Search results for: mechanism/s of action

Authors: Felice Elefant, Akanksha Bhatnaghar, Keegan Krick, Elizabeth Heller

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Context: The severity of Alzheimer’s Disease (AD) progression involves an interplay of genetics, age, and environmental factors orchestrated by histone acetyltransferase (HAT) mediated neuroepigenetic mechanisms. While disruption of Tip60 HAT action in neural gene control is implicated in AD, alternative mechanisms underlying Tip60 function remain unexplored. Altered RNA splicing has recently been highlighted as a widespread hallmark in the AD transcriptome that is implicated in the disease. Research Aim: The aim of this study was to identify a novel RNA binding/splicing function for Tip60 in human hippocampus and impaired in brains from AD fly models and AD patients. Methodology/Analysis: The authors used RNA immunoprecipitation using RNA isolated from 200 pooled wild type Drosophila brains for each of the 3 biological replicates. To identify Tip60’s RNA targets, they performed genome sequencing (DNB-SequencingTM technology, BGI genomics) on 3 replicates for Input RNA and RNA IPs by Tip60. Findings: The authors' transcriptomic analysis of RNA bound to Tip60 by Tip60-RNA immunoprecipitation (RIP) revealed Tip60 RNA targets enriched for critical neuronal processes implicated in AD. Remarkably, 79% of Tip60’s RNA targets overlap with its chromatin gene targets, supporting a model by which Tip60 orchestrates bi-level transcriptional regulation at both the chromatin and RNA level, a function unprecedented for any HAT to date. Since RNA splicing occurs co-transcriptionally and splicing defects are implicated in AD, the authors investigated whether Tip60-RNA targeting modulates splicing decisions and if this function is altered in AD. Replicate multivariate analysis of transcript splicing (rMATS) analysis of RNA-Seq data sets from wild-type and AD fly brains revealed a multitude of mammalian-like AS defects. Strikingly, over half of these altered RNAs were bonafide Tip60-RNA targets enriched for in the AD-gene curated database, with some AS alterations prevented against by increasing Tip60 in fly brain. Importantly, human orthologs of several Tip60-modulated spliced genes in Drosophila are well characterized aberrantly spliced genes in human AD brains, implicating disruption of Tip60’s splicing function in AD pathogenesis. Theoretical Importance: The authors' findings support a novel RNA interaction and splicing regulatory function for Tip60 that may underlie AS impairments that hallmark AD etiology. Data Collection: The authors collected data from RNA immunoprecipitation experiments using RNA isolated from 200 pooled wild type Drosophila brains for each of the 3 biological replicates. They also performed genome sequencing (DNBSequencingTM technology, BGI genomics) on 3 replicates for Input RNA and RNA IPs by Tip60. Questions: The question addressed by this study was whether Tip60 has a novel RNA binding/splicing function in human hippocampus and whether this function is impaired in brains from AD fly models and AD patients. Conclusions: The authors' findings support a novel RNA interaction and splicing regulatory function for Tip60 that may underlie AS impairments that hallmark AD etiology.

Keywords: Alzheimer's disease, cognition, aging, neuroepigenetics

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Authors: Brad Stappenbelt

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The phenomenon of vortex-induced vibration (VIV) for elastically restrained cylindrical structures in cross-flows is relatively well investigated. The utility of this mechanism in harvesting energy from marine current and tidal flows is however arguably still in its infancy. With relatively few moving components, a flow-induced vibration-based energy conversion device augers low complexity compared to the commonly employed turbine design. Despite the interest in this concept, a practical device has yet to emerge. It is desirable for optimal system performance to design for a very low mass or mass moment of inertia ratio. The device operating range, in particular, is maximized below the vortex-induced vibration critical point where an infinite resonant response region is realized. An unfortunate consequence of this requirement is large buoyancy forces that need to be mitigated by gravity-based, suction-caisson or anchor mooring systems. The focus of this paper is the testing of a novel VIV marine current energy harvesting configuration that utilizes a symmetrical and balanced pair of horizontal pivoted cylinders. The results of several years of experimental investigation, utilizing the University of Wollongong fluid mechanics laboratory towing tank, are analyzed and presented. A reduced velocity test range of 0 to 60 was covered across a large array of device configurations. In particular, power take-off damping ratios spanning from 0.044 to critical damping were examined in order to determine the optimal conditions and hence the maximum device energy conversion efficiency. The experiments conducted revealed acceptable energy conversion efficiencies of around 16% and desirable low flow-speed operating ranges when compared to traditional turbine technology. The potentially out-of-phase spanwise VIV cells on each arm of the device synchronized naturally as no decrease in amplitude response and comparable energy conversion efficiencies to the single cylinder arrangement were observed. In addition to the spatial design benefits related to the horizontal device orientation, the main advantage demonstrated by the current symmetrical horizontal configuration is to allow large velocity range resonant response conditions without the excessive buoyancy. The novel configuration proposed shows clear promise in overcoming many of the practical implementation issues related to flow-induced vibration marine current energy harvesting.

Keywords: flow-induced vibration, vortex-induced vibration, energy harvesting, tidal energy

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Authors: Ronald Croce, Timothy Quinn, John Miller

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Incomplete activation, or activation failure, of motor units during maximal voluntary contractions is often referred to as muscle inhibition (MI), and is defined as the inability of the central nervous system to maximally drive a muscle during a voluntary contraction. The purpose of the present study was to assess the interrelationship amongst peak torque (PT), muscle inhibition (MI; incomplete activation of motor units), and voluntary muscle activation (VMA) of the quadriceps’ muscle group as a function of knee angle and muscle length during maximal voluntary isometric contractions (MVICs). Nine young adult males (mean + standard deviation: age: 21.58 + 1.30 years; height: 180.07 + 4.99 cm; weight: 89.07 + 7.55 kg) performed MVICs in random order with the knee at 15, 55, and 95° flexion. MI was assessed using the interpolated twitch technique and was estimated by the amount of additional knee extensor PT evoked by the superimposed twitch during MVICs. Voluntary muscle activation was estimated by root mean square amplitude electromyography (EMGrms) and mechanomyography (MMGrms) of agonist (vastus medialis [VM], vastus lateralis [VL], and rectus femoris [RF]) and antagonist (biceps femoris ([BF]) muscles during MVICs. Data were analyzed using separate repeated measures analysis of variance. Results revealed a strong dependency of quadriceps’ PT (p < 0.001), MI (p < 0.001) and MA (p < 0.01) on knee joint position: PT was smallest at the most shortened muscle position (15°) and greatest at mid-position (55°); MI and MA were smallest at the most shortened muscle position (15°) and greatest at the most lengthened position (95°), with the RF showing the greatest change in MA. It is hypothesized that the ability to more fully activate the quadriceps at short compared to longer muscle lengths (96% contracted at 15°; 91% at 55°; 90% at 95°) might partly compensate for the unfavorable force-length mechanics at the more extended position and consequent declines in VMA (decreases in EMGrms and MMGrms muscle amplitude during MVICs) and force production (PT = 111-Nm at 15°, 217-NM at 55°, 199-Nm at 95°). Biceps femoris EMG and MMG data showed no statistical differences (p = 0.11 and 0.12, respectively) at joint angles tested, although there were greater values at the extended position. Increased BF muscle amplitude at this position could be a mechanism by which anterior shear and tibial rotation induced by high quadriceps’ activity are countered. Measuring and understanding the degree to which one sees MI and VMA in the QF muscle has particular clinical relevance because different knee-joint disorders, such ligament injuries or osteoarthritis, increase levels of MI observed and markedly reduced the capability of full VMA.

Keywords: electromyography, interpolated twitch technique, mechanomyography, muscle activation, muscle inhibition

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Authors: Shraddha Rane, Richard Warren, Stephen Eyre

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L-23 is a pro-inflammatory molecule that signals T cells to release cytokines such as IL-17A and IL-22. Psoriasis is driven by a dysregulated immune response, within which IL-23 is now thought to play a key role. Genome-wide association studies (GWAS) have identified a number of genetic risk loci that support the involvement of IL-23 signalling in psoriasis; in particular a robust susceptibility locus at a gene encoding a subunit of the IL-23 receptor (IL23R) (Stuart et al., 2015; Tsoi et al., 2012). The lead psoriasis-associated SNP rs9988642 is located approximately 500 bp downstream of IL23R but is in tight linkage disequilibrium (LD) with a missense SNP rs11209026 (R381Q) within IL23R (r2 = 0.85). The minor (G) allele of rs11209026 is present in approximately 7% of the population and is protective for psoriasis and several other autoimmune diseases including IBD, ankylosing spondylitis, RA and asthma. The psoriasis-associated missense SNP R381Q causes an arginine to glutamine substitution in a region of the IL23R protein between the transmembrane domain and the putative JAK2 binding site in the cytoplasmic portion. This substitution is expected to affect the receptor’s surface localisation or signalling ability, rather than IL23R expression. Recent studies have also identified a psoriatic arthritis (PsA)-specific signal at IL23R; thought to be independent from the psoriasis association (Bowes et al., 2015; Budu-Aggrey et al., 2016). The lead PsA-associated SNP rs12044149 is intronic to IL23R and is in LD with likely causal SNPs intersecting promoter and enhancer marks in memory CD8+ T cells (Budu-Aggrey et al., 2016). It is therefore likely that the PsA-specific SNPs affect IL23R function via a different mechanism compared with the psoriasis-specific SNPs. It could be hypothesised that the risk allele for PsA located within the IL23R promoter causes an increase IL23R expression, relative to the protective allele. An increased expression of IL23R might then lead to an exaggerated immune response. The independent genetic signals identified for psoriasis and PsA in this locus indicate that different mechanisms underlie these two conditions; although likely both affecting the function of IL23R. It is very important to further characterise these mechanisms in order to better understand how the IL-23 receptor and its downstream signalling is affected in both diseases. This will help to determine how psoriasis and PsA patients might differentially respond to therapies, particularly IL-23 biologics. To investigate this further we have developed an in vitro model using CD4 T cells which express either wild type IL23R and IL12Rβ1 or mutant IL23R (R381Q) and IL12Rβ1. Model expressing different isotypes of IL23R is also underway to investigate the effects on IL23R expression. We propose to further investigate the variants for Ps and PsA and characterise key intracellular processes related to the variants.

Keywords: IL23R, psoriasis, psoriatic arthritis, SNP

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Authors: Ghiwa Dandach

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By challenging the anti-failure bias and contributing to the theoretical territory of the attribution theory, this thesis develops a comprehensive process for entrepreneurial learning from failure. The practical implication of the findings suggests assisting entrepreneurs (current, failing, and nascent) in effectively anticipating and reflecting upon failure. Additionally, the process is suggested to enhance the level of institutional and private (accelerators and financers) support provided to entrepreneurs, the implications of which may improve future opportunities for entrepreneurial success. Henceforth, exploring learning from failure is argued to impact the potential survival of future ventures, subsequently revitalizing the economic contribution of entrepreneurship. This learning process can be enhanced with the cognitive development of causal ascriptions for failure, which eventually impacts learning outcomes. However, the mechanism with which entrepreneurs make sense of failure, reflect on the journey, and transform experience into knowledge is still under-researched. More specifically, the cognitive process of failure attribution is under-explored, majorly in the context of developing economies, calling for a more insightful understanding on how entrepreneurs ascribe failure. Responding to the call for more thorough research in such cultural contexts, this study expands the understanding of the dimensions of failure attributions as perceived by entrepreneurs and the impact of these dimensions on learning outcomes in the Lebanese context. The research adopted the exploratory interpretivism paradigm and collected data from interviews with industry experts first, followed by narratives of entrepreneurs using the qualitative multimethod approach. The holistic and categorical content analysis of narratives, preceded by the thematic analysis of interviews, unveiled how entrepreneurs ascribe failure by developing minor and major dimensions of each failure attribution. The findings have also revealed how each dimension impacts the learning from failure when accompanied by emotional resilience. The thesis concludes that exploring in-depth the dimensions of failure attributions significantly determines the level of learning generated. They are moving beyond the simple categorisation of ascriptions as primary internal or external unveiled how learning may occur with each attribution at the individual, venture, and ecosystem levels. This has further accentuated that a major internal attribution of failure combined with a minor external attribution generated the highest levels of transformative and double-loop learning, emphasizing the role of personal blame and responsibility on enhancing learning outcomes.

Keywords: attribution, entrepreneurship, reflection, sense-making, emotions, learning outcomes, failure, exit

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Authors: Valeria Velasco, Ana M. Bonilla, José L. Vergara, Alcides Lofa, Jorge Campos, Pedro Rojas-García

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Staphylococcus aureus is both commensal bacterium and opportunistic pathogen that can cause different diseases in humans and can rapidly develop antimicrobial resistance. Since this bacterium has the ability to colonize the nares and skin of humans and animals, there is a risk of contamination of food in different steps of the food chain supply. Emerging strains have been detected in food-producing animals and meat, such as methicillin-resistant S. aureus (MRSA). The aim of this study was to determine the prevalence and oxacillin susceptibility of S. aureus in the pork chain supply in Chile and to suggest some natural antimicrobials for control. A total of 487 samples were collected from pigs (n=332), carcasses (n=85), and retail pork meat (n=70). Presumptive S. aureus colonies were isolated by selective enrichment and culture media. The confirmation was carried out by biochemical testing (Api® Staph) and molecular technique PCR (detection of nuc and mecA genes, associated with S. aureus and methicillin resistance, respectively). The oxacillin (β-lactam antibiotic that replaced methicillin) susceptibility was assessed by minimum inhibitory concentration (MIC) using the Epsilometer test (Etest). A preliminary assay was carried out to test thymol, carvacrol, oregano essential oil (Origanum vulgare L.), Maqui or Chilean wineberry extract (Aristotelia chilensis (Mol.) Stuntz) as anti-staphylococcal agents using the disc diffusion method at different concentrations. The overall prevalence of S. aureus in the pork chain supply reached 33.9%. A higher prevalence of S. aureus was determined in carcasses (56.5%) than in pigs (28.3%) and pork meat (32.9%) (P ≤ 0.05). The prevalence of S. aureus in pigs sampled at farms (40.6%) was higher than in pigs sampled at slaughterhouses (23.3%) (P ≤ 0.05). The contamination of no packaged meat with S. aureus (43.1%) was higher than in packaged meat (5.3%) (P ≤ 0.05). The mecA gene was not detected in S. aureus strains isolated in this study. Two S. aureus strains exhibited oxacillin resistance (MIC ≥ 4µg/mL). Anti-staphylococcal activity was detected in solutions of thymol, carvacrol, and oregano essential oil at all concentrations tested. No anti-staphylococcal activity was detected in Maqui extract. Finally, S. aureus is present in the pork chain supply in Chile. Although the mecA gene was not detected, oxacillin resistance was found in S. aureus and could be attributed to another resistance mechanism. Thymol, carvacrol, and oregano essential oil could be used as anti-staphylococcal agents at low concentrations. Research project Fondecyt No. 11140379.

Keywords: antimicrobials, mecA gen, nuc gen, oxacillin susceptibility, pork meat

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Authors: Izzati Nabiyla Risfa

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The role of civil society has become an important issue in national and international level nowadays. Government all over the world started to realize that the involvement of civil society can boost up public services and better policy making. Global Policy Forum stated that there are five good reasons for civil society to be engaged in global governance; (1) to conferring legitimacy on policy decisions; (2) to increasing the pool of policy ideas; (3) to support less powerful governments; (4) countering a lack of political will; and (5) helping states to put nationalism aside. Indonesia also keeps up with this good trend. In November 2011, Indonesian Government set up LAPOR! (means “to report” in Indonesian), an online portal for complaints about public services, which is accessible through its website lapor.ukp.go.id. LAPOR! also accessible through social media (Twitter, Facebook) and text message. This program is an initiative from the government to provide an integrated and accessible portal for the Indonesian public to submit complaints and inquiries as a means of enhancing public participation in national development programs. LAPOR! aims to catalyze public participation as well as to have a more coordinated national complaint handling mechanism. The goal of this program is to increase the role of civil society in order to develop better public services. Thus, LAPOR! works in a simplest way possible. Public can submit any complaints or report their problem concerning development programs and public services simply through the website, short message services to 1708 and mobile applications for BlackBerry and Android. LAPOR! will then transfer every validated input to relevant institutions to be featured and responded on the website. LAPOR! is now integrated with 81 Ministries, 5 local government, and 44 State Owned Enterprise. Public can also give comments, likes or share them through Facebook and Twitter to have a discussion and to ensure the completeness of the reports. LAPOR! has unexpectedly contributed to various successful cases concerning public services. So far the portal has over 280,704 registered users, receiving an average of 1,000 reports every day. Government's response rate increase time to time, with 81% of complaints and inquiries have been solved or are being investigated. This paper will examine the effectiveness of LAPOR! as a tools to increase the role of civil society in order to develop better public services in Indonesia. Beside their promising story, there still are various difficulties that need to be solved. With qualitative approach as methodology for this research, writers will also explore potential improvement of LAPOR! so it can perform effectively as a leading national complaint handling system in Indonesia.

Keywords: civil society, government, Indonesia, public services

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Authors: Naod Mekonnen Anega

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The very objective of this paper was to empirically identify technology tailored determinants to the adoption and adoption intensity (extent of use) of agricultural water management technologies in Meda Welabu Woreda, Oromia regional state, Ethiopia. Meda Welabu Woreda which is one of the administrative Woredas of the Oromia regional state was selected purposively as this Woreda is one of the Woredas in the region where small scale irrigation practices and the use of agricultural water management technologies can be found among smallholders. Using the existence water management practices (use of water management technologies) and land use pattern as a criterion Genale Mekchira Kebele is selected to undergo the study. A total of 200 smallholders were selected from the Kebele using the technique developed by Krejeie and Morgan. The study employed the Logit and Tobit models to estimate and identify the economic, social, geographical, household, institutional, psychological, technological factors that determine adoption and adoption intensity of water management technologies. The study revealed that while 55 of the sampled households are adopters of agricultural water management technology the rest 140 were non adopters of the technologies. Among the adopters included in the sample 97% are using river diversion technology (traditional) with traditional canal while the rest 7% percent are using pond with treadle pump technology. The Logit estimation reveled that while adoption of river diversion is positively and significantly affected by membership to local institutions, active labor force, income, access to credit and land ownership, adoption of treadle pump technology is positively and significantly affected by family size, education level, access to credit, extension contact, income, access to market, and slope. The Logit estimation also revealed that whereas, group action requirement, distance to farm, and size of active labor force negative and significantly influenced adoption of river diversion, age and perception has negatively and significantly influenced adoption decision of treadle pump technology. On the other hand, the Tobit estimation reveled that while adoption intensity (extent of use) of agricultural water management is positively and significantly affected by education, credit, and extension contact, access to credit, access to market and income. This study revealed that technology tailored study on adoption of Agricultural water management technologies (AWMTs) should be considered to indentify and scale up best agricultural water management practices. In fact, in countries like Ethiopia, where there is difference in social, economic, cultural, environmental and agro ecological conditions even within the same Kebele technology tailored study that fit the condition of each Kebele would help to identify and scale up best practices in agricultural water management.

Keywords: water management technology, adoption, adoption intensity, smallholders, technology tailored approach

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Authors: Fatemeh Abbasi, Arne Hofemeier, Timo Betz

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Muscle growth and regeneration critically depend on satellite cells (SCs) which are muscle stem cells located between the basal lamina and myofibres. Upon damage, SCs become activated, enter the cell cycle, and give rise to myoblasts that form new myofibres, while a sub-population self-renew and re-populate the muscle stem cell niche. In aged muscle as well as in certain muscle diseases such as muscular dystrophy, some of the SCs lose their regenerative ability. Although it is demonstrated that the chemical composition of SCs quiescent niche is different from the activated niche, the mechanism initially activated in the SCs remains unknown. While extensive research efforts focused on potential chemical activation, no such factor has been identified to the author’s best knowledge. However, it is substantiated that niche mechanics affects SCs behaviors, such as stemness and engraftment. We hypothesize that mechanical stress in the healthy niche (homeostasis) is different from the regenerative niche and that this difference could serve as an early signal activating SCs upon fiber damage. To investigate this hypothesis, we develop a biomimetic system to reconstitute both, the mechanical and the chemical environment of the SC niche. Cells will be confined between two elastic polyacrylamide (PAA) hydrogels with controlled elastic moduli and functionalized surface chemistry. By controlling the distance between the PAA hydrogel surfaces, we vary the compression forces exerted by the substrates on the cells, while the lateral displacement of the upper hydrogel will create controlled shear forces. To establish such a system, a simplified system is presented. We engineered a sandwich-like configuration of two elastic PAA layer with stiffnesses between 1 and 10 kPa and confined a precursor myoblast cell line (C2C12) in between these layers. Our initial observations in this sandwich model indicate that C2C12 cells show different behaviors under mechanical compression if compared to a control one-layer gel without compression. Interestingly, this behavior is stiffness-dependent. While the shape of C2C12 cells in the sandwich consisting of two stiff (10 kPa) layers was much more elongated, showing almost a neuronal phenotype, the cell shape in a sandwich situation consisting of one stiff and one soft (1 kPa) layer was more spherical. Surprisingly, even in proliferation medium and at very low cell density, the sandwich situation stimulated cell differentiation with increased striation and myofibre formation. Such behavior is commonly found for confluent cells in differentiation medium. These results suggest that mechanical changes in stiffness and applied pressure might be a relevant stimulation for changes in muscle cell behavior.

Keywords: C2C12 cells, compression, force, satellite cells, skeletal muscle

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Authors: Ines Oliveira, Ana Reis

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Magnetic Pulse Welding (MPW) is a cold solid-state welding process, accomplished by the electromagnetically driven, high-speed and low-angle impact between two metallic surfaces. It has the same working principle of Explosive Welding (EXW), i.e. is based on the collision of two parts at high impact speed, in this case, propelled by electromagnetic force. Under proper conditions, i.e., flyer velocity and collision point angle, a permanent metallurgical bond can be achieved between widely dissimilar metals. MPW has been considered a promising alternative to the conventional welding processes and advantageous when compared to other impact processes. Nevertheless, MPW current applications are mostly academic. Despite the existing knowledge, the lack of consensus regarding several aspects of the process calls for further investigation. As a result, the mechanical resistance, morphology and structure of the weld interface in MPW of Al/Cu dissimilar pair were investigated. The effect of process parameters, namely gap, standoff distance and energy, were studied. It was shown that welding only takes place if the process parameters are within an optimal range. Additionally, the formation of intermetallic phases cannot be completely avoided in the weld of Al/Cu dissimilar pair by MPW. Depending on the process parameters, the intermetallic compounds can appear as continuous layer or small pockets. The thickness and the composition of the intermetallic layer depend on the processing parameters. Different intermetallic phases can be identified, meaning that different temperature-time regimes can occur during the process. It is also found that lower pulse energies are preferred. The relationship between energy increase and melting is possibly related to multiple sources of heating. Higher values of pulse energy are associated with higher induced currents in the part, meaning that more Joule heating will be generated. In addition, more energy means higher flyer velocity, the air existing in the gap between the parts to be welded is expelled, and this aerodynamic drag (fluid friction) is proportional to the square of the velocity, further contributing to the generation of heat. As the kinetic energy also increases with the square of velocity, the dissipation of this energy through plastic work and jet generation will also contribute to an increase in temperature. To reduce intermetallic phases, porosity, and melt pockets, pulse energy should be minimized. The bond formation is affected not only by the gap, standoff distance, and energy but also by the mandrel’s surface conditions. No correlation was clearly identified between surface roughness/scratch orientation and joint strength. Nevertheless, the aspect of the interface (thickness of the intermetallic layer, porosity, presence of macro/microcracks) is clearly affected by the surface topology. Welding was not established on oil contaminated surfaces, meaning that the jet action is not enough to completely clean the surface.

Keywords: bonding mechanisms, impact welding, intermetallic compounds, magnetic pulse welding, wave formation

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Authors: E. A. Abdel-Hakim

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The corn stemborer Sesamia cretica (Lederer), has been viewed in many parts of the world as a major pest of cultivated maize, graminaceous crops and sugarcane. Its life cycle is comprised of two different phases, one is the growth and developmental phase (non-diapause) and the other is diapause phase which takes place at the last larval instar. Several problems associated with the use of conventional insecticides, have strongly demonstrated the need for applying alternative safe compounds. Prominent among the prototypes of such prospective chemicals are the juvenoids; i.e. the insect (JH) mimics. In fact, the hormonal effect on metabolism has long been viewed as a secondary consequence of its direct action on specific energy-requiring biosynthetic mechanisms. Therefore, the present study was undertaken essentially in a rather systematic fashion as a contribution towards clarifying metabolic and energetic changes taking place during non-diapause wandering larvae as regulated by (JH) mimic. For this purpose, we applied two different doses of JH mimic (Ro 11-0111) in a single (standard) dose of 100µg or in a single dose of 20 µg/g bw in1µl acetone topically at the onset of nondiapause wandering larvae (WL). Energetic data were obtained by indirect calorimetry methods by conversion of respiratory gas exchange volumetric data, as measured manometrically using a Warburg constant respirometer, to caloric units (g-cal/g fw/h). The findings obtained can be given in brief; these treated larvae underwent supernumerary larval moults. However, this potential the wandering larvae proved to possess whereby restoration of larval programming for S. cretica to overcome stresses even at this critical developmental period. The results obtained, particularly with the high dose used, show that 98% wandering larvae were rescued to survive up to one month (vs. 5 days for normal controls), finally the formation of larval-adult intermediates. Also, the solvent controls had resulted in about 22% additional, but stationary moultings. The basal respiratory metabolism (O2 uptake and CO2 output) of the (WL), whether un-treated or larvae not had followed reciprocal U-shaped curves all along of their developmental duration. The lowest points stood nearly to the day of prepupal formation (571±187 µl O2/gfw/h and 553±181 µl CO2/gfw/h) during un-treated in contrast to the larvae treated with JH (210±48 µl O2/gfw/h and 335±81 µl CO2/gfw/h). Un-treated (normal) larvae proved to utilize carbohydrates as the principal source for energy supply; being fully oxidised without sparing any appreciable amount for endergonic conversion to fats. While, the juvenoid-treated larvae and compared with the acetone-treated control equivalents, there existed no distinguishable differences between them; both had been observed utilising carbohydrates as the sole source of energy demand and converting endergonically almost similar percentages to fats. The overall profile, treated and un-treated (WL) utilized carbohydrates as the principal source for energy demand during this stage.

Keywords: juvenile hormone, respiratory metabolism, Sesamia cretica, wandering phase

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Authors: Maria Krambia-Kapardis, Andreas Kapardis

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The paper discusses regulatory and legislative measures implemented by various nations in an effort to avert another financial crisis. More specifically, to address the financial crisis, the European Commission followed the practice of other developed countries and implemented a European Economic Recovery Plan in an attempt to overhaul the regulatory and supervisory framework of the financial sector. In 2010 the Commission introduced the European Systemic Risk Board and in 2011 the European System of Financial Supervision. Some experts advocated that the type and extent of financial regulation introduced in the European crisis in the wake of the 2008 crisis has been excessive and counterproductive. In considering how different countries responded to the financial crisis, global regulators have shown a more focused commitment to combat industry misconduct and to pre-empt abusive behavior. Regulators have also increased funding and resources at their disposal; have increased regulatory fines, with an increasing trend towards action against individuals; and, finally, have focused on market abuse and market conduct issues. Financial regulation can be effected, first of all, through legislation. However, neither ex ante or ex post regulation is by itself effective in reducing systemic risk. Consequently, to avert a financial crisis, in their endeavor to achieve both economic efficiency and financial stability, governments need to balance the two approaches to financial regulation. Fiduciary duty is another means by which the behavior of actors in the financial world is constrained and, thus, regulated. Furthermore, fiduciary duties extend over and above other existing requirements set out by statute and/or common law and cover allegations of breach of fiduciary duty, negligence or fraud. Careful analysis of the etiology of the 2008 financial crisis demonstrates the great importance of corporate governance as a way of regulating boardroom behavior. In addition, the regulation of professions including accountants and auditors plays a crucial role as far as the financial management of companies is concerned. In the US, the Sarbanes-Oxley Act of 2002 established the Public Company Accounting Oversight Board in order to protect investors from financial accounting fraud. In most countries around the world, however, accounting regulation consists of a legal framework, international standards, education, and licensure. Accounting regulation is necessary because of the information asymmetry and the conflict of interest that exists between managers and users of financial information. If a holistic approach is to be taken then one cannot ignore the regulation of legislators themselves which can take the form of hard or soft legislation. The science of averting a financial crisis is yet to be perfected and this, as shown by the preceding discussion, is unlikely to be achieved in the foreseeable future as ‘disaster myopia’ may be reduced but will not be eliminated. It is easier, of course, to be wise in hindsight and regulating unreasonably risky decisions and unethical or outright criminal behavior in the financial world remains major challenges for governments, corporations, and professions alike.

Keywords: financial crisis, legislation, regulation, financial regulation

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Authors: Etibar Guliyev, Durdana Jafarli

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The breakdown of the Soviet Union in the early 1990s and the 9/11 attacks resulted in the global changes created a totally new geopolitical situation for the Muslim populated republics of the former Soviet Union. Located between great powers such as China and Russia, as well as theocratic states like Iran and Afghanistan, the newly independent Central Asian states were facing a dilemma to choose a new politico-ideological course for development. Policies dubbed Perestroyka and Glasnost leading to the collapse of the world’s once superpower brought about a considerable rise in the national and religious self-consciousness of the Muslim population of the USSR where the religion was prohibited under the strict communist rule. Moreover, the religious movements prohibited during the Soviet era acted as a part of national straggle to gain their freedom from Moscow. The policies adopted by the Central Asian countries to manage the religious revival and extremism in their countries vary dramatically from each other. As Kazakhstan and Kyrgyzstan are located between Russia and China and hosting a considerable number of the Russian population, these countries treated Islamic revival more tolerantly trying benefit from it in the nation-building process. The importance of the topic could be explained with the fact that it investigates an alternative way of management of religious activities and movements. The recent developments in the Middle East, Syria and Iraq in particular, and the fact that hundreds of fighters from the Central Asian republics joined the ISIL terrorist organization once again highlights the implications of the proper regulation of religious activities not only for domestic, but also for regional and global politics. The paper is based on multiple research methods. The process trace method was exploited to better understand the Russification and anti-religious policies to which the Central Asian countries were subject during the Soviet era. The comparative analyse method was also used to better understand the common and distinct features of the politics of religion of Kazakhstan and Kyrgyzstan and the rest of the Central Asian countries. Various legislation acts, as well as secondary sources were investigated to this end. Mostly constructivist approach and a theory suggesting that religion supports national identity when there is a third cohesion that threatens both and when elements of national identity are weak. Preliminary findings suggest that in line with policies aimed at gradual reduction of Russian influence, as well as in the face of ever-increasing migration from China, the mentioned countries incorporated some Islamic elements into domestic policies as a part and parcel of national culture. Kazakhstan and Kyrgyzstan did not suppress religious activities, which was case in neighboring states, but allowed in a controlled way Islamic movements to have a relatively freedom of action which in turn led to the less violent religious extremism further boosting national identity.

Keywords: identity, Islam, nationalism, terrorism

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Authors: Anouar El Younssi

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This study seeks to shed some light on the political and social ramifications and implications of Haifaa al-Mansour’s 2012 film Wadjda. The film made international headlines following its release, and was touted as the first film ever to be shot in its entirety inside the Kingdom of Saudi Arabia, and also the first to be directed by a female (Haifaa al-Mansour). Wadjda revolves around a simple storyline: A teenage Saudi girl living in the capital city Riyadh—named Wadjda—wants to have a bicycle just like her male teenage neighbor and friend Abdullah, but her ultra-conservative Saudi society places so many constraints on its female population—including not allowing girls and women to ride bicycles. Wadjda, who displays a rebellious spirit, takes concrete steps to save money in order to realize her dream of buying a bicycle. For example, she starts making and selling sports bracelets to her school mates, and she decides to participate in a Qur’an competition in hopes of winning a sum of money that comes with the first prize. In the end, Wadjda could not beat the system on her own, but the film reverses course, and the audience gets a happy ending: Wadjda’s mother, whose husband has decided to take a second wife, defies the system and buys her daughter the very bicycle Wadjda has been dreaming of. It is quite significant that the mother takes her daughter’s side on the subject of the bicycle at the end of the film, for this shows that she finally came to the realization that she and her daughter are both oppressed by the cultural norms prevalent in Saudi society. It is no coincidence that this change of heart and action on the part of the mother takes place immediately after the wedding night celebrating her husband’s second marriage. Gender inequality is thus placed front and center in the film. Nevertheless, a major finding of this study is that the film carries out its social critique in a soft and almost covert manner. The female actors in the film never issue a direct criticism of Saudi society or government; the criticism is consistently implied and subtle throughout. It is a criticism that relies more on showing than telling. The film shows us—rather than tells us directly—what is wrong, and lets us, the audience, decide and make a judgment. In fact, showing could arguably be more powerful and impactful than telling. Regarding methodology, this study will focus on and analyze the visuals and a number of key utterances by the main actor Wadjda in order to corroborate the study’s argument about the film’s bent on critiquing patriarchy. This research will attempt to establish a link between the film as an art object and as a social text. Ultimately, Wadjda sends a message of hope, that change is possible and that it is already happening slowly inside the Kingdom. It also sends the message that an insurrectional approach regarding women’s rights in Saudi Arabia is perhaps not the right one, at least at this historical juncture.

Keywords: bicycle, gender inequality, social critique, Wadjda, women’s rights

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Authors: Sweta Agrawal, Sachin Chaugule, Gargi Rane, Shashank More, Madhavi Indap

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Angiogenesis and metastasis are two of the most important hallmarks of cancer. Hence, most of the cancer therapies nowadays are multi-targeted so as to reduce resistance and have better efficacy. As synthetic molecules arise with a burden of their toxicities and side-effects, more and more research is being focussed on exploiting the vast natural resources of drugs, in the form of plants and animals. Although, the idea of using marine organisms as a source of pharmaceuticals is not new, the pace at which marine drugs are being discovered, has definitely up surged! In the present study, we have assessed the anti-angiogenic and in vitro anti-metastatic activity of aqueous fraction from the extract of marine gastropod Euchelus asper. The soft body of Euchelus Asper was extracted with methanol and named EAME. Partition chromatography of EAME gave three fractions EAME I, II and III. Biochemical analysis revealed the presence of proteins in EAME III. Preliminary analysis had revealed the anti-angiogenic activity was exhibited by EAME III out of the three fractions. Hereafter, EAME III (concentration 25µg/ml-400µg/ml) was tested on chick chorioallantoic membrane (CAM) model for the detailed analysis of its potential anti-angiogenic effect. In vitro testing of the fraction (concentration 0.25µg/ml - 1µg/ml), involved cytotoxicity by SRB assay, cell cycle analysis by flow cytometry and anti-proliferative effect by scratch wound healing assay on A549 lung carcinoma cells. Apart from this, a portion of treated CAM as well as conditioned medium from treated A549 were subjected to gelatin zymography for assessment of matrix metalloproteinases MMP-2 and MMP-9 levels. Our results revealed that EAME III exhibited significant anti-angiogenic activity on CAM which was also supported by histological observations. During histological studies of CAM, it was found that EAME III caused reduction in angiogenesis by altering the extracellular matrix of the CAM membrane. In vitro analysis disclosed that EAME III exhibited moderate cytotoxic effect on A549 cells and its effect was not dose-dependent. The results of flow cytometry confirmed that EAME III caused cell cycle arrest in A549 cell line as almost all of the treated cells were found in G1 phase. Further, the migration and proliferation of A549 was significantly reduced by EAME III as observed from the scratch wound assay. Moreover, Gelatin zymography analysis revealed that EAME III caused suppression of MMP-2 in CAM membrane and reduced MMP-9 and MMP-2 expression in A549 cells. This verified that the anti-angiogenic and anti-metastatic effects of EAME III were correlated with the suppression of MMP-2 and -9. To conclude, EAME III shows dual anti-tumour action by reducing angiogenesis and exerting anti-metastatic effect on lung cancer cells, thus it has the potential to be used as an anti-cancer agent against lung carcinoma.

Keywords: angiogenesis, anti-cancer, marine drugs, matrix metalloproteinases

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Authors: Evanka Madan, Madhu Puri, Dan Zilberstein, Rohini Muthuswami, Rentala Madhubala

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The extensive interaction between the host and pathogen metabolic networks decidedly shapes the outcome of infection. Utilization of arginine by the host and pathogen is critical for determining the outcome of pathogenic infection. Infections with L. donovani, an intracellular parasite, will lead to an extensive competition of arginine between the host and the parasite donovani infection. One of the major amino acid (AA) sensing signaling pathways in mammalian cells are the mammalian target of rapamycin complex I (mTORC1) pathway. mTORC1, as a sensor of nutrient, controls numerous metabolic pathways. Arginine is critical for mTORC1 activation. SLC38A9 is the arginine sensor for the mTORC1, being activated during arginine sufficiency. L. donovani transport arginine via a high-affinity transporter (LdAAP3) that is rapidly up-regulated by arginine deficiency response (ADR) in intracellular amastigotes. This study, to author’s best knowledge, investigates the interaction between two arginine sensing systems that act in the same compartment, the lysosome. One is important for macrophage defense, and the other is essential for pathogen virulence. We hypothesize that the latter modulates lysosome arginine to prevent host defense response. The work presented here identifies an upstream regulatory role of LdAAP3 in regulating the expression of SLC38A9-mTORC1 pathway, and consequently, their function in L. donovani infected THP-1 cells cultured in 0.1 mM and 1.5 mM arginine. It was found that in physiological levels of arginine (0.1 mM), infecting THP-1 with Leishmania leads to increased levels of SLC38A9 and mTORC1 via an increase in the expression of RagA. However, the reversal was observed with LdAAP3 mutants, reflecting the positive regulatory role of LdAAP3 on the host SLC38A9. At the molecular level, upon infection, mTORC1 and RagA were found to be activated at the surface of phagolysosomes which was found to form a complex with phagolysosomal localized SLC38A9. To reveal the relevance of SLC38A9 under physiological levels of arginine, endogenous SLC38A9 was depleted and a substantial reduction in the expression of host mTORC1, its downstream active substrate, p-P70S6K1 and parasite LdAAP3, was observed, thereby showing that silencing SLC38A9 suppresses ADR. In brief, to author’s best knowledge, these results reveal an upstream regulatory role of LdAAP3 in manipulating SLC38A9 arginine sensing in host macrophages. Our study indicates that intra-macrophage survival of L. donovani depends on the availability and transport of extracellular arginine. An understanding of the sensing pathway of both parasite and host will open a new perspective on the molecular mechanism of host-parasite interaction and consequently, as a treatment for Leishmaniasis.

Keywords: arginine sensing, LdAAP3, L. donovani, mTORC1, SLC38A9, THP-1

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Authors: D. Y. Fong, C. Y. Kuo, Y. T. Chiang, W. C. Lin

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Objectives: Qigong is an ancient Chinese practice in pursuit of a healthier body and a more peaceful mindset. It emphasizes on the restoration of vital energy (Qi) in body, mind, and spirit. The practice is the combination of gentle movements and mild breathing which help the doers reach the condition of tranquility. On account of the features of Qigong, first, we use cross-sectional methodology to compare the differences among the varied levels of Qigong practitioners on cognitive function with event-related potential (ERP) and electroencephalography (EEG). Second, we use the longitudinal methodology to explore the effects on the Qigong trainees for pretest and posttest on ERP and EEG. Current study adopts Attentional Network Test (ANT) task to examine the participants’ cognitive function, and aging-related researches demonstrated a declined tread on the cognition in older adults and exercise might ameliorate the deterioration. Qigong exercise integrates physical posture (muscle strength), breathing technique (aerobic ability) and focused intention (attention) that researchers hypothesize it might improve the cognitive function in aging adults. Method: Sixty participants were involved in this study, including 20 young adults (21.65±2.41 y) with normal physical activity (YA), 20 Qigong experts (60.69 ± 12.42 y) with over 7 years Qigong practice experience (QE), and 20 normal and healthy adults (52.90±12.37 y) with no Qigong practice experience as experimental group (EG). The EG participants took Qigong classes 2 times a week and 2 hours per time for 24 weeks with the purpose of examining the effect of Qigong intervention on cognitive function. ANT tasks (alert network, orient network, and executive control) were adopted to evaluate participants’ cognitive function via ERP’s P300 components and P300 amplitude topography. Results: Behavioral data: 1.The reaction time (RT) of YA is faster than the other two groups, and EG was faster than QE in the cue and flanker conditions of ANT task. 2. The RT of posttest was faster than pretest in EG in the cue and flanker conditions. 3. No difference among the three groups on orient, alert, and execute control networks. ERP data: 1. P300 amplitude detection in QE was larger than EG at Fz electrode in orient, alert, and execute control networks. 2. P300 amplitude in EG was larger at pretest than posttest on the orient network. 3. P300 Latency revealed no difference among the three groups in the three networks. Conclusion: Taken together these findings, they provide neuro-electrical evidence that older adults involved in Qigong practice may develop a more overall compensatory mechanism and also benefit the performance of behavior.

Keywords: Qigong, cognitive function, aging, event-related potential (ERP)

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Authors: Anandkumar Rshindhe

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Patents are considered as good monopoly in India. It is a mechanism by which the inventor is encouraged to do invention and also to make available to the society at large with a new useful technology. Patent system does not provide any protection to the invention itself but to the claims (rights) which the patentee has identified in relation to his invention. Thus the patentee is granted monopoly to the extent of his recognition of his own rights in the form of utilities and all other utilities of invention are for the public. Thus we find both benefit to the inventor and the public at large that is the ultimate consumer. But developing any such technology is not free of cost. Inventors do a lot of investment in the coming out with a new technologies. One such example if of Pharmaceutical industries. These pharmaceutical Industries do lot of research and invest lot of money, time and labour in coming out with these invention. Once invention is done or process identified, in order to protect it, inventors approach Patent system to protect their rights in the form of claim over invention. The patent system takes its own time in giving recognition to the invention as patent. Even after the grant of patent the pharmaceutical companies need to comply with many other legal formalities to launch it as a drug (medicine) in market. Thus major portion in patent term is unproductive to patentee and whatever limited period the patentee gets would be not sufficient to recover the cost involved in invention and as a result price of patented product is raised very much, just to recover the cost of invent. This is ultimately a burden on consumer who is paying more only because the legislature has failed to provide for the delay and loss caused to patentee. This problem can be effectively remedied if Patent Term extension is done. Due to patent term extension, the inventor gets some more time in recovering the cost of invention. Thus the end product is much more cheaper compared to non patent term extension.The basic question here arises is that when the patent period granted to a patentee is only 20 years and out of which a major portion is spent in complying with necessary legal formalities before making the medicine available in market, does the company with the limited period of monopoly recover its investment made for doing research. Further the Indian patent Act has certain provisions making it mandatory on the part of patentee to make its patented invention at reasonable affordable price in India. In the light of above questions whether extending the term of patent would be a proper solution and a necessary requirement to protect the interest of patentee as well as the ultimate consumer. The basic objective of this paper would be to check the implications of Extending the Patent term on Indian Consumers. Whether it provides the benefits to the patentee, consumer or a hardship to the Generic industry and consumer.

Keywords: patent term extention, consumer interest, generic drug industry, pharmaceutical industries

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Authors: Gyaltsen Dakpa, K. J. Senthil Kumar, Nai-Wen Tsao, Sheng-Yang Wang

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Context: Coronavirus disease 2019 (COVID-19) is a severe respiratory illness caused by the SARS-CoV-2 virus. One of the hallmarks of COVID-19 is a change in metabolism, which can lead to increased severity and mortality. The mechanism of SARS-CoV-2-mediated perturbations of metabolic pathways has yet to be fully understood. Research Aim: This study aimed to investigate the metabolic alteration caused by SARS-CoV-2 spike protein in Phorbol 12-myristate 13-acetate (PMA)-induced human monocytes (THP-1) and to examine the regulatory effect of natural compounds like Antcins A on SARS-CoV-2 spike protein-induced metabolic alteration. Methodology: The study used a combination of proton nuclear magnetic resonance (1H-NMR) and MetaboAnalyst 5.0 software. THP-1 cells were treated with SARS-CoV-2 spike protein or control, and the metabolomic profiles of the cells were compared. Antcin A was also added to the cells to assess its regulatory effect on SARS-CoV-2 spike protein-induced metabolic alteration. Findings: The study results showed that treatment with SARS-CoV-2 spike protein significantly altered the metabolomic profiles of THP-1 cells. Eight metabolites, including glycerol-phosphocholine, glycine, canadine, sarcosine, phosphoenolpyruvic acid, glutamine, glutamate, and N, N-dimethylglycine, were significantly different between control and spike-protein treatment groups. Antcin A significantly reversed the changes in these metabolites. In addition, treatment with antacid A significantly inhibited SARS-CoV-2 spike protein-mediated up-regulation of TLR-4 and ACE2 receptors. Theoretical Importance The findings of this study suggest that SARS-CoV-2 spike protein can cause significant metabolic alterations in THP-1 cells. Antcin A, a natural compound, has the potential to reverse these metabolic alterations and may be a potential candidate for developing preventive or therapeutic agents for COVID-19. Data Collection: The data for this study was collected from THP-1 cells that were treated with SARS-CoV-2 spike protein or a control. The metabolomic profiles of the cells were then compared using 1H-NMR and MetaboAnalyst 5.0 software. Analysis Procedures: The metabolomic profiles of the THP-1 cells were analyzed using 1H-NMR and MetaboAnalyst 5.0 software. The software was used to identify and quantify the cells' metabolites and compare the control and spike-protein treatment groups. Questions Addressed: The question addressed by this study was whether SARS-CoV-2 spike protein could cause metabolic alterations in THP-1 cells and whether Antcin A can reverse these alterations. Conclusion: The findings of this study suggest that SARS-CoV-2 spike protein can cause significant metabolic alterations in THP-1 cells. Antcin A, a natural compound, has the potential to reverse these metabolic alterations and may be a potential candidate for developing preventive or therapeutic agents for COVID-19.

Keywords: SARS-CoV-2-spike, ¹H-NMR, metabolomics, antcin-A, taiwanofungus camphoratus

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Authors: Adewale O. Adegbenjo, Elsie Nsiah-Baafi, Mxolisi B. Shongwe, Mercy Ramakokovhu, Peter A. Olubambi

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The sintering step in powder metallurgy (P/M) processes is very sensitive as it determines to a large extent the properties of the final component produced. Spark plasma sintering over the past decade has been extensively used in consolidating a wide range of materials including metallic alloy powders. This novel, non-conventional sintering method has proven to be advantageous offering full densification of materials, high heating rates, low sintering temperatures, and short sintering cycles over conventional sintering methods. Ti6Al4V has been adjudged the most widely used α+β alloy due to its impressive mechanical performance in service environments, especially in the aerospace and automobile industries being a light metal alloy with the capacity for fuel efficiency needed in these industries. The P/M route has been a promising method for the fabrication of parts made from Ti6Al4V alloy due to its cost and material loss reductions and the ability to produce near net and intricate shapes. However, the use of this alloy has been largely limited owing to its relatively poor hardness and wear properties. The effect of sintering temperature on the densification, hardness, and wear behaviors of spark plasma sintered Ti6Al4V powders was investigated in this present study. Sintering of the alloy powders was performed in the 650–850°C temperature range at a constant heating rate, applied pressure and holding time of 100°C/min, 50 MPa and 5 min, respectively. Density measurements were carried out according to Archimedes’ principle and microhardness tests were performed on sectioned as-polished surfaces at a load of 100gf and dwell time of 15 s. Dry sliding wear tests were performed at varied sliding loads of 5, 15, 25 and 35 N using the ball-on-disc tribometer configuration with WC as the counterface material. Microstructural characterization of the sintered samples and wear tracks were carried out using SEM and EDX techniques. The density and hardness characteristics of sintered samples increased with increasing sintering temperature. Near full densification (99.6% of the theoretical density) and Vickers’ micro-indentation hardness of 360 HV were attained at 850°C. The coefficient of friction (COF) and wear depth improved significantly with increased sintering temperature under all the loading conditions examined, except at 25 N indicating better mechanical properties at high sintering temperatures. Worn surface analyses showed the wear mechanism was a synergy of adhesive and abrasive wears, although the former was prevalent.

Keywords: hardness, powder metallurgy, spark plasma sintering, wear

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Authors: Delphine Mukaneza, Lin Qiao, Wang Pengxin, Li Yan, Chen Yingyi

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Human activities on land use make the land-cover gradually change or transit. In this study, we examined the use of Landsat TM data to detect the land use change of Kigali between 1987 and 2009 using remote sensing techniques and analysis of data using ENVI and ArcGIS, a GIS software. Six different categories of land use were distinguished: bare soil, built up land, wetland, water, vegetation, and others. With remote sensing techniques, we analyzed land use data in 1987, 1999 and 2009, changed areas were found and a dynamic situation of land use in Kigali city was found during the 22 years studied. According to relevant Landsat data, the research focused on land use change in accordance with the role of remote sensing in the process of urbanization. The result of the work has shown the rapid increase of built up land between 1987 and 1999 and a big decrease of vegetation caused by the rebuild of the city after the 1994 genocide, while in the period of 1999 to 2009 there was a reduction in built up land and vegetation, after the authority of Kigali city established, a Master Plan where all constructions which were not in the range of the master Plan were destroyed. Rwanda's capital, Kigali City, through the expansion of the urban area, it is increasing the internal employment rate and attracts business investors and the service sector to improve their economy, which will increase the population growth and provide a better life. The overall planning of the city of Kigali considers the environment, land use, infrastructure, cultural and socio-economic factors, the economic development and population forecast, urban development, and constraints specification. To achieve the above purpose, the Government has set for the overall planning of city Kigali, different stages of the detailed description of the design, strategy and action plan that would guide Kigali planners and members of the public in the future to have more detailed regional plans and practical measures. Thus, land use change is significantly the performance of Kigali active human area, which plays an important role for the country to take certain decisions. Another area to take into account is the natural situation of Kigali city. Agriculture in the region does not occupy a dominant position, and with the population growth and socio-economic development, the construction area will gradually rise and speed up the process of urbanization. Thus, as a developing country, Rwanda's population continues to grow and there is low rate of utilization of land, where urbanization remains low. As mentioned earlier, the 1994 genocide massacres, population growth and urbanization processes, have been the factors driving the dramatic changes in land use. The focus on further research would be on analysis of Rwanda’s natural resources, social and economic factors that could be, the driving force of land use change.

Keywords: land use change, urbanization, Kigali City, Landsat

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Authors: Varsha Puri, Sharon Hudson, Ian Kim

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Background: Incest-related childhood sexual abuse (IRCSA) is challenging to study due to the shame and secrecy experienced by its survivors. Ramifications of IRCSA worsen when it is unidentified, and interventions are not made. IRCSA perspectives are essential for future prevention and intervention strategies. However, there is limited understanding of this population’s experiences, perspectives, and long-term struggles. To date, research for IRCSA has utilized data from treatment programs and qualitative research with cohorts of 10-20 people, much of the data is from 10-40 years prior. Methods. In June 2018, an anonymous online survey was posted to multiple social media sites (e.g., Facebook IRCSA groups) and sexual abuse resource sites. Survey responses were collected for a year. The survey collected non-identifying demographics, IRCSA experiences, and outcomes data. Results: We obtained 1310 completed surveys. Demographics of all ages, racial backgrounds, financial backgrounds, and genders were obtained; the majority identified as white (81%) and female (76%). Childhood sexual abuse (CSA) started before the age of 6 in 49% and was endured for more than one year in 84% of respondents, and 39% reported ten or more years of abuse. CSA by multiple perpetrators occurred in 58%, while 8% had ten or more perpetrators. CSA by perpetrators under 21 years old was reported by 46%. Female perpetrators were reported by 28% of respondents. Fathers were the highest reported sexual abusers at 60%, and mothers were reported at 17%. Only 16% reported that at least one of their perpetrators was prosecuted for sexual abuse of a minor. Respondents confirmed that 54% of the time, they informed an adult of the abuse; only 2% agreed that “an intervention was made by the family that protected me.” A majority reported that IRCSA has negatively impacted their intimate/sexual relationships (96%) and mental health (96%). A majority reported negative impacts on biological family relationships (88%), physical health (73%), finances (59%), educational achievement (57%), and employment (56%). When asked about suffering from addiction, 85% of respondents answered yes. Prevention strategies selected most by respondents include early school education around CSA prevention (67%), removing the statute of limitations for reporting CSA (69%), and improved laws protecting IRCSA survivors (63%). Conclusion: The data document that IRCSA can be pervasive, and the dearth of intervention and support for survivors have major lasting impacts. Survivors have a unique and valuable perspective on what interventions are needed to prevent IRCSA and support survivors; their voice has long been unheard in crafting prevention and intervention policies and services. These results thus provide an important call to action from these critical stakeholders. Pediatricians should recognize that perpetrators can be pediatric patients, women, and parents. Pediatricians can advocate for more early CSA prevention education and policy changes that remove the statute of limitations for reporting CSA.

Keywords: incest, childhood sexual abuse, incest-related childhood sexual abuse, incest survivor

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Authors: Mahmoud Reza Hosseini

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The universe is in a continuous expansion process, resulting in the reduction of its density and temperature. Also, by extrapolating back from its current state, the universe at its early times is studied, known as the big bang theory. According to this theory, moments after creation, the universe was an extremely hot and dense environment. However, its rapid expansion due to nuclear fusion led to a reduction in its temperature and density. This is evidenced through the cosmic microwave background and the universe structure at a large scale. However, extrapolating back further from this early state reaches singularity, which cannot be explained by modern physics, and the big bang theory is no longer valid. In addition, one can expect a nonuniform energy distribution across the universe from a sudden expansion. However, highly accurate measurements reveal an equal temperature mapping across the universe, which is contradictory to the big bang principles. To resolve this issue, it is believed that cosmic inflation occurred at the very early stages of the birth of the universe. According to the cosmic inflation theory, the elements which formed the universe underwent a phase of exponential growth due to the existence of a large cosmological constant. The inflation phase allows the uniform distribution of energy so that an equal maximum temperature can be achieved across the early universe. Also, the evidence of quantum fluctuations of this stage provides a means for studying the types of imperfections the universe would begin with. Although well-established theories such as cosmic inflation and the big bang together provide a comprehensive picture of the early universe and how it evolved into its current state, they are unable to address the singularity paradox at the time of universe creation. Therefore, a practical model capable of describing how the universe was initiated is needed. This research series aims at addressing the singularity issue by introducing a state of energy called a "neutral state," possessing an energy level that is referred to as the "base energy." The governing principles of base energy are discussed in detail in our second paper in the series "A Conceptual Study for Addressing the Singularity of the Emerging Universe," which is discussed in detail. To establish a complete picture, the origin of the base energy should be identified and studied. In this research paper, the mechanism which led to the emergence of this natural state and its corresponding base energy is proposed. In addition, the effect of the base energy in the space-time fabric is discussed. Finally, the possible role of the base energy in quantization and energy exchange is investigated. Therefore, the proposed concept in this research series provides a road map for enhancing our understating of the universe's creation from nothing and its evolution and discusses the possibility of base energy as one of the main building blocks of this universe.

Keywords: big bang, cosmic inflation, birth of universe, energy creation, universe evolution

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Authors: Marcel Meinhardt, Manfred Keuser, Thomas Braml

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Cracking of reinforced concrete is a complex phenomenon induced by direct loads or restraints affecting reinforced concrete structures as soon as the tensile strength of the concrete is exceeded. Hence it is important to predict where cracks will be located and how they will propagate. The bond theory and the crack formulas in the actual design codes, for example, DIN EN 1992-1-1, are all based on the assumption that the reinforcement bars are embedded in homogeneous concrete without taking into account the influence of transverse reinforcement and the real stress situation. However, it can often be observed that real structures such as walls, slabs or beams show a crack spacing that is orientated to the transverse reinforcement bars or to the stirrups. In most Finite Element Analysis studies, the smeared crack approach is used for crack prediction. The disadvantage of this model is that the typical strain localization of a crack on element level can’t be seen. The crack propagation in concrete is a discontinuous process characterized by different factors such as the initial random distribution of defects or the scatter of material properties. Such behavior presupposes the elaboration of adequate models and methods of simulation because traditional mechanical approaches deal mainly with average material parameters. This paper concerned with the modelling of the initiation and the propagation of cracks in reinforced concrete structures considering the influence of transverse reinforcement and the real stress distribution in reinforced concrete (R/C) beams/plates in bending action. Therefore, a parameter study was carried out to investigate: (I) the influence of the transversal reinforcement to the stress distribution in concrete in bending mode and (II) the crack initiation in dependence of the diameter and distance of the transversal reinforcement to each other. The numerical investigations on the crack initiation and propagation were carried out with a 2D reinforced concrete structure subjected to quasi static loading and given boundary conditions. To model the uncertainty in the tensile strength of concrete in the Finite Element Analysis correlated normally and lognormally distributed random filed with different correlation lengths were generated. The paper also presents and discuss different methods to generate random fields, e.g. the Covariance Matrix Decomposition Method. For all computations, a plastic constitutive law with softening was used to model the crack initiation and the damage of the concrete in tension. It was found that the distributions of crack spacing and crack widths are highly dependent of the used random field. These distributions are validated to experimental studies on R/C panels which were carried out at the Laboratory for Structural Engineering at the University of the German Armed Forces in Munich. Also, a recommendation for parameters of the random field for realistic modelling the uncertainty of the tensile strength is given. The aim of this research was to show a method in which the localization of strains and cracks as well as the influence of transverse reinforcement on the crack initiation and propagation in Finite Element Analysis can be seen.

Keywords: crack initiation, crack modelling, crack propagation, cracks, numerical simulation, random fields, reinforced concrete, stochastic

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Authors: Munqeth Othman Agha

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The historical formation of urban centres in the eastern Arab world was shaped by rapid urbanization and sudden transformation from the age of the pre-industrial to a post-industrial economy, coupled with uneven development, informal urban expansion, and constant surges in unemployment and poverty rates. The city was stratified accordingly as overlapping layers of division and inequality that have been built on top of each other, creating complex horizontal and vertical divisions based on economic, social, political, and ethno-sectarian basis. This has been further exacerbated during the neoliberal era, which transferred the city into a sort of dual city that is inhabited by heterogeneous and often antagonistic social groups. Economic deprivation combined with a growing sense of marginalization and inequality across the city planted the seeds of political instability, outbreaking in 2011. Unlike other popular uprisings that occupy central squares, as in Egypt and Tunisia, the Syrian uprising in 2011 took place mainly within inner streets and neighborhood squares, mobilizing primarily on more or less upon the lines of stratification. This has emphasized the role of micro-urban and social settings in shaping mobilization and resistance tactics, which necessitates us to understand the way the city was stratified and place it at the center of the city-conflict nexus analysis. This research aims to understand to what extent pre-conflict urban stratification lines played a role in determining the different trajectories of three cities’ neighborhoods (Homs, Dara’a and Deir-ez-Zor). The main argument of the paper is that the way the Syrian city has been stratified creates various social groups within the city who have enjoyed different levels of accessibility to life chances, material resources and social statuses. This determines their relationship with other social groups in the city and, more importantly, their relationship with the state. The advent of a political opportunity will be depicted differently across the city’s different social groups according to their perceived interests and threats, which consequently leads to either political mobilization or demobilization. Several factors, including the type of social structures, built environment, and state response, determine the ability of social actors to transfer the repertoire of contention to collective action or transfer from social actors to political actors. The research uses urban stratification lines as the basis for understanding the different patterns of political upheavals in urban areas while explaining why neighborhoods with different social and urban environment settings had different abilities and capacities to mobilize, resist state repression and then descend into a military conflict. It particularly traces the transformation from social groups to social actors and political actors by applying the Explaining-outcome Process-Tracing method to depict the causal mechanisms that led to including or excluding different neighborhoods from each stage of the uprising, namely mobilization (M1), response (M2), and control (M3).

Keywords: urban stratification, syrian conflict, social movement, process tracing, divided city

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Authors: Büşra Durmaz, Füsun Curaoğlu

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While technology-oriented developments in the modern world change our perceptions of time and speed, they also force our food consumption patterns, such as getting pleasure from what we eat and eating slowly. The habit of eating quickly and hastily causes not only the feeling of not understanding the taste of the food eaten but also the inability to postpone the feeling of satiety and, therefore, many health problems. In this context, especially in the last ten years, in the field of industrial design, food manufacturers for healthy living and consumption have been collaborating with industrial designers on food design. The consumers of the new century, who are in an uncontrolled time intensity, receive support from small snacks as a source of happiness and pleasure in the little time intervals they can spare. At this point, especially chocolate has been a source of happiness for its consumers as a source of both happiness and pleasure for hundreds of years. However, when the portions have eaten cannot be controlled, a pleasure food such as chocolate can cause both health problems and many emotional problems, especially the feeling of guilt. Fast food, which is called food that is prepared and consumed quickly, has been increasing rapidly around the world in recent years. This study covers the process and results of a chocolate design based on the user experience of a university-industry cooperation project carried out within the scope of Eskişehir Technical University graduation projects. The aim of the project is a creative product design that will enable the user to experience chocolate consumption with a healthy eating approach. For this, while concepts such as pleasure, satiety, and taste are discussed; A survey with 151 people and semi-structured face-to-face interviews with 7 people during the experience design process within the scope of the user-oriented design approach, mainly literature review, within the scope of main topics such as mouth anatomy, tongue structure, taste, the functions of the eating action in the brain, hormones and chocolate, video A case study based on the research paradigm of Qualitative Research was structured within the scope of different research processes such as analysis and project diaries. As a result of the research, it has been reached that the melting in the mouth is the preferred experience of the users in order to spread the experience of eating chocolate for a long time based on pleasure while eating chocolate with healthy portions. In this context, researches about the production of sketches, mock-ups and prototypes of the product are included in the study. As a result, a product packaging design has been made that supports the active role of the senses such as sight, smell and hearing, where consumption begins, in order to consume chocolate by melting and to actively secrete the most important stimulus salivary glands in order to provide a healthy and long-term pleasure-based consumption.

Keywords: chocolate, eating habit, pleasure, saturation, sense of taste

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Authors: Nicolas Peyret, Sylvain Courtois, Gaël Chevallier

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This article outlines the development of the Project Based Learning (PBL) at the level of a last year’s Bachelor’s Degree. This form of pedagogy has for objective to allow a better involving of the students from the beginning of the module. The theoretical contributions are introduced during the project to solving a technological problem. The module in question is the module of mechanical dimensioning method of Supméca a French engineering school. This school issues a Master’s Degree. While the teaching methods used in primary and secondary education are frequently renewed in France at the instigation of teachers and inspectors, higher education remains relatively traditional in its practices. Recently, some colleagues have felt the need to put the application back at the heart of their theoretical teaching. This need is induced by the difficulty of covering all the knowledge deductively before its application. It is therefore tempting to make the students 'learn by doing', even if it doesn’t cover some parts of the theoretical knowledge. The other argument that supports this type of learning is the lack of motivation the students have for the magisterial courses. The role-play allowed scenarios favoring interaction between students and teachers… However, this pedagogical form known as 'pedagogy by project' is difficult to apply in the first years of university studies because of the low level of autonomy and individual responsibility that the students have. The question of what the student actually learns from the initial program as well as the evaluation of the competences acquired by the students in this type of pedagogy also remains an open problem. Thus we propose to add to the pedagogy by project format a regressive part of interventionism by the teacher based on pedagogy by example. This pedagogical scenario is based on the cognitive load theory and Bruner's constructivist theory. It has been built by relying on the six points of the encouragement process defined by Bruner, with a concrete objective, to allow the students to go beyond the basic skills of dimensioning and allow them to acquire the more global skills of engineering. The implementation of project-based teaching coupled with pedagogy by example makes it possible to compensate for the lack of experience and autonomy of first-year students, while at the same time involving them strongly in the first few minutes of the module. In this project, students have been confronted with the real dimensioning problems and are able to understand the links and influences between parameter variations and dimensioning, an objective that we did not reach in classical teaching. It is this form of pedagogy which allows to accelerate the mastery of basic skills and so spend more time on the engineer skills namely the convergence of each dimensioning in order to obtain a validated mechanism. A self-evaluation of the project skills acquired by the students will also be presented.

Keywords: Bruner's constructivist theory, mechanisms dimensioning, pedagogy by example, problem based learning

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Authors: Mounir Baccar, Imen Jmal

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Because of the rise in energy costs, thermal storage systems designed for the heating and cooling of buildings are becoming increasingly important. Energy storage can not only reduce the time or rate mismatch between energy supply and demand but also plays an important role in energy conservation. One of the most preferable storage techniques is the Latent Heat Thermal Energy Storage (LHTES) by Phase Change Materials (PCM) due to its important energy storage density and isothermal storage process. This paper presents a numerical study of the solidification of a PCM (paraffin RT27) in a rectangular thermal storage exchanger for air conditioning systems taking into account the presence of natural convection. Resolution of continuity, momentum and thermal energy equations are treated by the finite volume method. The main objective of this numerical approach is to study the effect of natural convection on the PCM solidification time and the impact of fins number on heat transfer enhancement. It also aims at investigating the temporal evolution of PCM solidification, as well as the longitudinal profiles of the HTF circling in the duct. The present research undertakes the study of two cases: the first one treats the solidification of PCM in a PCM-air heat exchanger without fins, while the second focuses on the solidification of PCM in a heat exchanger of the same type with the addition of fins (3 fins, 5 fins, and 9 fins). Without fins, the stratification of the PCM from colder to hotter during the heat transfer process has been noted. This behavior prevents the formation of thermo-convective cells in PCM area and then makes transferring almost conductive. In the presence of fins, energy extraction from PCM to airflow occurs at a faster rate, which contributes to the reduction of the discharging time and the increase of the outlet air temperature (HTF). However, for a great number of fins (9 fins), the enhancement of the solidification process is not significant because of the effect of confinement of PCM liquid spaces for the development of thermo-convective flow. Hence, it can be concluded that the effect of natural convection is not very significant for a high number of fins. In the optimum case, using 3 fins, the increasing temperature of the HTF exceeds approximately 10°C during the first 30 minutes. When solidification progresses from the surfaces of the PCM-container and propagates to the central liquid phase, an insulating layer will be created in the vicinity of the container surfaces and the fins, causing a low heat exchange rate between PCM and air. As the solid PCM layer gets thicker, a progressive regression of the field of movements is induced in the liquid phase, thus leading to the inhibition of heat extraction process. After about 2 hours, 68% of the PCM became solid, and heat transfer was almost dominated by conduction mechanism.

Keywords: heat transfer enhancement, front solidification, PCM, natural convection

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Authors: Mohammad Ibrahim Alladin

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The Pedagogy of the Oppressed by Paulo Freire was first published in 1970. Since its publication it has become one of most cited book in the social sciences. Over a million copies have been sold worldwide. The Pedagogy of the Oppressed by Paulo Freire was published in 1970 (New York: Herder and Herder), The book has caused a “revolution” in the education world and his theory has been examined and analysed. It has influenced educational policy, curriculum development and teacher education. The revolution started half a century ago. “Paolo Freire’s Pedagogy of the Oppressed develops a theory of education fitted to the needs of the disenfranchised and marginalized members of capitalist societies. Combining educational and political philosophy, the book offers an analysis of oppression and a theory of liberation. Freire believes that traditional education serves to support the dominance of the powerful within society and thereby maintain the powerful’s social, political, and economic status quo. To overcome the oppression endemic to an exploitative society, education must be remade to inspire and enable the oppressed in their struggle for liberation. This new approach to education focuses on consciousness-raising, dialogue, and collaboration between teacher and student in the effort to achieve greater humanization for all. For Freire, education is political and functions either to preserve the current social order or to transform it. The theories of education and revolutionary action he offers in Pedagogy of the Oppressed are addressed educators committed to the struggle for liberation from oppression. Freire’s own commitment to this struggle developed through years of teaching literacy to Brazilian and Chilean peasants and laborers. His efforts at educational and political reform resulted in a brief period of imprisonment followed exile from his native Brazil for fifteen years. In Pedagogy of the Oppressed begins Freire asserts the importance of consciousness-raising, or conscientização, as the means enabling the oppressed to recognize their oppression and commit to the effort to overcome it, taking full responsibility for themselves in the struggle for liberation. He addresses the “fear of freedom,” which inhibits the oppressed from assuming this responsibility. He also cautions against the dangers of sectarianism, which can undermine the revolutionary purpose as well as serve as a refuge for the committed conservative. Freire provides an alternative view of education by attacking tradition education and knowledge. He is highly critical of how is imparted and how knowledge is structured that limits the learner’s thinking. Hence, education becomes oppressive and school functions as an institution of social control. Since its publication, education has gone through a series of reforms and in some areas total transformation. This paper addresses the following: The role of education in social transformation The teacher/learner relationship :Critical thinking The paper essentially examines what happened in the last fifty years since Freire’s book. It seeks to explain what happened to Freire’s education revolution, and what is the status of the movement that started almost fifty years ago.

Keywords: pedagogy, reform, curriculum, teacher education

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Authors: Xiaoqiang Fu, Baihao Li

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In 1895, the failure of Sino-Japanese prompted the trend of comprehensive and systematic study of western pattern in China. In urban planning and construction, urban reform movement sprang up slowly, which aimed at renovating and reconstructing the traditional cities into modern cities similar to the concessions. During the movement, Chinese traditional city initiated a process of modern urban planning for its modernization. Meanwhile, the traditional planning morphology and system started to disintegrate, on the contrary, western form and technology had become the paradigm. Therefore, the improvement of existing cities had become the prototype of urban planning of early modern China. Currently, researches of the movement mainly concentrate on large cities, concessions, railway hub cities and some special cities resembling those. However, the systematic research about the large number of traditional small and medium-sized cities is still blank, up to now. This paper takes the improvement constructions of small and medium-sized cities in Southern region of Jiangsu Province as the research object. First of all, the criteria of small and medium-sized cities are based on the administrative levels of general office and cities at the county level. Secondly, the suitability of taking the Southern Jiangsu as the research object. The southern area of Jiangsu province called Southern Jiangsu for short, was the most economically developed region in Jiangsu, and also one of the most economically developed and the highest urbanization regions in China. As the most developed agricultural areas in ancient China, Southern Jiangsu formed a large number of traditional small and medium-sized cities. In early modern times, with the help of the Shanghai economic radiation, geographical advantage and powerful economic foundation, Southern Jiangsu became an important birthplace of Chinese national industry. Furthermore, the strong business atmosphere promoted the widespread urban improvement practices, which were incomparable of other regions. Meanwhile, the demonstration of Shanghai, Zhenjiang, Suzhou and other port cities became the improvement pattern of small and medium-sized city in Southern Jiangsu. This paper analyzes the reform movement of the small and medium-sized cities in Southern Jiangsu (1895-1927), including the subjects, objects, laws, technologies and the influence factors of politic and society, etc. At last, this paper reveals the formation mechanism and characteristics of urban improvement movement in early modern China. According to the paper, the improvement of small-medium city was a kind of gestation of the local city planning culture in early modern China，with a fusion of introduction and endophytism.

Keywords: early modern China, improvement of small-medium city, southern region of Jiangsu province, urban planning history of China

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