Search results for: small molecule inhibitor

Authors: K. K. Lee, H. W. Han, H. L. Kang, T. A. Kim, S. H. Han

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For the robust optimization of the manufacturing product design, there are design objectives that must be achieved, such as a minimization of the mean and standard deviation in objective functions within the required sensitivity constraints. The authors utilized the sensitivity of objective functions and constraints with respect to the effective design variables to reduce the computational burden associated with the evaluation of the probabilities. The individual mean and sensitivity values could be estimated easily by using the 9 level orthogonal array based response surface models optimized by the stepwise regression. The present study evaluates a proposed procedure from the robust optimization of rubber domes that are commonly used for keyboard switching, by using the 9 level orthogonal array and stepwise regression along with a desirability function. In addition, a new robust optimization process, i.e., the I2GEO (Identify, Integrate, Generate, Explore and Optimize), was proposed on the basis of the robust optimization in rubber domes. The optimized results from the response surface models and the estimated results by using the finite element analysis were consistent within a small margin of error. The standard deviation of objective function is decreasing 54.17% with suggested sensitivity based robust optimization. (Business for Cooperative R&D between Industry, Academy, and Research Institute funded Korea Small and Medium Business Administration in 2017, S2455569)

Keywords: objective function, orthogonal array, response surface model, robust optimization, stepwise regression

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Authors: Coriolano Salvini, Ambra Giovannelli

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The use of renewable energy sources for electric power production leads to reduced CO2 emissions and contributes to improving the domestic energy security. On the other hand, the intermittency and unpredictability of their availability poses relevant problems in fulfilling safely and in a cost efficient way the load demand along the time. Significant benefits in terms of “grid system applications”, “end-use applications” and “renewable applications” can be achieved by introducing energy storage systems. Among the currently available solutions, CAES (Compressed Air Energy Storage) shows favorable features. Small-medium size plants equipped with artificial air reservoirs can constitute an interesting option to get efficient and cost-effective distributed energy storage systems. The present paper is addressed to the design and off-design analysis of the compression system of small size CAES plants suited to absorb electric power in the range of hundreds of kilowatt. The system of interest is constituted by an intercooled (in case aftercooled) multi-stage reciprocating compressor and a man-made reservoir obtained by connecting large diameter steel pipe sections. A specific methodology for the system preliminary sizing and off-design modeling has been developed. Since during the charging phase the electric power absorbed along the time has to change according to the peculiar CAES requirements and the pressure ratio increases continuously during the filling of the reservoir, the compressor has to work at variable mass flow rate. In order to ensure an appropriately wide range of operations, particular attention has been paid to the selection of the most suitable compressor capacity control device. Given the capacity regulation margin of the compressor and the actual level of charge of the reservoir, the proposed approach allows the instant-by-instant evaluation of minimum and maximum electric power absorbable from the grid. The developed tool gives useful information to appropriately size the compression system and to manage it in the most effective way. Various cases characterized by different system requirements are analysed. Results are given and widely discussed.

Keywords: artificial air storage reservoir, compressed air energy storage (CAES), compressor design, compression system management.

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Authors: Bruno Baptista, Andreia S. R. Oliveira, Patricia V. Mendonca, Jorge F. J. Coelho, Fani Sousa

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Drug delivery systems are designed to allow adequate protection and controlled delivery of drugs to specific locations. These systems aim to reduce side effects and control the biodistribution profile of drugs, thus improving therapeutic efficacy. This study involved the synthesis of polymeric nanoparticles, based on amphiphilic diblock copolymers, comprising a biocompatible, poly (oligo (ethylene oxide) methyl ether methacrylate (POEOMA) as hydrophilic segment and a pH-sensitive block, the poly (2-diisopropylamino)ethyl methacrylate) (PDPA). The objective of this work was the development of polymeric pH-responsive nanoparticles to encapsulate and carry small RNAs as a model to further develop non-coding RNAs delivery systems with therapeutic value. The responsiveness of PDPA to pH allows the electrostatic interaction of these copolymers with nucleic acids at acidic pH, as a result of the protonation of the tertiary amine groups of this polymer at pH values below its pKa (around 6.2). Initially, the molecular weight parameters and chemical structure of the block copolymers were determined by size exclusion chromatography (SEC) and nuclear magnetic resonance (1H-NMR) spectroscopy, respectively. Then, the complexation with small RNAs was verified, generating polyplexes with sizes ranging from 300 to 600 nm and with encapsulation efficiencies around 80%, depending on the molecular weight of the polymers, their composition, and concentration used. The effect of pH on the morphology of nanoparticles was evaluated by scanning electron microscopy (SEM) being verified that at higher pH values, particles tend to lose their spherical shape. Since this work aims to develop systems for the delivery of non-coding RNAs, studies on RNA protection (contact with RNase, FBS, and Trypsin) and cell viability were also carried out. It was found that they induce some protection against constituents of the cellular environment and have no cellular toxicity. In summary, this research work contributes to the development of pH-sensitive polymers, capable of protecting and encapsulating RNA, in a relatively simple and efficient manner, to further be applied on drug delivery to specific sites where pH may have a critical role, as it can occur in several cancer environments.

Keywords: drug delivery systems, pH-responsive polymers, POEOMA-b-PDPA, small RNAs

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Authors: Divya Kanchibhotla, Shashank Kulkarni, Shweta Singh

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Chronic stress and sleep quality reduces mental health and increases the risk of developing depression and anxiety as well. There is increasing evidence for the utility of meditation as an adjunct clinical intervention for conditions like depression and anxiety. The present study is an attempt to explore the impact of Sahaj Samadhi Meditation (SSM), a category of Automatic Self Transcending Meditation (ASTM), on perceived stress and sleep quality in adults. The study design was a single group pre-post assessment. Perceived Stress Scale (PSS) and the Pittsburgh Sleep Quality Index (PSQI) were used in this study. Fifty-two participants filled PSS, and 60 participants filled PSQI at the beginning of the program (day 0), after two weeks (day 16) and at two months (day 60). Significant pre-post differences for the perceived stress level on Day 0 - Day 16 (p < 0.01; Cohen's d = 0.46) and Day 0 - Day 60 (p < 0.01; Cohen's d = 0.76) clearly demonstrated that by practicing SSM, participants experienced reduction in the perceived stress. The effect size of the intervention observed on the 16th day of assessment was small to medium, but on the 60th day, a medium to large effect size of the intervention was observed. In addition to this, significant pre-post differences for the sleep quality on Day 0 - Day 16 and Day 0 - Day 60 (p < 0.05) clearly demonstrated that by practicing SSM, participants experienced improvement in the sleep quality. Compared with Day 0 assessment, participants demonstrated significant improvement in the quality of sleep on Day 16 and Day 60. The effect size of the intervention observed on the 16th day of assessment was small, but on the 60th day, a small to medium effect size of the intervention was observed. In the current study we found out that after practicing SSM for two months, participants reported a reduction in the perceived stress, they felt that they are more confident about their ability to handle personal problems, were able to cope with all the things that they had to do, felt that they were on top of the things, and felt less angered. Participants also reported that their overall sleep quality improved; they took less time to fall asleep; they had less disturbances in sleep and less daytime dysfunction due to sleep deprivation. The present study provides clear evidence of the efficacy and safety of non-pharmacological interventions such as SSM in reducing stress and improving sleep quality. Thus, ASTM may be considered a useful intervention to reduce psychological distress in healthy, non-clinical populations, and it can be an alternative remedy for treating poor sleep among individuals and decreasing the use of harmful sedatives.

Keywords: automatic self transcending meditation, Sahaj Samadhi meditation, sleep, stress

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Authors: V. Nigam, V. Nambiar

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Aegle Marmelos leaf has been used as a remedy for various gastrointestinal infections and lowering blood sugar level in traditional system of medicine in India due to the presence of various constituents such as flavonoids, tannins and alkaloids (eg. Aegelin, Marmelosin, Luvangetin).The objective of the present study was to evaluate the total antioxidant activity, total and individual phenol content of the wild and cultivated variety of Aegle marmelos leaves to assess the role of this plant in ethanomedicine in India. The methanolic extracts of the leaves were screened for total antioxidant capacity through Ferric Reducing Antioxidant Potential (FRAP) and 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay; Total Phenol content (TPC) through spectrophotometric technique based on Folin Ciocalteau assay and for qualitative estimation of phenols, High performance Liquid Chromatography was used. The TPC of wild and cultivated variety was 7.6% and 6.5% respectively whereas HPLC analysis for quantification of individual polyphenol revealed the presence of gallic acid, chlorogenic acid and Ferullic acid in wild variety whereas gallic acid, Ferullic acid and pyrocatechol in cultivated variety. FRAP values and IC 50 value (DPPH) for wild and cultivated variety was 14.65 μmol/l and 11.80μmol/l; 437 μg/ml and 620μg/ml respectively and thus it can be used as potential inhibitor of free radicals. The wild variety was having more antioxidant capacity than the cultivated one it can be exploited further for its therapeutic application. As Aegle marmelos is rich in antioxidant, it can be used as food additives to delay the oxidative deterioration of foods and as nutraceutical in medicinal formulation against degenerative diseases like diabetes.

Keywords: antioxidant activity, aegle marmelos, antidiabetic, nutraceutical

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Authors: David Calderon Villegas, Thomas Kaltizky

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Run-of-river (RoR) hydropower projects represent a viable, clean, and cost-effective alternative to dam-based plants and provide decentralized power production. However, RoR schemes cost-effectiveness depends on the proper selection of site and design flow, which is a challenging task because it requires multivariate analysis. In this respect, this study presents the development of an investment decision support tool for assessing the optimal size of an RoR scheme considering the technical, environmental, and cost constraints. The net present value (NPV) from a project perspective is used as an objective function for supporting the investment decision. The tool has been tested by applying it to an actual RoR project recently proposed in Colombia. The obtained results show that the optimum point in financial terms does not match the flow that maximizes energy generation from exploiting the river's available flow. For the case study, the flow that maximizes energy corresponds to a value of 5.1 m3/s. In comparison, an amount of 2.1 m3/s maximizes the investors NPV. Finally, a sensitivity analysis is performed to determine the NPV as a function of the debt rate changes and the electricity prices and the CapEx. Even for the worst-case scenario, the optimal size represents a positive business case with an NPV of 2.2 USD million and an IRR 1.5 times higher than the discount rate.

Keywords: small hydropower, renewable energy, RoR schemes, optimal sizing, objective function

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Authors: Ghodsieh Isapour Toutizad, Aiyong Wang, Joonsoo Han, Derek Creaser, Louise Olsson, Magnus Skoglundh, Hanna HaRelind

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Nitrous oxide (N2O), which is generally formed as a byproduct of industrial chemical processes and fossil fuel combustion, has attracted considerable attention due to its destructive role in global warming and ozone layer depletion. From various developed technologies used for lean NOx reduction, the selective catalytic reduction (SCR) of NOx with ammonia is presently the most applied method. Therefore, the development of catalysts for efficient lean NOx reduction without forming N2O in the process, or only forming it to a very small extent from the exhaust gases is of crucial significance. One type of catalysts that nowadays are used for this aim are zeolite-based catalysts. It is owing to their remarkable catalytic performance under practical reaction conditions such as high thermal stability and high N2 selectivity. Among all zeolites, copper ion-exchanged zeolites, with CHA, MFI, and BEA framework structure (like SSZ-13, ZSM-5 and Beta, respectively), represent higher hydrothermal stability, high activity and N2 selectivity. This work aims at investigating the effect of the zeolite framework structure on the formation of N2O during NH3-SCR reaction conditions over three Cu-based zeolites ranging from small-pore to large-pore framework structure. In the zeolite framework, Cu exists in two cationic forms, that can catalyze the SCR reaction by activating NO to form NO+ and/or surface nitrate species. The nitrate species can thereafter react with NH3 to form another intermediate, ammonium nitrate, which seems to be one source for N2O formation at low temperatures. The results from in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) indicate that during the NO oxidation step, mainly NO+ and nitrate species are formed on the surface of the catalysts. The intensity of the absorption peak attributed to NO+ species is higher for the Cu-CHA sample compared to the other two samples, indicating a higher stability of this species in small cages. Furthermore, upon the addition of NH3, through the standard SCR reaction conditions, absorption peaks assigned to N-H stretching and bending vibrations are building up. At the same time, negative peaks are evolving in the O-H stretching region, indicating blocking/replacement of surface OH-groups by NH3 and NH4+. By removing NH3 and adding NO2 to the inlet gas composition, the peaks in the N-H stretching and bending vibration regions show a decreasing trend in intensity, with the decrease being more pronounced for increasing pore size. It can probably be owing to the higher accumulation of ammonia species in the small-pore size zeolite compared to the other two samples. Furthermore, it is worth noting that the ammonia surface species are strongly bonded to the CHA zeolite structure, which makes it more difficult to react with NO2. To conclude, the framework structure of the zeolite seems to play an important role in the formation and reactivity of surface species relevant for the SCR process. Here we intend to discuss the connection between the zeolite structure, the surface species, and the formation of N2O during ammonia-SCR.

Keywords: fast SCR, nitrous oxide, NOx, standard SCR, zeolites

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Authors: E. H. Uguru, S. F. A. Sani, M. U. Khandaker, M. H. Rabir

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The beginning of cycle transient safety parameters is paramount for smooth reactor operation. The enhanced operational safety of UO₂ fuelled AP1000 reactor being the first using three fissile enrichment zones motivated this research for (Th, U)O₂ fuel. This study evaluated the impact of fissile enrichment, soluble boron, and gadolinia on the transient safety parameters to determine the basis for choosing the three fissile enrichment zones. Fuel assembly and core model of Westinghouse small modular reactor were investigated using different fuel and reactivity control arrangements. The Monte Carlo N-Particle eXtended (MCNPX) integrated with CINDER90 burn-up code was used for the calculations. The results show that the moderator temperature coefficient of reactivity (MTC) and the fuel temperature coefficient of reactivity (FTC) were respectively negative and decreased with increasing fissile enrichment. Soluble boron significantly decreased the MTC but slightly increased FTC while gadolinia followed the same trend with a minor impact. However, the MTC and FTC respectively decreased significantly with increasing change in temperature. These results provide a guide on the considerable factors in choosing the three fissile enrichment zones for (Th, U)O₂ fuel in anticipation of their impact on safety parameters. Therefore, this study provides foundational results on the factors that must be considered in choosing three fissile arrangement zones for (Th, U)O₂ fuel.

Keywords: reactivity, safety parameters, small modular reactor, soluble boron, thorium fuel cycle

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Authors: Ayman Othman, Tallat Ali

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A pavement maintenance management system (PMMS) was developed for the city of Aswan as a model of a small city to provide the road maintenance department in Aswan city with the capabilities for comprehensive planning of the maintenance activities needed to put the internal pavement network into desired physical condition in view of maintenance budget constraints. The developed system consists of three main stages. First is the inventory & condition survey stage where the internal pavement network of Aswan city was inventoried and its actual conditions were rated in segments of 100 meters length. Second is the analysis stage where pavement condition index (PCI) was calculated and the most appropriate maintenance actions were assigned for each segment. The total maintenance budget was also estimated and a parameter based ranking criteria were developed to prioritize maintenance activities when the available maintenance budget is not sufficient. Finally comes the packaging stage where approved maintenance budget is packed into maintenance projects for field implementation. System results indicate that, the system output maintenance budget is very reasonable and the system output maintenance programs agree to a great extent with the actual maintenance needs of the network. Condition survey of Aswan city road network showed that roughness is the most dominate distress. In general, the road network can be considered in a fairly reasonable condition, however, the developed PMMS needs to be officially adapted to maintain the road network in a desirable condition and to prevent further deterioration.

Keywords: pavement, maintenance, management, system, distresses, survey, ranking

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Authors: Akshita Jindal, Renu Chadha, Maninder Karan

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Supramolecular chemistry has gained recent eminence in a flurry of research documents demonstrating the formation of new crystalline forms with potentially advantageous characteristics. Mesalamine (5-amino salicylic acid) belongs to anti-inflammatory class of drugs, is used to treat ulcerative colitis and Crohn’s disease. Unfortunately, mesalamine suffer from poor solubility and therefore very low bioavailability. This work is focused on preparation and characterization of cocrystal of mesalamine with nicotinamide (MNIC) a coformer of GRAS status. Cocrystallisation was achieved by solvent drop grinding in stoichiometric ratio of 1:1 using acetonitrile as solvent and was characterized by various techniques including DSC (Differential Scanning Calorimetry), PXRD (X-ray Powder Diffraction), and FTIR (Fourier Transform Infrared Spectrometer). The co-crystal depicted single endothermic transitions (254°C) which were different from the melting peaks of both drug (288°C) and coformer (128°C) indicating the formation of a new solid phase. Different XRPD patterns and FTIR spectrums for the co-crystals from those of individual components confirms the formation of new phase. Enhancement in apparent solubility study and intrinsic dissolution study showed effectiveness of this cocrystal. Further improvement in pharmacokinetic profile has also been observed with 2 folds increase in bioavailability. To conclude, our results show that application of nicotinamide as a coformer is a viable approach towards the preparation of cocrystals of potential drug molecule having limited solubility.

Keywords: cocrystal, mesalamine, nicotinamide, solvent drop grinding

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Authors: Tzu-Jung Tseng, Pei-Hsuen Han, Tsung-Hsueh Lu

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Background: Choropleth mortality map is commonly used to identify areas with higher mortality risk. However, the use of choropleth map alone might result in the misinterpretation of differences in mortality rates between areas. Two areas with different color shades might not actually have a significant difference in mortality rates. The mortality rates estimated for an area with a small population would be less stable. We suggest of bringing the 95% confidence intervals (CI) into the choropleth mortality map to help users interpret the areal mortality rate difference more properly. Method: In the first choropleth mortality map, we used only three color to indicate standardized mortality ratio (SMR) for each district in Tainan, Taiwan. The red color denotes that the SMR of that district was significantly higher than the Tainan average; on the contrary, the green color suggests that the SMR of that district was significantly lower than the Tainan average. The yellow color indicates that the SMR of that district was not statistically significantly different from the Tainan average. In the second choropleth mortality map, we used traditional sequential color scheme (color ramp) for different SMR in 37 districts in Tainan City with bar chart of each SMR with 95% CI in which the users could examine if the line of 95% CI of SMR of two districts overlapped (nonsignificant difference). Results: The all-causes SMR of each district in Tainan for 2008 to 2013 ranged from 0.77 (95% CI 0.75 to 0.80) in East District to 1.39 Beimen (95% CI 1.25 to 1.52). In the first choropleth mortality map, only 16 of 37 districts had red color and 8 districts had green color. For different causes of death, the number of districts with red color differed. In the first choropleth mortality map we added a bar chart with line of 95% CI of SMR in each district, in which the users could visualize the SMR differences between districts. Conclusion: Through the use of 95% CI the users could interpret the aral mortality differences more properly.

Keywords: choropleth map, small area variation, standardized mortality ratio (SMR), Taiwan

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Authors: Akeem Akinboro, Bala Alhaj Kegun

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Haemoglobinopathy is a genetic disorder that has the potentiality to cause death of individuals in whom both the alpha (α) and beta (β) globin chains of the haemoglobin molecule are defective due to mutations in their genes. The haemoglobin genotype variants among some residents of Niger state, Nigeria, were determined using the secondary data available at Bida, Minna and Kotangora general hospitals of the state. A total of 1,639 data, representing 434, 655 and 550, collected from the outside patients who visited the medical laboratory units of the three general hospitals, respectively, over five years period (2015-2020) were analyzed into gene frequency, sex and age to determine their haemoglobin genotypes status. More males (51.6 – 58.7%) than females (41.3 – 48.4%) visited the three hospitals during the period covered and most of the patients were between 11 - 20 years old. The frequency of HbA allele in the human population was 0.72, 0.65, 0.68 for Bida, Minna and Kotangora, respectively, while it was 0.25, 0.29 and 0.28 for HbS allele. The HbC allele was prevalent at 0.03, 0.06 and 0.05 among the human population in Bida, Minna and Kotangora cities of Niger state. In overall, the prevalence of HbA, HbS and HbC alleles in Niger state of Nigeria was 0.68, 0.28 and 0.05. Minna being the capital city of Niger state and the most populous among the three cities in the state seems to have influx of more people who are carriers of abnormal haemoglobin genotypes which has resulted to higher frequency of HbS and HbC than those of the other two cities in this study. These results show that the pattern of haemoglobin genotypes frequency of Kontagora could be a prediction for the whole of Niger state. It is therefore necessary and important to take screening of blood for haemoglobin genotype serious among intending couples to prevent and reduce the possibility of having increase in the number of people with abnormal haemoglobin genotypes in the state.

Keywords: haemoglobin, genotype, niger state, gene frequency, general hospitals

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Authors: Vijaykumar Patel, P. Bahadur

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Microstructural evolution of a cationic gemini surfactant 12-4-12 micelles in the presence of bile salts has been investigated using different techniques. A negative value of interaction parameter evaluated from surface tension measurements is a signature of strong synergistic interaction between oppositely charged surfactants. Both the bile salts compete with each other in inducing the micellar transition of 12-4-12 micelles depending on their hydrophobicity. Viscosity measurements disclose that loading of bile salts induces morphological changes in 12-4-12 micelles; sodium deoxycholate is more efficient in altering the aggregation behaviour of 12-4-12 micelles compared to sodium cholate and presents pronounced increase in viscosity and micellar growth which is suppressed at elevated temperatures. A remarkable growth of 12-4-12 micelles in the presence of sodium deoxycholate at low pH has been ascribed to the solubilization of bile acids formed in acidic medium. Small angle neutron scattering experiments provided size and shape of 12-4-12/bile salt mixed micelles are explicated on the basis of hydrophobicity of bile salts. The location of bile salts in micelle was determined from nuclear overhauser effect spectroscopy. The present study characterizes 12-4-12 gemini-bile salt mixed systems which significantly enriches our knowledge, and such a structural transition provides an opportunity to use these bioamphiphiles as delivery vehicles and in some pharmaceutical formulations.

Keywords: gemini surfactants, bile salts, SANS (small angle neutron scattering), NOESY (nuclear overhauser effect spectroscopy)

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Authors: Nitin Dwivedi, Jigna Shah

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Aim and objective of study: This article indicates a comparison among various generations of dendrimers, a dendrimer is a bioactive material has repetitively branched molecule and used for delivery of various therapeutic active agents. This debut report compares the effect various generations of PPI dendrimers for brain targeting and management of neurodegenerative disorders potential on single platform. This report involves the study of the various mechanism of synthesis ligand anchored various generations PPI dendrimers deliver the drug directly to the CNS, prove their effectiveness in the management of the various neurodegenerative disease. Material and Methods: The Memantine an anti-Alzheimer drug loaded in different generations (3.0G, 4.0G, and 5.0G) of PPI dendrimers which were synthesized were synthesized. The various studies investigate the effect of PPI dendrimers generation on different characteristic parameters i.e. synthesis procedure, drug loading, release behavior, hemolysis profile at different concentration, MRI study for determine the route drug from olfactory transfer, animal model study in vitro, as well as in vivo performance. The outcomes of the investigation indicate drug delivery benefit as well as superior biocompatibility of 4.0G PPI dendrimer over 3.0G and 5.0G dendrimer, respectively. Results and Conclusion: The above study indicate the superiority of in drug delivery system with maximum drug utilization and minimize the drug dose for neurodegenerative disorder over 5.0G PPI dendrimers. So, 4.0G PPI dendrimers are the safe formulations for the symptomatic treatment of the neurodegenerative disorder. The fifth-generation poly(propyleneimine) (PPI) dendrimers, inherent toxicity due to the presence of many peripheral cationic groups is the major issue that limits their applicability.

Keywords: Alzheimer disease, generation, memantine, PPI

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Authors: Brahim Ouzaka, Said Ouhadi

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Family businesses (FB) represent the oldest and most resilient form of organization. However, they are weakened by problems of entrepreneurial discontinuity. The objective of this paper is to analyze the problem of the succession of FBs created by senior entrepreneurs. This study analyzes and explores the constructs of senior entrepreneurship and the strategy and takeover policies of the Moroccan Family owned Small and Medium-Sized Businesses. Our main research question is formulated as follows: how does senior entrepreneurship promote the takeover of Moroccan family SMEs? So we aim through this study to analyze the challenge of the takeover of the FB created by senior entrepreneurs in order to explore and understand the specificities, choices and strategies as well as the reality of the takeover process among this category of senior entrepreneurs. After a review of the literature on the relationship between the constructs of senior entrepreneurship and the takeover of FBs, the empirical study will consist of an exploratory qualitative approach of 3 family SMEs created by senior entrepreneurs and subsequently transmitted to their descendants. This qualitative research serves to explore the choices, the strategies as well as the specificities of the entrepreneurial acts and processes of this category of entrepreneurs. The interviews were conducted with senior entrepreneurs and successors of three Moroccan family SMEs, focusing on the specificity of entrepreneurial actions and strategies in the case of SMEs launched by senior entrepreneurs and on the reality of the conduct and preparation of the takeover process, the methods of socialization and training of buyers in the context of these companies.

Keywords: senior entrepreneurship, family SME, family business, takeover

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Authors: Shadia Al-Bahlani, Khadija Al-Bulushi, Zuweina Al-Hadidi, Buthaina Al-Dhahl, Nadia Al-Abri

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Breast cancer is the most common cancer in women worldwide. Triple-Negative Breast Cancer (TNBC) is an aggressive type of breast cancer, which is defined by the absence of Estrogen (ER), Progesterone (PR) and human epidermal growth factor (Her-2) receptors. The calpain system plays an important role in many cellular processes including apoptosis, necrosis, cell signaling and proliferation. However, the role of calpain in cisplatin (CDDP)-induced apoptosis in TNBC cells is not fully understood. Here, TNBC (MDA-MB231) cells were treated with different concentration of CDDP (0, 20 & 40 µM) and calpain activation and apoptosis were measured by western blot and Hoechst Stain respectively. In addition, calpain modulation by either activation and/or inhibition and its effect on CDDP-induced apoptosis were assessed by the same above approaches. Our findings showed that CDDP induced endoplasmic reticulum stress and thus Calcium release and subsequently activate calpain α-fodrin cleavage indicated by the increase in GRP78 and Calmodulin protein expression and respectively in MDA-MB231 cells. It also induced apoptosis as measured by Hoechst stain and caspase-12 cleavage. Calpain activation by both Cyclopiazonic acid and Thapsigargin showed similar effect and enhanced the sensitivity of these cells to CDDP treatment. On the other hand, calpain inhibition by either specific siRNA and/or exogenous inhibitor (Calpeptin) had an adverse effect where it attenuated calpain activation and thus CDDP- induced apoptosis in these cells. Altogether, these findings suggested that calpain activation play an essential role in sensitizing the TNBC cells to CDDP-induced apoptosis. This might lead to the discovery of novel treatment to over this aggressive type of breast cancer.

Keywords: calpain, cisplatin, apoptosis, breast cancer

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Authors: Akbar Rostamabadi, Adel Mazloumi, Abbas Rahimi Foroushani

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This study aimed to determine the Work Ability Index (WAI) and examine the influence of health dimensions and demographic variables on the work ability of Iranian farmers working in small farm enterprises. A cross-sectional study was conducted among 294 male farmers. The WAI and SF-36 questionnaires were used to determine work ability and health status. The effect of demographics variables on the work ability index was investigated with the independent samples t-test and one-way ANOVA. Also, multiple linear regression analysis was used to test the association between the mean WAI score and the SF-36 scales. The mean WAI score was 35.1 (SD=10.6). One-way ANOVA revealed a significant relationship between the mean WAI and age. Multiple linear regression analysis showed that work ability was more influenced by physical scales of the health dimensions, such as physical function, role-physical, and general health, whereas a lower association was found for mental scales such as mental health. The average WAI was at a moderate work ability level for the sample population of farmers in this study. Based on the WAI guidelines, improvement of work ability and identification of factors affecting it should be considered a priority in interventional programs. Given the influence of health dimensions on WAI, any intervention program for preservation and promotion work ability among the studied farmers should be based on balancing and optimizing the physical and psychosocial work environments, with a special focus on reducing physical work load.

Keywords: farmers, SF-36, Work Ability Index (WAI), Iran

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Authors: Elissavet Feloni, Ioannis Kourtis, Konstantinos Kotsifakis, Evangelos Baltas

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Water inadequacy in small dry islands scattered in the Aegean Sea (Greece) is a major problem regarding Water Resources Management (WRM), especially during the summer period due to tourism. In the present work, various WRM schemes are designed and presented. The WRM schemes take into account current infrastructure and include Rainwater Harvesting tanks and Reverse Osmosis Desalination Units. The energy requirements are covered mainly by wind turbines and/or a seawater pumped storage system. Sizing is based on the available data for population and tourism per island, after taking into account a slight increase in the population (up to 1.5% per year), and it guarantees at least 80% reliability for the energy supply and 99.9% for potable water. Evaluation of scenarios is carried out from a financial perspective, after calculating the Life Cycle Cost (LCC) of each investment for a lifespan of 30 years. The wind-powered desalination plant was found to be the most cost-effective practice, from an economic point of view. Finally, in order to estimate the Climate Change (CC) impact, six different CC scenarios were investigated. The corresponding rate of on-grid versus off-grid energy required for ensuring the targeted reliability for the zero and each climatic scenario was investigated per island. The results revealed that under CC the grid-on energy required would increase and as a result, the reduction in wind turbines and seawater pumped storage systems’ reliability will be in the range of 4 to 44%. However, the range of this percentage change does not exceed 22% per island for all examined CC scenarios. Overall, CC is proposed to be incorporated into the design process for WRM-related projects. Acknowledgements: This research is co-financed by Greece and the European Union (European Social Fund - ESF) through the Operational Program «Human Resources Development, Education and Lifelong Learning 2014-2020» in the context of the project “Development of a combined rain harvesting and renewable energy-based system for covering domestic and agricultural water requirements in small dry Greek Islands” (MIS 5004775).

Keywords: small dry islands, water resources management, climate change, desalination, RES, seawater pumped storage system, rainwater harvesting

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Authors: Lene Granzau Juel-Jacobsen

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The problem of beautification is an obvious concern of photography, claiming reference to reality, but it also lies at the very heart of social theory. As we become accustomed to sophisticated visualizations of statistical data in pace with the development of software programs, we should not only be inclined to ask new types of research questions, but we also need to confront social theories based on such visualization techniques with new types of questions. Correspondence Analysis, GIS analysis, Social Network Analysis, and Perceptual Maps are current examples of visualization techniques popular within the social sciences and neighboring disciplines. This article discusses correspondence analysis, arguing that the graphic plot of correspondence analysis is to be interpreted much similarly to a photograph. It refers no more evidently or univocally to reality than a photograph, representing social life no more truthfully than a photograph documents. Pierre Bourdieu’s theoretical corpus, especially his theory of fields, relies heavily on correspondence analysis. While much attention has been directed towards critiquing the somewhat vague conceptualization of habitus, limited focus has been placed on the equally problematic concepts of social space and field. Based on a re-reading of the Distinction, the article argues that the concepts rely on ‘a small graphic lie’ very similar to a photograph. Like any other piece of art, as Bourdieu himself recognized, the graphic display is a politically and morally loaded representation technique. However, the correspondence analysis does not necessarily serve the purpose he intended. In fact, it tends towards the pitfalls he strove to overcome.

Keywords: datavisualization, correspondance analysis, bourdieu, Field, visual representation

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Authors: Abdul Soofi, Katherine Wolf, Egon Ranghini, Gregory Dressler

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Obesity and its associated complications, such as insulin resistance and non-alcoholic fatty liver disease, are reaching epidemic proportions. In mice, the TGF-β superfamily is implicated in the regulation of white and brown adipose tissues differentiation. The Kielin/Chordin-like Protein (KCP) is a secreted regulator of the TGF-β superfamily pathways that can inhibit both TGF-β and Activin signals while enhancing the Bone Morphogenetic protein (BMP) signaling. However, the effects of KCP on metabolism and obesity have not been studied in animal models. Thus, we examined the effects of KCP loss or gain of function in mice that were maintained on either a regular or a high fat diet. Loss of KCP sensitized mice to obesity and associated complications such as hepatic steatosis and glucose intolerance. In contrast, transgenic mice that expressed KCP in the kidney, liver and adipose tissues were resistant to developing high fat diet induced obesity and had significantly reduced white adipose tissue. KCP over-expression was able to shift the pattern of Smad signaling in vivo, to increase the levels of P-Smad1 and decrease P-Smad3, resulting in resistance to high fat diet induced hepatic steatosis and glucose intolerance. In aging mice, loss of KCP promoted liver pathology even when mice were fed a normal diet. The data demonstrate that shifting the TGF-β superfamily signaling with a secreted inhibitor or enhancer can alter the physiology of adipose tissue to reduce obesity and can inhibit the initiation and progression of hepatic steatosis to significantly reduce the effects of high fat diet induced metabolic disease.

Keywords: adipose tissue, KCP, obesity, TGF-β, BMP, hepatic steatosis, metabolic syndrome

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Authors: Young Ik Suh, Taewook Chung, Glaucio Scremin, Tywan Martin

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In May of 2016, the Philadelphia 76ers announced that StubHub, the ticket resale company, will have advertising on the team’s jerseys beginning in the 2017-18 season. The 76ers and National Basketball Association (NBA) became the first team and league which embraced jersey sponsorships in the four major U.S. professional sports. Even though many professional teams and leagues in Europe, Asia, Africa, and South America have adopted jersey sponsorship actively, this phenomenon is relatively new in America. While the jersey sponsorship provides economic gains for the professional leagues and franchises, sport fans can have different points of view for the phenomenon of jersey sponsorship. For instance, since many sport fans in U.S. are not familiar with ads on jerseys, this movement can possibly cause negative reaction such as the decrease in ticket and merchandise sales. They also concern the small size of ads on jersey become bigger ads, like in the English Premier League (EPL). However, some sport fans seem they do not mind too much about jersey sponsorship because the ads on jersey will not affect their loyalty and fanship. Therefore, the assumption of this study was that the sport fans’ reaction about jersey sponsorship can be possibly different, especially based on different levels of the sport fans’ team identification and various sizes of ads on jersey. Unlike general sponsorship in sport industry, jersey sponsorship has received little attention regarding its potential impact on sport fans attitudes and buying intentions. Thus, the current study sought to identify how the various levels of team identification influence brand attitude and buying intention in terms of jersey sponsorship. In particular, this study examined the effect of team identification on brand attitude and buying intention when there are no ads, small size ads, and large size ads on jersey. 3 (large, small, and no ads) X 3 (Team Identification: high, moderate, low) between subject factorial design was conducted on attitude toward the brand and buying intention of jersey sponsorship. The ads on Philadelphia 76ers jersey were used. The sample of this study was selected from message board users provided by different sports websites (i.e., forums.realgm.com and phillysportscentral.com). A total of 275 respondents participated in this study by responding to an online survey questionnaire. The results showed that there were significant differences between fans with high identification and fans with low identification. The findings of this study are expected to have many theoretical and practical contributions and implications by extending the research and literature pertaining to the relationship between team identification and brand strategy based upon different levels of team identification.

Keywords: brand attitude, buying intention, Jersey sponsorship, team identification

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Authors: Timothy Antoniuk

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This paper will demonstrate why the most successful and livable cities in the future will require multi-disciplinary designers to develop a deep understanding of peoples’ changing lifestyles, and why new generations of deeply integrated products, services and experiences need to be created. Disseminating research from the UNEP Creative Economy Reports and through a variety of other consumption and economic-based statistics, a compelling argument will be made that it is peoples’ living spaces that offer the easiest and most significant affordances for inducing positive changes to their wellbeing, and to a city’s economic and environmental prosperity. This idea, that leveraging happiness, wellbeing and prosperity through creating new concepts and typologies of ‘home’, puts people and their needs, wants, desires, aspirations and lifestyles at the beginning of the design process, not at the end, as so often occurs with current-day multi-unit housing construction. As an important part of the creative-reflective and statistical comparisons that are necessary for this on-going body of research and practice, Professor Antoniuk created the Micro Habitation Lab (mHabLab) in 2016. By focusing on testing the functional and economic feasibility of activating small spaces with different types of architectural robotics, a variety of movable, expandable and interactive objects have been hybridized and integrated into the architectural structure of the Lab. Allowing the team to test new ideas continually and accumulate thousands of points of feedback from everyday consumers, a series of on-going open houses is allowing the public-at-large to see, physically engage with, and give feedback on the items they find most and least valuable. This iterative approach of testing has exposed two key findings: Firstly, that there is a clear opportunity to improve the macro and micro functionality of small living spaces; and secondly, that allowing people to physically alter smaller elements of their living space lessens feelings of frustration and enhances feelings of pride and a deeper perception of “home”. Equally interesting to these findings is a grouping of new research questions that are being exposed which relate to: The duality of space; how people can be in two living spaces at one time; and how small living spaces is moving the Extended Home into the public realm.

Keywords: architectural robotics, extended home, interactivity, micro living spaces

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Authors: Ömer Tamer, Davut Avcı, Yusuf Atalay

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Novel picolinate complex of manganese(II) ion, [Mn(pic)2] [pic: picolinate or 2-pyridinecarboxylate], was prepared and fully characterized by single crystal X-ray structure determination. The manganese(II) complex was characterized by FT-IR, FT-Raman and UV–Vis spectroscopic techniques. The C=O, C=N and C=C stretching vibrations were found to be strong and simultaneously active in IR and spectra. In order to support these experimental techniques, density functional theory (DFT) calculations were performed at Gaussian 09W. Although the supramolecular interactions have some influences on the molecular geometry in solid state phase, the calculated data show that the predicted geometries can reproduce the structural parameters. The molecular modeling and calculations of IR, Raman and UV-vis spectra were performed by using DFT levels. Nonlinear optical (NLO) properties of synthesized complex were evaluated by the determining of dipole moment (µ), polarizability (α) and hyperpolarizability (β). Obtained results demonstrated that the manganese(II) complex is a good candidate for NLO material. Stability of the molecule arising from hyperconjugative interactions and charge delocalization was analyzed using natural bond orbital (NBO) analysis. The highest occupied and the lowest unoccupied molecular orbitals (HOMO and LUMO) which is also known the frontier molecular orbitals were simulated, and obtained energy gap confirmed that charge transfer occurs within manganese(II) complex. Molecular electrostatic potential (MEP) for synthesized manganese(II) complex displays the electrophilic and nucleophilic regions. From MEP, the the most negative region is located over carboxyl O atoms while positive region is located over H atoms.

Keywords: DFT, picolinate, IR, Raman, nonlinear optic

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Authors: Tzu-Hao Li, Shie-Liang Hsieh, Han-Chieh Lin, Ying-Ying Yang

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TNF superfamily-stimulated pathogenic cascades and macrophage (M1)/kupffer cells (KC) polarization are important in the pathogenesis of ischemia-reperfusion (IR) liver injury in animals with hepatic steatosis (HS). Decoy receptor 3 (DcR3) is a common upstream inhibitor of the above-mentioned pathogenic cascades. The study evaluated whether modulation of these DcR3-related cascades was able to protect steatotic liver from IR injury. Serum and hepatic DcR3 levels were lower in patients and animals with HS. Accordingly, the effects of pharmacologic and genetic DcR3 replacement on the IR-related pathogenic changes were measured. Significantly, DcR3 replacement protected IR-Zucker(HS) rats and IR-DcR3-Tg(HS) mice from IR liver injury. The beneficial effects of DcR3 replacement were accompanied by decreased serum/hepatic TNF, soluble TNF-like cytokine 1A (TL1A), Fas ligand (Fas-L) and LIGHT, T-helper-cell-1 cytokine (INF) levels, neutrophil infiltration, M1 polarization, neutrophil-macrophage/KC-T-cell interaction, hepatocyte apoptosis and improved hepatic microcirculatory failure among animals with IR-injured steatotic livers. Additionally, TL1A, Fas-L, LIGHT and TLR4/NFB signals were found to mediate the DcR3-related protective effects of steatotic livers from IR injury. Using multimodal in vivo and in vitro approaches, we found that DcR3 was a potential agent to protect steatotic livers from IR injury by simultaneous blocking the multiple IR injury-related pathogenic changes.

Keywords: Decoy 3 receptor, ischemia-reperfusion injury, M1 polarization, TNF superfamily

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Authors: Anna Drzewicz, Marzena Tykarska

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The chiral liquid crystal phases form the helicoidal structure, which is characterized by the helical pitch and the helical twist sense. In anticlinic smectic phase with antiferroelectric properties three types of helix temperature dependence have been obtained: increased helical pitch with temperature and right-handed helix, decreased helical pitch with temperature and left-handed helix and the inversion of both. The change of helical twist sense may be observed during the transition from one liquid crystal phase to another or within one phase for the same substance. According to Gray and McDonnell theory, the helical handedness depends on the absolute configuration of the assymetric carbon atom and its position related to the rigid core of the molecule. However, this theory does not explain the inversion of helical twist sense phenomenon. It is supposed, that it may be caused by the presence of different conformers with opposite handendess, which concentration may change with temperature. In this work, the inversion of helical twist sense in the chiral liquid crystals differing in the length of alkyl chain, in the substitution the benzene ring by fluorine atoms and in the type of helix handedness was tested by vibrational spectroscopy (infrared and raman spectroscopy) and by nuclear magnetic resonance spectroscopy. The results obtained from the vibrational spectroscopy confirm the presence of different conformers. Moreover, the analysis of nuclear magnetic resonance spectra is very useful to check, on which structural fragments the change of conformations are important for the change of helical twist sense.

Keywords: helical twist sense, liquid crystals, nuclear magnetic resonance spectroscopy, vibrational spectroscopy

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Authors: Christolyn Raj, Lewis Levitz

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Introduction: Two cases of late presentation ( > five years ) of bilateral pseudophakic macula edema related to oral tyrosine kinase inhibitors are described. These cases are the first of their type in the published literature. A review of ocular inflammatory complications of tyrosine kinase inhibitors in the current literature is explored. Case Presentations(s): Case 1 is an 83-year-old female who has been stable on Ibrutinib (Imbruvica ®) for chronic lymphocytic leukemia (CLL). She presented with bilateral blurred vision from severe cystoid macula edema seven years following routine cataract surgery. She was treated with intravitreal steroids with complete resolution without relapse. Case 2 is a 76-year-old female who was on therapy for polycythemia vera with Ruxolitinib (Jakafi®). She presented with bilateral blurred vision from mild cystoid macula edema six years following routine cataract surgery. She responded well to topical steroids without relapse. In both cases, oral tyrosine kinase inhibitor agents were presumed to be the underlying cause and were ceased. Over the last five years, there have been increasing reports in the literature of the inflammatory effects of tyrosine kinase inhibitors on the retina, uvea and optic nerve. Conclusion: Late presentation of pseudophakic macula edema following routine cataract surgery is rare. Such presentations should prompt investigation of the chronic use of systemic medications, especially oral kinase inhibitors. Patients who must remain on these agents require ongoing ophthalmologic assessment in view of their long-term inflammatory side effects.

Keywords: macula edema, oral kinase inhibitors, retinal toxicity, pseudo-phakia

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Authors: Kadiri Kayode Ibrahim

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Small and Medium Enterprises (SMEs) play significant roles in the economic development of Nigeria. However, the performance of these SMEs is influenced by various factors, including cultural factors. Keffi Local Government Area (LGA) in Nasarawa State, Nigeria, has a large number of registered SMEs. Understanding the impact of cultural factors on the performance of these SMEs in Keffi LGA is essential for their growth and sustainability. Therefore, this study aims to investigate the effect of cultural factors on the performance of selected SMEs in Keffi LGA, Nasarawa State. A cross-sectional survey research design was used to collect data from 165 purposefully selected SME owners out of the 283 registered SMEs in Keffi LGA. The data was collected using a questionnaire divided into three sections, and analysed using descriptive and ordinary least square regression (OLS). The results indicate that socio-cultural factors and ethical values have a positive and significant effect on the performance of SMEs in Keffi LGA, while attitude has a negative and significant effect on the performance of SMEs in Keffi LGA. Therefore, the study recommends that SMEs in Keffi LGA should understand the socio-cultural elements of their operating environment, adopt socio-cultural factors as elements to guide their planning and strategizing and take into consideration the ethical values of the business environment when offering new products or services. Additionally, SME Managers should take cognisance of people’s attitudes and use them to gauge their activities and ensure they support the overall performance of the business.

Keywords: cultural, factors, performance, SMEs

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Authors: N. K. Thakur

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A major proportion of the formations drilled for the production of hydrocarbons consists of clay containing shales. The petroleum industry has hugely investigated the role of clay minerals and their subsequent effect on wellbore stability during the drilling and production of hydrocarbons. It has been found that when the shale formation comes in contact with water-based drilling fluid, the interaction of clay minerals like montmorillonite with infiltrated water leads to hydration of the clay minerals, which causes shale swelling. When shale swelling proceeds further, it may lead to major drilling complications like caving, pipe sticking, which invariably influences wellbore stability, wellbore diameter, the mechanical strength of shale, stress distribution in the wellbore, etc. These problems ultimately lead to an increase in nonproductive time and additional costs during drilling. Several additives are used to prevent shale instability. Among the popular additives used for shale inhibition in drilling muds, ionic liquids and nanoparticles are emerging to be the best additives. The efficiency of the proposed additives will be studied and compared with conventional clay inhibitors like KCl. The main objective is to develop a highly efficient water-based mud for mitigating shale instability and reducing fluid loss which is environmentally friendly and does not alter the formation permeability. The use of nanoparticles has been exploited to enhance the rheological and fluid loss properties in water-based drilling fluid ionic liquid have attracted significant research interest due to its unique thermal stability. It is referred to as ‘green chemical’. The preliminary experimental studies performed are promising. The application of more effective mud additives is always desirable to make the drilling process techno-economically proficient.

Keywords: ionic liquid, shale inhibitor, wellbore stability, unconventional

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Authors: Kun Chen, Yan Wang, Yangyu Zhao, Shufang Li, Lian Chen, Xiaoyue Guo, Jue Zhang, Jing Fang

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The coupling strength between uterine electromyography (UEMG) and Fetal heart rate (FHR) signals during peripartum reflects the fetal biophysical activities. Therefore, UEMG-FHR coupling characterization is instructive in assessing placenta function. This study introduced a physiological marker named elevated frequency of UEMG-FHR coupling (E-UFC) and explored its predictive value for pregnancies complicated by pre-eclampsia and small for gestational age (SGA). Placental insufficiency patients (n=12) and healthy volunteers (n=24) were recruited and participated. UEMG and FHR were recorded non-invasively by a trans-abdominal device in women at term with singleton pregnancy (32-37 weeks) from 10:00 pm to 8:00 am. The product of the wavelet coherence and the wavelet cross-spectral power between UEMG and FHR was used to weight these two effects in order to quantify the degree of the UEMG-FHR coupling. E-UFC was exacted from the resultant spectrogram by calculating the mean value of the high-coherence (r > 0.5) frequency band. Results showed the high-coherence between UEMG and FHR was observed in the frequency band (1/512-1/16Hz). In addition, E-UFC in placental insufficiency patients was weaker compared to healthy controls (p < 0.001) at group level. These findings suggested the proposed approach could be used to quantitatively characterize the fetal biophysical activities, which is beneficial for early detection of placental insufficiency and reduces the occurrence of adverse pregnancy.

Keywords: uterine electromyography, fetal heart rate, coupling analysis, wavelet analysis

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Authors: Irfan Ahmad, Raza Ghafoor, Hammad Raza Ahmad, Muhammad Asif, Farrakh Nawaz, M. Tahir Siddiqui

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Due to the exploding population of Pakistan the pressure on natural forests is increasing to meet the demands of wood and wood based products. Agroforestry is being practiced throughout the world on scientific basis but unfortunately the farmers of Pakistan are reluctant in its adoption. The presents study was designed to assess the adoption of agroforestry practices in Faisalabad with respect to land holdings of farmers and future suitability by using Geographic information system (GIS). Faisalabad is the third largest city of the country and is famous due to the textile industry. A comprehensive survey from target villages of the Lyallpur town of Faisalabad district was carried out. Out of total 65 villages, 40 were selected for study. From each selected village, one farmer who was actively engaged in farming activities was selected. It was observed that medium sized farmers having 10-20 acre were more in number as compared to small and large farmers. Number of trees was found maximum in large farm lands, ratio of diseased trees was almost similar in all categories with maximum in small farmlands (24.1%). Regarding the future prospects 35% farmer were interested in agroforestry practices 65% were not interested in the promotion of trees due to the non-availability of technical guidance and proper markets. Geographic images of the study site can further help the researchers and policy makers in the promotion of agroforestry.

Keywords: agroforestry trends, adoption, Faisalabad, geographic information system (GIS)

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