Search results for: seismic activation

Authors: Preetham Shankapal, Jill King, Kori Murray, Corby Martin, Paula Giselman, Jason Hicks, Owen Carmicheal

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Activation of reward and satiety networks in the brain while processing palatable food cues, as well as functional connectivity during rest has been studied using functional Magnetic Resonance Imaging of the brain in various obesity phenotypes. However, functional connectivity within the reward and satiety network during food cue processing is understudied. 14 obese individuals underwent two fMRI scans during viewing of Macronutrient Picture System images. Each scan included two blocks of images of High Sugar/High Fat (HSHF), High Carbohydrate/High Fat (HCHF), Low Sugar/Low Fat (LSLF) and also non-food images. Seed voxels within seven food reward relevant ROIs: Insula, putamen and cingulate, precentral, parahippocampal, medial frontal and superior temporal gyri were isolated based on a prior meta-analysis. Beta series correlation for task-related functional connectivity between these seed voxels and the rest of the brain was computed. Voxel-level differences in functional connectivity were calculated between: first and the second scan; individuals who saw novel (N=7) vs. Repeated (N=7) images in the second scan; and between the HC/HF, HSHF blocks vs LSLF and non-food blocks. Computations and analysis showed that during food image viewing, reward network ROIs showed significant functional connectivity with each other and with other regions responsible for attentional and motor control, including inferior parietal lobe and precentral gyrus. These functional connectivity values were heightened among individuals who viewed novel HS/HF images in the second scan. In the second scan session, functional connectivity was reduced within the reward network but increased within attention, memory and recognition regions, suggesting habituation to reward properties and increased recollection of previously viewed images. In conclusion it can be inferred that Functional Connectivity within reward network and between reward and other brain regions, varies by important experimental conditions during food photography viewing, including habituation to shown foods.

Keywords: fMRI, functional connectivity, task-based, beta series correlation

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Authors: K. Raghu, Sree Harsha

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The interrelationship between the technology and architecture of tall buildings is investigated from the emergence of tall buildings in late 19th century to the present. In the late 19th century early designs of tall buildings recognized the effectiveness of diagonal bracing members in resisting lateral forces. Most of the structural systems deployed for early tall buildings were steel frames with diagonal bracings of various configurations such as X, K, and eccentric. Though the historical research a filtering concept is developed original and remedial technology- through which one can clearly understand inter-relationship between the technical evolution and architectural esthetic and further stylistic transition buildings. Diagonalized grid structures – “diagrids” - have emerged as one of the most innovative and adaptable approaches to structuring buildings in this millennium. Variations of the diagrid system have evolved to the point of making its use non-exclusive to the tall building. Diagrid construction is also to be found in a range of innovative mid-rise steel projects. Contemporary design practice of tall buildings is reviewed and design guidelines are provided for new design trends. Investigated in depths are the behavioral characteristics and design methodology for diagrids structures, which emerge as a new direction in the design of tall buildings with their powerful structural rationale and symbolic architectural expression. Moreover, new technologies for tall building structures and facades are developed for performance enhancement through design integration, and their architectural potentials are explored. By considering the above data the analysis and design of 40-100 storey diagrids steel buildings is carried out using E-TABS software with diagrids of various angle to be found for entire building which will be helpful to reduce the steel requirement for the structure. The present project will have to undertake wind analysis, seismic analysis for lateral loads acting on the structure due to wind loads, earthquake loads, gravity loads. All structural members are designed as per IS 800-2007 considering all load combination. Comparison of results in terms of time period, top storey displacement and inter-storey drift to be carried out. The secondary effect like temperature variations are not considered in the design assuming small variation.

Keywords: diagrid, bracings, structural, building

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Authors: Mariya Dayana, Budhmal Jain

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Kannur International Airport Ltd. (KIAL) is a new Greenfield airport project with airside development on an undulating terrain with an average height of 90m above Mean Sea Level (MSL) and a maximum height of 142m. To accommodate the desired Runway length and Runway End Safety Area (RESA) at both the ends along the proposed alignment, it resulted in 45.5 million cubic meters in cutting and filling. The insufficient availability of land for the construction of free slope embankment at RESA 07 end resulted in the design and construction of Reinforced Soil Slope (RSS) with a maximum slope of 65 degrees. An embankment fill of average 70m height with steep slopes located in high rainfall area is a unique feature of this project. The design and construction was challenging being asymmetrical with curves and bends. The fill was reinforced with high strength Uniaxial geogrids laid perpendicular to the slope. Weld mesh wrapped with coir mat acted as the facia units to protect it against surface failure. Face anchorage were also provided by wrapping the geogrids along the facia units where the slope angle was steeper than 45 degrees. Considering high rainfall received on this table top airport site, extensive drainage system was designed for the high embankment fill. Gabion wall up to 10m height were also designed and constructed along the boundary to accommodate the toe of the RSS fill beside the jeepable track at the base level. The design of RSS fill was done using ReSSA software and verified in PLAXIS 2D modeling. Both slip surface failure and wedge failure cases were considered in static and seismic analysis for local and global failure cases. The site won excavated laterite soil was used as the fill material for the construction. Extensive field and laboratory tests were conducted during the construction of RSS system for quality assurance. This paper represents a case study detailing the design and construction of a very high embankment using geosynthetics for the provision of Runway length and RESA area.

Keywords: airport, embankment, gabion, high strength uniaxial geogrid, kial, laterite soil, plaxis 2d

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Authors: G. Krishnamoorthy, S. Anandhakumar

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The effect of D-Lysine (D-Lys) on collagen with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide(EDC)/N-hydroxysuccinimide(NHS) initiated cross linking using experimental and modelling tools are evaluated. The results of the Coll-D-Lys-EDC/NHS scaffold also indicate an increase in the tensile strength (TS), percentage of elongation (% E), denaturation temperature (Td), and decrease the decomposition rate compared to L-Lys-EDC/NHS. Scanning electron microscopic (SEM) and atomic force microscopic (AFM) analyses revealed a well ordered with properly oriented and well-aligned structure of scaffold. The D-Lys stabilizes the scaffold against degradation by collagenase than L-Lys. The cell assay showed more than 98% fibroblast viability (NIH3T3) and improved cell adhesions, protein adsorption after 72h of culture when compared with native scaffold. Cell attachment after 74h was robust, with cytoskeletal analysis showing that the attached cells were aligned along the fibers assuming a spindle-shape appearance, despite, gene expression analyses revealed no apparent alterations in mRNA levels, although cell proliferation was not adversely affected. D-Lysine (D-Lys) plays a pivotal role in the self-assembly and conformation of collagen fibrils. The D-Lys assisted EDC/NHS initiated cross-linking induces the formation of an carboxamide by the activation of the side chain -COOH group, followed by aminolysis of the O-iso acylurea intermediates by the -NH2 groups are directly joined via an isopeptides bond. This leads to the formation of intra- and inter-helical cross links. Modeling studies indicated that D-Lys bind with collagen-like peptide (CLP) through multiple H-bonding and hydrophobic interactions. Orientational changes in collagenase on CLP-D-Lys are observed which may decrease its accessibility to degradation and stabilize CLP against the action of the former. D-Lys has lowest binding energy and improved fibrillar-assembly and staggered alignment without the undesired structural stiffness and aggregations. The proteolytic machinery is not well equipped to deal with Coll-D-Lys than Coll-L-Lys scaffold. The information derived from the present study could help in designing collagenolytically stable heterochiral collagen based scaffold for biomedical applications.

Keywords: collagen, collagenase, collagen like peptide, D-lysine, heterochiral collagen scaffold

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Authors: Ayman Mutahar Alrassas, Shaoran Ren, Renyuan Ren, Hung Vo Thanh, Mohammed Hail Hakimi, Zhenliang Guan

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The significant effect of CO₂ on global climate and the environment has gained more concern worldwide. Enhance oil recovery (EOR) associated with sequestration of CO₂ particularly into the depleted oil reservoir is considered the viable approach under financial limitations since it improves the oil recovery from the existing oil reservoir and boosts the relation between global-scale of CO₂ capture and geological sequestration. Consequently, practical measurements are required to attain large-scale CO₂ emission reduction. This paper presents an integrated modeling workflow to construct an accurate 3D reservoir geological model to estimate the storage capacity of CO₂ under geological uncertainty in an unconventional oil reservoir of the Paleogene Shahejie Formation (Es1) in the block Nv32, Shenvsi oilfield, China. In this regard, geophysical data, including well logs of twenty-two well locations and seismic data, were combined with geological and engineering data and used to construct a 3D reservoir geological modeling. The geological modeling focused on four tight reservoir units of the Shahejie Formation (Es1-x1, Es1-x2, Es1-x3, and Es1-x4). The validated 3D reservoir models were subsequently used to calculate the theoretical CO₂ storage capacity in the block Nv32, Shenvsi oilfield. Well logs were utilized to predict petrophysical properties such as porosity and permeability, and lithofacies and indicate that the Es1 reservoir units are mainly sandstone, shale, and limestone with a proportion of 38.09%, 32.42%, and 29.49, respectively. Well log-based petrophysical results also show that the Es1 reservoir units generally exhibit 2–36% porosity, 0.017 mD to 974.8 mD permeability, and moderate to good net to gross ratios. These estimated values of porosity, permeability, lithofacies, and net to gross were up-scaled and distributed laterally using Sequential Gaussian Simulation (SGS) and Simulation Sequential Indicator (SIS) methods to generate 3D reservoir geological models. The reservoir geological models show there are lateral heterogeneities of the reservoir properties and lithofacies, and the best reservoir rocks exist in the Es1-x4, Es1-x3, and Es1-x2 units, respectively. In addition, the reservoir volumetric of the Es1 units in block Nv32 was also estimated based on the petrophysical property models and fund to be between 0.554368

Keywords: CO₂ storage capacity, 3D geological model, geological uncertainty, unconventional oil reservoir, block Nv32

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Authors: Khairy M. A. Zoheir, Nehma A. Ali, Ahmed M. Darwish, Mohamed S. Kishta, Ahmed A. Abd-Rabou, Mohamed A. Abdelhafez, Karima F. Mahrous

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The study comprehensively investigated the multifaceted therapeutic properties of the IQGAP1shRNA plasmid, encompassing its hepatoprotective, immunomodulatory, and anticancer activities. The study employed a Prednisolone-induced immunosuppressed rat model to assess the hepatoprotective and immunomodulatory effects of IQGAP1shRNA plasmid. Using this model, IQGAP1shRNA plasmid was found to modulate haematopoiesis, improving RBC, platelet, and WBC counts, underscoring its potential in hematopoietic homeostasis. Organ atrophy, a hallmark of immunosuppression in spleen, heart, liver, ovaries, and kidneys, was reversed with IQGAP1shRNA plasmid treatment, reinforcing its hepatotrophic and organotropic capabilities. Elevated hepatic biomarkers (ALT, AST, ALP, LPO) indicative of hepatocellular injury and oxidative stress were reduced with GST, highlighting its hepatoprotective and antioxidative effects. IQGAP1shRNA plasmid also restored depleted antioxidants (GSH and SOD), emphasizing its potent antioxidative and free radical scavenging capabilities. Molecular insights into immune dysregulation revealed downregulation of IQGAP1, IQGAP3 interleukin-2 (IL-2), and interleukin-4 (IL-4) mRNA expression in the liver of immunosuppressed rats. IL-2 and IL-4 play pivotal roles in immune regulation, T-cell activation, and B-cell differentiation. Notably, treatment with IQGAP1shRNA plasmid exhibited a significant upregulation of IL-2 and IL-4 mRNA expression, thereby accentuating its immunomodulatory potential in orchestrating immune homeostasis. Additionally, immune dysregulation was associated with increased levels of TNF-α. However, treatment with IQGAP1shRNA plasmid effectively decreased the levels of TNF-α, further underscoring its role in modulating inflammatory responses and restoring immune balance in immunosuppressed rats. Additionally, pharmacokinetics, bioavailability, drug-likeness, and toxicity risk assessment prediction suggest its potential as a pharmacologically favourable agent with no serious adverse effects. In conclusion, this study confirms the therapeutic potential of the IQGAP1shRNA plasmid, showcasing its effectiveness against hepatotoxicity, oxidative stress, immunosuppression, and its notable anticancer activity.

Keywords: IQGAP1, shRNA, cancer, liver, rat

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Authors: Majid Afkhami, Maryam Ehsanpour, Reza Khoshnood, Zahra Khoshnood, Rastin Afkhami

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Marine pollution is a global environmental problem. Different human activities on land, in the water and in the air contribute to the contamination of seawater, sediments and organisms with potentially toxic substances. Contaminants can be natural substances or artificially produced compounds. After discharge into the sea, contaminants can stay in the water in dissolved form or they can be removed from the water column through sedimentation to the bottom sediments. Histopathological alterations can be used as indicators for the effects of various anthropogenic pollutants on organisms and are a reflection of the overall health of the entire population in the ecosystem. These histo pathological biomarkers are closely related to other biomarkers of stress since many pollutants have to undergo metabolic activation in order to be able to provoke cellular change in the affected organism. In order to make evaluation of the effects of oil pollution, some heavy metals bioaccumulation and explore their histopathological effects on hepatocytes of Oriental sole (Euryglossa orientalis) and Deep flounder (Psettodes erumei), fishes caught from two areas of north coast of the Persian Gulf: Bandar Abbass and Bandar Lengeh. Concentrations of Ni and V in liver of both species in two sampling regions were in following order: Bandar abbass Bandar lengeh; also between two species, these quantities were higher in P. erumei than E. orientalis in both sampling regions. Histopathology of the liver shows some cellular alterations including: degeneration, necrosis and tissue disruption, and histopathological effects were severe in P. erumei than E. orientalis. Results showed that Bandar Abbass region was more polluted than Bandar Lengeh, and because Ni and V were oil pollution indicators, and two flat fishes were benthic, they can receive considerable amount of oil pollution through their biological activities like feeding. Also higher amounts of heavy metal concentrations and major histopathological effects in E. orientalis showed strong relationship between benthic habitat of the fish and amounts of received pollutants from water and sediments, because E. orientalis is more related to the bottom than P. erumei.

Keywords: heavy metals, flatfishes, Persian Gulf, oil pollution

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Authors: Katarzyna Sobczak

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Over the last few years extensive research on the Lower Palaeozic of the Baltic region has been carried out, associated with growing interest in the unconventional hydrocarbon resources of the area. The present study contributes to this investigation by providing relevant microfacies analysis of Ordovician and Silurian carbonate and clastic deposits of the Polish part of the Baltic Syneclise, using data from the Kętrzyn IG-1, Henrykowo 1 and Babiak 1 boreholes. The analytical data, encompassing sedimentological, palaeontological, and petrographic indicators enables the interpretation of the sedimentary environments and their control factors. The main microfacies types distinguished within the studied interval are: bioclastic wackestone, bioclastic packstone, carbonate-rich mudstone, marlstone, nodular limestone and bituminous claystone. The Ordovician is represented by redeposited carbonate rocks formed in a relatively high-energy environment (middle shelf setting). The Upper Ordovician-Lower Silurian rocks of the studied basin represent sedimentary succession formed during a distinctive marine transgression. Considering the sedimentological and petrological data from the Silurian, a low-energy sedimentary environment (offshore setting) with intermittent high-energy events (tempestites) can be inferred for the sedimentary basin of NE Poland. Slow sedimentation of carbonate ooze and fine-grained siliciclastic rocks, formed under oxygen-deficient conditions of the seabed, favoured organic matter preservation. The presence of the storm beds suggests an episodic nature of seabed oxygenation. A significant part of the analysed depositional successions shows characteristics indicative of deposition from gravity flows, but lacks evidence of its turbidity origins. There is, however, evidence for storms acting as a mechanism of flow activation. The discussed Ordovician-Silurian transition of depositional environments in the Baltic area fits well to the global environmental changes encompassing the Upper Ordovician and the Lower Silurian.

Keywords: Baltic Syneclise, microfacies analysis, Ordovician, Silurian, unconventional hydrocarbons

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Authors: Salina Yahya Saddick

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Ovarian cancer remains the most lethal gynecological malignancy due to the lack of highly sensitive and specific screening tools for detection of early-stage disease. The OSE provides the progenitor cells for 90% of human ovarian cancers. Recent morphologic, immunohistochemical and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer (EOC) based on a ualistic model of carcinogenesis that divides EOC into two broad categories designated Types I and II which are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN PIK3CA, ARID1A, and PPPR1A, which target specific cell signaling pathways. Type 1 tumors rarely harbor TP53. type I tumors are relatively genetically stable and typically display a variety of somatic sequence mutations that include KRAS, BRAF, PTEN, PIK3CA CTNNB1 (the gene encoding beta catenin), ARID1A and PPP2R1A but very rarely TP53 . The cancer stem cell (CSC) hypothesis postulates that the tumorigenic potential of CSCs is confined to a very small subset of tumor cells and is defined by their ability to self-renew and differentiate leading to the formation of a tumor mass. Potential protein biomarker miRNA, are promising biomarkers as they are remarkably stable to allow isolation and analysis from tissues and from blood in which they can be found as free circulating nucleic acids and in mononuclear cells. Recently, genomic anaylsis have identified biomarkers and potential therapeutic targets for ovarian cancer namely, FGF18 which plays an active role in controlling migration, invasion, and tumorigenicity of ovarian cancer cells through NF-κB activation, which increased the production of oncogenic cytokines and chemokines. This review summarizes update information on epithelial ovarian cancers and point out to the most recent ongoing research.

Keywords: epithelial ovarian cancers, somatic sequence mutations, cancer stem cell (CSC), potential protein, biomarker, genomic analysis, FGF18 biomarker

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Authors: Tsega Asresa Mengistu, Getahun Tigistu

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Computer vision is an artificial intelligence subfield that allows computers and systems to retrieve meaning from digital images. It is applied in various fields of study self-driving cars, video surveillance, agriculture, Quality control, Health care, construction, military, and everyday life. Aromatic and medicinal plants are botanical raw materials used in cosmetics, medicines, health foods, and other natural health products for therapeutic and Aromatic culinary purposes. Herbal industries depend on these special plants. These plants and their products not only serve as a valuable source of income for farmers and entrepreneurs, and going to export not only industrial raw materials but also valuable foreign exchange. There is a lack of technologies for the classification and identification of Aromatic and medicinal plants in Ethiopia. The manual identification system of plants is a tedious, time-consuming, labor, and lengthy process. For farmers, industry personnel, academics, and pharmacists, it is still difficult to identify parts and usage of plants before ingredient extraction. In order to solve this problem, the researcher uses a deep learning approach for the efficient identification of aromatic and medicinal plants by using a convolutional neural network. The objective of the proposed study is to identify the aromatic and medicinal plant Parts and usages using computer vision technology. Therefore, this research initiated a model for the automatic classification of aromatic and medicinal plants by exploring computer vision technology. Morphological characteristics are still the most important tools for the identification of plants. Leaves are the most widely used parts of plants besides the root, flower and fruit, latex, and barks. The study was conducted on aromatic and medicinal plants available in the Ethiopian Institute of Agricultural Research center. An experimental research design is proposed for this study. This is conducted in Convolutional neural networks and Transfer learning. The Researcher employs sigmoid Activation as the last layer and Rectifier liner unit in the hidden layers. Finally, the researcher got a classification accuracy of 66.4 in convolutional neural networks and 67.3 in mobile networks, and 64 in the Visual Geometry Group.

Keywords: aromatic and medicinal plants, computer vision, deep convolutional neural network

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Authors: Sakshi Kaul, Sundeep Verma

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The focus of the current paper is to evaluate the therapeutic power of words. This will be done by critically evaluating the impact reading, writing and storytelling have on individuals. When we read, tell or listen to a story we are exercising our imagination. Imagination becomes the source of activation of thoughts and actions. This enables and helps the reader, writer or the listener to express the suppressed emotions or desires. The stories told, untold may bring various human emotions and attributes to forth such as hope, optimism, fear, happiness. Each story narrated evokes different emotions, at times they help us unravel ourselves in the world of the teller thereby bringing solace. Stories heard or told add to individual’s life by creating a community around, giving wings of thoughts that enable individual to be more imaginative and creative thereby fostering positively and happiness. Reading if looked at from the reader’s point of view can broaden the horizon of information and ideas about facts and life laws giving more meaning to life. From ‘once upon a time’ to ‘to happily ever after’, all that stories talk about is life’s learning. The power of words sometimes may be negated, this paper would reiterate the power of words by critically evaluating how words can become powerful and therapeutic in various structures and forms in the society. There is a story behind every situation, action and reaction. Hence it is of prime importance to understand each story, to enable a person to deal with whatever he or she may be going through. For example, if a client is going through some trauma in his or her life, the counsellor needs to know exactly what is the turmoil that is being faced so that the client can be assisted accordingly. Counselling is considered a process of healing through words or as Talk therapy, where merely through words we try to heal the client. In a counselling session, the counsellor focuses on working with the clients to bring a positive change. The counsellor allows the client to express themselves which is referred to as catharsis. The words spoken, written or heard transcend to heal and can be therapeutic. The therapeutic power of words has been seen in various cultural practices and belief systems. The underlining belief that words have the power to heal, save and bring change has existed from ages. Many religious and spiritual practices also acclaim the power of the words. Through this empirical paper, we have tried to bring to light how reading, writing, and storytelling have been used as mediums of healing and have been therapeutic in nature.

Keywords: reading, storytelling, therapeutic, words

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Authors: Shu-Yen Wang, Shyh-Huei Hwang

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Designated as an important architectural complex of settlement by the Ministry of Culture, Hua-Zhai Settlement located in Wang-An Township, Peng-Hu County, of Taiwan has been progressively restored year by year and is now at the revitalization and reutilization stage. Over the last 5 years, YunTech has participated in the restoration project while being in compliance with the Bureau of Cultural Heritage’s spirit of 'Living Heritage Conservation'. In this study, reflections have been made to evaluate the contemporariness of traditional settlement development from the aspects of revitalization and reutilization. On the one hand, the connection between settlers’ experiences and emotions have been clarified through the living nodes, collective memory, and social-cultural connotation. On the other hand, activity design has promoted the reconstruction of living nodes and facilitated the reconnection of collective memory, enabling us to explore the contemporariness of living nodes after the reconstruction. With the adoption of literature review, participant observation, and interview analysis methods, this study concludes the following results: 1) The node reconstruction brings back the memories and makes emotional connections: the spatial collective memory is composed of different components. During the reconstruction of node space, villagers participated not only in the narration of the history but also in the restoration of the space. This process enables villagers to bring back their memories and make emotional connections thereto. 2) Villagers’ understanding towards revitalization has been facilitated through node reconstruction: as a medium of this project, activity design has facilitated node reconstruction by offering villagers a natural environment to build up emotional connections to the settlement. This also enables us to better understand the meaning of settlement activation for the local community. 3) New connections are established in life between villagers and the university through the construction of living nodes: through the local implementation of node reconstruction, new connections have been established in life between villagers who participated in the project and the university. In the meantime, the university’s entrance to the community has also been revalued.

Keywords: collective memory, local sense of belonging, reconstruction of living nodes, the important architectural complex of Wang-An Hua-Zhai settlement

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Authors: Ayca Bilginoglu, Belma Turan

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Metabolic syndrome, is associated impaired blood glucose level, insulin resistance, dyslipidemia caused by abdominal obesity. Also, it is related with cardiovascular risk accumulation and cardiomyopathy. The hypothesis of this study was to examine the effect of thiazolidinediones such as pioglitazone which is widely used insulin-sensitizing agents that improve glycemic control, on intracellular Na+ homeostasis in metabolic syndrome-induced cardiomyopathy in male rats. Male Wistar-Albino rats were randomly divided into three groups, namely control (Con, n=7), metabolic syndrome (MetS, n=7) and pioglitazone treated metabolic syndrome group (MetS+PGZ, n=7). Metabolic syndrome was induced by providing drinking water that was 32% sucrose, for 18 weeks. All of the animals were exposed to a 12 h light – 12 h dark cycle. Abdominal obesity and glucose intolerance had measured as a marker of metabolic syndrome. Intracellular Na+ ([Na+]i) is an important modulator of excitation–contraction coupling in heart. [Na+]i at rest and [Na+]i during pacing with electrical field stimulation in 0.2 Hz, 0.8 Hz, 2.0 Hz stimulation frequency were recorded in cardiomyocytes. Also, Na+ channel current (INa) density and I-V curve were measured to understand [Na+]i homeostasis. In results, high sucrose intake, as well as the normal daily diet, significantly increased body mass and blood glucose level of the rats in the metabolic syndrome group as compared with the non-treated control group. In MetS+PZG group, the blood glucose level and body inclined to decrease to the Con group. There was a decrease in INa density and there was a shift both activation and inactivation curve of INa. Pioglitazone reversed the shift to the control side. Basal [Na+]i either MetS and Con group were not significantly different, but there was a significantly increase in [Na+]i in stimulated cardiomyocytes in MetS group. Furthermore, pioglitazone had not effect on basal [Na+]i but it reversed the increase in [Na+]i in stimulated cardiomyocytes to the that of Con group. Results of the present study suggest that pioglitazone has a significant effect on the Na+ homeostasis in the metabolic syndrome induced cardiomyopathy in rats. All animal procedures and experiments were approved by the Animal Ethics Committee of Ankara University Faculty of Medicine (2015-2-37).

Keywords: insulin resistance, intracellular sodium, metabolic syndrome, sodium current

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Authors: Alina M. Udall, Judith de Groot, Simon de Jong, Avi Shankar

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There are many ways in which environmentally significant behavior can be explained. Dominant psychological theories, namely, the theory of planned behavior, the norm-activation theory, its extension, the value-belief-norm theory, and the theory of habit do not explain large parts of environmentally significant behaviors. A new and rapidly growing approach is to focus on how consumer’s identities predict environmentally significant behavior. Identity may be relevant because consumers have many identities that are assumed to guide their behavior. Therefore, we assume that many identities will guide environmentally significant behavior. Many identities can be relevant for environmentally significant behavior. In reviewing the literature, over 200 identities have been studied making it difficult to establish the key identities for explaining environmentally significant behavior. Therefore, this paper first aims to establish the key identities previously used for explaining environmentally significant behavior. Second, the aim is to test which key identities explain environmentally significant behavior. To address the aims, an online survey study (n = 578) is conducted. First, the exploratory factor analysis reveals 15 identity factors. The identity factors are namely, environmentally concerned identity, anti-environmental self-identity, environmental place identity, connectedness with nature identity, green space visitor identity, active ethical identity, carbon off-setter identity, thoughtful self-identity, close community identity, anti-carbon off-setter identity, environmental group member identity, national identity, identification with developed countries, cyclist identity, and thoughtful organisation identity. Furthermore, to help researchers understand and operationalize the identities, the article provides theoretical definitions for each of the identities, in line with identity theory, social identity theory, and place identity theory. Second, the hierarchical regression shows only 10 factors significantly uniquely explain the variance in environmentally significant behavior. In order of predictive power the identities are namely, environmentally concerned identity, anti-environmental self-identity, thoughtful self-identity, environmental group member identity, anti-carbon off-setter identity, carbon off-setter identity, connectedness with nature identity, national identity, and green space visitor identity. The identities explain over 60% of the variance in environmentally significant behavior, a large effect size. Based on this finding, the article reveals a new, theoretical framework showing the key identities explaining environmentally significant behavior, to help improve and align the field.

Keywords: environmentally significant behavior, factor analysis, place identity, social identity

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Authors: Y. Landkocz, C. Lepers, P.J. Martin, B. Fougère, F. Roy Saint-Georges. A. Verdin, F. Cazier, F. Ledoux, D. Courcot, F. Sichel, P. Gosset, P. Shirali, S. Billet

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In 2013, the International Agency for Research on Cancer (IARC) classified air pollution and fine particles as carcinogenic to humans. Causal relationships exist between elevated ambient levels of airborne particles and increase of mortality and morbidity including pulmonary diseases, like lung cancer. However, due to a double complexity of both physicochemical Particulate Matter (PM) properties and tumor mechanistic processes, mechanisms of action remain not fully elucidated. Furthermore, because of several common properties between air pollution PM and tobacco smoke, like the same route of exposure and chemical composition, potential mechanisms of synergy could exist. Therefore, smoking could be an aggravating factor of the particles toxicity. In order to identify some mechanisms of action of particles according to their size, two samples of PM were collected: PM0.03 2.5 and PM0.33 2.5 in the urban-industrial area of Dunkerque. The overall cytotoxicity of the fine particles was determined on human bronchial cells (BEAS-2B). Toxicological study focused then on the metabolic activation of the organic compounds coated onto PM and some genetic and epigenetic changes induced on a co-culture model of BEAS-2B and alveolar macrophages isolated from bronchoalveolar lavages performed in smokers and non-smokers. The results showed (i) the contribution of the ultrafine fraction of atmospheric particles to genotoxic (eg. DNA double-strand breaks) and epigenetic mechanisms (eg. promoter methylation) involved in tumor processes, and (ii) the influence of smoking on the cellular response. Three main conclusions can be discussed. First, our results showed the ability of the particles to induce deleterious effects potentially involved in the stages of initiation and promotion of carcinogenesis. The second conclusion is that smoking affects the nature of the induced genotoxic effects. Finally, the in vitro developed cell model, using bronchial epithelial cells and alveolar macrophages can take into account quite realistically, some of the existing cell interactions existing in the lung.

Keywords: air pollution, fine and ultrafine particles, genotoxic and epigenetic alterations, smoking

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Authors: Morenikeji Aliu Balaji

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Gender inequality is seen as persistent discrimination of one group of people based gender, and it manifests itself differently according to race, culture, politics, country and economic situation. Multiple explanations have been offered for gender differences in literacy skill development. Three prominent explanations that precipitated the gender differences are; biological, where the assumption is that differential brain structures and hemispheric activation patterns cause the sexes to be hardwired differently for reading, with girls developing the cognitive skills associated with reading before boys. Secondly, schooling favour girls and ‘girly’ behaviour, and that boys are, as a result, lagging behind on several behavioural, social and academic measures and thirdly, cultural influences, where literacy is defined as a feminine characteristic – propagated by an overrepresentation of female teachers – and that modern culture steers boys towards activities such as sport and computers. Therefore the study investigated the influence of gender inequality on pre – primary school children literacy skills development in Ojo Local Government Area, Lagos State. Descriptive survey research design was adopted for the study. 100 pre-primary school teachers were involved in the study. A self-designed instrument was used for data collection titled ‘Influence of Gender Inequality on Literacy Skill Development in Children Questionnaire (IGILSDCQ)’. The instrument was validated and tested for reliability. The reliability index for IGILSDCQ (α = 0.79). Five research questions were answered using descriptive (frequency count, simple percentage, mean and standard deviation). The findings showed that that gender inequality to some extent influence children phonemic awareness (WA=1.76), the extent to which gender inequality influence children awareness of print is high (WA=2.8), gender inequality to some extent influence children vocabulary development (WA = 2.4), the extent to which gender inequality influence children speaking skill development is high (WA = 2.5) and lastly, the extent to which gender inequality influence children comprehension ability is high (WA = 2.5). It was recommended among others that effort by the school administrators is necessary in the provision of reading materials and literacy skill development packages that are both male-oriented and female-oriented.

Keywords: pre-primart, literacy, awareness, phonemic, gender

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Authors: Jianming Cai

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Exposure to ionizing radiation causes severe damage to human body and an safe and effective radioprotector is urgently required for alleviating radiation damage. In 2008, flagellin, an agonist of TLR5, was found to exert radioprotective effects on radiation injury through activating NF-kB signaling pathway. From then, the radioprotective effects of TLR ligands has shed new lights on radiation protection. CpG-ODN is an unmethylated oligonucleotide which activates TLR9 signaling pathway. In this study, we demonstrated that CpG-ODN has therapeutic effects on radiation injuries induced by γ ray and 12C6+ heavy ion particles. Our data showed that CpG-ODN increased the survival rate of mice after whole body irradiation and increased the number of leukocytes as well as the bone marrow cells. CpG-ODN also alleviated radiation damage on intestinal crypt through regulating apoptosis signaling pathway including bcl2, bax, and caspase 3 etc. By using a radiation-induced pulmonary fibrosis model, we found that CpG-ODN could alleviate structural damage, within 20 week after whole–thorax 15Gy irradiation. In this model, Th1/Th2 imbalance induced by irradiation was also reversed by CpG-ODN. We also found that TGFβ-Smad signaling pathway was regulated by CpG-ODN, which accounts for the therapeutic effects of CpG-ODN in radiation-induced pulmonary injury. On another hand, for high LET radiation protection, we investigated protective effects of CpG-ODN against 12C6+ heavy ion irradiation and found that after CpG-ODN treatment, the apoptosis and cell cycle arrest induced by 12C6+ irradiation was reduced. CpG-ODN also reduced the expression of Bax and caspase 3, while increased the level of bcl2. Then we detected the effect of CpG-ODN on heavy ion induced immune dysfunction. Our data showed that CpG-ODN increased the survival rate of mice and also the leukocytes after 12C6+ irradiation. Besides, the structural damage of immune organ such as thymus and spleen was also alleviated by CpG-ODN treatment. In conclusion, we found that TLR9 ligand, CpG-ODN reduced radiation injuries in response to γ ray and 12C6+ heavy ion irradiation. On one hand, CpG-ODN inhibited the activation of apoptosis induced by radiation through regulating bcl2, bax and caspase 3. On another hand, through activating TLR9, CpG-ODN recruit MyD88-IRAK-TRAF6 complex, activating TAK1, IRF5 and NF-kB pathway, and thus alleviates radiation damage. This study provides novel insights into protection and therapy of radiation damages.

Keywords: TLR9, CpG-ODN, radiation injury, high LET radiation

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Authors: L. Szymanski, Z. Kolacinski, Z. Kamiński, G. Raniszewski, J. Fraczyk, L. Pietrzak

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In the article the development and demonstration of method and the model device for hyperthermic selective destruction of cancer cells are presented. This method was based on the synthesis and functionalization of carbon nanotubes serving as ferromagnetic material nano containers. Methodology of the production carbon - ferromagnetic nanocontainers includes: the synthesis of carbon nanotubes, chemical and physical characterization, increasing the content of ferromagnetic material and biochemical functionalization involving the attachment of the key addresses. Biochemical functionalization of ferromagnetic nanocontainers is necessary in order to increase the binding selectively with receptors presented on the surface of tumour cells. Multi-step modification procedure was finally used to attach folic acid on the surface of ferromagnetic nanocontainers. Folic acid is ligand of folate receptors which is overexpresion in tumor cells. The presence of ligand should ensure the specificity of the interaction between ferromagnetic nanocontainers and tumor cells. The chemical functionalization contains several step: oxidation reaction, transformation of carboxyl groups into more reactive ester or amide groups, incorporation of spacer molecule (linker), attaching folic acid. Activation of carboxylic groups was prepared with triazine coupling reagent (preparation of superactive ester attached on the nanocontainers). The spacer molecules were designed and synthesized. In order to ensure biocompatibillity of linkers they were built from amino acids or peptides. Spacer molecules were synthesized using the SPPS method. Synthesis was performed on 2-Chlorotrityl resin. The linker important feature is its length. Due to that fact synthesis of peptide linkers containing from 2 to 4 -Ala- residues was carried out. Independent synthesis of the conjugate of foilic acid with 6-aminocaproic acid was made. Final step of synthesis was connecting conjugat with spacer molecules and attaching it on the ferromagnetic nanocontainer surface. This article contains also information about special CVD and microvave plasma system to produce nanotubes and ferromagnetic nanocontainers. The first tests in the device for hyperthermal RF generator will be presented. The frequency of RF generator was in the ranges from 10 to 14Mhz and from 265 to 621kHz.

Keywords: synthesis of carbon nanotubes, hyperthermia, ligands, carbon nanotubes

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Authors: Semyachkina-Glushkovskaya Oxana, Fedosov Ivan, Blokhina Inna, Terskov Andrey, Evsukova Arina, Elovenko Daria, Adushkina Viktoria, Dubrovsky Alexander, Jürgen Kurths

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In modern neurobiology, sleep is considered a novel biomarker and a promising therapeutic target for brain diseases. This is due to recent discoveries of the nighttime activation of the brain lymphatic system (BLS), playing an important role in the removal of wastes and toxins from the brain and contributes neuroprotection of the central nervous system (CNS). In our review, we discuss that night stimulation of BLS might be a breakthrough strategy in a new treatment of Alzheimer’s and Parkinson’s disease, stroke, brain trauma, and oncology. Although this research is in its infancy, however, there are pioneering and promising results suggesting that night transcranial photostimulation (tPBM) stimulates more effectively lymphatic removal of amyloid-beta from mouse brain than daily tPBM that is associated with a greater improvement of the neurological status and recognition memory of animals. In our previous study, we discovered that tPBM modulates the tone and permeability of the lymphatic endothelium by stimulating NO formation, promoting lymphatic clearance of wastes and toxins from the brain tissues. We also demonstrate that tPBM can also lead to angio- and lymphangiogenesis, which is another mechanism underlying tPBM-mediated stimulation of BLS. Thus, photo-augmentation of BLS might be a promising therapeutic target for preventing or delaying brain diseases associated with BLS dysfunction. Here we present pioneering technology for simultaneous tPBM in humans and sleep monitoring for stimulation of BLS to remove toxins from CNS and modulation of brain immunity. The wireless-controlled gadget includes a flexible organic light-emitting diode (LED) source that is controlled directly by a sleep-tracking device via a mobile application. The designed autonomous LED source is capable of providing the required therapeutic dose of light radiation at a certain region of the patient’s head without disturbing of sleeping patient. To minimize patients' discomfort, advanced materials like flexible organic LEDs were used. Acknowledgment: This study was supported by RSF project No. 23-75-30001.

Keywords: brain diseases, brain lymphatic system, phototherapy, sleep

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Authors: Keshav Prasad Kandel, Balaram Khadka, Karan Bhatta, Basu Dev Ghimire

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Earthquakes still exist as a threating disaster. Being able to predict earthquakes will certainly help prevent substantial loss of life and property. Perhaps, Very Low Frequency/Low Frequency (VLF/LF) signal band (3-30 kHz), which is effectively reflected from D-layer of ionosphere, can be established as a tool to predict earthquake. On May 20 and May 29, 2012, earthquakes of magnitude 6.1 and 5.8 respectively struck Emilia-Romagna of Italy. A year back, on August 24, 2016, an earthquake of magnitude 6.2 struck Central Italy (42.7060 N and 13.2230 E) at 1:36 UT. We present the results obtained from the US Navy VLF Transmitter’s NSY signal of 45.9 kHz transmitted from Niscemi, in the province of Sicily, Italy and received at the Kiel Longwave Monitor, Germany for 2012 and 2016. We analyzed the terminator times, their individual differences and nighttime fluctuation counts. We also analyzed trends, dispersion and nighttime fluctuation which gave us a possible precursors to these earthquakes. Since perturbations in VLF amplitude could also be due to various other factors like lightning, geomagnetic activities (storms, auroras etc.) and solar activities (flares, UV flux, etc.), we filtered the possible perturbations due to these agents to guarantee that the perturbations seen in VLF/LF amplitudes were as a precursor to Earthquakes. As our TRGCP path is North-south, the sunrise and sunset time in transmitter and receiver places matches making pathway for VLF/LF smoother and therefore hoping to obtain more natural data. To our surprise, we found many clear anomalies (as precursors) in terminator times 5 days to 16 days before the earthquakes. Moreover, using night time fluctuation method, we found clear anomalies 5 days to 13 days prior to main earthquakes. This exactly correlates with the findings of previous authors that ionospheric perturbations are seen few days to one month before the seismic activity. In addition to this, we were amazed to observe unexpected decrease of dispersion on certain anomalies where it was supposed to increase, thereby not supporting our finding to some extent. To resolve this problem, we devised a new parameter called dispersion nighttime (dispersion). On analyzing, this parameter decreases significantly on days of nighttime anomalies thereby supporting our precursors to much extent.

Keywords: D-layer, TRGCP (Transmitter Receiver Great Circle Path), terminator times, VLF/LF

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Authors: Julian Mehler, Marcus Fischer, Martin Hartmann, Peter S. Schulz

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During the last two decades, the synthesis of metal-organic frameworks (MOFs) has gained ever increasing attention. Based on their pore size and shape as well as host-guest interactions, they are of interest for numerous fields related to porous materials, like catalysis and gas separation. Usually, MOF-synthesis takes place in an organic solvent between room temperature and approximately 220 °C, with mixtures of polyfunctional organic linker molecules and metal precursors as substrates. Reaction temperatures above the boiling point of the solvent, i.e. solvothermal reactions, are run in autoclaves or sealed glass vessels under autogenous pressures. A relatively new approach for the synthesis of MOFs is the so-called ionothermal synthesis route. It applies an ionic liquid as a solvent, which can serve as a structure-directing template and/or a charge-compensating agent in the final coordination polymer structure. Furthermore, this method often allows for less harsh reaction conditions than the solvothermal route. Here a variation of the ionothermal approach is reported, where the ionic liquid also serves as an organic linker source. By using 1-ethyl-3-methylimidazolium terephthalates ([EMIM][Hbdc] and [EMIM]₂[bdc]), the one-step synthesis of MIL-53(Al)/Boehemite composites with interesting features is possible. The resulting material is already formed at moderate temperatures (90-130 °C) and is stabilized in the usually unfavored ht-phase. Additionally, in contrast to already published procedures for MIL-53(Al) synthesis, no further activation at high temperatures is mandatory. A full characterization of this novel composite material is provided, including XRD, SS-NMR, El-Al., SEM as well as sorption measurements and its interesting features are compared to MIL-53(Al) samples produced by the classical solvothermal route. Furthermore, the syntheses of the applied ionic liquids and salts is discussed. The influence of the degree of ionicity of the linker source [EMIM]x[H(2-x)bdc] on the crystal structure and the achievable synthesis temperature are investigated and give insight into the role of the IL during synthesis. Aside from the synthesis of MIL-53 from EMIM terephthalates, the use of the phosphonium cation in this approach is discussed as well. Additionally, the employment of ILs in the preparation of other MOFs is presented briefly. This includes the ZIF-4 framework from the respective imidazolate ILs and chiral camphorate based frameworks from their imidazolium precursors.

Keywords: ionic liquids, ionothermal synthesis, material synthesis, MIL-53, MOFs

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Authors: Renzhi Qi, Zhaoping Zhong

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Under the dual pressure of the global energy crisis and environmental pollution, avoiding the consumption of non-renewable fossil fuels based on carbon as the energy carrier and developing and utilizing non-carbon energy carriers are the basic requirements for the future new energy economy. Electrocatalyst for water splitting plays an important role in building sustainable and environmentally friendly energy conversion. The oxygen evolution reaction (OER) is essentially limited by the slow kinetics of multi-step proton-electron transfer, which limits the efficiency and cost of water splitting. In this work, CeO₂@NiCo-NRGO/NF hybrid materials were prepared using nickel foam (NF) and nitrogen-doped reduced graphene oxide (NRGO) as conductive substrates by multi-step hydrothermal method and were used as highly efficient catalysts for OER. The well-connected nanosheet array forms a three-dimensional (3D) network on the substrate, providing a large electrochemical surface area with abundant catalytic active sites. The doping of CeO₂ in NiCo-NRGO/NF electrocatalysts promotes the dispersion of substances and its synergistic effect in promoting the activation of reactants, which is crucial for improving its catalytic performance against OER. The results indicate that CeO₂@NiCo-NRGO/NF only requires a lower overpotential of 250 mV to drive the current density of 10 mA cm-2 for an OER reaction of 1 M KOH, and exhibits excellent stability at this current density for more than 10 hours. The double layer capacitance (Cdl) values show that CeO₂@NiCo-NRGO/NF significantly affects the interfacial conductivity and electrochemically active surface area. The hybrid structure could promote the catalytic performance of oxygen evolution reaction, such as low initial potential, high electrical activity, and excellent long-term durability. The strategy for improving the catalytic activity of NiCo-LDH can be used to develop a variety of other electrocatalysts for water splitting.

Keywords: CeO₂, reduced graphene oxide, NiCo-layered double hydroxide, oxygen evolution reaction

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Authors: Shuang Luo, Er-Xiang Song

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Many problems in geotechnical engineering, such as foundation deformation, groundwater seepage, seismic wave propagation and geothermal transfer problems, may involve analysis in the ground which can be seen as extending to infinity. To that end, consideration has to be given regarding how to deal with the unbounded domain to be analyzed by using numerical methods, such as finite element method (FEM), finite difference method (FDM) or finite volume method (FVM). A simple artificial boundary approach derived from the analytical solutions for transient radial seepage problems, is introduced. It should be noted, however, that the analytical solutions used to derive the artificial boundary are particular solutions under certain boundary conditions, such as constant hydraulic head at the origin or constant pumping rate of the well. When dealing with unbounded domains with unsteady boundary conditions, a more sophisticated artificial boundary approach to deal with the infinity of the domain is presented. By applying Laplace transforms and introducing some specially defined auxiliary variables, the global artificial boundary conditions (ABCs) are simplified to local ones so that the computational efficiency is enhanced significantly. The introduced two local ABCs are implemented in a finite element computer program so that various seepage problems can be calculated. The two approaches are first verified by the computation of a one-dimensional radial flow problem, and then tentatively applied to more general two-dimensional cylindrical problems and plane problems. Numerical calculations show that the local ABCs can not only give good results for one-dimensional axisymmetric transient flow, but also applicable for more general problems, such as axisymmetric two-dimensional cylindrical problems, and even more general planar two-dimensional flow problems for well doublet and well groups. An important advantage of the latter local boundary is its applicability for seepage under rapidly changing unsteady boundary conditions, and even the computational results on the truncated boundary are usually quite satisfactory. In this aspect, it is superior over the former local boundary. Simulation of relatively long operational time demonstrates to certain extents the numerical stability of the local boundary. The solutions of the two local ABCs are compared with each other and with those obtained by using large element mesh, which proves the satisfactory performance and obvious superiority over the large mesh model.

Keywords: transient seepage, unbounded domain, artificial boundary condition, numerical simulation

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Authors: Ufuk Tosun, Reza Aghazadeh, Mehmet Bülent Özer

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This study puts forward a method to analyze the sloshing characteristics of liquid in a tuned sloshing absorber system by using image processing tools. Tuned sloshing vibration absorbers have recently attracted researchers’ attention as a seismic load damper in constructions due to its practical and logistical convenience. The absorber is liquid which sloshes and applies a force in opposite phase to the motion of structure. Experimentally characterization of the sloshing behavior can be utilized as means of verifying the results of numerical analysis. It can also be used to identify the accuracy of assumptions related to the motion of the liquid. There are extensive theoretical and experimental studies in the literature related to the dynamical and structural behavior of tuned sloshing dampers. In most of these works there are efforts to estimate the sloshing behavior of the liquid such as free surface motion and total force applied by liquid to the wall of container. For these purposes the use of sensors such as load cells and ultrasonic sensors are prevalent in experimental works. Load cells are only capable of measuring the force and requires conducting tests both with and without liquid to obtain pure sloshing force. Ultrasonic level sensors give point-wise measurements and hence they are not applicable to measure the whole free surface motion. Furthermore, in the case of liquid splashing it may give incorrect data. In this work a method for evaluating the sloshing wave height by using camera records and image processing techniques is presented. In this method the motion of the liquid and its container, made of a transparent material, is recorded by a high speed camera which is aligned to the free surface of the liquid. The video captured by the camera is processed frame by frame by using MATLAB Image Processing toolbox. The process starts with cropping the desired region. By recognizing the regions containing liquid and eliminating noise and liquid splashing, the final picture depicting the free surface of liquid is achieved. This picture then is used to obtain the height of the liquid through the length of container. This process is verified by ultrasonic sensors that measured fluid height on the surface of liquid.

Keywords: fluid structure interaction, image processing, sloshing, tuned liquid damper

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Authors: Ayesha Waqar Khan, Mariam Altaf, Jamil Ahmad, Shaheen Shahzad

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Kidney fibrosis is an anticipated outcome of possibly all types of progressive chronic kidney disease (CKD). Epithelial-mesenchymal transition (EMT) signaling pathway is responsible for production of matrix-producing fibroblasts and myofibroblasts in diseased kidney. In this study, a discrete model of TGF-beta (transforming growth factor) and CTGF (connective tissue growth factor) was constructed using Rene Thomas formalism to investigate renal fibrosis turn over. The kinetic logic proposed by Rene Thomas is a renowned approach for modeling of Biological Regulatory Networks (BRNs). This modeling approach uses a set of constraints which represents the dynamics of the BRN thus analyzing the pathway and predicting critical trajectories that lead to a normal or diseased state. The molecular connection between TGF-beta, Smad 2/3 (transcription factor) phosphorylation and CTGF is modeled using GenoTech. The order of BRN is CTGF, TGF-B, and SMAD3 respectively. The predicted cycle depicts activation of TGF-B (TGF-β) via cleavage of its own pro-domain (0,1,0) and presentation to TGFR-II receptor phosphorylating SMAD3 (Smad2/3) in the state (0,1,1). Later TGF-B is turned off (0,0,1) thereby activating SMAD3 that further stimulates the expression of CTGF in the state (1,0,1) and itself turns off in (1,0,0). Elevated CTGF expression reactivates TGF-B (1,1,0) and the cycle continues. The predicted model has generated one cycle and two steady states. Cyclic behavior in this study represents the diseased state in which all three proteins contribute to renal fibrosis. The proposed model is in accordance with the experimental findings of the existing diseased state. Extended cycle results in enhanced CTGF expression through Smad2/3 and Smad4 translocation in the nucleus. The results suggest that the system converges towards organ fibrogenesis if CTGF remains constructively active along with Smad2/3 and Smad 4 that plays an important role in kidney fibrosis. Therefore, modeling regulatory pathways of kidney fibrosis will escort to the progress of therapeutic tools and real-world useful applications such as predictive and preventive medicine.

Keywords: CTGF, renal fibrosis signaling pathway, system biology, qualitative modeling

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Authors: Esmael Makarian, Ayub Elyasi, Fatemeh Saberi, Olusegun Stanley Tomomewo

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Geothermal reservoirs (GTRs) have garnered global recognition as a sustainable energy source. The Thermo-Hydro-Mechanical-Chemical (THMC) integration coupling proves to be a practical and effective method for optimizing production in GTRs. The study outcomes demonstrate that THMC coupling serves as a versatile and valuable tool, offering in-depth insights into GTRs and enhancing their operational efficiency. This is achieved through temperature analysis and pressure changes and their impacts on mechanical properties, structural integrity, fracture aperture, permeability, and heat extraction efficiency. Moreover, THMC coupling facilitates potential benefits assessment and risks associated with different geothermal technologies, considering the complex thermal, hydraulic, mechanical, and chemical interactions within the reservoirs. However, THMC-coupling utilization in GTRs presents a multitude of challenges. These challenges include accurately modeling and predicting behavior due to the interconnected nature of processes, limited data availability leading to uncertainties, induced seismic events risks to nearby communities, scaling and mineral deposition reducing operational efficiency, and reservoirs' long-term sustainability. In addition, material degradation, environmental impacts, technical challenges in monitoring and control, accurate assessment of resource potential, and regulatory and social acceptance further complicate geothermal projects. Addressing these multifaceted challenges is crucial for successful geothermal energy resources sustainable utilization. This paper aims to illuminate the challenges and opportunities associated with THMC coupling in enhanced geothermal systems. Practical solutions and strategies for mitigating these challenges are discussed, emphasizing the need for interdisciplinary approaches, improved data collection and modeling techniques, and advanced monitoring and control systems. Overcoming these challenges is imperative for unlocking the full potential of geothermal energy making a substantial contribution to the global energy transition and sustainable development.

Keywords: geothermal reservoirs, THMC coupling, interdisciplinary approaches, challenges and opportunities, sustainable utilization

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Authors: Hoda M. Eid, Abir Nachar, Farah Thong, Gary Sweeney, Pierre S. Haddad

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Caffeic acid methyl ester (CAME) and caffeic ethyl esters (CAEE) were previously reported to potently stimulate glucose uptake in cultured C2C12 skeletal muscle cells via insulin-independent mechanisms involving the activation of adenosine monophosphate-activated protein kinase (AMPK). In the present study, we investigated the effect of the two compounds on the translocation of glucose transporter GLUT4 in L6 skeletal muscle cells. The cells were treated with the optimum non-toxic concentration (50 µM) of either CAME or CAEE for 18 h. Levels of GLUT4myc at the cell surface were measured by O-phenylenediamine dihydrochloride (OPD) assay. The effects of CAME and CAEE on GLUT1 and GLUT4 protein content were also measured by western immunoblot. Our results show that CAME and CAEE significantly increased glucose uptake, GLUT4 translocation and GLUT4 protein content. Furthermore, the effect of the two CA esters on two insulin-sensitive cell lines: H4IIE rat hepatoma and 3T3-L1 adipocytes were investigated. CAME and CAEE reduced the enzymatic activity of the key hepatic gluconeogenic enzyme glucose-6-phosphatase in a concentration-dependent manner. In addition, they exerted a concentration-dependent antiadipogenic effect on 3T3-L1 cells. Mitotic clonal expansion (MCE), a prerequisite for adipocytes differentiation was also concentration-dependently inhibited. The two compounds abrogated lipid droplet accumulation, blocked MCE and maintained cells in fibroblast-like state when applied at the maximum non-toxic concentration (100 µM). In addition, the expression of the early key adipogenic transcription factors CCAAT enhancer-binding protein beta (C/EBP-β) and the master regulator of adipogenesis peroxisome-proliferator-activated receptor gamma (PPAR-γ) were inhibited. We, therefore, conclude that CAME and CAEE exert pleiotropic benefits in several insulin-sensitive cell lines through insulin-independent mechanisms involving AMPK, hence they may treat obesity, diabetes and other metabolic diseases.

Keywords: type 2 diabetes mellitus, insulin resistance, GLUT4, Akt, AMPK.

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Authors: Shouta Sora, Shizuki Kuriu, Radhika Mishra, Ariunbuyan Sukhbaatar, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

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Lymph node (LN) metastasis accounts for 20 - 30 % of all deaths in patients with head and neck cancer. Therefore, the control of metastatic lymph nodes (MLNs) is necessary to improve the life prognosis of patients with cancer. In a classical metastatic theory, tumor cells are thought to metastasize hematogenously through a bead-like network of lymph nodes. Recently, a lymph node-mediated hematogenous metastasis theory has been proposed, in which sentinel LNs are regarded as a source of distant metastasis. Therefore, the treatment of MLNs at the early stage is essential to prevent distant metastasis. Radiation therapy is one of the primary therapeutic modalities in cancer treatment. In addition, total body irradiation (TBI) has been reported to act as activation of natural killer cells and increase of infiltration of CD4+ T-cells to tumor tissues. However, the treatment effect of TBI for MLNs remains unclear. This study evaluated the possibilities of low-dose total body irradiation (L-TBI) and middle-dose total body irradiation (M-TBI) for the treatment of MLNs. Mouse breast cancer FM3A-Luc cells were injected into subiliac lymph node (SiLN) of MXH10/Mo/LPR mice to induce the metastasis to the proper axillary lymph node (PALN) and lung. Mice were irradiated for the whole body on 4 days after tumor injection. The L-TBI and M-TBI were defined as irradiations to the whole body at 0.2 Gy and 1.0 Gy, respectively. Tumor growth was evaluated by in vivo bioluminescence imaging system. In the non-irradiated group, tumor activities on SiLN and PALN significantly increased over time, and the metastasis to the lung from LNs was confirmed 28 days after tumor injection. The L-TBI led to a tumor growth delay in PALN but did not control tumor growth in SiLN and metastasis to the lung. In contrast, it was found that the M-TBI significantly delayed the tumor growth of both SiLN and PALN and controlled the distant metastasis to the lung compared with non-irradiated and L-TBI groups. These results suggest that the M-TBI is an effective treatment method for MLNs in the early stage and distant metastasis from lymph nodes via blood vessels connected with LNs.

Keywords: metastatic lymph node, lung metastasis, radiation therapy, total body irradiation, lymphatic system

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Authors: Siti Aisya Gany, Swee Ching Tan, Sook Yee Gan

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Diminished antioxidant defense or increased production of reactive oxygen species in the biological system can result in oxidative stress which may lead to various neurodegenerative diseases including Alzheimer’s disease (AD). Microglial activation also contributes to the progression of AD by producing several pro-inflammatory cytokines, nitric oxide (NO), and prostaglandin E2 (PGE2). Oxidative stress and inflammation have been reported to be possible pathophysiological mechanisms underlying AD. In addition, the cholinergic hypothesis postulates that memory impairment in patient with AD is also associated with the deficit of cholinergic function in the brain. Although a number of drugs have been approved for the treatment of AD, most of these synthetic drugs have diverse side effects and yield relatively modest benefits. Marine algae have great potential in pharmaceutical and biomedical applications as they are valuable sources of bioactive properties such as anti-coagulation, anti-microbial, anti-oxidative, anti-cancer and anti-inflammatory. Hence, this study aimed to provide an overview of the properties of Malaysian seaweeds (Padina australis, Sargassum polycystum and Caulerpa racemosa) in inhibiting oxidative stress, neuroinflammation and cholinesterase enzymes. All tested samples significantly exhibit potent DPPH and moderate Superoxide anion radical scavenging ability (P<0.05). Hexane and methanol extracts of S. polycystum exhibited the most potent radical scavenging ability with IC50 values of 0.1572 ± 0.004 mg/ml and 0.8493 ± 0.02 for DPPH and ABTS assays, respectively. Hexane extract of C. racemosa gave the strongest superoxide radical inhibitory effect (IC50 of 0.3862± 0.01 mg/ml). Most seaweed extracts significantly inhibited the production of cytokine (IL-6, IL-1 β, TNFα) and NO in a concentration-dependent manner without causing significant cytotoxicity to the lipopolysaccharide (LPS)-stimulated microglia cells (P<0.05). All extracts suppressed cytokine and NO level by more than 80% at the concentration of 0.4mg/ml. In addition, C. racemosa and S. polycystum also showed anti-acetylcholinesterase activities with the IC50 values ranging from 0.086-0.115 mg/ml. Moreover, C. racemosa and P. australis were also found to be active against butyrylcholinesterase with IC50 values ranging from 0.118-0.287 mg/ml.

Keywords: anti-cholinesterase, anti-oxidative, neuroinflammation, seaweeds

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Authors: Philip Friedlander, John Rutledge, Jason Suh

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Inhibition of programmed death-1 (PD-1) or its ligand PD-L1 confers therapeutic efficacy in a wide range of solid tumor malignancies. Primary or acquired resistance can develop through activation of immunosuppressive immune cells such as tumor-associated macrophages. The renin angiotensin system (RAS) systemically regulates fluid and sodium hemodynamics, but components are expressed on and regulate the activity of immune cells, particularly of myeloid lineage. We hypothesized that inhibition of RAS would improve the efficacy of PD-1/PD-L-1 treatment. A retrospective analysis was performed through a chart review of patients with solid metastatic malignancies treated with a PD-1/PD-L1 inhibitor between 1/2013 and 6/2019 at Valley Hospital, a community hospital in New Jersey, USA. Efficacy was determined by medical oncologist documentation of clinical benefit in visit notes and by the duration of time on immunotherapy treatment. The primary endpoint was the determination of efficacy differences in patients treated with an inhibitor of RAS ( ace inhibitor, ACEi, or angiotensin blocker, ARB) compared to patients not treated with these inhibitors. To control for broader antihypertensive effects, efficacy as a function of treatment with beta blockers was assessed. 173 patients treated with PD-1/PD-L-1 inhibitors were identified of whom 52 were also treated with an ACEi or ARB. Chi-square testing revealed a statistically significant relationship between being on an ACEi or ARB and efficacy to PD-1/PD-L-1 therapy (p=0.001). No statistically significant relationship was seen between patients taking or not taking beta blocker antihypertensives (p= 0.33). Kaplan-Meier analysis showed statistically significant improvement in the duration of therapy favoring patients concomitantly treated with ACEi or ARB compared to patients not exposed to antihypertensives and to those treated with beta blockers. Logistic regression analysis revealed that age, gender, and cancer type did not have significant effects on the odds of experiencing clinical benefit (p=0.74, p=0.75, and p=0.81, respectively). We conclude that retrospective analysis of the treatment of patients with solid metastatic tumors with anti-PD-1/PD-L1 in a community setting demonstrates greater clinical benefit in the context of concomitant ACEi or ARB inhibition, irrespective of gender or age. This data supports the development of prospective assessment through randomized clinical trials.

Keywords: angiotensin, cancer, immunotherapy, PD-1, efficacy

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