuma

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Background: Comorbidity between posttraumatic stress disorder (PTSD) and other psychological problems is common. Recent studies focused to investigate the underlying relationship between PTSD and comorbid psychopathologies. Among adolescents, higher rates of emotional and behavioral problems (EBP) have been reported following trauma, often coexisted with PTSD. The current study, thus, examined the relationship of posttraumatic stress symptoms to EBP in adolescents exposed to a variety of traumatic events. Further, the study investigated the relationship of trauma and comorbid PTSS to the self-perceived negative impact of EBP on daily functioning. Methods: Participants were 729 Sri Lankan adolescents (age 12 to 16 years; 54.9% female) living in areas impacted in varying degrees by the 2004 tsunami. In 2008, school-based screening was conducted and completed measures of, trauma exposure, PTSS, EBP, and related functional impairment. Results: Participants reported a high prevalence of trauma exposure (n = 438), including interpersonal violence (n = 155). DSM-IV criteria for full or partial PTSD were met by 23.7% of the trauma-exposed sample. Across all participants, 13.4% and 16.7% displayed clinically relevant levels of EBP and functional impairment, respectively. Among the trauma-exposed, 7% met criteria for both EBP and PTSD. EBP total scores and caseness were significantly higher in trauma-exposed adolescents with PTSD than in either those without PTSD or the non-traumatized control group. In subscale analysis, higher prevalence of serious emotional, conduct, and hyperactivity problems were reported in the PTSD positive group; the PTSD negative group did not differ significantly from the control group on any of the problem scales. In regression analyses, PTSS (β = .28, p < .001) and interpersonal violence (β = .13, p = .033) were significant predictors of EBP, cumulative trauma (β = .11, p = .076) showed no significant effect. Further, PTSS exacerbated the impact of EBP on daily functioning (β = 0.29, p = .023). Conclusion: PTSS were closely linked to EBP in adolescents, even years after the traumatic experience. PTSD and emotional and behavioral problems together pose a heightened risk for impaired daily functioning. Longitudinal studies are needed to clarify the causal pathway.

Keywords: adolescents, comorbidity, emotional and behavioral problems, functional impairment, posttraumatic stress, traumatic events

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Authors: B. M. Md-Zain, N. A. Rahman, M. A. B. Abdul-Latiff, W. M. R. Idris

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We conducted molecular research to portray phylogenetic relationships of Malaysian primates particularly in the genus of Macaca. We have sequenced cytochrome C oxidase subunit I (COI) of mitochondrial DNA of several individuals from M. fascicularis and M. arctoides. PCR amplifications were performed and COI DNA sequences were aligned using ClustalW. Phylogenetic trees were constructed using distance analyses by employing neighbor-joining algorithm (NJ). We managed to sequence 700 bp of COI DNA sequences. The tree topology showed that M. fascicularis did not clump based on phyleogeography division in Peninsular Malaysia. Individuals from Negeri Sembilan merged together with samples from Perak and Penang into one clade. In addition, phylogenetic analyses indicated that M. arctoides was classified into sinica group instead of fascicularis group supported by genetic distance data. COI gene is an effective locus to clarify phylogenetic position of M. arctoides but not in discriminating M. fascicularis population in Peninsular Malaysia.

Keywords: cercopithecine, long-tailed macaque, Macaca fascicularis, Macaca arctoides

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Authors: Christine Pichler

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The German word Bildung in a comprehensive understanding can be defined as the development of the personality and as a process, which lasts from birth, or even before birth, until death. Gaining experience, acquiring abilities and knowledge as a lifelong learning process is what Bildung means. The development of the personality is intransitive because of the personality’s development itself, and transitive because of influences on the formation of a person by individuals and institutions. In public and political discussions, the term Bildung is understood with a constricted usage as education at schools. This leads to the research question, which consequences this limited comprehension of the term Bildung implies and how a comprehensive term of Bildung has to be defined. In discussions, Bildung is limited to its formal part. The limited understanding prevents from accurate analyses and discussions as well as adequate actions. This hypothesis and the research issue will be processed by theoretical analyses of the factors of Bildung, guideline-controlled expert interviews and a qualitative content analysis. The limited understanding on the term Bildung is a methodological problem. This results in inaccuracies in the analysis of the processes of Bildung and their effects on the development of personality structures. On the one hand, an individual is influenced by formal structures in the system of Bildung (e.g. schools) and on the other hand an individual is influenced by gained individual and informal personality and character attributes. In general, too little attention is given to these attributes and individual qualifications. The aim of this work is to demonstrate informative terms so the educational process with all its facets could be considered and applicable analyses can be made. If the informative terms can be defined, it´s also possible to identify and discuss the components of a comprehensive term Bildung to enable correct action.

Keywords: Bildung, development of personality, education, formative process, organized and non-organized Bildung

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Authors: Jose Carlos Rodriguez, Mario Gomez

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In the last years, the concept of entrepreneurial ecosystems has gained popularity. It reveals the importance of a supportive community and adequate economic environment for entrepreneurial activity, and thus the possibility of developing a different perspective on the innovation system. On the other hand, the (regional/technology) innovation system approach lacks in its analyses the presence of an entrepreneur as a key actor that develops innovations. In this regard, this paper examines the foundations of both theoretical approaches (the entrepreneurial ecosystems and the regional/technology systems of innovation) and their contributions to understand entrepreneurial activity at different levels of analyses, namely national, regional or local. The paper makes a literature review on both perspectives of innovation stressing the role played by entrepreneurs in these theoretical approaches. It concludes remarking that the regional/technology innovation systems approach and the entrepreneurial ecosystem approach have established themselves in their own right, but the regional/technology innovation system approach is a predecessor of the entrepreneurial ecosystem approach.

Keywords: entrepreneurial ecosystems, innovation systems, entrepreneurial activity, comparative analysis

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Authors: Rachel Hetherington, Chad Deering, Ann Maclean, Snehamoy Chatterjee

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The U.S. Geological Survey conducted a soil survey and subsequent mineralogical and geochemical analyses of over 4800 samples taken across the contiguous United States between the years 2007 and 2013. At each location, samples were taken from the top 5 cm, the A-horizon, and the C-horizon. Many studies have looked at the correlation between the mineralogical and geochemical content of soils and influencing factors such as parent lithology, climate, soil type, and age, but it seems little has been done in relation to quantifying and assessing the correlation between elements in the soil on a national scale. GIS was used for the mapping and multivariate interpolation of over 40 major and trace elements for surficial soils (0-5 cm depth). Qualitative analysis of the spatial distribution across the U.S. shows distinct patterns amongst elements both within the same periodic groups and within different periodic groups, and therefore with different behavioural characteristics. Results show the emergence of 4 main patterns of high concentration areas: vertically along the west coast, a C-shape formed through the states around Utah and northern Arizona, a V-shape through the Midwest and connecting to the Appalachians, and along the Appalachians. The Band Collection Statistics tool in GIS was used to quantitatively analyse the geochemical raster datasets and calculate a correlation matrix. Patterns emerged, which were not identified in qualitative analysis, many of which are also amongst elements with very different characteristics. Preliminary results show 41 element pairings with a strong positive correlation ( ≥ 0.75). Both qualitative and quantitative analyses on this scale could increase knowledge on the relationships between element distribution and behaviour in surficial soils of the U.S.

Keywords: correlation matrix, geochemical analyses, spatial distribution of elements, surficial soils

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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: Razieh Zarei, Hassan zm, Abolghasem Ajami, Darush Moslemi, Narges Afsary, Amrollah Mostafa-zade

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Introduction: IL-23 is responsible for the differentiation and expansion of Th17/ThIL-17 cells from naive CD4+ T cells. Therefore, may be IL-23/IL17 axis involve in a variety of allergic and autoimmune diseases, such as RA, MS, inflammatory bowel disease (IBD), and asthma. TGF-β is also share for the differentiation Th17 producing IL-17 and CD4+CD25+Foxp3hiT regulatory cells from naïve CD4+ T cells which are involved in the regulation of immune response, maintaining immunological self-tolerance and immune homeostasis ,and the control of autoimmunity and cancer surveillance. Therefore, T regulatory cells play a key role in autoimmunity, allergy, cancer, infectious disease, and the induction of transplantation tolerance. Vitamin A and it's derivatives (retinoids) inhibit or reverse the carcinogenic process in some types of cancers in oral cavity,head and neck, breast, skin, liver, and blood cells. Shark is a murine organism and its cartilage has antitumor peptides to prevent angiogenesis, in vitro. Our purpose is whether simultaneous oral treatment vitamin A and shark cartilage can modulate IL-23/IL-17 and CD4CD25Foxp3 T regulatory cell/TGF-β pathways and Th1/Th2 immunity in patients with gastric cancer. Materials and Methods: First investigated an imbalanced supernatant of cytokines exist in patients with gastric cancer by ELISA. Associated with cytokines measuring such as IL-23,IL-17,TGF-β,IL-4 and γ-IFN, then flow cytometry was employed to determine whether the peripheral blood mononuclear cells such as CD4+CD25+Foxp3highT regulatory cells in patients with gastric cancer were changed correspondingly. Results: An imbalance between IL-17 secretion and TGF-β/Foxp3 t regulatory cell pathway and so, Th1 immunity (γ-IFN production) and TH2 immunity (IL-4 secretion) was not seen in patients with gastric cancer treated by vitamin A and shark cartilage. But, the simultaneously presented down-regulation of IL-23 indicated, at least cytokine level. Conclusion: Il-23, as a pro-angiogenesis cytokine, probably, help to tumor growth. Hence, suggested that down-regulation of IL-23, at least cytokine level, is useful for anti-tumor immune responses in patients with gastric cancer.

Keywords: IL-23/IL17 axis, TGF-β/CD4CD25Foxp3 T regulatory pathway, γ-IFN, IL-4, shark cartilage and gastric cancer

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Authors: Min Wei

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Objectives: Experience tourism represents an advanced stage of tourism compared with sightseeing tourism and relaxation tourism. Experience tourism reflects the full respect of experience economy to the human natures. This paper chose one of the most popular ocean tourism products in Zhoushan, as a subject and investigated the constructive elements in tourist experience based on the needs of tourists. Methods: This paper started with the influences of tourism product innovation on tourist experience, then proposed a model of the relationship between tourist experience, tourist satisfaction, and the following behavior of tourists, and concluded that tourist experience improves tourist satisfaction and thereby enhances tourist loyalty based on the developmental pathway of experience tourism. To ensure the accuracy of the collected data of the research results, the sample of this questionnaire survey is chosen by the method of occasional sampling, combined with the judgment of the investigators and the convenience of the questionnaire survey, the survey objects are selected from the scenic spots of Putuo Mountain, Zhujiajian, Taohua Island, waiting room of passenger terminal, etc. Before filling in the questionnaire, the author and the respondents have a short communication. On the premise that the respondents can fully understand the purpose and content of the questionnaire, tourists fill in the questionnaire independently and collect it on the spot. Results: The research results of this paper are mainly embodied in the following aspects: it is concluded that there are many constructive factors of tourists' experience in Zhoushan tourism products. Based on Zhoushan tourism products, this paper explores the constructive factors of tourists' experience in Zhoushan tourism products from three aspects: attracting object experience, facility experience and service experience. At present, there are still big differences between Zhoushan tourism products, tourists’ expectations and tourists' experience, mainly in the aspects of transportation, publicity and tour guide service. Corresponding measures should be taken to improve tourists' experience quality and satisfaction. Conclusions: The influence factors of island tourism products are discriminated, and established a structural model of tourist experience, which includes three basic elements: attractions, facilities, and services. This model was further verified by questionnaires and analyses in Putuo Shan, Zhujia Jian, and Taohua Island. Finally, we combined this model and made some suggestions on boost the satisfaction of Zhoushan islands.

Keywords: experience tourism, tourists’ expectations, tourists' experience, tourism products

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