Search results for: induced pluripotent stem cells

Authors: Changhan Ouyang, Zhonglin Xie

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In response to proatherosclerotic factors such as oxidized lipids, or to therapeutic interventions such as angioplasty, stents, or bypass surgery, vascular smooth muscle cells (VSMCs) migrate from the media to the intima, resulting in intimal hyperplasia, restenosis, graft failure, or atherosclerosis. These proatherosclerotic factors also activate autophagy in VSMCs. However, the functional role of autophagy in vascular health and disease remains poorly understood. In the present study, we determined the role of autophagy in the regulation of VSMC migration. Autophagy activity in cultured human aortic smooth muscle cells (HASMCs) and mouse carotid arteries was measured by Western blot analysis of microtubule-associated protein 1 light chain 3 B (LC3B) and P62. The VSMC migration was determined by scratch wound assay and transwell migration assay. Ex vivo smooth muscle cell migration was determined using aortic ring assay. The in vivo SMC migration was examined by staining the carotid artery sections with smooth muscle alpha actin (alpha SMA) after carotid artery ligation. To examine the relationship between autophagy and neointimal hyperplasia, C57BL/6J mice were subjected to carotid artery ligation. Seven days after injury, protein levels of Atg5, Atg7, Beclin1, and LC3B drastically increased and remained higher in the injured arteries three weeks after the injury. In parallel with the activation of autophagy, vascular injury-induced neointimal hyperplasia as estimated by increased intima/media ratio. The en face staining of carotid artery showed that vascular injury enhanced alpha SMA staining in the intimal cells as compared with the sham operation. Treatment of HASMCs with platelet-derived growth factor (PDGF), one of the major factors for vascular remodeling in response to vascular injury, increased Atg7 and LC3 II protein levels and enhanced autophagosome formation. In addition, aortic ring assay demonstrated that PDGF treated aortic rings displayed an increase in neovessel formation compared with control rings. Whole mount staining for CD31 and alpha SMA in PDGF treated neovessels revealed that the neovessel structures were stained by alpha SMA but not CD31. In contrast, pharmacological and genetic suppression of autophagy inhibits VSMC migration. Especially, gene silencing of Atg7 inhibited VSMC migration induced by PDGF. Furthermore, three weeks after ligation, markedly decreased neointimal formation was found in mice treated with chloroquine, an inhibitor of autophagy. Quantitative morphometric analysis of the injured vessels revealed a marked reduction in the intima/media ratio in the mice treated with chloroquine. Conclusion: Autophagy activation increases VSMC migration while autophagy suppression inhibits VSMC migration. These findings suggest that autophagy suppression may be an important therapeutic strategy for atherosclerosis and intimal hyperplasia.

Keywords: autophagy, vascular smooth muscle cell, migration, neointimal formation

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Authors: Shujun Xie, Shirong Zhang, Shenglin Ma

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Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.

Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor

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Authors: Petnamnueng Dettipponpong, Shuen E. Chen

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Heat stress is known to have negative effects on reproductive functions, such as follicular development and ovulation. This study aimed to investigate the specific effects of heat stress on steroid hormone secretion of ovarian follicle cells, particularly in relation to the expression of Apolipoprotein B (ApoB) and microsomal triglyceride transfer protein (MTP). The aim of the study was to understand the impact of heat stress on steroid hormone secretion in ovarian follicle cells and to explore the role of ApoB and MTP in this process. Primary granulosa and theca cells were collected from follicles and cultured under heat stress conditions (42 °C) for various time periods. Controls were maintained under normal conditions (37.5 °C ). The culture medium was collected at different time points to measure levels of progesterone and estradiol using ELISA kits. ApoB and MTP expression levels were analyzed using homemade antibodies and western blot. Data were assessed by a one-way ANOVA comparison test with Duncan’s new multiple-range test. Results were expressed as mean±S.E. Difference was considered significant at P<0.05. The results showed that heat stress significantly increased progesterone secretion in granulosa cells, with the peak observed after 13 hours of recovery under thermoneutral conditions. Estradiol secretion by theca cells was not affected. Heat stress also had a significant negative effect on granulosa cell viability. Additionally, the expression of ApoB and MTP was found to be differentially regulated by heat stress. ApoB expression in theca cells was transiently promoted, while ApoB expression in granulosa cells was consistently suppressed. MTP expression increased after 5 hours of recovery in both cell types. These findings suggest a mechanism by which chicken follicle cells export cellular lipids as very low-density lipoprotein (VLDL) in response to thermal stress. These contribute to our understanding of the role of ApoB and MTP steroidogenesis and lipid metabolism under heat stress conditions. The study involved the collection of primary granulosa and theca cells, culture under different temperature conditions, and analysis of the culture medium for hormone levels using ELISA kits. ApoB and MTP expression levels were assessed using homemade antibodies and western blot. This study aimed to address the effects of heat stress on steroid hormone secretion in ovarian follicle cells, as well as the role of ApoB and MTP in this process. The study demonstrates that heat stress stimulates steroidogenesis in granulosa cells, affecting progesterone secretion. ApoB and MTP expression were found to be differentially regulated by heat stress, indicating a potential mechanism for the export of cellular lipids in response to thermal stress.

Keywords: heat stress, granulosa cells, theca cells, steroidogenesis, chicken, apolipoprotein B, microsomal triglyceride transfer protein

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Authors: Boroka Gács, Tibor Szolcsányi, Árpad Csathó

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Background: Individuals frequently show habituation to repeated noxious heat. However, given the defensive function of human pain processing, it is reasonable to assume that individuals imagine that they would become increasingly sensitive to repeated thermal pain stimuli. To the best of the authors' knowledge, no previous studies have, however, been addressed to this assumption. Therefore, in the current study, we investigated how healthy human individuals imagine the intensity of repeated thermal pain stimulations, and compared this with the intensity ratings given after physically induced thermal pain trials. Methods: Healthy participants (N = 20) gave pain intensity ratings in two conditions: imagined and real thermal pain. In the real pain condition thermal pain stimuli of two intensities (minimal and moderate pain) were delivered in four consecutive trials. The duration of the peak temperature was 20s, and stimulation was always delivered to the same location. In each trial, participants rated the pain intensity twice, 5s and 15s after the onset of the peak temperature. In the imagined pain condition, participants were subjected to a reference pain stimulus and then asked to imagine and rate the same sequence of stimulations as in the induced pain condition. Results: Ratings of imagined pain and physically induced pain followed opposite courses over repeated stimulation: Ratings of imagined pain indicated sensitization whereas ratings for physically induced pain indicated habituation. The findings were similar for minimal and moderate pain intensities. Conclusions: The findings suggest that, rather than habituating to pain, healthy individuals imagine that they would become increasingly sensitive to repeated thermal pain stimuli.

Keywords: habituation, imagined pain, pain perception, thermal stimulation

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Authors: Mostafa Sefidgar, Kaamran Raahemifar, Hossein Bazmara, Madjid Soltani

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The computational methods provide condition for investigation related to the process of drug delivery, such as convection and diffusion of drug in extracellular matrices, and drug extravasation from microvascular. The information of this process clarifies the mechanisms of drug delivery from the injection site to absorption by a solid tumor. In this study, an advanced numerical method is used to solve fluid flow and solute transport equations simultaneously to show how capillary network structure induced by tumor affects drug delivery. The effect of heterogeneous capillary network induced by tumor on interstitial fluid flow and drug delivery is investigated by this multi scale method. The sprouting angiogenesis model is used for generating capillary network induced by tumor. Fluid flow governing equations are implemented to calculate blood flow through the tumor-induced capillary network and fluid flow in normal and tumor tissues. The Starling’s law is used for closing this system of equations and coupling the intravascular and extravascular flows. Finally, convection-diffusion-reaction equation is used to simulate drug delivery. The dynamic approach which changes the capillary network structure based on signals sent by hemodynamic and metabolic stimuli is used in this study for more realistic assumption. The study indicates that drug delivery to solid tumors depends on the tumor induced capillary network structure. The dynamic approach generates the irregular capillary network around the tumor and predicts a higher interstitial pressure in the tumor region. This elevated interstitial pressure with irregular capillary network leads to a heterogeneous distribution of drug in the tumor region similar to in vivo observations. The investigation indicates that the drug transport properties have a significant role against the physiological barrier of drug delivery to a solid tumor.

Keywords: solid tumor, physiological barriers to drug delivery, angiogenesis, microvascular network, solute transport

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Authors: Ya-Ting Chuang, Krystle Leung, Ya-Jen Chang, Rosemarie H. DeKruyff, Paul B. Savage, Richard Cruse, Christophe Benoit, Dirk Elewaut, Nicole Baumgarth, Dale T. Umetsu

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We examined characteristics of a Natural Killer T (NKT) cell subpopulation that developed during influenza infection in neonatal mice, and that suppressed the subsequent development of allergic asthma in a mouse model. This NKT cell subset expressed CD38 but not CD4, produced IFN-γ, but not IL-17, IL-4 or IL-13, and inhibited the development of airway hyperreactivity (AHR) through contact-dependent suppressive activity against helper CD4 T cells. The NKT subset expanded in the lungs of neonatal mice after infection with influenza, but also after treatment of neonatal mice with a Th1-biasing α-GalCer glycolipid analogue, Nu-α-GalCer. These results suggest that early/neonatal exposure to infection or to antigenic challenge can affect subsequent lung immunity by altering the profile of cells residing in the lung and that some subsets of NKT cells can have direct inhibitory activity against CD4+ T cells in allergic asthma. Importantly, our results also suggest a potential therapy for young children that might provide protection against the development of asthma.

Keywords: NKT subset, asthma, airway hyperreactivity, hygiene hypothesis, influenza

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Authors: Maryam Zahedifard, Fadhil Lafta Faraj, Maryam Hajrezaie, Nazia Abdul Majid, Mahmood Ameen Abdulla, Hapipah Mohd Ali

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In the current study, we prepared two new quinazoline schiff bases through condensation reaction of 2-aminobenzhydrazide with 5-bromosalicylaldehyde and 3-methoxy-5-bromosalicylaldehyde. The chemical structures of both newly synthesized compounds (1 and 2) were confirmed by FT-IR and X-ray crystallography studies. The cytotoxic effect of compounds was investigated against MCF-7 human breast cancer cells. MTT results showed that (1) and (2) decreased the viability of MCF-7 cells in a time-dependent manner, exhibiting an IC50 value of 3.23 ± 0.28 µg/mL and 3.41 ± 0.34 µg/mL, respectively, after a 72-hours treatment period. In contrast, they did not show significant anti-proliferative effect towards MCF-10A normal breast cells and WRL-68 normal liver cells. We found a perturbation in mitochondrial membrane potential and increased cytochrome c release from the mitochondria to the cytosol, suggesting an activation of apoptosis by compounds, which was confirmed by activation of the initiator caspase-9 and the executioner caspases-3/7. (1) was also able to trigger extrinsic pathway via activation of caspase-8 and inhibition of NF-κB translocation. The acute toxicity test showed no toxicity effect of the compounds in rats. Our results showed that the selected synthesized compounds are highly potent to induce apoptosis in MCF-7 cells via either intrinsic or extrinsic mitochondrial pathway.

Keywords: Quinazoline Schiff base, apoptosis, MCF-7 human breast cancer cell line, caspase, NF-κB translocation

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Authors: Alaa E. El-sisi, Sherin Zakaria

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Rebamipide is an antiulcer drug with unique properties such as anti-inflammatory action. It induces endogenous prostaglandin e2 (PGE2). PGE2 is considered as a potent physiological suppressor of liver fibrosis. Aim of study: This study investigated the effect of rebamipide on hepatic fibrosis. Material and Method: Hepatic fibrosis was induced by intraperitoneal injections (IP) injection of CCl4 (0.45 mL/kg) in corn oil 1:5 twice a week for 4 weeks. Rats were divided into four groups as follow: Group 1 treated with CCL4 only, group 2 and 3 treated with CCL4 and rebamipide 60 mg/kg/day (group2) or 100 mg/kg/day (group3), and the fourth group was considered as control group and treated with vehicles. ALT, AST, and Bilirubin were assayed in serum. Antioxidant markers such as malondialdhyde (MDA) and superoxide dismutase (SOD) and fibrotic markers such as hyaluronic acid (HA) and procollagen-III (procol-III) were evaluated in liver tissues. IL-10 as well as PGE2 were also assayed in liver tissues. Pathologic changes in the liver were detected by hematoxylin and eosin staining. Collagen precipitation in liver tissues was visualized using masson trichrom stain. Results: Rebamipide inhibit CCL4 induced increase in ALT and AST significantly (p < 0.05). Rebamipide exerted an antioxidant effect as it inhibits CCL4 induced increased MDA level and decreased SOD activity. Fibrotic markers assay revealed that repamipide (60 or 100 mg/kg/day) decreased the level of procol-III and HA compared to CCl4 (p < 0.05). Oral administration of Rebamipide was associated with a significant increase (p < 0.05) of PGE2 and IL-10. Rebamipide especially at the dose of (100 mg/kg/day) restores liver histology structure and abolish collagen precipitation in liver tissues. Conclusion: Rebamipide retards hepatic fibrosis induced by CCL4 may be through the induction of PGE2 level.

Keywords: fibrotic markers, hepatic fibrosis, PGE2, rebamipide

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Authors: Mitesh Rathod, Jungho Ahn, Noo Li Jeon, Junghoon Lee

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Endothelial cells respond to cues from both biochemical as well as micro mechanical environment. Significant effort has been directed to understand the effects of biochemical signaling, however, relatively little is known about regulation of endothelial cell biology by the micro mechanical environment. Numerous studies have been performed to understand how physical forces regulate endothelial cell behavior. In this regard, past studies have majorly focused on exploring how fluid shear stress governs endothelial cell behavior. Parallel plate flow chambers and rectangular microchannels are routinely employed for applying fluid shear force on endothelial cells. However, these studies fall short in mimicking the in vivo like micro environment from topological aspects. Few studies have only used circular microchannels to replicate in vivo like condition. Seldom efforts have been directed to elucidate the combined effect of topology, substrate rigidity and fluid shear stress on endothelial cell response. In this regard, we demonstrate a facile fabrication process to develop a hybrid polydimethylsiloxane microfluidic platform to study endothelial cell biology. On a single chip microchannels with different cross sections i.e., circular, rectangular and square have been fabricated. In addition, our fabrication approach allows variation in the substrate rigidity along the channel length. Two different variants of polydimethylsiloxane, namely Sylgard 184 and Sylgard 527, were utilized to achieve the variation in rigidity. Moreover, our approach also enables in creating Y bifurcation circular microchannels. Our microfluidic platform thus facilitates for conducting studies pertaining to endothelial cell morphology with respect to change in topology, substrate rigidity and fluid flow on a single chip. The hybrid platform was tested by culturing Human Umbilical Vein Endothelial Cells in circular microchannels with varying substrate rigidity, and exposed to fluid shear stress of 12 dynes/cm² and static conditions. Results indicate the cell area response to flow induced shear stress was governed by the underlying substrate mechanics.

Keywords: hybrid, microfluidic platform, PDMS, shear flow, substrate rigidity

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Authors: Hashaam Akhtar

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IFNλR1 and IL10R2 collectively construct a heterodimer, which is an acknowledged functional receptor for all type III interferons (IFNs). Expression of IFNλR1 is highly tissue specific, which can help in making type III IFNs a drug of choice as comparable to its analogue, type I IFNs, for treating hepatitis C in the near future. Although, expression of IFNλR1 also varies with the concentration of type I IFNs, but in this study it was shown that the expression of IFNλR1 varies with the protein titers of IFN-α, IFN-λ3 and the newly discovered IFN-λ4. High dosage of IFN-α reduces the expression of IFNλR1 in HepG2 cells, which can affect the antiviral activity of type III IFNs in vivo. We premeditated an experimental strategy to differentiate monocytes into dendritic cells (DCs), type I and type II macrophages in vitro and quantified the expression of the IFNλR1 by qPCR. The exposure of newly discovered IFN-λ4 to macrophages and DCs also raised the expression of its own receptor, which shows that expression of IFN-λ4 protein in hepatitis C patient may augment type I treatment and help ease off viral titers. The results of this study may contribute in some understanding towards the mechanisms involved in the selective expression of IFNLR1 and exceptionalities associated with the receptor.

Keywords: IFNLR1, Interferon Lambda 4 (IFN-λ4), Mononuclear Phagocyte Cells (MPCs), expression

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Authors: Sourabh Jain, Vikas Jain, Dharmendra Kumnar

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The present study investigated the antidiabetic potential of Cedrus deodara heart wood aqueous extract and its relationship in alloxan-induced diabetic rats. Aqueous extract of Cedrus deodara was found to reduce blood sugar level in alloxan induced diabetic rats. Reduction in blood sugar could be seen from 5th day after continuous administration of the extract and on 21st day sugar levels were found to be reduced by 40.20%. Oxidative stress produced by alloxan was found to be significantly lowered by the administration of Cedrus deodara aqueous extract (500 mg/kg). This was evident from a significant decrease in lipid per oxidation level in liver induced by alloxan. The level of Glutathione, Catalase, Superoxide dismutase and Glutathione-S-Transferase in liver, kidney and pancreas tissue were found to be increased significantly after drug administration. The results obtained in the present study suggest that the Cedrus deodara aqueous extract effectively and significantly reduced the oxidative stress induced by alloxan and produced a reduction in blood sugar level.

Keywords: Cedrus deodara, heartwood, antioxidant, anti-diabetic, anti-inflammatory

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Authors: Mohamed Bakry Mohamed Ali, Mohamed Ehab El-Din Mustafa, Joseph Naiem Sabet Aziz, Sarah Mahmoud Ali Kaooh

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Background: Acute lung injury (ALI) is one of the major challenges in intensive care medicine. The most common extrapulmonary cause of ALI is sepsis, accounting more than 30% of the cases in humans. Lipopolysaccharide (LPS) has gained wide acceptance as a clinically relevant model of ALI. Lipopolysaccharide is a glycoprotein forming the major constituent of bacterial endotoxin. Losartan is angiotensin II type 1 (AT1) receptor antagonists. It is widely used for management of hypertension. It was recently suggested that losartan protects against septic ALI. It would thereby prevent LPS-induced ALI. Aim of the work and design of the experiment: This work investigated the injurious effect of lipopolysaccharide (LPS) and ALI on adult male albino rat at 24 hours and 14 days of LPS administration and the possible protective role of losartan pretreatment. LPS has deteriorated animal survival and behavior. It increased lung weight and induced lung histological damage. These changes could be much reduced by the losartan pretreatment. Conclusion: Administration of losartan before LPS could largely reduce these LPS/ ALI induced short and long term alterations. It could be recommended that patients susceptible to developing ALI, as in ICU, should receive a protective dose of angitensin II type 1 (AT1) receptor blocker as losartan.

Keywords: acute lung injury (ALI), lipopolysaccharide (LPS), losartan

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Authors: Astrid Tannert, Anuradha Ramoji, Christina Ebert, Frederike Gladigau, Lorena Tuchscherr, Jürgen Popp, Ute Neugebauer

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Staphylococcus aureus is a facultative intracellular pathogen, which by entering host cells may evade immunologic host response as well as antimicrobial treatment. In that way, S. aureus can cause persistent intracellular infections which are difficult to treat. Depending on the strain, S. aureus may persist at different intracellular locations like the phagolysosome. The first barrier invading pathogens from the blood stream that they have to cross are the endothelial cells lining the inner surface of blood and lymphatic vessels. Upon proceeding from an acute to a chronic infection, intracellular pathogens undergo certain biochemical and structural changes including a deceleration of metabolic processes to adopt for long-term intracellular survival and the development of a special phenotype designated as small colony variant. In this study, the endothelial cell line Ea.hy 926 was used as a model for acute and chronic S. aureus infection. To this end, Ea.hy 926 cells were cultured on QIAscout™ Microraft Arrays, a special graded cell culture substrate that contains around 12,000 microrafts of 200 µm edge length. After attachment to the substrate, the endothelial cells were infected with GFP-expressing S. aureus for 3 weeks. The acute infection and the development of persistent bacteria was followed by confocal laser scanning microscopy, scanning the whole Microraft Array for the presence and for detailed determination of the intracellular location of fluorescent intracellular bacteria every second day. After three weeks of infection representative microrafts containing infected cells, cells with protruded infections and cells that did never show any infection were isolated and fixed for Raman micro-spectroscopic investigation. For comparison, also microrafts with acute infection were isolated. The acquired Raman spectra are correlated with the fluorescence microscopic images to give hints about a) the molecular alterations in endothelial cells during acute and chronic infection compared to non-infected cells, and b) metabolic and structural changes within the pathogen when entering a mode of persistence within host cells. We thank Dr. Ruth Kläver from QIAGEN GmbH for her support regarding QIAscout technology. Financial support by the BMBF via the CSCC (FKZ 01EO1502) and from the DFG via the Jena Biophotonic and Imaging Laboratory (JBIL, FKZ PO 633/29-1, BA 1601/10-1) is highly acknowledged.

Keywords: correlative image analysis, intracellular infection, pathogen-host adaption, Raman micro-spectroscopy

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Authors: Rashmi Ranade, Neelu Joshi

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Barleria prionitis L. is a well explored Indian medicinal plant valued for its stem and leaf which forms an important ingredient of many Ayurvedic formulations. It is used for the treatment of various disorders like toothache, bleeding gums, strengthening gums, whooping cough, inflammation, arthritis, enlargement of scrotum and sciatica etc. The plant is propagated vegetatively through stem cuttings. Frequent harvesting of this plant has led to the shortage of planting material, and it has acquired the status of vulnerable plant species. Plant tissue culture technology offers a very good alternative for propagation and conservation of such plant species. The present investigation was undertaken to develop in vitro regeneration protocol for B. prionitis L. via callus organogenesis pathway. Stem and leaf explants were used for this purpose. Different media and plant growth regulators were optimized to develop the protocol. The problem of phenol secretion and browning and in vitro cultures at the establishment phase was successfully curbed with the usage of antibrowning agents such as ascorbic acid and activated charcoal. Optimum shoot multiplication was achieved by the use of liquid media and incorporation of silver nitrate and TIBA (triiodobenzoic acid) into the media. High percent rooting (76%) was observed on WPM media supplemented with IBA (2.0 mg/l), IAA (0.5 mg/l), GA3(0.5) and activated charcoal(500 mg/l). The rooted plantlets were subjected to in vitro hardening on sterile potting mix (soil:farmyard manure:compost; 1:2:1) and acclimatized under greenhouse conditions. Around 85% survival of plantlets was recorded upon acclimatization. This lab scale protocol would be tested for in vitro scaling up production of B. prionitis L.

Keywords: explant browning, liquid culture, micropropagation, shoot multiplication, phenolic secretion

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Authors: Azzeddine Abdelalim, Fatiha Rogti

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The degradation phenomenon in polymer solar cells (PCSs) has not been clearly explained yet. In fact, there are many causes that show up and influence these cells in a variety of ways. Also, there has been a growing concern over this degradation in the photovoltaic community. One of the main variables deciding PSCs photovoltaic output is defect states. In this research, devices modeling is carried out to analyze the multiple effects of degradation by applying high defect states (HDS) on ideal PSCs, mainly poly(3-hexylthiophene) (P3HT) absorber layer. Besides, a comparative study is conducted between P3HT and other PSCs by a simulation program called Solar Cell Capacitance Simulator (SCAPS). The adjustments to the defect parameters in several absorber layers explain the effect of HDS on the total output properties of PSCs. The performance parameters for HDS, quantum efficiency, and energy band were therefore examined. This research attempts to explain the degradation process of PSCs and the causes of their low efficiency. It was found that the defects often affect PSCs performance, but defect states have a little effect on output when the defect level is less than 1014cm-3, which gives similar performance values with P3HT cells when these defects is about 1019cm-3. The high defect states can cause up to 11% relative reduction in conversion efficiency of ideal P3HT. In the center of the band gap, defect states become more noxious. This approach is for one of the degradation processes potential of PSCs especially that use fullerene derivative acceptors.

Keywords: degradation, high defect states, polymer solar cells, SCAPS-1D

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Authors: Luxi He, Tianfang Zhang, Zhengbin He, Songlin Yi

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Heat treatment has been widely recognized for its effectiveness in enhancing the physicochemical properties of wood, including hygroscopicity and dimensional stability. Nonetheless, the non-negligible volumetric shrinkage and loss of mechanical strength resulting from heat treatment may diminish the wood recovery and its product value. In this study, tung oil was used to alleviate heat-induced shrinkage and reduction in mechanical properties of wood during heat treatment. Tung oil was chosen as a modifier because it is a traditional Chinese plant oil that has been widely used for over a thousand years to protect wooden furniture and buildings due to its biodegradable and non-toxic properties. The effects of different heating media (air, tung oil) and their effective treatment parameters (temperature, duration) on the changes in the physical properties (morphological characteristics, pore structures, micromechanical properties), and chemical properties (chemical structures, chemical composition) of wood were investigated by using scanning electron microscopy, confocal laser scanning microscopy, atomic force microscopy, X-ray photoelectron spectroscopy, and dynamic vapor sorption. Meanwhile, the correlation between the mass changes and the color change, volumetric shrinkage, and hygroscopicity was also investigated. The results showed that the thermal degradation of wood cell wall components was the most important factor contributing to the changes in heat-induced shrinkage, color, and moisture adsorption of wood. In air-heat-treated wood samples, there was a significant correlation between mass change and heat-induced shrinkage, brightness, and moisture adsorption. However, the presence of impregnated tung oil in oil-heat-treated wood appears to disrupt these correlations among physical properties. The results of micromechanical properties demonstrated a significant decrease in elastic modulus following high-temperature heat treatment, which was mitigated by tung oil treatment. Chemical structure and compositional analyses indicated that the changes in chemical structure primarily stem from the degradation of hemicellulose and cellulose, and the presence of tung oil created an oxygen-insulating environment that slowed down this degradation process. Morphological observation results showed that tung oil permeated the wood structure and penetrated the cell walls through transportation channels, altering the micro-morphology of the cell wall surface, obstructing primary water passages (e.g., vessels and pits), and impeding the release of volatile degradation products as well as the infiltration and diffusion of water. In summary, tung oil treatment represents an environmentally friendly and efficient method for maximizing wood recovery and increasing product value. This approach holds significant potential for industrial applications in wood heat treatment.

Keywords: tung oil, heat treatment, physicochemical properties, wood cell walls

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Authors: Farhad Farahvash, Parya Mobaseri

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Weeds control based on their critical period leads to less production costs and risks of wide chemical application of weeds control methods. The present study considered effect of weeds control time (weeds interference after 20, 40 and 60 days, weeds full control, weeds interference and weeds control after 20, 40 and 60 days) on growth and yield of forage maize 454. The experiment based on full-randomized blocks design with three replications was conducted at research farm of Islamic Azad University of Tabriz located at 15th km of East Tabriz in 2013. According to the results, weeds interference after 40 and 60 days as well as weeds control after 20 days prevented from decrease of maize biomass resulted from weeds presence while weeds interference after 20 days, weeds interference and weeds control after 40 and 60 days led respectively to 41.2%, 35%, 25% and 32.5% decrease of forage maize biomass. The weeds-influenced decrease was manifested at different parts of the plant depending on presence period of weeds. Decrease of fresh weight of ear and fresh weight of leaf and stem was observed due to weeds interference after 20 days and weeds interference. If weeds are controlled after 60 days, decrease of ear weight and fresh weight of stem will lead to biomass decrease. Also, if weeds are controlled after 40 days, decrease of fresh weight of maize stems will result in biomass decrease. Ear traits were affected by weeds control treatment. Being affected by treatments of weeds interference after 20 days, weeds non-interference, weeds control after 40 and 60 days, ear length was shortened 29.9 %, 41.4 %, 27.6 % and 37.2 %, respectively. The stem diameter demonstrated a significant decrease although it was only affected by treatments of weeds interference and weeds control after 60 days. Considering results of the present study, generally, it is suggested to control weeds during initial 20-60 days of maize growth in order to prevent undesirable effect of weeds on growth, production and production biomass of maize and decrease of production costs.

Keywords: maize, competition, weed, biomass

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Authors: Yasmin M. Attia, Hanan S. El-Abhar, Mahmoud M. Al Marzabani, Samia A. Shouman

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Background: Tamoxifen (TAM) is the most commonly used hormone therapy for the treatment of early and metastatic breast cancer. Although it significantly decreases the tumor recurrence rate and provides an overall benefit, as much as 20–30% of women still relapse during or after long-term therapy. 3-Bromopyruvate (3-BP) is a promising agent with impressive antitumor effects in several models of animal tumors and cell lines. Aim: This study was designed to investigate the combined effect of (TAM) and (3-BP) in breast cancer cells and to explore their molecular interaction via assessment of apoptotic, angiogenic, and metastatic markers. Methods: In vitro cytotoxicity study was carried out for both compounds to determine the combination regimen producing a synergistic effect and mechanistic pathways were studied using RT-PCR and western techniques. Moreover, the anti-oncolytic and anti-angiogenic potentials were assessed in mice bearing solid Ehrlich carcinoma (SEC). Results: The combined treatment significantly increased the expressions and protein levels of caspase 7, 9, and 3 and decreased of angiogenic markers VEGF, HIF-1α, and HK2 compared to cells treated with either drug individually. However, there were no significant changes in MMP-2 and MMP-9 protein levels. Interestingly, the in vivo results supported the in vitro findings; there was a decrease in the tumor volume and VEFG using immunohistochemistry in the combination-treated groups compared to either TAM or 3-BP treated one. Conclusion: 3-BP synergizes the cytotoxic effect of TAM by increasing apoptosis and decreasing angiogenesis which makes this combination a promising regimen to be applied clinically.

Keywords: tamoxifen, 3-bromopyruvate, breast cancer, cytotoxicity, angiogenesis

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Authors: Marisa Rio, Sharanya Bola, Richard H. W. Funk, Gerald Gerlach

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Cell migration, wound healing and regeneration are some of the physiological phenomena in which electric fields (EFs) have proven to have an important function. Physiologically, cells experience electrical signals in the form of transmembrane potentials, ion fluxes through protein channels as well as electric fields at their surface. As soon as a wound is created, the disruption of the epithelial layers generates an electric field of ca. 40-200 mV/mm, directing cell migration towards the wound site, starting the healing process. In vitro electrotaxis, experiments have shown cells respond to DC EFs polarizing and migrating towards one of the poles (cathode or anode). A standard electrotaxis experiment consists of an electrotaxis chamber where cells are cultured, a DC power source and agar salt bridges that help delaying toxic products from the electrodes to attain the cell surface. The electric field strengths used in such an experiment are uniform and homogeneous. In contrast, the endogenous electric field strength around a wound tend to be multi-field and non-homogeneous. In this study, we present a custom device that enables electrotaxis experiments in non-homogeneous DC electric fields. Its main feature involves the replacement of conventional metallic electrodes, separated from the electrotaxis channel by agarose gel bridges, through electrolyte-filled microchannels. The connection to the DC source is made by Ag/AgCl electrodes, incased in agarose gel and placed at the end of each microfluidic channel. An SU-8 membrane closes the fluidic channels and simultaneously serves as the single connection from each of them to the central electrotaxis chamber. The electric field distribution and current density were numerically simulated with the steady-state electric conduction module from ANSYS 16.0. Simulation data confirms the application of nonhomogeneous EF of physiological strength. To validate the biocompatibility of the device cellular viability of the photoreceptor-derived 661W cell line was accessed. The cells have not shown any signs of apoptosis, damage or detachment during stimulation. Furthermore, immunofluorescence staining, namely by vinculin and actin labelling, allowed the assessment of adhesion efficiency and orientation of the cytoskeleton, respectively. Cellular motility in the presence and absence of applied DC EFs was verified. The movement of individual cells was tracked for the duration of the experiments, confirming the EF-induced, cathodal-directed motility of the studied cell line. The in vitro monolayer wound assay, or “scratch assay” is a standard protocol to quantitatively access cell migration in vitro. It encompasses the growth of a confluent cell monolayer followed by the mechanic creation of a scratch, representing a wound. Hence, wound dynamics was monitored over time and compared for control and applied the electric field to quantify cellular population motility.

Keywords: DC non-homogeneous electric fields, electrotaxis, microfluidic biochip, wound healing

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Authors: Vladimir Vinnikov

Abstract:

The paper proposes a model of an inhomogeneous rock mass with initially random distribution of microcracks on mineral grain boundaries. It describes the behavior of cracks in a medium under the effect of thermal field, the medium heated instantaneously to a predetermined temperature. Crack growth occurs according to the concept of fracture mechanics provided that the stress intensity factor K exceeds the critical value of Kc. The modeling of thermally induced acoustic emission memory effects is based on the assumption that every event of crack nucleation or crack growth caused by heating is accompanied with a single acoustic emission event. Parameters of the thermally induced acoustic emission memory effect produced by cyclic heating and cooling (with the temperature amplitude increasing from cycle to cycle) were calculated for several rock texture types (massive, banded, and disseminated). The study substantiates the adaptation of the proposed model to humidity interference with the thermally induced acoustic emission memory effect. The influence of humidity on the thermally induced acoustic emission memory effect in quasi-homogeneous and banded rocks is estimated. It is shown that such modeling allows the structure and texture of rocks to be taken into account and the influence of interference factors on the distinctness of the thermally induced acoustic emission memory effect to be estimated. The numerical modeling can be used to obtain information about the thermal impacts on rocks in the past and determine the degree of rock disturbance by means of non-destructive testing.

Keywords: crack growth, cyclic heating and cooling, rock texture, thermo acoustic emission memory effect

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Authors: Vijayakameswara Rao Neralla, Jueun Jeon, Jae Hyung Park

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To develop a potential nanocarrier for diagnosis and treatment of rheumatoid arthritis (RA), we prepared a hyaluronic acid (HA)-5β-cholanic acid (CA) conjugate with an acid-labile ketal linker. This conjugate could self-assemble in aqueous conditions to produce pH-responsive HA-CA nanoparticles as potential carriers of the anti-inflammatory drug methotrexate (MTX). MTX was rapidly released from nanoparticles under inflamed synovial tissue in RA. In vitro cytotoxicity data showed that pH-responsive HA-CA nanoparticles were non-toxic to RAW 264.7 cells. In vivo biodistribution results confirmed that, after their systemic administration, pH-responsive HA-CA nanoparticles selectively accumulated in the inflamed joints of collagen-induced arthritis mice. These results indicate that pH-responsive HA-CA nanoparticles represent a promising candidate as a drug carrier for RA therapy.

Keywords: rheumatoid arthritis, hyaluronic acid, nanocarrier, self-assembly, MTX

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Authors: Stefanie Rukavina, Sascha Gruss, Steffen Walter, Holger Hoffmann, Harald C. Traue

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OPEN-EmoRecII is an open multimodal corpus with experimentally induced emotions. In the first half of the experiment, emotions were induced with standardized picture material and in the second half during a human-computer interaction (HCI), realized with a wizard-of-oz design. The induced emotions are based on the dimensional theory of emotions (valence, arousal and dominance). These emotional sequences - recorded with multimodal data (mimic reactions, speech, audio and physiological reactions) during a naturalistic-like HCI-environment one can improve classification methods on a multimodal level. This database is the result of an HCI-experiment, for which 30 subjects in total agreed to a publication of their data including the video material for research purposes. The now available open corpus contains sensory signal of: video, audio, physiology (SCL, respiration, BVP, EMG Corrugator supercilii, EMG Zygomaticus Major) and mimic annotations.

Keywords: open multimodal emotion corpus, annotated labels, intelligent interaction

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Authors: A. Guechi, M. Chegaar

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This study investigates how AlGaAs/GaAs thin film solar cells perform under varying global solar spectrum due to the changes of environmental parameters such as the air mass and the atmospheric turbidity. The solar irradiance striking the solar cell is simulated using the spectral irradiance model SMARTS2 (Simple Model of the Atmospheric Radiative Transfer of Sunshine) for clear skies on the site of Setif (Algeria). The results show a reduction in the short circuit current due to increasing atmospheric turbidity, it is 63.09% under global radiation. However increasing air mass leads to a reduction in the short circuit current of 81.73%.The efficiency decrease with increasing atmospheric turbidity and air mass.

Keywords: AlGaAs/GaAs, solar cells, environmental parameters, spectral variation, SMARTS

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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: I. Ahmad, A. Hannan, S. Ahmad, M. Asif, M. F. Nawaz, M. A. Tanvir, M. F. Azhar

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During this research, a comprehensive survey of tree growing areas of Faisalabad district of Pakistan was conducted to observe the symptoms, spectrum, occurrence and severity of A. nilotica and E. camaldulensis decline. Objective of current research was to investigate specific fungal pathogens involved in decline of A. nilotica and E. camaldulensis. For this purpose, infected roots, bark, neck portion, stem, branches, leaves and infected soils were collected to identify associated fungi. Potato dextrose agar (PDA) and Czepak dox agar media were used for isolations. Identification of isolated fungi was done microscopically and different fungi were identified. During survey of urban locations of Faisalabad, disease incidence on Kikar and Eucalyptus was recorded as 3.9-7.9% and 2.6-7.1% respectively. Survey of Agroforest zones of Faisalabad revealed decline incidence on kikar 7.5% from Sargodha road while on Satiana and Jhang road it was not planted. In eucalyptus trees, 4%, 8% and 0% disease incidence was observed on Jhang road, Sargodha road and Satiana road respectively. The maximum fungus isolated from the kikar tree was Drechslera australiensis (5.00%) from the stem part. Aspergillus flavus also gave the maximum value of (3.05%) from the bark. Alternaria alternata gave the maximum value of (2.05%) from leaves. Rhizopus and Mucor spp. were recorded minimum as compared to the Drechslera, Alternaria and Aspergillus. The maximum fungus isolated from the Eucalyptus tree was Armillaria luteobubalina (5.00%) from the stem part. The other fungi isolated were Macrophamina phaseolina and A. niger.

Keywords: decline, frequency of mycoflora, A. nilotica and E. camaldulensis, Drechslera australiensis, Armillaria luteobubalina

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Authors: Hatem A. El-Mezayen, Ahmed Abdelmajeed, Fatehya Metwally, Usama Elsaly, Salwa Atef

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Tumor metastasis involves the dissemination of malignant cells into the basement membrane and vascular system contributes to the circulating pool of these markers. In this context our aim has been focused on development of a non-invasive. Circulating tumor cells (CTCs) represent a unique liquid biopsy carrying comprehensive biological information of the primary tumor. Herein, we sought to develop a novel score based on the combination of the most significant CTCs biomarkers with and routine laboratory tests for accurate detection of metastatic breast cancer. Methods: Cytokeratin 18 (CK18), Cytokeratin 19 (CK19), and CA15.3 were assayed in metastatic breast cancer (MBC) patients (75), non-MBC patients (50) and healthy control (20). Results: Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named MBC-CTCs = CA15.3 (U/L) × 0.08 + CK 18 % × 2.9 + CK19 × 3.1– 510. That function correctly classified 87% of metastatic breast cancer at cut-off value = 0.55. (i.e great than 0.55 indicates patients with metastatic breast cancer and less than 0.55 indicates patients with non-metastatic breast cancer). Conclusion: MBC-CTCs is a novel, non-invasive and simple can applied to discriminate patients with metastatic breast cancer.

Keywords: metastatic breast cancer, circulating tumor cells, cytokeratin, EpiCam

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Authors: Shiyin He, Zheng Huang

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In this paper, deep learning methods are applied in bio-medical field to detect and count different types of cells in an automatic way instead of manual work in medical practice, specifically in bone marrow examination. The process is mainly composed of two steps, detection and recognition. Mask-Region-Convolutional Neural Networks (Mask-RCNN) was used for detection and image segmentation to extract cells and then Convolutional Neural Networks (CNN), as well as Deep Residual Network (ResNet) was used to classify. Result of cell detection network shows high efficiency to meet application requirements. For the cell recognition network, two networks are compared and the final system is fully applicable.

Keywords: cell detection, cell recognition, deep learning, Mask-RCNN, ResNet

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Authors: Zhipeng Feng, Huanhuan Qi, Pingchuan Shen, Fenggang Zang, Yixiong Zhang

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Numerical simulations of vortex-induced vibration of a three-dimensional flexible tube under uniform turbulent flow are calculated when Reynolds number is 1.35×10⁴. In order to achieve the vortex-induced vibration, the three-dimensional unsteady, viscous, incompressible Navier-Stokes equation and LES turbulence model are solved with the finite volume approach, the tube is discretized according to the finite element theory, and its dynamic equilibrium equations are solved by the Newmark method. The fluid-tube interaction is realized by utilizing the diffusion-based smooth dynamic mesh method. Considering the vortex-induced vibration system, the variety trends of lift coefficient, drag coefficient, displacement, vertex shedding frequency, phase difference angle of tube are analyzed under different frequency ratios. The nonlinear phenomena of locked-in, phase-switch are captured successfully. Meanwhile, the limit cycle and bifurcation of lift coefficient and displacement are analyzed by using trajectory, phase portrait, and Poincaré sections. The results reveal that: when drag coefficient reaches its minimum value, the transverse amplitude reaches its maximum, and the “lock-in” begins simultaneously. In the range of lock-in, amplitude decreases gradually with increasing of frequency ratio. When lift coefficient reaches its minimum value, the phase difference undergoes a suddenly change from the “out-of-phase” to the “in-phase” mode.

Keywords: vortex induced vibration, limit cycle, LES, CFD, FEM

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Authors: Dongqin Cheng

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The n-dimensional balanced hypercube BHn (n ≥ 1) has been proved to be a bipartite graph. Let P be a set of edges whose induced subgraph consists of pairwise vertex-disjoint paths. For any two vertices u, v from different partite sets of V (BHn). In this paper, we prove that if |P| ≤ 2n − 2 and the subgraph induced by P has neither u nor v as internal vertices, or both of u and v as end-vertices, then BHn contains a Hamiltonian path joining u and v passing through P. As a corollary, if |P| ≤ 2n−1, then the BHn contains a Hamiltonian cycle passing through P.

Keywords: interconnection network, balanced hypercube, Hamiltonian cycle, prescribed edges

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Authors: Adisorn Banhan, Toansakul Santiboon, Prasong Saihong

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Using the Socio-Scientific Issues-Based Learning Method is to compare of the blended instruction of STEM education with a sample consisted of 84 students in 2 classes at the 11th grade level in Sarakham Pittayakhom School. The 2-instructional models were managed of five instructional lesson plans in the context of electronic wave issue. These research procedures were designed of each instructional method through two groups, the 40-experimental student group was designed for the instructional STEM education (STEMe) and 40-controlling student group was administered with the Socio-Scientific Issues-Based Learning (SSIBL) methods. Associations between students’ learning achievements of each instructional method and their science attitudes of their predictions to their exploring activities toward physics with the STEMe and SSIBL methods were compared. The Measuring Reasonable Ethics Test (MRET) was assessed students’ reasonable ethics with the STEMe and SSIBL instructional design methods on two each group. Using the pretest and posttest technique to monitor and evaluate students’ performances of their reasonable ethics on electromagnetic wave issue in the STEMe and SSIBL instructional classes were examined. Students were observed and gained experience with the phenomena being studied with the Socio-Scientific Issues-Based Learning method Model. To support with the STEM that it was not just teaching about Science, Technology, Engineering, and Mathematics; it is a culture that needs to be cultivated to help create a problem solving, creative, critical thinking workforce for tomorrow in physics. Students’ attitudes were assessed with the Test Of Physics-Related Attitude (TOPRA) modified from the original Test Of Science-Related Attitude (TOSRA). Comparisons between students’ learning achievements of their different instructional methods on the STEMe and SSIBL were analyzed. Associations between students’ performances the STEMe and SSIBL instructional design methods of their reasonable ethics and their science attitudes toward physics were associated. These findings have found that the efficiency of the SSIBL and the STEMe innovations were based on criteria of the IOC value higher than evidence as 80/80 standard level. Statistically significant of students’ learning achievements to their later outcomes on the controlling and experimental groups with the SSIBL and STEMe were differentiated between students’ learning achievements at the .05 level. To compare between students’ reasonable ethics with the SSIBL and STEMe of students’ responses to their instructional activities in the STEMe is higher than the SSIBL instructional methods. Associations between students’ later learning achievements with the SSIBL and STEMe, the predictive efficiency values of the R2 indicate that 67% and 75% for the SSIBL, and indicate that 74% and 81% for the STEMe of the variances were attributable to their developing reasonable ethics and science attitudes toward physics, consequently.

Keywords: socio-scientific issues-based learning method, STEM education, science attitudes, measurement, reasonable ethics, physics classes

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