Search results for: distant cellular interaction

Authors: Vincent Murray

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The glycopeptide bleomycin is used in the treatment of testicular cancer, Hodgkin's lymphoma, and squamous cell carcinoma. Bleomycin damages and cleaves DNA in human cells, and this is considered to be the main mode of action for bleomycin's anti-tumor activity. In particular, double-strand breaks are thought to be the main mechanism for the cellular toxicity of bleomycin. Using Illumina next-generation DNA sequencing techniques, the genome-wide sequence specificity of bleomycin-induced double-strand breaks was determined in human cells. The degree of bleomycin cleavage was also assessed at the transcription start sites (TSSs) of actively transcribed genes and compared with non-transcribed genes. It was observed that bleomycin preferentially cleaved at the TSSs of actively transcribed human genes. There was a correlation between the degree of this enhanced cleavage at TSSs and the level of transcriptional activity. Bleomycin cleavage is also affected by chromatin structure and at TSSs, the peaks of bleomycin cleavage were approximately 200 bp apart. This indicated that bleomycin was able to detect phased nucleosomes at the TSSs of actively transcribed human genes. The genome-wide cleavage pattern of the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin was also investigated in human cells. As found for bleomycin, these bleomycin analogues also preferentially cleaved at the TSSs of actively transcribed human genes. The cytotoxicity (IC₅₀ values) of these bleomycin analogues was determined. It was found that the degree of enhanced cleavage at TSSs was inversely correlated with the IC₅₀ values of the bleomycin analogues. This suggested that the level of cleavage at the TSSs of actively transcribed human genes was important for the cytotoxicity of bleomycin and analogues. Hence this study provided a deeper understanding of the cellular processes involved in the cancer chemotherapeutic activity of bleomycin.

Keywords: anti-tumour activity, bleomycin analogues, chromatin structure, genome-wide study, Illumina DNA sequencing

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Authors: Fakhrosadat Sajjadian

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In the USA, about 5% of women diagnosed with breast cancer annually are affected by Inflammatory Breast Cancer (IBC), which is a highly aggressive type of Locally Advanced Breast Cancer (LABC). It is a type of LABC that is clinically and pathologically different, known for its rapid growth, invasiveness, and ability to promote the growth of blood vessels. Almost all women are found to have lymph nodes affected upon diagnosis, while around 36% show obvious distant metastases. Even with the latest improvements in multimodality therapies, the outlook for patients with IBC remains bleak, as the average disease-free survival time is less than 2.5 years. Recent research on the genetic factors responsible for the IBC phenotype has resulted in the discovery of genes that play a role in the advancement of this illness. The development of primary human cell lines and animal models has assisted in this research. These advancements offer new possibilities for future actions in identifying and treating IBC.

Keywords: breast cancer, inflammation, diagnosis, IBC, LABC

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Authors: Thauane Silva, Gabrielle do Vale, Andre Ferreira, Marilda Siqueira, Thiago Moreno L. Souza, Milene D. Miranda

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The exposure of A(H1N1)pdm09-infected epithelial cells (HeLa) to HIV-1 viral particles, or its gp120, enhanced interferon-induced transmembrane protein (IFITM3) content, a viral restriction factor (RF), resulting in a decrease in influenza replication. The gp120 binds to CCR5 (R5) or CXCR4 (X4) cell receptors during HIV-1 infection. Then, it is possible that the endogenous ligands of these receptors also modulate the expression of IFITM3 and other cellular factors that restrict influenza virus replication. Thus, the aim of this study is to analyze the role of cellular receptors R5 and X4 in modulating RFs in order to inhibit the replication of the influenza virus. A549 cells were treated with 2x effective dose (ED50) of endogenous R5 or X4 receptor agonists, CCL3 (20 ng/ml), CCL4 (10 ng/ml), CCL5 (10 ng/ml) and CXCL12 (100 ng/mL) or exogenous agonists, gp120 Bal-R5, gp120 IIIB-X4 and its mutants (5 µg/mL). The interferon α (10 ng/mL) and oseltamivir (60 nM) were used as a control. After 24 h post agonists exposure, the cells were infected with virus influenza A(H3N2) at 2 MOI (multiplicity of infection) for 1 h. Then, 24 h post infection, the supernatant was harvested and, the viral titre was evaluated by qRT-PCR. To evaluate IFITM3 and SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) protein levels, A549 were exposed to agonists for 24 h, and the monolayer was lysed with Laemmli buffer for western blot (WB) assay or fixed for indirect immunofluorescence (IFI) assay. In addition to this, we analyzed other RFs modulation in A549, after 24 h post agonists exposure by customized RT² Profiler Polymerase Chain Reaction Array. We also performed a functional assay in which SAMHD1-knocked-down, by single-stranded RNA (siRNA), A549 cells were infected with A(H3N2). In addition, the cells were treated with guanosine to assess the regulatory role of dNTPs by SAMHD1. We found that R5 and X4 agonists inhibited influenza replication in 54 ± 9%. We observed a four-fold increase in SAMHD1 transcripts by RFs mRNA quantification panel. After 24 h post agonists exposure, we did not observe an increase in IFITM3 protein levels through WB or IFI assays, but we observed an upregulation up to three-fold in the protein content of SAMHD1, in A549 exposed to agonists. Besides this, influenza replication enhanced in 20% in cell cultures that SAMDH1 was knockdown. Guanosine treatment in cells exposed to R5 ligands further inhibited influenza virus replication, suggesting that the inhibitory mechanism may involve the activation of the SAMHD1 deoxynucleotide triphosphohydrolase activity. Thus, our data show for the first time a direct relationship of SAMHD1 and inhibition of influenza replication, and provides perspectives for new studies on the signaling modulation, through cellular receptors, to induce proteins of great importance in the control of relevant infections for public health.

Keywords: chemokine receptors, gp120, influenza, virus restriction factors

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Authors: Galal Elkobrosy, Amr M. Abdelrazek, Bassuny M. Elsouhily, Mohamed E. Khidr

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Crank shaft length, connecting rod length, crank angle, engine rpm, cylinder bore, mass of piston and compression ratio are the inputs that can control the performance of the slider crank mechanism and then its efficiency. Several combinations of these seven inputs are used and compared. The throughput engine torque predicted by the simulation is analyzed through two different regression models, with and without interaction terms, developed according to multi-linear regression using LU decomposition to solve system of algebraic equations. These models are validated. A regression model in seven inputs including their interaction terms lowered the polynomial degree from 3^rd degree to 1^st degree and suggested valid predictions and stable explanations.

Keywords: design of experiments, regression analysis, SI engine, statistical modeling

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Authors: Ruswanto Ruswanto, Richa Mardianingrum, Tita Nofianti, Nur Rahayuningsih

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Tuberculosis (TB) is a chronic disease as a result of Mycobacterium tuberculosis. It can affect all age groups, and hence, is a global health problem that causes the death of millions of people every year. One of the drugs used in tuberculosis treatment is isonicotinohydrazide. In this study, N'-benzoylisonicotinohydrazide derivative compounds (a-l) were prepared using acylation reactions between isonicotinohydrazide and benzoyl chloride derivatives, through the reflux method. Molecular docking studies suggested that all of the compounds had better interaction with Mycobacterium tuberculosis enoyl-acyl carrier protein reductase (InhA) than isonicotinohydrazide. It can be concluded that N'-benzoylisonicotinohydrazide derivatives (a-l) could be used as anti-tuberculosis candidates. From the docking results revealed that all of the compounds interact well with InhA, with compound g (N'-(3-nitrobenzoyl)isonicotinohydrazide) exhibiting the best interaction.

Keywords: anti-tuberculosis , docking, InhA, N'-benzoylisonicotinohydrazide, synthesis

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Authors: M. Al Azri, M. Elzain, K. Bouziane, S. M. Chérif

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The electronic and magnetic properties of 6H-SiC with Mn impurities have been calculated using ab-initio calculations. Various configurations of Mn sites and Si and C vacancies were considered. The magnetic coupling between the two Mn atoms at substitutional and interstitials sites with and without vacancies is studied as a function of Mn atoms interatomic distance. It was found that the magnetic interaction energy decreases with increasing distance between the magnetic atoms. The energy levels appearing in the band gap due to vacancies and due to Mn impurities are determined. The calculated DOS’s are used to analyze the nature of the exchange interaction between the impurities. The band coupling model based on the p-d and d-d level repulsions between Mn and SiC has been used to describe the magnetism observed in each configuration. Furthermore, the impacts of applying U to Mn-d orbital on the magnetic moment have also been investigated. The results are used to understand the experimental data obtained on Mn- 6H-SiC (as-implanted and as –annealed) for various Mn concentration (CMn = 0.7%, 1.6%, 7%).

Keywords: ab-initio calculations, diluted magnetic semiconductors, magnetic properties, silicon carbide

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Authors: Carlos Ferreira, Paulo Freitas, Valentim Freitas

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Creative industries’ workers are becoming more prominent as countries move towards intellectual-based economies. Consequently, the nature and essence of the workplace needs to be reconfigured so that creativity and productivity can be better promoted at these spaces. Using a multidisciplinary approach and a user-centered methodology, combining product design, electronic engineering, software and human-computer interaction, we have designed and developed a new seat that uses embedded sensors and actuators to increase the overall well-being of its users, their productivity and their creativity. Our contribution focuses on the parameters that most affect the user’s work on these kinds of spaces, which are, according to our study, noise and temperature. We describe the design process for a new interactive seat targeted at improving workspace productivity.

Keywords: human-computer interaction, usability, user interface, creativity, ergonomics

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Authors: Jozsef Katona, Attila Kovari, Tibor Ujbanyi, Gergely Sziladi

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By the development of IT systems, human-computer interaction is also developing even faster and newer communication methods become available in human-machine interaction. In this article, the application of a hand gesture controlled human-computer interface is being introduced through the example of a mobile robot. The control of the mobile robot is implemented in a realistic virtual environment that is advantageous regarding the aspect of different tests, parallel examinations, so the purchase of expensive equipment is unnecessary. The usability of the implemented hand gesture control has been evaluated by test subjects. According to the opinion of the testing subjects, the system can be well used, and its application would be recommended on other application fields too.

Keywords: human-machine interface (HCI), mobile robot, hand control, virtual environment

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Authors: Sarwat Sultan, Frasat Kanwal, Motasem Mirza

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The impact of religiosity on people’s lives has always been found complex because some of them turn to religion to get comfort and relief from their fear, guilt, and illness, whereas some become away due to the perception that God is revengeful and distant for their conduct. The overarching aim of this study was to know whether the relationship between religious struggles (comfort/strain) and life satisfaction is mediated by psychological well-being. The participants of this study were 529 Muslim students who provided their responses on the measures of religious comfort/strain, psychological well-being, and life satisfaction. Results revealed that religious comfort predicted well-being and life satisfaction positively, while religious strain predicted negatively. Findings showed that psychological well-being mediated the prediction of religious comfort and strain for life satisfaction. These findings have implications for students’ mental health because their teachers and professionals can enhance their well-being by teaching them positive aspects of religion and God.

Keywords: attitude towards god, religious comfort, religious strain, life satisfaction, psychological wellbeing

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Authors: Tamrat Tesfaye, Tilahun Seyoum, K. Shabaridharan

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The objective of this paper was to determine the effect of NaOH concentration, soaking time, soaking temperature and their interaction on percentage yield of fibre extract using Response Surface Methodology (RSM). A Box-Behnken design was employed to optimize the extraction process of cellulosic fibre from sugar cane by-product bagasse using low alkaline extraction technique. The quadratic model with the optimal technological conditions resulted in a maximum fibre yield of 56.80% at 0.55N NaOH concentration, 4 h steeping time and 60ᵒC soaking temperature. Among the independent variables concentration was found to be the most significant (P < 0.005) variable and the interaction effect of concentration and soaking time leads to securing the optimized processes.

Keywords: sugarcane bagasse, low alkaline, Box-Behnken, fibre

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Authors: Rifqi Irvansyah, Abdullah Abdullah, Yunita Idris, Bunga Raihanda

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Banda Aceh is particularly susceptible to heightened vulnerability during natural disasters due to its concentrated exposure to multi-hazard risks. Despite urgent priorities during the aftermath of natural disasters, such as the 2004 Indian Ocean earthquake and tsunami, several public facilities, including school buildings, sustained damage yet continued operations without adequate repairs, even though they were submerged by the tsunami. This research aims to evaluate the consequences of column damage induced by tsunami inundation on the structural integrity of buildings. The investigation employs interaction diagrams for columns to assess their capacity, taking into account factors such as rebar deterioration and corrosion. The analysis result shows that one-fourth of the K1 columns on the first floor fall outside of the column interaction diagram, indicating that the column structure cannot handle the load above it, as evidenced by the presence of Pu and Mu, which are greater than the column's design strength. This suggests that the five columns of K1 should be cause for concern, as the column's capacity is decreasing. These results indicate that the structure of the building cannot sustain the applied load because the column cross-section has deteriorated. In contrast, all K2 columns meet the design strength, indicating that the column structure can withstand the structural loads.

Keywords: tsunami inundation, column damage, column interaction diagram, mitigation effort

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Authors: Lei Zhang, Li Ji

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Formal learning and informal learning represent two distinct learning styles: one is systematic and organized, another is causal and unstructured. Although there are many factors influencing online learning satisfaction, including self-regulation, self-efficacy, and interaction, factors influencing online formal learning and informal learning satisfaction may differ from each other. This paper investigated and compared influential factors of online formal and informal learning. Two questionnaires were created based on previous studies to explore factors influencing online formal learning and online informal learning satisfaction, respectively. A sample of 105 college students from different departments in a university located in the eastern part of China was selected to participate in this study. They all had an online learning experience and agreed to fill out questionnaires. Correlation analysis, variance analysis, and regression analysis were employed in this study. In addition, five participants were chosen for interviews. The study found that student-content, interaction, self-regulation, and self-efficacy related positively to both online formal learning and informal learning satisfaction. In addition, compared to online formal learning, student-content interaction in informal learning was the most influential factor for online learning satisfaction, perhaps that online informal learning was more goal-oriented and learners paid attention to the quality of content. In addition, results also revealed that interactions among students or teachers had little impact on online informal learning satisfaction. This study compared influential factors in online formal and informal learning satisfaction helped to add discussions to online learning satisfaction and contributed to further practices of online learning.

Keywords: learning satisfaction, formal learning, informal learning, online learning

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Authors: Louis N. Y. Wong

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En-echelon fractures are commonly found in rocks, which appear as a special set of regularly oriented and spaced fractures. By using both experimental and numerical approaches, this study investigates the interaction among them, and how this interaction finally contributes to the development of a shear rupture (fault), especially in brittle natural rocks. Firstly, uniaxial compression tests are conducted on marble specimens containing en-echelon flaws. The latter is cut by using the water abrasive jet into the rock specimens. The fracturing processes of these specimens leading to the formation of a fault are observed in detail by the use of a high speed camera. The influences of the flaw geometry on the production of tensile cracks and shear cracks, which in turn dictate the coalescence patterns of the entire set of en-echelon flaws are comprehensively studied. Secondly, a numerical study based on a recently developed contact model, flat-joint contact model using the discrete element method (DEM) is carried out to model the present laboratory experiments. The numerical results provide a quantitative assessment of the interaction of en-echelon flaws. Particularly, the evolution of the stress field, as well as the characteristics of new crack initiation, propagation and coalescence associated with the generation of an eventual shear rupture are studied in detail. The numerical results are found to agree well with the experimental results obtained in both microscopic and macroscopic observations.

Keywords: discrete element method, en-echelon flaws, fault, marble

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Authors: Manuel A. Alonso-Tarajano, Roberto Mosca, Patrick Aloy

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Protein kinases participate in a myriad of cellular processes of major biomedical interest. The in vivo substrate specificity of these enzymes is a process determined by several factors, and despite several years of research on the topic, is still far from being totally understood. In the present work, we have quantified the contributions to the kinase substrate specificity of i) the phosphorylation sites and their surrounding residues in the sequence and of ii) the association of kinases to adaptor or scaffold proteins. We have used position-specific scoring matrices (PSSMs), to represent the stretches of sequences phosphorylated by 93 families of kinases. We have found negative correlations between the number of sequences from which a PSSM is generated and the statistical significance and the performance of that PSSM. Using a subset of 22 statistically significant PSSMs, we have identified specificity determinant residues (SDRs) for 86% of the corresponding kinase families. Our results suggest that different SDRs can function as positive or negative elements of substrate recognition by the different families of kinases. Additionally, we have found that human proteins with known function as adaptors or scaffolds (kAS) tend to interact with a significantly large fraction of the substrates of the kinases to which they associate. Based on this characteristic we have identified a set of 279 potential adaptors/scaffolds (pAS) for human kinases, which is enriched in Pfam domains and functional terms tightly related to the proposed function. Moreover, our results show that for 74.6% of the kinase– pAS association found, the pAS colocalize with the substrates of the kinases they are associated to. Finally, we have found evidence suggesting that the association of kinases to adaptors and scaffolds, may contribute significantly to diminish the in vivo substrate crossed- specificity of protein kinases. In general, our results indicate the relevance of several SDRs for both the positive and negative selection of phosphorylation sites by kinase families and also suggest that the association of kinases to pAS proteins may be an important factor for the localization of the enzymes with their set of substrates.

Keywords: kinase, phosphorylation, substrate specificity, adaptors, scaffolds, cellular colocalization

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Authors: Jie Zhang, Chaomin Zhang

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Based on the network theory, this paper selects three Emerging-Market Multinationals Enterprises (EMNEs) as the research object and takes the typical overseas market opportunities constructed by them as the analysis unit to research the internal mechanism of overseas market opportunity construction of the EMNEs. The results show that: (1) EMNEs overseas market opportunity construction is a complex process, through the continuous interaction between enterprises and entities in the internal and external networks to achieve opportunity prototype, opportunity creation, and opportunity optimization in overseas markets. (2) Governments, foreign institutions and industry associations in the institutional network and competitors, partners, and customers in the commercial networks are the important entities in the construction of overseas market opportunities. Through the interaction of entity perception, relationship construction, and utilization, enterprises can obtain the necessary information, resources, and political asylum in the process of opportunity construction. (3) Organizations, project teams, and organizational sub-units within the enterprise are important internal entities for the construction of overseas market opportunities. Through the connection between different entities, they can achieve the circulation of resources within the organization and promote the opportunity construction of overseas markets. The research conclusions expand the relevant research on international opportunities and have inspiring and guiding significance for the expansion of EMNEs overseas markets.

Keywords: international (overseas) opportunities, opportunity construction, network entities, interaction, resource circulation

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Authors: Xin Zhao. Xuerong Zheng. Andrey L. Rogach

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Using single metal atoms has been considered an efficient way to develop new HER and OER catalysts. MXenes, a class of two-dimensional materials, have attracted tremendous interest as promising substrates for single-atom metal catalysts. However, there is still a lack of systematic investigations on the interaction mechanisms between various MXenes substrates and single atoms. Besides, due to the poor interaction between metal atoms and substrates resulting in low loading and stability, dual-atom MXenes-based catalysts have not been successfully synthesized. We summarized the electrocatalytic enhancement mechanism of three MXenes-based single-atom catalysts through experimental and theoretical results demonstrating the stronger hybridization between Co 3d and surface-terminated O 2p orbitals, optimizing the electronic structure of Co single atoms in the composite. This, in turn, lowers the OER and HER energy barriers and accelerates the catalytic kinetics in the case of the Co@V2CTx composite. The poor interaction between single atoms and substrates can be improved by a surface modification to synthesize dual-atom catalysts. The synergistic electronic structure enhances the stability and electrocatalytic activity of the catalyst. Our study provides guidelines for designing single-atom and dual-atom MXene-based electrocatalysts and sheds light on the origins of the catalytic activity of single-atoms on MXene substrates.

Keywords: dual-atom catalyst, single-atom catalyst, MXene substrates, water splitting

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Authors: Saman Khan, Imrana Naseem

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Copper is an essential trace element required for pro-angiogenic co-factors including vascular endothelial growth factor (VEGF). Elevated levels of copper are found in various types of cancer including prostrate, colon, breast, lung and liver for angiogensis and metastasis. Therefore, targeting copper via copper-specific chelators in cancer cells can be developed as effective anticancer treatment strategy. In continuation of our pursuit to design and synthesize copper chelators, herein we opted for a reaction to incorporate di-(2-picolyl) amine in 3-(bromoacetyl) coumarin (parent backbone) for the synthesis of complex 1. We evaluated lipid peroxidation, protein carbonylation, ROS generation, DNA damage and consequent apoptosis by complex 1 in exogenously added Cu(II) in human peripheral lymphocytes (simulate malignancy condition). Results showed that Cu(II)-complex 1 interaction leads to cell proliferation inhibition, apoptosis, ROS generation and DNA damage in human lymphocytes, and these effects were abrogated by cuprous chelator neocuproine and ROS scavengers (thiourea, catalase, SOD). This indicates that complex 1 cytotoxicity is due to redox cycling of copper to generate ROS which leads to pro-oxidant cell death in cancer cells. To further confirm our hypothesis, using the rat model of diethylnitrosamine (DEN) induced hepatocellular carcinoma; we showed that complex 1 mediates DNA breakage and cell death in isolated carcinoma cells. Membrane permeant copper chelator, neocuproine, and ROS scavengers inhibited the complex 1-mediated cellular DNA degradation and apoptosis. In summary, complex 1 anticancer activity is due to its copper chelation capability. These results will provide copper chelation as an effective targeted cancer treatment strategy for selective cytotoxic action against malignant cells without affecting normal cells.

Keywords: cancer treatment, copper chelation, ROS generation, DNA damage, redox cycling, apoptosis

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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: Madhav Khadilkar

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Construction of a large standby reservoir was required to provide secure water supply. The new reservoir was required to be constructed at the same location of an abandoned old open pond due to space constraints. Some investigations were carried out earlier to improvise and re-commission the existing pond. But due to a lack of quantified risk of settlement from voids in the underlying limestone, the shallow foundations were not found feasible. Since the reservoir was resting on hard strata for about three-quarter of plan area and one quarter was resting on soil underlying with limestone and considerably low subgrade modulus. Further investigations were carried out to ascertain the locations and extent of voids within the limestone. It was concluded that the risk due to lime dissolution was acceptably low, and the site was found geotechnically feasible. The hazard posed by limestone dissolution was addressed through the integrated structural and geotechnical analysis and design approach. Finite Element Analysis was carried out to quantify the stresses and differential settlement due to various probable loads and soil-structure interaction. Walls behaving as cantilever under operational loads were found undergoing in-plane bending and tensile forces due to soil-structure interaction. Sensitivity analysis for varying soil subgrade modulus was carried out to check the variation in the response of the structure and magnitude of stresses developed. The base slab was additionally checked for the loss of soil contact due to lime pocket formations at random locations. The expansion and contraction joints were planned to receive minimal additional forces due to differential settlement. The reservoir was designed to sustain the actions corresponding to allowable deformation limits per code, and geotechnical measures were proposed to achieve the soil parameters set in structural analysis.

Keywords: differential settlement, limestone dissolution, reservoir, soil structure interaction

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Authors: Samar Alharbi, Yota Dimitriadi

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The literature on educational technology in Saudi Arabia reveals female learners’ unwillingness to study fully online courses in higher education despite the fact that Saudi universities have offered a variety of online degree programmes to undergraduate students in many regions of the country. The root causes keeping female students from successfully learning in online environments are limited social interaction, lack of motivation and difficulty with the use of e-learning platforms. E-immediacy remains an important method of online teaching to enhance students’ interaction and support their online learning. This study explored Saudi female students’ perceptions, as well as the experiences of lecturers’ immediacy behaviours in online environments, who participate in fully online courses using Blackboard at a Saudi university. Data were collected through interviews with focus groups. The three focus groups included five to seven students each. The female participants were asked about lecturers’ e-immediacy behaviours and which e-immediacy behaviours were important for an effective learning environment. A thematic analysis of the data revealed three main themes: the encouragement of student interaction, the incorporation of social media and addressing the needs of students. These findings provide lecturers with insights into instructional designs and strategies that can be adopted in using e-immediacy in effective ways, thus improving female learners’ interactions as well as their online learning experiences.

Keywords: e-learning, female students, higher education, immediacy

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Authors: Ozlem Oral, Seval Kilic, Ozlem Yedier, Serap Dokmeci, Devrim Gozuacik

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Autophagy is a degradation pathway, activating under stress conditions. It digests macromolecules, such as abnormal proteins and long-lived organelles by engulfing them and by subsequent delivery of the cargo to lysosomes. The members of the phospholipid-dependent serine/threonine kinases, involved in many signaling pathways, which are necessary for the regulation of cellular metabolic activation. Previous studies implicate that, serine/threonine kinases have crucial roles in the mechanism of many diseases depend on the activated and/or inactivated signaling pathway. Data indicates, the signaling pathways activated by serine/threonine kinases are also involved in activation of autophagy mechanism. However, the information about the effect of serine/threonine kinases on autophagy mechanism and the roles of these effects in disease formation is limited. In this study, we investigated the effect of activated serine/threonine kinases on autophagic pathway. We performed a commonly used autophagy technique, GFP-LC3 dot formation and by using microscopy analyses, we evaluated promotion and/or inhibition of autophagy in serine/threonine kinase-overexpressed fibroblasts as well as cancer cells. In addition, we carried out confocal microscopy analyses and examined autophagic flux by utilizing the differential pH sensitivities of RFP and GFP in mRFP-GFP-LC3 probe. Based on the shRNA-library based screening, we identified autophagy-related proteins affected by serine/threonine kinases. We further studied the involvement of serine/threonine kinases on the molecular mechanism of newly identified autophagy proteins and found that, autophagic pathway is indirectly controlled by serine/threonine kinases via specific autophagic proteins. Our data indicate the molecular connection between two critical cellular mechanisms, which have important roles in the formation of many disease pathologies, particularly cancer. This project is supported by TUBITAK-1001-Scientific and Technological Research Projects Funding Program, Project No: 114Z836.

Keywords: autophagy, GFP-LC3 dot formation assay, serine/threonine kinases, shRNA-library screening

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Authors: Mei Hong, Wei Liu, Xuemin Dai, Yanxiong Pan, Xiangling Ji

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Polyamic acid (PAA) is the precursor of polyimide (PI) prepared by a two-step method, its molecular weight and molecular weight distribution not only play an important role during the preparation and processing, but also influence the final performance of PI. However, precise characterization on molecular weight of PAA is still a challenge because of the existence of very complicated interactions in the solution system, including the electrostatic interaction, hydrogen bond interaction, dipole-dipole interaction, etc. Thus, it is necessary to establisha suitable strategy which can completely suppress these complex effects and get reasonable data on molecular weight. Herein, the gel permeation chromatography (GPC) coupled with differential refractive index (RI) and multi-angle laser light scattering (MALLS) detectors were applied to measure the molecular weight of (6FDA-DMB) PAA using different mobile phases, LiBr/DMF, LiBr/H3PO4/THF/DMF, LiBr/HAc/THF/DMF, and LiBr/HAc/DMF, respectively. It was found that combination of LiBr with HAc can shield the above-mentioned complex interactions and is more conducive to the separation of PAA than only addition of LiBr in DMF. LiBr/HAc/DMF was employed for the first time as a mild mobile phase to effectively separate PAA and determine its molecular weight. After a series of conditional experiments, 0.02M LiBr/0.2M HAc/DMF was fixed as an optimized mobile phase to measure the relative and absolute molecular weights of (6FDA-DMB) PAA prepared, and the obtained Mw from GPC-MALLS and GPC-RI were 35,300 g/mol and 125,000 g/mol, respectively. Particularly, such a mobile phase is also applicable to other PAA samples with different structures, and the final results on molecular weight are also reproducible.

Keywords: Polyamic acids, Polyelectrolyte effects, Gel permeation chromatography, Mobile phase, Molecular weight

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Authors: Peter Križan, Juraj Beniak, Ľubomír Šooš, Miloš Matúš

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Biomass treatment through densification is very suitable and important technology before its effective energy recovery. Densification process of biomass is significantly influenced by various technological and also material parameters which are ultimately reflected on the final solid Biofuels quality. The paper deals with the experimental research of the relationship between technological and material parameters during densification of fast-growing trees, roundly fast-rowing willow. The main goal of presented experimental research is to determine the relationship between pressing pressure raw material fraction size from a final briquettes density point of view. Experimental research was realized by single-axis densification. The impact of fraction size with interaction of pressing pressure and stabilization time on the quality properties of briquettes was determined. These parameters interaction affects the final solid biofuels (briquettes) quality. From briquettes production point of view and also from densification machines constructions point of view is very important to know about mutual interaction of these parameters on final briquettes quality. The experimental findings presented here are showing the importance of mentioned parameters during the densification process.

Keywords: briquettes density, densification, fraction size, pressing pressure, stabilization time

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Authors: Vrushali Guhe, Shailza Singh

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Cutaneous leishmaniasis is neglected tropical disease present worldwide caused by the protozoan parasite Leishmania major, the therapeutic armamentarium for leishmaniasis are showing several limitations as drugs are showing toxic effects with increasing resistance by a parasite. Thus identification of novel therapeutic targets is of paramount importance. Previous studies have shown that autophagy, a cellular process, can either facilitate infection or aid in the elimination of the parasite, depending on the specific parasite species and host background in leishmaniasis. In the present study, our objective was to target the essential autophagy protein ATG8, which plays a crucial role in the survival, infection dynamics, and differentiation of the Leishmania parasite. ATG8 in Leishmania major and its homologue, LC3, in Homo sapiens, act as autophagic markers. Present study manifested the crucial role of ATG8 protein as a potential target for combating Leishmania major infection. Through bioinformatics analysis, we identified non-conserved motifs within the ATG8 protein of Leishmania major, which are not present in LC3 of Homo sapiens. Against these two non-conserved motifs, we generated a peptide library of 60 peptides on the basis of physicochemical properties. These peptides underwent a filtering process based on various parameters, including feasibility of synthesis and purification, compatibility with Selective Reaction Monitoring (SRM)/Multiple reaction monitoring (MRM), hydrophobicity, hydropathy index, average molecular weight (Mw average), monoisotopic molecular weight (Mw monoisotopic), theoretical isoelectric point (pI), and half-life. Further filtering criterion shortlisted three peptides by using molecular docking and molecular dynamics simulations. The direct interaction between ATG8 and the shortlisted peptides was confirmed through Surface Plasmon Resonance (SPR) experiments. Notably, these peptides exhibited the remarkable ability to penetrate the parasite membrane and exert profound effects on Leishmania major. The treatment with these peptides significantly impacted parasite survival, leading to alterations in the cell cycle and morphology. Furthermore, the peptides were found to modulate autophagosome formation, particularly under starved conditions, suggesting their involvement in disrupting the regulation of autophagy within Leishmania major. In vitro, studies demonstrated that the selected peptides effectively reduced the parasite load within infected host cells. Encouragingly, these findings were corroborated by in vivo experiments, which showed a reduction in parasite burden upon peptide administration. Additionally, the peptides were observed to affect the levels of LC3II within host cells. In conclusion, our findings highlight the efficacy of these novel peptides in targeting Leishmania major’s ATG8 and disrupting parasite survival. These results provide valuable insights into the development of innovative therapeutic strategies against leishmaniasis via targeting autophagy protein ATG8 of Leishmania major.

Keywords: ATG8, leishmaniasis, surface plasmon resonance, MD simulation, molecular docking, peptide designing, therapeutics

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Authors: Sharmi Mukherjee, Anindita Chakraborty

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Cellular irradiation incites complex responses including arrest of cell cycle progression. This article accentuates the effects of radiation on cell cycle status of radiation non-targeted cells. Human Hepatoma HepG2 cells were exposed to increasing doses of γ radiations (1, 2, 4, 6 Gy) and their cell culture media was transferred to non-targeted HepG2 cells cultured in other Petri plates. These radiation non-targeted cells cultured in the ICCM (Irradiated cell conditioned media) were the bystander cells on which cell cycle analysis was performed using flow cytometry. An apparent decrease in the distribution of bystander cells at G0/G1 phase was observed with increased radiation doses upto 4 Gy representing a linear relationship. This was accompanied by a gradual increase in cellular distribution at G2/M phase. Interestingly the number of cells in G2/M phase at 1 and 2 Gy irradiation was not significantly different from each other. However, the percentage of G2 phase cells at 4 and 6 Gy doses were significantly higher than 2 Gy dose indicating the IC50 dose to be between 2 and 4 Gy. Cell cycle arrest is an indirect indicator of genotoxic damage in cells. In this study, bystander stress signals through the cell culture media of irradiated cells disseminated the radiation induced DNA damages in the non-targeted cells which resulted in arrest of the cell cycle progression at G2/M phase checkpoint. This implies that actual radiation biological effects represent a penumbra with effects encompassing a larger area than the actual beam. This article highlights the existence of genotoxic damages as bystander effects of γ rays in human Hepatoma cells by cell cycle analysis and opens up avenues for appraisal of bystander stress communications between tumor cells. Contemplation of underlying signaling mechanisms can be manipulated to maximize damaging effects of radiation with minimum dose and thus has therapeutic applications.

Keywords: bystander effect, cell cycle, genotoxic damage, hepatoma

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Authors: A. Armin, R. Fotouhi, W. Szyszkowski

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This paper is part of a study to develop robots for farming. As such power requirement to operate equipment attach to such robots become an important factor. Soil-tool interaction play major role in power consumption, thus predicting accurately the forces which act on the blade during the farming is prime importance for optimal designing of farm equipment. In this paper a finite element investigation for tillage tools and soil interaction is described by using an inelastic constitutive material law for agriculture application. A 3-dimentional (3D) nonlinear finite element analysis (FEA) is developed to examine behavior of a blade with different rake angles moving in a block of soil, and to estimate the blade force. The soil model considered is an elastic-plastic with non-associated Drucker-Prager material model. Special use of contact elements are employed to consider connection between soil-blade and soil-soil surfaces. The FEA results are compared with experiment ones, which show good agreement in accurately predicting draft forces developed on the blade when it moves through the soil. Also, a very good correlation was obtained between FEA results and analytical results from classical soil mechanics theories for straight blades. These comparisons verified the FEA model developed. For analyzing complicated soil-tool interactions and for optimum design of blades, this method will be useful.

Keywords: finite element analysis, soil-blade contact modeling, blade force, mechanical engineering

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Authors: Neha Bhadauria, Indu Gaur, Shilpi Shilpi, Susmita Goswami, Prabir K. Paul

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The aerial surface of plants colonized by Human Enteric Pathogens ()has been implicated in outbreaks of enteric diseases in humans. Practice of organic farming primarily using animal dung as manure and sewage water for irrigation are the most significant source of enteric pathogens on the surface of leaves, fruits and vegetables. The present work aims to have an insight into the molecular mechanism of interaction of Human Enteric Pathogens or their metabolites with cell wall receptors in plants. Tomato plants grown under aseptic conditions at 12 hours L/D photoperiod, 25±1°C and 75% RH were inoculated individually with S. fonticola and K. pneumonia. The leaves from treated plants were sampled after 24 and 48 hours of incubation. The cell wall and cytoplasmic proteins were extracted and isocratically separated on 1D SDS-PAGE. The sampled leaves were also subjected to formaldehyde treatment prior to isolation of cytoplasmic proteins to study protein-protein interactions induced by Human Enteric Pathogens. Protein bands extracted from the gel were subjected to MALDI-TOF-TOF MS analysis. The foremost interaction of Human Enteric Pathogens on the plant surface was found to be cell wall bound receptors which possibly set ups a wave a critical protein-protein interaction in cytoplasm. The study revealed the expression and suppression of specific cytoplasmic and cell wall-bound proteins, some of them being important components of signaling pathways. The results also demonstrated HEP induced rearrangement of signaling pathways which possibly are crucial for adaptation of these pathogens to plant surface. At the end of the study, it can be concluded that controlling the over-expression or suppression of these specific proteins rearrange the signaling pathway thus reduces the outbreaks of food-borne illness.

Keywords: cytoplasmic protein, cell wall-bound protein, Human Enteric Pathogen (HEP), protein-protein interaction

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Authors: Filomena Lopes, Miguel Magalhaes, Carla Santos Pereira, Natercia Durao, Cristina Costa-Lobo

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The option to implement curricular internships with undergraduate students is a pedagogical option with some good results perceived by academic staff, employers, and among graduates in general and IT (Information Technology) in particular. Knowing that this type of exercise has never been so relevant, as one tries to give meaning to the future in a landscape of rapid and deep changes. We have as an example the potential disruptive impact on the jobs of advances in robotics, artificial intelligence and 3-D printing, which is a focus of fierce debate. It is in this context that more and more students and employers engage in the pursuit of career-promoting responses and business development, making their investment decisions of training and hiring. Three decades of experience and research in computer science degree and in information systems technologies degree at the Portucalense University, Portuguese private university, has provided strong evidence of its advantages. The Human Interaction Skills development as well as the attractiveness of such experiences for students are topics assumed as core in the Ccnception and management of the activities implemented in these study cycles. The objective of this paper is to gather evidence of the Human Interaction Skills explained and valued within the curriculum internship experiences of IT students employability. Data collection was based on the application of questionnaire to intern counselors and to students who have completed internships in these undergraduate courses in the last decade. The trainee supervisor, responsible for monitoring the performance of IT students in the evolution of traineeship activities, evaluates the following Human Interaction Skills: Motivation and interest in the activities developed, interpersonal relationship, cooperation in company activities, assiduity, ease of knowledge apprehension, Compliance with norms, insertion in the work environment, productivity, initiative, ability to take responsibility, creativity in proposing solutions, and self-confidence. The results show that these undergraduate courses promote the development of Human Interaction Skills and that these students, once they finish their degree, are able to initiate remunerated work functions, mainly by invitation of the institutions in which they perform curricular internships. Findings obtained from the present study contribute to widen the analysis of its effectiveness in terms of future research and actions in regard to the transition from Higher Education pathways to the Labour Market.

Keywords: human interaction skills, employability, internships, information technology, higher education

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Authors: Masoud Baghalian, Musa Arshad

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In order to investigate the effect of foliar application of calcium chloride on the resistance of fruits such as Red and Golden Lebanese apple varieties to blue mold, a split plot experiment in time and space, based on accidental blocks, with three replications under foliar application were done (Control, one in a thousand, two in thousands) and the results of the variance analysis showed that there is a significant difference between the levels of foliar and variety at 5% level and between time, there is significant difference in interaction of variety × time and three way interaction of foliar×variety×time, at 1% level. The highest resistance to the blue mold disease in foliar application was observed at two in thousands calcium (calcium chloride) level.

Keywords: apple, blue mold, foliar calcium, resistance

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Authors: Valentina Rodas, Luis Almache

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The interaction effects between the existing soil and the substructure of a 5-story building with an underground one were evaluated in such a way that the structural-geotechnical concepts were validated through the method of impedance factors with a program based on the method of the finite elements. The continuous wall-type foundation had a constant thickness and followed inclined and orthogonal directions, while the ground had homogeneous and medium-type characteristics. The soil considered was type C according to the Ecuadorian Construction Standard (NEC) and the corresponding foundation comprised a depth of 4.00 meters and a basement wall thickness of 40 centimeters. This project is part of a mid-rise building in the city of Azogues (Ecuador). The hypotheses raised responded to the objectives in such a way that the model implemented with springs had a variation with respect to the embedded base, obtaining conservative results.

Keywords: interaction, soil, substructure, springs, effects, modeling , embedment

Procedia PDF Downloads 231