Search results for: GABAA/bezodiazepine receptor complex

Authors: A. Dehghani, S. Shirin

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We propose in this article a new configuration of quantum states, |α, β> := |α>×|β>. Which are composed of vector products of two different copies of spin coherent states, |α> and |β>. Some mathematical as well as physical properties of such states are discussed. For instance, it has been shown that the cross products of two coherent vectors remain coherent again. They admit a resolution of the identity through positive definite measures on the complex plane. They represent packets similar to the true coherent states, in other words we would not expect to take spin squeezing in any of the field quadratures Lˆx, Lˆy and Lˆz. Depending on the particular choice of parameters in the above scenarios, they can be converted into the so-called Dicke states which minimize the uncertainty relations of each pair of the angular momentum components.

Keywords: vector (Cross-)products, minimum uncertainty, angular momentum, measurement, Dicke states

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Authors: Maria V. Morozova, Zoya A. Mikhaylovskaya, Elena S. Buyanova, Sofia A. Petrova, Ksenia V. Arishina, Robert G. Zaharov

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The present work is devoted to the investigation of two series of doped bismuth molybdates: Bi₂₆-₂ₓMn₂ₓMo₁₀O₆₉-d and Bi₂₆Mo₁₀-₂yMn₂yO₆₉-d. Complex oxides were synthesized by conventional solid state technology and by co-precipitation method. The products were identified by powder diffraction. The powders and ceramic samples were examined by means of densitometry, laser diffraction, and electron microscopic methods. Porosity of the ceramic materials was estimated using the hydrostatic method. The electrical conductivity measurements were carried out using impedance spectroscopy method.

Keywords: bismuth molybdate, columnar structures, impedance spectroscopy, oxygen ionic conductors

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Authors: Tomilola J. Ajayi

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A category of nanovalves system containing the α-cyclodextrin (α-CD) ring on a stalk tethered to the pores of mesoporous silica nanoparticles (MSN) is theoretically and computationally modelled. This functions to control opening and blocking of the MSN pores for efficient targeted drug release system. Modeling of the nanovalves is based on the interaction between α-CD and the stalk (p-anisidine) in relation to pH variation. Conformational analysis was carried out prior to the formation of the inclusion complex, to find the global minimum of both neutral and protonated stalk. B3LYP/6-311G**(d, p) basis set was employed to attain all theoretically possible conformers of the stalk. Six conformers were taken into considerations, and the dihedral angle (θ) around the reference atom (N17) of the p-anisidine stalk was scanned from 0° to 360° at 5° intervals. The most stable conformer was obtained at a dihedral angle of 85.3° and was fully optimized at B3LYP/6-311G**(d, p) level of theory. The most stable conformer obtained from conformational analysis was used as the starting structure to create the inclusion complexes. 9 complexes were formed by moving the neutral guest into the α-CD cavity along the Z-axis in 1 Å stepwise while keeping the distance between dummy atom and OMe oxygen atom on the stalk restricted. The dummy atom and the carbon atoms on α-CD structure were equally restricted for orientation A (see Scheme 1). The generated structures at each step were optimized with B3LYP/6-311G**(d, p) methods to determine their energy minima. Protonation of the nitrogen atom on the stalk occurs at acidic pH, leading to unsatisfactory host-guest interaction in the nanogate; hence there is dethreading. High required interaction energy and conformational change are theoretically established to drive the release of α-CD at a certain pH. The release was found to occur between pH 5-7 which agreed with reported experimental results. In this study, we applied the theoretical model for the prediction of the experimentally observed pH-responsive nanovalves which enables blocking, and opening of mesoporous silica nanoparticles pores for targeted drug release system. Our results show that two major factors are responsible for the cargo release at acidic pH. The higher interaction energy needed for the complex/nanovalve formation to exist after protonation as well as conformational change upon protonation are driving the release due to slight pH change from 5 to 7.

Keywords: nanovalves, nanogate, mesoporous silica nanoparticles, cargo

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Authors: É. Vincze

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Demand on plant oils has increased to an enormous extent that is due to the change of human nutrition habits on the one hand, while on the other hand to the increase of raw material demand of some industrial sectors, just as to the increase of biofuel production. Besides the determining importance of sunflower in Hungary the production area, just as in part the average yield amount of rapeseed has increased among the produced oil crops. The variety/hybrid palette has changed significantly during the past decade. The available varieties’/hybrids’ palette has been extended to a significant extent. It is agreed that rapeseed production demands professionalism and local experience. Technological elements are successive; high yield amounts cannot be produced without system-based approach. The aim of the present work was to execute the complex study of one of the most critical production technology element of rapeseed production, that was sowing technology. Several sowing technology elements are studied in this research project that are the following: biological basis (the hybrid Arkaso is studied in this regard), sowing time (sowing time treatments were set so that they represent the wide period used in industrial practice: early, optimal and late sowing time) plant density (in this regard reaction of rare, optimal and too dense populations) were modelled. The multifactorial experimental system enables the single and complex evaluation of rapeseed sowing technology elements, just as their modelling using experimental result data. Yield quality and quantity have been determined as well in the present experiment, just as the interactions between these factors. The experiment was set up in four replications at the Látókép Plant Production Research Site of the University of Debrecen. Two different sowing times were sown in the first experimental year (2014), while three in the second (2015). Three different plant densities were set in both years: 200, 350 and 500 thousand plants ha-1. Uniform nutrient supply and a row spacing of 45 cm were applied. Winter wheat was used as pre-crop. Plant physiological measurements were executed in the populations of the Arkaso rapeseed hybrid that were: relative chlorophyll content analysis (SPAD) and leaf area index (LAI) measurement. Relative chlorophyll content (SPAD) and leaf area index (LAI) were monitored in 7 different measurement times.

Keywords: inner quality, plant density, rapeseed, sowing time

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Authors: Manohar Salla, Mark S. Butler, Ruby Pelingon, Geraldine Kaeslin, Daniel E. Croker, Janet C. Reid, Jong Min Baek, Paul V. Bernhardt, Elizabeth M. J. Gillam, Matthew A. Cooper, Avril A. B. Robertson

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MCC950 is a potent and selective inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome that shows early promise for treatment of inflammatory diseases. The identification of major metabolites of lead molecule is an important step during drug development process. It provides an information about the metabolically labile sites in the molecule and thereby helping medicinal chemists to design metabolically stable molecules. To identify major metabolites of MCC950, the compound was incubated with human liver microsomes and subsequent analysis by (+)- and (−)-QTOF-ESI-MS/MS revealed a major metabolite formed due to hydroxylation on 1,2,3,5,6,7-hexahydro-s-indacene moiety of MCC950. This major metabolite can lose two water molecules and three possible regioisomers were synthesized. Co-elution of major metabolite with each of the synthesized compounds using HPLC-ESI-SRM-MS/MS revealed the structure of the metabolite (±) N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. Subsequent synthesis of individual enantiomers and coelution in HPLC-ESI-SRM-MS/MS using a chiral column revealed the metabolite was R-(+)- N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. To study the possible cytochrome P450 enzyme(s) responsible for the formation of major metabolite, MCC950 was incubated with a panel of cytochrome P450 enzymes. The result indicated that CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C18, CYP2C19, CYP2J2 and CYP3A4 are most likely responsible for the formation of the major metabolite. The biological activity of the major metabolite and the other synthesized regioisomers was also investigated by screening for for NLRP3 inflammasome inhibitory activity and cytotoxicity. The major metabolite had 170-fold less inhibitory activity (IC50-1238 nM) than MCC950 (IC50-7.5 nM). Interestingly, one regioisomer had shown nanomolar inhibitory activity (IC50-232 nM). However, no evidence of cytotoxicity was observed with any of these synthesized compounds when tested in human embryonic kidney 293 cells (HEK293) and human liver hepatocellular carcinoma G2 cells (HepG2). These key findings give an insight into the SAR of the hexahydroindacene moiety of MCC950 and reveal a metabolic soft spot which could be blocked by chemical modification.

Keywords: Cytochrome P450, inflammasome, MCC950, metabolite, microsome, NLRP3

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Authors: Damith Tennakoon, Mojgan Jadidi, Seyedreza Razavialavi

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With recent advancements of automation in robotics, from self-driving cars to autonomous 4-legged quadrupeds, one industry that has been stagnant is the construction industry. The methodologies used in a modern-day construction site consist of arduous physical labor and the use of heavy machinery, which has not changed over the past few decades. The dangers of a modern-day construction site affect the health and safety of the workers due to performing tasks such as lifting and moving heavy objects and having to maintain unhealthy posture to complete repetitive tasks such as painting, installing drywall, and laying bricks. Further, training for heavy machinery is costly and requires a lot of time due to their complex control inputs. The main focus of this research is using immersive wearable technology and robotic arms to perform the complex and intricate skills of modern-day construction workers while alleviating the physical labor requirements to perform their day-to-day tasks. The methodology consists of mounting a stereo vision camera, the ZED Mini by Stereolabs, onto the end effector of an industrial grade robotic arm, streaming the video feed into the Virtual Reality (VR) Meta Quest 2 (Quest 2) head-mounted display (HMD). Due to the nature of stereo vision, and the similar field-of-views between the stereo camera and the Quest 2, human-vision can be replicated on the HMD. The main advantage this type of camera provides over a traditional monocular camera is it gives the user wearing the HMD a sense of the depth of the camera scene, specifically, a first-person view of the robotic arm’s end effector. Utilizing the built-in cameras of the Quest 2 HMD, open-source hand-tracking libraries from OpenXR can be implemented to track the user’s hands in real-time. A mixed-reality (XR) Unity application can be developed to localize the operator's physical hand motions with the end-effector of the robotic arm. Implementing gesture controls will enable the user to move the robotic arm and control its end-effector by moving the operator’s arm and providing gesture inputs from a distant location. Given that the end effector of the robotic arm is a gripper tool, gripping and opening the operator’s hand will translate to the gripper of the robot arm grabbing or releasing an object. This human-robot interaction approach provides many benefits within the construction industry. First, the operator’s safety will be increased substantially as they can be away from the site-location while still being able perform complex tasks such as moving heavy objects from place to place or performing repetitive tasks such as painting walls and laying bricks. The immersive interface enables precision robotic arm control and requires minimal training and knowledge of robotic arm manipulation, which lowers the cost for operator training. This human-robot interface can be extended to many applications, such as handling nuclear accident/waste cleanup, underwater repairs, deep space missions, and manufacturing and fabrication within factories. Further, the robotic arm can be mounted onto existing mobile robots to provide access to hazardous environments, including power plants, burning buildings, and high-altitude repair sites.

Keywords: construction automation, human-robot interaction, hand-tracking, mixed reality

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Authors: Barnabás Körmöndi

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The recent crises have affected societies worldwide, resulting in the irresponsible exploitation of natural resources and the unattainability of sustainability. Regions that are economically underdeveloped, such as the Bodrogköz in Eastern Hungary and Slovakia, experience these issues more severely. The aim of this study is to analyze the natural and social resources of the Bodrogköz area for the planning of complex development based on ecotourism. The objective is to develop ecotourism opportunities in this least developed area of the borderland of Hungary and Slovakia. The study utilizes desk research, deep interviews, focus group meetings, and remote sensing methods. Desk research is aimed at providing a comprehensive understanding of the area, while deep interviews and focus group meetings were conducted to understand the stakeholders' perspectives on the potential for ecotourism. Remote sensing methods were used to better understand changes in the natural environment. The study identified the potential for ecotourism development in the Bodrogköz area due to its near-natural habitats along its bordering rivers and rich cultural heritage. The analysis revealed that ecotourism could promote the region's sustainable development, which is essential for its economic growth. Additionally, the study identified the possible threats to the natural environment during ecotourism development and suggested strategies to mitigate these threats. This study highlights the significance of ecotourism in promoting sustainable development in underdeveloped areas such as the Bodrogköz. It provides a basis for future research on ecotourism development and sustainable planning in similar regions. The analysis is based on the data collected through desk research, deep interviews, focus group meetings, and remote sensing. The assessment was conducted through content analysis, which allowed for the identification of themes and patterns in the data. The study addressed the question of how to develop ecotourism in the least developed area of the borderland of Hungary and Slovakia and promote sustainable development in the region. In conclusion, the study highlights the potential for ecotourism development in Bodrogköz and identifies the natural and social resources that contribute to its development. The study emphasizes the need for sustainable development to promote economic growth and mitigate any environmental threats. The findings can inform the development of future strategic plans for ecotourism, promoting sustainable development in underdeveloped regions.

Keywords: ecotourism, natural resources, remote sensing, social development

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Authors: Richard Joseph, Nerey Mvungi

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An electric power system includes a generating, a transmission, a distribution and consumers subsystems. An electrical power network in Tanzania keeps growing larger by the day and become more complex so that, most utilities have long wished for real-time monitoring and remote control of electrical power system elements such as substations, intelligent devices, power lines, capacitor banks, feeder switches, fault analyzers and other physical facilities. In this paper, the concept of automation of management of power systems from generation level to end user levels was determined by using Power System Simulator for Engineering (PSS/E) version 30.3.2.

Keywords: automation, distribution subsystem, generating subsystem, PSS/E, TANESCO, transmission subsystem

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

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Anti-estrogen treatment resistant is a noteworthy reason for disease relapse and mortality in estrogen receptor alpha (ERα)- positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependance of breast malignancy cells on INT3 signaling. Here, we researched the contribution of Quercetin and INT3 signaling in endocrine resistant breast cancer cells. Methods: We utilized two models of endocrine therapies resistant (ETR-) breast cancer: tamoxifen-resistant (TamR) and long term estrogen-deprived (LTED) MCF7 cells. We assessed the migratory and invasive limit of these cells by Transwell assay. Expression of epithelial to mesenchymal transition (EMT) controllers and in addition INT3 receptors and targets were assessed by real-time PCR and western blot analysis. Besides, we tried in vitro anti-Quercetin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. At last, we created stable Quercetin over expessing MCF7 cells and assessed their EMT features and response to tamoxifen. Results:We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we detected higher level of INT3 however lower levels of INT31 and INT32 proposing a switch to targeting through distinctive INT3 receptors after obtaining of resistance. Anti-Quercetin monoclonal antibodies and the GSI PF03084014 were effective in obstructing the Quercetin/INT3 axis and in part inhibiting the EMT process. As a consequence of this, cell migration and invasion were weakened and the stem cell like population was considerably decreased. Genetic hushing of Quercetin and INT3 prompted proportionate impacts. Finally, stable overexpression of Quercetin was adequate to make MCF7 lethargic to tamoxifen by INT3 activation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives invasive conduct. Anti-Quercetin mAbs and GSI PF03084014 lessen expression of EMT molecules decreasing cellular invasiveness. Quercetin overexpression instigates tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and/or INT3 warrants further clinical assessment as substantial therapeutic methodologies in endocrine-resistant breast cancer.

Keywords: quercetin, INT3, mesenchymal transition, MCF7 breast cancer cells

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Authors: Elena Listo Ubeda, Miguel Marchamalo Sacristan

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The demand for water doubles every twenty years, at a rate which is twice as fast as the world´s population growth. Despite it´s great importance, water is one of the most degraded natural resources in the world, mainly because of the reduction of natural vegetation coverage, population growth, contamination and changes in the soil use which reduces its capacity to collect water. This situation is especially serious in Central America, as reflected in the Human Development reports. The objective of this project is to assist in the improvement of water production and quality in Central America. In order to do these two watersheds in Costa Rica were selected as experiments: that of the Virilla-Durazno River, located in the extreme north east of the central valley which has an Atlantic influence; and that of the Jabillo River, which flows directly into the Pacific. The Virilla river watershed is located over andisols, and that of the Jabillo River is over alfisols, and both are of great importance for water supply to the Greater Metropolitan Area and the future tourist resorts respectively, as well as for the production of agriculture, livestock and hydroelectricity. The hydrological reaction in different soil-cover complexes, varying from the secondary forest to natural vegetation and degraded pasture, was analyzed according to the evaluation of the properties of the soil, infiltration, soil compaction, as well as the effects of the soil cover complex on erosion, calculated by the C factor of the Revised Universal Soil Loss Equation (RUSLE). A water balance was defined for each watershed, in which the volume of water that enters and leaves were estimated, as well as the evapotranspiration, runoff, and infiltration. Two future scenarios, representing the implementation of reforestation and deforestation plans, were proposed, and were analyzed for the effects of the soil cover complex on the water balance in each case. The results obtained show an increase of the ground water recharge in the humid forest areas, and an extension of the study of the dry areas is proposed since the ground water recharge here is diminishing. These results are of great significance for the planning, design of Payment Schemes for Environmental Services and the improvement of the existing water supply systems. In Central America spatial planning is a priority, as are the watersheds, in order to assess the water resource socially and economically, and securing its availability for the future.

Keywords: Costa Rica, infiltration, soil, water

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Authors: Supanan Chansap, Werachon Cheukamud, Pornanan Kueakhai, Narin Changklungmoa

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Fasciola species (Fasciola spp.) is caused fasciolosis in ruminants such as cattle, sheep, and buffalo. Fasciola gigantica (F.gigantica) commonly infects tropical regions. Fasciola hepatica (F.hepatica) in temperate regions. Liver fluke infection affects livestock economically, for example, reduced milk and meat production, weight loss, sterile animals. Currently, Triclabendazole is used to treat liver flukes. However, liver flukes have also been found to be resistant to drugs in countries. Therefore, vaccination is an attractive alternative to prevent liver fluke infection. Peptide vaccines are new vaccine technologies that mimic epitope antigens that trigger an immune response. An interesting antigen used in vaccine production is catepsin L, a family of proteins that play an important role in the life of the parasite in the host. This study aims to identify immunogenic regions of protein and construct a multi-epidetope vaccine using an immunoinformatic tool. Fasciola gigantica Cathepsin L1 (FgCatL1), Fasciola gigantica Cathepsin L1G (FgCatL1G), and Fasciola gigantica Cathepsin L1H (FgCatL1H) were predicted B-cell and Helper T lymphocytes (HTL) by Immune Epitope and Analysis Resource (IEDB) servers. Both B-cell and HTL epitopes aligned with cathepsin L of the host and Fasciola hepatica (F. hepatica). Epitope groups were selected from non-conserved regions and overlapping sequences with F. hepatica. All overlapping epitopes were linked with the GPGPG and KK linker. GPGPG linker was linked between B-cell epitope. KK linker was linked between HTL epitope and B-cell and HTL epitope. The antigenic scores of multi-epitope peptide vaccine was 0.7824. multi-epitope peptide vaccine was non-allergen, non-toxic, and good soluble. Multi-epitope peptide vaccine was predicted tertiary structure and refinement model by I-Tasser and GalaxyRefine server, respectively. The result of refine structure model was good quality that was generated by Ramachandran plot analysis. Discontinuous and linear B-cell epitopes were predicted by ElliPro server. Multi-epitope peptide vaccine model was two and seven of discontinuous and linear B-cell epitopes, respectively. Furthermore, multi-epitope peptide vaccine was docked with Toll-like receptor 2 (TLR-2). The lowest energy ranged from -901.3 kJ/mol. In summary, multi-epitope peptide vaccine was antigenicity and probably immune response. Therefore, multi-epitope peptide vaccine could be used to prevent F. gigantica infections in the future.

Keywords: fasciola gigantica, Immunoinformatic tools, multi-epitope, Vaccine

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Authors: Barbara Pemberton

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Now that people of all faiths are experiencing suffering due to many global issues, shared narratives may provide common ground in which true understanding of each other may take root. This paper will consider the all too common problem of suffering and address how adherents of the three great monotheistic religions seek understanding and the appropriate believer’s response from the same story found within their respective sacred texts. Most scholars from each of these three traditions—Judaism, Christianity, and Islam— consider the writings of the Tanakh/Old Testament to at least contain divine revelation. While they may not agree on the extent of the revelation or the method of its delivery, they do share stories as well as a common desire to glean God’s message for God’s people from the pages of the text. One such shared story is that of Job, the servant of Yahweh--called Ayyub, the prophet of Allah, in the Qur’an. Job is described as a pious, righteous man who loses everything—family, possessions, and health—when his faith is tested. Three friends come to console him. Through it, all Job remains faithful to his God who rewards him by restoring all that was lost. All three hermeneutic communities consider Job to be an archetype of human response to suffering, regarding Job’s response to his situation as exemplary. The story of Job addresses more than the distribution of the evil problem. At stake in the story is Job’s very relationship to his God. Some exegetes believe that Job was adapted into the Jewish milieu by a gifted redactor who used the original ancient tale as the “frame” for the biblical account (chapters 1, 2, and 4:7-17) and then enlarged the story with the complex center section of poetic dialogues creating a complex work with numerous possible interpretations. Within the poetic center, Job goes so far as to question God, a response to which Jews relate, finding strength in dialogue—even in wrestling with God. Muslims only embrace the Job of the biblical narrative frame, as further identified through the Qur’an and the prophetic traditions, considering the center section an errant human addition not representative of a true prophet of Islam. The Qur’anic injunction against questioning God also renders the center theologically suspect. Christians also draw various responses from the story of Job. While many believers may agree with the Islamic perspective of God’s ultimate sovereignty, others would join their Jewish neighbors in questioning God, not anticipating answers but rather an awareness of his presence—peace and hope becoming a reality experienced through the indwelling presence of God’s Holy Spirit. Related questions are as endless as the possible responses. This paper will consider a few of the many Jewish, Christian, and Islamic insights from the ancient story, in hopes adherents within each tradition will use it to better understand the other faiths’ approach to suffering.

Keywords: suffering, Job, Qur'an, tanakh

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Authors: Liudmila Garzanova, Lidia Ananyeva, Olga Koneva, Olga Ovsyannikova, Oxana Desinova, Mayya Starovoytova, Rushana Shayahmetova, Anna Khelkovskaya-Sergeeva

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Abstract Objectives. Rituximab (RTX) shown a positive effect in the treatment of systemic sclerosis (SSc). But there is still not enough data on comparing the effectiveness of RTX with immunosuppressants (IS). The aim of our study was to compare changes of lung function and skin score in SSc between two groups of patients (pts) - on RXT therapy (prescribed after ineffectiveness of previous therapy with IS) and on therapy with IS only. Methods. This study included 103 pts received RTX as an addition to previous therapy (group 1) and 65 pts received therapy with IS and prednisolone (group 2). The mean follow-up period was 12.6±10.7months. In group 1 the mean age was 47±12.9 years, female – 88 pts (84%), the diffuse cutaneous subset of the disease had 55 pts (53%). The mean disease duration was 6.2±5.5 years. 82% pts had interstitial lung disease (ILD) and 92% were positive for ANA, 67% of them were positive for antitopoisomerase-1. All pts received prednisolone at a dose of 11.3±4.5 mg/day, IS at inclusion received 47% of them. The cumulative mean dose of RTX was 1.7±0.6 g. In group 2 the mean age was 50.8±13.8 years, female-53 pts (82%), the diffuse cutaneous subset of the disease had 44 pts (68%). The mean disease duration was 8.8±7.7 years. 81% pts had ILD and 88% were positive for ANA, 58% of them were positive for antitopoisomerase-1. All pts received prednisolone at a dose of 8.69±4.28 mg/day, IS received 57% of them. Cyclophosphamide (CP) received 45% of pts. The cumulative mean dose of CP was 10.2±15.1g. D-penicillamine received 30% of pts. Other pts was on mycophenolate mofetil or methotrexate therapy in single cases. The pts of the compared groups did not differ in the main demographic and clinical parameters. The results are presented as delta (Δ) - difference between the baseline parameter and follow up point. Results. In group 1 there was an improvement of all outcome parameters: increased of forced vital capacity, % predicted - ΔFVC=4% (p=0.0004); Diffusing capacity for carbon monoxide, % predicted remained stable (ΔDLCO=0.1%); improvement of the Rodnan skin score-ΔmRss=3.4 (p=0.001); decrease of Activity index (EScSG-AI) - ΔActivity index=1.7 (p=0.001). In group 2 the changes was insignificant: ΔFVC=-2.3%, ΔmRss=0.87, ΔActivity index=0.3. But there was a significant decrease of DLCO: ΔDLCO=-5.1% (p=0.001). Conclusion. The results of our study confirm the data on the positive effect of RTX in complex therapy in pts with SSc (decrease of skin induration, increase of FVC, stabilization of DLCO). Meantime, pts on IS and prednisolone therapy shown the worsening of lung function and insignificant changes of other clinical parameters. RTX could be considered as a more effective option in complex treatment of SSc in comparison with IS therapy

Keywords: immunosuppressants, interstitial lung disease, systemic sclerosis, rituximab

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Authors: Qian Zhao, Shi-Qi Liu, Bo Guo, Zhi-Jun Cheng, Xiao-Yue Wu

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Cold standby redundancy is considered to be an effective mechanism for improving system reliability and is widely used in industrial engineering. However, because of the complexity of the reliability structure, there is little literature studying on the residual life of cold standby system consisting of complex components. In this paper, a simulation method is presented to predict the residual life of k-out-of-n cold standby system. In practical cases, failure information of a system is either unknown, partly unknown or completely known. Our proposed method is designed to deal with the three scenarios, respectively. Differences between the procedures are analyzed. Finally, numerical examples are used to validate the proposed simulation method.

Keywords: cold standby system, k-out-of-n, residual life, simulation sampling

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Authors: Maki Mizogami, Hironori Tsuchiya, Yoshiroh Hayabuchi, Kenji Shigemi

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Since drugs exhibit significant structure-dependent differences in activity and toxicity, their differentiation based on the mechanism of action should have implications for comparative drug efficacy and safety. We aimed to differentiate drug stereoisomers by their stereostructure-selective membrane interactions underlying pharmacological and toxicological effects. Biomimetic lipid bilayer membranes were prepared with phospholipids and sterols (either cholesterol or epicholesterol) to mimic the lipid compositions of neuronal and cardiomyocyte membranes and to provide these membranes with the chirality. The membrane preparations were treated with different classes of stereoisomers at clinically- and pharmacologically-relevant concentrations (25-200 μM), followed by measuring fluorescence polarization to determine the membrane interactivity of drugs to change the physicochemical property of membranes. All the tested drugs acted on lipid bilayers to increase or decrease the membrane fluidity. Drug stereoisomers could not be differentiated when interacting with the membranes consisting of phospholipids alone. However, they stereostructure-selectively interacted with neuro-mimetic and cardio-mimetic membranes containing 40 mol% cholesterol ((3β)-cholest-5-en-3-ol) to show the relative potencies being local anesthetic R(+)-bupivacaine > rac-bupivacaine > S(‒)-bupivacaine, α2-adrenergic agonistic D-medetomidine > rac-medetomidine > L-medetomidine, β-adrenergic antagonistic R(+)-propranolol > rac-propranolol > S(–)-propranolol, NMDA receptor antagonistic S(+)-ketamine > rac-ketamine, analgesic monoterpenoid (+)-menthol > (‒)-menthol, non-steroidal anti-inflammatory S(+)-ibuprofen > rac-ibuprofen > R(‒)-ibuprofen, and bioactive flavonoid (+)-epicatechin > (‒)-epicatechin. All of the order of membrane interactivity were correlated to those of beneficial and adverse effects of the tested stereoisomers. In contrast, the membranes prepared with epicholesterol ((3α)-chotest-5-en-3-ol), an epimeric form of cholesterol, reversed the rank order of membrane interactivity to be S(‒)-enantiomeric > racemic > R(+)-enantiomeric bupivacaine, L-enantiomeric > racemic > D-enantiomeric medetomidine, S(–)-enantiomeric > racemic > R(+)-enantiomeric propranolol, racemic > S(+)-enantiomeric ketamine, (‒)-enantiomeric > (+)-enantiomeric menthol, R(‒)-enantiomeric > racemic > S(+)-enantiomeric ibuprofen, and (‒)-enantiomeric > (+)-enantiomeric epicatechin. The opposite configuration allows drug molecules to interact with chiral sterol membranes enantiomer-selectively. From the comparative results, it is speculated that a 3β-hydroxyl group in cholesterol is responsible for the enantioselective interactions of drugs. In conclusion, the differentiation of drug stereoisomers by their stereostructure-selective membrane interactions would be useful for designing and predicting drugs with higher activity and/or lower toxicity.

Keywords: chiral membrane, differentiation, drug stereoisomer, enantioselective membrane interaction

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Authors: Belachew Gebrewold

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The Horn of Africa is marred by complex and systematic internal and external political, economic and social-cultural causes of conflict that result in internal displacement and migration. This paper engages with them and shows how such a study can help us to understand migration, both in this region and more generally. The conflict has occurred within states, between states, among proxies, between armies. Human insecurities as a result of the state collapse of Somalia, the rise of Islamic fundamentalism in the whole region, recurrent drought affecting the livelihoods of subsistence farmers as well as nomads, exposure to hunger, environmental degradation, youth unemployment, rapid growth of slums around big cities, and political repression (especially in Eritrea) have been driving various segments of the regional population into regional and international migration. Eritrea has been going through a brutal dictatorship which pushes many Eritreans to flee their country and be exposed to human trafficking, torture, detention, and agony on their way to Europe mainly through Egypt, Libya and Israel. Similarly, Somalia has been devastated since 1991 by unending civil war, state collapse, and radical Islamists. There are some important aspects to highlight in the conflict-migration nexus in the Horn of Africa: first, the main push factor for the Somalis and Eritreans to leave their countries and risk their lives is the physical insecurity they have been facing in their countries. Secondly, as a result of the conflict the economic infrastructure is massively destroyed. Investment is rare; job opportunities are out of sight. Thirdly, in such a grim situation the politically and economically induced decision to migrate is a household decision, not only an individual decision. Based on this third point this research study took place in the Horn of Africa between 2014 and 2016 during different occasions. The main objective of the research was to understanding how the increasing migration is affecting the socio-economic and socio-political environment, and conversely how the socio-economic and socio-political environments are increasing migration decisions; and whether and how these decisions are individual or family decisions. The main finding is the higher the human insecurity, the higher the family decision; the lower the human insecurity, the higher the individual decision. These findings apply not only to the Eritrean, Somali migrants but also to Ethiopian migrants. But the general impacts of migration on sending countries’ human security is quite mixed and complex.

Keywords: Eritrea, Ethiopia, Horn of Africa, insecurity, migration, Somalia

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Authors: Ayat-Allah Bouramdane

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Power generation from offshore wind energy does not emit carbon dioxide or other air pollutants and therefore play a role in reducing greenhouse gas emissions from the energy sector. In addition, these systems are considered more efficient than onshore wind farms, as they generate electricity from the wind blowing across the sea, thanks to the higher wind speed and greater consistency in direction due to the lack of physical interference that the land or human-made objects can present. This means offshore installations require fewer turbines to produce the same amount of energy as onshore wind farms. However, offshore wind farms require more complex infrastructure to support them and, as a result, are more expensive to construct. In addition, higher wind speeds, strong seas, and accessibility issues makes offshore wind farms more challenging to maintain. This study uses a combination of Geographic Referenced Information (GRI) and Analytic Hierarchy Process (AHP) to identify the most suitable sites for offshore wind farm development in Morocco, with a particular focus on the Dakhla city. A range of environmental, socio-economic, and technical criteria are taken into account to solve this complex Multi-Criteria Decision-Making (MCDM) problem. Based on experts' knowledge, a pairwise comparison matrix at each level of the hierarchy is performed, and fourteen sub-criteria belong to the main criteria have been weighted to generate the site suitability of offshore wind plants and obtain an in-depth knowledge on unsuitable areas, and areas with low-, moderate-, high- and very high suitability. We find that wind speed is the most decisive criteria in offshore wind farm development, followed by bathymetry, while proximity to facilities, the sediment thickness, and the remaining parameters show much lower weightings rendering technical parameters most decisive in offshore wind farm development projects. We also discuss the potential of other marine renewable energy potential, in Morocco, such as wave and tidal energy. The proposed approach and analysis can help decision-makers and can be applied to other countries in order to support the site selection process of offshore wind farms.

Keywords: analytic hierarchy process, dakhla, geographic referenced information, morocco, multi-criteria decision-making, offshore wind, site suitability

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Authors: Alexander P. Eremeev, Ivan E. Kurilenko, Pavel R. Varshavskiy

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In this paper, the problem of the application of temporal reasoning and case-based reasoning in intelligent decision support systems is considered. The method of case-based reasoning with temporal dependences for the solution of problems of real-time diagnostics and forecasting in intelligent decision support systems is described. This paper demonstrates how the temporal case-based reasoning system can be used in intelligent decision support systems of the car access control. This work was supported by RFBR.

Keywords: analogous reasoning, case-based reasoning, intelligent decision support systems, temporal reasoning

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Authors: Gagandeep Kaur, Sonal Chawla

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In a Cloud Computing environment, resource provisioning, resource allocation and resource scheduling is the most complex issues these days. Cloud User expects the best resource utilization and Cloud Provider expects revenue maximization by considering budget and time constraints. In this research paper, Resource Management Framework has been proposed to allocate the resources to Cloud Users and Cloud Providers in Cloud environment. The main aim of the proposed work is to provide the resources and services to Cloud Providers and Cloud Users in an efficient and effective manner. The proposed framework has been simulated and tested using the CloudSim simulator tool.

Keywords: cloud computing, resource allocation, auction, provisioning

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Authors: Yuliya Leonidovna Kiva-Khamzina

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The legal nature of the contract for educational services causes a lot of controversies. In particular, it raises the question about industry sector relationships, which require making a contract for educational services. The article describes the different types of contracts classifications for services provision from the perspective of civil law, deals with the specifics of the contract on rendering educational services; the author makes the conclusion that the contract for the provision of educational services is a complex institution that includes elements of the civil and administrative law. The following methods were used to conduct the study: dialectical method of cognition, the historical method, systemic analysis, classification.

Keywords: administrative aspect, civil aspect, educational service, industry, legal nature, services provision

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Authors: John Kabuba

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The study investigated the implementation of the Neural Network (NN) techniques for prediction of the loading of Cu ions onto clinoptilolite. The experimental design using analysis of variance (ANOVA) was chosen for testing the adequacy of the Neural Network and for optimizing of the effective input parameters (pH, temperature and initial concentration). Feed forward, multi-layer perceptron (MLP) NN successfully tracked the non-linear behavior of the adsorption process versus the input parameters with mean squared error (MSE), correlation coefficient (R) and minimum squared error (MSRE) of 0.102, 0.998 and 0.004 respectively. The results showed that NN modeling techniques could effectively predict and simulate the highly complex system and non-linear process such as ion-exchange.

Keywords: clinoptilolite, loading, modeling, neural network

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Authors: Fatemeh Nemati, Lucinda Leonard, Gwyn Lintern, Richard Thomson

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In this study, we will use modern numerical modeling approaches to estimate tsunami risks to the southern coast of British Columbia from landslides. Wave generation is to be simulated using the NHWAVE model, which solves the Navier-Stokes equations due to the more complex behavior of flow near the landslide source; far-field wave propagation will be simulated using the simpler model FUNWAVE_TVD with high-order Boussinesq-type wave equations, with a focus on the accurate simulation of wave propagation and regional- or coastal-scale inundation predictions.

Keywords: FUNWAVE-TVD, landslide-generated tsunami, NHWAVE, tsunami risk

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Authors: Amanbek Jainakov, Abdikerim Kurbanaliev

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The work presents the results of mathematical modeling of large-scale flows in areas with a complex topographic relief. The Reynolds-averaged Navier—Stokes equations constitute the basis of the three-dimensional unsteady modeling. The well-known Volume of Fluid method implemented in the solver interFoam of the open package OpenFOAM 2.3 is used to track the free-boundary location. The mathematical model adequacy is checked by comparing with experimental data. The efficiency of the applied technology is illustrated by the example of modeling the breakthrough of the dams of the Andijan (Uzbekistan) and Papan (near the Osh town, Kyrgyzstan) reservoir.

Keywords: three-dimensional modeling, free boundary, the volume-of-fluid method, dam break, flood, OpenFOAM

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Authors: Najeh Lakhoua

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Introduction: Scientific developments and techniques for the systemic approach generate several names to the systemic approach: systems analysis, systems analysis, structural analysis. The main purpose of these reflections is to find a multi-disciplinary approach which organizes knowledge, creates universal language design and controls complex sets. In fact, system analysis is structured sequentially by steps: the observation of the system by various observers in various aspects, the analysis of interactions and regulatory chains, the modeling that takes into account the evolution of the system, the simulation and the real tests in order to obtain the consensus. Thus the system approach allows two types of analysis according to the structure and the function of the system. The purpose of this paper is to present an application of system analysis of Unmanned Aerial Vehicle (UAV) components in order to represent the architecture of this system. Method: There are various analysis methods which are proposed, in the literature, in to carry out actions of global analysis and different points of view as SADT method (Structured Analysis and Design Technique), Petri Network. The methodology adopted in order to contribute to the system analysis of an Unmanned Aerial Vehicle has been proposed in this paper and it is based on the use of SADT. In fact, we present a functional analysis based on the SADT method of UAV components Body, power supply and platform, computing, sensors, actuators, software, loop principles, flight controls and communications). Results: In this part, we present the application of SADT method for the functional analysis of the UAV components. This SADT model will be composed exclusively of actigrams. It starts with the main function ‘To analysis of the UAV components’. Then, this function is broken into sub-functions and this process is developed until the last decomposition level has been reached (levels A1, A2, A3 and A4). Recall that SADT techniques are semi-formal; however, for the same subject, different correct models can be built without having to know with certitude which model is the good or, at least, the best. In fact, this kind of model allows users a sufficient freedom in its construction and so the subjective factor introduces a supplementary dimension for its validation. That is why the validation step on the whole necessitates the confrontation of different points of views. Conclusion: In this paper, we presented an application of system analysis of Unmanned Aerial Vehicle components. In fact, this application of system analysis is based on SADT method (Structured Analysis Design Technique). This functional analysis proved the useful use of SADT method and its ability of describing complex dynamic systems.

Keywords: system analysis, unmanned aerial vehicle, functional analysis, architecture

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Authors: Amir Ghasem Norouzi, Mahdi Zowghi

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This study propose a framework based on the fuzzy T-Norms, T-conorm, a novel operator, and multi-expert approach to help organizations build awareness of the critical influential factors on the success of knowledge management (KM) implementation, analysis the failure of knowledge management. This study considers the complex uncertainty concept that is in knowledge management implementing capability (KMIC) and it is used by fuzzy logic for this reason. The contribution of our paper is shown with an empirical study in a nonprofit educational organization evaluation.

Keywords: fuzzy logic, knowledge management, multi expert analysis, consensus oriented average operator

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Authors: Eusèbe Gnonlonfoun, Xavier Framboisier, Michel Fick, Emmanuel Rondags

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Pathogenic fungi represent a generic problem for cereals, including barley, as they can produce a number of thermostable toxic metabolites such as mycotoxins that contaminate plants and food products, leading to serious health issues for humans and animals and causing significant losses in global food production. In addition, mycotoxins represent a significant technological concern for the malting and brewing industries, as they may affect the quality and safety of raw materials (barley and malt) and final products (beer). Moreover, this situation is worsening due to the highly variable climatic conditions that favor microbial development and the societal desire to reduce the use of phytosanitary products, including fungicides. In this complex environmental, regulatory and economic context for the French barley-malt-beer industry, this project aims to develop an innovative biocontrol process by using technological bacteria, isolated from infection-resistant barley cultures, that are able to reduce the development of spoilage fungi and the associated mycotoxin production. The experimental approach consists of i) coculturing bacterial and pathogenic fungal strains in solid and liquid media to access the growth kinetics of these microorganisms and to evaluate the impact of these bacteria on fungal growth and mycotoxin production; then ii) the results will be used to carry out a micro-malting process in order to develop the aforementioned process, and iii) the technological and sanitary properties of the generated barley malts will finally be evaluated in order to validate the biocontrol process developed. The process is expected to make it possible to guarantee, with controlled costs, an irreproachable hygienic and technological quality of the malt, despite the increasingly complex and variable conditions for barley production. Thus, the results will not only make it possible to maintain the dominant world position of the French barley-malt chain but will also allow it to conquer emerging markets, mainly in Africa and Asia. The use of this process will also contribute to the reduction of the use of phytosanitary products in the field for barley production while reducing the level of contamination of malting plant effluents. Its environmental impact would therefore be significant, especially considering that barley is the fourth most-produced cereal in the world.

Keywords: barley, pathogenic fungi, mycotoxins, malting, bacterial biocontrol

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Authors: Achiron Anat, Mathilda Mandel, Mayust Sue, Achiron Reuven, Gurevich Michael

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Introduction: As coronavirus disease 2019 (COVID-19) vaccination is currently spreading around the world, it is of importance to assess the ability of multiple sclerosis (MS) patients to mount an appropriate immune response to the vaccine in the context of disease-modifying treatments (DMT’s). Objectives: Evaluate immunity generated following COVID-19 vaccination in MS patients, and assess factors contributing to protective humoral and cellular immune responses in MS patients vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) virus infection. Methods: Review our recent data related to (1) the safety of PfizerBNT162b2 COVID-19 mRNA vaccine in adult MS patients; (2) the humoral post-vaccination SARS-CoV2 IgG response in MS vaccinees using anti-spike protein-based serology; and (3) the cellular immune response of memory B-cells specific for SARS-CoV-2 receptor-binding domain (RBD) and memory T-cells secreting IFN-g and/or IL-2 in response to SARS-CoV2 peptides using ELISpot/Fluorospot assays in MS patients either untreated or under treatment with fingolimod, cladribine, or ocrelizumab; (4) covariate parameters related to mounting protective immune responses. Results: COVID-19 vaccine proved safe in MS patients, and the adverse event profile was mainly characterised by pain at the injection site, fatigue, and headache. Not any increased risk of relapse activity was noted and the rate of patients with acute relapse was comparable to the relapse rate in non-vaccinated patients during the corresponding follow-up period. A mild increase in the rate of adverse events was noted in younger MS patients, among patients with lower disability, and in patients treated with DMTs. Following COVID-19 vaccination protective humoral immune response was significantly decreased in fingolimod- and ocrelizumab- treated MS patients. SARS-CoV2 specific B-cell and T-cell cellular responses were respectively decreased. Untreated MS patients and patients treated with cladribine demonstrated protective humoral and cellular immune responses, similar to healthy vaccinated subjects. Conclusions: COVID-19 BNT162b2 vaccine proved as safe for MS patients. No increased risk of relapse activity was noted post-vaccination. Although COVID-19 vaccination is new, accumulated data demonstrate differences in immune responses under various DMT’s. This knowledge can help to construct appropriate COVID-19 vaccine guidelines to ensure proper immune responses for MS patients.

Keywords: covid-19, vaccination, multiple sclerosis, IgG

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Authors: Leon C. Prieto, Simone T. A. Phipps

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There is a need to promote social entrepreneurship in order to solve some of the complex problems facing various countries in Africa (poverty, unemployment, crime, HIV, etc.). For example, one possible consequence of the HIV/AIDS crisis in Zimbabwe and elsewhere is a deterioration in the educational opportunities for orphans and other vulnerable children. Given that high returns are associated with education, the loss of education for a large segment of the population would likely worsen the already dire economic consequences of the HIV/AIDS crisis. Using a systems approach, this paper argues that social entrepreneurship can be used as a vehicle to promote national human resource development, which will assist in the alleviation of societal ills on the national level as well as throughout Africa.

Keywords: human resource development, pan-african, social entrepreneurship, social enterprise

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Authors: Chaimaa Messaoudi, Rachida Fissoune, Hassan Badir

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Technological advances of computer science and data analysis are helping to provide continuously huge volumes of biological data, which are available on the web. Such advances involve and require powerful techniques for data integration to extract pertinent knowledge and information for a specific question. Biomedical exploration of these big data often requires the use of complex queries across multiple autonomous, heterogeneous and distributed data sources. Semantic integration is an active area of research in several disciplines, such as databases, information-integration, and ontology. We provide a survey of some approaches and techniques for integrating biological data, we focus on those developed in the ontology community.

Keywords: biological ontology, linked data, semantic data integration, semantic web

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Authors: Parveen K. Saini, Mayank Kushwaha

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The influence of material property variation on stress concentration factor (SCF) due to the presence of a circular hole in a functionally graded material (FGM) plate is studied in this paper. A numerical method based on complex variable theory of elasticity is used to investigate the problem. To achieve the material property, variation plate is decomposed into a number of rings. In this research work, Young's modulus is assumed to be varying exponentially and it is found that stress concentration factor can be reduced by increasing Young’s modulus progressively away from the hole.

Keywords: stress concentration, circular hole, FGM plate, bending

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