Search results for: spatial gene

Authors: Mateen A Khan, Taj Mohammad, Md. Imtaiyaz Hassan

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Alzheimer’s disease is characterized by the accumulation of the processing products of the amyloid beta peptide cleaved by amyloid precursor protein (APP). Iron increases the synthesis of amyloid beta peptides, which is why iron is present in Alzheimer's disease patients' amyloid plaques. Iron misregulation in the brain is linked to the overexpression of APP protein, which is directly related to amyloid-β aggregation in Alzheimer’s disease. The APP 5'-UTR region encodes a functional iron-responsive element (IRE) stem-loop that represents a potential target for modulating amyloid production. Targeted regulation of APP gene expression through the modulation of 5’-UTR sequence function represents a novel approach for the potential treatment of AD because altering APP translation can be used to improve both the protective brain iron balance and provide anti-amyloid efficacy. The molecular docking analysis of APP IRE RNA with eukaryotic translation initiation factors yields several models exhibiting substantial binding affinity. The finding revealed that the interaction involved a set of functionally active residues within the binding sites of eIF4F. Notably, APP IRE RNA and eIF4F interaction were stabilized by multiple hydrogen bonds with residues of APP IRE RNA and eIF4F. It was evident that APP IRE RNA exhibited a structural complementarity that tightly fit within binding pockets of eIF4F. The simulation studies further revealed the stability of the complexes formed between RNA and eIF4F, which is crucial for assessing the strength of these interactions and subsequent roles in the pathophysiology of Alzheimer’s disease. In addition, MD simulations would capture conformational changes in the IRE RNA and protein molecules during their interactions, illustrating the mechanism of interaction, conformational change, and unbinding events and how it may affect aggregation propensity and subsequent therapeutic implications. Our binding studies correlated well with the translation efficiency of APP mRNA. Overall, the outcome of this study suggests that the genomic modification and/or inhibiting the expression of amyloid protein by targeting APP IRE RNA can be a viable strategy to identify potential therapeutic targets for AD and subsequently be exploited for developing novel therapeutic approaches.

Keywords: Alzheimer's disease, Protein-RNA interaction analysis, molecular docking simulations, conformational dynamics, binding stability, binding kinetics, protein synthesis.

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Authors: Shveta Bathla, Preeti Rawat, Sudarshan Kumar, Rubina Baithalu, Jogender Singh Rana, Tushar Kumar Mohanty, Ashok Kumar Mohanty

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Pregnancy is a complex process which includes series of events such as fertilization, formation of blastocyst, implantation of embryo, placental formation and development of fetus. The success of these events depends on various interactions which are synchronized by endocrine interaction between a receptive dam and competent embryo. These interactions lead to change in expression of hormones and proteins. But till date no protein biomarker is available which can be used to detect successful completion of these events. We employed quantitative proteomics approach to develop putative serological biomarker which has diagnostic applicability for early detection of pregnancy in cows. For this study, sera were collected from control (non-pregnant, n=6) and pregnant animals on successive days of pregnancy (7, 19, 45, n=6). The sera were subjected to depletion for removal of albumin using Norgen depletion kit. The tryptic peptides were labeled with iTRAQ. The peptides were pooled and fractionated using bRPLC over 80 min gradient. Then 12 fractions were injected to nLC for identification and quantitation in DDA mode using ESI. Identification using Mascot search revealed 2056 proteins out of which 352 proteins were differentially expressed. Twenty proteins were upregulated and twelve proteins were down-regulated with fold change > 1.5 and < 0.6 respectively (p < 0.05). The gene ontology studies of DEPs using Panther software revealed that majority of proteins are actively involved in catalytic activities, binding and enzyme regulatory activities. The DEP'S such as NF2, MAPK, GRIPI, UGT1A1, PARP, CD68 were further subjected to pathway analysis using KEGG and Cytoscape plugin Cluego that showed involvement of proteins in successful implantation, maintenance of pluripotency, regulation of luteal function, differentiation of endometrial macrophages, protection from oxidative stress and developmental pathways such as Hippo. Further efforts are continuing for targeted proteomics, western blot to validate potential biomarkers and development of diagnostic kit for early pregnancy diagnosis in cows.

Keywords: bRPLC, Cluego, ESI, iTRAQ, KEGG, Panther

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Authors: A. Alli-Oluwafuyi, A. Amin, S. M. Fii, S. O. Amusa, A. Imam, N. T. Asogwa, W. I. Abdulmajeed, F. Olaseinde, B. V. Owoyele

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Chronic stress or prolonged glucocorticoid administration impairs higher cognitive functions in rodents and humans. However, the mechanisms are not fully clear. Insulin and receptors are expressed in the brain and are involved in cognition. Insulin resistance accompanies Alzheimer’s disease and associated cognitive decline. The goal of this study was to evaluate the effects of sub-chronic administration of a glucocorticoid, dexamethasone (DEX) on behavior and biochemical changes in prefrontal cortex (PFC). Male Wistar rats were administered DEX (2, 4 & 8 mg/kg, IP) or saline for seven consecutive days and behavior was assessed in the following paradigms: “Y” maze, elevated plus maze, Morris’ water maze and novel object recognition (NOR) tests. Insulin, lactate dehydrogenase (LDH) and Superoxide Dismutase (SOD) activity were evaluated in homogenates of the prefrontal cortex. DEX-treated rats exhibited impaired prefrontal cortex function manifesting as reduced locomotion, impaired novel object exploration and impaired short- and long-term spatial memory compared to normal controls (p < 0.05). These effects were not consistently dose-dependent. These behavioral alterations were accompanied by a decrease in insulin concentration observed in PFC of 4 mg/kg DEX-treated rats compared to control (10μIU/mg vs. 50μIU/mg; p < 0.05) but not 2mg/kg. Furthermore, we report a modification of brain stress markers LDH and SOD (p > 0.05). These results indicate that prolonged activation of GCs disrupt prefrontal cortex function which may be related to insulin impairment. These effects may not be attributable to a non-specific elevation of oxidative stress in the brain. Future studies would evaluate mechanisms of GR-induced insulin loss.

Keywords: dexamethasone, insulin, memory, prefrontal cortex

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Authors: Abu S. Mustafa, Mohammad W. Khan, Faraz Shaheed Khan, Nazima Habibi

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Brucellosis is a zoonotic disease of worldwide prevalence. There are at least four species and several strains of Brucella that cause human disease. Brucella genomes have very limited variation across strains, which hinder strain identification using classical molecular techniques, including PCR and 16 S rDNA sequencing. The aim of this study was to perform whole genome sequencing of clinical isolates of Brucella and perform bioinformatics and comparative genomics analyses to determine the existence of genetic differences across the isolates of a single Brucella species and strain. The draft sequence data were generated from 15 clinical isolates of Brucella melitensis (biovar 2 strain 63/9) using MiSeq next generation sequencing platform. The generated reads were used for further assembly and analysis. All the analysis was performed using Bioinformatics work station (8 core i7 processor, 8GB RAM with Bio-Linux operating system). FastQC was used to determine the quality of reads and low quality reads were trimmed or eliminated using Fastx_trimmer. Assembly was done by using Velvet and ABySS softwares. The ordering of assembled contigs was performed by Mauve. An online server RAST was employed to annotate the contigs assembly. Annotated genomes were compared using Mauve and ACT tools. The QC score for DNA sequence data, generated by MiSeq, was higher than 30 for 80% of reads with more than 100x coverage, which suggested that data could be utilized for further analysis. However when analyzed by FastQC, quality of four reads was not good enough for creating a complete genome draft so remaining 11 samples were used for further analysis. The comparative genome analyses showed that despite sharing same gene sets, single nucleotide polymorphisms and insertions/deletions existed across different genomes, which provided a variable extent of diversity to these bacteria. In conclusion, the next generation sequencing, bioinformatics, and comparative genome analysis can be utilized to find variations (point mutations, insertions and deletions) across different genomes of Brucella within a single strain. This information could be useful in surveillance and epidemiological studies supported by Kuwait University Research Sector grants MI04/15 and SRUL02/13.

Keywords: brucella, bioinformatics, comparative genomics, whole genome sequencing

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Authors: Nasim Hossein Hamzeh, Karim Shukurov, Abbas Ranjbar Saadat Abadi, Alaa Mhawish, Christian Opp

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Deserts are the main dust sources in the world. Also, recently driedLake beds have caused environmental problems inthe surrounding areas in the world. In this study, the Urmia Lake was the source of dustfromApril 24 to April 25, 2017.The local dust storm was combined with another large-scale dust storm that originated from Saudi Arabia and Iraq 1-2 days earlier. Synoptic investigation revealed that the severe dust storm was made by a strong Black Sea cyclone and a low-pressure system over the Middle East and Central Iraq in conjunction a high-pressure system and associated with a high gradient contour and a quasi-stationary long-wave trough over the east and south of the Mediterranean Sea. Based on HYSPLIT 72 hours backward and forward trajectories, the most probable dust transport routes to and from the Urmia Lake region are estimated. Using the concentration weighted trajectory (CWT) method based on 24 hours backward and 24 hours forward trajectories, the spatial distributions of potential sources of PM10 observed in the Urmia Lake region on April 23-26, 2017. Also, the vertical profile of dust particles using the WRF-Chem model with two dust schemes showed dust ascending up to 5 km from the lake. Also, the dust schemes outputs shows that the PM10 fluctuating changes are 12 hours earlier than the measured surface PM10 at five air pollution monitoring stations around the Urmia Lake in 23-26 April 2017.

Keywords: dust storm, synoptic investigation, WRF-chem model, urmia lake, lagrangian trajectory

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Authors: Olalekan Sunday Alabi, Titus Adeyemi Alonge, Olumuyiwa Idowu Ojo

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Agricultural land suitability analysis and mapping play an imperative role for sustainable utilization of scarce physical land resources. The objective of this study was to prepare spatial database of physical land resources for irrigated agriculture and to assess land suitability for irrigation and developing suitable area map of the study area. The study was conducted at Kampe-Omi irrigation scheme located at Yagba West Local Government Area of Kogi State, Nigeria. Temperature and rainfall data of the study area were collected for 10 consecutive years (2005-2014). Geographic Information System (GIS) techniques were used to develop irrigation land suitability map of the study area. Attribute parameters such as the slope, soil properties, topography of the study area were used for the analysis. The available data were arranged, proximity analysis of Arc-GIS was made, and this resulted into five mapping units. The final agricultural land suitability map of the study area was derived after overlay analysis. Based on soil composition, slope, soil properties and topography, it was concluded that; Kampe-Omi has rich sandy loam soil, which is viable for agricultural purpose, the soil composition is made up of 60% sand and 40% loam. The land-use pattern map of Kampe-Omi has vegetal area and water-bodies covering 55.6% and 19.3% of the total assessed area respectively. The landform of Kampe-Omi is made up of 41.2% lowlands, 37.5% normal lands and 21.3% highlands. Kampe-Omi is adequately suitable for agricultural purpose while an extra of 20.2% of the area is highly suitable for agricultural purpose making 72.6% while 18.7% of the area is slightly suitable.

Keywords: remote sensing, GIS, Kampe–Omi, land suitability, mapping

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Authors: Juan Zhou, Lusan Liu, Yanzhong Zhu, Kuixuan Lin, Wenqian Cai, Yu Wang, Xing Wang

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During the past few decades, there has been an increase in the number of coastal land reclamation projects for residential, commercial and industrial purposes in more and more coastal cities of China, which led to the destruction of the wetlands and loss of the sensitive marine habitats. Meanwhile, the influences and nature of these projects attract widespread public and academic concern. For identifying the trend of landscape (esp. Coastal reclamation) and ecological environment changes, understanding of which interacted, and offering a general science for the development of regional plans. In the paper, a case study was carried out in Bohai Bay area, based on the analysis of remote sensing data. Land use maps were created for 1954, 1970, 1981, 1990, 2000 and 2010. Landscape metrics were calculated and illustrated that the degree of reclamation changes was linked to the hydrodynamic environment and macrobenthos community. The results indicated that the worst of the loss of initial areas occurred during 1954-1970, with 65.6% lost mostly to salt field; to 2010, Coastal reclamation area increased more than 200km² as artificial landscape. The numerical simulation of tidal current field in 2003 and 2010 respectively showed that the flow velocity in offshore became faster (from 2-5 cm/s to 10-20 cm/s), and the flow direction seem to go astray. These significant changes of coastline were not conducive to the spread of pollutants and degradation. Additionally, the dominant macrobenthos analysis from 1958 to 2012 showed that Musculus senhousei (Benson, 1842) spread very fast and had been the predominant species in the recent years, which was a disturbance tolerant species.

Keywords: Bohai Bay, coastal reclamation, landscape change, spatial patterns

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Authors: Dimakatso Machetele, Clare Kelso, Thea Schoeman

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In developing countries such as India, China, and South Africa, disposal of household solid waste in rural areas is of great concern. Rural communities face numerous challenges that include the absence of waste collection services and sanitation facilities. The inadequate provision of waste collection and sanitation services results to the occurrence of infectious diseases e.g., malaria. The gap in the management of household solid waste between rural and urban communities, whereby urban communities have better waste management services compared to rural areas is an environmental injustice towards rural communities. The unequal distribution of infrastructure in South Africa’s waste management is a concern that stems from the spatial inequalities of the country’s apartheid history. The Limpopo province has a higher proportion of households without waste collection services from the municipality. The present research objectives are to investigate the public’s perceptions and factors contributing to the management of household solid waste in two contrasting rural Wards in the Greater Tzaneen Municipality. There is limited data and studies that have been conducted to understand the management of household solid waste in rural areas, and specifically, for the Greater Tzaneen Municipality located in the Limpopo province, South Africa. The findings of the study will propose recommendations to the Greater Tzaneen Municipality, rural municipalities in South Africa, and globally to explore sustainable methods to manage household solid waste and explore economic opportunities within the waste management sector to alleviate poverty in rural communities.

Keywords: rural, household solid wase, perceptions, waste management

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Authors: Virve Pääkkönen, Heidi M. Cuffaro, Leo Tjäderhane

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Objectives: Odontoblasts are the outermost cell layer of dental pulp and form the dentin. Importance of bacterial products, e.g. lipoteichoic acid (LTA), a cell wall component of Gram-positive bacteria and lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria, have been indicated in the pathogenesis of pulpitis. Gram-positive bacteria are more prevalent in superficial carious lesion while the amount gram-negative is higher in the deep lesions. Objective of this study was to investigate the effect of these bacterial products on inflammatory response of pulp tissue. Interleukins (IL) were of special interest. Various ILs have been observed in the dentin-pulp complex of carious tooth in vivo. Methods: Tissue culture method was used for testing the effect of LTA and LPS on human odontoblasts. Enzymatic isolation technique was used to extract living odontoblasts for cell cultures. DNA microarray and quantitative PCR (qPCR) were used to characterize the changes in the expression profile of the tissue cultured odontoblasts. Laser microdissection was used to cut healthy and affected dentin and odontoblast layer directly under carious lesion for experiments. Cytokine array detecting 80 inflammatory cytokines was used to analyze the protein content of conditioned culture media as well as dentin and odontoblasts from the carious teeth. Results: LPS caused increased gene expression IL-1α, and -8 and decrease of IL-1β, 12 , -15 and -16 after 1h treatment, while after 24h treatment decrease of IL-8, -11 and 23 mRNAs was observed. LTA treatment caused cell death in the tissue cultured odontoblasts but in in the cell culture but not in cell culture. Cytokine array revealed at least 2-fold down-regulation of IL-1β, -10 and -12 in response to LPS treatment. Cytokine array of odontoblasts of carious teeth, as well as LPS-treated tissue-cultured odontoblasts, revealed increased protein amounts of IL-16, epidermal growth factor (EGF), angiogenin and IGFBP-1 as well as decreased amount of fractalkine. In carious dentin, increased amount of IL-1β, EGF and fractalkine was observed, as well as decreased level of GRO-1 and HGF. Conclusion: LPS caused marked changes in the expression of inflammatory cytokines in odontoblasts. Similar changes were observed in the odontoblasts cut directly under the carious lesion. These results help to shed light on the inflammatory processes happening during caries.

Keywords: inflammation, interleukin, lipoteichoic acid, odontoblasts

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Authors: Moin Uddin, M. Masroor A. Khan, Faisal Rasheed, Tariq Ahmad Dar, Akbar Ali, Lalit Varshney

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Oligomers, obtained by exposing the natural polysaccharides (alginate, carrageenan, chitosan, etc.) to cobalt-60 generated gamma radiation may prove as potent plant growth promoters when applied as foliar sprays to the plants. They function as endogenous growth elicitors, triggering the synthesis of different enzymes and modulating various plant responses by exploiting the gene expression. Exogenous application of Jasmonic acid or of its methyl ester, methyl jasmonate (MeJ) has been reported to increase the secondary metabolites production in medicinal and aromatic plants. Keeping this in mind, three pot experiments were conducted to test whether the foliar application of irradiated-chitosan (IC) and MeJ, applied alone or in combination, could augment the active constituents as well as growth, physiological and yield attributes of Catharanthus roseus, which carries anticancer alkaloids, viz. vincristine and vinblastine, in its leaves in addition to various other useful alkaloids. Totally, 5 spray treatments, comprising various aqueous solutions of IC [20, 40, 80 and 160 mg L-1 (Experiment 1)], MeJ (10, 20, 30 and 40 mg L-1 (Experiment 2)] and those of IC+MeJ [40+20, 40+30, 80+20, 80+30, 160+20 and 160+30 mg L-1 (Experiment 3)], were applied at seven days interval. Total leaf-alkaloids content as well as growth, physiological and yield parameters, evaluated at 120 days after sowing, were significantly enhanced by IC application. IC application could not increase the leaf-content of vincristine and vinblastine; nonetheless, it significantly augmented the yield of these alkaloids owing to enhancing the dry mass of leaves per plant. MeJ application, particularly at 30 mg L-1, increased both content (17%) and yield (48%) of total leaf-alkaloids as well as the content and yield of vincristine ( 29 and 63%, respectively) and vinblastine (14 and 44%, respectively) alkaloids, though it significantly decreased most other parameters studied, particularly at higher concentrations (30 and 40 mg L-1 of MeJ). As compared to the control (water-spray treatment), collective application of IC (80 mg L-1) and MeJ (20 mg L-1) resulted in the highest values of most of the parameters studied. However, 80 mg L-1 of IC applied with 30 mg L-1 of MeJ gave the best results for the content and yield of total as well as anticancer leaf-alkaloids (vincristine and vinblastine). Comparing the control, it increased the content and yield of total leaf-alkaloids (37 and 118%, respectively) and those of vincristine (65 and 163%, respectively) and vinblastine (31 and 107%, respectively). Conclusively, the applied technique significantly enhanced the production of total as well as anticancer alkaloids of Catharanthus roseus.

Keywords: anticancer alkaloids (vincristine and vinblastine), catharanthus roseus, irradiated chitosan, methyl jasmonate

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Authors: Sumaira Hafeez, Saira Akram

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Albeit the populace in metropolitan regions on the planet develops each year, the urban communities battling to adapt to the expanded metropolitan movement grow at different rates. Land Surface Temperature and other atmospheric parameters of the area of not really settled using Landsat pictures more than 10 years isolated. The LULC types were moreover arranged using managed gathering techniques. Quick urbanization is changing the current examples of Land Use Land Cover (LULC) all around the world, which is thusly expanding the Land Surface Temperature (LST) other atmospheric parameters in numerous districts. Present review was centered around assessing the current and recreating the future LULC and Land Surface Temperature patterns in the elevated climate of lower Himalayan district of Pakistan. Past examples of LULC and Land Surface Temperature were distinguished through the multi-unearthly Landsat satellite pictures during the 1995–2019 information period. The future forecasts were made for the year 2030 to work out LULC and LST changes separately, utilizing their previous examples. The review presumes that the reliably extending encroachment of the city's as of late advanced provincial regions over the totally open have went with an overall warming of the district's typical. Meteorological parameters over the earlier ten years and that permitting the land to lie void for a significant long time resulting to clearing the country fields for future metropolitan improvement is a preparation that has lamentable natural effects.

Keywords: surface urban heat island, land surface temperature, urban climate change, spatial analysis of meterological and atmospheric science

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Authors: Shaimaa Eltanani, Thangal Yumnamcha, Ahmed S. Ibrahim

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Purpose: Mitochondria dysfunction is central to breaking the barrier integrity of retinal endothelial cells (RECs) in various blinding eye diseases such as diabetic retinopathy and retinopathy of prematurity. Therefore, we aimed to dissect the role of different mitochondrial components, specifically, those of oxidative phosphorylation (OxPhos), in maintaining the barrier function of RECs. Methods: Electric cell-substrate impedance sensing (ECIS) technology was used to assess in real-time the role of different mitochondrial components in the total impedance (Z) of human RECs (HRECs) and its components; the capacitance (C) and the total resistance (R). HRECs were treated with specific mitochondrial inhibitors that target different steps in OxPhos: Rotenone for complex I; Oligomycin for ATP synthase; and FCCP for uncoupling OxPhos. Furthermore, data were modeled to investigate the effects of these inhibitors on the three parameters that govern the total resistance of cells: cell-cell interactions (Rb), cell-matrix interactions (α), and cell membrane permeability (Cm). Results: Rotenone (1 µM) produced the greatest reduction in the Z, followed by FCCP (1 µM), whereas no reduction in the Z was observed after the treatment with Oligomycin (1 µM). Following this further, we deconvoluted the effect of these inhibitors on Rb, α, and Cm. Firstly, rotenone (1 µM) completely abolished the resistance contribution of Rb, as the Rb became zero immediately after the treatment. Secondly, FCCP (1 µM) eliminated the resistance contribution of Rb only after 2.5 hours and increased Cm without considerable effect on α. Lastly, Oligomycin had the lowest impact among these inhibitors on Rb, which became similar to the control group at the end of the experiment without noticeable effects on Cm or α. Conclusion: These results demonstrate differential roles for complex I, complex V, and coupling of OxPhos in maintaining the barrier functionality of HRECs, in which complex I being the most important component in regulating the barrier functionality and the spreading behavior of HRECs. Such differences can be used in investigating gene expression as well as for screening selective agents that improve the functionality of complex I to be used in the therapeutic approach for treating REC-related retinal diseases.

Keywords: human retinal endothelial cells (hrecs), rotenone, oligomycin, fccp, oxidative phosphorylation, oxphos, capacitance, impedance, ecis modeling, rb resistance, α resistance, and barrier integrity

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Authors: Silvija Šiljeg, Ivan Marić, Ante Šiljeg

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The accessibility of urban green spaces (UGS) is an integral element in the quality of life. Due to rapid urbanization, UGS studies have become a key element in urban planning. The potential benefits of space for its inhabitants are frequently analysed. A functional transport network system and the optimal spatial distribution of urban green surfaces are the prerequisites for maintaining the environmental equilibrium of the urban landscape. An accessibility analysis was conducted as part of the Urban Green Belts Project (UGB). The development of a GIS database for Zadar was the first step in generating the UGS accessibility indicator. Data were collected using the supervised classification method of multispectral LANDSAT images and manual vectorization of digital orthophoto images (DOF). An analysis of UGS accessibility according to the ANGst standard was conducted in the first phase of research. The accessibility indicator was generated on the basis of seven objective measurements, which included average UGS surface per capita and accessibility according to six functional levels of green surfaces. The generated indicator was compared with subjective measurements obtained by conducting a survey (718 respondents) within statistical units. The collected data reflected individual assessments and subjective evaluations of UGS accessibility. This study highlighted the importance of using objective and subjective measures in the process of understanding the accessibility of urban green surfaces. It may be concluded that when evaluating UGS accessibility, residents emphasize the immediate residential environment, ignoring higher UGS functional levels. It was also concluded that large areas of UGS within a city do not necessarily generate similar satisfaction with accessibility. The heterogeneity of output results may serve as guidelines for the further development of a functional UGS city network.

Keywords: urban green spaces (UGS), accessibility indicator, subjective and objective measurements, Zadar

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Authors: Yelin Zhao, Xinxiu Li, Martin Smelik, Oleg Sysoev, Firoj Mahmud, Dina Mansour Aly, Mikael Benson

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Background: Early diagnosis of pancreatic cancer is clinically challenging due to vague, or no symptoms, and lack of biomarkers. Polygenic risk score (PRS) scores may provide a valuable tool to assess increased or decreased risk of PC. This study aimed to develop such PRS by filtering genetic variants identified by GWAS using transcriptional programs identified by single-cell RNA sequencing (scRNA-seq). Methods: ScRNA-seq data from 24 pancreatic ductal adenocarcinoma (PDAC) tumor samples and 11 normal pancreases were analyzed to identify differentially expressed genes (DEGs) in in tumor and microenvironment cell types compared to healthy tissues. Pathway analysis showed that the DEGs were enriched for hundreds of significant pathways. These were clustered into 40 “programs” based on gene similarity, using the Jaccard index. Published genetic variants associated with PDAC were mapped to each program to generate program PRSs (pPRSs). These pPRSs, along with five previously published PRSs (PGS000083, PGS000725, PGS000663, PGS000159, and PGS002264), were evaluated in a European-origin population from the UK Biobank, consisting of 1,310 PDAC participants and 407,473 non-pancreatic cancer participants. Stepwise Cox regression analysis was performed to determine associations between pPRSs with the development of PC, with adjustments of sex and principal components of genetic ancestry. Results: The PDAC genetic variants were mapped to 23 programs and were used to generate pPRSs for these programs. Four distinct pPRSs (P1, P6, P11, and P16) and two published PRSs (PGS000663 and PGS002264) were significantly associated with an increased risk of developing PC. Among these, P6 exhibited the greatest hazard ratio (adjusted HR[95% CI] = 1.67[1.14-2.45], p = 0.008). In contrast, P10 and P4 were associated with lower risk of developing PC (adjusted HR[95% CI] = 0.58[0.42-0.81], p = 0.001, and adjusted HR[95% CI] = 0.75[0.59-0.96], p = 0.019). By comparison, two of the five published PRS exhibited an association with PDAC onset with HR (PGS000663: adjusted HR[95% CI] = 1.24[1.14-1.35], p < 0.001 and PGS002264: adjusted HR[95% CI] = 1.14[1.07-1.22], p < 0.001). Conclusion: Compared to published PRSs, scRNA-seq-based pPRSs may be used not only to assess increased but also decreased risk of PDAC.

Keywords: cox regression, pancreatic cancer, polygenic risk score, scRNA-seq, UK biobank

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Authors: Galuh Pramesti

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In Indonesia, the rise of the middle class and consumer purchasing power has created a trend of shifting the traditional into a modern retail market. Development of the creative economy as an impact of the global economy has invaded the traditional market, due to low rents and minimum innovation, raising the issue of sustainability and urban resilience for survival of the traditional market. The study aims to understand the current market conditions by examining the challenges, resiliency, and identify the relationship between the traditional market and creative market. Using a single-case study approach as the research methodology, Santa Market has been chosen as the case study. It is a pilot project of collaboration between a traditional market and creative economy in Jakarta, Indonesia. The research was conducted as a qualitative study through in-depth interviews with the market vendors and the market management, besides a desk-based study of the leasing data and spatial analysis. The findings indicate traffic fluctuation as the main challenge. It is related to the tenant’s presence, rental fluctuation, gentrification, infrastructure, and market competition. Thus, the findings on resilience show a different response for creative and traditional markets. The traditional market’s response remained stable with minimum innovation, whereas the creative market relies on technological development. Regarding the relationship, supply and demand have become the main relationship occurring in Santa Market. It is then developed into the context of society and regulation. The conclusion provides recommendations for more solid regulation to protect the market tenants from stakeholder interests that can disrupt market viability, and a critical discussion on the concept of collaboration between traditional and creative markets. There is also a suggestion for further study on relation with the surroundings, to create a holistic study on how the collaboration can work well in the traditional market.

Keywords: creative economy, market sustainability, traditional market, urban resilience

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Authors: Sang-Ju Yu

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This paper examines the changing essences and effects of ‘affective atmosphere’ during the COVID-19 pandemic crisis, which have been facilitated and shaped the ‘affective governance’ in Taiwan. Due to long-term uncertainty and unpredictability, the COVID-19 pandemic not only caused unprecedented global crisis but triggered the public’s negative emotional responses. This paper unravels how the shortage of Personal Protective Equipment and the proliferating fake news heightened people’s fear and anxiety and how specific affective atmospheres can be provoked and manipulated to harness emotional appeals of citizens strategically in Taiwan. Through the in-depth interviews with diverse stakeholders involved, it unfolds the dynamics and strategies of affective governance, wherein public emotions and concerns are now given significant consideration in both policy measures and the affective expression of leadership, spatial arrangement, service delivery, and the interaction with citizens. Addressing psychosocial and emotional needs has become the core of crisis response mechanisms suited to dynamic affective atmospheres and pandemic situation. This paper also demonstrates that epidemic prevention and control is not merely the production of neutral or rational policy-making processes, as it is dominated by multiple emotions resulted from unexpected and salient events at different moments. It provides explicit insight into how different prevention scenarios operated effectively through political and affective mobilisation to strengthen emotional bonding and collective identity which energises collective action. Basically, successful affective governance calls for both negative and positive emotions, for both scientific and political decision-making, for both community and bureaucracy, and both quality and efficiency of private–public collaboration.

Keywords: affective atmospheres, affective governance, COVID-19 pandemic, private-public collaboration

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Authors: Pascal Rey, Anaïs Weber

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Many mining projects are being developed in Africa the last decades. Due to the economic opportunities they offer, these projects result in a massive and rapid influx of migrants to the surrounding area. In areas where central government representation is low and local administration lack financial resources, urban development is often anarchical, beyond all public control. It leads to socio-spatial segregation, insecurity and the risk of social conflicts rising. Aware that their economic development is very correlated with local situation, mining companies get more and more involved in regional planning in setting up tools and Strategic Directions document. One of the commonly used tools in this regard is the “Influx Management Plan”. It consists in looking at the region’s absorption capacities in order to ensure its coherent development and by developing several urban centers than one macrocephalic city. It includes many other measures such as urban governance support, skills transfer, creation of strategic guidelines, financial support (local taxes, mining taxes, development funds etc.) local development projects. Through various examples of mining projects in Guinea, A country that is host to many large mining projects, we will look at the implications of regional and urban planning of which mining companies are key playor as well as public authorities. While their investment capacity offers advantages and accelerates development, their actions raise questions of the unilaterality of interests and local governance. By interfering in public affairs are mining companies not increasing the risk of central and local government shirking their responsibilities in terms of regional development, or even calling their legitimacy into question? Is such public-private collaboration really sustainable for the region as a whole and for all stakeholders?

Keywords: Africa, guinea, mine, urban planning

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Authors: Yavuz Arat, Ugur Tuztasi, Mehmet Uysal

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Anatolia has been the host of many civilizations and a site where architectural structures of many cultural layers were interpreted. Most significantly the Turks who settled in Central Asia brought their architectural dynamics and cultural accumulation to Anatolia after the 12th century. The tomb structures first observed in Central Asia under the influence of Islamic faith and Turkish cultural heritage has blossomed under Great Seljuk Empire and with the Anatolian Seljuk Empire these tombs changed both in size and form with rich and beautiful samples from Ahlat to Sivas to Kayseri and Konya. This tomb tradition which started during 13th century has continued during the Ottoman Empire period with some alterations of form and evolved into the rarely observed mausoleum type tombs. The Ottoman tradition of building tombs inside mosque gardens and their forms present the clues of an important burial tradition. However this understanding was abandoned in 20th century Turkey. This tradition was abandoned with regard to legal regulations and health conditions. This study investigates the vestiges of this tradition and its spatial reflections over a sample. The present sample is representative of a tradition that started in 1970s and the case of building tombs inside mosque gardens will be illustrated over the tomb of Hacı Kemal Onsun and his wife which is located in Konya, the capital of the Anatolian Seljuks. The building process of this tomb will be evaluated with regard to burial traditions and architectural stylization.

Keywords: tomb, language of architectural form, Anatolian Seljuk tombs, Ottoman tombs

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Authors: Saurabh Basu, Sudin Ganguly

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Conductance in graphene nanoribbons (GNR) in presence of magnetic (for example, Iron) and non-magnetic (for example, Gold) adatoms are explored theoretically within a Kane-Mele model for their possible spintronic applications and topologically non-trivial properties. In our work, we have considered the magnetic adatoms to induce a Rashba spin-orbit coupling (RSOC) and an exchange bias field, while the non-magnetic ones induce an RSOC and an intrinsic spin-orbit (SO) coupling. Even though RSOC is present in both, they, however, represent very different physical situations, where the magnetic adatoms do not preserve the time reversal symmetry, while the non-magnetic case does. This has important implications on the topological properties. For example, the non-magnetic adatoms, for moderately strong values of SO, the GNR denotes a quantum spin Hall insulator as evident from a 2e²/h plateau in the longitudinal conductance and presence of distinct conducting edge states with an insulating bulk. Since the edge states are protected by time reversal symmetry, the magnetic adatoms in GNR yield trivial insulators and do not possess any non-trivial topological property. However, they have greater utility than the non-magnetic adatoms from the point of view of spintronic applications. Owing to the broken spatial symmetry induced by the presence of adatoms of either type, all the x, y and z components of the spin-polarized conductance become non-zero (only the y-component survives in pristine Graphene owing to a mirror symmetry present there) and hence become suitable for spintronic applications. However, the values of the spin polarized conductances are at least two orders of magnitude larger in the case of magnetic adatoms than their non-magnetic counterpart, thereby ensuring more efficient spintronic applications. Further the applications are tunable by altering the adatom densities.

Keywords: magnetic and non-magnetic adatoms, quantum spin hall phase, spintronic applications, spin polarized conductance, time reversal symmetry

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Authors: Nion Sirimongkonlertkun, Vivard Phonekeo

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This research focused on open burning occurrence in Greater Mekong Sub-Region countries that influences the increase of PM10concentrations. Thailand, Myanmar, and Laos were chosen as a case study, and 2009, 2010, and 2012 were chosen as the year for case study. Hotspot detected by MODIS (Moderate Resolution Imaging Specto radiometer) sensor on board of Terra/Aqua satellites and provided by Rapid Response System was used to represent open burning location in the region. Hotspot was selected through fire confidence with confidence levels of 80-100%. The spatial analysis by GIS was used as the main tool for analyzing and defining the location of open burning at study sites as hotspot with the pixel size of 1 km by 1 km. The total hotspot counts in the study period of four years (2007, 2009, 2010, and January-April 2012) at the regional level, including Thailand, Laos, and Myanmar were 255,177 hotspots or a very high yearly average of 63,795 hotspots. The highest amount was seen in Myanmar (50%), followed by Laos (36%), and Thailand (14%). For Thailand, the majority of burning or 64% occurred in the northern region with the density of 5 hotspots per 100 km2. According to statistics of the 4 years, the increasing rate of hotspot from January to February was 10 times and from February to March was 4 times. After that period, the hotspot started to decline by 2 times from March to April. Therefore, in order to develop a policy which aims to lessen open burning conduction, the government should seriously focus on this problem during the peak period—February to March in every year when hotspot and open burning area is significantly increased.

Keywords: PM10, hotspot, greater mekong sub-region, open burning

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Authors: Xvelian Qin

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Urban "organic renewal" based on the development of existing resources in high-density urban areas has become the mainstream of urban development in the new era. As an important stock resource of public space in high-density urban areas, promoting its value remodeling is an effective way to alleviate the shortage of public space resources. However, due to the lack of evaluation links in the process of underpass space renewal, a large number of underpass space resources have been left idle, facing the problems of low space conversion efficiency, lack of accuracy in development decision-making, and low adaptability of functional positioning to citizens' needs. Therefore, it is of great practical significance to construct the evaluation system of under-bridge space renewal potential and explore the renewal mode. In this paper, some of the under-bridge spaces in the main urban area of Chongqing are selected as the research object. Through the questionnaire interviews with the users of the built excellent space under the bridge, three types of six levels and twenty-two potential evaluation indexes of "objective demand factor, construction feasibility factor and construction suitability factor" are selected, including six levels of land resources, infrastructure, accessibility, safety, space quality and ecological environment. The analytical hierarchy process and expert scoring method are used to determine the index weight, construct the potential evaluation system of the space under the bridge in high-density urban areas of Chongqing, and explore the direction of renewal and utilization of its suitability. To provide feasible theoretical basis and scientific decision support for the use of under bridge space in the future.

Keywords: high density urban area, potential evaluation, space under bridge, updated using

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Authors: Maryam Zarabian, Hector Guzman, Pedro Pereira-Almao, Abraham Fapojuwo

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Dry reforming of methane (DRM) has sparked significant industrial and scientific interest not only as a viable alternative for addressing the environmental concerns of two main contributors of the greenhouse effect, i.e., carbon dioxide (CO₂) and methane (CH₄), but also produces syngas, i.e., a mixture of hydrogen (H₂) and carbon monoxide (CO) utilized by a wide range of downstream processes as a feedstock for other chemical productions. In this study, we develop an AI-enable syngas production model to tackle the problem of achieving an equivalent H₂/CO ratio [1:1] with respect to the most efficient conversion. Firstly, the unsupervised density-based spatial clustering of applications with noise (DBSAN) algorithm removes outlier data points from the original experimental dataset. Then, random forest (RF) and deep neural network (DNN) models employ the error-free dataset to predict the DRM results. DNN models inherently would not be able to obtain accurate predictions without a huge dataset. To cope with this limitation, we employ reusing pre-trained layers’ approaches such as transfer learning and greedy layer-wise pretraining. Compared to the other deep models (i.e., pure deep model and transferred deep model), the greedy layer-wise pre-trained deep model provides the most accurate prediction as well as similar accuracy to the RF model with R² values 1.00, 0.999, 0.999, 0.999, 0.999, and 0.999 for the total outlet flow, H₂/CO ratio, H₂ yield, CO yield, CH₄ conversion, and CO₂ conversion outputs, respectively.

Keywords: artificial intelligence, dry reforming of methane, artificial neural network, deep learning, machine learning, transfer learning, greedy layer-wise pretraining

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Authors: Mirna Guevara, Edgar Santoyo, Daniel Perez-Zarate, Erika Almirudis

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The Acoculco caldera located in Puebla (Mexico) has been preliminary identified as a blind hot-dry rock geothermal system. Two drilled wells suggest the existence of high temperatures >300°C and non-conventional tools are been applied to study this system. A comprehensive survey of soil-gas (CO₂) flux measurements (1,500 sites) was carried out during the dry seasons over almost two years (2015 and 2016). Isotopic analyses of δ¹³CCO₂ were performed to discriminate the origin source of the CO2 fluxes. The soil CO2 flux measurements were made in situ by the accumulation chamber method, whereas gas samples for δ13CCO2 were selectively collected from the accumulation chamber with evacuated gas vials via a septum. Two anomalous geothermal zones were identified as a result of these campaigns: Los Azufres (19°55'29.4'' N; 98°08'39.9'' W; 2,839 masl) and Alcaparrosa (19°55'20.6'' N; 98°08'38.3'' W; 2,845 masl). To elucidate the origin of the C in soil CO₂ fluxes, the isotopic signature of δ¹³C was used. Graphical Statistical Analysis (GSA) and a three end-member mixing diagram were used to corroborate the presence of distinctive statistical samples, and trends for the diffuse gas fluxes. Spatial and temporal distributions of the CO₂ fluxes were studied. High CO₂ emission rates up to 38,217 g/m2/d and 33,706 g/m2/d were measured for the Los Azufres and Alcaparrosa respectively; whereas the δ¹³C signatures showed values ranging from -3.4 to -5.5 o/oo for both zones, confirming their magmatic origin. This study has provided a valuable framework to set the direction of further exploration campaigns in the Acoculco caldera. Acknowledgements: The authors acknowledge the funding received from CeMIE-Geo P09 project (SENER-CONACyT).

Keywords: accumulation chamber method, carbon dioxide, diffusive degassing, geothermal exploration

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Authors: Joy Ghosh, Debasmita Biswas

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The road network of any area is the most important indicator of regional planning. For proper utilization of urban road networks, the structural parameters such as connectivity and accessibility should be analyzed and evaluated. This paper aims to explain the application of GIS on urban road network connectivity and accessibility analysis with a case study of Chandannagar City. This paper has been made to analyze the road network connectivity through various connectivity measurements like the total number of nodes and links, Cyclomatic Number, Alpha Index, Beta Index, Gamma index, Eta index, Pi index, Theta Index, and Aggregated Transport Score, Road Density based on existing road network in Chandannagar city in India. Accessibility is measured through the shortest Path Matrix, associate Number, and Shimbel Index. Various urban services, such as schools, banks, Hospitals, petrol pumps, ATMs, police stations, theatres, parks, etc., are considered for the accessibility analysis for each ward. This paper also highlights the relationship between urban land use/ land cover (LULC) and urban road network and population density using various spatial and statistical measurements. The datasets were collected through a field survey of 33 wards of the Chandannagar Municipal Corporation area, and the secondary data were collected through an open street map and satellite image of LANDSAT8 OLI & TIRS from USGS. Chandannagar was actually once a French colony, and at that time, various sort of planning was applied, but now Chandannagar city continues to grow haphazardly because that city is facing some problems; the knowledge gained from this paper helps to create a more efficient and accessible road network. Therefore, it would be suggested that some wards need to improve their connectivity and accessibility for the future growth and development of Chandannagar.

Keywords: accessibility, connectivity, transport, road network

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Authors: Daria Reczynska, Justyna Jarczak, Michal Czopowicz, Danuta Sloniewska, Karina Horbanczuk, Wieslaw Jarmuz, Jaroslaw Kaba, Emilia Bagnicka

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Since people, animals and plants are constantly exposed to pathogens they have developed very complex systems of defense. Among ca. 1000 antimicrobial peptides from different families so far identified, approximately 30 belonging to cathelicidin family can be found in mammals. Cathelicidins probably constitute the first line of defense because they can act at a physiological salt concentration which is present in healthy tissues. Moreover, the low salt concentration which is present in infected tissues inhibits their activity. In goat bactenecin 7.5 (BAC7.5), bactenecin 5 (BAC5), myeloid antimicrobial peptide 28 (MAP28), myeloid antimicrobial peptide 34 (MAP34 A and B), goat bactenecin3.4 (ChBac3.4) were identified. Caprine arthritis-encephalitis (CAE) caused by small ruminant lentivirus (SRLV) is economic problem. The main CAE symptoms are weight loss, arthritis, pneumonia and mastitis (significant elevation of the somatic cell count and deterioration of some technological parameters). The study was conducted on 24 dairy goats. The animals were divided into two groups: experimental (SRLV-infected) and control (non-infected). The blood samples were collected five times: on the 1st, 7th, 30th, 90th and 150thday of lactation. The levels of transcripts of BAC7.5, BAC5, MAP28 and MAP34 genes in blood leucocytes were measured using qPCR method. There were no differences in mRNA levels of studied genes between stages of lactation. The differences were observed in expressions of BAC5, MAP28 and MAP34 genes with lower levels in the experimental group. There was no difference in BAC7.5 expression between groups. The decreased levels of transcripts of cathelicidin genes in blood leucocytes of SRLV-infected goats may indicate the disturbances of homeostasis in organisms. It can be concluded that SRLV infection seems to inhibit expression of cathelicidin genes. The study was financed by a grant from the National Scientific Center No. UMO-2013/09/B/NZ/03514.

Keywords: goat, CAEV, cathelicidins, blood leukocytes, gene expression

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Authors: N. N. Pandey, Raghvendra Singh, Biju S. Kamlam, Bipin K. Vishwakarma, Preetam Kala

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The rainbow trout (Oncorhynchus mykiss) is an exotic salmonid fish, well known for its fast growth, tremendous ability to thrive in diverse conditions, delicious flesh and hard fighting nature in Europe and other countries. Rainbow trout farming has a great potential for its contribution to the mainstream economy of Himalayan states in India and other temperate countries. These characteristics establish them as one of the most widely introduced and cultured fish across the globe, and its farming is also prominent in the cold water regions of India. Nevertheless, genetic fatigue, slow growth, early maturity, and low productivity are limiting the expansion of trout production. Moreover, farms adjacent to natural streams or other water sources are subject to escape of domesticated rainbow trout into the wild, which is a serious environmental concern as the escaped fish is subject to contaminate and disrupt the receiving ecosystem. A decline in production traits due to early maturity prolongs the culture duration and affects the profit margin of rainbow trout farms in India. A viable strategy that could overcome these farming constraints in large scale operation is the production of triploid fish that are sterile and more heterozygous. For better triploidy induction rate (TR), heat shock at 28°C for 10 minutes and pressure shock 9500 psi pressure for 5 minutes is applied to green eggs with 90-100% of triploidy success and 72-80% survival upto swim-up fry stage. There is 20% better growth in aquaculture with triploids rainbow trout over diploids. As compared to wild diploid fish, larger sized and fitter triploid rainbow trout in natural waters attract to trout anglers, and support the development of recreational fisheries by state fisheries departments without the risk of contaminating existing gene pools and disrupting local fish diversity. Overall, enhancement of productivity in rainbow trout farms and trout production in coldwater regions, development of lucrative trout angling and better ecological management is feasible with triploid rainbow trout.

Keywords: rainbow trout, triploids fish, heat shock, pressure shock, trout angling

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Authors: Basma Hassabo, Sarah Ahmed, Aisha Hameed

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Aims and Objectives: To determine the incidence of maternal mortality amongst pregnant women with sickle cell disease (SCD) in the United Kingdom and to determine exact cause of death in these women. Background: SCD is caused by the ‘sickle’ gene and is characterized by episodes of severe bone pain and other complications like acute chest syndrome, chronic pulmonary hypertension, stroke, retinopathy, chronic renal failure, hepato-splenic crises, avascular bone necrosis, sepsis and leg ulcers. SCD is a continual cause of maternal mortality and fetal complications, and it comprises 1.5% of all Direct and Indirect deaths in the UK. Sepsis following premature rupture of membranes with ascending infection, post-partum infection and pre-labour overwhelming septic shock is one of its leading causes of death. Over the last fifty years of maternal mortality reports in UK, between 1 to 4 pregnant women died in each triennium. Material and Method: This is a retrospective study that involves pregnant women who died from SCD complications in the UK between 1952-2012. Data were collected from the UK Confidential Enquiries into Maternal Death and its causes between 1952–2012. Prior to 1985, exact cause of death in this cohort was not recorded. Results: 33 deaths reported between 1964 and 1984. 17 deaths were reported due to sickle cell disease between 1985 and 2012. Five women in this group died of sickle cell crisis, one woman had liver sequestration crisis, two women died of venous thromboembolism, two had myocardial fibrosis and three died of sepsis. Remaining women died of amniotic fluid embolism, SUDEP, myocardial ischemia and intracranial haemorrhage. Conclusion: The leading causes of death in sickle cell sick pregnant women are sickle cell crises, sepsis, venous thrombosis and thromboembolism. Prenatal care for women with SCD should be managed by a multidisciplinary team that includes an obstetrician, nutritionist, primary care physician, and haematologist. In every sick Sickle Cell woman Sickle Cell crises should be on the top of the list of differential diagnosis. Aggressive treatment of complications with low threshold to commence broad-spectrum antibiotics and LMWH contribute to better outcomes.

Keywords: incidence, maternal mortality, sickle cell disease (SCD), uk

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Authors: Yildirim Ortaoglan

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The attempt to make thought school-like by fitting it into various frameworks with the institutionalization of it is almost simultaneous with philosophy itself. What once sprouted in the “academia” of old has institutionalized under the enlightenment's light, becoming the fundamental space reflecting the spirit of its age. However, the shift from the thinking temple where truth's knowledge was sought to functional spaces where power/power relations are constructed indicates a significant rupture in the meaning of school. Therefore, a genealogical inquiry into the meaning of the school can provide us with a path toward understanding how it should be approached in contemporary times. From this perspective, it is essential to highlight how power/power relations operate in the school in terms of disciplinary practices, temporal management, and spatial organization to construct a distinct subjectivation. Recognizing that the changing and evolving nature of education is related to the structure of space can be understood by revealing how disciplinary power and bio-power, two fundamental aspects of genealogical research, operate. In disciplinary power, the relationship of the subject with discipline, temporal management, and space is about improvement and normalization, while in biopower, it manifests in maximizing utility, increasing free time, and constructing spaces that seem more vital. These indicators not only facilitate the formation of students as a subjectivation but also enable the condition of the possibility of power/power relations. Because power is not applied to subjects but used by them for passage, and behind this lies the idea that the individual is already one of the components of power. As one of the components of power, in terms of subjectivation type, the student is one of the primary targets of power relations. Therefore, conducting a genealogical inquiry of the student as a type of subjectivation and the school as its living area from the philosophical foundations of education may offer a new opportunity for thinking about the contemporary crisis of thought. Within the framework of this possibility, our investigation will consider which aspects of the school and the student, brought together for educational purposes, can be thought of within and beyond power/power relations.

Keywords: power, education, space, school, student, discipline

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Authors: Fan Yang, Ye-Lu Wang, Yang Zhao

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The dynamic load allowance, as an application result of the vehicle-bridge coupled vibration theory, is an important parameter for bridge design and evaluation. Based on the coupled vehicle-bridge vibration theory, the current work establishes a full girder model of a dynamic load allowance, selects a planar five-degree-of-freedom three-axis vehicle model, solves the coupled vehicle-bridge dynamic response using the APDL language in the spatial finite element program ANSYS, selects the pivot point 2 sections as the representative of the negative moment section, and analyzes the effects of parameters such as travel speed, unevenness, vehicle frequency, span diameter, span number and forced displacement of the support on the negative moment dynamic load allowance through orthogonal tests. The influence of parameters such as vehicle speed, unevenness, vehicle frequency, span diameter, span number, and forced displacement of the support on the negative moment dynamic load allowance is analyzed by orthogonal tests, and the influence law of each influencing parameter is summarized. It is found that the effects of vehicle frequency, unevenness, and speed on the negative moment dynamic load allowance are significant, among which vehicle frequency has the greatest effect on the negative moment dynamic load allowance; the effects of span number and span diameter on the negative moment dynamic load allowance are relatively small; the effects of forced displacement of the support on the negative moment dynamic load allowance are negligible.

Keywords: continuous T-girder bridge, dynamic load allowance, sensitivity analysis, vehicle-bridge coupling

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Authors: Rafael Mineiro, André Furtado, Isabel Gonçalves, Cecília Santos, Telma Quintela

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The choroid plexus (CP) epithelial cells form the blood-cerebrospinal fluid barrier. This barrier is highly important for brain protection by physically separating the blood from the cerebrospinal fluid, controlling the trafficking of molecules, including therapeutic drugs, from blood to the brain. The control is achieved by tight junctions between epithelial cells, membrane receptors and transport proteins from the solute carrier and ATP-binding cassette superfamily on the choroid plexus epithelial cells membrane. Previous research of our group showed a functional molecular clock in the CP. The key findings included a rhythmic expression of Bmal1, Per2, and Cry2 in female rat CP. and a rhythmic expression of Cry2 and Per2 in male rat CP. Furthermore, in cultured rat CP epithelial cells we already showed that 17β-estradiol upregulates the expression of Bmal1 and Per1, where the Per1 and Per2 upregulation was abrogated in the presence of the estrogen receptors antagonist ICI. These findings, together with the fact that the CP produces robust rhythms, prompt us to understand the impact of sex hormones and circadian rhythms in CP drug transporters expression, which is a step towards the development and optimization of therapeutic strategies for efficiently delivering drugs to the brain. For that, we analyzed the circadian rhythmicity of the Abcb1, Abcc2, Abcc4 Abcg2, and Oat3 drug transporters at the CP of male and female rats. This analysis was performed by accessing the gene expression of the mentioned transporters at 4 time points by RT-qPCR and the presence of rhythms was evaluated by the CircWave software. Our findings showed a rhythmic expression of Abcc1 in the CP of male rats, of Abcg2 in female rats, and of Abcc4 and Oat3 in both male and female rats with an almost antiphasic pattern between male and female rats for Abcc4. In conclusion, these findings translated to a functional point of view may account for daily variations in brain permeability for several therapeutic drugs, making our findings important data for the future establishment and development of therapeutic strategies according to daytime.

Keywords: choroid plexus, circadian rhythm, membrane transporters, sex hormones

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