Search results for: target receptor

Authors: Kai-Yao Huang, Tzong-Yi Lee, Pin-Hao Ho, Tzu-Hao Chang, Cheng-Wei Chang

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Background: Human cytomegalovirus (HCMV) infects much people around the world, and there were many researches mention that many diseases were caused by HCMV. To understand the mechanism of HCMV lead to diseases during infection. We observe a microRNA (miRNA) – miRNA interaction between HCMV and host during infection. We found HCMV miRNA sequence component complementary with host miRNA precursors, and we also found that the host miRNA abundances were decrease in HCMV infection. Hence, we focus on the host miRNA which may target by the other HCMV miRNA to find theirs target mRNAs expression and analysis these mRNAs affect what kind of signaling pathway. Interestingly, we found the affected mRNA play an important role in some diseases related pathways, and these diseases had been annotated by HCMV infection. Results: From our analysis procedure, we found 464 human miRNAs might be targeted by 26 HCMV miRNAs and there were 291 human miRNAs shows the concordant decrease trend during HCMV infection. For case study, we found hcmv-miR-US22-5p may regulate hsa-mir-877 and we analysis the KEGG pathway which built by hsa-mir-877 validate target mRNA. Additionally, through survey KEGG Disease database found that these mRNA co-regulate some disease related pathway for instance cancer, nerve disease. However, there were studies annotated that HCMV infection casuse cancer and Alzheimer. Conclusions: This work supply a different scenario of miRNA target interactions(MTIs). In previous study assume miRNA only target to other mRNA. Here we wonder there is possibility that miRNAs might regulate non-mRNA targets, like other miRNAs. In this study, we not only consider the sequence similarity with HCMV miRNAs and human miRNA precursors but also the expression trend of these miRNAs. Then we analysis the human miRNAs validate target mRNAs and its associated KEGG pathway. Finally, we survey related works to validate our investigation.

Keywords: human cytomegalovirus, HCMV, microRNA, miRNA

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Authors: Hao Yuan, Yongjian Shen, Xiangjun He, Yuheng Li, Zhouzhou Zhang, Pengyu Zhang, Minkang Cai

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Remote sensing data can provide support for decision-making in disaster assessment or disaster relief. The traditional processing methods of sensitive targets in remote sensing mapping are mainly based on manual retrieval and image editing tools, which are inefficient. Methods based on deep learning for sensitive target hiding are faster and more flexible. But these methods have disadvantages in training time and cost of calculation. This paper proposed a target hiding model Self Attention (SA) Deepfill, which used self-attention modules to replace part of gated convolution layers in image inpainting. By this operation, the calculation amount of the model becomes smaller, and the performance is improved. And this paper adds free-form masks to the model’s training to enhance the model’s universal. The experiment on an open remote sensing dataset proved the efficiency of our method. Moreover, through experimental comparison, the proposed method can train for a longer time without over-fitting. Finally, compared with the existing methods, the proposed model has lower computational weight and better performance.

Keywords: remote sensing mapping, image inpainting, self-attention mechanism, target hiding

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Authors: Koirala Abarodh, Maghaiya Ujjwal, Guragain Phani Raj

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This analysis focuses on defining the spectrum evaluation model for telecom operators in terms of total cost of ownership (TCO). A quantitative approach for specific case analysis research methodology was used for identifying the results. Specific input parameters like target User experience, year on year traffic growth, capacity site limit per year, target additional spectrum type, bandwidth, spectrum efficiency, UE penetration have been used for the spectrum evaluation process and desired outputs in terms of the number of sites, capex in USD and required spectrum bandwidth have been calculated. Furthermore, this study gives a comparison of capex investment for target growth with and without addition spectrum. As a result, the combination of additional spectrum bands of 700 and 2600 MHz has a better evaluation in terms of TCO and performance. It is our recommendation to use these bands for expansion rather than expansion in the current 1800 and 2100 bands.

Keywords: spectrum, capex planning, case study methodology, TCO

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Authors: Jean Berger, Nassirou Lo, Martin Noel

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Perfectly suited for natural or man-made emergency and disaster management situations such as flood, earthquakes, tornadoes, or tsunami, multi-target search path planning for a team of rescue agents is known to be computationally hard, and most techniques developed so far come short to successfully estimate optimality gap. A novel mixed-integer linear programming (MIP) formulation is proposed to optimally solve the multi-target multi-agent discrete search and rescue (SAR) path planning problem. Aimed at maximizing cumulative probability of successful target detection, it captures anticipated feedback information associated with possible observation outcomes resulting from projected path execution, while modeling agent discrete actions over all possible moving directions. Problem modeling further takes advantage of network representation to encompass decision variables, expedite compact constraint specification, and lead to substantial problem-solving speed-up. The proposed MIP approach uses CPLEX optimization machinery, efficiently computing near-optimal solutions for practical size problems, while giving a robust upper bound obtained from Lagrangean integrality constraint relaxation. Should eventually a target be positively detected during plan execution, a new problem instance would simply be reformulated from the current state, and then solved over the next decision cycle. A computational experiment shows the feasibility and the value of the proposed approach.

Keywords: search path planning, search and rescue, multi-agent, mixed-integer linear programming, optimization

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Authors: Mohammad Hossein Modarressi, Mozhgan Mondeali, Khabat Barkhordari, Ali Etemadi

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The COVID-19 pandemic, caused by SARS-CoV-2, has led to significant concerns worldwide due to its catastrophic effects on public health. The SARS-CoV-2 infection is initiated with the binding of the receptor-binding domain (RBD) in its spike protein to the ACE2 receptor in the host cell membrane. Due to the error-prone entity of the viral RNA-dependent polymerase complex, the virus genome, including the coding region for the RBD, acquires new mutations, leading to the appearance of multiple variants. These variants can potentially impact transmission, virulence, antigenicity and evasive immune properties. S477N mutation located in the RBD has been observed in the SARS-CoV-2 omicron (B.1.1. 529) variant. In this study, we investigated the consequences of S477N mutation at the molecular level using computational approaches such as molecular dynamics simulation, protein-protein interaction analysis, immunoinformatics and free energy computation. We showed that displacement of Ser with Asn increases the stability of the spike protein and its affinity to ACE2 and thus increases the transmission potential of the virus. This mutation changes the folding and secondary structure of the spike protein. Also, it reduces antibody neutralization, raising concern about re-infection, vaccine breakthrough and therapeutic values.

Keywords: S477N, COVID-19, molecular dynamic, SARS-COV2 mutations

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Authors: Giorgio Visentin, Inna S. Kalinina, Alexei A. Buchachenko

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In the ambit of intermolecular interactions, a combination rule is defined as a relation linking a potential parameter for the interaction of two unlike species with the same parameters for interaction pairs of like species. Some of their most exemplificative applications cover the construction of molecular dynamics force fields and dispersion-corrected density functionals. Here, an extended combination rule is proposed, relating the dipole-dipole dispersion coefficients for the interaction of like target species to the same coefficients for the interaction of the target and a set of partner species. The rule can be devised in two different ways, either by uniform discretization of the Casimir-Polder integral on a Gauss-Legendre quadrature or by relating the dynamic polarizabilities of the target and the partner species. Both methods return the same system of linear equations, which requires the knowledge of the dispersion coefficients for interaction between the partner species to be solved. The test examples show a high accuracy for dispersion coefficients (better than 1% in the pristine test for the interaction of Yb atom with rare gases and alkaline-earth metal atoms). In contrast, the rule does not ensure correct monotonic behavior of the dynamic polarizability of the target species. Acknowledgment: The work is supported by Russian Science Foundation grant # 17-13-01466.

Keywords: combination rule, dipole-dipole dispersion coefficient, Casimir-Polder integral, Gauss-Legendre quadrature

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Authors: Sweta Pandey, Samridhi Dhyani, Susmita Chaudhuri

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Klebsiella pneumoniae causes a wide range of infections, including urinary tract infections, sepsis, bacteremia, pneumonia, and liver abscesses. The emergence of multi-drug resistance in this bacterium led to a major setback for clinical management. WHO also endorsed a need for finding alternative therapy to antibiotics for the treatment of these infections. Development of vaccines and passive antibody therapy has been proven as a potent alternative to antibiotics in the case of MDR, XDR, and PDR Klebsiella infections. Siderophore receptors have been demonstrated to be overexpressed for the internalization of iron siderophore complexes during infections in most Gram-negative bacteria. For the present study, immune response to siderophore receptors to establish this protein as a potential immunogen for the development of therapeutic leads was explored. Clinical strains of Klebsiella pneumoniae were grown in iron-deficient conditions, and the iron-regulated outer membrane proteins were extracted and characterized through mass spectrometry for specific identification. The gene for identified protein was cloned in pET- 28a vector and expressed in E. coli. The native protein and the recombinant protein were isolated and purified and used as antigens for the generation of immune response in BALB/c mice. The native protein of Klebsiella pneumoniae grown in iron-deficient conditions was identified as FepA (Ferrienterobactin receptor) and other siderophore receptors. This 80 kDa protein generated an immune response in BALB/c mice. The antiserum from mice after subsequent booster doses was collected and showed binding with FepA protein in western blot and phagocytic uptake of the K. pneumoniae in the presence antiserum from immunized mice also observed from the animal studies after bacterial challenge post immunisation in mice have shown bacterial clearance. The antiserum from mice showed binding and clearance of the Klebsiella pneumoniae bacteria in vitro and in vivo. These antigens used for generating an active immune response in mice can further be used for therapeutic monoclonal antibody development against Klebsiella pneumoniae infections.

Keywords: antiserum, FepA, Klebsiella pneumoniae, multi drug resistance, siderophore receptor

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Authors: Michael Ayomoh, Adriaan Roux, Oyindamola Omotuyi

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This paper presents an efficient robot navigation model in a multi-target domain amidst static and dynamic workspace obstacles. The problem is that of developing an optimal algorithm to minimize the total travel time of a robot as it visits all target points within its task domain amidst unknown workspace obstacles and finally return to its initial position. In solving this problem, a classical algorithm was first developed to compute the optimal number of paths to be travelled by the robot amidst the network of paths. The principle of shortest distance between robot and targets was used to compute the target point visitation order amidst workspace obstacles. Algorithm premised on the standard polar coordinate system was developed to determine the length of obstacles encountered by the robot hence giving room for a geometrical estimation of the total surface area occupied by the obstacle especially when classified as a relevant obstacle i.e. obstacle that lies in between a robot and its potential visitation point. A stochastic model was developed and used to estimate the likelihood of a dynamic obstacle bumping into the robot’s navigation path and finally, the navigation/obstacle avoidance algorithm was hinged on the hybrid virtual force field (HVFF) method. Significant modelling constraints herein include the choice of navigation path to selected target points, the possible presence of static obstacles along a desired navigation path and the likelihood of encountering a dynamic obstacle along the robot’s path and the chances of it remaining at this position as a static obstacle hence resulting in a case of re-routing after routing. The proposed algorithm demonstrated a high potential for optimal solution in terms of efficiency and effectiveness.

Keywords: multi-target, mobile robot, optimal path, static obstacles, dynamic obstacles

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Authors: Anika Chebrolu

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Mono-targeted drugs can be of limited efficacy against complex diseases. Recently, multi-target drug design has been approached as a promising tool to fight against these challenging diseases. However, the scope of current computational approaches for multi-target drug design is limited. DeepLig presents a de-novo drug discovery platform that uses reinforcement learning to generate and optimize novel, potent, and multitargeted drug candidates against protein targets. DeepLig’s model consists of two networks in interplay: a generative network and a predictive network. The generative network, a Stack- Augmented Recurrent Neural Network, utilizes a stack memory unit to remember and recognize molecular patterns when generating novel ligands from scratch. The generative network passes each newly created ligand to the predictive network, which then uses multiple Graph Attention Networks simultaneously to forecast the average binding affinity of the generated ligand towards multiple target proteins. With each iteration, given feedback from the predictive network, the generative network learns to optimize itself to create molecules with a higher average binding affinity towards multiple proteins. DeepLig was evaluated based on its ability to generate multi-target ligands against two distinct proteins, multi-target ligands against three distinct proteins, and multi-target ligands against two distinct binding pockets on the same protein. With each test case, DeepLig was able to create a library of valid, synthetically accessible, and novel molecules with optimal and equipotent binding energies. We propose that DeepLig provides an effective approach to design multi-targeted drug therapies that can potentially show higher success rates during in-vitro trials.

Keywords: drug design, multitargeticity, de-novo, reinforcement learning

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Authors: Aoxue Yang, Weili Tian, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Glucocorticoids (GCs) are used to treat GBM-associated edema. However, glucocorticoids participate in the physiological response to psychosocial stress, linked to poor cancer prognosis. This raises concern that glucocorticoids affect the tumor and BTSCs. Identifying markers specifically expressed by brain tumor stem cells (BTSCs) may enable specific therapies that spare their regular tissue-resident counterparts. By ribosome profiling analysis, we have identified that glycerol-3-phosphate dehydrogenase 1 (GPD1) is expressed by dormant BTSCs but not by NSCs. Through different stress-induced experiments in vitro, we found that only dexamethasone (DEXA) can significantly increase the expression of GPD1 in NSCs. Adversely, mifepristone (MIFE) which is classified as glucocorticoid receptors antagonists, could decrease GPD1 protein level and weaken the proliferation and stemness in BTSCs. Furthermore, DEXA can induce GPD1 expression in tumor-bearing mice brains and shorten animal survival, whereas MIFE has a distinct adverse effect that prolonged mice lifespan. Knocking out GR in NSC can block the upregulation of GPD1 inducing by DEXA, and we find the specific sequences on GPD1 promotor combined with GR, thus improving the efficiency of GPD1 transcription from CHIP-Seq. Moreover, GR and GPD1 are highly co-stained on GBM sections obtained from patients and mice. All these findings confirmed that GR could regulate GPD1 and loss of GPD1 Impairs Multiple Pathways Important for BTSCs Maintenance GPD1 is also a critical enzyme regulating glycolysis and lipid synthesis. We observed that DEXA and MIFE could change the metabolic profiles of BTSCs by regulating GPD1 to shift the transition of cell dormancy. Our transcriptome and lipidomics analysis demonstrated that cell cycle signaling and phosphoglycerides synthesis pathways contributed a lot to the inhibition of GPD1 caused by MIFE. In conclusion, our findings raise concern that treatment of GBM with GCs may compromise the efficacy of chemotherapy and contribute to BTSC dormancy. Inhibition of GR can dramatically reduce GPD1 and extend the survival duration of GBM-bearing mice. The molecular link between GPD1 and GR may give us an attractive therapeutic target for glioblastoma.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides

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Authors: Yousif Mohamed Y. Abdallah

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This is an experimental study deals with detection, measurement and analysis of the periodic physiological organ motion during external beam radiotherapy; to improve the accuracy of the radiation field placement, and to reduce the exposure of healthy tissue during radiation treatments. The importance of this study is to detect the maximum path of the mobile structures during radiotherapy delivery, to define the planning target volume (PTV) and irradiated volume during both inspiration and expiration period and to verify the target volume. In addition to its role to highlight the importance of the application of Intense Guided Radiotherapy (IGRT) methods in the field of radiotherapy. The results showed (body contour was equally (3.17 + 0.23 mm), for left lung displacement reading (2.56 + 0.99 mm) and right lung is (2.42 + 0.77 mm) which the radiation oncologist to take suitable countermeasures in case of significant errors. In addition, the use of the image registration technique for automatic position control is predicted potential motion. The motion ranged between 2.13 mm and 12.2 mm (low and high). In conclusion, individualized assessment of tumor mobility can improve the accuracy of target areas definition in patients undergo Sterostatic RT for stage I, II and III lung cancer (NSCLC). Definition of the target volume based on a single CT scan with a margin of 10 mm is clearly inappropriate.

Keywords: respiratory motion, external beam radiotherapy, image processing, lung

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Authors: Siamak Shahidi, Nasrin Hashemi-Firouzi, Sara Soleimani-Asl, Alireza Komaki

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Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory and cognitive performance. Recently, an involvement of the serotonergic system and their receptors are suspected in the AD progression. In the present behavioral study, the effects of BIMU (selective 5-HT4 receptor agonist) on cognition and memory in the rat model of AD was investigated. Material and Methods: The animal model of the AD was induced by intracerebroventricular (Icv) injection of amyloid beta (Aβ) in adult male Wistar rats. Animals were divided into experimental groups included control, sham, Aβ, Aβ +BIMU groups. The treatment substances were icv injected (1 μg/μL) for thirty consecutive days. Then, novel object recognition (NOR) and passive avoidance learning (PAL) tests were applied to investigate memory and cognitive performance. Results: Aβ decrease the discrimination index of NOR test. Also, it increases the time spent in the dark compartment during PAL test, as compared with sham and control groups. In addition, compared to Aβ groups, BIMU significantly increased the discrimination index of NOR test and decreased the time spent in the dark compartment of PAL test. Conclusion: These findings suggest that 5-HT4 receptor activation prevents progression of memory and cognitive impairment in a rat model of AD.

Keywords: Alzheimer disease, cognition, memory, serotonin receptors

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Authors: Nipun Manirajan, Heeralal Gargama, Sushil Guhe, Manoj Prabhakaran

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In railway industry, train sets are designed based on contractual requirements (mission profile), where reliability targets are measured in terms of mean distance between failures (MDBF). However, during the beginning of revenue services, trains do not achieve the designed mission profile distance (mileage) within the timeframe due to infrastructure constraints, scarcity of commuters or other operational challenges thereby not respecting the original design inputs. Since trains do not run sufficiently and do not achieve the designed mileage within the specified time, car builder has a risk of not achieving the contractual MDBF target. This paper proposes a constant failure rate based model to deal with the situations where mileage accumulation is not a part of the design mission profile. The model provides appropriate MDBF target to be demonstrated based on actual accumulated mileage. A case study of rolling stock running in the field is undertaken to analyze the failure data and MDBF target demonstration during low mileage accumulation. The results of case study prove that with the proposed method, reliability targets are achieved under low mileage accumulation.

Keywords: mean distance between failures, mileage-based reliability, reliability target appropriations, rolling stock reliability

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

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

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

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Authors: Maaly Jarrah

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Oral fluency in the target language is what many second language learners hope to achieve by living abroad. Research in the past has demonstrated the role informal environments play in improving L2 learners' oral fluency. However, living in the target country and being part of its community does not ensure the development of oral fluency skills. L2 learners' desire to communicate and access to speaking opportunities in the host community are key in achieving oral fluency in the target language. This study attempts to identify differences in oral fluency, specifically speech rate, between learners who communicate in the L2 outside the classroom and those who do not. In addition, as the desire to communicate is a crucial factor in developing oral fluency, this study investigates whether or not learners' desire to speak the L2 outside the classroom plays a role in their frequency of L2 use outside the classroom. Finally, given the importance of the availability of speaking opportunities for L2 learners in order to practice their speaking skills, this study reports on the participants' perceptions of the speaking opportunities accessible to them in the target community while probing whether or not their perceptions differed based on their oral fluency level and their desire to communicate. The results suggest that exposure to the target language and daily communication with the native speakers is strongly related to the development of learners' oral fluency. Moreover, the findings suggest that learners' desire to communicate affects their frequency of communication in their L2 outside the classroom. At the same time, all participants, regardless of their oral fluency level and their desire to communicate, asserted that speaking opportunities beyond the classroom are very limited. Finally, the study finds there are marked differences in the perceptions learners have regarding opportunities for learning offered by the same language program. After reporting these results, the study concludes with recommendations for ESL programs that serve international students.

Keywords: ESL programs, L2 Learners, oral fluency, second language

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Authors: Laura Ulitzky, Dougbeh-Chris Nyan, Manuel M. Lafer, Erica Silberstein, Nicoleta Cehan, Deborah R. Taylor

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Hepatitis C virus (HCV)-associated hepatocellular carcinoma, fibrosis and cirrhosis are more frequent in men and postmenopausal women than in premenopausal women and women receiving hormone replacement therapy, suggesting that β-estradiol (estrogen) plays an innate role in preventing viral infection and liver disease. Estrogen classically acts through nuclear estrogen receptors or, alternatively, through the membrane-bound G-protein-coupled estrogen receptor (GPR30 or GPER). We observed a marked decrease in detectable virus when HCV-infected human hepatoma cells were treated with estrogen. The effect was mimicked by both Tamoxifen (Tam) and G1, a GPR30-specific agonist, and was reversed by the GPR30-specific antagonist, G15. Through GPR30, estrogen-mediated the down-regulation of occludin; a tight junction protein and HCV receptor, by promoting activation of matrix metalloproteinases (MMPs). Activated MMP-9 was secreted in response to estrogen, cleaving occludin in the extracellular Domain D, the motif required for HCV entry and spread. This pathway gives new insight into a novel innate immune pathway and the disparate host-virus responses to HCV demonstrated by the two sexes. Moreover, these data suggest that hormone replacement therapy may have beneficial antiviral properties for HCV-infected postmenopausal women and show promise for new antiviral treatments for both men and women.

Keywords: HCV, estrogen, occludin, MMPs

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Authors: Chinmayee Choudhury

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Human Melanocortin 4 Receptor (HMC4R) is one of the most potential drug targets for the treatment of obesity which controls the appetite. A deletion of the residues 88-92 in HMC4R is sometimes the cause of severe obesity in the humans. In this study, two homology models are constructed for the normal as well as mutated HMC4Rs and some phytochemicals present in Green Tea, Honey and Cinnamon have been docked to them to study their differential binding to the normal and mutated HMC4R as compared to the natural agonist α- MSH. Two homology models have been constructed for the normal as well as mutated HMC4Rs using the Modeller9v7. Some of the phytochemicals present in Green Tea, Honey, and Cinnamon, which have appetite suppressant activities are constructed, minimized and docked to these normal and mutated HMC4R models using ArgusLab 4.0.1. The mode of binding of the phytochemicals with the Normal and Mutated HMC4Rs have been compared. Further, the mode of binding of these phytochemicals with that of the natural agonist α- Melanocyte Stimulating Hormone(α-MSH) to both normal and mutated HMC4Rs have also been studied. It is observed that the phytochemicals Kaempherol, Epigallocatechin-3-gallate (EGCG) present in Green Tea and Honey, Isorhamnetin, Chlorogenic acid, Chrysin, Galangin, Pinocambrin present in Honey, Cinnamaldehyde, Cinnamyl acetate and Cinnamyl alcohol present in Cinnamon have capacity to form more stable complexes with the Mutated HMC4R as compared to α- MSH. So they may be potential agonists of HMC4R to suppress the appetite.

Keywords: HMC4R, α-MSH, docking, photochemical, appetite suppressant, homology modelling

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Authors: Bingqing Xu, Wenxing Shuai

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This study investigates the priming effects of different Chinese compound words by native Mandarin speakers. There are lots of homonym, polysemy, and synonym in Chinese. However, it is unclear which kind of words have the biggest priming effect. Native Mandarin speakers were tested in a visual-word lexical decision experiment. The stimuli, which are all two-character compound words, consisted of two parts: primes and targets. Five types of relationships were used in all stimuli: morphologically related condition, in which the prime and the target contain the same morpheme; orthographically related condition, in which the target and the prime contain the different morpheme with the same form; phonologically related condition, in which the target and the prime contain the different morpheme with the same phonology; semantically related condition, in which the target and the prime contain the different morpheme with similar meanings; totally unrelated condition. The time since participants saw the target to respond was recorded. Analyses on reaction time showed that the average reaction time of morphologically related targets was much shorter than others, suggesting the morphological priming effect is the biggest. However, the reaction time of the phonologically related conditions was the longest, even longer than unrelated conditions. According to scatter plots analyses, 86.7% of participants had priming effects in morphologically related conditions, only 20% of participants had priming effects in phonologically related conditions. These results suggested that morphologically related conditions had the biggest priming effect. The orthographically and semantically related conditions also had priming effects, whereas the phonologically related conditions had few priming effects.

Keywords: priming effect, morphology, phonology, semantics, orthography

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Authors: Surapong Vongvatcharanon, Fardeela Binalee, Wandee Udomuksorn, Ekkasit Kumarnsit, Uraporn Vongvatcharanon

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Hypogonadism is characterized by a decline in sex hormone levels, especially testosterone. It has been shown to be an important contributor to the decrease in muscle mass, muscle strength and performance, a condition known as sarcopenia. Preparations from Butea superba Roxb. (red Kwao Krua) have been reported to have androgenic properties. The active compounds are proposed to be flavonoids and flavonoid glycosides. Treatment with B. superba has been shown to improve erectile dysfunction in males. Parvalbumin (PV) is a relaxing factor and identified in fast twitch fibers. Alterations of the PV levels affects skeletal muscle functions. This study aimed to investigate the effects of orhchidectomy, testosterone replacement and different doses of Butea superba Roxb. on the structure, performance, levels of parvalbumin, parvalbumin and androgen receptor immunoreactivities in the extensor digitorum longus (EDL) and gastrocnemius muscles of orchidectomized rats. Twelve-week old male Wistar rats were randomly divided into 6 groups; sham-operated (SHAM), orchidectomized (BS-0), orchidectomized group that was treated with testosterone replacement of 6 µg/kg (TP) or an orchidectomized group that was treated with various doses of an extract from Butea superba Roxb.; 5 mg/kg (BS-5), 50 mg/kg (BS-50) and 500 mg/kg (BS-500) all for 90 days. The testosterone level, epididymis, seminal vesicle, prostate gland, vas deference weight, muscle fiber size, strength and endurance in both the EDL and gastrocnemius muscle were decreased in the BS-0 group but increased in the testosterone replacement group. Treatment with the B. superba Roxb. extract replacement group improved muscle fiber size, strength and endurance, but not total testosterone levels, or the epididymis, seminal vesicle, prostate gland, vas deference weight. Furthermore, the parvalbumin level, parvalbumin and androgen receptor immunoreactivities were reduced in the BS-0 group but increased in the testosterone replacement group and the B. superba Roxb. extract groups for both the EDL and gastrocnemius muscle. This study indicated that the reduction of testosterone level led to a decrease of the androgen receptor density resulting in a decline in the muscle mass and parvalbumin levels. The decrease of parvalbumin levels affected muscle performance. Testosterone replacement increased the androgen receptor density and led to an increase of muscle mass and parvalbumin levels. The increase in the parvalbumin levels may result in an improvement of muscle performance. This may explain one mechanism of testosterone on muscle mass and strength in the testosterone dependent sarcopenia. The B. superba Roxb. extract groups also had improved muscle mass, strength and endurance, parvalbumin level, parvalbumin and androgen immunoreactivities compared to the BS-O group . Butea superba Roxb. Extracts contains a flavonoid (3, 7, 3'-Trihydroxy-4'-methoxyflavone), flavonoiglycoside (3, 3'-dihydroxy-4'-methoxyflavone-7-O-β-D-glucopyranoside) and isoflavanolignans (butesuperins A and butesuperins B) all known to inhibit the cAMP phosphodiesterase enzyme. Therefore, cAMP signaling may have adaptive effects on skeletal muscle by increasing muscle mass, strength and endurance.

Keywords: Butea superba, parvalbumin, skeletal muscle, orchidectomy

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Authors: Güldane Zengin

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Advertisers often make use of humorous elements in advertisements they create. Advertisements that contain such elements play a great role in creating awareness and attaining positive attitudes. Caricature, which is an element of humour, is interesting, eye catching, entertaining and memorable by its very nature. Because of these characteristics of caricatures, they are being used for advertising purposes. Advertisements with caricatures are spreading rapidly and embraced by consumers easily. Especially in the last ten years, companies in different sectors use advertisements with caricatures to publicize their products and services. These companies have different target audiences with different characteristics. They all have differences in opinions, attitudes, perceptions and buying behaviours. Target audiences’ brand choices depend on many different factors. Advertising is an important factor in brand choice. Using attention grabbing methods like advertising with caricatures affects their buying behaviours. This study examines the use of caricatures in Sütaş advertisements. Target audiences’ opinions, perceptions and attitudes about advertisements with caricatures are examined in this descriptive study.

Keywords: advertising, advertisements with caricatures, caricature, communication, humour, Sütaş caricatures

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Authors: Mina Dabirinezhad, Mohsen Bayat Pour, Amin Dabirinejad

Abstract:

This paper is intended to introduce the technology to solve some of the deficiencies of the direct digital radiology. Nowadays, digital radiology is the latest progression in dental imaging, which has become an essential part of dentistry. There are two main parts of the direct digital radiology comprised of an intraoral X-ray machine and a sensor (digital image receptor). The dentists and the dental nurses experience afflictions during the taking image process by the direct digital X-ray machine. For instance, sometimes they need to readjust the sensor in the mouth of the patient to take the X-ray image again due to the low quality of that. Another problem is, the position of the sensor may move in the mouth of the patient and it triggers off an inappropriate image for the dentists. It means that it is a time-consuming process for dentists or dental nurses. On the other hand, taking several the X-ray images brings some problems for the patient such as being harmful to their health and feeling pain in their mouth due to the pressure of the sensor to the jaw. The author provides a technology to solve the above-mentioned issues that is called “Self-Recognition Direct Digital Radiology” (SDDR). This technology is based on the principle that the intraoral X-ray machine is capable to diagnose the location of the sensor in the mouth of the patient automatically. In addition, to solve the aforementioned problems, SDDR technology brings out fewer environmental impacts in comparison to the previous version.

Keywords: Dental direct digital imaging, digital image receptor, digital x-ray machine, and environmental impacts

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Authors: Yaqing Hu

Abstract:

This paper puts forward a syntactic analysis involving multidominance and rightward movement in Chinese bi-comparatives, as in 'Yuehan bi Mali gao (John is taller than Mary).' It is argued here that the predicate of comparison is a shared constituent in two small clauses, namely one for the target and one for the standard; and then it moves rightward to form a degree phrase with the comparative morpheme. This proposal comes from four aspects. First, the example above can also be expressed in this way, 'A: Yuehan he Mali, shui gao? (John and Mary, who is taller?) B: Yuehan gao./Yuehan geng gao. (John is taller).' This shows that the gradable adjective is predicated of the target. In addition, according to a constraint on Chinese bi-comparatives, namely the target and the standard must be arguments of the predicate simultaneously, it is not unreasonable to assume that the gradable adjective may also be predicated of the standard. Second, subcomparatives are totally disallowed in Chinese, as in '*zhe-zhang zhuozi bi zhe-zhang yizi kuan chang. (This table is longer than this chair is wide.)' In order to save it from ungrammaticality, the target and the standard should be compared along the same dimension denoted by the gradable adjective. It may follow that in Chinese comparatives, having equal roles in the same eventuality, the target and the standard bear the same thematic relationship with the predicate of comparison. Third, verb-copy can appear in Chinese bi-comparatives, as in 'Yuehan qi ma bi Mali qi ma qi de kuai. (John rides horses faster than Mary does.)' The predicate qi seems to form a small clause with both the target and the standard. This might be supporting evidence that both the target and the standard share the predicate of comparison. Fourth, Chinese comparatives do have comparative morphemes, as in 'Yuehan bi Mali geng gao. (John is taller than Mary)', which is semantically equivalent to the first example above. Thus, it follows that one feature of Chinese comparative morphemes is that they can remain overt or covert in the syntax, which will not affect semantics. This further shows that comparative morphemes in bi-comparatives may not be able to saturate the degree argument denoted by the predicate of comparison due to its optionality in the structure. These four aspects present a challenge to the Direct Analysis used in Chinese comparatives since this approach would presume that the target and the standard somehow show independency with the predicate in the syntax. Meanwhile, this study also rejects the previous analysis of multidomiance in bi-comparatives in which the degree phrase comprised of the comparative morpheme and the gradable adjective may be shared by the standard when the comparative morpheme is covert. This syntactic analysis proposed in this study will therefore offer a different perspective of how to treat degree phrase in Chinese comparatives and may offer evidence to argue whether there is degree phrase movement in bi-comparatives as in its English counterparts.

Keywords: Chinese comparatives, degree phrase, movement, multidominance, syntactic analysis

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Authors: Salina Yahya Saddik

Abstract:

The present study is designed to demonstrate the Ovarian Surface Epithelial cells (OSE) Estrogen Receptor α (ERα) and Progesterone Receptor (PR) during pregnancy and estrous cycle in rat. Moreover, determination of the levels of plasma progesterone, estradiol, FSH and LH were also made. The levels of plasma progesterone, estradiol, FSH and LH concentrations were determined on days 7 (n=5), 14 (n=5), and 21(n=5) of pregnancy in three groups of rats and during the estrous cycle (n=5) using ELISA kit. Immunohistochemical method for PR and ERα expression was also made on the ovary. During pregnancy, FSH and LH remained low except at term when LH levels began to increase from 16 ng/ml to 47 ng/ml. Progesterone levels significantly exceeded estradiol values in all pregnant rats with a peak value of 202 ng/ml on day 14. Elevated progesterone levels were associated negatively with LH and estradiol levels during pregnancy. The levels of estradiol surged significantly on day 21. Immunohistochemistry of the ovary showed low levels of OSE cells staining positive for ERα expression. ERα positive cells were absent on day 7 and 14 of pregnancy, only day 21 recorded a very low percentage of immunostaining (0.5%) within the nuclei of OSE cells. On the contrary, immunostaining of PR was not observed within the nuclei of OSE cells in all groups of study. In conclusions, these results may suggest that progesterone effect during pregnancy seems to be overriding the positive effect of estrogens on OSE cells. High progesterone levels may have a direct negative effect on gonadotropin production and thereby it might inhibit events leading to both follicular development and OSE proliferation. Understanding the factors affecting OSE proliferation may help elucidating the mechanism(s) of assisted diseases such as ovarian cancer.

Keywords: ovarian surface, pregnancy, gonadotropins, steroids

Procedia PDF Downloads 292

Authors: Blanche Aguida, Marootpong Pooam, Nathalie Jourdan, Margaret Ahmad

Abstract:

COVID-19-related morbidity is associated with exaggerated inflammation and cytokine production in the lungs, leading to acute respiratory failure. The cellular mechanisms underlying these so-called ‘cytokine storms’ are regulated through the Toll-like receptor 4 (TLR4) signaling pathway and by reactive oxygen species (ROS). Both light (photobiomodulation) and magnetic fields (e.g., pulsed electromagnetic field) stimulation are non-invasive therapies known to confer anti-inflammatory effects and regulate ROS signaling pathways. Here we show that daily exposure to two 10-minute intervals of moderate-intensity infra-red light significantly lowered the inflammatory response induced via the TLR4 receptor signaling pathway in human cell cultures. Anti-inflammatory effects were likewise achieved by electromagnetic field exposure of cells to daily 10-minute intervals of either pulsed electromagnetic fields (PEMF) or to low-level static magnetic fields. Because current illumination and electromagnetic field therapies have no known side effects and are already approved for some medical uses, we have here developed protocols for verification in clinical trials of COVID 19 infection. These treatments are affordable, simple to implement, and may help to resolve the acute respiratory distress of COVID 19 patients both in the home and in the hospital.

Keywords: COVID 19, electromagnetic fields therapy, inflammation, photobiomodulation therapy

Procedia PDF Downloads 122

Authors: Aleksandra Twarda, Dobrosława Krzemień, Grzegorz Dubin, Tad A. Holak

Abstract:

Stabilin-2 belongs to the group of scavenger receptors and plays a crucial role in clearance of more than 10 ligands from the bloodstream, including hyaluronic acid, products of degradation of extracellular matrix and metabolic products. The Link domain, a defining feature of stabilin-2, has a sequence similar to Link domains in other hyaluronic acid receptors, such as CD44 or TSG-6, and is responsible for most of ligands binding. Present knowledge of signal transduction by stabilin-2, as well as ligands’ recognition and binding mechanism, is limited. Until now, no experimental structures have been solved for any segments of stabilin-2. It has recently been demonstrated that the stabilin-2 knock-out or blocking of the receptor by an antibody effectively opposes cancer metastasis by elevating the level of circulating hyaluronic acid. Moreover, loss of expression of stabilin-2 in a peri-tumourous liver correlates with increased survival. Solving of the crystal structure of stabilin-2 and elucidation of the binding mechanism of hyaluronic acid could enable the precise characterization of the interactions in the binding site. These results may allow for designing specific small-molecule inhibitors of stabilin-2 that could be used in cancer therapy. To carry out screening for crystallization of stabilin-2, we cloned constructs of the Link domain of various lengths with or without surrounding domains. The folding properties of the constructs were checked by nuclear magnetic resonance (NMR). It is planned to show the binding of hyaluronic acid to the Link domain using several biochemical methods, i.a. NMR, isothermal titration calorimetry and fluorescence polarization assay.

Keywords: stabilin-2, Link domain, X-ray crystallography, NMR, hyaluronic acid, cancer

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Authors: Maximilian Cedzich, Ingo Dietz Von Bayer, Roland Jochem

Abstract:

In order for industrial companies to continue to succeed in dynamic, globalized markets, they must be able to train their employees in an agile manner and at short notice in line with the exogenous conditions that arise. For this purpose, it is indispensable to operate a proactive competence management system for employees that recognizes qualification needs timely in order to be able to address them promptly through qualification measures. However, there are hardly any approaches to be found in the literature that includes systematic, proactive competence management. In order to help close this gap, this publication presents a process model that systematically develops bottom-up, future-oriented target competence profiles based on the tasks of the employees. Concretely, in the first step, the tasks of the individual employees are examined for assumed future conditions. In other words, qualitative scenarios are considered for the individual tasks to determine how they are likely to change. In a second step, these scenario-based future tasks are translated into individual future-related target competencies of the employee using a matrix of generic task properties. The final step pursues the goal of validating the target competence profiles formed in this way within the framework of a management workshop. This process model provides industrial companies with a tool that they can use to determine the competencies required by their own employees in the future and compare them with the actual prevailing competencies. If gaps are identified between the target and the actual, these qualification requirements can be closed in the short term by means of qualification measures.

Keywords: dynamic globalized markets, employee competence management, industrial companies, knowledge management

Procedia PDF Downloads 175

Authors: Youngsun Moon, Yeong-Ju Go, Jong-Soo Choi

Abstract:

Most drones that currently have surveillance/reconnaissance missions are basically equipped with optical equipment, but we also need to use a microphone array to estimate the location of the acoustic source. This can provide additional information in the absence of optical equipment. The purpose of this study is to estimate Direction of Arrival (DOA) based on Time Difference of Arrival (TDOA) estimation of the acoustic source in the drone. The problem is that it is impossible to measure the clear target acoustic source because of the drone noise. To overcome this problem is to separate the drone noise and the target acoustic source using Blind Source Separation(BSS) based on Independent Component Analysis(ICA). ICA can be performed assuming that the drone noise and target acoustic source are independent and each signal has non-gaussianity. For maximized non-gaussianity each signal, we use Negentropy and Kurtosis based on probability theory. As a result, we can improve TDOA estimation and DOA estimation of the target source in the noisy environment. We simulated the performance of the DOA algorithm applying BSS algorithm, and demonstrated the simulation through experiment at the anechoic wind tunnel.

Keywords: aeroacoustics, acoustic source detection, time difference of arrival, direction of arrival, blind source separation, independent component analysis, drone

Procedia PDF Downloads 142

Authors: Rajiv Jash, Himangshusekhar Maji

Abstract:

Phytomolecules have long been associated with the effective treatment of various disorders since ages. This study focuses on identifying the immunomodulatory pure molecules isolated from plants, which can be studied for their effect in alleviating IgAN. All the phytomolecules mentioned here have inflammation-reducing properties, and IgAN, being an autoimmune disease, can be a good target of these phytomolecules. Various pathological pathways of IgA nephropathy can be targeted with these phytomolecules, and this study is an effort to find out the rationale behind the choice of the molecules based on their ability to target the effector molecules of those pathological pathways.

Keywords: IgAN, fibrosis, inflammation, ESRD, TGFβ

Procedia PDF Downloads 73

Authors: Yoon-Cheol Park

Abstract:

This research focuses on examining the information structures in the old Chinese character-Korean translation of the Vajrachedika-prajna-paramita sutra. The background of this research comes from the fact that there were no previous researches which looked into the information structures in the target text of the Vajrachedika-prajna-paramita sutra by now. The existing researches on the Buddhist scripture translation mainly put weight on message conveyance by literal and semantic translation methods. But the message conveyance from one language to another has a necessity to be delivered with equivalent information structure. Thus, this research is intended to investigate on the flow of old and new information in the target text of Buddhist scripture, compared with source text. The Vajrachedika-prajna-paramita sutra unlike other Buddhist scriptures is composed of conversational structures between Buddha and his disciple, Suboli. This implies that the information flow can be changed by utterance context and some propositions. So, this research tries to analyze the flow of old and new information within the source and target text. As a result of analysis, this research can discover the following facts; firstly, there are the differences of the information flow in the message conveyance between the old Chinese character and Korean by language features. The old Chinese character reveals that old-new information flow is developed, while Korean indicates new-old information flow because of word order. Secondly, the source text of the Vajrachedika-prajna-paramita sutra includes abstruse terminologies, jargon and abstract words. These make influence on the target text and cause the change of the information flow. But the repetitive expressions of these words provide the old information in the target text. Lastly, the Vajrachedika-prajna-paramita sutra offers the expository structure from conversations between Buddha and Suboli. It means that the information flow is developed in the way of explaining specific subjects and of paraphrasing unfamiliar phrases and expressions. From the results of analysis above, this research can verify that the information structures in the target text of the Vajrachedika-prajna-paramita sutra are changed by specific subjects and terminologies, developed with the new-old information flow by repetitive expressions or word order and reveal the information structures familiar to target culture. It also implies that the translation of the Vajrachedika-prajna-paramita sutra as a religious book needs the message conveyance to take into account the information structures of two languages.

Keywords: abstruse terminologies, the information structure, new and old information, old Chinese character-Korean translation

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Authors: Chanho Park, Juneseok You, Kuewhan Jang, Sungsoo Na

Abstract:

Detection technique of nanotoxic materials is strongly imperative, because nano-toxic materials can harmfully influence human health and environment as their engineering applications are growing rapidly in recent years. In present work, we report the DNA immobilized quartz crystal microbalance (QCM) based sensor for detection of nano-toxic materials such as silver ions, Hg2+ etc. by using functionalization of quartz crystal with a target-specific DNA. Since the mass of a target material is comparable to that of an atom, the mass change caused by target binding to DNA on the quartz crystal is so small that it is practically difficult to detect the ions at low concentrations. In our study, we have demonstrated fast and in situ detection of nanotoxic materials using quartz crystal microbalance. We report the label-free and highly sensitive detection of silver ion for present case, which is a typical nano-toxic material by using QCM and silver-specific DNA. The detection is based on the measurement of frequency shift of Quartz crystal from constitution of the cytosine-Ag+-cytosine binding. It is shown that the silver-specific DNA measured frequency shift by QCM enables the capturing of silver ions below 100pM. The results suggest that DNA-based detection opens a new avenue for the development of a practical water-testing sensor.

Keywords: nano-toxic ions, quartz crystal microbalance, frequency shift, target-specific DNA

Procedia PDF Downloads 301