Search results for: multi-element expression pattern

Authors: Kamel Abd Elaziz Mohamed

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Introduction: Drug related problems (DRPs) are of major concern, affecting patients of both sex. They impose considerable economic burden on the society and the health-care systems. Aim of the work: The aim of this work was to identify and categorize drug-related problems in adult intensive care unit. Patients and methods: The study was a prospective, observational study as eighty six patients were included. They were consecutively admitted to ICU through the emergency room or transferred from the general ward due to DRPs. Parameters included in the study as length of stay in ICU, need for cardiovascular support or mechanical ventilation, dialysis, as well as APACHE II score were recorded. Results: Drug related problems represent 3.6% of the total ICU admission. The median (range) of APACHE II score for 86 patients included in the study was 17 (10-23), and length of ICU stay was 2.4 (1.5-4.2) days. In 45 patients (52%), DRP was drug over dose (group 1), while other DRP was present in the other 41 patients (48%, group 11). Patients in group 1 were older (39 years versus 32 years in group 11), with significant impaired renal function. The need of inotropic drugs and mechanical ventilation as well as the length of stay (LOS) in ICU was significantly higher in group 1. There were no significant difference in GCS between both groups, however APACHE II score was significantly higher in group 1. Only four patients (4.6%) were admitted by suicidal attempt as well as three patients (3.4%) due to trauma drug-related admissions, all were in (group 1). Nineteen percent of the patients had drug related problem due to hypoglycaemic medication followed by tranquilizer (15%). Adverse drug effect followed by failure to receive medication were the most causes of drug problem in (group11).The total mortality rate was 4.6%, all of them were eventually non preventable. Conclusion: The critically ill patients admitted due to drug related problems represented a small proportion (3.6%) of admissions to the ICU. Hypoglycaemic medication was one of the most common causes of admission by drug related problems.

Keywords: drug related problems, ICU, cost, safety

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Authors: Adrián D. García-Soto, Alejandro Hernández-Martínez, Jesús G. Valdés-Vázquez, Reyna A. Vizguerra-Alvarez

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Reinforced concrete bridges designed by code are intended to achieve target reliability levels adequate for the geographical environment where the code is applicable. Several methods can be used to estimate such reliability levels. Many of them require the establishment of an explicit limit state function (LSF). When such LSF is not available as a close-form expression, the simulation techniques are often employed. The simulation methods are computing intensive and time consuming. Note that if the reliability of real bridges designed by code is of interest, numerical schemes, the finite element method (FEM) or computational mechanics could be required. In these cases, it can be quite difficult (or impossible) to establish a close-form of the LSF, and the simulation techniques may be necessary to compute reliability levels. To overcome the need for a large number of simulations when no explicit LSF is available, the point estimate method (PEM) could be considered as an alternative. It has the advantage that only the probabilistic moments of the random variables are required. However, in the PEM, fitting of the resulting moments of the LSF to a probability density function (PDF) is needed. In the present study, a very simple alternative which allows the assessment of the reliability levels when no explicit LSF is available and without the need of extensive simulations is employed. The alternative includes the use of the PEM, and its applicability is shown by assessing reliability levels of reinforced concrete bridges in Mexico when a numerical scheme is required. Comparisons with results by using the Monte Carlo simulation (MCS) technique are included. To overcome the problem of approximating the probabilistic moments from the PEM to a PDF, a well-known distribution is employed. The approach mixes the PEM and other classic reliability method (first order reliability method, FORM). The results in the present study are in good agreement whit those computed with the MCS. Therefore, the alternative of mixing the reliability methods is a very valuable option to determine reliability levels when no close form of the LSF is available, or if numerical schemes, the FEM or computational mechanics are employed.

Keywords: structural reliability, reinforced concrete bridges, combined approach, point estimate method, monte carlo simulation

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Authors: KuiDong Kang, Hye Bin Yim, Su Ah Kim

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Purpose: Tectorigenin is an isoflavone derived from the rhizome of Belamacanda chinensis. In this study, oxygen-induced retinopathy was used to characterize the anti-angiogenic properties of tectorigenin in mice. Methods: ICR neonatal mice were exposed to 75% oxygen from postnatal day P7 until P12 and returned to room air (21% oxygen) for five days (P12 to P17). Mice were subjected to daily intraperitoneal injection of tectorigenin (1 mg/kg, 10 mg/kg) and vehicle from P12 to P17. Retro-orbital injection of FITC-dextran was performed and retinal flat mounts were viewed by fluorescence microscopy. The Central avascular area was quantified from the digital images in a masked fashion using image analysis software (NIH ImageJ). Neovascular tufts were quantified by using SWIFT_NV and neovascular lumens were quantified from a histologic section in a masked fashion. Immunohistochemistry and Western blot analysis were also performed to demonstrate the anti-angiogenic activity of this compound in vivo. Results: In the retina of tectorigenin injected mouse (10mg/kg), the central non-perfusion area was significantly decreased compared to the vehicle injected group (1.76±0.5 mm2 vs 2.85±0.6 mm2, P<0.05). In vehicle-injected group, 33.45 ± 5.51% of the total retinal area was avascular, whereas the retinas of pups treated with high-dose (10 mg/kg) tectorigenin showed avascular retinal areas of 21.25 ±4.34% (P<0.05). High dose of tectorigenin also significantly reduced the number of vascular lumens in the histologic section. Tectorigenin (10 mg/kg) significantly reduced the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), MMP-9, and angiotensin II compared to the vehicle injected group. Tectorigenin did not affect CD31 abundance at any tested dose. Conclusions: Our results show that tectorigenin possesses powerful anti-angiogenic properties and can attenuate new vessel formation in the retina after systemic administration. These results imply that this compound can be considered as a candidate substance for therapeutic inhibition of retinal angiogenesis.

Keywords: tectorigenin, anti-angiogenic, retinopathy, Belamacanda chinensis

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Authors: Mrinal Mukherjee, Gargi Seal, Bitopan Mazumdar, Prakhar Agarwal

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The central sector of Palghat-Cauvery Shear zone Tamil Nadu, India, had been studied with reference to development, mode of occurrence, interrelationship and variation of structural elements. The litho assemblages of the study area include gneisses migmatites granites and bear signature of multistage deformation patterns. The early deformation D1 is characterized in migmatites and gneisses by the development of tight to isoclinal, recumbent to reclined folds within the compositional bands that are refolded subsequently to produce D2 deformation structures ranging from type-II to type-III superposed geometry. The granite, in general, is undeformed, save a few places where strong mylonitic foliation developed with stretching lineation on it. The D1-D2 structures of gneisses and migmatites were affected by a D3 stage- E-W trending shear zone (Palghat-Cauvery Shear zone) that dips steeply towards north. The shear zone is characterized by the development of mylonite zone with stretching lineation on foliation, shear band structures, modification of geometry and orientation of earlier folds and foliations within the shear zone and development of shear induced folds and foliations. Several anastomosing lenses of shear zones define the larger Palghat-Cauvery Shear zone. The orientation of the shear induced folds and foliations and deflections of earlier foliation and folds within the Palghat-Cauvery shear zone indicate an oblique-slip thrust-shear with north-towards-east sense of displacement. The E-W trending shear zone is further openly folded along N-S in the D4 stage of deformation.

Keywords: deformation, migmatites, mylonites, shear zones

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Authors: Rumana Keyani, Haleema Sadia, Asia Nosheen, Rabia Naz, Humaira Yasmin, Sidra Zahoor

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Tomato is a significant crop of the world and is one of the staple foods of Pakistan. A vast number of plant pathogens from simple viruses to complex parasites cause diseases in tomatoes but fungal infection in our country is quite high. Sometimes the symptoms are too harsh destroying the crop altogether. Countries like our own with continuously increasing massive population and limited resources cannot afford such an economic loss. There is an array of morphological, genetic, biochemical and molecular processes involved in plant resistance mechanisms to biotic stress. The study of different metabolic pathways like Jasmonic acid (JA) pathways and most importantly signaling molecules like ROS/RNS and their redoxin enzymes i.e. TRX and NRX is crucial to disease management, contributing to healthy plant growth. So, improving tolerance in crop plants against biotic stresses is a dire need of our country and world as whole. In the current study, fungal pathogenic strains Alternaria solani and Rhizoctonia solani were used to inoculate tomatoes to check the defense responses of tomato plant against these pathogens at molecular as well as phenotypic level with jasmonic acid and spermidine pretreatment. All the growth parameters (root and shoot length, dry and weight root, shoot weight measured 7 days post-inoculation, exhibited that infection drastically declined the growth of the plant whereas jasmonic acid and spermidine assisted the plants to cope up with the infection. Thus, JA and Spermidine treatments maintained comparatively better growth factors. Antioxidant assays and expression analysis through real time quantitative PCR following time course experiment at 24, 48 and 72 hours intervals also exhibited that activation of JA defense genes and a polyamine Spermidine helps in mediating tomato responses against fungal infection when used alone but the two treatments combined mask the effect of each other.

Keywords: fungal infection, jasmonic acid defence, tomato, spermidine

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Authors: Jeroen Vinkx, Jan A. Delcour, Bart Goderis

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Complete aqueous dissolution of starch is notoriously difficult. A high-temperature autoclaving process is necessary, followed by cooling the solution below its boiling point. The cooled solution is inherently unstable over time. Gelation and retrogradation processes, along with aggregation-induced by undissolved starch remnants, result in starch precipitation. We recently observed the spontaneous gelatinization of native maize starch (MS) in aqueous sodium salicylate (NaSal) solutions at room temperature. A hydrotropic mode of solubilization is hypothesized. Differential scanning calorimetry (DSC) and polarized optical microscopy (POM) of starch dispersions in NaSal solution were used to demonstrate the room temperature gelatinization of MS at different concentrations of MS and NaSal. The DSC gelatinization peak shifts to lower temperatures, and the gelatinization enthalpy decreases with increasing NaSal concentration. POM images confirm the same trend through the disappearance of the ‘Maltese cross’ interference pattern of starch granules. The minimal NaSal concentration to induce complete room temperature dissolution of MS was found to be around 15-20 wt%. The MS content of the dispersion has little influence on the amount of NaSal needed to dissolve it. The effect of the NaSal solution on the MS molecular weight was checked with HPSEC. It is speculated that, because of its amphiphilic character, NaSal enhances the solubility of MS in water by association with the more hydrophobic MS moieties, much like urea, which has also been used to enhance starch dissolution in alkaline aqueous media. As such small molecules do not tend to form micelles in water, they are called hydrotropes rather than surfactants. A minimal hydrotrope concentration (MHC) is necessary for the hydrotropes to structure themselves in water, resulting in a higher solubility of MS. This is the case for the system MS/NaSal/H₂O. Further investigations into the putative hydrotropic dissolution mechanism are necessary.

Keywords: hydrotrope, dissolution, maize starch, sodium salicylate, gelatinization

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Authors: Marden Silva, Danielle Guerra

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Some studies have indicated that pronunciation teaching hasn’t been paid enough attention by teachers regarding EFL contexts. In particular, segmental and suprasegmental features through genre-based approach may be an opportunity on how to integrate pronunciation into a more meaningful learning practice. Therefore, the aim of this project was to carry out a survey on some aspects related to English pronunciation that Brazilian students consider more difficult to learn, thus enabling the discussion of strategies that can facilitate the development of oral skills in English classes by integrating the teaching of phonetic-phonological aspects into the genre-based approach. Notions of intelligibility, fluency and accuracy were proposed by some authors as an ideal didactic sequence. According to their proposals, basic learners should be exposed to activities focused on the notion of intelligibility as well as intermediate students to the notion of fluency, and finally more advanced ones to accuracy practices. In order to test this hypothesis, data collection was conducted during three high school English classes at Federal Center for Technological Education of Minas Gerais (CEFET-MG), in Brazil, through questionnaires and didactic activities, which were recorded and transcribed for further analysis. The genre debate was chosen to facilitate the oral expression of the participants in a freer way, making them answering questions and giving their opinion about a previously selected topic. The findings indicated that basic students demonstrated more difficulty with aspects of English pronunciation than the others. Many of the intelligibility aspects analyzed had to be listened more than once for a better understanding. For intermediate students, the speeches recorded were considerably easier to understand, but nevertheless they found it more difficult to pronounce the words fluently, often interrupting their speech to think about what they were going to say and how they would talk. Lastly, more advanced learners seemed to express their ideas more fluently, but still subtle errors related to accuracy were perceptible in speech, thereby confirming the proposed hypothesis. It was also seen that using genre-based approach to promote oral communication in English classes might be a relevant method, considering the socio-communicative function inherent in the suggested approach.

Keywords: EFL, genre-based approach, oral skills, pronunciation

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Authors: Ojo F. M., Nwekeocha C. C., Faluyi J. O.

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Morphological studies were carried out on Andropogongayanus-Andropogontectorum complex collected in Southwestern Nigeria to provide full characterizationof the two species of Andropogon; elucidating their population dynamics. Morphological data from selected accessions of A. gayanus and A. tectorum from different parts of Southwestern Nigeria were collected and characterized using an adaptation of the Descriptors for Wild and Cultivated Rice (Oryza spp). Preliminary morphological descriptions were carried out at the points of collection. Garden populations were raised from the vegetative parts of some accessions, and hybrids were maintained in Botanical Garden of the Obafemi Awolowo University, Ile- Ife. The data obtained were subjected to inferential tests and Duncan’s multiple range test. This study has revealed distribution pattern of the two species in the area of study, which suggests a south-ward migration of Andropogongayanus from the northern vegetational zones of Nigeria to the southern ecological zones. The migration of A. gayanus around Igbeti with occasional occurrence of A. tectorum along the roadsides without any distinct phenotypic hybrid and Budo-Ode in Oyo State has been established as the southern limit of the spread of A. gayanus, the migration of A. gayanus to the South is not an invasion but a slow process. A. gayanus was not encountered in Osun, Ondo, Ekiti, and Ogun States. Andropogongayanus and Andropogon tectorum not only emerge from the rootstocks rapidly but can also produce independent propagules by rooting at some nodes. The plants can spread by means of these propagules even if it does not produce sexual or apomictic seeds. This potential for vegetative propagation, in addition to the perennial habit, confer considerable advantage for colonization by the Andropogongayanus-AndropogontectorumComplex.

Keywords: accessions, distribution, migration, propagation

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Authors: Ajit Kumar Behera, Saranya P., Sudhir Kumar, Krishnakumar A

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The stable isotope (δ¹⁸ O and δ²H) composition of groundwater of the coastal areas of Periyar and Mahanadi basins falling along East and West coast of India during North-East (NE) monsoon season have been studied. The east and west coast regions are surrounded by the Bay of Bengal and the Arabian Sea respectively, which are considered to be the primary sources for precipitation over India. The major difference between the Bay of Bengal and the Arabian Sea is that a number of large rivers feed the Bay of Bengal, whereas the Arabian Sea is fed by very few small rivers, resulting in enriched stable isotopic composition of the Arabian Sea than the Bay of Bengal. Previous studies have reported depleted ratios of stable isotopes during Northeast monsoon along East and West coasts due to the influence of the Bay of Bengal moisture source. The isotopic composition of groundwater of the Mahanadi delta in the east coast region varies from -6.87 ‰ to -3.40 ‰ for δ¹⁸ O and -45.42 ‰ to -22.43‰ for δ²H. However, the groundwater of the Periyar basin in the west coast has enriched stable isotope value varying from -4.3‰ to -2.5 ‰ for δ¹⁸ O and for δ²H from -23.7 to -6.4 ‰ which is a characteristic of South-West monsoon season. This suggests the groundwater system of the Mahanadi delta and the Periyar basins are influenced by dissimilar moisture sources. The δ¹⁸ O and δ² H relationship (δ²H= 6.513 δ¹⁸ O - 1.39) and d-excess value (< 10) in the east coast region indicates the influence of NE monsoon implying the quick groundwater recharge after precipitation with significant amount of evaporation. In contrast, the δ¹⁸ O and δ²H regression line (δ²H= 8.408 δ¹⁸ O + 11.71) with high d-excess value (>10) in the west coast region implies delayed recharge due to SW monsoon. The observed isotopic enrichment in west coast suggests that NE winter monsoon rainfall does not replenish groundwater quick enough to produce isotopic depletion during the season.

Keywords: Arabian sea, bay of Bengal, groundwater, monsoon, stable isotope

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Authors: Prima Fithri, Lusi Susanti, Karin Bestarina

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Indonesia's electrification ratio is still around 80.1%, which means that approximately 19.9% of households in Indonesia have not been getting the flow of electrical energy. Household electricity consumptions in Indonesia are generally still dominated by the public urban. In the city of Padang, West Sumatera, Indonesia, about 94.10% are power users of government services (PLN). The most important thing of the issue is human resources efficient energy. Consumer behavior in utilizing electricity becomes significant. Intensive questioner survey, in-depth interview and statistical analysis are carried out to collect scientific evidences of the behavioral based changes instruments to reduce electricity consumption in household sector. The questioner was developed to include five factors assuming affect the electricity consumption pattern in household sector. They are: attitude, energy price, household income, knowledge and other determinants. The survey was carried out in Padang, West Sumatra Province Indonesia. About 210 questioner papers were proportionally distributed to households in 11 districts in Padang. Stratified sampling was used as a method to select respondents. The results show that the household size, income, payment methods and size of house are factors affecting electricity saving behavior in residential sector. Household expenses on electricity are strongly influenced by gender, type of job, level of education, size of house, income, payment method and level of installed power. These results provide a scientific evidence for stakeholders on the potential of controlling electricity consumption and designing energy policy by government in residential sector.

Keywords: electricity, energy saving, household, behavior, policy

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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: Harunori Kawabe, Hideyuki Aoshima, Koji Murakami, Minoru Kawakami, Yuka Nakano, David D. Ordinario, C. W. Crawford, Iri Sato-Baran

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With the recent advances in gene editing technologies allowing the rewriting of genetic sequences, additional market growth in the global floriculture market beyond previous trends is anticipated through increasingly sophisticated plant breeding techniques. As a prerequisite for gene editing, the gene sequence of the target plant must first be identified. This necessitates the genetic analysis of plants with unknown gene sequences, the extraction of RNA, and comprehensive expression analysis. Consequently, a technology capable of consistently and effectively extracting high-purity DNA and RNA from plants is of paramount importance. Although model plants, such as Arabidopsis and tobacco, have established methods for DNA and RNA extraction, floricultural species such as roses present unique challenges. Different techniques to extract DNA and RNA from various floricultural species were investigated. Upon sampling and grinding the petals of several floricultural species, it was observed that nucleic acid extraction from the ground petal solutions of low viscosity was straightforward; solutions of high viscosity presented a significant challenge. It is postulated that the presence of substantial quantities of polysaccharides and polyphenols in the plant tissue was responsible for the inhibition of nucleic acid extraction. Consequently, attempts were made to extract high-purity DNA and RNA by improving the CTAB method and combining it with commercially available nucleic acid extraction kits. The quality of the total extracted DNA and RNA was evaluated using standard methods. Finally, the effectiveness of the extraction method was assessed by determining whether it was possible to create a library that could be applied as a suitable template for a next-generation sequencer. In conclusion, a method was developed for consistent and accurate nucleic acid extraction from high-viscosity floricultural samples. These results demonstrate improved techniques for DNA and RNA extraction from flowers, help facilitate gene editing of floricultural species and expand the boundaries of research and commercial opportunities.

Keywords: floriculture, gene editing, next-generation sequencing, nucleic acid extraction

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Authors: Mohammad Saber Eslamlou

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Morphology of Islamic cities has been extensively studied by researchers of Islamic cities and different theories could be found about it. In this regard, there exist much difference in method of analysis, classification, recognition, confrontation and comparative method of urban morphology. The present paper aims to examine the previous methods, approaches and insights and that how Dr. Giulia Annalinda Neglia dealt with the analysis of morphology of Islamic cities. Neglia is assistant professor in University of Bari, Italy (UNIBA) who has published numerous papers and books on Islamic cities. I introduce her works in the field of morphology of Islamic cities. And then, her thoughts, insights and research methodologies are presented and analyzed in critical perspective. This is a qualitative research on her written works, which have been classified in three major categories. The first category consists mainly of her works on morphology and physical shape of Islamic cities. The results of her works’ review suggest that she has used Moratoria typology in investigating morphology of Islamic cities. Moreover, overall structure of the cities under investigation is often described linear; however, she’s against to define a single framework for the recognition of morphology in Islamic cities. She states that ‘to understand the physical complexity and irregularities in Islamic cities, it is necessary to study the urban fabric by typology method, focusing on transformation processes of the buildings’ form and their surrounding open spaces’ and she believes that fabric of each region in the city follows from the principles of an specific period or urban pattern, in particular, Hellenistic and Roman structures. Furthermore, she believes that it is impossible to understand the morphology of a city without taking into account the obvious and hidden developments associated with it, because form of building and their surrounding open spaces are written history of the city.

Keywords: city, Islamic city, Giulia Annalinda Neglia, morphology

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Authors: Marjan Moradi Fard, Hossein Rassi, Masoud Houshmand

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Aim: Breast cancer is one of the most common cancers affecting the morbidity and mortality of Iranian women. This disease is a result of collective alterations of oncogenes and tumor suppressor genes. Studies have produced conflicting results concerning the role of p53 codon 72 polymorphism (G>C) and miR-146a rs2910164 polymorphism (G>C) on the risk of several cancers; therefore, a research was performed to estimate the association between the p53 codon 72 polymorphism and miR-146a rs2910164 polymorphism in breast cancer. Methods and Materials: A total of 45 archival breast cancer samples from khatam hospital and 40 healthy samples were collected. Verification of each cancer reported in a relative was sought through the pathology reports of the hospital records. Then, DNA extracted from all samples by standard methods and p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes were analyzed using multiplex PCR. The tubules, mitotic activity, necrosis, polymorphism and grade of breast cancer were staged by Nottingham histological grading and immunohistochemical staining of the sections from the paraffin wax embedded tissues for the expression of ER, PR and p53 was carried out using a standard method. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Successful DNA extraction was assessed by PCR amplification of b-actin gene (99 bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of breast cancer in the study population. In this study, we established that tumors of p53 GG genotype and miR-146a rs2910164 CC genotype exhibited higher mitotic activity, higher polymorphism, lower necrosis, lower tubules, higher ER- and PR-negatives and lower TP53-positives than the other genotypes. Conclusion: The present study provided preliminary evidence that a p53 GG genotype may effect breast cancer risk in the study population, interacting synergistically with miR-146a rs2910164 CC genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with clinical parameters can serve as major risk factors in the early identification of breast cancers.

Keywords: breast cancer, p53 codon 72 polymorphism, miR-146a rs2910164 polymorphism, genotypes

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Authors: Aoxue Yang, Weili Tian, Yonghe Wu, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Little progress has been made in therapeutic treatment of glioblastoma in the last decade despite rapid progress in molecular understanding of brain tumors1. Here we show that the stress hormone glucocorticoid is essential for the maintenance of brain tumor stem cells (BTSCs), which are resistant to conventional therapy. The glucocorticoid receptor (GR) regulates metabolic plasticity and chemoresistance of the dormant BTSC via controlling expression of GPD1 (glycerol-3-phosphate dehydrogenase 1), which is an essential regulator of lipid metabolism in BTSCs. Genomic, lipidomic and cellular analysis confirm that GR/GPD1 regulation is essential for BTSCs metabolic plasticity and survival. We further demonstrate that the GR agonist dexamethasone (DEXA), which is commonly used to control edema in glioblastoma, abolishes the effect of chemotherapy drug temozolomide (TMZ) by upregulating GPD1 and thus promoting tumor cell dormancy in vivo, this provides a mechanistic explanation and thus settle the long-standing debate of usage of steroid in brain tumor patient edema control. Pharmacological inhibition of GR/GPD1 pathway disrupts metabolic plasticity of BTSCs and prolong animal survival, which is superior to standard chemotherapy. Patient case study shows that GR antagonist mifepristone blocks tumor progression and leads to symptomatic improvement. This study identifies an important mechanism regulating cancer stem cell dormancy and provides a new opportunity for glioblastoma treatment.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides.

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Authors: Jon Gunnar Bernburg

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The present study addresses a topic that is fundamental to social movement theory, namely, the contingent link between movement support and movement participation. Usually, only a small fraction of those who agree with the cause of a social movement is mobilized into participating in it (a pattern sometimes referred to as 'the collective action problem'). However, historical moments sometimes emerge when many supporters become mobilized to participate in the movement, greatly enhancing the chance of movement success. By studying a case in point, this paper addresses the limited work on how support and participation are related at such critical moments. Specifically, the paper examines the association between supporting and participating in a huge 'pro-democracy' protest in Iceland in April 2016, in the wake of the global Panama Papers scandal. Organized via social media by only a handful of activists, but supported by a majority of Icelanders, the protest attracted about a fourth of the urban population, leading to a snap election and government change. Surveying Iceland’s urban population, this paper tests hypotheses about the processes mobilizing supporters to participate in the protest. The findings reveal how variables derived from the theories of biographical availability (males vs. females, working class vs. professionals), critical mass (expectations, prior protest success), and social embeddedness (close ties with protesters) moderate the association between protest support and participation. The study helps to account for one of the largest protests in Iceland’s history while contributing to the theory about how historical contexts shape the behavior of movement supporters.

Keywords: Iceland, crisis, protest support vs. participation, theories of mass mobilization

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Authors: Bienvenu Gael Fouda Mbanga

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This study reports a new approach of preparation of carbon nanoparticles coated cerium oxide nanorods (CNPs/CeONRs) nanocomposite and reusing the spent adsorbent of Cd2+- CNPs/CeONRs nanocomposite for latent fingerprint detection (LFP) after removing Cd2+ ions from aqueous solution. CNPs/CeONRs nanocomposite was prepared by using CNPs and CeONRs with adsorption processes. The prepared nanocomposite was then characterized by using UV-visible spectroscopy (UV-visible), Fourier transforms infrared spectroscopy (FTIR), X-ray diffraction pattern (XRD), scanning electron microscope (SEM), Transmission electron microscopy (TEM), Energy-dispersive X-ray spectroscopy (EDS), Zeta potential, X-ray photoelectron spectroscopy (XPS). The average size of the CNPs was 7.84nm. The synthesized CNPs/CeONRs nanocomposite has proven to be a good adsorbent for Cd2+ removal from water with optimum pH 8, dosage 0. 5 g / L. The results were best described by the Langmuir model, which indicated a linear fit (R2 = 0.8539-0.9969). The adsorption capacity of CNPs/CeONRs nanocomposite showed the best removal of Cd2+ ions with qm = (32.28-59.92 mg/g), when compared to previous reports. This adsorption followed pseudo-second order kinetics and intra particle diffusion processes. ∆G and ∆H values indicated spontaneity at high temperature (40oC) and the endothermic nature of the adsorption process. CNPs/CeONRs nanocomposite therefore showed potential as an effective adsorbent. Furthermore, the metal loaded on the adsorbent Cd2+- CNPs/CeONRs has proven to be sensitive and selective for LFP detection on various porous substrates. Hence Cd2+-CNPs/CeONRs nanocomposite can be reused as a good fingerprint labelling agent in LFP detection so as to avoid secondary environmental pollution by disposal of the spent adsorbent.

Keywords: Cd2+-CNPs/CeONRs nanocomposite, cadmium adsorption, isotherm, kinetics, thermodynamics, reusable for latent fingerprint detection

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Authors: Deepthinath Reghunathan, Satheesha Nayak, Sudarshan S., Prasad Alathady Maloor, Prakash Shetty

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Lumbar plexus is formed by the union of ventral rami of T12, L1, L2, L3 spinal nerves and the larger upper division of L4 lumbar spinal nerves. Variations in the normal anatomy of the lumbar and sacral plexus might be seen in some cases and are reported in the literature, but finding such an unusual case comprising of multiple variations which is normally not expected in a clinical setup, proves to be a vital piece of information for clinicians and medical practitioners. During the dissection of the abdomen and pelvis of an approximately 70 year old cadaver, we observed the following variations in the formation of the lumbar and sacral nerves. 1. The genitofemoral nerve bifurcated at a higher level; genital branch of genitofemoral nerve gave branches to the anterior abdominal wall muscles, 2. A communicating branch was given from the lateral cutaneous nerve of thigh to the medial cutaneous nerve of thigh, 3. A muscular branch was given from femoral nerve to psoas major, 4. There was absence of contribution of L4 spinal nerve in the formation of the lumbosacral trunk and 5. Lumbosacral trunk gave communicating branches to the femoral and obturator nerves. Most of the variations found were rare and finding all the above said variations in a single cadaver is even rare. Documentation of such rare cases with multiple variations in the formation of nerves from the lumbar plexus provides vital information on such occurrences. This information would in turn improve the knowledge of clinicians and surgeons dealing with this region. Emphasizing such knowledge of this region would prevent accidental damage to the structures with a variant anatomy.

Keywords: femoral nerve, genitofemoral nerve, lumbar plexus, lumbosacral trunk

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Authors: Maryam Karimi, Rouzbeh Nazari

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Introduction: Understanding thermal distribution in the micro-urban climate has now been necessary for urban planners or designers due to the impact of complex micro-scale features of Urban Heat Island (UHI) on the built environment and public health. Hence, understanding the interrelation between urban components and thermal pattern can assist planners in the proper addition of vegetation to build-environment, which can minimize the UHI impact. To characterize the need for urban green infrastructure (UGI) through better urban planning, this study proposes the use of RayMan model to measure the impact of air quality and increased temperature based on urban morphology in the selected metropolitan cities. This project will measure the impact of build environment for urban and regional planning using human biometeorological evaluations (Tmrt). Methods: We utilized the RayMan model to estimate the Tmrt in an urban environment incorporating location and height of buildings and trees as a supplemental tool in urban planning and street design. The estimated Tmrt value will be compared with existing surface and air temperature data to find the actual temperature felt by pedestrians. Results: Our current results suggest a strong relationship between sky-view factor (SVF) and increased surface temperature in megacities based on current urban morphology. Conclusion: This study will help with Quantifying the impacts of the built environment and surface properties on surrounding temperature, identifying priority urban neighborhoods by analyzing Tmrt and air quality data at the pedestrian level, and characterizing the need for urban green infrastructure cooling potential.

Keywords: built environment, urban planning, urban cooling, extreme heat

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Authors: Reena Aggarwal

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Wall art is a manifestation of the human mind and an absorbing form of cultural expression. Solapur wall hanging making art reflects cultural values, regional sensibilities, beliefs, and identity and helps to preserve the many different communities. The tango of warp and weft in many ways than one tells the story of civilization itself. Solapur wall hanging is a poem in multicolor, written with the warp and weft having long, rich, and complex history with indigenous design vocabularies made by the Padmasali communities. The wall-hanging weaving of Solapur has remained unaltered for years, from being very basic and monochrome having landscapes and portraits catering only to the local market, thereby becoming a potential family income generation tool. The study focuses on the need for contemporization of the Solapur wall hanging and also deliberates on the fact that wherever the culture of native people has been aided by intervention, in nearly every case, the quality of their craft has began to be enhanced. The study also found the underlying reason for diminishing sales to a declining market, low sales, lack of innovation in design, and product development. Keeping in mind that the artisans of Solapur have heroically always hold on to their ancient beliefs and practices, which give them strength and identity, and a sense of pride, an intervention program was developed with an objective of widening the market and help artisans have a sustaining income which include urban consumers and create designs suitable for the urban market. The process of defining and measuring the advantages of design intervention was achieved by using qualitative research methods. An ethnographic research methodology was adopted, which includes six months of close interface with artisans from ten families engaged in making of wall hanging in Solapur. Design solutions were proposed in terms of product diversification and design extensions of the existing product line for increased variety. A collection of contemporary wall arts (wall decor) and room dividers were designed and developed.

Keywords: wall hanging, Solapur, contemporization, traditional, sustainable

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Authors: Marilei Amadeu Sabino

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Idiomatic expressions are linguistic phraseologisms present in natural languages. Known to be metaphorical linguistic combinations, a good majority of them provide elements that reveal important cultural aspects of their linguistic community through their metaphors. With the advent of Cognitive Linguistics (more specifically of Cognitive Semantics), the metaphor ceased to be related to poetic language and rhetorical embellishment and came to be seen as part of simple everyday language, reflecting the way human beings think, act and conceive reality, i. e., a fundamental mechanism of human conceptualizations of the world. In this sense, it came to be conceived as an inevitable mechanism for representing the nature of thought and language. The speakers, in conceptualizing reality, often use metaphorically parts of the body in expressions known as somatic. Several conceptual metaphors appear to be potentially universal or near-universal, because people across the world share certain bodily experiences. In these terms, many linguistic metaphors may be identical or very similar in several languages. These similarities, according to the Theory of Conceptual Metaphor, derive from universal aspects of the human body. Thus, this research aims to investigate the nature of some metaphors underlying somatic idiomatic expressions of Portuguese, Italian and English languages, establishing a pattern of similarities and differences among them from a trilingual perspective. The analysis shows that much of the studied expressions are really structurally, semantically and metaphorically identical or similar in the three languages. These findings incite relevant discussions concerning mother and foreign language learning and aim to contribute to the teaching of phraseological Lexicon as well as to materials development in mono and multilingual perspectives.

Keywords: idiomatic expressions, materials development, metaphors, phraseological lexicon, teaching and learning

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Authors: Saeed Yazdani, Sima Mohamadi Amidabadi, Amir Mohamadi Nejad, Farahnaz Nekoofar

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As a result of uncertainty and doubts about the quantity of agricultural products, greater significance has been attached to risk management in the agricultural sector. Normally, farmers seek to minimize risks, and crop diversity has always been a means to reduce risk. The study at hand seeks to explore the long-term impact of crop diversity on income risk reduction. The timeframe of the study is 1998 to 2018. Initially, the Herfindahl index was used to estimate crop diversity in different periods, and next, the Hodrick-Prescott filter was applied to estimate income risk both in nominal and real terms. Finally, using the Vector Error Correction Model (VECM), the long-term impact of crop diversity on two modes of risk for the farmer's income has been estimated. Given the long-term pattern’s results, it is evident that in the long-run, crop diversity can reduce income fluctuations in two nominal and real terms. Moreover, results showed that in case the fluctuation shock affects the agricultural income in the short run, to balance out the shock in nominal and real terms, 4 and 3 cycles are needed respectively. In other words, in each cycle, 25% and 33% of the shock impact can be removed, respectively. Thus, as the results of the error correction coefficient showed, policies need to be put in place to prevent income shocks. In case of a shock, they need to be balanced out in a four-year period, taking inflation into account, and in a three-year period irrespective of the inflation and reparative policies such as insurance services should be developed.

Keywords: risk, long-term model, Herfindahl index, time series model, vector error correction model

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Authors: Min-Chien Su, Tzu-Hsuan Hsu, Guan-Xuan Wu, Shyh-Ming Kuo

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Lung cancer is one of the clinically challenging malignant diseases worldwide. For efficient therapeutics in cancer, combination therapy has developed to acquire a better outcome. PLK-1 was one of the major factors affecting cell mitosis in cancer cells, its inhibitor Bi6727 was proven effective in treating several different cancers namely oral cancer, colon cancer and lung cancer. Despite its low toxicity toward normal cells compared to traditional chemotherapy, it is still yet to be evaluated in detail. Livistona Chinensis (LC) is a Chinese herb that used as a traditional prescription to treat lung cancer. Due to the uncertainty of the efficacy of LC, we utilized a water extraction method to extract the Livistona Chinensis and then lyophilized into powder for further study. In this study we investigated the antiproliferation activities of Bi6727 and LC extracts (LCE) on A549 non-small lung cancer cells. The IC50 of Bi6727 and LCE on A549 are 60 nM and 0.8 mg/mL, respectively. The fluorescent staining images shown nucleolus damage in cells treated with Bi6727 and mitochondrial damage after treated with LCE. A549 cells treated with Bi6727 and LCE showed increased expression of Bax, Caspase-3 and Caspase-9 proteins from Western blot assay. LCE also inhibited A549 cells growth keeping cells at G2-M phase from cell cycle assay. Apoptosis assay results showed that LCE induced late apoptosis of A549 cells. JC-1 assay showed that the mitochondria damaged at the LCE concentration of 0.4 mg/mL. In our preliminary anti-proliferation test of combined LCE and Bi-6727 on A549 cells, we found a dramatically decrease in proliferation after treated with LCE first for 24-h and then Bi-6727 for extra 24-h. This was an important finding regarding synergistic anti-proliferation effect of these drugs, However, the usage, the application sequence of LCE and Bi-6727 on A549 cells and their related mechanisms still need to be evaluated. In summary, the drugs exerted anti-proliferation effect on A549 cells independently. We hopefully combine the usage of these two drugs will bring a different and potential outcome in treating lung cancer.

Keywords: anti-proliferation, A549, Livistona Chinensis fruit extracts, PLK-1 inhibitor

Procedia PDF Downloads 141

Authors: Edmaritz Hernandez-Pagan, Kanjana Laosuntisuk, Alex Harris, Allison Haynes, David Buitrago, Michael Kudenov, Colleen Doherty

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Rare Earth Elements (REEs) are critical metals for modern electronics, green technologies, and defense systems. However, due to their dispersed nature in the Earth’s crust, frequent co-occurrence with radioactive materials, and similar chemical properties, acquiring and purifying REEs is costly and environmentally damaging, restricting access to these metals. Plants could serve as resources for bioengineering REE mining systems. Although there is limited information on how REEs affect plants at a cellular and molecular level, plants with high REE tolerance and hyperaccumulation have been identified. This dissertation aims to develop a plant-based system for harvesting REEs from industrial waste material with a focus on Acid Mine Drainage (AMD), a toxic coal mining product. The objectives are 1) to develop a non-destructive, in vivo detection method for REE detection in Phytolacca plants (REE hyperaccumulator) plants utilizing fluorescence spectroscopy and with a primary focus on dysprosium, 2) to characterize the uptake of REE and Heavy Metals in Phytolacca americana and Phytolacca acinosa (REE hyperaccumulator) in AMD for potential implementation in the plant-based system, 3) to implement the REE detection method to identify REE-binding proteins and peptides for potential enhancement of uptake and selectivity for targeted REEs in the plants implemented in the plant-based system. The candidates are known REE-binding peptides or proteins, orthologs of known metal-binding proteins from REE hyperaccumulator plants, and novel proteins and peptides identified by comparative plant transcriptomics. Lanmodulin, a high-affinity REE-binding protein from methylotrophic bacteria, is used as a benchmark for the REE-protein binding fluorescence assays and expression in A. thaliana to test for changes in REE plant tolerance and uptake.

Keywords: phytomining, agromining, rare earth elements, pokeweed, phytolacca

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Authors: Israel B. Bitton

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“Memory” is associated with various phenomena, from physical to mental, personal to collective and historical to cultural. As part of a broader exploration of memory studies in philosophy and science (slated for academic publication October 2021), this specific study employs analytical methods of cognitive psychology and philosophy of memory to theorize that A) the primary human will (drive) is to significance, in that every human action and expression can be rooted in a most primal desire to be cosmically significant (however that is individually perceived); and B) that the will to significance manifests as the will to memorability, an innate desire to be remembered by others after death. In support of these broad claims, a review of various popular culture “touchpoints”—historic and contemporary records spanning literature, film and television, traditional news media, and social media—is presented to demonstrate how this very theory is repeatedly and commonly expressed (and has been for a long time) by many popular public figures as well as “everyday people.” Though developed before COVID, the crisis only increased the theory’s relevance: so many people were forced to die alone, leaving them and their loved ones to face even greater existential angst than what ordinarily accompanies death since the usual expectations for one’s “final moments” were shattered. To underscore this issue of, and response to, what can be considered a sociocultural “memory gap,” this study concludes with a summary of several projects launched by journalists at the height of the pandemic to document the memorable human stories behind COVID’s tragic warped speed death toll that, when analyzed through the lens of Viktor E. Frankl’s psychoanalytical perspective on “existential meaning,” shows how countless individuals were robbed of the last wills and testaments to their self-significance and memorability typically afforded to the dying and the aggrieved. The resulting insight ought to inform how government and public health officials determine what is truly “non-essential” to human health, physical and mental, at times of crisis.

Keywords: cognitive psychology, covid, neuroscience, philosophy of memory

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Authors: Yugander Arra, Florence Auguy, Melissa Stiebner, Sophie Chéron, Michael M. Wudick, Van Schepler-Luu, Sébastien Cunnac, Wolf B. Frommer, Laurence Albar

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Rice yellow mottle virus (RYMV) is one of the most important diseases affecting rice in Africa. The most promising strategy to reduce yield losses is the use of highly resistant varieties. The resistance gene RYMV2 is homolog of the Arabidopsis constitutive expression of pathogenesis related protein-5 (AtCPR5) nucleoporin gene. Resistance alleles are originating from African cultivated rice Oryza glaberrima, rarely cultivated, and are characterized by frameshifts or early stop codons, leading to a non-functional or truncated protein. Rice possesses two paralogs of CPR5 and function of these genes are unclear. Here, we evaluated the role of the two rice candidate nucleoporin paralogs OsCPR5.1 (pathogenesis-related gene 5; RYMV2) and OsCPR5.2 by CRISPR/Cas9 genome editing. Despite striking sequence and structural similarity, only loss-of-function of OsCPR5.1 led to full resistance, while loss-of-function oscpr5.2 mutants remained susceptible. Short N-terminal deletions in OsCPR5.1 also did not lead to resistance. In contrast to Atcpr5 mutants, neither OsCPR5.1 nor OsCPR5.2 knock out mutants showed substantial growth defects. Taken together, the candidate nucleoporin OsCPR5.1, but not its close homolog OsCPR5.2, plays a specific role for the susceptibility to RYMV, possibly by impairing the import of viral RNA or protein into the nucleus. Whereas gene introgression from O. glaberrima to high yielding O. sativa varieties is impaired by strong sterility barriers and the negative impact of linkage drag, genome editing of OsCPR5.1, while maintaining OsCPR5.2 activity, thus provides a promising strategy to generate O. sativa elite lines that are resistant to RYMV.

Keywords: CRISPR Cas9, genome editing, knock out mutant, recessive resistance, rice yellow mottle virus

Procedia PDF Downloads 118

Authors: Naci Büyükkaracığan

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Hydroclimatic observation values ​​are used in the planning of the project of water resources. Climate variables are the first of the values ​​used in planning projects. At the same time, the climate system is a complex and interactive system involving the atmosphere, land surfaces, snow and bubbles, the oceans and other water structures. The amount and distribution of precipitation, which is an important climate parameter, is a limiting environmental factor for dispersed living things. Trend analysis is applied to the detection of the presence of a pattern or trend in the data set. Many trends work in different parts of the world are usually made for the determination of climate change. The detection and attribution of past trends and variability in climatic variables is essential for explaining potential future alteration resulting from anthropogenic activities. Parametric and non-parametric tests are used for determining the trends in climatic variables. In this study, trend tests were applied to annual total precipitation data obtained in period of 1972 and 2012, in the Konya Basin. Non-parametric trend tests, (Sen’s T, Spearman’s Rho, Mann-Kendal, Sen’s T trend, Wald-Wolfowitz) and parametric test (mean square) were applied to annual total precipitations of 15 stations for trend analysis. The linear slopes (change per unit time) of trends are calculated by using a non-parametric estimator developed by Sen. The beginning of trends is determined by using the Mann-Kendall rank correlation test. In addition, homogeneities in precipitation trends are tested by using a method developed by Van Belle and Hughes. As a result of tests, negative linear slopes were found in annual total precipitations in Konya.

Keywords: trend analysis, precipitation, hydroclimatology, Konya

Procedia PDF Downloads 219

Authors: Chua Bee Seok, Getrude Cosmas, Jasmine Adela Mutang, Shazia Iqbal Hashmi

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The aims of this study were to determine the factor structure and psychometric properties (i.e., reliability and convergent validity) of the employees trust scale, a newly created instrument by the researchers. The employees trust scale initially contained 82 items to measure employee’s trust toward their supervisors. A sample of 818 (343 females, 449 males) employees were selected randomly from public and private organization sectors in Kota Kinabalu, Sabah, Malaysia. Their ages ranged from 19 to 67 years old with the mean of 34.55 years old. Their average tenure with their current employer was 11.2 years (s.d. = 7.5 years). The respondents were asked to complete the employees trust scale, as well as a managerial trust questionnaire from Mishra. The exploratory factor analysis on employee’s trust toward their supervisor’s extracted three factors, labeled 'trustworthiness' (32 items), 'position status' (11 items) and 'relationship' (6 items) which accounted for 62.49% of the total variance. Trustworthiness factors were re-categorized into three sub factors: competency (11 items), benevolence (8 items) and integrity (13 items). All factors and sub factors of the scales demonstrated clear reliability with internal consistency of Cronbach’s Alpha above 0.85. The convergent validity of the Scale was supported by an expected pattern of correlations (positive and significant correlation) between the score of all factors and sub factors of the scale and the score on the managerial trust questionnaire which measured the same construct. The convergent validity of employees trust scale was further supported by the significant and positive inter correlation between the factors and sub factors of the scale. The results suggest that the employees trust scale is a reliable and valid measure. However, further studies need to be carried out in other groups of sample as to further validate the Scale.

Keywords: employees trust scale, psychometric properties, trustworthiness, position status, relationship

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Authors: Hanjun Yun, Gun Bae, Nabin Paul, Cheolhee Moon

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Flexible OLED is an important technology for the next generation display over various kinds of applications. However, the organic materials of OLEDs degrade rapidly under the invasion of oxygen and water moisture. The degradation causes the formation of non-emitting areas which gradually suppress the device brightness, ultimately the lifetime of the device decreasing rapidly. Until now, the most suitable sealing process of the flexible OLED devices is a thin film encapsulation (TFE). However, TFE consists of a multilayer thin-film structure with organic-inorganic materials, so the cost is expensive and the process time is long. Another problem is that the blocking characteristics from the moisture and oxygen are not perfect. Therefore, the encapsulation of the flexible OLED device is a still key technical issue for the successful market entry. In this study, we are to introduce an auxiliary sealing line between the two flexible substrates. The electrode lines were formed on the substrates which have a SiNx barrier coating layer. To induce the solid phase diffusion process between the SiNx layer and the electrode lines, the electrode materials were determined as Al-Si composition. Thermal energy was supplied for both the SiNx layer and Al-Si electrode lines within the furnace to induce the interfacial bonding through the solid phase diffusion of Si. We printed a test pattern for the edge of the flexible PET substrate of 3cm*3cm size. Experimental conditions such as heating temperature, heating time were optimized to get enough adhesion strength which was estimated through the competitive bending test. Finally, OLED devices with flexible PET substrate of 3cm*3cm size were manufactured to investigate the blocking characteristics as an encapsulation layer.

Keywords: barrier, encapsulation, OLED, solid phase diffusion

Procedia PDF Downloads 237

Authors: Sukumar Namineni, Tracy O'Connor, Ulrich Kalinke, Percy Knolle, Mathias Heikenwaelder

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The liver is one of the pivotal organs in vertebrate animals, serving a multitude of functions such as metabolism, detoxification and protein synthesis and including a predominant role in innate immunity. The innate immune mechanisms pertaining to liver in controlling viral infections have largely been attributed to the Kupffer cells, the locally resident macrophages. However, all the cells of liver are equipped with innate immune functions including, in particular, the hepatocytes. Hence, our aim in this study was to elucidate the innate immune contribution of hepatocytes in viral clearance using mice lacking Ikkβ specifically in the hepatocytes, termed IkkβΔᴴᵉᵖ mice. Blockade of Ikkβ activation in IkkβΔᴴᵉᵖ mice affects the downstream signaling of canonical NF-κB signaling by preventing the nuclear translocation of NF-κB, an important step required for the initiation of innate immune responses. Interestingly, infection of IkkβΔᴴᵉᵖ mice with lymphocytic choriomeningitis virus (LCMV) led to strongly increased hepatic viral titers – mainly confined in clusters of infected hepatocytes. This was due to reduced interferon stimulated gene (ISG) expression during the onset of infection and a reduced CD8+ T-cell-mediated response. Decreased ISG production correlated with increased liver LCMV protein and LCMV in isolated hepatocytes from IkkβΔᴴᵉᵖ mice. A similar phenotype was found in LCMV-infected mice lacking interferon signaling in hepatocytes (IFNARΔᴴᵉᵖ) suggesting a link between NFkB and interferon signaling in hepatocytes. We also observed a failure of interferon-mediated inhibition of HBV replication in HepaRG cells treated with NF-kB inhibitors corroborating our initial findings with LCMV infections. Collectively, these results clearly highlight a previously unknown and influential role of hepatocytes in the induction of innate immune responses leading to viral clearance during a systemic viral infection with LCMV-WE.

Keywords: CD8+ T cell responses, innate immune mechanisms in the liver, interferon signaling, interferon stimulated genes, NF-kB signaling, viral clearance

Procedia PDF Downloads 191