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Authors: Ben Main Piotr Ozieranski

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State government spending on pharmaceuticals stands at 1 trillion USD globally, promoting criticism of the pharmaceutical industry's monetization of drug efficacy, product cost overvaluation, and health injustice. This paper elucidates the mechanisms behind a state-institutional response to this problem through the sociological lens of the strategic relational approach to state power. To do so, 30 expert interviews, legal and policy documents are drawn on to explain how state elites in New Zealand have successfully contested a 30-year “pharmaceutical spending containment policy”. Proceeding from Jessop's notion of strategic “selectivity”, encompassing analyses of the enabling features of state actors' ability to harness state structures, a theoretical explanation is advanced. First, a strategic context is described that consists of dynamics around pharmaceutical dealmaking between the state bureaucracy, pharmaceutical pricing strategies (and their effects), and the industry. Centrally, the pricing strategy of "bundling" -deals for packages of drugs that combine older and newer patented products- reflect how state managers have instigated an “incentivization game” that is played by state and industry actors, including HTA professionals, over pharmaceutical products (both current and in development). Second, a protective context is described that is comprised of successive legislative-judicial responses to the strategic context and characterized by the regulation and the societalisation of commercial law. Third, within the policy, the achievement of increased pharmaceutical coverage (pharmaceutical “mix”) alongside contained spending is conceptualized as a state defence of a "social profit". As such, in contrast to scholarly expectations that political and economic cultures of neo-liberalism drive pharmaceutical policy-making processes, New Zealand's state elites' approach is shown to be antipathetic to neo-liberals within an overall capitalist economy. The paper contributes an analysis of state pricing strategies and how they are embedded in state regulatory structures. Additionally, through an analysis of the interconnections of state power and pharmaceutical value Abrahams's neo-liberal corporate bias model for pharmaceutical policy analysis is problematised.

Keywords: pharmaceutical governance, pharmaceutical bureaucracy, pricing strategies, state power, value theory

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Authors: Priscila A. Bernardes, Marcos E. Buzanskas, Luciana C. A. Regitano, Ricardo V. Ventura, Danisio P. Munari

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Genotype imputation has been used to reduce genomic selections costs. In order to increase haplotype detection accuracy in methods that considers the linkage disequilibrium, another approach could be used, such as combined genotype data from different panels. Therefore, this study aimed to evaluate the linkage disequilibrium and haplotype blocks in two high-density panels before and after the imputation to a combined panel in Nelore beef cattle. A total of 814 animals were genotyped with the Illumina BovineHD BeadChip (IHD), wherein 93 animals (23 bulls and 70 progenies) were also genotyped with the Affymetrix Axion Genome-Wide BOS 1 Array Plate (AHD). After the quality control, 809 IHD animals (509,107 SNPs) and 93 AHD (427,875 SNPs) remained for analyses. The combined genotype panel (CP) was constructed by merging both panels after quality control, resulting in 880,336 SNPs. Imputation analysis was conducted using software FImpute v.2.2b. The reference (CP) and target (IHD) populations consisted of 23 bulls and 786 animals, respectively. The linkage disequilibrium and haplotype blocks studies were carried out for IHD, AHD, and imputed CP. Two linkage disequilibrium measures were considered; the correlation coefficient between alleles from two loci (r²) and the |D’|. Both measures were calculated using the software PLINK. The haplotypes' blocks were estimated using the software Haploview. The r² measurement presented different decay when compared to |D’|, wherein AHD and IHD had almost the same decay. For r², even with possible overestimation by the sample size for AHD (93 animals), the IHD presented higher values when compared to AHD for shorter distances, but with the increase of distance, both panels presented similar values. The r² measurement is influenced by the minor allele frequency of the pair of SNPs, which can cause the observed difference comparing the r² decay and |D’| decay. As a sum of the combinations between Illumina and Affymetrix panels, the CP presented a decay equivalent to a mean of these combinations. The estimated haplotype blocks detected for IHD, AHD, and CP were 84,529, 63,967, and 140,336, respectively. The IHD were composed by haplotype blocks with mean of 137.70 ± 219.05kb, the AHD with mean of 102.10kb ± 155.47, and the CP with mean of 107.10kb ± 169.14. The majority of the haplotype blocks of these three panels were composed by less than 10 SNPs, with only 3,882 (IHD), 193 (AHD) and 8,462 (CP) haplotype blocks composed by 10 SNPs or more. There was an increase in the number of chromosomes covered with long haplotypes when CP was used as well as an increase in haplotype coverage for short chromosomes (23-29), which can contribute for studies that explore haplotype blocks. In general, using CP could be an alternative to increase density and number of haplotype blocks, increasing the probability to obtain a marker close to a quantitative trait loci of interest.

Keywords: Bos taurus indicus, decay, genotype imputation, single nucleotide polymorphism

Procedia PDF Downloads 279

Authors: Mohkammad Nur Cahyadi, Hepi Hapsari Handayani, Agus Budi Raharjo, Ronny Mardianto, Daud Wahyu Imani, Arizal Bawazir, Luki Adi Triawan

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PDAM (local water company) determines customer charges by considering the customer's building or house. Charges determination significantly affects PDAM income and customer costs because the PDAM applies a subsidy policy for customers classified as small households. Periodic updates are needed so that pricing is in line with the target. A thorough customer survey in Surabaya is needed to update customer building data. However, the survey that has been carried out so far has been by deploying officers to conduct one-by-one surveys for each PDAM customer. Surveys with this method require a lot of effort and cost. For this reason, this research offers a technology called moblie mapping, a mapping method that is more efficient in terms of time and cost. The use of this tool is also quite simple, where the device will be installed in the car so that it can record the surrounding buildings while the car is running. Mobile mapping technology generally uses lidar sensors equipped with GNSS, but this technology requires high costs. In overcoming this problem, this research develops low-cost mobile mapping technology using a webcam camera sensor added to the GNSS and IMU sensors. The camera used has specifications of 3MP with a resolution of 720 and a diagonal field of view of 78⁰. The principle of this invention is to integrate four camera sensors, a GNSS webcam, and GPS to acquire photo data, which is equipped with location data (latitude, longitude) and IMU (roll, pitch, yaw). This device is also equipped with a tripod and a vacuum cleaner to attach to the car's roof so it doesn't fall off while running. The output data from this technology will be analyzed with artificial intelligence to reduce similar data (Cosine Similarity) and then classify building types. Data reduction is used to eliminate similar data and maintain the image that displays the complete house so that it can be processed for later classification of buildings. The AI method used is transfer learning by utilizing a trained model named VGG-16. From the analysis of similarity data, it was found that the data reduction reached 50%. Then georeferencing is done using the Google Maps API to get address information according to the coordinates in the data. After that, geographic join is done to link survey data with customer data already owned by PDAM Surya Sembada Surabaya.

Keywords: mobile mapping, GNSS, IMU, similarity, classification

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Authors: J. Knight, E. Barberà

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Language learning strategies have been defined as thoughts and actions, consciously chosen and operationalized by language learners, to help them in carrying out a multiplicity of tasks from the very outset of learning to the most advanced levels of target language performance. While research in the field of Second Language Acquisition has focused on ‘good’ language learners, the effectiveness of strategy-use and orchestration by effective learners in face-to-face classrooms much less research has attended to learner strategies in online contexts, particular strategies in relation to technological tool use which can be part of a task design. In addition, much research on learner strategies and strategy use has been explored focusing on cognitive, attitudinal and metacognitive behaviour with less research focusing on the social aspect of strategies. This study focuses on how learners mediate with a technological tool designed to support synchronous spoken interaction and how this shape their spoken interaction in the opening of their talk. A case study approach is used incorporating notions from communities of practice theory to analyse and understand learner strategies of dyads carrying out a role play task. The study employs analysis of transcripts of spoken interaction in the openings of the talk along with log files of tool use. The study draws on results of previous studies pertaining to the same tool as a form of triangulation. Findings show how learners gain pre-task planning time through technological tool control. The strategies involving learners’ choices to enter and exit the tool shape their spoken interaction qualitatively, with some cases demonstrating long silences whilst others appearing to start the pedagogical task immediately. Who/what learners orientate to in the openings of the talk: an audience (i.e. the teacher), each other and/or screen-based signifiers in the opening moments of the talk also becomes a focus. The study highlights how tool use as a social practice should be considered a learning strategy in online contexts whereby different usages may be understood in the light of the more usual asynchronous social practices of the online community. The teachers’ role in the community is also problematised as the evaluator of the practices of that community. Results are pertinent for task design for synchronous speaking tasks. The use of community of practice theory supports an understanding of strategy use that involves both metacognition alongside social context revealing how tool-use strategies may need to be orally (socially) negotiated by learners and may also differ from an online language community.

Keywords: learner strategy, tool use, community of practice, speaking task

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Authors: Nigatu Tadesse, Li Juan, Liuhong Ming

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Gastric cancer (GC) is the fifth most common and fourth deadly cancer in the world with limited treatment options at late advanced stage in which surgical therapy is not recommended with chemotherapy remain as the mainstay of treatment. However, the occurrence of chemoresistance as well as intera-tumoral and inter-tumoral heterogeneity of response to targeted and immunotherapy underlined a clear unmet treatment need in gastroenterology. Several molecular and cellular alterations ascribed for chemo resistance in GC including cancer stem cells (CSC) and tumor microenvironment (TME) remodeling. Cancer cells including CSC bears higher metabolic demand and major changes in TME involves alterations of gut microbiota interacting with nutrients metabolism. Metabolic upregulation in lipids, carbohydrates, amino acids, fatty acids biosynthesis pathways identified as a common hall mark in GC. Metabolic addiction to methionine metabolism occurs in many cancer cells to promote the biosynthesis of S-Adenosylmethionine (SAM), a universal methyl donor molecule for high rate of transmethylation in GC and promote cell proliferation. Targeting methionine metabolism found to promotes chemo-sensitivity with treatment non-heterogeneity. Methionine restriction (MR) promoted the arrest of cell cycle at S/G2 phase and enhanced downregulation of GC cells resistance to apoptosis (including ferroptosis), which suggests the potential of synergy with chemotherapies acting at S-phase of the cell cycle as well as inducing cell apoptosis. Accumulated evidences showed both the biogenesis as well as intracellular metabolism of exogenous methionine could be safe and effective target for therapy either alone or in combination with chemotherapies. This review article provides an over view of the upregulation in methionine biosynthesis pathway and the molecular signaling through the PI3K/Akt/mTOR-c-MYC axis to promote metabolic reprograming through activating the expression of L-type aminoacid-1 (LAT1) transporter and overexpression of Methionine adenosyltransferase 2A(MAT2A) for intercellular metabolic conversion of exogenous methionine to SAM in GC, and the potential of targeting with novel therapeutic agents such as methioninase (METase), Methionine adenosyltransferase 2A (MAT2A), c-MYC, methyl like transferase 16 (METTL16) inhibitors that are currently under clinical trial development stages and future perspectives.

Keywords: gastric cancer, methionine metabolism, pi3k/akt/mtorc1-c-myc axis, gut microbiota, MAT2A, c-MYC, METTL16, methioninase

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Authors: Sayyed Mostafa Ahmadi, Neda Raeesi

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Background and Objectives: Cervical spondylosis is a common problem that affects the adult spine and is the most common cause of radiculopathy and myelopathy in older patients. Anterior discectomy and fusion is a well-known technique in degenerative cervical disc disease. However, one of the late undesirable complications is adjacent disc degeneration, which affects about 91% of patients in ten years. Many factors can be effective in causing this complication, but some are still debatable. Discovering these risk factors and eliminating them can improve the quality of life. Methods: This is a retrospective cohort study. All patients who underwent anterior discectomy and fusion surgery in the neurosurgery ward of Imam Khomeini Hospital between 2013 and 2016 were evaluated. Their demographic information was collected. All patients were visited and examined for radiculopathy, myelopathy, and muscular force. At the same visit, all patients were asked to have a facelift, and neck profile, as well as a neck MRI(General Tesla 3). Preoperative graphs were used to measure the diameter of the cervical canal(Pavlov ratio) and to evaluate sagittal alignment(Cobb Angle). Preoperative MRI of patients was reviewed for anterior and posterior longitudinal ligament calcification. Result: In this study, 57 patients were studied. The mean age of patients was 50.63 years, and 49.1% were male. Only 3.5% of patients had anterior and posterior longitudinal ligament calcification. Symptomatic ASD was observed in 26.6%. The X-rays and MRIs showed evidence of 80.7% radiological ASD. Among patients who underwent one-level surgery, 20% had symptomatic ASD, but among patients who underwent two-level surgery, the rate of ASD was 50%.In other words, the higher the number of surfaces that are operated and fused, the higher the probability of symptomatic ASD(P-value <0.05). The X-rays and MRIs showed 80.7% of radiological ASD. Among patients who underwent surgery at one level, 78% had radiological ASD, and this number was 92% among patients who underwent two-level surgery(P-value> 0.05). Demographic variables such as age, sex, height, weight, and BMI did not have a significant effect on the incidence of radiological ASD(P-value> 0.05), but sex and height were two influential factors on symptomatic ASD(P-value <0.05). Other related variables such as family history, smoking and exercise also have no significant effect(P-value> 0.05). Radiographic variables such as Pavlov ratio and sagittal alignment were also unaffected by the incidence of radiological and symptomatic ASD(P-value> 0.05). The number of surgical surfaces and the incidence of anterior and posterior longitudinal ligament calcification before surgery also had no statistically significant effect(P-value> 0.05). In the study of the ability of the neck to move in different directions, none of these variables are statistically significant in the two groups with radiological and symptomatic ASD and the non-affected group(P-value> 0.05). Conclusion: According to the findings of this study, this disease is considered to be a multifactorial disease. The incidence of radiological ASD is much higher than symptomatic ASD (80.7% vs. 26.3%) and sex, height and number of fused surfaces are the only factors influencing the incidence of symptomatic ASD and no variable influences radiological ASD.

Keywords: risk factors, anterior neck disectomy and fusion, adjucent segment degeneration, complication

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Authors: H. Pegram, R. Stevens, L. De Girolamo

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Aligned electrospun nanofibres act as effective neuronal and glial cell scaffolds that can be layered to contain multiple sheets harboring different cell populations. This allows personalised biofunctional prostheses to be manufactured with both acellular and cellularised layers for the treatment of spinal cord injury. Additionally, the manufacturing route may be configured to produce in-vitro 3D cell based model of spinal cord injury to aid drug development and enhance prosthesis performance. The goal of this investigation was to optimise the multi-layer scaffold design parameters for prosthesis manufacture, to enable the development of multi-layer patient specific implant therapies. The work has also focused on the fabricating aligned nanofibre scaffolds that promote in-vitro neuronal and glial cell population growth, cell-to-cell interaction and long-term survival following trauma to mimic an in-vivo spinal cord lesion. The approach has established reproducible lesions and has identified markers of trauma and regeneration marked by effective neuronal migration across the lesion with glial support. The investigation has advanced the development of an in-vitro model of traumatic spinal cord injury and has identified a route to manufacture prostheses which target the repair spinal cord injury. Evidence collated to investigate the multi-layer concept suggests that physical cues provided by nanofibres provide both a natural extra-cellular matrix (ECM) like environment and controls cell proliferation and migration. Specifically, aligned nanofibre layers act as a guidance system for migrating and elongating neurons. On a larger scale, material type in multi-layer systems also has an influence in inter-layer migration as cell types favour different material types. Results have shown that layering nanofibre membranes create a multi-level scaffold system which can enhance or prohibit cell migration between layers. It is hypothesised that modifying nanofibre layer material permits control over neuronal/glial cell migration. Using this concept, layering of neuronal and glial cells has become possible, in the context of tissue engineering and also modelling in-vitro induced lesions.

Keywords: electrospinning, layering, lesion, modeling, nanofibre

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Authors: D. P. N. De Silva, N. P. P. Liyanage

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Zebrafish (Danio rerio) in the family Cyprinidae, is a tropical freshwater fish widely used as a model organism in scientific research. Use of effective and economical anaesthetic is very important when handling fish. Clove oil (active ingredient: eugenol) was identified as a natural product which is safer and economical compared to synthetic chemicals like methanesulfonate (MS-222). Therefore, the aim of this study was to identify the most effective dosage of clove oil solution as an anaesthetic on mature Zebrafish. Clove oil solution was prepared by mixing pure clove oil with 94% ethanol at a ratio of 1:9 respectively. From that solution, different volumes were selected as (0.4 ml, 0.6 ml and 0.8 ml) and dissolved in one liter of conditioned water (dosages : 0.4 ml/L, 0.6 ml/L and 0.8 ml/L). Water quality parameters (pH, temperature and conductivity) were measured before and after adding clove oil solution. Mature Zebrafish with similar standard length (2.76 ± 0.1 cm) and weight (0.524 ± 0.1 g) were selected for this experiment. Time taken for loss of equilibrium (initiation phase) and complete loss of movements including opercular movement (anaesthetic phase) were measured. To detect the efficacy on anaesthetic recovery, time taken to begin opercular movements (initiation of recovery phase) until swimming (post anaesthetic phase) were observed. The results obtained were analyzed according to the analysis of variance (ANOVA) and Tukeys’ method using SPSS version 17.0 at 95% confidence interval (p<0.5). According to the results, there was no significant difference at the initiation phase of anaesthesia in all three doses though the time taken was varied from 0.14 to 0.41 minutes. Mean value of the time taken to complete the anaesthetic phase at 0.4 ml/L dosage was significantly different with 0.6 ml/L and 0.8 ml/L dosages independently (p=0.01). There was no significant difference among recovery times at all dosages but 0.8 ml/L dosage took longer time compared to 0.6 ml/L dosage. The water quality parameters (pH and temperature) were stable throughout the experiment except conductivity, which increased with the higher dosage. In conclusion, the best dosage need to anaesthetize Zebrafish using clove oil solution was 0.6 ml/L due to its fast initiation of anaesthesia and quick recovery compared to the other two dosages. Therefore clove oil can be used as a good substitute for synthetic anaesthetics because of its efficacy at a lower dosage with higher safety at a low cost.

Keywords: anaesthetics, clove oil, zebrafish, Cyprinidae

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Authors: Mostafa Shahriari, Theophile Chaumont-Frelet, David Pardo

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Resistivity measurements are used to characterize the Earth’s subsurface. They are categorized into two different groups: (a) those acquired on the Earth’s surface, for instance, controlled source electromagnetic (CSEM) and Magnetotellurics (MT), and (b) those recorded with borehole logging instruments such as Logging-While-Drilling (LWD) devices. LWD instruments are mostly used for geo-steering purposes, i.e., to adjust dip and azimuthal angles of a well trajectory to drill along a particular geological target. Modern LWD tools measure all nine components of the magnetic field corresponding to three orthogonal transmitter and receiver orientations. In order to map the Earth’s subsurface and perform geo-steering, we invert measurements using a gradient-based method that utilizes the derivatives of the recorded measurements with respect to the inversion variables. For resistivity measurements, these inversion variables are usually the constant resistivity value of each layer and the bed boundary positions. It is well-known how to compute derivatives with respect to the constant resistivity value of each layer using semi-analytic or numerical methods. However, similar formulas for computing the derivatives with respect to bed boundary positions are unavailable. The main contribution of this work is to provide an adjoint-based formulation for computing derivatives with respect to the bed boundary positions. The key idea to obtain the aforementioned adjoint state formulations for the derivatives is to separate the tangential and normal components of the field and treat them differently. This formulation allows us to compute the derivatives faster and more accurately than with traditional finite differences approximations. In the presentation, we shall first derive a formula for computing the derivatives with respect to the bed boundary positions for the potential equation. Then, we shall extend our formulation to 3D Maxwell’s equations. Finally, by considering a 1D domain and reducing the dimensionality of the problem, which is a common practice in the inversion of resistivity measurements, we shall derive a formulation to compute the derivatives of the measurements with respect to the bed boundary positions using a 1.5D variational formulation. Then, we shall illustrate the accuracy and convergence properties of our formulations by comparing numerical results with the analytical derivatives for the potential equation. For the 1.5D Maxwell’s system, we shall compare our numerical results based on the proposed adjoint-based formulation vs those obtained with a traditional finite difference approach. Numerical results shall show that our proposed adjoint-based technique produces enhanced accuracy solutions while its cost is negligible, as opposed to the finite difference approach that requires the solution of one additional problem per derivative.

Keywords: inverse problem, bed boundary positions, electromagnetism, potential equation

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Authors: Veerle Van Hoeck, Ingrid Somers, Dany Morisset

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Anti-nutritional factors such as non-starch polysaccharides (NSP) are present in viscous cereals used to feed poultry. Therefore, exogenous carbohydrases are commonly added to monogastric feed to degrade these NSP. Our hypothesis is that xylanase not only improves laying hen performance and digestibility but also induces a significant shift in microbial composition within the intestinal tract and, thereby, can cause a prebiotic effect. In this context, a better understanding of whether and how the chicken gut flora can be modulated by xylanase is needed. To do so, in the herein laying hen study, the effects of dietary supplementation of xylanase on performance, digestibility, and cecal microbiome were evaluated. A total of 96 HiSex laying hens was used in this experiment (3 diets and 16 replicates of 2 hens). Xylanase was added to the diets at concentrations of 0, 45,000 (15 g/t XygestTM HT) and 90,000 U/kg (30 g/t Xygest HT). The diets were based on wheat (~55 %), soybean, and sunflower meal. The lowest dosage, 45,000 U/kg, significantly increased average egg weight and improved feed efficiency compared to the control treatment (p < 0.05). Egg quality parameters were significantly improved in the experiment in response to the xylanase addition. For example, during the last 28 days of the trial, the 45,000 U/kg and the 90,000 U/kg treatments exhibited an increase in Haugh units and albumin heights (p < 0.05). Compared with the control, organic matter digestibility and N retention were drastically improved in the 45,000 U/kg treatment group, which implies better nutrient digestibility at this lowest recommended dosage compared to the control (p < 0.05). Furthermore, gross energy and crude fat digestibility were improved significantly for birds fed 90,000 U/kg group compared to the control. Importantly, 16S rRNA gene analysis revealed that xylanase at 45,000 U/kg dosages can exert a prebiotic effect. This conclusion was drawn based on studying the sequence variation in the 16S rRNA gene in order to characterize diverse microbial communities of the cecal content. A significant increase in beneficial bacteria (Lactobacilli spp and Enterococcus casseliflavus) was documented when adding 45,000 U/kg xylanase to the diet of laying hens. In conclusion, dietary supplementation of xylanase, even at the lowest dose of (45,000 U/kg), significantly improved laying hen performance and digestibility. Furthermore, it is generally accepted that a proper bacterial balance between the number of beneficial bacteria and pathogenic bacteria in the intestine is vital for the host. It seems that the xylanase enzyme is able to modulate the laying hen microbiome beneficially and thus exerts a prebiotic effect. This microbiome plasticity in response to the xylanase provides an attractive target for stimulating intestinal health.

Keywords: laying hen, prebiotic, XygestTM HT, xylanase

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Authors: Laura Vitola, Diana Bajare, Genadijs Sahmenko, Girts Bumanis

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About 8 % of CO2 emission in the world is produced by concrete industry therefore replacement of cement in concrete composition by additives with pozzolanic activity would give a significant impact on the environment. Material which contains silica SiO2 or amorphous silica SiO2 together with aluminum dioxide Al2O3 is called pozzolana type additives in the concrete industry. Pozzolana additives are possible to obtain from recycling industry and different production by-products such as processed bulb boric silicate (DRL type) and lead (LB type) glass, coal combustion bottom ash, utilized brick pieces and biomass ash, thus solving utilization problem which is so important in the world, as well as practically using materials which previously were considered as unusable. In the literature, there is no summarized method which could be used for quick waste-product pozzolana activity evaluation without the performance of wide researches related to the production of innumerable concrete contents and samples in the literature. Besides it is important to understand which parameters should be predicted to characterize the efficiency of waste-products. Simple methods of pozzolana activity increase for different types of waste-products are also determined. The aim of this study is to evaluate effectiveness of the different types of waste materials and industrial by-products (coal combustion bottom ash, biomass ash, waste glass, waste kaolin and calcined illite clays), and determine which parameters have the greatest impact on pozzolanic activity. By using materials, which previously were considered as unusable and landfilled, in concrete industry basic utilization problems will be partially solved. The optimal methods for treatment of waste materials and industrial by–products were detected with the purpose to increase their pozzolanic activity and produce substitutes for cement in the concrete industry. Usage of mentioned pozzolanic allows us to replace of necessary cement amount till 20% without reducing the compressive strength of concrete.

Keywords: cement substitutes, micro and nano fillers, pozzolanic properties, specific surface area, particle size, waste products

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Authors: Jasmin Cowin, Amany Alkhayat

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This paper will concentrate on a comparative analysis of both the advantages and limitations of using digital learning resources (DLRs). DLRs covered will be Virtual Reality (VR), Mobile Learning (M-learning) and Computer-Assisted Language Learning (CALL) together with their subset, Mobile Assisted Language Learning (MALL) in language education. In addition, best practices for language teaching and the application of established language teaching methodologies such as Communicative Language Teaching (CLT), the audio-lingual method, or community language learning will be explored. Education has changed dramatically since the eruption of the pandemic. Traditional face-to-face education was disrupted on a global scale. The rise of distance learning brought new digital tools to the forefront, especially web conferencing tools, digital storytelling apps, test authoring tools, and VR platforms. Language educators raced to vet, learn, and implement multiple technology resources suited for language acquisition. Yet, questions remain on how to harness new technologies, digital tools, and their ubiquitous availability while using established methods and methodologies in language learning paired with best teaching practices. In M-learning language, learners employ portable computing devices such as smartphones or tablets. CALL is a language teaching approach using computers and other technologies through presenting, reinforcing, and assessing language materials to be learned or to create environments where teachers and learners can meaningfully interact. In VR, a computer-generated simulation enables learner interaction with a 3D environment via screen, smartphone, or a head mounted display. Research supports that VR for language learning is effective in terms of exploration, communication, engagement, and motivation. Students are able to relate through role play activities, interact with 3D objects and activities such as field trips. VR lends itself to group language exercises in the classroom with target language practice in an immersive, virtual environment. Students, teachers, schools, language institutes, and institutions benefit from specialized support to help them acquire second language proficiency and content knowledge that builds on their cultural and linguistic assets. Through the purposeful application of different language methodologies and teaching approaches, language learners can not only make cultural and linguistic connections in DLRs but also practice grammar drills, play memory games or flourish in authentic settings.

Keywords: language teaching methodologies, computer-assisted language learning, mobile learning, virtual reality

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Authors: Seulki Lee, Seoung Bum Kim

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Statistical process control (SPC) is a practical and effective method for quality control. The most important and widely used technique in SPC is a control chart. The main goal of a control chart is to detect any assignable changes that affect the quality output. Most conventional control charts, such as Hotelling’s T2 charts, are commonly based on the assumption that the quality characteristics follow a multivariate normal distribution. However, in modern complicated manufacturing systems, appropriate control chart techniques that can efficiently handle the nonnormal processes are required. To overcome the shortcomings of conventional control charts for nonnormal processes, several methods have been proposed to combine statistical learning algorithms and multivariate control charts. Statistical learning-based control charts, such as support vector data description (SVDD)-based charts, k-nearest neighbors-based charts, have proven their improved performance in nonnormal situations compared to that of the T2 chart. Beside the nonnormal property, time-varying operations are also quite common in real manufacturing fields because of various factors such as product and set-point changes, seasonal variations, catalyst degradation, and sensor drifting. However, traditional control charts cannot accommodate future condition changes of the process because they are formulated based on the data information recorded in the early stage of the process. In the present paper, we propose a SVDD algorithm-based control chart, which is capable of adaptively monitoring time-varying and nonnormal processes. We reformulated the SVDD algorithm into a time-adaptive SVDD algorithm by adding a weighting factor that reflects time-varying situations. Moreover, we defined the updating region for the efficient model-updating structure of the control chart. The proposed control chart simultaneously allows efficient model updates and timely detection of out-of-control signals. The effectiveness and applicability of the proposed chart were demonstrated through experiments with the simulated data and the real data from the metal frame process in mobile device manufacturing.

Keywords: multivariate control chart, nonparametric method, support vector data description, time-varying process

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Authors: Binger Lu

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It remains unclear whether second language (L2) speakers could use discourse context cues to predict upcoming information as native speakers do during online comprehension. Some researchers propose that L2 learners may have a reduced ability to generate predictions during discourse processing. At the same time, there is evidence that discourse-level cues are weighed more heavily in L2 processing than in L1. Previous studies showed that L1 prediction is sensitive to the global validity of predictive cues. The current study aims to explore whether and to what extent L2 learners can dynamically and strategically adjust their prediction in accord with the global validity of predictive cues in L2 discourse comprehension as native speakers do. In a self-paced reading experiment, Chinese native speakers (N=128), C-E bilinguals (N=128), and English native speakers (N=128) read high-predictable (e.g., Jimmy felt thirsty after running. He wanted to get some water from the refrigerator.) and low-predictable (e.g., Jimmy felt sick this morning. He wanted to get some water from the refrigerator.) discourses in two-sentence frames. The global validity of predictive cues was manipulated by varying the ratio of predictable (e.g., Bill stood at the door. He opened it with the key.) and unpredictable fillers (e.g., Bill stood at the door. He opened it with the card.), such that across conditions, the predictability of the final word of the fillers ranged from 100% to 0%. The dependent variable was reading time on the critical region (the target word and the following word), analyzed with linear mixed-effects models in R. C-E bilinguals showed reliable prediction across all validity conditions (β = -35.6 ms, SE = 7.74, t = -4.601, p< .001), and Chinese native speakers showed significant effect (β = -93.5 ms, SE = 7.82, t = -11.956, p< .001) in two of the four validity conditions (namely, the High-validity and MedLow conditions, where fillers ended with predictable words in 100% and 25% cases respectively), whereas English native speakers didn’t predict at all (β = -2.78 ms, SE = 7.60, t = -.365, p = .715). There was neither main effect (χ^²(3) = .256, p = .968) nor interaction (Predictability: Background: Validity, χ^²(3) = 1.229, p = .746; Predictability: Validity, χ^²(3) = 2.520, p = .472; Background: Validity, χ^²(3) = 1.281, p = .734) of Validity with speaker groups. The results suggest that prediction occurs in L2 discourse processing but to a much less extent in L1, witha significant effect in some conditions of L1 Chinese and anull effect in L1 English processing, consistent with the view that L2 speakers are more sensitive to discourse cues compared with L1 speakers. Additionally, the pattern of L1 and L2 predictive processing was not affected by the global validity of predictive cues. C-E bilinguals’ predictive processing could be partly transferred from their L1, as prior research showed that discourse information played a more significant role in L1 Chinese processing.

Keywords: bilingualism, discourse processing, global validity, prediction, self-paced reading

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Authors: Ali Kassem, Yhea Kishik, Ali Hassan, Mohamed Abdelwahab

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Introduction: Accelerated coronary and peripheral vascular atherosclerosis is one of the most common and chronic complications of diabetes mellitus. A recent aspect of coronary artery disease in this condition is its silent nature. The aim of the work: Detection of the prevalence of silent myocardial ischemia (SMI) in Upper Egypt type 2 diabetic males and to select male diabetic population who should be screened for SMI. Patients and methods: 100 type 2 diabetic male patients with a negative history of angina or anginal equivalent symptoms and 30 healthy control were included. Full medical history and thorough clinical examination were done for all participants. Fasting and post prandial blood glucose level, lipid profile, (HbA1c), microalbuminuria, and C-reactive protein were done for all participants Resting ECG, trans-thoracic echocardiography, treadmill exercise ECG, myocardial perfusion imaging were done for all participants and patients positive for one or more NITs were subjected for coronary angiography. Results Twenty nine patients (29%) were positive for one or more NITs in the patients group compared to only one case (3.3%) in the controls. After coronary angiography, 20 patients were positive for significant coronary artery stenosis in the patients group, while it was refused to be done by the patient in the controls. There were statistical significant difference between the two groups regarding, hypertension, dyslipidemia and obesity, family history of DM and IHD with higher levels of microalbuminuria, C-reactive protein, total lipids in patient group versus controls According to coronary angiography, patients were subdivided into two subgroups, 20 positive for SMI (positive for coronary angiography) and 80 negative for SMI (negative for coronary angiography). No statistical difference regarding family history of DM and type of diabetic therapy was found between the two subgroups. Yet, smoking, hypertension, obesity, dyslipidemia and family history of IHD were significantly higher in diabetics positive versus those negative for SMI. 90% of patients in subgroup positive for SMI had two or more cardiac risk factors while only two patients had one cardiac risk factor (10%). Uncontrolled DM was detected more in patients positive for SMI. Diabetic complications were more prevalent in patients positive for SMI versus those negative for SMI. Most of the patients positive for SMI have DM more than 5 years duration. Resting ECG and resting Echo detected only 6 and 11 cases, respectively, of the 20 positive cases in group positive for SMI compared to treadmill exercise ECG and myocardial perfusion imaging that detected 16 and 18 cases respectively, Conclusion: Type 2 diabetic male patients should be screened for detection of SMI when aged above 50 years old, diabetes duration is more than 5 years, presence of two or more cardiac risk factors and/or patients suffering from one or more of the chronic diabetic complications. CRP, is an important parameter for selection of type 2 diabetic male patients who should be screened for SMI. Non invasive cardiac tests are reliable for screening of SMI in these patients in our locality.

Keywords: C-reactive protein, Silent myocardial ischemia, Stress tests, type 2 DM

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Authors: Ebim Matthew Abua

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In Chinua Achebe’s Things Fall Apart (henceforth, TFA), the character Unoka is portrayed as a weakling and indolent person even when he was a creative artist, a talented musician, and a mathematician. His lack of achievement becomes the barometer for measuring his success. Right from time, music is considered to be of great significance because of its capacity to recreate and retell social events. To this end, music is both a social act and a creative art. As a social act, music is a discursive medium that exploits the dynamics of art in its evaluation of society. Music is so much a part of human existence that its presence in literature can help readers relate to fictional situations and characters. In this paper, the character Unoka is examined against the backdrop of his musical proclivities and his contributions to the overall development of TFA. Unfortunately, Achebe’s Things Fall Apart, a product of artistic creativity, portrays the personality of Unoka as lazy and uninspiring because he (Unoka) is a musician who is busy playing his flute and hardly doing anything productive. This paper is significant because it examines the literary and or linguistic depiction of Unoka and the aftermath of that depiction on the entire novel and, by extension, the larger society. Methodologically, this paper adopted the qualitative approach from the ethnography of communication (EOC), which is the analysis of communication within the wider context of the social and cultural practices and beliefs of the members of a particular culture or speech community. The aim of this qualitative research method includes the ability to discern which communication acts and/or codes are important to different groups, what types of meanings groups apply to different communication events, and how group members learn these codes to provide insight into particular communities. The study reveals that the people of Umuofia were mono-directional in their economy, and there was no room for diversification. One was either a farmer, or such a person was relegated to the background. Unoka, taking up a new challenge of diversifying the economy from the perspective of entertainment, was viewed as a misnomer. This study opens the door to other areas of studying Achebe’s epic novel apart from the critical works of literary artists that have been dished out over time.

Keywords: literature, popular culture, unoka, things fall apart

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Authors: Inkeri Jaaskelainen

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The aim of this study is to shed light on what is it like to study in apprenticeship training using intermediate (or even lower level) Finnish. The aim is to find out and describe these students' experiences and feelings while acquiring a profession in Finnish as it is important to understand how immigrant background adult learners learn and how their needs could be better taken into account. Many students choose apprenticeships and start vocational training while their language skills in Finnish are still very weak. At work, students should be able to simultaneously learn Finnish and do vocational studies in a noisy, demanding, and stressful environment. Learning and understanding new things is very challenging under these circumstances, and sometimes students get exhausted and experience a lot of stress - which makes learning even more difficult. Students are different from each other, and so are their ways to learn. Both duties at work and school assignments require reasonably good general language skills, and, especially at work, language skills are also a safety issue. The empirical target of this study is a group of students with an immigrant background who studied in various fields with intensive L2 support in 2016–2018 and who by now have completed a vocational upper secondary qualification. The interview material for this narrative study was collected from those who completed apprenticeship training in 2019–2020. The data collection methods used are a structured thematic interview, a questionnaire, and observational data. Interviewees with an immigrant background have an inconsistent cultural and educational background - some have completed an academic degree in their country of origin while others have learned to read and write only in Finland. The analysis of the material utilizes thematic analysis, which is used to examine learning and related experiences. Learning a language at work is very different from traditional classroom teaching. With evolving language skills, at an intermediate level at best, rushing and stressing makes it even more difficult to understand and increases the fear of failure. Constant noise, rapidly changing situations, and uncertainty undermine the learning and well-being of apprentices. According to preliminary results, apprenticeship training is well suited to the needs of an adult immigrant student. In apprenticeship training, students need a lot of support for learning and understanding a new communication and working culture. Stress can result in, e.g., fatigue, frustration, and difficulties in remembering and understanding. Apprenticeship training can be seen as a good path to working life. However, L2 support is a very important part of apprenticeship training, and it indeed helps students to believe that one day they will graduate and even get employed in their new country.

Keywords: apprenticeship training, vocational basic degree, Finnish learning, wee-being

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Authors: B. Orser, A. Riding, Y. Li

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To inform government about how gender gaps in SME ( small and medium-sized enterprise) contracting might be redressed, the research question was: What are the key obstacles to, and response strategies for, increasing the engagement of women business owners among SME suppliers to the government of Canada? Thirty-five interviews with senior policymakers, supplier diversity organization executives, and expert witnesses to the Canadian House of Commons, Standing Committee on Government Operations and Estimates. Qualitative data were conducted and analysed using N’Vivo 11 software. High order response categories included: (a) SME risk mitigation strategies, (b) SME procurement program design, and (c) performance measures. Primary obstacles cited were government red tape and long and complicated requests for proposals (RFPs). The majority of 'common' complaints occur when SMEs have questions about the federal procurement process. Witness responses included use of outcome-based rather than prescriptive procurement practices, more agile procurement, simplified RFPs, making payment within 30 days a procurement priority. Risk mitigation strategies included provision of procurement officers to assess risks and opportunities for businesses and development of more agile procurement procedures and processes. Recommendations to enhance program design included: improved definitional consistency of qualifiers and selection criteria, better co-ordination across agencies; clarification about how SME suppliers benefit from federal contracting; goal setting; specification of categories that are most suitable for women-owned businesses; and, increasing primary contractor awareness about the importance of subcontract relationships. Recommendations also included third-party certification of eligible firms and the need to enhance SMEs’ financial literacy to reduce financial errors. Finally, there remains the need for clear and consistent pre-program statistics to establish baselines (by sector, issuing department) performance measures, targets based on percentage of contracts granted, value of contract, percentage of target employee (women, indigenous), and community benefits including hiring local employees. The study advances strategies to enhance federal procurement programs to facilitate socio-economic policy objectives.

Keywords: procurement, small business, policy, women

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Authors: Medani Prasad Rijal

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Forest itself is a factory as well as product. It supplies tangible and intangible goods and services. It supplies timber, fuel wood, fodder, grass leaf litter as well as non timber edible goods and medicinal and aromatic products additionally provides environmental services. These environmental services are of local, national or even global importance. In Nepal, more than 19 thousands community forests are providing environmental service in less economic benefit than actual efficiency. There is a risk of cost of management of those forest exceeds benefits and forests get converted to open access resources in future. Most of the environmental goods and services do not have markets which mean no prices at which they are available to the consumers, therefore the valuation of these services goods and services establishment of paying mechanism for such services and insure the benefit to community is more relevant in local as well as global scale. There are few examples of carbon trading in domestic level to meet the country wide emission goal. In this contest, the study aims to explore the public attitude towards carbon offsetting and their responsibility over service providers. This study helps in promotion of environment service awareness among general people, service provider and community forest. The research helps to unveil the carbon pool scenario in community forest and willingness to pay for carbon offsetting of people who are consuming more energy than general people and emitting relatively more carbon in atmosphere. The study has assessed the carbon pool status in two community forest and valuated carbon service from community forest through willingness to pay in Dharan municipality situated in eastern. In the study, in two community forests carbon pools were assessed following the guideline “Forest Carbon Inventory Guideline 2010” prescribed by Ministry of Forest and soil Conservation, Nepal. Final outcomes of analysis in intensively managed area of Hokse CF recorded as 103.58 tons C /ha with 6173.30 tons carbon stock. Similarly in Hariyali CF carbon density was recorded 251.72 mg C /ha. The total carbon stock of intensively managed blocks in Hariyali CF is 35839.62 tons carbon.

Keywords: carbon, offsetting, sequestration, valuation, willingness to pay

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Authors: Aarti M. Shetty, Estela Davoodi, Subrata Gangooly, Anita Rao-Coppisetty

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Background: Testing Patency of Fallopian Tubes is among one of the several protocols for investigating Subfertile Couples. Both, Hysterosalpingogram (HSG) and Laparoscopy and dye test have been used as Tubal patency test for several years, with well-known limitation. Hysterosalpingo Contrast Sonography (HyCoSy) can be used as an alternative tool to HSG, to screen patency of Fallopian tubes, with an advantage of being non-ionising, and also, use of transvaginal scan to diagnose pelvic pathology. Aim: To determine the indication and analyse the performance of transvaginal scan and HyCoSy in Broomfield Hospital. Methods: We retrospectively analysed fertility workup of 282 women, who attended HyCoSy clinic at our institution from January 2015 to June 2016. An Audit proforma was designed, to aid data collection. Data was collected from patient notes and electronic records, which included patient demographics; age, parity, type of subfertility (primary or secondary), duration of subfertility, past medical history and base line investigation (hormone profile and semen analysis). Findings of the transvaginal scan, HyCoSy and Laparoscopy were also noted. Results: The most common indication for referral were as a part of primary fertility workup on couples who had failure to conceive despite intercourse for a year, other indication for referral were recurrent miscarriage, history of ectopic pregnancy, post reversal of sterilization(vasectomy and tuboplasty), Post Gynaecology surgery(Loop excision, cone biopsy) and amenorrhea. Basic Fertility workup showed 34% men had abnormal semen analysis. HyCoSy was successfully completed in 270 (95%) women using ExEm foam and Transvaginal Scan. Of the 270 patients, 535 tubes were examined in total. 495/535 (93%) tubes were reported as patent, 40/535 (7.5%) tubes were reported as blocked. A total of 17 (6.3%) patients required laparoscopy and dye test after HyCoSy. In these 17 patients, 32 tubes were examined under laparoscopy, and 21 tubes had findings similar to HyCoSy, with a concordance rate of 65%. In addition to this, 41 patients had some form of pelvic pathology (endometrial polyp, fibroid, cervical polyp, fibroid, bicornuate uterus) detected during transvaginal scan, who referred to corrective surgeries after attending HyCoSy Clinic. Conclusion: Our audit shows that HyCoSy and Transvaginal scan can be a reliable screening test for low risk women. Furthermore, it has competitive diagnostic accuracy to HSG in identifying tubal patency, with an additional advantage of screening for pelvic pathology. With addition of 3D Scan, pulse Doppler and other non-invasive imaging modality, HyCoSy may potentially replace Laparoscopy and chromopertubation in near future.

Keywords: hysterosalpingo contrast sonography (HyCoSy), transvaginal scan, tubal infertility, tubal patency test

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Authors: Katie Emerson, Sara Perez-Ojalvo, Jim Komorowski, Danielle Greenberg

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The purpose of this study was to evaluate arginase activity levels in response to combinations of an inositol-stabilized arginine silicate (ASI; Nitrosigine®), L-arginine, and Inositol. Arginine acts as a vasodilator that promotes increased blood flow resulting in enhanced delivery of oxygen and nutrients to the brain and other tissues. ASI alone has been shown to improve performance on cognitive tasks. Arginase, found in human serum, catalyzes the conversion of arginine to ornithine and urea, completing the last step in the urea cycle. Decreasing arginase levels maintains arginine and results in increased nitric oxide production. This study aimed to determine the most effective combination of ASI, L-arginine and inositol for minimizing arginase levels and therefore maximize ASI’s effect on cognition. Serum was taken from untreated healthy donors by separation from clotted factors. Arginase activity of serum in the presence or absence of test products was determined (QuantiChrom™, DARG-100, Bioassay Systems, Hayward CA). The remaining ultra-filtrated serum units were harvested and used as the source for the arginase enzyme. ASI alone or combined with varied levels of Inositol were tested as follows: ASI + inositol at 0.25 g, 0.5 g, 0.75 g, or 1.00 g. L-arginine was also tested as a positive control. All tests elicited changes in arginase activity demonstrating the efficacy of the method used. Adding L-arginine to serum from untreated subjects, with or without inositol only had a mild effect. Adding inositol at all levels reduced arginase activity. Adding 0.5 g to the standardized amount of ASI led to the lowest amount of arginase activity as compared to the 0.25g 0.75g or 1.00g doses of inositol or to L-arginine alone. The outcome of this study demonstrates an interaction of the pairing of inositol with ASI on the activity of the enzyme arginase. We found that neither the maximum nor minimum amount of inositol tested in this study led to maximal arginase inhibition. Since the inhibition of arginase activity is desirable for product formulations looking to maintain arginine levels, the most effective amount of inositol was deemed preferred. Subsequent studies suggest this moderate level of inositol in combination with ASI leads to cognitive improvements including reaction time, executive function, and concentration.

Keywords: arginine, inositol, arginase, cognitive benefits

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Authors: Parikshit Gogo, N. N. Dutta

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The oxidative enzymes specially laccase (benzenediol: oxygen oxidoreductase, E.C.1.10.3.2) from bacteria, fungi and plants have been playing an important role in green technologies due to their specific advantageous properties. Laccase from different sources and in different forms was used as a biocatalyst in many oxidation and conjugation reactions starting from phenol to hydrocarbons. Tea polyphenols and its derivatives attract the scientific community because of their potential use as antioxidants in food, pharmaceutical and cosmetic industries. Conjugate of polyphenols emerged as a novel materials which shows better stability and antioxidant properties in applied fields. The conjugation reaction of catechin with poly (allylamine) has been studied using free, immobilized and cross-linked enzyme crystals (CLEC) of laccase from Trametes versicolor with particular emphasis on the effect of pertinent variables and kinetic aspects of the reaction. The stability and antioxidant property of the conjugated product was improved as compared to the unconjugated tea polyphenols. The reaction was studied in 11 different solvents in order to deduce the solvent effect through an attempt to correlate the initial reaction rate with solvent properties such as hydrophobicity (logP), water solubility (logSw), electron pair acceptance (ETN) and donation abilities (DNN), polarisibility and dielectric constant which exhibit reasonable correlations. The study revealed, in general that polar solvents favour the initial reaction rate. The kinetics of the conjugation reaction conformed to the so-called Ping-Pong-Bi-Bi mechanism with catechin inhibition. The stability as well as activity of the CLEC was better than the free enzymes and immobilized laccase for practical application. In case of immobilized laccase system marginal diffusional limitation could be inferred from the experimental data. The kinetic parameters estimated by non-linear regression analysis were found to be KmPAA(mM) = 0.75, 1.8967 and Kmcat (mM) = 11.769, 15.1816 for free and immobilized laccase respectively. An attempt has been made to assess the activity of the laccase for the conjugation reaction in relation to other reactions such as dimerisation of ferulic acids and develop a protocol to enhance polyphenol antioxidant activity.

Keywords: laccase, catechin, conjugation reaction, antioxidant properties

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Authors: Taha Anjamrooz, Sareh Rajabi, Hasan Mahmmud, Ghassan Abulebdeh

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Water availability, as well as water demand, are not uniformly distributed in time and space. Numerous extra-large water diversion projects are launched in Amazon to alleviate water scarcities. This research utilizes statistical analysis to examine the temporal and spatial features of 40 extra-large water diversion projects in Amazon. Using a network analysis method, the correlation between seven major basins is measured, while the impact analysis method is employed to explore the associated economic, environmental, and social impacts. The study unearths that the development of water diversion in Amazon has witnessed four stages, from a preliminary or initial period to a phase of rapid development. It is observed that the length of water diversion channels and the quantity of water transferred have amplified significantly in the past five decades. As of 2015, in Amazon, more than 75 billion m³ of water was transferred amidst 12,000 km long channels. These projects extend over half of the Amazon Area. The River Basin E is currently the most significant source of transferred water. Through inter-basin water diversions, Amazon gains the opportunity to enhance the Gross Domestic Product (GDP) by 5%. Nevertheless, the construction costs exceed 70 billion US dollars, which is higher than any other country. The average cost of transferred water per unit has amplified with time and scale but reduced from western to eastern Amazon. Additionally, annual total energy consumption for pumping exceeded 40 billion kilowatt-hours, while the associated greenhouse gas emissions are assessed to be 35 million tons. Noteworthy to comprehend that ecological problems initiated by water diversion influence the River Basin B and River Basin D. Due to water diversion, more than 350 thousand individuals have been relocated, away from their homes. In order to enhance water diversion sustainability, four categories of innovative measures are provided for decision-makers: development of water tradeoff projects strategies, improvement of integrated water resource management, the formation of water-saving inducements, and pricing approach, and application of ex-post assessment.

Keywords: sustainability, water trade-off projects, environment, Amazon

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Authors: Jae-Hyeon Kim, Michael Lee

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Intrinsic and acquired resistance limits the therapeutic benefits of oncogenic BRAF inhibitors in melanoma. MicroRNAs (miRNA) regulate the expression of target mRNAs by repressing their translation. Thus, we investigated miRNA expression patterns in melanoma cell lines to identify candidate biomarkers for acquired resistance to BRAF inhibitor. Here, we used Affymetrix miRNA V3.0 microarray profiling platform to compare miRNA expression levels in three cell lines containing BRAF inhibitor-sensitive A375P BRAF V600E cells, their BRAF inhibitor-resistant counterparts (A375P/Mdr), and SK-MEL-2 BRAF-WT cells with intrinsic resistance to BRAF inhibitor. The miRNAs with at least a two-fold change in expression between BRAF inhibitor-sensitive and –resistant cell lines, were identified as differentially expressed. Averaged intensity measurements identified 138 and 217 miRNAs that were differentially expressed by 2 fold or more between: 1) A375P and A375P/Mdr; 2) A375P and SK-MEL-2, respectively. The hierarchical clustering revealed differences in miRNA expression profiles between BRAF inhibitor-sensitive and –resistant cell lines for miRNAs involved in intrinsic and acquired resistance to BRAF inhibitor. In particular, 43 miRNAs were identified whose expression was consistently altered in two BRAF inhibitor-resistant cell lines, regardless of intrinsic and acquired resistance. Twenty five miRNAs were consistently upregulated and 18 downregulated more than 2-fold. Although some discrepancies were detected when miRNA microarray data were compared with qPCR-measured expression levels, qRT-PCR for five miRNAs (miR-3617, miR-92a1, miR-1246, miR-1936-3p, and miR-17-3p) results showed excellent agreement with microarray experiments. To further investigate cellular functions of miRNAs, we examined effects on cell proliferation. Synthetic oligonucleotide miRNA mimics were transfected into three cell lines, and proliferation was quantified using a colorimetric assay. Of the 5 miRNAs tested, only miR-1246 altered cell proliferation of A375P/Mdr cells. The transfection of miR-1246 mimic strongly conferred PLX-4720 resistance to A375P/Mdr cells, implying that miR-1246 upregulation confers acquired resistance to BRAF inhibition. We also found that PLX-4720 caused much greater G2/M arrest in A375P/Mdr cells transfected with miR-1246mimic than that seen in scrambled RNA-transfected cells. Additionally, miR-1246 mimic partially caused a resistance to autophagy induction by PLX-4720. These results indicate that autophagy does play an essential death-promoting role inPLX-4720-induced cell death. Taken together, these results suggest that miRNA expression profiling in melanoma cells can provide valuable information for a network of BRAF inhibitor resistance-associated miRNAs.

Keywords: microRNA, BRAF inhibitor, drug resistance, autophagy

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Authors: Zuhal Mohammed, Khalid Siddig, Harald Grethe

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Vocational training (VT) has been identified as a potential engine for achieving economic and social development, particularly in developing countries, while during the last two decades it is deemed as an essential determinant of human capital accumulation. Furthermore, it has a crucial role in reducing inequality, wage gaps and unemployment and in promoting skill decomposition. Government plays an important role in the human capital formulation by providing finance for education. In some countries, a large portion of the public educational investment is devoted to academic education (primary, secondary and tertiary). This is reflected in disproportionately increasing investment in various education sectors other than vocational education and VT. Nevertheless, the finance of VT system is not likely to increase or even remain at its existing level. This paper conducts an in-depth analysis to quantify the impacts of various options for expanding the public expenditure on education as well as vocational training in the Sudan. The study uses a recursive dynamic CGE modelling framework that accommodates VT and allows depicting the impact of various policies targeting the vocational training system with special focus on the agricultural sector. This allows for depicting the potential effects of various resource allocation policies not only among education versus non-education sectors, but also between the various types of education and training. Moreover, the study assesses the role of VT system in the economy through its influence on workers’ skill improvement and their movement across sectors. The results show that an increase in the public educational investment will lead to decrease the supply of low and high educated workers as results of increasing the school participation of the students in the short run. While in the medium to long run, this measure guides to increase the productivity of the labour and thus the growth rate of the gross domestic product (GDP). Therefore, the findings of the study provide Sudanese policymakers with needed information to help to adopt measures to reduce unemployment, enhance workers’ skill and ultimately improve livelihoods.

Keywords: vocational training, recursive dynamic CGE, skill level, labour market, economic growth, Sudan

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Authors: Ilze Dimanta, Zane Rutkovska, Vizma Nikolajeva, Janis Kleperis, Indrikis Muiznieks

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Majority of word’s steadily increasing energy consumption is provided by non-renewable fossil resources. Need to find an alternative energy resource is essential for further socio-economic development. Hydrogen is renewable, clean energy carrier with high energy density (142 MJ/kg, accordingly – oil has 42 MJ/kg). Biological hydrogen production is an alternative way to produce hydrogen from renewable resources, e.g. using organic waste material resource fermentation that facilitate recycling of sewage and are environmentally benign. Hydrogen gas is produced during the fermentation process of bacteria in anaerobic conditions. Bacteria are producing hydrogen in the liquid phase and when thermodynamic equilibrium is reached, hydrogen is diffusing from liquid to gaseous phase. Because of large quantities of available crude glycerol and the highly reduced nature of carbon in glycerol per se, microbial conversion of it seems to be economically and environmentally viable possibility. Such industrial organic waste product as crude glycerol is perspective for usage in feedstock for hydrogen producing bacteria. The process of biodiesel production results in 41% (w/w) of crude glycerol. The developed lab-scale test system (experimental bioreactor) with hydrogen micro-electrode (Unisense, Denmark) was used to determine hydrogen production yield and rate in the liquid phase. For hydrogen analysis in the gas phase the RGAPro-100 mass-spectrometer connected to the experimental test-system was used. Fermentative bacteria strains were tested for hydrogen gas production rates. The presence of hydrogen in gaseous phase was measured using mass spectrometer but registered concentrations were comparatively small. To decrease the hydrogen partial pressure in liquid phase reactor with a system for continuous bubbling with inert gas was developed. H2 production rate for the best producer in liquid phase reached 0,40 mmol H2/l, in gaseous phase - 1,32 mmol H2/l. Hydrogen production rate is time dependent – higher rate of hydrogen production is at the fermentation process beginning when concentration increases, but after three hours of fermentation, it decreases.

Keywords: bio-hydrogen, fermentation, experimental bioreactor, crude glycerol

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Authors: Joel Bonales, Venecia Solorzano, Carlos Garcia

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A great percentage of the wastewater generated in developing countries don’t receive any treatment, which leads to numerous environmental impacts. In response to this, a paradigm change in the current wastewater treatment model based on large scale plants towards a small and medium scale based model has been proposed. Nevertheless, small scale wastewater treatment (SS-WTTP) with novel technologies such as anaerobic digesters, as well as the utilization of derivative co-products such as biogas, still presents diverse environmental impacts which must be assessed. This study consisted in a Life Cycle Assessment (LCA) performed to a SS-WWTP which treats wastewater from a small commercial block in the city of Morelia, Mexico. The treatment performed in the SS-WWTP consists in anaerobic and aerobic digesters with a daily capacity of 5,040 L. Two different scenarios were analyzed: the current plant conditions and a hypothetical energy use of biogas obtained in situ. Furthermore, two different allocation criteria were applied: full impact allocation to the system’s main product (treated water) and substitution credits for replacing Mexican grid electricity (biogas) and clean water pumping (treated water). The results showed that the analyzed plant had bigger impacts than what has been reported in the bibliography in the basis of wastewater volume treated, which may imply that this plant is currently operating inefficiently. The evaluated impacts appeared to be focused in the aerobic digestion and electric generation phases due to the plant’s particular configuration. Additional findings prove that the allocation criteria applied is crucial for the interpretation of impacts and that that the energy use of the biogas obtained in this plant can help mitigate associated climate change impacts. It is concluded that SS-WTTP is a environmentally sound alternative for wastewater treatment from a systemic perspective. However, this type of studies must be careful in the selection of the allocation criteria and replaced products, since these factors have a great influence in the results of the assessment.

Keywords: biogas, life cycle assessment, small scale treatment, wastewater treatment

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Authors: Caroline Lavratti, Pedro Dal Lago, Gustavo Reinaldo, Gilson Dorneles, Andreia Bard, Laira Fuhr, Daniela Pochmann, Alessandra Peres, Luciane Wagner, Viviane Elsner

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Approximately 1% of the world's population is affected by schizophrenia (SZ), a chronic and debilitating neurodevelopmental disorder. Among possible factors, reduced levels of Brain-derived neurotrophic factor (BDNF) has been recognized in physiopathogenesis and course of SZ. In this context, peripheral BDNF levels have been used as a biomarker in several clinical studies, since this neurotrophin is able to cross the blood-brain barrier in a bi-directional manner and seems to present a strong correlation with the central nervous system fluid levels. The patients with SZ usually adopts a sedentary lifestyle, which has been partly associated with the increase in obesity incidence rates, metabolic syndrome, type 2 diabetes and coronary heart disease. On the other hand, exercise, a non-invasive and low cost intervention, has been considered an important additional therapeutic option for this population, promoting benefits to physical and mental health. To our knowledge, few studies have been pointed out that the positive effects of exercise in SZ patients are mediated, at least in part, to enhanced levels of BDNF after training. However, these studies are focused on evaluating the effect of single bouts of exercise of chronic interventions, data concerning the short- and long-term exercise outcomes on BDNF are scarce. Therefore, this study aimed to evaluate the effect of a concurrent exercise protocol (CEP) on plasma BDNF levels of SZ patients in different time-points. Material and Methods: This study was approved by the Research Ethics Committee of the Centro Universitário Metodista do IPA (no 1.243.680/2015). The participants (n=15) were subbmited to the CEP during 90 days, 3 times a week for 60 minutes each session. In order to evaluate the short and long-term effects of exercise, blood samples were collected pre, 30, 60 and 90 days after the intervention began. Plasma BDNF levels were determined with the ELISA method, from Sigma-Aldrich commercial kit (catalog number RAB0026) according to manufacturer's instructions. Results: A remarkable increase on plasma BDNF levels at 90 days after training compared to baseline (p=0.006) and 30 days (p=0.007) values were observed. Conclusion: Our data are in agreement with several studies that show significant enhancement on BDNF levels in response to different exercise protocols in SZ individuals. We might suggest that BDNF upregulation after training in SZ patients acts in a dose-dependent manner, being more pronounced in response to chronic exposure. Acknowledgments: This work was supported by Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS)/Brazil.

Keywords: exercise, BDNF, schizophrenia, time-points

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Authors: Hesam Gholami

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Elevated suspended sediment loads in riverine systems resulting from accelerated erosion due to human activities are a serious threat to the sustainable management of watersheds and ecosystem services therein worldwide. Therefore, mitigation of deleterious sediment effects as a distributed or non-point pollution source in the catchments requires reliable provenance information. Sediment tracing or sediment fingerprinting, as a combined process consisting of sampling, laboratory measurements, different statistical tests, and the application of mixing or unmixing models, is a useful technique for discriminating the sources of sediments. From 1996 to the present, different aspects of this technique, such as grouping the sources (spatial and individual sources), discriminating the potential sources by different statistical techniques, and modification of mixing and unmixing models, have been introduced and modified by many researchers worldwide, and have been applied to identify the provenance of fine materials in agricultural, rural, mountainous, and coastal catchments, and in large catchments with numerous lakes and reservoirs. In the last two decades, efforts exploring the uncertainties associated with sediment fingerprinting results have attracted increasing attention. The frameworks used to quantify the uncertainty associated with fingerprinting estimates can be divided into three groups comprising Monte Carlo simulation, Bayesian approaches and generalized likelihood uncertainty estimation (GLUE). Given the above background, the primary goal of this study was to apply geochemical fingerprinting within the GLUE framework in the estimation of sub-basin spatial sediment source contributions in the arid Mehran River catchment in southern Iran, which drains into the Persian Gulf. The accuracy of GLUE predictions generated using four different sets of statistical tests for discriminating three sub-basin spatial sources was evaluated using 10 virtual sediments (VS) samples with known source contributions using the root mean square error (RMSE) and mean absolute error (MAE). Based on the results, the contributions modeled by GLUE for the western, central and eastern sub-basins are 1-42% (overall mean 20%), 0.5-30% (overall mean 12%) and 55-84% (overall mean 68%), respectively. According to the mean absolute fit (MAF; ≥ 95% for all target sediment samples) and goodness-of-fit (GOF; ≥ 99% for all samples), our suggested modeling approach is an accurate technique to quantify the source of sediments in the catchments. Overall, the estimated source proportions can help watershed engineers plan the targeting of conservation programs for soil and water resources.

Keywords: sediment source tracing, generalized likelihood uncertainty estimation, virtual sediment mixtures, Iran

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Authors: Ibtissem Hosni, Lilia Bennaceur Farah, Saber Mohamed Naceur

Abstract:

In order to assess the water availability in the soil, it is crucial to have information about soil distributed moisture content; this parameter helps to understand the effect of humidity on the exchange between soil, plant cover and atmosphere in addition to fully understanding the surface processes and the hydrological cycle. On the other hand, aerodynamic roughness length is a surface parameter that scales the vertical profile of the horizontal component of the wind speed and characterizes the surface ability to absorb the momentum of the airflow. In numerous applications of the surface hydrology and meteorology, aerodynamic roughness length is an important parameter for estimating momentum, heat and mass exchange between the soil surface and atmosphere. It is important on this side, to consider the atmosphere factors impact in general, and the natural erosion in particular, in the process of soil evolution and its characterization and prediction of its physical parameters. The study of the induced movements by the wind over soil vegetated surface, either spaced plants or plant cover, is motivated by significant research efforts in agronomy and biology. The known major problem in this side concerns crop damage by wind, which presents a booming field of research. Obviously, most models of soil surface require information about the aerodynamic roughness length and its temporal and spatial variability. We have used a bi-dimensional multi-scale (2D MLS) roughness description where the surface is considered as a superposition of a finite number of one-dimensional Gaussian processes each one having a spatial scale using the wavelet transform and the Mallat algorithm to describe natural surface roughness. We have introduced multi-layer aspect of the humidity of the soil surface, to take into account a volume component in the problem of backscattering radar signal. As humidity increases, the dielectric constant of the soil-water mixture increases and this change is detected by microwave sensors. Nevertheless, many existing models in the field of radar imagery, cannot be applied directly on areas covered with vegetation due to the vegetation backscattering. Thus, the radar response corresponds to the combined signature of the vegetation layer and the layer of soil surface. Therefore, the key issue of the numerical estimation of soil moisture is to separate the two contributions and calculate both scattering behaviors of the two layers by defining the scattering of the vegetation and the soil blow. This paper presents a synergistic methodology, and it is for estimating roughness and soil moisture from C-band radar measurements. The methodology adequately represents a microwave/optical model which has been used to calculate the scattering behavior of the aerodynamic vegetation-covered area by defining the scattering of the vegetation and the soil below.

Keywords: aerodynamic, bi-dimensional, vegetation, synergistic

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