Search results for: Ca 2+ -dependent calmodulin kinase IIa

Authors: Jui-Pui Hung, Yong-Run Chen, Wei-Cheng Shih, Shen-He Tsui, Kung-Da Wu

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This paper presents the effect on the tooling conditions on the machining stabilities of a milling machine tool. The machining stability was evaluated in different feeding direction in the X-Y plane, which was referred as the orientation-dependent machining stability. According to the machining mechanics, the machining stability was determined by the frequency response function of the cutter. Thus, we first conducted the vibration tests on the spindle tool of the milling machine to assess the tool tip frequency response functions along the principal direction of the machine tool. Then, basing on the orientation dependent stability analysis model proposed in this study, we evaluated the variation of the dynamic characteristics of the spindle tool and the corresponding machining stabilities at a specific feeding direction. Current results demonstrate that the stability boundaries and limited axial cutting depth of a specific cutter were affected to vary when it was fixed in the tool holder with different overhang length. The flute of the cutter also affects the stability boundary. When a two flute cutter was used, the critical cutting depth can be increased by 47 % as compared with the four flute cutter. The results presented in study provide valuable references for the selection of the tooling conditions for achieving high milling performance.

Keywords: tooling condition, machining stability, milling machine, chatter

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Authors: Riddhi Trivedi, Shrenik Shah

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For Si RNA to be delivered various biodegradable polymers are trialed by many researchers. One of them is Chitosan (CS) nanoparticles which have been extensively studied for siRNA delivery but the stability and efficacy of such particles are highly dependent on the types of cross-linker used. Hence the attempts are made in this study with PGA To address this issue, three common cross-linkers; Ethylene glycol diacrylate (ED) and poly-D-glutamic acid (PGA) were used to prepare siRNA loaded CS-ED/PGA nanoparticles by ionic gelation method. The nanoparticles which were obtained were compared for its characterization in terms of its physicochemical properties i.e. particle size of the resultant particles, zeta potential, its encapsulation capacity in the polymer. Among all the formulations prepared with different crosslinker PGA siRNA had the smallest particle size (ranged from 120 ± 1.7 to 500 ± 10.9 nm) with zeta potential ranged from 22.1 ± 1.5 to +32.4 ± 0.5 mV, and high entrapment ( > 91%) and binding efficiencies. Similarly, CS-ED nanoparticles showed better siRNA protection during storage at 4˚C and as determined by serum protection assay. TEM micrographs revealed the assorted morphology of CS-PGA-siRNA nanoparticles in contrast to irregular morphology displayed by CS-ED-siRNA. All siRNA loaded nanoparticles were found to give initial burst release which after some time followed by a sustained release of siRNA which were loaded inside. All the formulations showed concentration-dependent cytotoxicity with when cytotoxicity performed by HeLa and normal vero cell lines.

Keywords: chitosan, siRNA, cytotoxicity, cell line study

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Authors: Seyed Hossein Iranmanesh, Hassan Nouri, Seyed Reza Iranmanesh

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In the dynamic and complex landscape of today’s business, organizations often face challenges in impactful decision-making across multi-project settings. To efficiently allocate resources, coordinate tasks, and optimize project outcomes, establishing robust decision-making processes is essential. Furthermore, the increasing importance of information systems and their integration within organizational workflows introduces an additional layer of complexity. This research proposes the use of blockchain technology as a suitable solution to enhance decision-making in multi-project environments, particularly within the realm of information systems. The conceptual framework in this study comprises four independent variables and one dependent variable. The identified independent variables for the targeted research include: Blockchain Layer in Integrated Systems, Quality of Generated Information ,User Satisfaction with Integrated Systems and Utilization of Integrated Systems. The project’s performance, considered as the dependent variable and moderated by organizational policies and procedures, reflects the impact of blockchain technology adoption on organizational effectiveness1. The results highlight the significant influence of blockchain implementation on organizational performance.

Keywords: multi-project environments, decision support systems, information systems, blockchain technology, decentralized systems.

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Authors: Tahseen Saad, Halim Ceylan, Jonathan Weaver, Osman Nuri Çelik, Onur Gungor Sahin

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A new concept of uniform delay offset dependent mathematical optimization problem is derived as the main objective for this study using a differential evolution algorithm. To control the coordination problem, which depends on offset selection and to estimate uniform delay based on the offset choice in a traffic signal network. The assumption is the periodic sinusoidal function for arrival and departure patterns. The cycle time is optimized at the entry links and the optimized value is used in the non-entry links as a common cycle time. The offset optimization algorithm is used to calculate the uniform delay at each link. The results are illustrated by using a case study and are compared with the canonical uniform delay model derived by Webster and the highway capacity manual’s model. The findings show new model minimizes the total uniform delay to almost half compared to conventional models. The mathematical objective function is robust. The algorithm convergence time is fast.

Keywords: area traffic control, traffic flow, differential evolution, sinusoidal periodic function, uniform delay, offset variable

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Authors: Abdelbary Prince, Said Moussa, Hyungkyu Kim, Eman Gouda, Jin Han

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We compared the dynamic alterations of mitochondrial proteome of control, ischemia-reperfusion (IR) and ischemic preconditioned (IPC) rabbit hearts. Using 2-DE, we identified 29 mitochondrial proteins that were differentially expressed in the IR heart compared with the control and IPC hearts. For two of the spots, the expression patterns were confirmed by Western blotting analysis. These proteins included succinate dehydrogenase complex, Acyl-CoA dehydrogenase, carnitine acetyltransferase, dihydrolipoamide dehydrogenase, Atpase, ATP synthase, dihydrolipoamide succinyltransferase, ubiquinol-cytochrome c reductase, translation elongation factor, acyl-CoA dehydrogenase, actin alpha, succinyl-CoA Ligase, dihydrolipoamide S-succinyltransferase, citrate synthase, acetyl-Coenzyme A dehydrogenase, creatine kinase, isocitrate dehydrogenase, pyruvate dehydrogenase, prohibitin, NADH dehydrogenase (ubiquinone) Fe-S protein, enoyl Coenzyme A hydratase, superoxide dismutase [Mn], and 24-kDa subunit of complex I. Interestingly, most of these proteins are associated with the mitochondrial respiratory chain, antioxidant enzyme system, and energy metabolism. The results provide clues as to the cardioprotective mechanism of ischemic preconditioning at the protein level and may serve as potential biomarkers for detection of ischemia-induced cardiac injury.

Keywords: ischemic preconditioning, mitochondria, proteome, cardioprotection

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Authors: Dong-An Wang

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All kinds of microspheres have been extensively employed as carriers for drug, gene and therapeutic cell delivery. Most therapeutic cell delivery microspheres rely on a two-step methodology: fabrication of microspheres and subsequent seeding of cells onto them. In this study, we have developed a novel one-step cell encapsulation technique using a convenient and instant water-in-oil single emulsion approach to form cell-encapsulated gelatin microspheres. This technology is adopted for hyaline cartilage tissue engineering, in which autologous chondrocytes are used as therapeutic cells. Cell viability was maintained throughout and after the microsphere formation (75-100 µm diameters) process that avoids involvement of any covalent bonding reactions or exposure to any further chemicals. Further encapsulation of cell-laden microspheres in alginate gels were performed under 4°C via a prompt process. Upon the formation of alginate constructs, they were immediately relocated into CO2 incubator where the temperature was maintained at 37°C; under this temperature, the cell-laden gelatin microspheres dissolved within hours to yield similarly sized cavities and the chondrocytes were therefore suspended within the cavities inside the alginate gel bulk. Hence, the gelatin cell-laden microspheres served two roles: as cell delivery vehicles which can be removable through temperature curing, and as porogens within an alginate hydrogel construct to provide living space for cell growth and tissue development as well as better permeability for mutual diffusions. These cell-laden microspheres, namely “temperature-cured dissolvable gelatin microsphere based cell carriers” (tDGMCs), were further encapsulated in a chondrocyte-laden alginate scaffold system and analyzed by WST-1, gene expression analyses, biochemical assays, histology and immunochemistry stains. The positive results consistently demonstrated the promise of tDGMC technology in delivering these non-anchorage dependent cells (chondrocytes). It can be further conveniently translated into delivery of other non-anchorage dependent cell species, including stem cells, progenitors or iPS cells, for regeneration of tissues in internal organs, such as engineered hepatogenesis or pancreatic regeneration.

Keywords: biomaterials, tissue engineering, microsphere, hydrogel, porogen, anchorage dependence

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Authors: Adenike Adesanya, Nonthaphat Wong, Xiang-Yun Lan, Shea Ping Yip, Chien-Ling Huang

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Background: The most challenging mutation of the oncokinase BCR-ABL protein T315I, which is commonly known as the “gatekeeper” mutation and is notorious for its strong resistance to almost all tyrosine kinase inhibitors (TKIs), especially imatinib. Therefore, this study aims to identify T315I-dependent downstream microRNA (miRNA) pathways associated with drug resistance in chronic myeloid leukemia (CML) for prognostic and therapeutic purposes. Methods: T315I-carrying K562 cell clones (K562-T315I) were generated by the CRISPR-Cas9 system. Imatinib-treated K562-T315I cells were subjected to small RNA library preparation and next-generation sequencing. Putative lncRNA-miRNA-mRNA networks were analyzed with (i) DESeq2 to extract differentially expressed miRNAs, using Padj value of 0.05 as cut-off, (ii) STarMir to obtain potential miRNA response element (MRE) binding sites of selected miRNAs on lncRNA H19, (iii) miRDB, miRTarbase, and TargetScan to predict mRNA targets of selected miRNAs, (iv) IntaRNA to obtain putative interactions between H19 and the predicted mRNAs, (v) Cytoscape to visualize putative networks, and (vi) several pathway analysis platforms – Enrichr, PANTHER and ShinyGO for pathway enrichment analysis. Moreover, mitochondria isolation and transcript quantification were adopted to determine the new mechanism involved in T315I-mediated resistance of CML treatment. Results: Verification of the CRISPR-mediated mutagenesis with digital droplet PCR detected the mutation abundance of ≥80%. Further validation showed the viability of ≥90% by cell viability assay, and intense phosphorylated CRKL protein band being detected with no observable change for BCR-ABL and c-ABL protein expressions by Western blot. As reported by several investigations into hematological malignancies, we determined a 7-fold increase of H19 expression in K562-T315I cells. After imatinib treatment, a 9-fold increment was observed. DESeq2 revealed 171 miRNAs were differentially expressed K562-T315I, 112 out of these miRNAs were identified to have MRE binding regions on H19, and 26 out of the 112 miRNAs were significantly downregulated. Adopting the seed-sequence analysis of these identified miRNAs, we obtained 167 mRNAs. 6 hub miRNAs (hsa-let-7b-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-129-5p, and hsa-miR-372-3p) and 25 predicted genes were identified after constructing hub miRNA-target gene network. These targets demonstrated putative interactions with H19 lncRNA and were mostly enriched in pathways related to cell proliferation, senescence, gene silencing, and pluripotency of stem cells. Further experimental findings have also shown the up-regulation of mitochondrial transcript and lncRNA MALAT1 contributing to the lncRNA-miRNA-mRNA networks induced by BCR-ABL T315I mutation. Conclusions: Our results have indicated that lncRNA-miRNA regulators play a crucial role not only in leukemogenesis but also in drug resistance, considering the significant dysregulation and interactions in the K562-T315I cell model generated by CRISPR-Cas9. In silico analysis has further shown that lncRNAs H19 and MALAT1 bear several complementary miRNA sites. This implies that they could serve as a sponge, hence sequestering the activity of the target miRNAs.

Keywords: chronic myeloid leukemia, imatinib resistance, lncRNA-miRNA-mRNA, T315I mutation

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Authors: Pitsanu Poonpetpun

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This research paper consisted of three objectives: 1) to investigate actual perception of Suan Sunandha Rajabhat University’s members towards roles and performances of the Coordinating Council Office under the University Council; 2) to investigate expectation of Suan Sunandha Rajabhat University’s members towards roles and performances of the Coordinating Council Office under the University Council; and 3) to compare actual perception and expectation of Suan Sunandha Rajabhat University’s members towards roles and performances of the Coordinating Council Office under the University Council. A total of 316 samples from the population of the members of Suan Sunandha Rajabhat University were selected by use of the simple random sampling technique. Descriptive statistics and Dependent T- Test for paired samples were used, where the Dependent T- Test was for an analysis of a comparison of actual perception and expectation of Suan Sunandha Rajabhat University’s members towards roles and performances of the Coordinating Council Office under the University Council. The findings unveiled significantly high levels for the following roles: [i] appropriately circulating agendas and meeting files before time; [ii] preparing appropriate amount and quality of audio- visual equipment for meetings; [iii] compiling and keeping up-to-date documents; [iv] coordinating and working on linking all useful information to serve for the university uses for strategic policing; and [v] preparing appropriate meeting venues.

Keywords: coordinating council office of the university council, expected role, perceived role, performances of duties

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Authors: Nivedita Ghosh

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In his critique of Lefebvre’s view that ‘technological capacities’ are class-dependent, Francois Hetman argues that technology today is participatory, allowing the entry of individuals from different levels of social stratification. As a result, we are entering into an era of technology operators or ‘clerks’ who become the new decision-makers because of the knowledge they possess of the use of technologies. In response to Hetman’s thesis, this paper argues that knowledge of technology, while indeed providing a momentary space for decision-making, does not necessarily restructure social hierarchies. Through case studies presented from the world of Indian documentary filmmaking, this paper puts forth the view that Hetman’s clerks, despite being technologically advanced, do not break into the filmmaking hierarchical order. This remains true even for a situation where technical knowledge rests most with those in the lowest rungs of the filmmaking ladder. Instead, technological knowledge provides the space for other kinds of relationships to evolve, such as those of ‘trusting the technician’ or ‘admiration for the technician’s work’. Furthermore, what continues to define documentary filmmaking hierarchy is conceptualization capacities of the practitioners, which are influenced by a similarity in socio-cultural backgrounds and film school training accessible primarily to the filmmakers instead of the technicians. Accordingly, the paper concludes with the argument that more than ‘technological-capacities’, it is ‘conceptualization capacities’ which are class-dependent, especially when we study the field of documentary filmmaking.

Keywords: documentary filmmaking, India, technology, knowledge, hierarchy

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Authors: Asma Salman, Brian Gabbitas, Peng Cao, Deliang Zhang

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The performance of a coating is strongly dependent upon its microstructure, which in turn is dependent on the characteristics of the feedstock powder. This study involves the evaluation and performance of a titanium-based composite coating produced by the HVOF (high-velocity oxygen fuel) spraying method. The feedstock for making the composite coating was produced using high energy mechanical milling of TiO2 and Al powders followed by a combustion reaction. The characteristics of the feedstock powder were improved by treating it with an organic binder. Two types of coatings were produced using treated and untreated feedstock powders. The microstructures and characteristics of both types of coatings were studied, and their thermal shock resistance was accessed by dipping into molten aluminum. The results of this study showed that feedstock treatment did not have a significant effect on the microstructure of the coatings. However, it did affect the uniformity, thickness and surface roughness of the coating on the steel substrate. A coating produced by an untreated feedstock showed better thermal shock resistance in molten aluminum compared with the one produced by PVA (polyvinyl alcohol) treatment.

Keywords: coating, feedstock, powder processing, thermal shock resistance, thermally spraying

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Authors: Martin Doran, Roy Sterritt, George Wilkie

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NASA, ESA, and NSSC space agencies have plans to put planetary rovers on Mars in 2020. For these future planetary rovers to succeed, they will heavily depend on sensors to detect obstacles. This will also become of vital importance in the future, if rovers become less dependent on commands received from earth-based control and more dependent on self-configuration and self-decision making. These planetary rovers will face harsh environments and the possibility of hardware failure is high, as seen in missions from the past. In this paper, we focus on using Autonomic principles where self-healing, self-optimization, and self-adaption are explored using the MAPE-K model and expanding this model to encapsulate the attributes such as Awareness, Analysis, and Adjustment (AAA-3). In the experimentation, a Pioneer P3-DX research robot is used to simulate a planetary rover. The sonar sensors on the P3-DX robot are used to simulate the sensors on a planetary rover (even though in reality, sonar sensors cannot operate in a vacuum). Experiments using the P3-DX robot focus on how our software system can be adapted with the loss of sonar sensor functionality. The autonomic manager system is responsible for the decision making on how to make use of remaining ‘enabled’ sonars sensors to compensate for those sonar sensors that are ‘disabled’. The key to this research is that the robot can still detect objects even with reduced sonar sensor capability.

Keywords: autonomic, self-adaption, self-healing, self-optimization

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Authors: Naila Sher, Mushtaq Ahmed, Nadia Mushtaq, Rahmat Ali Khan

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In cancer therapy, nanoparticles (NPs) shall be applied possibly by inoculation in the veins of humans. This action will connect them with white (WBCs) and red blood cells (RBCs) in the bloodstream before they reach their main targeted cancer cells. However, possible effects of silver, gold, and silver/gold bimetallic NPs (Ag, Au, and Ag/Au BNPs) on baby hamster kidney-21 (BHK-21) cells were studied by MTT assay. Here, Ag, Au, and their Ag/Au BNPs (bimetallic nanoparticles) were synthesized by using Hippeastrum hybridum (HH) extract. These NPs were characterized by UV-visible spectroscopy, FT-IR, XRD, and EDX, and SEM analysis. XRD analysis conferring the crystal structure with an average size of 13.3, 10.72, and 8.34nm of Ag, Au, and Ag/Au BNPs, respectively. SEM showed that Ag, Au, and Ag/Au BNPs had irregular morphologies, with nano measures calculated sizes of 40, 30, and 20 nm respectively. EDX spectrometers confirmed the presence of elemental Ag signal of the AgNPs with 22.75%, Au signal of the AuNPs with 48.08%, Ag signal with 12%, and Au signal with 38.26% of the Ag/Au BNPs. The BHK-21cells were incubated in the existence of doxorubicin, plant extract, Ag, Au, and Ag/Au BNPs. The cytotoxic effects could be observed in a dose-dependent mode; doxorubicin and Ag/Au BNPs were more toxic than plant extract, Ag, and Au NPs. It is demonstrated that NPs interact with BHK-21cells and significantly reduce cell viability in a concentration-dependent manner. However, to reduce the potential threats of NPs further studies are recommended.

Keywords: hippeastrum hybridum, nanoparticle, BHK-21cells

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Authors: S. Khosravi, X. Chelius, A. Unger, D. Rieger, J. Frickel, T. Sachsenheimer, C. Luechtenborg, R. Schieweck, B. Bruegger, B. Westermann, T. Klecker, W. Neupert, M. E. Harner

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The use of Saccharomyces cerevisiae as a model organism to study eukaryotic cell functions has been used successfully for decades. Like virtually all eukaryotic cells, they contain mitochondria as essential organelles performing various functions, including participation in lipid metabolism. They are separated from the cytosol by a double membrane system consisting of the mitochondrial inner membrane (MIM) and the mitochondrial outer membrane (MOM). This physical separation of the mitochondria requires an exchange of metabolites, proteins, and lipids. Proteinaceous contact sites are thought to be important for this communication. Recently, it was found that Cqd1, in cooperation with Cqd2, controls the distribution of Coenzyme Q within the cell. In this study, a contact site is described, formed by the MOM protein complex Por1-Om14 and the UbiB protein kinase-like MIM protein Cqd1. The present results suggest the additional involvement of Cqd1 in the homeostasis of phospholipids. Moreover, we show that overexpression of the UbiB family proteins also causes tethering of the mitochondria to the endoplasmatic reticulum. Due to the conservation of the subunits of this contact site to higher eukaryotes, its identification in S. cerevisiae might provide promising avenues for further research in other organisms.

Keywords: contact sites, mitochondrial architecture, mitochondrial proteins, yeast mitochondria

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Authors: Hui-Chieh Li

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Circular economy promotes greater resource productivity and avoids pollution through greater recycling and re-use which bring benefits for both the environment and the economy. The concept is contrast to a linear economy which is ‘take, make, dispose’ model of production. A well-design reverse logistics service strategy could enhance the willingness of recycling of the users and reduce the related logistics cost as well as carbon emissions. Moreover, the recycle brings the manufacturers most advantages as it targets components for closed-loop reuse, essentially converting materials and components from worn-out product into inputs for new ones at right time and right place. This study considers demand-supply interaction, time-dependent recycle demand, time-dependent surplus value of recycled product and constructs models on recycle service strategy for the recyclable waste collector. A crucial factor in optimizing a recycle service strategy is consumer demand. The study considers the relationships between consumer demand towards recycle and product characteristics, surplus value and user behavior. The study proposes a recycle service strategy which differs significantly from the conventional and typical uniform service strategy. Periods with considerable demand and large surplus product value suggest frequent and short service cycle. The study explores how to determine a recycle service strategy for recyclable waste collector in terms of service cycle frequency and duration and vehicle type for all service cycles by considering surplus value of recycled product, time-dependent demand, transportation economies and demand-supply interaction. The recyclable waste collector is responsible for the collection of waste product for the manufacturer. The study also examines the impacts of utilization rate on the cost and profit in the context of different sizes of vehicles. The model applies mathematical programming methods and attempts to maximize the total profit of the distributor during the study period. This study applies the binary logit model, analytical model and mathematical programming methods to the problem. The model specifically explores how to determine a recycle service strategy for the recycler by considering product surplus value, time-dependent recycle demand, transportation economies and demand-supply interaction. The model applies mathematical programming methods and attempts to minimize the total logistics cost of the recycler and maximize the recycle benefits of the manufacturer during the study period. The study relaxes the constant demand assumption and examines how service strategy affects consumer demand towards waste recycling. Results of the study not only help understanding how the user demand for recycle service and product surplus value affects the logistics cost and manufacturer’s benefits, but also provide guidance such as award bonus and carbon emission regulations for the government.

Keywords: circular economy, consumer demand, product surplus value, recycle service strategy

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Authors: S. Pradhan, D. Pradhan, G. Tripathy, T. Dasmohapatra

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Suppressors of cytokine signalling (SOCS3), a newly indentified anti-apoptotic molecule is a downstream effecter of the receptor tyrosine kinase-Ras signalling pathway. Current study has uncovered that SOCS3 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS3 on MDR, we analyzed the expression of P-gp and SOCS3 by immune-histochemistry and found there was positive correlation between them. At that point we effectively interfered with RNA translation by the contamination of siRNA of SOCS3 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flowcytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS3 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: SOCS3gene, breast cancer, multidrug resistance, MDR1 gene, RNA interference

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Authors: Azhar Jabareen, Mahmoud Huleihel

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BRCA-1 is a multifunctional tumor suppressor, whose expression is activated by the estrogen (E2)-liganded ERα receptor. The activated ERα is a transcriptional factor which activates various genes either by direct binding to the DNA at E2-responsive elements (EREs) and indirectly associated with a range of alternative non-ERE elements. Interference with BRCA-1 expression and/or functions leads to high risk of breast or/and ovarian cancer. Our lab investigated the involvement of Human T-cell leukemia Virus Type 1 (HTLV-1) in breast cancer, since HTLV-1 Tax was found to strongly inhibit BRCA-1 expression. In addition, long exposure of 12-O-tetradecanoylphorbol-13-acetate (TPA), which is one of the stress-inducing agents activated the HTLV-1 promoter. So here the involvement of TPA in breast cancer had been examined by testing the effect of TPA on BRCA-1 and ERE expression. The results showed that TPA activated both BRCA-1 and ERE expression. In the 12 hours TPA activated the tow promoters more than others time, and after 24 hours the level of the tow promoters was decreased. Tax inhibited BRCA-1 expression but did not succeed to inhibit the effect of TPA. Then the activation of the two promoters was not through ERα pathway because TPA had no effect on ERα binding to the two promoters of the BRCA-1 and ERE. Also, the activation was not via nuclear factor kappa B (NF-κB) pathway because when the inhibitory of NF-κB had been added to the TPA, it still activated the tow promoters. However, it seems that 53BP1 may be involved in TPA activation of these promoters because ectopic high expression of 53BP1 significantly reduced the TPA activity. In addition, in the presence of Bisindolylmaleimide-I (BI)- the inhibitor of Protein Kinase C (PKC)- there was no activation for the two promoters, so the PKC is agonized BRCA-1 and ERE activation.

Keywords: BRCA-1, ERE, HTLV-1, TPA

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Authors: Elham Ahmadi, Mehrdad Ravanshad, Joyce Fingeroth, Mazyar Ziyaeyan, Rajesh Panigrahi, Jun Xie, Gao Guangping

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B-cell proliferative disorders often occur among persons that are T-cell compromised. These disorders are primarily EBV+ and can first present with a focal lesion. Direct introduction of oncolytic viruses into localized tumors provides theoretical advantages over chemotherapy and immunotherapy by reducing systemic toxicity, to which the immunocompromised host is most vulnerable. Widely studied as a vehicle for gene therapy, AAV has only rarely been applied to treat cancer. As a prelude to development of a therapeutic vehicle, we assessed the ability of 15 distinct recombinant AAV serotypes (rAAV1, rAAV2, rAAV3b, rAAV4, rAAV5, rAAV6, rAAV6.2, rAAV6TM, rAAV7, rAAV8, rAAVrh8, rAAV9, rAAVrh10, rAAV39, rAAV43) bearing eGFP to infect human B-cell tumor lines compared with primary B-cells in vitro. Enhanced infection of tumor lines by AAV 6.2 was demonstrated by flow cytometry. EBV superinfection of EBV negative B-cell tumor lines increased susceptibility to AAV6.2 infection. As proof of concept, AAV6.2 bearing HSV-1 thymidine kinase in place of eGFP eliminated tumor cells upon exposure to ganciclovir.

Keywords: AAV, gene therapy, lymphoma, malignancy, tropism

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Authors: Fateme Afkhami, Mohsen Ehsanpour, Majid Afkhami, Maryam Ehsanpour

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Normal reference ranges of biochemical parameters are considered important for assessing and monitoring the health status of sea turtles. For this means, serum biochemistry determinations were analyzed in normal adult nesting and foraging hawksbill turtles (Eretmochelys imbricata). Blood samples were collected in March–April during nesting season and December-November in the foraging season. Plasma biochemistry values, except for creatinine and lipase were significant between the two periods. FBS, cholesterol, triglycerides, ALP (alkaline phosphatase), AST (aspartate aminotransferase), bilirubin, total protein, LDH (lactate dehydrogenase), CK (creatine kinase) and amylase were significantly higher in nesting season than foraging season (P<0.05). On the other hand urea, ALT (alanine aminotransferase) and albumin in the nesting season were significantly lower than foraging season (P<0.05). It was concluded that the nesting E. imbricata showed significant variation in their biochemical profile due to reproductive output. This study has produced working reference intervals useful for hawksbill turtles for future conservation and rehabilitation projects in the Persian Gulf and may be of assistance in similar programs worldwide.

Keywords: plasma biochemistry, nesting, foraging, hawksbill turtles, Persian Gulf

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Authors: M. H. Aldahrob, A. Kokce, S. Altindal, H. E. Lapa

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In order to obtain the detailed information about the effect of (Zn-doped PVA) interfacial layer, surface states (Nss) and series resistance (Rs) on electrical characteristics, both Au/n- type 4H-SiC (MS) with and without (Zn doped PVA) interfacial layer were fabricated to compare. The main electrical parameters of them were investigated using forward and reverse bias current-voltage (I-V), capacitance-voltage (C-V) and conductance –voltage (G/W –V) measurements were performed at room temperature. Experimental results show that the value of ideality factor (n), zero –bias barrier height (ΦBo), Rs, rectifier rate (RR=IF/IR) and the density of Nss are strong functions interfacial layer and applied bias voltage. The energy distribution profile of Nss was obtained from forward bias I-V data by taking into account voltage dependent effective BH (ΦBo) and ideality factor (n(V)). Voltage dependent profile of Rs was also obtained both by using Ohm’s law and Nicollian and Brew methods. The other main diode parameters such as the concentration of doping donor atom (ND), Fermi energy level (EF).BH (ΦBo), depletion layer with (WD) were obtained by using the intercept and slope of the reverse bias C-2 vs V plots. It was found that (Zn-doped PVA) interfacial layer lead to a quite decrease in the values Nss, Rs and leakage current and increase in shunt resistance (Rsh) and RR. Therefore, we can say that the use of thin (Zn-doped PVA) interfacial layer can quite improved the performance of MS structure.

Keywords: interfacial polymer layer, thickness dependence, electric and dielectric properties, series resistance, interface state

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Authors: Yun Sun, Meng Xun, Jingtao Zhou, Ming Li, Qiang Kan, Zhi Jin, Xinyu Liu, Dexin Wu

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Higher speed short-wavelength vertical-cavity surface-emitting lasers (VCSELs) working at high temperature are required for future optical interconnects. In this work, the high-speed 850 nm VCSELs are designed, fabricated and characterized. The temperature dependent static and dynamic performance of devices are investigated by using current-power-voltage and small signal modulation measurements. Temperature-stable high-speed properties are obtained by employing highly strained multiple quantum wells and short cavity length of half wavelength. The temperature dependent photon lifetimes and carrier radiative times are determined from damping factor and resonance frequency obtained by fitting the intrinsic optical bandwidth with the two-pole transfer function. In addition, an analytical theoretical model including the strain effect is development based on model-solid theory. The calculation results indicate that the better high temperature performance of VCSELs can be attributed to the strong confinement of holes in the quantum wells leading to enhancement of the carrier transit time.

Keywords: vertical cavity surface emitting lasers, high speed modulation, optical interconnects, semiconductor lasers

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Authors: Ashna Babu, Deepshikha Jaiswal Nagar

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Cuprate high-temperature superconductors (HTSCs) have been immensely studied during the past few decades because of their structure which is described as a superlattice of superconducting CuO₂ layers. In particular, YBa₂Cu₃O₆₊δ (YBCO), with its critical temperature of 93 K, has received the most attention due to its well-defined metal stoichiometry and variable oxygen content that determines the carrier doping level. Substitution of metal ions at the Cu site is known to increase the critical current density without destroying superconductivity in YBCO. The construction of vortex phase diagrams is very important for such doped YBCO materials both from a fundamental perspective as well as from a technological perspective. By measuring field-dependent magnetization on annealed single crystals of Al-doped YBCO, YBa₂Cu₃₋ₓAlₓO₆₊δ (Al-YBCO), we were able to observe a second magnetization peak anomaly (SMP) in a very large part of the phase diagram. We were also able to observe the SMP anomaly in temperature-dependent magnetization measurements, the first observation to our knowledge. Critical current densities were calculated using Bean’s critical state model, flux jumps associated with symmetry reorientation of vortex lattice were studied, the oxygen cluster distribution was also analysed, and by incorporating all observations, we made a vortex phase diagram for oxygenated Al-YBCO single crystal.

Keywords: oxygen deficient clusters, second magnetization peak anomaly, flux jumps, vortex phase diagram

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Authors: Ons Sassi, Wahiba Ramdane Cherif-Khettaf, Ammar Oulamara

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In this paper, we consider a new real-life Heterogenous Electric Vehicle Routing Problem with Time Dependant Charging Costs and a Mixed Fleet (HEVRP-TDMF), in which a set of geographically scattered customers have to be served by a mixed fleet of vehicles composed of a heterogenous fleet of Electric Vehicles (EVs), having different battery capacities and operating costs, and Conventional Vehicles (CVs). We include the possibility of charging EVs in the available charging stations during the routes in order to serve all customers. Each charging station offers charging service with a known technology of chargers and time-dependent charging costs. Charging stations are also subject to operating time windows constraints. EVs are not necessarily compatible with all available charging technologies and a partial charging is allowed. Intermittent charging at the depot is also allowed provided that constraints related to the electricity grid are satisfied. The objective is to minimize the number of employed vehicles and then minimize the total travel and charging costs. In this study, we present a Mixed Integer Programming Model and develop a Charging Routing Heuristic and a Local Search Heuristic based on the Inject-Eject routine with three different insertion strategies. All heuristics are tested on real data instances.

Keywords: charging problem, electric vehicle, heuristics, local search, optimization, routing problem

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Authors: Rouhallah Bagheri, Morteza Mahmoudi, Hadi Moheb-Alizadeh

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This paper aims at developing a multi-objective model for supplier selection and order allocation problem in stochastic environment, where purchasing cost, percentage of delivered items with delay and percentage of rejected items provided by each supplier are supposed to be stochastic parameters following any arbitrary probability distribution. In this regard, dependent chance programming is used which maximizes probability of the event that total purchasing cost, total delivered items with delay and total rejected items are less than or equal to pre-determined values given by decision maker. The abovementioned stochastic multi-objective programming problem is then transformed into a stochastic single objective programming problem using minimum deviation method. In the next step, the further problem is solved applying a genetic algorithm, which performs a simulation process in order to calculate the stochastic objective function as its fitness function. Finally, the impact of stochastic parameters on the given solution is examined via a sensitivity analysis exploiting coefficient of variation. The results show that whatever stochastic parameters have greater coefficients of variation, the value of the objective function in the stochastic single objective programming problem is deteriorated.

Keywords: supplier selection, order allocation, dependent chance programming, genetic algorithm

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Authors: Debasish Pradhan, Shaktiprasad Pradhan, Rakesh Kumar Pradhan, Gitanjali Tripathy

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Suppressors of cytokine signalling (SOCS1), a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signalling pathway. The current study has uncovered that SOCS1 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS1 on MDR, we analyzed the expression of P-gp and SOCS1 by immunohistochemistry and found there was a positive correlation between them. At that point, we effectively interfered with RNA translation by the contamination of siRNA of SOCS1 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi, the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise, the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flow cytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS1 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: breast cancer, multidrug resistance, SOCS1 gene, MDR1 gene, RNA interference

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Authors: Elena G. Salina, Laurent R. Chiarelli, Maria R. Pasca, Vadim A. Makarov

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Tuberculosis is one of the most challenging threats to human health, confronted by the problem of drug resistance. Evidently, new drugs for tuberculosis are urgently needed. Thienopyrimidine TP053 is one of the most promising new antitubercular prodrugs. Mycothiol-dependent reductase Mrx2, encoded by rv2466c, is known to be a TP053 activator; however, the precise mode of action of this compound remained unclear. Being highly active against both replicating and non-replicating tuberculosis bacilli, TP053 also revealed dose-escalating activity for M. tuberculosis-infected murine macrophages. The chemical structure of TP053 is characterized by the presence of NO₂ group which was suggested to be responsible for the toxic effects of the activated compound. Reduction of a nitroaromatic moiety of TP53 by Mrx2 was hypothesized to result in NO release. Analysis of the products of enzymatic activation of TP053 by Mrx2 by the Greiss reagent clearly demonstrated production of nitric oxide in a time-dependent manner. Mass-spectra of cell lysates of TP-treated M. tuberculosis bacilli demonstrated the transformation of TP053 to its non-active metabolite with Mw=261 that corresponds NO release. The mechanism of NO toxicity for bacteria includes DNA damage and degradation of iron-sulfur centers, especially under oxygen depletion. Thus, TP-053 drug-like scaffold is prospective for further development of novel anti-TB drug. This work was financially supported by the Russian Foundation for Basic Research (Grant 17-04-00342).

Keywords: drug discovery, M. tuberculosis, nitric oxide, NO donors

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Authors: Theodorou Kyriaki, Ypsilantis George

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Vocabulary learning has attracted a lot of attention in recent years, contrary to the neglected part of the past. Along with the interest in finding successful vocabulary teaching strategies, many scholars focused on locating learning strategies used by language learners. As a result, more and more studies in the area of language pedagogy have been investigating the use of strategies in vocabulary learning by different types of learners. A common instrument in this field is the questionnaire, a tool of work that was enriched by questions involving current technology, and it was further implemented to a sample of 300 Greek students whose age varied from 9 and 17 years. Strategies located were grouped into the three categories of memory, cognitive, and compensatory type and associations between these dependent variables were investigated. In addition, relations between dependent and independent variables (such as age, sex, type of school, cultural background, and grade in English) were pursued to investigate the impact on strategy selection. Finally, results were compared to findings of other studies in the same field to contribute to a hypothesis of ethnic differences in strategy selection. Results initially discuss preferred strategies of all participants and further indicate that: a) technology affects strategy selection while b) differences between ethnic groups are not statistically significant. A number of successful strategies are presented, resulting from correlations of strategy selection and final school grade in English.

Keywords: acquisition of English, internet technology, research among Greek students, vocabulary learning strategies

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Authors: Y. S. Mohamed, L. A. Ahmed, H. A. Salem, A. M. Agha

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Liver Fibrosis is one of the most serious conditions that affect the Egyptian society. In the present study, the effect of nicorandil was investigated in experimentally-induced liver fibrosis by bile duct ligation in rats. Nicorandil (3mg/kg/day) was given orally 24 h after bile duct ligation for 14 days till the end of the experiment. Nicorandil group showed a significant improvement in liver function tests (ALT and ALP) as well as a significant decrease in oxidative stress biomarkers (TBARS and GSH), area of fibrosis and activity of hepatic stellate cells as indicated by decreased expression of alpha smooth muscle actin.Moreover, nicorandil treatment decreased HSCs proliferation due to its inhibitory effects on protein kinase C(PKC) and Platelet derived growth factor (PDGF) . Oral administration of either glibenclamide (10 mg/kg/day)(a KATP channel blocker) or L-NAME (30 mg/kg/day) (an inhibitor of nitric oxide synthase) blocked the protective effects of nicorandil. However, nicorandil and L-NAME treated group showed more or less results similar to that of untreated bile duct ligated group. In conclusion, nicorandil was effective against the development of bile duct ligated-induced liver fibrosis in rats where activation of the NO pathway plays an important role in the protective effect nicorandil.

Keywords: hepatic stellate cells, nicorandil, nitric oxide donor, liver fibrosis

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Authors: Hamid Mustafa, Adeela Ajmal, Kim EuiSoo, Noor-ul-Ain

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World wild, buffalo production is considered as most important component of food industry. Efficient buffalo production is related with reproductive performance of this species. Lack of knowledge of reproductive efficiency and its related genes in buffalo species is a major constraint for sustainable buffalo production. In this study, we performed some bioinformatics analysis on Follicle Stimulating Hormone Receptor (FSHR) gene and explored the possible relationship of this gene among different buffalo breeds and with other farm animals. We also found the evolution pattern for this gene among these species. We investigate CDS lengths, Stop codon variation, homology search, signal peptide, isoelectic point, tertiary structure, motifs and phylogenetic tree. The results of this study indicate 4 different motif in this gene, which are Activin-recp, GS motif, STYKc Protein kinase and transmembrane. The results also indicate that this gene has very close relationship with cattle, bison, sheep and goat. Multiple alignment (MA) showed high conservation of motif which indicates constancy of this gene during evolution. The results of this study can be used and applied for better understanding of this gene for better characterization of Follicle Stimulating Hormone Receptor (FSHR) gene structure in different farm animals, which would be helpful for efficient breeding plans for animal’s production.

Keywords: buffalo, FSHR gene, bioinformatics, production

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Authors: Joseph Fitoussi, Mohammadali Shirinbayan, Abbas Tcharkhtchi

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Due to material flow during processing, short fiber reinforced composites structures obtained by injection or compression molding generally present strong spatial microstructure variation. On the other hand, quasi-static, dynamic, and fatigue behavior of these materials are highly dependent on microstructure parameters such as fiber orientation distribution. Indeed, because of complex damage mechanisms, SFRC structures design is a key challenge for safety and reliability. In this paper, we propose a micromechanical model allowing prediction of damage behavior of real structures as a function of microstructure spatial distribution. To this aim, a statistical damage criterion including strain rate and fatigue effect at the local scale is introduced into a Mori and Tanaka model. A critical local damage state is identified, allowing fatigue life prediction. Moreover, the multi-scale model is coupled with an experimental intrinsic link between damage under monotonic loading and fatigue life in order to build an abacus giving Tsai-Wu failure criterion parameters as a function of microstructure and targeted fatigue life. On the other hand, the micromechanical damage model gives access to the evolution of the anisotropic stiffness tensor of SFRC submitted to complex thermomechanical loading, including quasi-static, dynamic, and cyclic loading with temperature and amplitude variations. Then, the latter is used to fill out microstructure dependent material cards in finite element analysis for design optimization in the case of complex loading history. The proposed methodology is illustrated in the case of a real automotive component made of sheet molding compound (PSA 3008 tailgate). The obtained results emphasize how the proposed micromechanical methodology opens a new path for the automotive industry to lighten vehicle bodies and thereby save energy and reduce gas emission.

Keywords: short fiber reinforced composite, structural design, damage, micromechanical modelling, fatigue, strain rate effect

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Authors: Kamran Siddique, Hiroyuki Asada, Yoshifumi Ogami

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Micro gas turbine (MGT) nowadays has a wide variety of applications from drones to hybrid electric vehicles. As microfabrication technology getting better, the size of MGT is getting smaller. Overall performance of MGT is dependent on the individual components. Each component’s performance is dependent and interrelated with another component. Therefore, careful consideration needs to be given to each and every individual component of MGT. In this study, the focus is on improving the performance of the compressor in order to improve the overall performance of MGT. Computational Fluid Dynamics (CFD) is being performed using the software FLUENT to analyze the design of a micro compressor. Operating parameters like mass flow rate and RPM, and design parameters like inner blade angle (IBA), outer blade angle (OBA), blade thickness and number of blades are varied to study its effect on the performance of the compressor. Pressure ratio is used as a tool to measure the performance of the compressor. Higher the pressure ratio, better the design is. In the study, target mass flow rate is 0.2 g/s and RPM to be less than or equal to 900,000. So far, a pressure ratio of above 3 has been achieved at 0.2 g/s mass flow rate with 5 rotor blades, 0.36 mm blade thickness, 94.25 degrees OBA and 10.46 degrees IBA. The design in this study differs from a regular centrifugal compressor used in conventional gas turbines such that compressor is designed keeping in mind ease of manufacturability. So, this study proposes a compressor design which has a good pressure ratio, and at the same time, it is easy to manufacture using current microfabrication technologies.

Keywords: computational fluid dynamics, FLUENT microfabrication, RPM

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